Microplastic contamination in the agricultural soil-mitigation strategies, heavy metals contamination, and impact on human health: a review.

Microplastic pollution has emerged as a critical global environmental issue due to its widespread distribution, persistence, and potential adverse effects on ecosystems and human health. Although research on microplastic pollution in aquatic environments has gained significant attention. However, a limited literature has summarized the impacts of microplastic pollution the agricultural land and human health. Therefore, In the current review, we have discussed how microplastic(s) affect the microorganisms by ingesting the microplastic present in the soil, alternatively affecting the belowground biotic and abiotic components, which further elucidates the negative effects on the above-ground properties of the crops. In addition, the consumption of these crops in the food chain revealed a potential risk to human health throughout the food chain. Moreover, microplastic pollution has the potential to induce a negative impact on agricultural production and food security by altering the physiochemical properties of the soil, microbial population, nutrient cycling, and plant growth and development. Therefore, we discussed in detail the potential hazards caused by microplastic contamination in the soil and through the consumption of food and water by humans in daily intake. Furthermore, further study is urgently required to comprehend how microplastic pollution negatively affects terrestrial ecosystems, particularly agroecosystems which drastically reduces the productivity of the crops. Our review highlights the urgent need for greater awareness, policy interventions, and technological solutions to address the emerging threat of microplastic pollution in soil and plant systems and mitigation strategies to overcome its potential impacts on human health. Based on existing studies, we have pointed out the research gaps and proposed different directions for future research.

Biochar and saline soil: mitigation strategy by incapacitating the ecological threats to agricultural land.

Soil salinity caused a widespread detrimental issue that hinders productivity in agriculture and ecological sustainability, while waste-derived soil amendments like biochar have drawn attention for their capacity to act as a mitigating agent, by enhancing the physical and chemical features of soil, and contributing to the recovery of agricultural waste resources. However, the information concerning biochar and salinity which affect the physicochemical characteristics of soils, crop physiology, and growth is limited. To investigate whether biochar mitigates the salinity stress on wheat crop seedlings, we grow them with salinity stress (120 mM), and biochar (20 tons ha-1), and its interactive effects. The soil properties of soil organic carbon (SOC), soil organic matter (SOM), dissolved organic carbon (DOC), and soil available phosphorus (SAP) decreased in the saline soil by 36.71%, 46.97%, 26.31%, and 15.00%, while biochar treatment increased SOC, DOC, and SAP contents by 7.42%, 31.57%, and 15.00%, respectively. On the other hand, dissolved organic nitrogen (DON) contents decreased in all the treatments compared to the control. The root growth traits, SPAD values, leaf nitrogen, photosynthetic parameters, antioxidant enzymes, and reactive oxygen species decreased in the saline treatment while increasing in the biochar and interactive treatment. Thus, these activities resulted in higher leaves and root biomass in the biochar treatment alone and interactive treatment of salinity and biochar. According to principal component analysis, redundancy analysis, and the mantel test, using biochar in conjunction with salinity treatment was found to be more effective than salinity treatment alone. The results of this study suggest that biochar can be used as a sustainable agricultural technique and a means of mitigation agent by lowering soil salinity while increasing the biomass of crops.

Biochar improves the physical and nutritional quality of soil and plant function.Salinity stress declined the physiological activities and biomass of the crop.Biochar mitigates the salinity stress in soil and enhances the plant functioning.Exposure to both treatments enhances the antioxidant enzyme activity and biomass.

Soil nutrient levels regulate the effect of soil microplastic contamination on microbial element metabolism and carbon use efficiency.

