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Medication nonadherence is a known problem after renal transplantation and can vary from one setting to another. Since it can lead to negative outcomes, it is important to develop intervention strategies to enhance adherence in a given setting using determinants identified through exploratory studies. We explored nonadherence in renal transplant recipients. A longitudinal survey was done with adult renal transplant recipients at a tertiary care public and two private hospitals of Kolkata. Subjects were followed-up for 1 year. After screening for medication adherence status by the four-item Morisky Medication Adherence Scale, those admitting to potential nonadherence were probed further. A patient was deemed to be nonadherent if failing to take medicines on appointed time (doses missed or delayed by more than 2 h) more than three times in any month during the observation period. A pretested questionnaire was used to explore potential determinants of nonadherence. Data of 153 patients recruited over a 2-year were analyzed. The extent of nonadherence with immunosuppressant regimens was about 31% overall; 44% in the public sector and 19% in the private sector (P < 0.001). Nonadherence with other medication was around 19% in both the sectors. Several potential demographic, socioeconomic and psychosocial determinants of nonadherence were identified on univariate analysis. However, logistic regression analysis singled out only the economic status. This study had updated the issue of nonadherence in renal transplant recipients in the Indian setting. Strategies to improve medication adherence can be planned by relevant stakeholders on the basis of these findings. [ABSTRACT FROM AUTHOR]

With one-third of the population living in drought-prone areas, Africa is considered the most vulnerable continent to climate change. This article reviews the impacts of population growth and climate change on water resources across eight East African countries, namely, Ethiopia, Kenya, Malawi, Mozambique, Rwanda, Uganda, Tanzania, and Zambia. Total population in the region is projected to exceed 800 million by 2060 and 1,150 million by 2090, compared to 286 million in 2012. Based on per capita water availability, six of the eight countries are either already water stressed or close to it. By the end of this century, per capita water availability will drop to water scarcity level in all the countries reviewed except Mozambique. ENSO is currently a dominant force that drives the climate in the region; however, future changes in this phenomenon are not well understood. Temperature projections show a 0.9°C to 3.4°C increase by the 2060s and 1.3°C to 5.5°C increase by the 2090s. However, precipitation projections are less certain in both the direction and magnitude of change, although the projections are more inclined toward positive change. For example, findings from an ensemble of models under the A2, A1B, and B1 scenarios projected a 15% reduction to a 48% increase in precipitation by 2090 in the countries studied. Projected runoff trends are largely dependent on precipitation variability and short-term rainfall distribution, which are highly uncertain in future climate scenarios. Although climate models are uncertain, runoff is generally predicted to increase in the eastern part of the region and decrease in the southern part. Glaciers and ice covers in the region are projected to disappear in next few decades; however, the impact of this disappearance on water resources in the region is predicted to be minimal. Evaporative demand is projected to increase with the increase in temperature and may reach as much as 53%, increasing water demand and moisture stress. Groundwater resources are more resilient than surface water resources; however, there is an overall lack of knowledge on how groundwater responds to climate change at the local scale. In order to mitigate the impact of climate change on water resources, water conservation and development of irrigation facilities have been recommended. [ABSTRACT FROM AUTHOR]

Ozone (O 3 ) is a ubiquitous pollutant known to produce acute, transient inflammation through oxidative injury and inflammation. These effects are exacerbated in susceptible populations, such as the elderly and those exhibiting genetic mutations in central nodes of pulmonary function. To comprehend the impact of these predisposing factors, the present study examines structural, mechanical, and immunological responses to single acute O 3 exposure (0.8 ppm, 3h) in young (8-14 week old), middle-aged (44-52 week old), and old (>80 week old) mice. Furthermore, this work compares the impact of a clinically relevant mutation in the gene encoding for the alveolar epithelial type 2 specific surfactant protein C. Aging was associated with reduced lung resistance and increases in respiratory elastic properties, the latter of which was exacerbated in SP-C mutant mice. Ozone exposure produced focal injury localized at the terminal bronchiole-to-alveolar junctions and enlarged alveoli in aged SP-C mutant lungs. Flow cytometric analysis revealed increases in mononuclear myeloid abundance in aged SP-C mutant lungs, paired with a contraction in CD8 + expressing cells. Expansion of tertiary lymphoid tissues was also noted in aged groups, more evident in the mutant mice. Spatial transcriptomics of CD68 + macrophages and CD45 - non-immune parenchymal cells highlighted age-dependent shifts in inflammatory and extracellular matrix organization signaling, and enrichment in senescence and chromatin remodeling pathways. These results illustrate the structural and immunological impact of O 3 in the aging wild type and mutant lung and emphasize the significance of modeling environmental exposure in at-risk populations.

Over the past two decades, the utilization of protein cages has witnessed exponential growth driven by their extensive applications in biotechnology and therapeutics. In the context of the recent Covid-19 pandemic, protein-cage-based scaffolds played a pivotal role in vaccine development. Beyond vaccines, these protein cages have proven valuable in diverse drug delivery applications thanks to their distinctive architecture and structural stability. Among the various types of protein cages, ferritin-based cages have taken the lead in drug delivery applications. This is primarily attributed to their ease of production, exceptional thermal stability, and nontoxic nature. While ferritin-based cages are commonly employed in anticancer drug delivery and contrast agent delivery, their efficacy in malarial drug delivery had not been explored until this study. In this investigation, several antimalarial drugs were encapsulated within horse spleen ferritin, and the binding and loading processes were validated through both experimental and computational techniques. The data unequivocally demonstrate the facile incorporation of antimalarial drugs into ferritin without disrupting its three-dimensional structure. Computational docking and molecular dynamics simulations were employed to pinpoint the precise location of the drug binding site within ferritin. Subsequent efficacy testing on Plasmodium revealed that the developed nanoconjugate, comprising the drug-ferritin conjugate, exhibited significant effectiveness in eradicating the parasite. In conclusion, the findings strongly indicate that ferritin-based carrier systems hold tremendous promise for the future of antimalarial drug delivery, offering high selectivity and limited side effects.

