Publications by authors named "Avinash Patil"

95 Publications

Effect of Correction of Hyperthyroidism with Anti-thyroid Drugs on the Glycated Hemoglobin in Non-diabetic Patients with Primary Hyperthyroidism.

Int J Endocrinol Metab 2021 Jan 19;19(1):e105751. Epub 2021 Jan 19.

Department of Pathology, Sri Venkateswara Institute of Medical Sciences, Tirupati, India.

Background: Glycated hemoglobin (HbA1c) levels are dependent not only on the average blood glucose levels over the preceding 2 - 3 months but also on the turnover of erythrocytes. Hyperthyroidism is known to be associated with an increase in erythrocyte turnover that may falsely lower the HbA1c in relation to the level of glycemia.

Objectives: To assess the impact of medical correction of hyperthyroidism on HbA1c, independent of changes in the fasting plasma glucose and 2-hour post-oral glucose tolerance test plasma glucose.

Methods: Adult patients with overt hyperthyroidism (n = 36) were tested for their hemoglobin, reticulocyte percentage, HbA1c and fasting and post-oral glucose tolerance test (OGTT) 2-hour plasma glucose, both at baseline and following at least three months of near normalization of serum thyroxin on Carbimazole treatment.

Results: Correction of hyperthyroidism in 36 patients was associated with an increase in the hemoglobin (P = 0.004) and a rise in HbA1c (P = 0.025), even though no significant change was observed in both the fasting (P = 0.28) and post OGTT two-hour plasma glucose (P = 0.54). Also, the proportion of patients with HbA1c ≥ 5.7% rose from 3/36 to 10/36; P = 0.016, while the proportion of patients with either abnormal fasting or abnormal post OGTT 2-hour plasma glucose or both did not show any significant change (P = 0.5). The sensitivity of HbA1c to diagnose prediabetes increased from 20% to 50% post- treatment.

Conclusions: Glycated hemoglobin is falsely low in relation to glycemia in patients with untreated hyperthyroidism.
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http://dx.doi.org/10.5812/ijem.105751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010563PMC
January 2021

Quality of life and mental health status of hansen disease patients, attending a designated leprosy care center in South-India.

Int J Mycobacteriol 2021 Jan-Mar;10(1):31-36

Department of Community Medicine, SDM College of Medical Sciences and Hospital, Shri Dharmasthala Manjunatheshwara Unoversity, Dharwad, Karnataka, India.

Background: "Quality of life (QOL)" is relatively a new concept, which originates from the World Health Organization (WHO) "health" definition. The WHO defines "health" as a state of complete physical, mental, and social well-being and not merely an absence of disease or infirmity. It introduces a word, "well-being," which has two components, one the objective component and the second subjective component. The objective component mainly includes all the material possession by an individual, whereas the subjective component includes the perception of health by an individual, i.e., "QoL." It has been observed that most of the persons affected by Hansen's Disease (leprosy) have good economic conditions, but they continue to suffer from social, psychological, and physical problems which makes their life miserable. Hence, an attempt has been made to assess their QOL and factors determining them.

Method: A convenient sampling technique was used and 114 persons affected with Hansen's disease were studied. The study was conducted for a period of 1 year from November 2012 to October 2013. QOL was assessed using the WHO QOL-BREF Questionnaire and mental health status by the Self-Reporting Questionnaire. The results were obtained using SPSS 17.0 software, statistical tests such as Chi-square test, ANOVA, and standard multiple logistic regression analysis were used.

Results: Quality of leprosy patients was poor. The mean WHOQOL-BREF total score was below average (mean score <65). Physical QOL of leprosy was more affected in females (mean WHOQOL-BREF score = 20.80). Mental distress was more prevalent in males (74.6%) compared to females (25.4%). Presence of deformities, female sex of the patient, and advanced age of the patient showed the greatest association with adverse QOL.

Conclusion: Presence of physical disabilities or deformities and advanced age of leprosy patients adversely affect QOL of leprosy patients, whereas low level of education and poor socioeconomic status do not have a significant effect on QOL.
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http://dx.doi.org/10.4103/ijmy.ijmy_214_20DOI Listing
March 2021

Prediction of neonatal morbidity and very preterm delivery using maternal steroid biomarkers in early gestation.

PLoS One 2021 6;16(1):e0243585. Epub 2021 Jan 6.

Department of Obstetrics and Gynecology, Indiana University School of Medicine, Indianapolis, Indianapolis, United States of America.

Background: Preterm delivery is a common pregnancy complication that can result in significant neonatal morbidity and mortality. Limited tools exist to predict preterm birth, and none to predict neonatal morbidity, from early in pregnancy. The objective of this study was to determine if the progesterone metabolites 11-deoxycorticosterone (DOC) and 16-alpha hydroxyprogesterone (16α-OHP), when combined with patient demographic and obstetric history known during the pregnancy, are predictive of preterm delivery-associated neonatal morbidity, neonatal length of stay, and risk for spontaneous preterm delivery prior to 32 weeks' gestation.

Methods And Findings: We conducted a cohort study of pregnant women with plasma samples collected as part of Building Blocks of Pregnancy Biobank at the Indiana University School of Medicine. The progesterone metabolites, DOC and 16α-OHP, were quantified by mass spectroscopy from the plasma of 58 pregnant women collected in the late first trimester/early second trimester. Steroid levels were combined with patient demographic and obstetric history data in multivariable logistic regression models. The primary outcome was composite neonatal morbidity as measured by the Hassan scale. Secondary outcomes included neonatal length of stay and spontaneous preterm delivery prior to 32 weeks' gestation. The final neonatal morbidity model, which incorporated antenatal corticosteroid exposure and fetal sex, was able to predict high morbidity (Hassan score ≥ 2) with an area under the ROC curve (AUROC) of 0.975 (95% CI 0.932, 1.00), while the model without corticosteroid and fetal sex predictors demonstrated an AUROC of 0.927 (95% CI 0.824, 1.00). The Hassan score was highly correlated with neonatal length of stay (p<0.001), allowing the neonatal morbidity model to also predict increased neonatal length of stay (53 [IQR 22, 76] days vs. 4.5 [2, 31] days, above and below the model cut point, respectively; p = 0.0017). Spontaneous preterm delivery prior to 32 weeks' gestation was also predicted with an AUROC of 0.94 (95% CI 0.869, 1.00).