Microplastics (MPs) are emerging environmental contaminants in soil ecosystems that disrupt the soil carbon (C) pool. Therefore, the response of microbial metabolism to MP-contaminated soil is crucial for soil-C stabilization. We undertook factorial experiments in a greenhouse with three types of soil microplastics with three levels of soil nutrients and undertook soil physiochemical analyses after 60 days. The present study revealed how the presence of degradable polylactic acid (PLA) and non-degradable polyethylene (PE) MPs affects soil microbial nutrient limitation and C use efficiency (CUE) at varying nutrient concentrations. The presence of PLA in soil with low nutrient levels led to a significant increase (29%) in the activities of nitrogen (N)-acquiring enzymes. In contrast, the presence of MPs had no effect on C- and N-acquiring enzymes. The occurrence of PE caused a 41% reduction in microbial C limitation in high-nutrient soils, and microbial nutrient metabolism was limited by the occurrence of MPs in soils amended with nutrients. A strong positive correlation between microbial C and nutrient limitation in the soil indicates that addressing C limitation followed by amendment of soil with MPs could potentially intensify microbial N limitation in soils with varying nutrients. In comparison, the microbial CUE increased by 10% with the application of degradable MPs (PLA) to soils with a low nutrient status. These findings highlight the significant influence of both degradable PLA and non-degradable PE MPs on soil microbial processes and C dynamics. In conclusion, PLA enhances metabolic efficiency in nutrient-rich soils, potentially aiding C utilization, whereas PE reduces microbial C limitation, offering promise for soil C sequestration strategies. Our findings underscore the importance of considering MPs in soil ecosystem studies and in broader sustainability efforts.

Effect of polymeric stabilizers on the size and stability of PLGA paclitaxel nanoparticles.

The aim of this study is to formulate polymeric paclitaxel nanoparticles with various stabilizers to improve solubility, enhance stability, maximize therapeutic efficacy and minimize detrimental toxicities of paclitaxel. In this study, trastuzumab-guided poly lactic-co-glycolic acid (PLGA)-loaded paclitaxel nanoparticles were formulated with pluronic F-127, polyvinyl alcohol (PVA), poloxamer 407, Tween-80, span 20, sodium dodecyl sulfate (SDS), and sodium lauryl sulfate (SLS) at different concentrations (0.5, 1, 1.5 and 2%) using the solvent evaporation method. The nanoparticles were evaluated for physicochemical characteristics and short and long-term stability. The optimum particle size (190 nm ± 12.42 to 350 nm ± 11.1), PDI (0.13 ± 0.02 to 0.2 ± 0.01), surface charge (-19.1mv ± 1.5 to -40.4mv ± 1.6), drug loading (2.43 to 9.5 %) and encapsulation efficiency (greater than 80 %) were obtained with these stabilizers while keeping the polymer concentration, temperature, probe size, amplitude and sonication time constant. The nanoformulations were stably stored at 4 °C. The nanoformulations of paclitaxel with pluronic F-127, polyvinyl alcohol (PVA), and poloxamer 407 were found to be more soluble, stable, uniform in physicochemical properties, and efficient in drug loading and encapsulation for improved therapeutic effects.

Efficacy of oral methotrexate (MTX) monotherapy vs oral MTX plus narrowband ultraviolet light B phototherapy in palmoplantar psoriasis.

Palmoplantar psoriasis (PPP) is a chronic, inflammatory dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. We aim to compare the effect of oral methotrexate (MTX) monotherapy vs MTX plus narrowband ultraviolet light B (NB-UVB) in the treatment of recalcitrant PPP. This was a comparative clinical trial involving 90 patients of PPP. Eligible patients were randomly assigned to one of the two treatment groups. We aim patients in group A received 10 mg oral MTX weekly, and patients in group B received oral MTX 10 mg weekly and NB-UVB sessions twice weekly for 12 weeks. There was a statistically significant difference in reduction of modified PPP Area Severity Index (m-PPPASI) of patients in MTX plus NB-UVB at week 12. The mean m-PPPASI at week 12 was 3.66 ± 2.11 in MTX plus NB-UVB group and 6.51 ± 2.04 in MTX only group (P < .001). Marked improvement (m-PPPASI 75) was achieved in 20 (44.44%) patients in MTX plus NB-UVB group compared with 6 (13.3%) in MTX monotherapy group (P < .001). Combination of MTX and NB-UVB phototherapy helps to attain a better clinical response (reduction in m-PPPASI score) than MTX monotherapy in the treatment of recalcitrant PPP.

Comparative pharmacokinetics of Omeprazole and its metabolites in poor and extensive metabolizer Pakistani healthy volunteers and a review of different studies.