A novel calcium-based metal-organic framework (CaMOF@LSB) was designed and synthesized, exhibiting dual functionality for both selective detection and removal of Cu 2+ ions from aqueous solutions. The framework's stability, including solvent and pH variations, was established with notable thermal resilience. Colorimetric Cu 2+ detection (≥5 ppm) with a high capture capacity of 484.2 mg g -1 by CaMOF@LSB places this material among the few that ensure efficient colorimetric detection and high removal capabilities of Cu 2+ ions. Batch adsorption experiments revealed pH-dependent behavior and competitive interactions. Langmuir and pseudo-second-order kinetics models aptly described adsorption isotherms and kinetics, respectively. Thermodynamic assessments confirmed spontaneous and endothermic adsorption. Mechanistically, nanoparticle deposition contributes to the Cu 2+ uptake. CaMOF@LSB also exhibited one of the best removal behaviour of Cu 2+ by means of oxide formation on the surface. Regeneration of CaMOF@LSB was achieved by simple sonication in 0.1 M aqueous NaOH solution. The recyclability was also tested up to 5 cycles, and it exhibited a small decrease in adsorption capacity observed across the cycles. This research presents a promising avenue for addressing heavy metal pollution using metal-organic frameworks, thereby offering potential applications in water purification and environmental pollution monitoring and remediation., (© 2024 Wiley-VCH GmbH.)

The lung is constantly exposed to a myriad of exogenous stressors. Ground-level ozone represents a ubiquitous and extremely reactive anthropogenic toxicant, impacting the health of millions across the globe. While abundant, epidemiological, in vivo , and in vitro data focuses the ozone toxicity in individual cell types (e.g. epithelial type II, alveolar macrophages) or signaling pathways involved in the injury (e.g., akt, glutathione). When appropriately used, bulk and single cell RNA sequencing techniques have the potential to provide complete, and in certain cases unbiased, information of the molecular events taking place in the steady state and injured lung, and even capture the phenotypic diversity of neighboring cells. To this end, this review compiles information pertaining to the latest understanding of lung cell identity and activation in the steady state and ozone exposed lung. In addition, it discusses the value and benefits of multi-omics approaches and other tools developed to predict cell-cell communication and dissect spatial heterogeneity., Competing Interests: Conflict of Interest: The authors declare that no conflict of interest exists.

Anatomical configurations where the viscero-atrial structures do not follow the usual arrangement or mirror-imaged arrangement is described conventionally as heterotaxy. Isomerism in the context of the congenitally malformed heart is a situation where some paired structures on opposite sides of the left-right axis of the body are, in morphologic terms, symmetrical mirror images of each other. It encompasses two separate entities, right and left isomerism, the former being usually associated with asplenia and the latter with polysplenia. We report herein a rare case of left isomerism that is associated with asplenia in a 4-year-old girl., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Annals of Pediatric Cardiology.)

The Retinoid X receptor alpha-Thyroid hormone receptor beta (RXRα-THRβ) heterodimer plays an important role in physiological function of humans specially in the growth and development. Extensive MD-simulation studies on the aquated complexes of modelled RXRα-THRβ heterodimer with DNA-duplex have indicated the role of some conserved/semiconserved water molecules in the complexation process in presence or absence of Triiodothyronine (T3) and 9-cis retinoic acid (9CR) in the respective Ligand Binding Domain (LBD) domain. Among the seventeen conserved/semi-conserved water molecules, the W1-W4 water centers have been observed to mediate the interaction between the residues of A-chain (DBD of RXR) to consensus sequence (C-chain) of DNA. The W5-W8 water centers involve in recognition of the residues of B-chain (DBD of THR) to C-chain of DNA. The W9-W13 centers have connected the different residues of B-chain (THR) to D-chain of DNA through H-bonds, whereas W14-W17 water molecules were involved in the interaction of A-chain ' s (RXR) residues to D-chain of DNA. In our previous study with homodimeric THRβ from Rattus norvegicus we have identified fifteen conserved water molecules at the DNA-DBD interface. Moreover, the conformational flexibility of Met313 (in the LBD of THR) from open to close form in presence or absence of T3 molecule in the holo and Apo-protein may provide a plausible rational on the possible role of that residue to acts as gate which could restrict the solvent molecules to enter into the hydrophobic T3-binding pocket of LBD during the absence of ligand molecule and thus could help the stabilization of that domain in THRβ structure.Communicated by Ramaswamy H. Sarma.

Septoria nodorum blotch (SNB), caused by Parastagonospora nodorum , is a major disease of winter wheat that occurs frequently in the central and southeastern United States. Quantitative resistance to SNB in wheat is determined by various disease resistance components and their interaction with environmental factors. A study was conducted in North Carolina from 2018 to 2020 to characterize SNB lesion size and growth rate and to quantify the effects of temperature and relative humidity on lesion expansion in winter wheat cultivars with different levels of resistance. Disease was initiated in the field by spreading P. nodorum -infected wheat straw in experimental plots. Cohorts (groups of foliar lesions arbitrarily selected and tagged as an observational unit) were sequentially selected and monitored throughout each season. Lesion area was measured at regular intervals, and weather data were collected using in-field data loggers and the nearest weather stations. Final mean lesion area was approximately seven times greater on susceptible than on moderately resistant cultivars, and lesion growth rate was approximately four times higher on susceptible than on moderately resistant cultivars. Across trials and cultivars, temperature had a strong effect of increasing lesion growth rates ( P < 0.001), while relative humidity had no significant effect ( P = 0.34). Lesion growth rate declined slightly and steadily over the duration of cohort assessment. Our results demonstrate that restricting lesion growth is an important component of SNB resistance in the field and suggest that the ability to limit lesion size may be a useful breeding goal., Competing Interests: The author(s) declare no conflict of interest.

Background: The gut microbiome is a critical modulator of host immunity and is linked to the immune response to respiratory viral infections. However, few studies have gone beyond describing broad compositional alterations in severe COVID-19, defined as acute respiratory or other organ failure., Methods: We profiled 127 hospitalized patients with COVID-19 (n = 79 with severe COVID-19 and 48 with moderate) who collectively provided 241 stool samples from April 2020 to May 2021 to identify links between COVID-19 severity and gut microbial taxa, their biochemical pathways, and stool metabolites., Results: Forty-eight species were associated with severe disease after accounting for antibiotic use, age, sex, and various comorbidities. These included significant in-hospital depletions of Fusicatenibacter saccharivorans and Roseburia hominis, each previously linked to post-acute COVID syndrome or "long COVID," suggesting these microbes may serve as early biomarkers for the eventual development of long COVID. A random forest classifier achieved excellent performance when tasked with classifying whether stool was obtained from patients with severe vs. moderate COVID-19, a finding that was externally validated in an independent cohort. Dedicated network analyses demonstrated fragile microbial ecology in severe disease, characterized by fracturing of clusters and reduced negative selection. We also observed shifts in predicted stool metabolite pools, implicating perturbed bile acid metabolism in severe disease., Conclusions: Here, we show that the gut microbiome differentiates individuals with a more severe disease course after infection with COVID-19 and offer several tractable and biologically plausible mechanisms through which gut microbial communities may influence COVID-19 disease course. Further studies are needed to expand upon these observations to better leverage the gut microbiome as a potential biomarker for disease severity and as a target for therapeutic intervention., (© 2023. The Author(s).)