Conclusions: Plasma levels of DOC and 16α-OHP in early gestation can be combined with patient demographic and clinical data to predict significant neonatal morbidity, neonatal length of stay, and risk for very preterm delivery, though validation studies are needed to verify these findings. Early identification of pregnancies at risk for preterm delivery and neonatal morbidity allows for timely implementation of multidisciplinary care to improve perinatal outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243585PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787372PMC
January 2021

Synthesis of New 3-Arylaminophthalides and 3-Indolyl-phthalides using Ammonium Chloride, Evaluation of their Anti-Mycobacterial Potential and Docking Study.

Comb Chem High Throughput Screen 2020 ;23(8):723-739

Bioinformatics Centre, The Department of Biotechnology and Department of Chemistry, Savitribai Phule Pune University, Pune, India

Objective: The study aims at the derivatization of "Phthalides" and synthesizes 3- arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and antioxidant activities. The study has also intended to employ the in silico methods for the identification of possible drug targets in Mycobacterium and evaluate the binding affinities of synthesized compounds.

Methods: This report briefly explains the synthesis of phthalide derivatives using ammonium chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the synthesized compounds. An in-silico pharmacophore probing approach was used for target identification in Mycobacterium. The structural level interaction between the identified putative drug target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software.

Results And Discussion: In the present study, we report an effective, environmentally benign scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a putative drug target in Mycobacterium. The docking results clearly showed the interactive involvement of conserved residues of dCTP with the synthesized phthalide compounds.

Conclusion: On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied activities of the compounds in the present study demonstrates the enormous significance of these newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular agents. The docking results from the current report provide a structural rationale for the promising anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.
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http://dx.doi.org/10.2174/1386207323666200422082754DOI Listing
January 2020

Alterations in endogenous progesterone metabolism associated with spontaneous very preterm delivery.

Hum Reprod Open 2020 6;2020(2):hoaa007. Epub 2020 Apr 6.

Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

Study Question: Do maternal serum levels of progesterone metabolites early in pregnancy correspond to an increased risk for very preterm delivery prior to 32 weeks?

Summary Answer: Maternal serum levels of 11-deoxycorticosterone (DOC) measured during the late first trimester or early second trimester correlate with an increased risk for preterm delivery prior to 32 weeks, and the correlation becomes stronger when the ratio of DOC to 16-alpha-hydroxyprogesterone was measured.

What Is Known Already: Progesterone is a pro-gestational steroid hormone that has been shown to decrease the risk of preterm birth in some pregnant women. Progesterone is metabolized by the body into various metabolites including members of the mineralocorticoid and glucocorticoid families. Our group has previously demonstrated that some progesterone metabolites enhance myometrial contractility in an system, while others result in myometrial relaxation. The current exploratory study was designed to determine if pre-specified metabolites of progesterone measured early in pregnancy were associated with a woman's risk for delivery prior to 32 weeks, which is referred to as a very preterm delivery.

Study Design Size Duration: The Building Blocks of Pregnancy Biobank (BBPB) is a biorepository at Indiana University (IU) that follows women prospectively through their pregnancy. A variety of biospecimens are collected at various time points during a woman's pregnancy. Women participating in the IU BBPB who were enrolled after 8 weeks' gestation with pregnancy outcome data were eligible for participation.

Participants/materials Setting Methods: Women delivering prior to 37 weeks (preterm) and at or after 37 weeks (term) who had blood samples collected during the late first trimester/early second trimester and/or during the early third trimester were identified. These samples were then processed for mass spectroscopy, and the amount of progesterone and progesterone metabolites in the samples were measured. Mean values of each measured steroid metabolite were calculated and compared among women delivering at less than 32 weeks, less than 37 weeks and greater than or equal to 37 weeks. Receiver operating characteristic (ROC) curves were constructed and threshold levels determined for each compound to identify a level above or below which best predicted a woman's risk for delivery prior to 32 and prior to 37 weeks. Mann-Whitney nonparametric testing with Holm-Bonferroni correction for multiple comparisons was utilized to identify steroid ratios that could differentiate women delivering spontaneously at less than 32 weeks from all other pregnancies.

Main Results And The Role Of Chance: Steroid hormone levels and pregnancy outcome data were available for 93 women; 28 delivering prior to 32 weeks, 40 delivering between 32 0/7 and 36 6/7 weeks and 25 delivering at or greater than 37 weeks: the mean gestational age at delivery within the three groups was 27.0, 34.4 and 38.8 weeks, respectively. Among women delivering spontaneously at less than 37 weeks, maternal 11-deoxycorticosterone (DOC) levels drawn in the late first trimester/early second trimester were significantly associated with spontaneous preterm delivery prior to 32 weeks; a threshold level of 47.5 pg/ml had 78% sensitivity, 73% specificity and an AUC of 0.77 ( = 0.044). When DOC levels were analyzed as a ratio with other measured steroid hormones, the ratio of DOC to 16-alpha-hydroxyprogesterone among women delivering spontaneously prior to 37 weeks was able to significantly discriminate women delivering prior to 32 weeks from those delivering at or greater than 32 weeks, with a threshold value of 0.2 with 89% sensitivity, 91% specificity and an AUC of 0.92 ( = 0.002). When the entire study cohort population was considered, including women delivering at term and women having an iatrogenic preterm delivery, the ratio of DOC to 16-alpha-hydroxyprogesterone was able to discriminate women delivering spontaneously prior to 32 weeks from the rest of the population at a threshold of 0.18 and 89% sensitivity, 59% specificity and an AUC of 0.81 ( = 0.003).

Limitations Reasons For Caution: This is a discovery study, and the findings have not been validated on an independent cohort. To mitigate issues with multiple comparisons, we limited our study to pre-specified metabolites that are most representative of the major metabolic pathways for progesterone, and adjustments for multiple comparisons were made.

Wider Implications Of The Findings: Spontaneous preterm birth is increasingly being recognized to represent a common end pathway for a number of different disease phenotypes that include infection, inflammation, premature rupture of the membranes, uterine over distension, cervical insufficiency, placental dysfunction and genetic predisposition. In addition to these phenotypes, longitudinal changes in the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis also likely contribute to a significant proportion of the disease burden of spontaneous preterm birth. Here, we demonstrate that differential production of steroid metabolites is associated with very early preterm birth. The identified biomarkers may hint at a pathophysiologic mechanism and changes in the maternal-fetal dyad that result in preterm delivery. The early identification of abnormal changes in HPA axis metabolites may allow for targeted interventions that reverse the aberrant steroid metabolic profile to a more favorable one, thereby decreasing the risk for early delivery. Further research is therefore required to validate and extend the results presented here.

