Mesoporous Phosphate-Based Glasses Prepared via Sol-Gel

In the present study, a mesoporous phosphate-based glass (MPG) in the P2O5-CaO-Na2O system was synthesised, for the first time, using a combination of sol-gel chemistry and supramolecular templating. A comparison between the structural properties, bioactivity and biocompatibility of the MPG with a non-porous phosphate-based glass (PG) of analogous composition prepared via the same sol-gel synthesis method, but in the absence of a templating surfactant is also presented. Results indicate that the MPG has enhanced bioactivity and biocompatibility compared to the PG, despite having similar local structure and dissolution properties. In contrast to the PG, the MPG shows formation of hydroxyl carbonate apatite (HCA) on its surface after 24 hours of immersion in simulated body fluid. Moreover, MPG shows enhanced viability of Saos-2 osteosarcoma cells after 7 days of culturing. This suggests that textural properties (porosity and surface area) play a crucial role in the kinetics of HCA formation and in interaction with cells. Increased efficiency of drug loading and release over non-porous PG systems was proved using the antimicrobial tetracycline hydrochloride as a drug model. This study represents a significant advance in the field of mesoporous materials for drug delivery and bone tissue regeneration as it reports, for the first time, the synthesis, structural characterisation and biocompatibility of mesoporous calcium phosphate glasses.In the present study, a mesoporous phosphate-based glass (MPG) in the P2O5-CaO-Na2O system was synthesised, for the first time, using a combination of sol-gel chemistry and supramolecular templating. A comparison between the structural properties, bioactivity and biocompatibility of the MPG with a non-porous phosphate-based glass (PG) of analogous composition prepared via the same sol-gel synthesis method, but in the absence of a templating surfactant is also presented. Results indicate that the MPG has enhanced bioactivity and biocompatibility compared to the PG, despite having similar local structure and dissolution properties. In contrast to the PG, the MPG shows formation of hydroxyl carbonate apatite (HCA) on its surface after 24 hours of immersion in simulated body fluid. Moreover, MPG shows enhanced viability of Saos-2 osteosarcoma cells after 7 days of culturing. This suggests that textural properties (porosity and surface area) play a crucial role in the kinetics of HCA formation and in interaction with cells. Increased efficiency of drug loading and release over non-porous PG systems was proved using the antimicrobial tetracycline hydrochloride as a drug model. This study represents a significant advance in the field of mesoporous materials for drug delivery and bone tissue regeneration as it reports, for the first time, the synthesis, structural characterisation and biocompatibility of mesoporous calcium phosphate glasses

Hierarchy of piecewise non-linear maps with non-ergodicity behavior

We study the dynamics of hierarchy of piecewise maps generated by one-parameter families of trigonometric chaotic maps and one-parameter families of elliptic chaotic maps of $\mathbf{cn}$ and $\mathbf{sn}$ types, in detail. We calculate the Lyapunov exponent and Kolmogorov-Sinai entropy of the these maps with respect to control parameter. Non-ergodicity of these piecewise maps is proven analytically and investigated numerically . The invariant measure of these maps which are not equal to one or zero, appears to be characteristic of non-ergodicity behavior. A quantity of interest is the Kolmogorov-Sinai entropy, where for these maps are smaller than the sum of positive Lyapunov exponents and it confirms the non-ergodicity of the maps.Comment: 18 pages, 8 figure

The adjuvants dmLT and mmCT enhance humoral immune responses to a pneumococcal conjugate vaccine after both parenteral or mucosal immunization of neonatal mice

Immaturity of the neonatal immune system contributes to increased susceptibility to infectious diseases and poor vaccine responses. Therefore, better strategies for early life vaccination are needed. Adjuvants can enhance the magnitude and duration of immune responses. In this study we assessed the effects of the adjuvants dmLT and mmCT and different immunization routes, subcutaneous (s.c.) and intranasal (i.n.), on neonatal immune response to a pneumococcal conjugate vaccine Pn1-CRM197. Pn1-specific antibody (Ab) levels of neonatal mice immunized with Pn1-CRM197 alone were low. The adjuvants enhanced IgG Ab responses up to 8 weeks after immunization, more after s.c. than i.n. immunization. On the contrary, i.n. immunization with either adjuvant enhanced serum and salivary IgA levels more than s.c. immunization. In addition, both dmLT and mmCT enhanced germinal center formation and accordingly, dmLT and mmCT enhanced the induction and persistence of Pn1-specific IgG+ Ab-secreting cells (ASCs) in spleen and bone marrow (BM), irrespective of the immunization route. Furthermore, i.n. immunization enhanced Pn1-specific IgA+ ASCs in BM more than s.c. immunizatiofimmu.2022.1078904n. However, a higher i.n. dose of the Pn1-CRM197 was needed to achieve IgG response comparable to that elicited by s.c. immunization with either adjuvant. We conclude that dmLT and mmCT enhance both induction and persistence of the neonatal immune response to the vaccine Pn1-CRM197, following mucosal or parenteral immunization. This indicates that dmLT and mmCT are promising adjuvants for developing safe and effective early life vaccination strategies