Prediction models that aid growers in making decisions on timing of fungicide application are important components of integrated management programs for several foliar diseases of wheat. The risk of Septoria nodorum blotch (caused by Parastagonospora nodorum ) onset in winter wheat has been reported to be influenced by location, amount of wheat residue in the field, and cumulative daily infection values 2 weeks prior to day of year (DOY) 102. A model previously developed based on these predictor variables was evaluated for its ability to predict disease onset under field conditions. An experiment was conducted at three locations in North Carolina in 2018, 2019, and 2020, where plots were either treated with >20% wheat residue or received no residue treatment. Plots were monitored for disease symptoms, and disease onset was defined to have occurred when mean disease incidence in a plot was 50%. Of the 298 disease cases recorded, disease onset occurred early (i.e., prior to DOY 102) in 257 cases, while onset was late (i.e., on or after DOY 102) in 41 cases. Model accuracy based on correct classification ranged from 0.67 to 0.95, with a mean of 0.87 across the study period. Similarly, sensitivity rates of the model ranged from 0.88 to 1.0 with a mean of 0.98 across all years. However, the model had low specificity, with a mean rate of 0.15 across the study period. Overall, there was no significant difference in the frequency of observed and predicted cases in the study (χ 2 = 0.50, P = 0.7788, df = 2). Time to disease onset was significantly correlated with grain yield and explained 26% of variation in yield ( P < 0.0001). Results indicated that the disease onset model performs well in predicting early disease onset but requires further evaluation and improvement, particularly in the Piedmont, where it over-predicted early onset in 2 successive years.

Two multiyear field trials were conducted to evaluate boxwood cultivars for their susceptibility to the blight pathogens Calonectria pseudonaviculata and C. henricotiae in northern Germany. Fifteen cultivars were included in the first trial from 2007 to 2012, and 46 cultivars were included in the second trial from 2014 to 2017. Both trials were done in a naturally infested field that was supplemented with infected plant tissue added to the soil before planting. Each cultivar had three replicate hedge sections with 10 plants per section, and they were assessed annually for blight severity expressed as proportion of leaves blighted and fallen. Blight severity varied significantly among years ( P < 0.0001) and cultivars ( P < 0.05) within each trial. In the first trial, mean severity ranged from 0.03 to 0.11 for the most resistant cultivars and 0.35 to 0.96 for the most susceptible ones. Similarly, in the second trial, mean severity ranged from 0.06 to 0.27 and 0.71 to 0.97 for the most resistant and susceptible cultivars, respectively. 'Suffruticosa' was consistently the most susceptible cultivar, followed by 'Marianne', 'Myosotidifolia', 'Raket', and 'Morris Midget'. 'Herrenhausen' was the most resistant cultivar, followed by B. microphylla var. japonica , B. microphylla var. koreana , 'Green Mound', 'Faulkner', and 'Winter Beauty'. This study provides field data showing the performance of boxwood cultivars under different levels of disease pressure in an area where C. henricotiae was dominant. This knowledge will help boxwood growers and gardeners to choose less susceptible cultivars and help plant breeders to select for disease resistance.

The weighted ensemble (WE) strategy has been demonstrated to be highly efficient in generating pathways and rate constants for rare events such as protein folding and protein binding using atomistic molecular dynamics simulations. Here we present two sets of tutorials instructing users in the best practices for preparing, carrying out, and analyzing WE simulations for various applications using the WESTPA software. The first set of more basic tutorials describes a range of simulation types, from a molecular association process in explicit solvent to more complex processes such as host-guest association, peptide conformational sampling, and protein folding. The second set ecompasses six advanced tutorials instructing users in the best practices of using key new features and plugins/extensions of the WESTPA 2.0 software package, which consists of major upgrades for larger systems and/or slower processes. The advanced tutorials demonstrate the use of the following key features: (i) a generalized resampler module for the creation of "binless" schemes, (ii) a minimal adaptive binning scheme for more efficient surmounting of free energy barriers, (iii) streamlined handling of large simulation datasets using an HDF5 framework, (iv) two different schemes for more efficient rate-constant estimation, (v) a Python API for simplified analysis of WE simulations, and (vi) plugins/extensions for Markovian Weighted Ensemble Milestoning and WE rule-based modeling for systems biology models. Applications of the advanced tutorials include atomistic and non-spatial models, and consist of complex processes such as protein folding and the membrane permeability of a drug-like molecule. Users are expected to already have significant experience with running conventional molecular dynamics or systems biology simulations., Competing Interests: 10Potentially Conflicting Interests The authors declare the following competing financial interests): L.T.C. is a current member of the Scientific Advisory Board of OpenEye Scientific and an Open Science Fellow with Psivant Sciences. S Zhang, JP Thompson, and DN LeBard are employees of OpenEye Scientific.