Study Funding/competing Interests: Funding for this study was provided from the Office of the Vice Chancellor for Research at IUPUI, 'Funding Opportunities for Research Commercialization and Economic Success (FORCES) grant'.Both A.S.P. and C.A.G. are affiliated with Nixxi, a biotech startup. The remaining authors report no conflict of interest.

Trial Registration Number: Not applicable.
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http://dx.doi.org/10.1093/hropen/hoaa007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133115PMC
April 2020

Hydrogel-Immobilized Coacervate Droplets as Modular Microreactor Assemblies.

Angew Chem Int Ed Engl 2020 04 10;59(17):6853-6859. Epub 2020 Mar 10.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

Immobilization of compartmentalized microscale objects in 3D hydrogels provides a step towards the modular assembly of soft functional materials with tunable architectures and distributed functionalities. Herein, we report the use of a combination of micro-compartmentalization, immobilization, and modularization to fabricate and assemble hydrogel-based microreactor assemblies comprising millions of functionalized polysaccharide-polynucleotide coacervate droplets. The heterogeneous hydrogels can be structurally fused by interfacial crosslinking and coupled as input and output modules to implement a UV-induced photocatalytic/peroxidation nanoparticle/DNAzyme reaction cascade that generates a spatiotemporal fluorescence read-out depending on the droplet number density, intensity of photoenergization, and chemical flux. Our approach offers a route to heterogeneous hydrogels with endogenous reactivity and reconfigurable architecture, and provides a step towards the development of soft modular materials with programmable functionality.
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http://dx.doi.org/10.1002/anie.201916481DOI Listing
April 2020

Catalytic processing in ruthenium-based polyoxometalate coacervate protocells.

Nat Commun 2020 01 3;11(1):41. Epub 2020 Jan 3.

Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

The development of programmable microscale materials with cell-like functions, dynamics and collective behaviour is an important milestone in systems chemistry, soft matter bioengineering and synthetic protobiology. Here, polymer/nucleotide coacervate micro-droplets are reconfigured into membrane-bounded polyoxometalate coacervate vesicles (PCVs) in the presence of a bio-inspired Ru-based polyoxometalate catalyst to produce synzyme protocells (RuPCVs) with catalase-like activity. We exploit the synthetic protocells for the implementation of multi-compartmentalized cell-like models capable of collective synzyme-mediated buoyancy, parallel catalytic processing in individual horseradish peroxidase-containing RuPCVs, and chemical signalling in distributed or encapsulated multi-catalytic protocell communities. Our results highlight a new type of catalytic micro-compartment with multi-functional activity and provide a step towards the development of protocell reaction networks.
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http://dx.doi.org/10.1038/s41467-019-13759-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941959PMC
January 2020

Effect of the Periapical "Inflammatory Plug" on Dental Pulp Regeneration: A Histologic In Vivo Study.

J Endod 2020 Jan;46(1):51-56

Center for Craniofacial Regeneration, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Endodontics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Periodontics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address:

Introduction: In the current study, we investigate the effect of the inflammation occupying the apical foramen-a phenomenon we refer to as "inflammatory plug"-on the regenerative potential of a root canal therapy.

Methods: We performed root canal treatment (RCT) in 12 canine root canals while aseptically instrumenting the apex to a 0.5-mm-wide foramen and obturating the canals with the following materials: collagen sponge, platelet-rich fibrin, and blood clot (no material introduced).

Results: We were successful in maintaining the integrity of the periapical tissue in 8 of 12 RCTs. Injury to the periapical tissue occurred during the remaining 4 RCTs, which initiated inflammation accompanied by bone and dentin resorption. Our histologic analyses showed that the resulting inflammatory plug contained abundant M1 macrophages and was associated with an absence of intracanal cellular infiltration. On the contrary, noninflamed samples showed signs of repair, as indicated by the migration of periapical cells throughout the root canal.

Conclusions: We conclude that controlling periapical inflammation is key while attempting to achieve dental pulp regeneration.
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http://dx.doi.org/10.1016/j.joen.2019.10.006DOI Listing
January 2020

Progesterone Metabolites Inhibit the Human Ether-a-go-go-Related Gene and Predict QT Interval Length.

J Clin Pharmacol 2019 Dec 12. Epub 2019 Dec 12.

Department of Pharmacy Practice, College of Pharmacy, Purdue University, West Lafayette, Indiana, USA.

A decrease in the human ether-a-go-go-related gene (hERG/KCNH2)-related channel has been linked to intrauterine fetal death. The formation of cytochrome P450 (CYP) 3A-mediated progesterone metabolites, 6-beta-hydroxy-progesterone (6β-OHP) and 16α-hydroxy-progesterone (16α-OHP), is variable among adults and differs from fetal metabolism. The primary objective of this study was to assess the potential for progesterone metabolites to inhibit hERG-related current and predict QTc intervals. Whole-cell voltage-clamp electrophysiology was performed on human embryonic kidney 293 cells stably expressing hERG exposed to progesterone or metabolites. Both 6β-OHP and 16α-OHP positively shifted the voltage dependence of activation relative to vehicle from -4.0 ± 0.8 to -0.3 ± 0.8 mV, P < .01; and 1.0 ± 0.6 mV, P < .01, respectively. In addition, 6β-OHP decreased maximal outward tail currents from 49.4 ± 4.9 to 32.5 ± 4.1 pA/pF, P < 0.01, and reduced the expression of fully glycosylated hERG by 42%. Healthy female subjects were administered progesterone 400 mg orally for 7 days, ibutilide 0.003 mg/kg was infused, and serial electrocardiograms and blood samples collected. Relationships between rate-corrected QT intervals (QTcI) with circulating hormones and metabolites were assessed. The 6β-OHP and 16α-OHP metabolites were independent predictors of QTcI intervals prior to and following ibutilide administration. In conclusion, the progesterone metabolites formed via CYP3A cause inhibitory effects on hERG channels and predict QTcI intervals in healthy women pretreated with progesterone. Further study into maternal and fetal exposure to these metabolites and potential to prolong cardiac repolarization is warranted.
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http://dx.doi.org/10.1002/jcph.1563DOI Listing
December 2019

Impact of toothpaste on oral health-related quality of life in people with dentine hypersensitivity.