The adjuvants dmLT and mmCT enhance humoral immune responses to a pneumococcal conjugate vaccine after both parenteral or mucosal immunization of neonatal mice

Funding Information: JM was a recipient of a doctoral study grant from the University of Iceland Research Fund (2019-22). This study was financially supported by grants from the Icelandic Research Fund (RSJ207287) and the University of Iceland Research Fund (2019-21). Acknowledgments Publisher Copyright: Copyright © 2023 Molina Estupiñan, Aradottir Pind, Foroutan Pajoohian, Jonsdottir and Bjarnarson.Immaturity of the neonatal immune system contributes to increased susceptibility to infectious diseases and poor vaccine responses. Therefore, better strategies for early life vaccination are needed. Adjuvants can enhance the magnitude and duration of immune responses. In this study we assessed the effects of the adjuvants dmLT and mmCT and different immunization routes, subcutaneous (s.c.) and intranasal (i.n.), on neonatal immune response to a pneumococcal conjugate vaccine Pn1-CRM197. Pn1-specific antibody (Ab) levels of neonatal mice immunized with Pn1-CRM197 alone were low. The adjuvants enhanced IgG Ab responses up to 8 weeks after immunization, more after s.c. than i.n. immunization. On the contrary, i.n. immunization with either adjuvant enhanced serum and salivary IgA levels more than s.c. immunization. In addition, both dmLT and mmCT enhanced germinal center formation and accordingly, dmLT and mmCT enhanced the induction and persistence of Pn1-specific IgG+ Ab-secreting cells (ASCs) in spleen and bone marrow (BM), irrespective of the immunization route. Furthermore, i.n. immunization enhanced Pn1-specific IgA+ ASCs in BM more than s.c. immunizatiofimmu.2022.1078904n. However, a higher i.n. dose of the Pn1-CRM197 was needed to achieve IgG response comparable to that elicited by s.c. immunization with either adjuvant. We conclude that dmLT and mmCT enhance both induction and persistence of the neonatal immune response to the vaccine Pn1-CRM197, following mucosal or parenteral immunization. This indicates that dmLT and mmCT are promising adjuvants for developing safe and effective early life vaccination strategies.Peer reviewe

Drone-based Water Sampling and Characterization of Three Freshwater Harmful Algal Blooms in the United States

Freshwater harmful algal blooms (HABs), caused mostly by toxic cyanobacteria, produce a range of cyanotoxins that threaten the health of humans and domestic animals. Climate conditions and anthropogenic influences such as agricultural run-off can alter the onset and intensity of HABs. Little is known about the distribution and spread of freshwater HABs. Current sampling protocols in some lakes involve teams of researchers that collect samples by hand from a boat and/or from the shoreline. Water samples can be collected from the surface, from discrete-depth collections, and/or from depth-integrated intervals. These collections are often restricted to certain months of the year, and generally are only performed at a limited number of collection sites. In lakes with active HABs, surface samples are generally sufficient for HAB water quality assessments. We used a unique DrOne Water Sampling SystEm (DOWSE) to collect water samples from the surface of three different HABs in Ohio (Grand Lake St Marys, GLSM and Lake Erie) and Virginia (Lake Anna), United States in 2019. The DOWSE consisted of a 3D-printed sampling device tethered to a drone (uncrewed aerial system, or UAS), and was used to collect surface water samples at different distances (10–100 m) from the shore or from an anchored boat. One hundred and eighty water samples (40 at GLSM, 20 at Lake Erie, and 120 at Lake Anna) were collected and analyzed from 18 drone flights. Our methods included testing for cyanotoxins, phycocyanin, and nutrients from surface water samples. Mean concentrations of microcystins (MCs) in drone water samples were 15.00, 1.92, and 0.02 ppb for GLSM, Lake Erie, and Lake Anna, respectively. Lake Anna had low levels of anatoxin in nearly all (111/120) of the drone water samples. Mean concentrations of phycocyanin in drone water samples were 687, 38, and 62 ppb for GLSM, Lake Erie, and Lake Anna, respectively. High levels of total phosphorus were observed in the drone water samples from GLSM (mean of 0.34 mg/L) and Lake Erie (mean of 0.12 mg/L). Lake Anna had the highest variability of total phosphorus with concentrations that ranged from 0.01 mg/L to 0.21 mg/L, with a mean of 0.06 mg/L. Nitrate levels varied greatly across sites, inverse with bloom biomass, ranging from below detection to 3.64 mg/L, with highest mean values in Lake Erie followed by GLSM and Lake Anna, respectively. Drones offer a rapid, targeted collection of water samples from virtually anywhere on a lake with an active HAB without the need for a boat which can disturb the surrounding water. Drones are, however, limited in their ability to operate during inclement weather such as rain and heavy winds. Collectively, our results highlight numerous opportunities for drone-based water sampling technologies to track, predict, and respond to HABs in the future