This study was designed to evaluate a comparative single dose (40mg) pharmacokinetics (PK) of Omeprazole (OMP) and its two metabolites, 5-hydroxy Omeprazole (5-OH-OMP) and Omeprazole sulphone (OMP-S) in poor (PM) and extensive (EM) metabolizer Pakistani healthy adult volunteers. The frequency of CYP2C19 and CYP3A4 varies widely in different populations. The present study was conducted to evaluate the PK of OMP and its two metabolites in Pakistani population and to review different studies conducted after administration of single dose of OMP. Twenty two subjects were enrolled in this study and divided into two groups. The CYP2C19 phenotyping was evaluated by the metabolic ratio of OMP to 5-OH-OMP. It was a single dose, open label study and the blood samples from subjects were collected at different time intervals until 24 hours. The PK parameters were calculated using the PK-summit software. The metabolic ratio of area under the plasma concentration-time curve AUCOMP/5-OH-OMP was 1.86 ± 0.572 and13.84 ± 2.504 for EM and PM, respectively; maximum plasma concentration (Cmax) of OMP was increased by two folds for PM while the AUC∞ was increased by 3 folds; the Cmax and AUC∞ of 5-OH-OMP decreased for PM by 2 folds while there was 3 fold increase observed in the Cmax and AUC∞ of OMP-S. The PK of OMP and its metabolites in different populations were also discussed, and issues regarding CYP2C19 and CYP3A4 genotyping were also extensively reviewed. In EM of CYP2C19 the concentration of 5-OH-OMP is higher while that of OMP-S is lower. This study as well as reported studies reveals that in PM of CYP2C19 more drugs are available for CYP3A4 to be metabolized. A correlation between CYP2C19 EM and PM activity with CYP3A4 needs to be established.

Gamma crystallins of the human eye lens.

BACKGROUND: Protein crystallins co me in three types (α, ß and γ) and are found predominantly in the eye, and particularly in the lens, where they are packed into a compact, plastic, elastic, and transparent globule of proper refractive power range that aids in focusing incoming light on to the retina. Of these, the γ-crystallins are found largely in the nuclear region of the lens at very high concentrations (>400 mg/ml). The connection between their structure and inter-molecular interactions and lens transparency is an issue of particular interest. SCOPE OF REVIEW: We review the origin and phylogeny of the gamma crystallins, their special structure involving the use of Greek key supersecondary structural motif, and how they aid in offering the appropriate refractive index gradient, intermolecular short range attractive interactions (aiding in packing them into a transparent ball), the role that several of the constituent amino acid residues play in this process, the thermodynamic and kinetic stability and how even single point mutations can upset this delicate balance and lead to intermolecular aggregation, forming light-scattering particles which compromise transparency. We cite several examples of this, and illustrate this by cloning, expressing, isolating and comparing the properties of the mutant protein S39C of human γS-crystallin (associated with congenital cataract-microcornea), with those of the wild type molecule. In addition, we note that human γ-crystallins are also present in other parts of the eye (e.g., retina), where their functions are yet to be understood. MAJOR CONCLUSIONS: There are several 'crucial' residues in and around the Greek key motifs which are essential to maintain the compact architecture of the crystallin molecules. We find that a mutation that replaces even one of these residues can lead to reduction in solubility, formation of light-scattering particles and loss of transparency in the molecular assembly. GENERAL SIGNIFICANCE: Such a molecular understanding of the process helps us construct the continuum of genotype-molecular structural phenotype-clinical (pathological) phenotype. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Structural study of the G57W mutant of human gamma-S-crystallin, associated with congenital cataract.