BMC Oral Health 2019 10 22;19(1):226. Epub 2019 Oct 22.

Intertek CRS Ltd., 119 Station Road, Ellesmere Port, Cheshire, CH65 4BW, UK.

Background: Dentine hypersensitivity can impact functional status and everyday activities such as eating and talking. This study aimed to assess changes in oral health-related quality of life measures in individuals with dentine hypersensitivity following long-term use (24 weeks) of a commercially available toothpaste marketed for dentine hypersensitivity relief.

Methods: This study was conducted across two sites and enrolled 75 adults with ≥2 non-adjacent sensitive teeth. Participants were assigned to twice-daily brushing with toothpaste containing 0.454% w/w stannous fluoride (1100 ppm fluoride). Every 4 weeks, participant-reported outcomes were assessed using the Dentine Hypersensitivity Experience Questionnaire (DHEQ), a condition specific oral health-related quality of life scale that has five domains and includes questions on social and emotional impact, restrictions, adaptations and effect on life overall. Responses to a clinically applied evaporative (air) stimulus were assessed using the examiner-observed Schiff sensitivity scale and Labelled Magnitude Scales (LMS), which included dentine hypersensitivity-specific descriptors of intensity, duration, tolerability and descriptive qualities of the participant's response.

Results: Participant-reported outcomes demonstrated reduction of the impact of dentine hypersensitivity over time on health-related quality of life, as measured by the DHEQ. This reached statistical significance from Week 8 onwards (p < 0.0001 versus baseline) for the Total DHEQ score, with scores continually decreasing at each timepoint. Most domain scores followed a similar pattern. Statistically significant reductions were also detected for the examiner-observed Schiff Sensitivity Scale scores at all timepoints (including at 4 weeks) (p < 0.05), which were mirrored by LMS responses. The toothpaste was generally well-tolerated.

Conclusions: These results show that long-term use of a sensitivity toothpaste containing 0.454% w/w stannous fluoride has a beneficial, ongoing, impact on the oral health-related quality of life of people with dentine hypersensitivity.

Trial Registration: This study was registered at Clinicaltrials.gov ( https://clinicaltrials.gov/ct2/show/NCT02752958 ) on April 27, 2016.
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http://dx.doi.org/10.1186/s12903-019-0919-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805594PMC
October 2019

Qualitative HPTLC phytochemical profiling of Roxb. bark, leaves and seeds.

3 Biotech 2019 Aug 30;9(8):311. Epub 2019 Jul 30.

1Department of Biotechnology, B. K. Birla College of Arts, Science and Commerce (Autonomous), Kalyan (West), Maharashtra India.

Roxb. (Family: Lecythidaceae is commonly called as Slow match tree and is an important medicinal plant. Its different parts viz. bark, leaves and seeds have been reported to show many pharmacological activities. High-performance thin-layer chromatography (HPTLC) is a simple, fast and precise technique for the detection of phytochemicals present in the plant. Therefore, the objective of the present study was to characterize the phytochemical profile for various secondary metabolites using HPTLC for bark, leaves and seeds extracts, which revealed the confirmation of these phytochemicals. The present study suggested that the bark contains all the classes of compounds tested namely alkaloids, anthracene derivatives, arbutin derivatives, bitter compounds, cardiac glycosides, coumarin derivatives, essential oils, flavonoids, lignans, pungent-tasting principles, saponins, triterpenes and valepotriates. Whereas, alkaloids are not detected in leaves, and alkaloids and arbutin derivatives are not detected in seeds.
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http://dx.doi.org/10.1007/s13205-019-1846-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667510PMC
August 2019

Artificial morphogen-mediated differentiation in synthetic protocells.

Nat Commun 2019 07 25;10(1):3321. Epub 2019 Jul 25.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

The design and assembly of artificial protocell consortia displaying dynamical behaviours and systems-based properties are emerging challenges in bottom-up synthetic biology. Cellular processes such as morphogenesis and differentiation rely in part on reaction-diffusion gradients, and the ability to mimic rudimentary aspects of these non-equilibrium processes in communities of artificial cells could provide a step to life-like systems capable of complex spatiotemporal transformations. Here we expose acoustically formed arrays of initially identical coacervate micro-droplets to uni-directional or counter-directional reaction-diffusion gradients of artificial morphogens to induce morphological differentiation and spatial patterning in single populations of model protocells. Dynamic reconfiguration of the droplets in the morphogen gradients produces a diversity of membrane-bounded vesicles that are spontaneously segregated into multimodal populations with differentiated enzyme activities. Our results highlight the opportunities for constructing protocell arrays with graded structure and functionality and provide a step towards the development of artificial cell platforms capable of multiple operations.
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http://dx.doi.org/10.1038/s41467-019-11316-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6658542PMC
July 2019

A randomised bite force study assessing two currently marketed denture adhesive products compared with no-adhesive control.

Clin Exp Dent Res 2019 06 14;5(3):276-283. Epub 2019 May 14.

Oral Health Research Institute Indiana University School of Dentistry Indianapolis Indiana.

Unlike other oral care products, there are limited technologies in the denture adhesive category with the majority based on polymethyl vinyl ether/maleic anhydride (PVM/MA) polymer. Carbomer-based denture adhesives are less well studied, and there are few clinical studies directly comparing performance of denture adhesives based on different technologies. This single-centre, randomised, three-treatment, three-period, examiner-blind, crossover study compared a carbomer-based denture adhesive (Test adhesive) with a PVM/MA-based adhesive (Reference adhesive) and no adhesive using incisal bite force measurements (area over baseline over 12 hr; AOB) in participants with a well-made and at least moderately well-fitting complete maxillary denture. Eligible participants were randomised to a treatment sequence and bit on a force transducer with increasing force until their maxillary denture dislodged. This procedure was performed prior to treatment application (baseline) and at 0.5, 1, 3, 6, 9, and 12 hr following application. Forty-four participants were included in the modified intent-to-treat population. AOB favoured both Test adhesive to No adhesive (difference: 2.12 lbs; 95% CI [1.25, 3.00];  < 0.0001) and Reference adhesive to No adhesive (difference: 2.76 lbs; 95% CI [1.89, 3.63];  < 0.0001). There was a numerical difference in AOB for Test versus Reference adhesive (-0.63 lbs; [-1.51, 0.25]); however, this was not statistically significant ( = 0.1555). Treatments were generally well tolerated. Both PVM/MA and carbomer-based denture adhesives demonstrated statistically significantly superior denture retention compared with no adhesive over 12 hr, with no statistically significant difference between adhesives.
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http://dx.doi.org/10.1002/cre2.182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585581PMC
June 2019

Modulation of Higher-order Behaviour in Model Protocell Communities by Artificial Phagocytosis.