Antibiotics, the primary drugs used to cure bacterial diseases, are increasingly becoming ineffective due to the emergence of multiple drug resistance (MDR) leading to recurrence of previously sensitive pathogens. Human gut microbiome (GM), known to play an important role in various physiological processes, consists of pool of diverse microbes. Indiscriminate use of antibiotics during the life span of an individual may lead to development of resistant microbes e.g. Vibrio, Acinetobacter, Escherichia, Klebsiella, Clostridia, etc. in the human GM. Transmission of antibiotic resistant genes (ARGs) between pathogenic and commensal bacteria occurs more frequently in microbiome communities wherein bacteria communicate and exchange cellular constituents both among themselves and with the host. Additionally, co-factors like 'early vs. late' exposure, type of antibiotics and duration of treatment modulate the adverse effects of antibiotics on GM maturation. Furthermore, factors like mode of birth, ethnicity, malnutrition, demography, diet, lifestyle, etc., which influence GM composition, can also indirectly alter the host response to antibiotics. Currently, advanced 'omics' and culturomics approaches are revealing novel avenues to study the interplay between antibiotics and the microbiome and to identify resistant genes in these bacterial communities. Here, we discuss the recent developments that have given insights into the effects of antibiotics on the homeostatic balance of the gut microbiome and thus on human health., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Introduction and Importance: Amyand hernia is an accidental finding that occurs in 0.19-1.7% of patients with inguinal hernia, with children being more commonly affected than adults. However, the management depends on the guidelines given by Losanoff and Basson., Case Presentation: A 62-year-old male presented with complaints of progressive swelling in the right inguinal region without any clinical spectrum of bowel obstruction or strangulation. Examination revealed a right-sided indirect inguinal hernia with positive Ziemann technique. Open hernioplasty revealed an appendix within a hernia sac and was found to be adhered to the surrounding structure with a fibrotic band. According to the Losanoff and Basson protocol, the patient had an appendectomy and an open mesh repair with polypropylene mesh without any post-operative complications., Clinical Discussion: Amyand hernia are often predominantly present in children, with a rare presence in the elderly. Pre-operative clinical diagnosis remains a challenge, and the management depends upon the Losanoff and Basson protocol. Appendectomy of the normal appendix within the hernia sac is often recommended to prevent the sequelae (appendicitis, rupture) following manipulation during hernioplasty., Conclusion: Amyand's hernia is a rare clinical entity and difficult to diagnose due to its uncomplicated presentation. Nevertheless, the progress of appendix inflammation, the possibility of abdominal sepsis, and co-morbidities should all be taken into consideration when deciding how to manage individual patients., (© 2022 The Authors.)

SARS-CoV-2 can cause acute respiratory distress and death in some patients 1 . Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear 2 . Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) and the release of potent inflammatory mediators 3 . Here we show that about 6% of blood monocytes of patients with COVID-19 are infected with SARS-CoV-2. Monocyte infection depends on the uptake of antibody-opsonized virus by Fcγ receptors. The plasma of vaccine recipients does not promote antibody-dependent monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in the supernatants of cultures of infected monocytes. Instead, infected cells undergo pyroptosis mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and gasdermin D. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from lung autopsies from patients with COVID-19 have activated inflammasomes. Taken together, these findings suggest that antibody-mediated SARS-CoV-2 uptake by monocytes and macrophages triggers inflammatory cell death that aborts the production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: This work aims to examine the vitreous of autopsy patients with COVID-19 for the presence of SARS-CoV-2 RNA., Methods: Four deceased patients with COVID-19 had an autopsy at Massachusetts General Hospital. Two control specimens were obtained from patients undergoing retinal detachment repair with negative preoperative polymerase chain reaction (PCR) testing for SARS-CoV-2 RNA. Vitreous specimens were obtained from autopsy patients with COVID-19 after povidone was placed on the ocular surface to decrease the risk of contamination of the vitreous specimen. SARS-CoV-2 RNA for gene N (nucleocapsid) was tested using reverse transcription-PCR., Results: SARS-CoV-2 RNA was detected in the vitreous of 2 of 4 autopsy patients who died from complications of COVID-19., Conclusions: SARS-CoV-2 RNA can penetrate into the vitreous of systemically infected patients, which might present risks to operating room personnel during ophthalmic surgical procedures., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Anterior cruciate ligament is a commonly injured and reconstructed ligament in the knee. Unlike in urban areas where sports activities and road accidents are common mechanisms of injuries, the semi-urban and rural population has a different mode of injuries, needs, and expectations. This study explores the prevalence of successful outcome of anterior cruciate ligament reconstruction in by hamstring tendon for anterior cruciate ligament deficit knee at a university hospital., Methods: A descriptive cross-sectional study was conducted at Dhulikhel Hospital, Kathmandu University Hospital from 2018 February to 2020 January among patients having anterior cruciate ligament injuries after ethical approval. Whole sampling technique was used. Functional outcome was assessed with Lysholm scale at the end of at least one year. Data was analysed using Statistical Package for Social Sciences version 11. Point estimate at 95% Confidence Interval was calculated, with frequency and percentage., Results: Out of 66 anterior cruciate ligament reconstruction, 35 (59%) cases had successful outcomes. Excellent outcomes were seen in 9 (15%) cases and 26 (44%) had good outcomes. The mean Lysholm score was 84., Conclusions: Anterior cruciate ligament injuries were seen in heterogeneous populations during their activities of daily living or recreational sports activities. Anatomic anterior cruciate ligamentreconstruction with hamstring grafts provided good functional outcomes, especially among the young population. Our findings are similar to current studies on anterior cruciate ligament-reconstruction.

Pregnant individuals infected with SARS-CoV-2 have higher rates of intensive care unit admission, oxygen requirement, need for mechanical ventilation, and death than nonpregnant individuals. Increased COVID-19 disease severity may be associated with an increased risk of viremia and placental infection. Maternal SARS-CoV-2 infection is also associated with pregnancy complications such as preeclampsia and preterm birth, which can be either placentally mediated or reflected in the placenta. Maternal viremia followed by placental infection may lead to maternal-fetal transmission (vertical), which affects 1% to 3% of exposed newborns. However, there is no agreed-upon or standard definition of placental infection. The National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development convened a group of experts to propose a working definition of placental infection to inform ongoing studies of SARS-CoV-2 during pregnancy. Experts recommended that placental infection be defined using techniques that allow virus detection and localization in placental tissue by one or more of the following methods: in situ hybridization with antisense probe (detects replication) or a sense probe (detects viral messenger RNA) or immunohistochemistry to detect viral nucleocapsid or spike proteins. If the abovementioned methods are not possible, reverse transcription polymerase chain reaction detection or quantification of viral RNA in placental homogenates, or electron microscopy are alternative approaches. A graded classification for the likelihood of placental infection as definitive, probable, possible, and unlikely was proposed. Manuscripts reporting placental infection should describe the sampling method (location and number of samples collected), method of preservation of tissue, and detection technique. Recommendations were made for the handling of the placenta, examination, and sampling and the use of validated reagents and sample protocols (included as appendices)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The spread of novel coronavirus strain, Severe Acute Respiratory Syndrome 2 (SARS-CoV-2) causes Coronavirus disease (COVID-19) has now spread worldwide and effecting the entire human race. The viral genetic material is transcripted and replicated by 3 C-like protease, as a result, it is an important drug target for COVID-19. Hydroxychloroquine (HCQ) report promising results against this drug target so, we perform molecular docking followed by MD-simulation studies of HCQ and modelled some ligand (Mod-I and Mod-II) molecules with SARS-CoV-2-main protease which reveals the structural organization of the active site residues and presence of a conserve water-mediated catalytic triad that helps in the recognition of Mod-I/II ligand molecules. The study may be helpful to gain a detailed structural insight on the presence of water-mediated catalytic triad which could be useful for inhibitor modelling. Communicated by Ramaswamy H. Sarma.