PURPOSE: Human γS-crystallin (CrygS) is an important component of the human eye lens nucleus and cortex. The mutation G57W in the molecule is reported to be associated with congenital cataract in children. We compare the conformational features and aggregation properties of the mutant protein G57W with the wild-type CrygS to understand how the structural changes in the mutant are related to the mechanism of opacification. METHODS: Wild-type and mutant proteins were cloned, expressed, and purified, and their structural properties were studied in solution. Conformational features and the structural stability of the proteins were compared in solution, using circular dichroism (CD) and fluorescence spectroscopic analysis, and the proteins' tendencies to aggregate were compared using extrinsic spectral probes. In addition, we analyzed the proteins' structural differences with extensive molecular modeling in silico. RESULTS: CD and intrinsic fluorescence analysis suggested the secondary and tertiary structures of the mutant are slightly altered. Experiments using extrinsic spectral probes revealed that the compact close-packed structure is loosened somewhat, and the mutant tends to self-aggregate. Denaturation (both thermal and chemical) studies indicate that the replacement of glycine (G) in position 57 by tryptophan (W) lowered the structural stability of the molecule. Further, the mutant had a tendency to precipitate and scatters light more easily than the wild-type. CONCLUSIONS: The replacement of glycine at position 57 by the tryptophan residue in human γS-crystallin weakens the stability of the mutant molecule and causes the molecule to self-aggregate, thus generating light-scattering particles. This set of changes in the mutant offers a molecular insight into the mechanism of opacification.

Development and evaluation of pluronic- and methylcellulose-based thermoreversible drug delivery system for insulin.

The objective of the current work was to develop and evaluate thermoreversible subcutaneous drug delivery system for Insulin. Thermoreversible in-situ gel system was developed and evaluated both in-vitro and in-vivo comprising of pluronic F-127 alone or in combination with methylcellulose in different ratios. The drug release kinetics and mechanism was predicted by applying various mathematical models to the in-vitro dissolution data. Rabbits were used as animal model following subcutaneous injection to predict various pharmacokinetic parameters by applying Pk-Summit® software. The in-vitro and in-vivo data revealed that the formulation IPM 15/3 consisting of the pluronic F-127 (15% w/v) and methylcellulose (3% w/v) was the most robust and capable formulation for extending the drug release and maintaining basal plasma insulin level between 10 and 40 µU/ml for 240 h (10 d).

Knowledge of modifiable risk factors of cardiovascular diseases among patients with acute myocardial infarction.

BACKGROUND: Cardiovascular disease is a major cause of mortality and morbidity in Pakistan. Knowledge regarding any disease is an important pre-requisite for implementation of preventive and control measures. This study aimed to evaluate the knowledge of modifiable risk factors of cardiovascular diseases in acute myocardial infarction (MI) patients admitted to Ayub Teaching Hospital, Abbottabad, Pakistan. METHODS: It was a hospital based cross sectional descriptive study carried out in cardiology unit of Ayub Teaching Hospital, on 150 patients with first attack of acute MI. knowledge of four modifiable risk factors; fatty food consumption, smoking, physical activities and obesity, was assessed. RESULTS: Among 150 subjects, 103 (68.7%) were males while 47 (31.3%) were females. Forty three (28.7%) of the patients were having good level of knowledge. Male gender and educational status were associated with good level of knowledge. CONCLUSION: There is a lack of good level of knowledge among patients admitted with acute MI. Implementing aggressive educational strategies is of utmost importance in Pakistani population for preventing the rising prevalence of this disease to combat the burdeni of MI.

Underestimation of SARS-CoV-2 in wastewater due to single or double mutations in the N1 qPCR probe binding region.

Wastewater surveillance using RT-qPCR has now been widely adopted to track circulating levels of SARS-CoV-2 virus in many sewersheds. The CDC qPCR assays targeting two regions (N1 and N2) within the N gene are commonly used, but a discrepancy between the two biomarkers has been noticed by independent studies using these methods since late 2021. The reason is presumed to be due to mutations in regions targeted by the N1 qPCR probe. In this study, we systematically investigated and unequivocally confirmed that the underlying reason for this discrepancy was mutations in the N1 probe target, and that a single mutation could cause a significant drop in signal. We first confirmed the proportion of related mutations in wastewater samples (Jan 2021-Dec 2022) using nested PCR and LC-MS. Based on relative proportions of N1 alleles, we separated the wastewater data into four time periods corresponding to different variant waves: Period I (Alpha and Delta waves with 0 mutation), Period II (BA.1/BA.2 waves with a single mutation found in all Omicron strains), Period III (BA.5.2* wave with two mutations), and Period IV (BQ.1* wave with two mutations). Significantly lower N1 copies relative to N2 copies in samples from Periods II-IV compared to those from Period I was observed in wastewater. To further pinpoint the extent to which each mutation impacted N1 quantification, we compared the qPCR response among different synthetic oligomers with corresponding mutations. This study highlighted the impact of even just one or two mutations on qPCR-based wastewater surveillance of SARS-CoV-2.