Angew Chem Int Ed Engl 2019 05 2;58(19):6333-6337. Epub 2019 Apr 2.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

Collective behaviour in mixed populations of synthetic protocells is an unexplored area of bottom-up synthetic biology. The dynamics of a model protocell community is exploited to modulate the function and higher-order behaviour of mixed populations of bioinorganic protocells in response to a process of artificial phagocytosis. Enzyme-loaded silica colloidosomes are spontaneously engulfed by magnetic Pickering emulsion (MPE) droplets containing complementary enzyme substrates to initiate a range of processes within the host/guest protocells. Specifically, catalase, lipase, or alkaline phosphatase-filled colloidosomes are used to trigger phagocytosis-induced buoyancy, membrane reconstruction, or hydrogelation, respectively, within the MPE droplets. The results highlight the potential for exploiting surface-contact interactions between different membrane-bounded droplets to transfer and co-locate discrete chemical packages (artificial organelles) in communities of synthetic protocells.
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http://dx.doi.org/10.1002/anie.201901469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519160PMC
May 2019

Nonequilibrium Spatiotemporal Sensing within Acoustically Patterned Two-Dimensional Protocell Arrays.

ACS Cent Sci 2018 Nov 14;4(11):1551-1558. Epub 2018 Nov 14.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, U.K.

Acoustically trapped periodic arrays of horseradish peroxidase (HRP)-loaded poly(diallydimethylammonium chloride) / adenosine 5'-triphosphate coacervate microdroplet-based protocells exhibit a spatiotemporal biochemical response when exposed to a codiffusing mixture of substrate molecules (-phenylenediamine (-PD) and hydrogen peroxide (HO)) under nonequilibrium conditions. Unidirectional propagation of the chemical concentration gradients gives rise to time- and position-dependent fluorescence signal outputs from individual coacervate microdroplets, indicating that the organized protocell assembly can dynamically sense encoded information in the advancing reaction-diffusion front. The methodology is extended to arrays comprising spatially separated binary populations of HRP- or glucose oxidase-containing coacervate microdroplets to internally generate a HO signal that chemically connects the two protocell communities via a concerted biochemical cascade reaction. Our results provide a step toward establishing a systematic approach to study dynamic interactions between organized protocell consortia and propagating reaction-diffusion gradients, and offer a new methodology for exploring the complexity of protocellular communication networks operating under nonequilibrium conditions.
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http://dx.doi.org/10.1021/acscentsci.8b00555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276052PMC
November 2018

Randomized Controlled Clinical Study to Determine the Oral and Dermal Tolerability of an Experimental Denture Wipe.

J Prosthodont 2019 Feb 28;28(2):138-145. Epub 2018 Nov 28.

Salus Research Inc., Fort Wayne, IN.

Purpose: To evaluate oral and dermal tolerance following use and user acceptability of an experimental denture-cleansing wipe. An exploratory objective was to develop a method to assess denture wipe effectiveness in removing debris from denture surfaces.

Materials And Methods: This was a single-center, randomized, controlled, parallel-group, examiner-blind study in participants with ≥1 full/partial denture. Participants were randomized to clean their dentures with the denture wipe (n = 76) or water (n = 76) up to 4 times per day for 14 days. Tolerability was assessed by treatment-emergent adverse events (TEAEs), oral soft tissue examination, and lead hand dermatological assessment. Acceptability was assessed by questionnaire. The feasibility of a methodology to assess the efficacy of the wipe at removing food particles was also evaluated through determination of the mass of chewed peanut particles that the wipe removed after a single use (n = 31).

Results: The proportion of participants experiencing oral TEAEs by day 14 was 0.039% with the denture wipe (lip injury [n = 1], mouth injury [n = 2]) and 0.013% with the water rinse (coated tongue [n = 1]). There were no dermal TEAEs and no TEAE-related study withdrawals. Skin irritation scores with the denture wipe remained unchanged from baseline. Comparing before vs. after cleaning with the denture wipe, a higher proportion of participants rated their dentures as feeling extremely/very fresh (28.9% pre-/85.5% post-cleaning), feeling extremely/very clean (34.2%/86.8%) and looking extremely/very clean (43.5%/85.5%). More denture-wipe group participants than water-rinse group participants were extremely/very satisfied with the amount of debris removed from their dentures (88.1% vs 72.4%). The methodology used to assess the weight of peanut particles captured from the wipes/dentures appeared to be a feasible investigation technique.

Conclusions: The denture wipe was generally well-tolerated and had good user acceptability. The methodology for assessing the mass of peanut particles removed by denture wipes was successful.
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http://dx.doi.org/10.1111/jopr.12992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328799PMC
February 2019

Ionization of Submicrometer-Sized Particles by Laser-Induced Radiofrequency Plasma for Mass Spectrometric Analysis.

Anal Chem 2018 11 5;90(22):13236-13242. Epub 2018 Nov 5.

Department of Physics , National Dong Hwa University , Shoufeng , Hualien , Taiwan 97401.

A laser-induced rf plasma (LIRFP) ion source was developed to ionize submicrometer-sized particles for the first time. The LIRFP ion source can increase the charge of those particles to several thousand charges via charge exchange reactions so that those particles can be trapped and analyzed with a charge detection quadrupole ion trap-mass spectrometer (CD QIT-MS). Different reagent gases for charge exchange reaction were investigated, viz. argon, nitrogen, oxygen, methane, helium, krypton, xenon, argon/methane (with ratios of 10:1 and 2:1), argon/nitrogen (with a ratio of 1:1), nitrogen/oxygen (10:1), krypton/methane (10:1), and air. The average charge of 0.75 μm polystyrene particles could reach 1631 using an argon/methane mixture with a ratio of ∼10:1. The average charges for freeze-dried Escherichia coli EC11303, Escherichia coli strain W, and Staphylococcus aureus were 842, 1112, and 971, respectively, with a mass-to-charge ratio ( m/ z) range from 10 to 10; and the average masses were 3.5 × 10 Da, 6.0 × 10 Da, and 5.6 × 10 Da, respectively. The average mass and charge of the vaccinia virus were ∼9.1 × 10 Da and ∼708 with a m/ z of ∼10. This LIRFP CD QIT-MS method was rapid with only 20 min for each sample measurement.
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http://dx.doi.org/10.1021/acs.analchem.8b03983DOI Listing
November 2018

The Effect of Blood Loss on Cefazolin Levels in Women Undergoing Cesarean Delivery.