Sphingolipids are both structural molecules that are essential for cell architecture and second messengers that are involved in numerous cell functions. Ceramide is the central hub of sphingolipid metabolism. In addition to being the precursor of complex sphingolipids, ceramides induce cell cycle arrest and promote cell death and inflammation. At least some of the enzymes involved in the regulation of sphingolipid metabolism are altered in carcinogenesis, and some are targets for anticancer drugs. A number of scientific reports have shown how alterations in sphingolipid pools can affect cell proliferation, survival and migration. Determination of sphingolipid levels and the regulation of the enzymes that are implicated in their metabolism is a key factor for developing novel therapeutic strategies or improving conventional therapies. The present review highlights the importance of bioactive sphingolipids and their regulatory enzymes as targets for therapeutic interventions with especial emphasis in carcinogenesis and cancer dissemination.

Thyroid hormone receptor (THR) belongs to the nuclear receptor (NR) superfamily that is activated by binding of appropriate ligand molecules (thyroid hormones). These receptors directly bind to specific DNA sequences for gene expression, which is essential for metabolism, homeostasis, and the development of organisms, making it an important drug target. Extensive MD-simulation studies of triiodothyronine (T3) docked modeled rnTHRβ1 structures have indicated the presence of twelve conserved water molecules at the DNA-DBD (DNA binding domain) interface. The W1-W5 water centers have been involved in the recognition between the A-chain of DBD to C-chain of DNA, W6 and W7 mediated the interaction between A-chain of DBD and D-chain of DNA, W8 and W9 recognized the B-chain of DBD and C-chain of DNA, and W9-W12 centers conjugated the residues of B-chain of DBD to D-chain of DNA through hydrogen bonds. The conformation flexibility of Phe272 and Met313 residues in the absence of T3 at the LBD (ligand-binding domain) region have been observed and reported.

Electrospun nanofiber (EN) technology has been used in the past to generate electrostatically charged multilayer-nanofibers. This platform offers versatile applications including in tissue engineering, drug delivery, wound dressings, and high-efficiency particulate air filters. In this study, we synthesized for the first time nanonet-nanofiber electrospun meshes (NNEMs) of polycaprolactone (PCL)-chitosan (CH) using EN technology. The fabricated NNEMs were utilized for high payload delivery and controlled release of a water-soluble drug. Diclofenac Sodium (DS), a hydrophilic anti-inflammatory drug, was selected as a model drug because of its high aqueous solubility and poor compatibility with insoluble polymers. Various compositions of DS drug-loaded NNEMs (DS-NNEMs) were synthesized. The physicochemical properties such as structure, morphology, and aqueous stability and the chemical properties of DS-NNEMs were evaluated. High drug entrapment efficiency and concentration-dependent drug release patterns were investigated for up to 14 days. Furthermore, the biocompatibility of the DS-NNEMs was tested with NIH 3T3 cells. The physicochemical characterization results showed that the DS drug is a key contributing factor in the generation of nanonet-nanofiber networks during electrospinning. DS-NNEMs also enhanced 3T3 cell adhesion, viability, and proliferation in the nanonet-nano fiber network through the controlled release of DS. The presented EN technology-based biodegradable NNEM material is not only limited for the controlled release of hydrophilic anti-inflammatory drugs, but also can be a suitable platform for loading and release of antiviral drugs.

Handwashing with soap is an effective and economical means to reduce the likelihood of Escherichia coli infection from indirect contact with contaminated surfaces during food preparation. The purpose of this study was to conduct a quantitative microbial risk assessment (QMRA) to evaluate the risk of infection from indirect contact with fomites contaminated with E. coli after hand washing with antimicrobial hand soaps. A Monte Carlo simulation was done with a total of 10,000 simulations to compare the effectiveness of two antimicrobial and one control (non-antimicrobial) bar soaps in reducing the exposure and infection risk compared to no hand washing. The numbers of E. coli on several fomites commonly found in household kitchens, as well as the transfer rates between fomites and onto fingertips, were collected from the literature and experimental data. The sponsor company provided the E. coli survival on hands after washing with antimicrobial and control soaps. A number of scenarios were evaluated at two different exposure doses (high and low). Exposure scenarios included transfer of E. coli between meat-to-cutting board surface-to-hands, meat-to-knife surface-to-hands, and from a countertop surface-to-hands, kitchen sponge-to-hands, hand towel-to-hands, and dishcloth-to-hands. Results showed that the risks of illness after washing with the control soap was reduced approximately 5-fold compared to no handwashing. Washing with antimicrobial soap reduced the risk of E. coli infection by an average of about 40-fold compared with no handwashing. The antimicrobial soaps ranged from 3 to 32 times more effective than the non-antimicrobial soap, depending on the specific exposure scenario. Importance: The Centers for Disease Control and Prevention indicate the yearly incidence rate of Shiga Toxin producing E. coli infections is about 1.7/100,000, with about 10% of cases leading to life-threatening hemolytic uremic syndrome and 3-5% leading to death. Our findings confirm handwashing with soap reduces the risks associated with indirect transmission of E. coli infection from contact with fomites during food preparation. Further, in these exposure scenarios, antimicrobial soaps were more effective overall than the non-antimicrobial soap in reducing exposure to E. coli and risk of infection.

Congenital Adrenal Hyperplasia is a group of autosomal recessive disorders due to deficiencies of enzymes involved in steroidogenesis. The most common form is a 21-hydroxylase deficiency which can be classical or non-classical. The severe form also called Classical Congenital Adrenal Hyperplasia is usually detected after birth to infant period. If Congenital Adrenal Hyperplasia is not diagnosed and treated early, neonates are susceptible to sudden death in the early weeks of life. We report a case of thirty-five days male with a salt-wasting variant of congenital adrenal hyperplasia. The diagnosis was based on an elevated level of 17-hydroxyprogesterone. He was managed and life long oral Prednisolone and Fludrocortisone were prescribed. Keywords: 21-hydroxylase, congenital adrenal hyperplasia, case report.