Multidisciplinary Management of Obstructed Hemivagina and Ipsilateral Renal Anomaly (OHVIRA) Syndrome in an Adolescent With Complex Congenital Anomalies: A Case Report.

Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome presents with complex diagnostic and therapeutic challenges and is characterized by uterine didelphys, obstructed hemivagina, and ipsilateral renal anomaly. A 14-year-old female with a history of anorectal malformation and urogenital sinus anomaly presented with menstrual blood in her urine, abdominal pain, and distension. Investigations revealed a bicornuate uterus, vesicovaginal fistula, and right ovarian cyst, leading to the diagnosis of OHVIRA syndrome. A multidisciplinary approach resulted in salpingo-oophorectomy and subtotal hysterectomy. This case highlights the diagnostic challenges and emphasizes the role of advanced imaging and a multidisciplinary team in managing such complex conditions. It stresses the importance of patient-centered surgical planning tailored to the individual's anatomy and reproductive goals. Early recognition and a tailored, multidisciplinary approach are crucial in managing OHVIRA syndrome and improving outcomes for patients with rare congenital anomalies.

Assessing the impact of biochar and nitrogen application on yield, water-nitrogen use efficiency and quality of intercropped maize and soybean.

Introduction: Biochar (BC) and nitrogen (N) application have the potential to increase grain yield and resource use efficiency in intercropping systems. However, the effects of different levels of BC and N application in these systems remain unclear. To address this gap, the study is intended to ascertain the impact of various combinations of BC and N fertilizer on the performance of maize-soybean intercropping and determine the optimum application of BC and N for maximizing the effect of the intercropping system. Methods: A two-year (2021-2022) field experiment was conducted in Northeast China to assess the impact of BC (0, 15, and 30 t ha-1) and N application (135, 180, and 225 kg ha-1) on plant growth, yield, water use efficiency (WUE), N recovery efficiency (NRE) and quality in an intercropping system. Maize and soybean were selected as materials in the experiment, where every 2 rows of maize were intercropped with 2 rows of soybean. Results and discussion: The results showed that the combination of BC and N significantly affected the yield, WUE, NRE and quality of intercropped maize and soybean. The treatment of 15 t ha-1 BC and 180 kg ha-1 N increased grain yield and WUE, while that of 15 t ha-1 BC and 135 kg ha-1 N enhanced NRE in both years. Nitrogen promoted the protein and oil content of intercropped maize, but decreased the protein and oil content of intercropped soybean. BC did not enhance the protein and oil content of intercropped maize, especially in the first year, but increased maize starch content. BC was found to have no positive impact on soybean protein, but it unexpectedly increased soybean oil content. The TOPSIS method revealed that the comprehensive assessment value first increased and then declined with increasing BC and N application. BC improved the performance of maize-soybean intercropping system in terms of yield, WUE, NRE, and quality while N fertilizer input was reduced. The highest grain yield in two years was achieved for BC of 17.1-23.0 t ha-1 and N of 156-213 kg ha-1 in 2021, and 12.0-18.8 t ha-1 BC and 161-202 kg ha-1 N in 2022. These findings provide a comprehensive understanding of the growth of maize-soybean intercropping system and its potential to enhance the production in northeast China.

Evaluating the influence of straw mulching and intercropping on nitrogen uptake, crop growth, and yield performance in maize and soybean.