Am J Perinatol 2019 06 18;36(7):688-694. Epub 2018 Oct 18.

Division of Maternal-Fetal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Objective: To quantify the effects of operative blood loss during cesarean on tissue and plasma cefazolin concentrations.

Study Design: This was a prospective observational study of singleton pregnancies undergoing scheduled cesarean between 34 and 40 weeks. Cefazolin administered prior to skin incision. Maternal plasma samples were obtained (Time 1[T1]: immediately, T2: 20 minutes, T3: 40 minutes, and T4: 60 minutes after cefazolin infusion). Subcutaneous adipose tissue sampled before and after fascia. Primary outcome was subcutaneous adipose cefazolin level after fascial closure. Formal quantitative blood loss (QBL) performed. Women with higher QBL, those at/above 75% of QBL in this population, were compared with those with lower QBL (QBL below 75%). Data analyzed using bivariable statistics.

Results: Ninety-two women were screened, 32 were eligible, and 20 enrolled. Median QBL was 630 mL (interquartile range [IQR]: 473-818) and 1,160 mL (IQR: 1,000-1,560) in the low and high QBL groups, respectively. Demographics and operative characteristics were similar. Median adipose cefazolin level after fascial closure did not differ between the groups (3.5 vs. 3.9 μg/g,  = 0.75). No differences in maternal plasma cefazolin concentrations between the groups at any time point or in pharmacokinetic parameters were seen.

Conclusion: Intraoperative maternal plasma concentrations and adipose levels of cefazolin are similar between women with high and low blood loss at the time of cesarean delivery.
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http://dx.doi.org/10.1055/s-0038-1673654DOI Listing
June 2019

Programmed assembly of synthetic protocells into thermoresponsive prototissues.

Nat Mater 2018 12 8;17(12):1145-1153. Epub 2018 Oct 8.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, UK.

Although several new types of synthetic cell-like entities are now available, their structural integration into spatially interlinked prototissues that communicate and display coordinated functions remains a considerable challenge. Here we describe the programmed assembly of synthetic prototissue constructs based on the bio-orthogonal adhesion of a spatially confined binary community of protein-polymer protocells, termed proteinosomes. The thermoresponsive properties of the interlinked proteinosomes are used collectively to generate prototissue spheroids capable of reversible contractions that can be enzymatically modulated and exploited for mechanochemical transduction. Overall, our methodology opens up a route to the fabrication of artificial tissue-like materials capable of collective behaviours, and addresses important emerging challenges in bottom-up synthetic biology and bioinspired engineering.
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http://dx.doi.org/10.1038/s41563-018-0183-5DOI Listing
December 2018

Enzyme-powered motility in buoyant organoclay/DNA protocells.

Nat Chem 2018 11 20;10(11):1154-1163. Epub 2018 Aug 20.

Centre for Protolife Research and Centre for Organized Matter Chemistry, School of Chemistry, University of Bristol, Bristol, UK.

Reconstitution and simulation of cellular motility in microcompartmentalized colloidal objects have important implications for microcapsule-based remote sensing, environmentally induced signalling between artificial cell-like entities and programming spatial migration in synthetic protocell consortia. Here we describe the design and construction of catalase-containing organoclay/DNA semipermeable microcapsules, which in the presence of hydrogen peroxide exhibit enzyme-powered oxygen gas bubble-dependent buoyancy. We determine the optimum conditions for single and/or multiple bubble generation per microcapsule, monitor the protocell velocities and resilience, and use remote magnetic guidance to establish reversible changes in the buoyancy. Co-encapsulation of catalase and glucose oxidase is exploited to establish a spatiotemporal response to antagonistic bubble generation and depletion to produce protocells capable of sustained oscillatory vertical movement. We demonstrate that the motility of the microcapsules can be used for the flotation of macroscopic objects, self-sorting of mixed protocell communities and the delivery of a biocatalyst from an inert to chemically active environment. These results highlight new opportunities to constructing programmable microcompartmentalized colloids with buoyancy-derived motility.
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http://dx.doi.org/10.1038/s41557-018-0119-3DOI Listing
November 2018

Forced dried droplet method for MALDI sample preparation.

Anal Chim Acta 2018 Nov 23;1031:128-133. Epub 2018 May 23.

Department of Physics, National Dong Hwa University, Shoufeng, Hualien 97401, Taiwan. Electronic address:

A forced dried droplet method (FDD) is developed to overcome the drawbacks of the conventional dried-droplet (DD) method for matrix assisted laser desorption/ionization (MALDI) sample preparation. The crystals produced by the DD method are heterogeneous and irregularly distributed, and thus many methods have tried to solve the problems. However, most of them spend more time or need additional instruments to generate homogeneous microcrystals. The FDD sample preparation method can produce uniform microcrystals with homogeneous size distribution in few minutes without additional instruments. Stirring the sample spot solution (an agitation process) with a pipette tip can change the crystal size distribution which is observed by the microscope. Mass spectrometric analysis shows that the smaller the crystal size is, the better the ion signal intensity is. The formation of microcrystals can be explained with the effective rate of secondary nucleation. The relative standard deviation (RSD) of the FDD method is ∼16% which is comparable to the two-layer (TL) method and is better than the DD method.
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http://dx.doi.org/10.1016/j.aca.2018.05.056DOI Listing
November 2018

Construction of supramolecular hydrogels using photo-generated nitric oxide radicals.