Middle Eastern respiratory syndrome, an emerging viral infection with a global case fatality rate of 35.5%, caused major outbreaks first in 2012 and 2015, though new cases are continuously reported around the world. Transmission is believed to mainly occur in healthcare settings through aerosolized particles. This study uses Quantitative Microbial Risk Assessment to develop a generalizable model that can assist with interpreting reported outbreak data or predict risk of infection with or without the recommended strategies. The exposure scenario includes a single index patient emitting virus-containing aerosols into the air by coughing, leading to short- and long-range airborne exposures for other patients in the same room, nurses, healthcare workers, and family visitors. Aerosol transport modeling was coupled with Monte Carlo simulation to evaluate the risk of MERS illness for the exposed population. Results from a typical scenario show the daily mean risk of infection to be the highest for the nurses and healthcare workers (8.49 × 10 -4 and 7.91 × 10 -4 , respectively), and the lowest for family visitors and patients staying in the same room (3.12 × 10 -4 and 1.29 × 10 -4 , respectively). Sensitivity analysis indicates that more than 90% of the uncertainty in the risk characterization is due to the viral concentration in saliva. Assessment of risk interventions showed that respiratory masks were found to have a greater effect in reducing the risks for all the groups evaluated (>90% risk reduction), while increasing the air exchange was effective for the other patients in the same room only (up to 58% risk reduction)., (© 2019 Society for Risk Analysis.)

. In order to determine the relationship between an exposure dose of Staphylococcus aureus ( S. a ureus ) on the skin and the risk of infection, an understanding of the bacterial growth and decay kinetics is very important. Models are essential tools for understanding and predicting bacterial kinetics and are necessary to predict the dose of organisms post-exposure that results in a skin infection. One of the challenges in modeling bacterial kinetics is the estimation of model parameters, which can be addressed using an inverse problem approach. The objective of this study is to construct a microbial kinetic model of S. aureus on human skin and use the model to predict concentrations of S. aureus that result in human infection. In order to model the growth and decay of S. aureus on skin, a Gompertz inactivation model was coupled with a Gompertz growth model. A series of analyses, including ordinary least squares regression, scaled sensitivity coefficient analysis, residual analysis, and parameter correlation analysis were conducted to estimate the parameters and to describe the model uncertainty. Based on these analyses, the proposed model parameters were estimated with high accuracy. The model was then used to develop a new dose-response model for S. aureus using the exponential dose-response model. The new S. aureus model has an optimized k parameter equivalent to 8.05 × 10 -8 with 95 th percentile confidence intervals between 6.46 × 10 -8 and 1.00 × 10 -7 ., Competing Interests: The authors declare no conflict of interest.

Magnesium (Mg) metal is of great interest in biomedical applications, especially in tissue engineering. Mg exhibits excellent in vivo biocompatibility, biodegradability and, during degradation, releases Mg ions (Mg 2+ ) with the potential to improve tissue repair. We used electrospinning technology to incorporate Mg particles into nanofibers. Various ratios of Mg metal microparticles (<44 µm diameter) were incorporated into nanofiber polycaprolactone (PCL) meshes. Physicochemical properties of the meshes were analyzed by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), mechanical tensile testing, X-ray diffractometry and UV-VIS spectrophotometry. Biological properties of meshes were evaluated in vitro and in vivo. Under mammalian cell culture conditions, Mg-containing meshes released hydrogen gas and relative amounts of free Mg 2+ that reflected the Mg/PCL ratios. All meshes were non-cytotoxic for 3T3 fibroblasts and PC-12 pheochromocytoma cells. In vivo implantation under the skin of mice for 3, 8 and 28 days showed that Mg-containing meshes were well vascularized, with improved measures of inflammation and healing compared to meshes without Mg. Evidence included an earlier appearance and infiltration of tissue repairing macrophages and, after 28 days, evidence of more mature tissue remodeling. Thus, these new composite nanofiber meshes have promising material properties that mitigated inflammatory tissue responses to PCL alone and improved tissue healing, thus providing a suitable matrix for use in clinically relevant tissue engineering applications. STATEMENT OF SIGNIFICANCE: The biodegradable metal, magnesium, safely biodegrades in the body, releasing beneficial byproducts. To improve tissue delivery, magnesium metal particles were incorporated into electrospun nanofiber meshes composed of a biodegradable, biocompatible polymer, polycaprolactone (PCL). Magnesium addition, at several concentrations, did not alter PCL chemistry, but did alter physical properties. Under cell culture conditions, meshes released magnesium ions and hydrogen gas and were not cytotoxic for two cell types. After implantation in mice, the mesh with magnesium resulted in earlier appearance of M2-like, reparative macrophages and improved tissue healing versus mesh alone. This is in agreement with other studies showing beneficial effects of magnesium metal and provides a new type of scaffold material that will be useful in clinically relevant tissue engineering applications., (Published by Elsevier Ltd.)

Despite the development of massively parallel computing hardware including inexpensive graphics processing units (GPUs), it has remained infeasible to simulate the folding of atomistic proteins at room temperature using conventional molecular dynamics (MD) beyond the microsecond scale. Here, we report the folding of atomistic, implicitly solvated protein systems with folding times τ ranging from ∼10 μs to ∼100 ms using the weighted ensemble (WE) strategy in combination with GPU computing. Starting from an initial structure or set of structures, WE organizes an ensemble of GPU-accelerated MD trajectory segments via intermittent pruning and replication events to generate statistically unbiased estimates of rate constants for rare events such as folding; no biasing forces are used. Although the variance among atomistic WE folding runs is significant, multiple independent runs are used to reduce and quantify statistical uncertainty. Folding times are estimated directly from WE probability flux and from history-augmented Markov analysis of the WE data. Three systems were examined: NTL9 at low solvent viscosity (yielding τ f = 0.8-9 μs), NTL9 at water-like viscosity (τ f = 0.2-2 ms), and Protein G at low viscosity (τ f = 3-200 ms). In all cases, the folding time, uncertainty, and ensemble properties could be estimated from WE simulation; for Protein G, this characterization required significantly less overall computing than would be required to observe a single folding event with conventional MD simulations. Our results suggest that the use and calibration of force fields and solvent models for precise estimation of kinetic quantities is becoming feasible.