Introduction: Intercropping and straw mulching are sustainable agricultural practices that can positively affect crop growth and development, especially together. Methods: A split-plot experimental design was used to investigate the effects of intercropping and straw mulching on crop growth, crop yield, nitrogen uptake, and photosynthetic characteristics. The main plot focused on three planting patterns: soybean monoculture (S), maize monoculture (M), and maize/soybean intercropping (I). The subplot structure consisted of four levels of straw mulching (0, 4.8, 7.2, 9.6 t ha-1). Results: Interaction and variance analyses showed that straw mulching, intercropping, and their interaction had significant effects on plant height, stem diameter, leaf area index, chlorophyll content, nitrogen uptake, photosynthetic characteristics, and crop yield. Based on two-year averages for maize and soybean, the net photosynthetic rate (Pn) was up to 51.6% higher, stomatal conductance (Sc) was up to 44.0% higher, transpiration rate (Tr) was up to 46.6% higher, and intercellular carbon dioxide concentration (Ci) was up to 25.7% lower relative to no mulching. The maximum increases of Pn, Sc, and Tr of intercropped maize were 15.48%, 17.28%, and 23.94%, respectively, and the maximum Ci was 17.75% lower than that of monoculture maize. The maximum increase of Pn, Sc, and Tr of monoculture soybean was 24.58%, 16.90%, and 17.91%, respectively, and the maximum Ci was 13.85% lower than that of intercropped soybean. The nitrogen uptake of maize and soybean in the mulching treatment was 24.3% higher than that in the non-mulching treatment; the nitrogen uptake of intercropped maize was 34.2% higher than that of monoculture maize, and the nitrogen uptake of monoculture soybean was 15.0% higher than that of intercropped soybean. The yield of maize and soybean in the mulching treatment was 66.6% higher than that in the non-mulching treatment, the maize yield under intercropping was 15.4% higher than that under monoculture, and the yield of monoculture soybean was 9.03% higher than that of intercropped soybean. Discussion: The growth index and photosynthesis of crops are important parts of yield formation. The results of this study confirmed that straw mulching, intercropping, and their interaction can ultimately increase crop yield by improving crop growth, nitrogen uptake, and photosynthesis. This result can be used as the theoretical basis for the combined application of these measures in agriculture.

Association between type 2 diabetes and chronic arsenic exposure in drinking water: a cross sectional study in Bangladesh.

BACKGROUND: Chronic exposure to high level of inorganic arsenic in drinking water has been associated with Type 2 Diabetes (T2D). Most research has been ecological in nature and has focused on high levels of arsenic exposure with few studies directly measuring arsenic levels in drinking water as an index of arsenic exposure. The effect of low to moderate levels of arsenic exposure on diabetes risk is largely unknown thus our study is adding further knowledge over previous works. METHODS: This cross sectional study was conducted in 1004 consenting women and men from 1682 eligible participants yielding a participation rate of 60%. These participants are aged >30 years and were living in Bangladesh and had continuously consumed arsenic-contaminated drinking water for at least 6 months. T2D cases were diagnosed using glucometer following the new diagnostic criteria (Fasting Blood Glucose > 126 mg/dl) from the WHO guideline (WHO 2006), or a self-reported physician diagnosis of type 2 diabetes. Association between T2D and chronic arsenic exposure was estimated by multiple logistic regression with adjustment for age, sex, education, Body Mass Index (BMI) and family history of T2D. RESULTS: A total of 1004 individuals participated in the study. The prevalence of T2D was 9% (95% CI 7-11%). After adjustment for diabetes risk factors, an increased risk of type 2 diabetes was observed for arsenic exposure over 50 µg/L with those in the highest category having almost double the risk of type 2 diabetes (OR=1.9 ; 95% CI 1.1-3.5). For most levels of arsenic exposure, the risk estimates are higher with longer exposure; a dose-response pattern was also observed. CONCLUSIONS: These findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic for more than 10 years.

Design and Characterization of Paclitaxel-Loaded Polymeric Nanoparticles Decorated With Trastuzumab for the Effective Treatment of Breast Cancer.