Soft Matter 2018 Jul;14(29):5950-5954

Centre for Organized Matter Chemistry and Centre for Protocell Research, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

Photo-generated nitric oxide radicals (NO˙) derived from sodium nitroprusside dihydrate (SNP) are employed for the construction of supramolecular hydrogels based on an amino acid derivative precursor, N-fluorenylmethyloxycarbonyl tyrosine phosphate (FYP), which through dephosphorylation produces the gelator, N-fluorenylmethyloxycarbonyl tyrosine (FY). Self-assembly of the amphiphilic gelator yields high-aspect ratio nanofilaments that entangle to form self-supporting, viscoelastic hydrogels. The presence of photolyzed SNP yields periodically twisted nanofilaments with opposite chirality to filaments formed through conventional hydrogelation routes.
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http://dx.doi.org/10.1039/c8sm00651bDOI Listing
July 2018

Bioinformatics characterization of envelope glycoprotein from Kyasanur Forest disease virus.

Indian J Med Res 2018 Feb;147(2):195-201

ICMR-National Institute of Virology, Pune, India.

Background & Objectives: Kyasanur Forest disease (KFD) is a febrile illness characterized by haemorrhages and caused by KFD virus (KFDV), which belongs to the Flaviviridae family. It is reported to be an endemic disease in Shimoga district of Karnataka State, India, especially in forested and adjoining areas. Several outbreaks have been reported in newer areas, which raised queries regarding the changing nature of structural proteins if any. The objective of the study was to investigate amino acid composition and antigenic variability if any, among the envelope glycoprotein (E-proteins) from old and new strains of KFDV.

Methods: Bioinformatic tools and techniques were used to predict B-cell epitopes and three-dimensional structures and to compare envelope glycoprotein (E-proteins) between the old strains of KFDV and those from emerging outbreaks till 2015.

Results: The strain from recent outbreak in Thirthahalli, Karnataka State (2014), was similar to the older strain of KFDV (99.2%). Although mutations existed in strains from 2015 in Kerala KFD sequences, these did not alter the epitopes.

Interpretation & Conclusions: The study revealed that though mutations existed, there were no drastic changes in the structure or antigenicity of the E-proteins from recent outbreaks. Hence, no correlation could be established between the mutations and detection in new geographical areas. It seems that KFDV must be present earlier also in many States and due to availability of testing system and alertness coming into notice now.
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http://dx.doi.org/10.4103/ijmr.IJMR_1445_16DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991130PMC
February 2018

Fabrication of Micropatterned Dipeptide Hydrogels by Acoustic Trapping of Stimulus-Responsive Coacervate Droplets.

Small 2018 06 27;14(26):e1800739. Epub 2018 May 27.

Centre for Organized Matter Chemistry and Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

Acoustic standing waves offer an excellent opportunity to trap and spatially manipulate colloidal objects. This noncontact technique is used for the in situ formation and patterning in aqueous solution of 1D or 2D arrays of pH-responsive coacervate microdroplets comprising poly(diallyldimethylammonium) chloride and the dipeptide N-fluorenyl-9-methoxy-carbonyl-D-alanine-D-alanine. Decreasing the pH of the preformed droplet arrays results in dipeptide nanofilament self-assembly and subsequent formation of a micropatterned supramolecular hydrogel that can be removed as a self-supporting monolith. Guest molecules such as molecular dyes, proteins, and oligonucleotides are sequestered specifically within the coacervate droplets during acoustic processing to produce micropatterned hydrogels containing spatially organized functional components. Using this strategy, the site-specific isolation of multiple enzymes to drive a catalytic cascade within the micropatterned hydrogel films is exploited.
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http://dx.doi.org/10.1002/smll.201800739DOI Listing
June 2018

Severity of congenital heart defects associated with assisted reproductive technologies: Case series and review of the literature.

Birth Defects Res 2018 05;110(8):654-661

Center for Personalized Obstetric Medicine, Valley Perinatal Services, Phoenix, Arizona.

Objective: Assisted reproductive technology (ART) has been associated with a higher incidence of congenital anomalies, including a specific increase in the rate of congenital heart defects (CHD). In this study, the rate of CHD in pregnancies resulting from ART at a single high-risk pregnancy referral center are compared to the published literature.

Methods: Pregnancies were screened by fetal echocardiography for the indication of ART over a 2-year period. CHD were classified as either mild or severe based on the need for postnatal surgical intervention. Results were compared to findings from a literature review of studies examining CHD in pregnancies resulting from ART since 1980.

Results: Over the course of two years, 363 fetuses in 264 pregnancies from our cohort were screened for CHD. The incidence of mild CHD in fetuses from ART pregnancies was 2.75% (10 out of 363 fetuses). None of the affected fetuses had severe CHD. Review of the literature yielded 20 studies since 1980 that examined CHD in pregnancies resulting from ART. Composite data from the studies was described based on characterization of severity of the CHD anomalies. The incidence of mild CHD in ART pregnancies was 2.2%, compared to 1% in non-ART pregnancies (out of 332,157 infants). The incidence of severe CHD in ART pregnancies and naturally conceived pregnancies was 1.4% and 1.2%, respectively (out of 661,455 infants). The incidence of unspecified CHD in ART pregnancies was 1.8%, compared to 1% in naturally conceived pregnancies (out of 1,593,277 infants).

Conclusion: The greatest increase in risk appears to be for mild CHD (nonsurgical), which may inform counseling of patients prior to use of assisted reproductive technologies.
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http://dx.doi.org/10.1002/bdr2.1228DOI Listing
May 2018

In vivo study of self-assembled alkylsilane coated degradable magnesium devices.

J Biomed Mater Res B Appl Biomater 2019 02 11;107(2):342-351. Epub 2018 Apr 11.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, 15261.

Magnesium (Mg) and its alloys are candidate materials for resorbable implantable devices, such as orthopedic devices or cardiovascular stents. Mg has a number advantages, including mechanical properties, light weight, its osteogenic effects and the fact that its degradation products are nontoxic and naturally present in the body. However, production of H gas during the corrosion reaction can cause formation of gas pockets at the implantation site, posing a barrier to clinical applications of Mg. It is therefore desirable to develop methods to control corrosion rate and gas pocket formation around the implants. Here we evaluate the potential of self-assembled multilayer alkylsilane (AS) coatings to control Mg device corrosion and formation of gas pockets in vivo and to assess effects of the AS coatings on the surrounding tissues in a subcutaneous mouse model over a 6 weeks' period. The coating significantly slowed down corrosion and gas pocket formation as evidenced by smaller gas pockets around the AS coated implants (ANOVA; p = 0.013) and decrease in the weight loss values (t test; p = 0.07). Importantly, the microCT and profilometry analyses demonstrated that the coating inhibited the pitting corrosion. Specifically, the roughness of the coated samples was ∼30% lower than uncoated specimen (p = 0.02). Histological assessment of the tissues under the implant revealed no inflammation or foreign body reaction. Overall, our results demonstrate the feasibility of use of the seld assembled AS coatings for reduction of gas pocket formation around the resorbable Mg devices. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 342-351, 2019.
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http://dx.doi.org/10.1002/jbm.b.34126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371401PMC
February 2019

An exploratory study to investigate stain build-up with long term use of a stannous fluoride dentifrice.