The weighted ensemble (WE) strategy has been demonstrated to be highly efficient in generating pathways and rate constants for rare events such as protein folding and protein binding using atomistic molecular dynamics simulations. Here we present five tutorials instructing users in the best practices for preparing, carrying out, and analyzing WE simulations for various applications using the WESTPA software. Users are expected to already have significant experience with running standard molecular dynamics simulations using the underlying dynamics engine of interest (e.g. Amber, Gromacs, OpenMM). The tutorials range from a molecular association process in explicit solvent to more complex processes such as host-guest association, peptide conformational sampling, and protein folding., Competing Interests: 9Potentially Conflicting Interests The authors declare no conflicting interests.

Agricultural nonpoint source pollution is the leading source of water quality degradation in United States, which has led to the development of programs that aim to mitigate this pollution. One common approach to mitigating nonpoint source pollution is the use of best management practices (BMPs). However, it can be challenging to evaluate the effectiveness of implemented BMPs due to polices that limit data sharing. In this study, the uncertainty introduced by data sharing limitations is quantified through the use of a watershed model. Results indicated that BMP implementation improved the overall water quality in the region (up to ∼15% pollution reduction) and that increasing the area of BMP implementation resulted in higher pollution reduction. However, the model outputs also indicated that uncertainty caused by data sharing limitations resulted in variabilities ranging from -160% to 140%. This shows the importance of data sharing among agencies to better guide current and future conservation programs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

To evaluate the corrosion inhibition efficacy of the derivatives of naturally available organics, mono and di-4-((2-hydroxyethyl)piperazin-1-yl)methyl derivatives of quercetin, a flavonoid, have been synthesized. Their potential as anti-corrosive agents is assessed for mild steel in 1 M HCl employing the weight-loss technique as well as electrochemical methods. Comparing the rate of corrosion in uninhibited and inhibited solutions as a function of temperature, the thermodynamic parameters of adsorption of these derivatives on mild steel surfaces and the kinetic parameters of the corrosion process are evaluated. These parameters together with information derived from electrochemical methods are further used to ascertain the mechanism of corrosion and mode of adsorption of inhibitors with intricate detail. Density functional theory (DFT) calculations were employed to explain the relative corrosion inhibition propensity between the studied mono and di quercetin derivatives. Molecular dynamics (MD) simulations were carried out to obtain the interaction energy between the inhibitor molecules and the metal surface. Results show that both derivatives, acting as mixed-type inhibitors, exert profound anti-corrosive influence (around 95% inhibition efficiency at 1 mM concentration at 313 K). Theoretical studies suggest that the trihydroxy chromone ring and dihydroxy phenyl ring of quercetin maintain a planar orientation with respect to each other and are adsorbed on the metal surface (mostly chemisorption).

The intestinal epithelium holds an immense regenerative capacity mobilized by intestinal stem cells (ISCs), much of it supported by Wnt pathway activation. Several unique regulatory mechanisms ensuring optimal levels of Wnt signaling have been recognized in ISCs. Here, we identify another Wnt signaling amplifier, CKIε, which is specifically upregulated in ISCs and is essential for ISC maintenance, especially in the absence of its close isoform CKIδ. Co-ablation of CKIδ/ε in the mouse gut epithelium results in rapid ISC elimination, with subsequent growth arrest, crypt-villous shrinking, and rapid mouse death. Unexpectedly, Wnt activation is preserved in all CKIδ/ε-deficient enterocyte populations, with the exception of Lgr5 + ISCs, which exhibit Dvl2-dependent Wnt signaling attenuation. CKIδ/ε-depleted gut organoids cease proliferating and die rapidly, yet survive and resume self-renewal upon reconstitution of Dvl2 expression. Our study underscores a unique regulation mode of the Wnt pathway in ISCs, possibly providing new means of stem cell enrichment for regenerative medicine., (© 2017 The Authors.)

Freshwater resources are vital for human and natural systems. However, anthropogenic activities, such as agricultural practices, have led to the degradation of the quality of these limited resources through pollutant loading. Agricultural Best Management Practices (BMPs), such as wetlands, are recommended as a valuable solution for pollutant removal. However, evaluation of their long-term impacts is difficult and requires modeling since performing in-situ monitoring is expensive and not feasible at the watershed scale. In this study, the impact of natural wetland implementation on total phosphorus reduction was evaluated both at the subwatershed and watershed levels. The study area is the Saginaw River Watershed, which is largest watershed in Michigan. The phosphorus reduction performances of four different wetland sizes (2, 4, 6, and 8 ha) were evaluated within this study area by implementing one wetland at a time in areas identified to have the highest potential for wetland restoration. The subwatershed level phosphorus loads were obtained from a calibrated Soil and Water Assessment Tool (SWAT) model. These loads were then incorporated into a wetland model (System for Urban Stormwater Treatment and Analysis IntegratioN-SUSTAIN) to evaluate phosphorus reduction at the subwatershed level and then the SWAT model was again used to route phosphorus transport to the watershed outlet. Statistical analyses were performed to evaluate the spatial impact of wetland size and placement on phosphorus reduction. Overall, the performance of 2 ha wetlands in total phosphorus reduction was significantly lower than the larger sizes at both the subwatershed and watershed levels. Regarding wetland implementation sites, wetlands located in headwaters and downstream had significantly higher phosphorus reduction than the ones located in the middle of the watershed. More specifically, wetlands implemented at distances ranging from 200 to 250 km and 50-100 km from the outlet had the highest impact on phosphorus reduction at the subwatershed and watershed levels, respectively. A multi criteria decision making (MCDM) method named VIKOR was successfully executed to identify the most suitable wetland size and location for each subwatershed considering the phosphorus reduction and economic cost associated with wetland implementation. The methods introduced in this study can be easily applied to other watersheds for selection and placement of wetlands while considering environmental benefits and economic costs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Droughts are known as the world's costliest natural disasters impacting a variety of sectors. Despite their wide range of impacts, no universal drought definition has been defined. The goal of this study is to define a universal drought index that considers drought impacts on meteorological, agricultural, hydrological, and stream health categories. Additionally, predictive drought models are developed to capture both categorical (meteorological, hydrological, and agricultural) and overall impacts of drought. In order to achieve these goals, thirteen commonly used drought indices were aggregated to develop a universal drought index named MASH. The thirteen drought indices consist of four drought indices from each meteorological, hydrological, and agricultural categories, and one from the stream health category. Cluster analysis was performed to find the three closest indices in each category. Then the closest drought indices were averaged in each category to create the categorical drought score. Finally, the categorical drought scores were simply averaged to develop the MASH drought index. In order to develop predictive drought models for each category and MASH, the ReliefF algorithm was used to rank 90 variables and select the best variable set. Using the best variable set, the adaptive neuro-fuzzy inference system (ANFIS) was used to develop drought predictive models and their accuracy was examined using the 10-fold cross validation technique. The models' predictabilities ranged from R 2  = 0.75 for MASH to R 2  = 0.98 for the hydrological drought model. The results of this study can help managers to better position resources to cope with drought by reducing drought impacts on different sectors., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Collapse of bubbles, microscopic or nanoscopic, due to their interaction with the impinging pressure wave produces a jet of particles moving in the direction of the wave. If there is a surface nearby, the high-speed jet particles hit it, and as a result damage to the surface is produced. This cavitation effect is well known and intensely studied in case of microscopic sized bubbles. It can be quite damaging to materials, including biological tissues, but it can also be beneficial when controlled, like in case of sonoporation of biological membranes for the purpose of drug delivery. Here we consider recent simulation work performed to study collapse of nanobubbles exposed to shock waves, in order to understand the detailed mechanism of the cavitation induced damage to soft materials, such as biological membranes. We also discuss the connection of the cavitation effect with the traumatic brain injury caused by blasts. Specifically, we consider possible damage to model membranes containing lipid bilayers, bilayers with embedded ion channel proteins like the ones found in neural cells and also protein assemblies found in the tight junction of the blood brain barrier.