The aim of the study was to design and formulate an antibody-mediated targeted, biodegradable polymeric drug delivery system releasing drug in a controlled manner to achieve a therapeutic goal for the effective treatment of breast cancer. Antibody-mediated paclitaxel-loaded PLGA polymeric nanoformulations were prepared by the solvent evaporation method using different experimental parameters and compatibility studies. The optimized formulations were selected for in vitro and in vivo evaluation and cytotoxicity studies. The in vitro drug release studies show a biphasic release pattern for the paclitaxel-loaded PLGA nanoparticles showing a burst release for 24 h followed by an extended release for 14 days; however, a more controlled and sustained release was observed for antibody-conjugated polymeric nanoparticles. The cytotoxicity of reference drug and paclitaxel-loaded PLGA nanoparticles with and without antibody was determined by performing MTT assay against MCF-7 cells. Rabbits were used as experimental animals for the assessment of various in vivo pharmacokinetic parameters of selected formulations. The pharmacokinetic parameters such as Cmax (1.18-1.33 folds), AUC0-t (39.38-46.55 folds), MRT (10.04-12.79 folds), t1/2 (3.06-4.6 folds), and Vd (6.96-8.38 folds) have been increased significantly while clearance (4.34-4.61 folds) has been decreased significantly for the selected nanoformulations as compared to commercially available paclitaxel formulation (Paclixil®). The surface conjugation of nanoparticles with trastuzumab resulted in an increase in in vitro cytotoxicity as compared to plain nanoformulations and commercially available conventional brand (Paclixil®). The developed PLGA-paclitaxel nanoformulations conjugated with trastuzumab have the desired physiochemical characteristics, surface morphology, sustained release kinetics, and enhanced targeting.

Improved Ocular Bioavailability of Moxifloxacin HCl using PLGA Nanoparticles: Fabrication, Characterization, In-vitro and In-vivo Evaluation.

Improving the bioavailability of a drug at the ocular surface presents a profound challenge. Due to ocular physiological barriers, conventional eye drops exhibit poor bioavailability of drugs. Sustained-release nanoparticles may improve the residence time and hence increase absorption of the drug from the corneal surface. The current study focuses on the development of a nanoparticle-based system for the ophthalmic sustained delivery of moxifloxacin, to enhance ocular retention and bioavailability of the drug. PLGA was used as the matrix-forming polymer in the nanoparticle formulation. Nanoparticles were manufactured using a double emulsion (w/o/w) solvent evaporation technique. The formulation was optimized based on physicochemical properties, including size, polydispersity index, and stability. Nanoparticles were also evaluated for in-vitro drug release and pharmacokinetic evaluation in a rabbit model. The optimized formulation exhibited a relatively high initial release rate for six hours followed by sustained release of a drug via diffusion. The in-vivo ocular tolerance studies confirmed that moxifloxacin-loaded PLGA nanoparticles were non-irritating to the eye. The pharmacokinetic studies revealed that the nanoparticles provided a high Cmax, AUC, MRT, and low clearance rate when compared to commercial eye drops. It can be concluded that such PLGA nanoparticles offer the potential for improved bioavailability of moxifloxacin HCl.

Online Kidney Stone Educational Materials Do Not Meet Recommended Readability Standards.

INTRODUCTION: The prevalence of kidney stones is rising and there is an increasing demand for reliable, easy to understand information for patients. To evaluate the readability of common Internet-based resources for kidney stones, we examined whether the most popular online educational materials may be contributing to decreased health literacy for this chronic condition. METHODS: Websites for readability analysis were chosen based on a Google.com search using the search term "kidney stones." The top 10 websites were chosen for analysis and their quality was assessed by the presence or absence of a HONcode certificate. Readability was determined using 6 readability assessment tools: Flesch Reading Ease, FORCAST, Fry, Gunning Fog, Raygor Estimate and Simple Measure of Gobbledygook. Each website was then analyzed by subsections, with emphasis on the treatment and prevention of kidney stones. RESULTS: Of the 10 websites analyzed 8 had HONcode certification. Grade level calculations ranged from 7-13.9. All 10 websites were found to have readability levels above the recommended sixth-grade reading level. Mean Flesch Reading Ease score was 59 (range 47-73). With respect to treatment and prevention sections, 6/10 and 5/10 websites had readability levels above a tenth-grade level, respectively. CONCLUSIONS: The most commonly accessed websites regarding kidney stones have readability scores above what is comprehensible to the general public, with most exceeding grade level recommendations from the American Medical Association. Websites pertaining to kidney stones need to be simplified to facilitate patient understanding, especially with respect to the treatment and prevention of kidney stones.