Am J Dent 2018 Apr;31(2):71-75

Salus Research, Fort Wayne, Indiana, USA.

Purpose: To monitor extrinsic stain formation over 24 weeks with twice-daily use of an anhydrous 0.454% SnF2 dentifrice containing 5% sodium tripolyphosphate (STP) ('Test'), compared to a standard fluoride dentifrice (0.76% fluoride as sodium monofluorophosphate [SMFP\) ('Comparator') following a professional prophylaxis.

Methods: Primary efficacy variables were between-treatment differences in extrinsic dental stain of anterior teeth after 4, 8, 12, and 24 weeks' use using mean area and intensity scores of the MacPherson modification of the Lobene stain index (MLSI), and to monitor oral tolerability.

Results: Overall, 214 subjects were randomized to treatment. The Test dentifrice group demonstrated statistically significantly less stain compared with the Comparator at each timepoint for all outcome variables (MLSI - Area × Intensity, Area only, and Intensity only) with the exception of MLSI (Area × Intensity) at Week 12. Products were generally well tolerated with 26 treatment-related adverse events (TRAEs) reported (10 with Test, 16 with Comparator). Five subjects withdrew from the 24-week study due to TRAEs, three in the Test group, two in the Comparator group. Statistically significantly less anterior tooth staining was observed with up to 24 weeks twice-daily brushing with a 0.454% SnF2/5% STP anhydrous dentifrice compared to a marketed fluoride dentifrice with 0.76% SMFP.

Clinical Significance: Long term use of a SnF2/STP dentifrice demonstrated minimal stain build-up after 24 weeks, twice-daily use; products were generally well-tolerated.
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April 2018

Chloroplast-containing coacervate micro-droplets as a step towards photosynthetically active membrane-free protocells.

Chem Commun (Camb) 2018 Apr;54(29):3594-3597

Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol, BS8 1TS, UK.

Encapsulation of structurally and functionally intact chloroplasts within coacervate micro-droplets is used to prepare membrane-free protocells capable of light-induced electron transport.
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http://dx.doi.org/10.1039/c8cc01129jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885784PMC
April 2018

Differences in Type I interferon response in human lung epithelial cells infected by highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses.

Virus Genes 2018 Jun 24;54(3):414-423. Epub 2018 Mar 24.

Avian Influenza Group, Microbial Containment Complex, ICMR-National Institute of Virology, 130/1 Sus Road, Pashan, Pune, 411021, India.

Influenza A virus infection induces type I interferons (IFNs α/β) which activate host antiviral responses through a cascade of IFN signaling events. Herein, we compared highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses isolated from India, for their replication kinetics and ability to induce IFN-β and interferon-stimulating genes (ISGs). The H5N1 virus showed a higher replication rate and induced less IFN-β and ISGs compared to the H11N1 virus when grown in the human lung epithelial A549 cells, reflecting the generation of differential innate immune responses during infection by these viruses. The non-structural 1 (NS1) protein, a major IFN-antagonist, known to help the virus in evading host innate immune response was compared from both the strains using bioinformatics tools. Analyses revealed differences in the composition of the NS1 proteins from the two strains that may have an impact on the modulation of the innate immune response. Intriguingly, H5N1 virus attenuated IFN-β response in a non-NS1 manner, suggesting the possible involvement of other viral proteins (PB2, PA, PB1/PB1-F2) of H5N1 in synergy with NS1. Preliminary analyses of the above proteins of the two strains by sequence comparison show differences in charged residues. The insight gained will be useful in designing experimental studies to elucidate a probable role of the polymerase protein(s) in association with NS1 in inhibiting the IFN signaling and understanding the molecular mechanism governing the difference.
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http://dx.doi.org/10.1007/s11262-018-1556-1DOI Listing
June 2018

Potassium oxalate oral rinses for long-term relief from dentinal hypersensitivity: Three randomised controlled studies.

J Dent 2018 03 11;70:23-30. Epub 2017 Dec 11.

Salus Research, Inc., 1220 Medical Park Drive Building #4, Fort Wayne, IN 46825, USA. Electronic address:

Objectives: To evaluate effectiveness of oral rinses containing dipotassium oxalate monohydrate (KOX) in relieving dentinal hypersensitivity (DH) after 8 w use adjunctive to brushing.

Methods: Three 8-week, randomised, controlled, double-blind, parallel-group, single-centre studies were conducted in adults with DH. In each study, participants were randomised to one of two experimental rinses or a placebo in a matrix design, such that each experimental rinse was evaluated in two studies. Rinses A (pH 4.5) and B (pH 7.0) contained 1.5% KOX and were fluoride-free; Rinse C (pH 4.5) contained 2.0% KOX and 45 ppm fluoride as NaF; the placebo rinse (pH 4.5) did not contain KOX or fluoride. Participants brushed with a fluoride dentifrice for 1 min, briefly rinsed with water, then rinsed with their assigned oral rinse for 1 min twice daily for 8 w. DH was assessed at baseline and following 4 and 8 w use by response to an evaporative (air) stimulus (evaluated by Schiff sensitivity score and a 10-point visual rating scale) and a tactile stimulus (Yeaple probe).

Results: All rinses in each study were associated with statistically significant improvements from baseline in measures of DH after 4 and 8 w treatment. However, between-treatment comparisons were inconsistent across the studies, with only Study 3 demonstrating a significant difference between the experimental (Rinses B and C) and placebo rinses. A number of treatment-related adverse events (all mild) were reported.

Conclusions: Rinses containing 1.5-2.0% KOX did not consistently demonstrate a benefit over placebo in relieving DH after 8 w use.

Clinical Significance: While favourable results were found in one of the investigations, this suite of studies shows that the possibility of inconsistent results exists even with the best designed and executed trials.
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http://dx.doi.org/10.1016/j.jdent.2017.12.004DOI Listing
March 2018