Chitosan based porous scaffolds are of great interest in biomedical applications especially in tissue engineering because of their excellent biocompatibility in vivo , controllable degradation rate and tailorable mechanical properties. This paper presents a study of the fabrication and characterization of bioactive scaffolds made of chitosan (CS), carboxymethyl chitosan (CMC) and magnesium gluconate (MgG). Scaffolds were fabricated by subsequent freezing-induced phase separation and lyophilization of polyelectrolyte complexes of CS, CMC and MgG. The scaffolds possess uniform porosity with highly interconnected pores of 50-250 μm size range. Compressive strengths up to 400 kPa, and elastic moduli up to 5 MPa were obtained. The scaffolds were found to remain intact, retaining their original three-dimensional frameworks while testing in in-vitro conditions. These scaffolds exhibited no cytotoxicity to 3T3 fibroblast and osteoblast cells. These observations demonstrate the efficacy of this new approach to preparing scaffold materials suitable for tissue engineering applications.

To study the interaction between poloxamer molecules and lipid bilayers using molecular dynamics simulation technique with the united-atom resolution, we augmented the GROMOS force-field to include poloxamers. We validated the force-field by calculating the radii of gyration of two poloxamers, P85 and P188, solvated in water and by considering the poloxamer density distributions at the air/water interface. The emphasis of our simulations was on the study of the interaction between poloxamers and lipid bilayer. At the water/lipid bilayer interface, we observed that both poloxamers studied, P85 and P188, behaved like surfactants: the hydrophilic blocks of poloxamers became adsorbed at the polar interface, while their hydrophobic block penetrated the interface into the aliphatic tail region of the lipid bilayer. We also observed that when P85 and P188 poloxamers interacted with damaged membranes that contained pores, the hydrophobic blocks of copolymers penetrated into the membrane in the vicinity of the pore and compressed the membrane. Due to this compression, water molecules were evacuated from the pore.

Poly(lactic-co-glycolic acid) (PLGA) based nanoparticles have gained increasing attention in delivery applications due to their capability for controlled drug release characteristics, biocompatibility, and tunable mechanical, as well as degradation, properties. However, thorough study is always required while evaluating potential toxicity of the particles from dose dumping, inconsistent release and drug-polymer interactions. In this research, we developed PLGA nanoparticles modified by chitosan (CS), a cationic and pH responsive polysaccharide that bears repetitive amine groups in its backbone. We used a model drug, diclofenac sodium (DS), a nonsteroidal anti-inflammatory drug (NSAID), to study the drug loading and release characteristics. PLGA nanoparticles were synthesized by double-emulsion solvent evaporation technique. The nanoparticles were evaluated based on their particle size, surface charge, entrapment efficacy, and effect of pH in drug release profile. About 390-420 nm of average diameters and uniform morphology of the particles were confirmed by scanning electron microscope (SEM) imaging and dynamic light scattering (DLS) measurement. Chitosan coating over PLGA surface was confirmed by FTIR and DLS. Drug entrapment efficacy was up to 52%. Chitosan coated PLGA showed a pH responsive drug release in in vitro. The release was about 45% more at pH 5.5 than at pH 7.4. The results of our study indicated the development of chitosan coating over PLGA nanoparticle for pH dependent controlled release DS drug for therapeutic applications., Competing Interests: The authors declare no conflict of interest.

To study the properties of poloxamer molecules P85 and P188 and micelles containing these poloxamers in bulk water and also next to lipid bilayers, we performed coarse-grained molecular dynamics computer simulations. We used MARTINI force-field and adjusted Lennard-Jones nonbonded interaction strength parameters for poloxamer beads to take into account the presence of polarizable water. Simulations of systems containing poloxamer molecules or micelles solvated in bulk water showed that structural properties, such as radii of gyration of the molecules and micelles, agree with the ones inferred from experiments. We observed that P85 micelle is almost spherical in shape, whereas the P188 micelle is distorted from being spherical. Simulations containing systems with the water-lipid bilayer interface showed that hydrophilic blocks of poloxamers interact with lipid headgroups of the bilayer and remain at the interface, whereas hydrophobic blocks prefer to insert into the central hydrophobic region of the bilayer. Simulations containing poloxamer micelles next to lipid bilayer showed no permeation of these micelles into the bilayer. To study the "healing" properties of P188 poloxamer, we performed simulations on a system containing a P188 micelle next to "damaged" lipid bilayer containing a pore. We observed that hydrophobic chains of poloxamers got inserted into the bilayer through the pore region, ultimately closing the pore.