Correlation of refractory hypoxemia with biochemical markers and clinical outcomes of COVID-19 patients in a developing country: A retrospective observational study: Running head: Predictors of hypoxemia in COVID-19.

INTRODUCTION: COVID-19 is mainly a respiratory illness, causing hypoxemia in the majority of those been infected. In our study, we aimed to correlate the biochemical markers with hypoxemia and predicting the prognosis of COVID-19 patients. MATERIALS AND METHODS: A retrospective, observational study was conducted to include all the admitted COVID-19 patients (n = 183) diagnosed by a real-time Polymerase chain reaction and evaluated those for hypoxemia and disease outcomes by utilizing the biochemical markers. RESULTS: Out of the 183 patients, 117 were in the ward, 66 were in ICU, 148 of them recovered, while 35 deaths were reported, 89 patients were having persisting hypoxemia (despite oxygen therapy) during the hospital stay, and the remaining 94 were non-hypoxemic with or without supplemental oxygen therapy. There were significant differences in mean hemoglobin (p = 0.028), total leukocyte count (p = 0.005), Neutrophil-to-Lymphocyte ratio (p = 0.001), serum urea and creatinine (p = 0.002), serum potassium (p = 0.009), C-reactive protein (p = 0.001), Lactate dehydrogenase (p = 0.005), and Ferritin (p = 0.042) of the hypoxemic patients versus non-hypoxemic group. Amongst the deceased patients, there was significant leukocytosis (p = 0.008), increased Neutrophil-to-Lymphocyte ratio (p = 0.001), elevated C-reactive protein (p = 0.001), and Lactate dehydrogenase (p = 0.009). Receiver operating characteristic curves showed Neutrophil-to-Lymphocyte ratio (p < 0.001), C-reactive protein (p < 0.001), and Lactate dehydrogenase (p < 0.001) most significantly associated with hypoxemia and death. CONCLUSION: The inflammatory markers are a good guide for predicting the hypoxemia and disease outcome. The results concluded Neutrophil-to-Lymphocyte ratio, C-reactive protein, and Lactate dehydrogenase were effective biomarkers in predicting a severe course of COVID-19, but could not establish significant associations of serum Ferritin, Procalcitonin, and D-Dimer.

Regulation of the human cardiac mitochondrial Ca2+ uptake by 2 different voltage-gated Ca2+ channels.

BACKGROUND: Impairment of intracellular Ca(2+) homeostasis and mitochondrial function has been implicated in the development of cardiomyopathy. Mitochondrial Ca(2+) uptake is thought to be mediated by the Ca(2+) uniporter (MCU) and a thus far speculative non-MCU pathway. However, the identity and properties of these pathways are a matter of intense debate, and possible functional alterations in diseased states have remained elusive. METHODS AND RESULTS: By patch clamping the inner membrane of mitochondria from nonfailing and failing human hearts, we have identified 2 previously unknown Ca(2+)-selective channels, referred to as mCa1 and mCa2. Both channels are voltage dependent but differ significantly in gating parameters. Compared with mCa2 channels, mCa1 channels exhibit a higher single-channel amplitude, shorter openings, a lower open probability, and 3 to 5 subconductance states. Similar to the MCU, mCa1 is inhibited by 200 nmol/L ruthenium 360, whereas mCa2 is insensitive to 200 nmol/L ruthenium 360 and reduced only by very high concentrations (10 micromol/L). Both mitochondrial Ca(2+) channels are unaffected by blockers of other possibly Ca(2+)-conducting mitochondrial pores but were activated by spermine (1 mmol/L). Notably, activity of mCa1 and mCa2 channels is decreased in failing compared with nonfailing heart conditions, making them less effective for Ca(2+) uptake and likely Ca(2+)-induced metabolism. CONCLUSIONS: Thus, we conclude that the human mitochondrial Ca(2+) uptake is mediated by these 2 distinct Ca(2+) channels, which are functionally impaired in heart failure. Current properties reveal that the mCa1 channel underlies the human MCU and that the mCa2 channel is responsible for the ruthenium red-insensitive/low-sensitivity non-MCU-type mitochondrial Ca(2+) uptake.