Clinical Utility of a Unique Genome-Wide DNA Methylation Signature for KMT2A-Related Syndrome

Wiedemann\u2013Steiner syndrome (WDSTS) is a Mendelian syndromic intellectual disability (ID) condition associated with hypertrichosis cubiti, short stature, and characteristic facies caused by pathogenic variants in the KMT2A gene. Clinical features can be inconclusive in mild and unusual WDSTS presentations with variable ID (mild to severe), facies (typical or not) and other associated malformations (bone, cerebral, renal, cardiac and ophthalmological anomalies). Interpretation and classification of rare KMT2A variants can be challenging. A genome-wide DNA methylation episignature for KMT2A-related syndrome could allow functional classification of variants and provide insights into the pathophysiology of WDSTS. Therefore, we assessed genome-wide DNA methylation profiles in a cohort of 60 patients with clinical diagnosis for WDSTS or Kabuki and identified a unique highly sensitive and specific DNA methylation episignature as a molecular biomarker of WDSTS. WDSTS episignature enabled classification of variants of uncertain significance in the KMT2A gene as well as confirmation of diagnosis in patients with clinical presentation of WDSTS without known genetic variants. The changes in the methylation profile resulting from KMT2A mutations involve global reduction in methylation in various genes, including homeobox gene promoters. These findings provide novel insights into the molecular etiology of WDSTS and explain the broad phenotypic spectrum of the disease

Air pollution perception in ten countries during the COVID-19 pandemic

As largely documented in the literature, the stark restrictions enforced worldwide in 2020 to curb the COVID-19 pandemic also curtailed the production of air pollutants to some extent. This study investigates the perception of the air pollution as assessed by individuals located in ten countries: Australia, Brazil, China, Ghana, India, Iran, Italy, Norway, South Africa and the USA. The perceptions towards air quality were evaluated by employing an online survey administered in May 2020. Participants (N = 9394) in the ten countries expressed their opinions according to a Likert-scale response. A reduction in pollutant concentration was clearly perceived, albeit to a different extent, by all populations. The survey participants located in India and Italy perceived the largest drop in the air pollution concentration; conversely, the smallest variation was perceived among Chinese and Norwegian respondents. Among all the demographic indicators considered, only gender proved to be statistically significant

Potential cost savings with terrestrial rabies control

BACKGROUND: The cost-benefit of raccoon rabies control strategies such as oral rabies vaccination (ORV) are under evaluation. As an initial quantification of the potential cost savings for a control program, the collection of selected rabies cost data was pilot tested for five counties in New York State (NYS) in a three-year period. METHODS: Rabies costs reported to NYS from the study counties were computerized and linked to a human rabies exposure database. Consolidated costs by county and year were averaged and compared. RESULTS: Reported rabies-associated costs for all rabies variants totalled $2.1 million, for human rabies postexposure prophylaxes (PEP) (90.9$784,529). Average costs associated with the raccoon variant varied across counties from $440 to$1,885 per PEP, $14 to$44 per specimen, and $0.33 to$15 per pet vaccinated. CONCLUSION: Rabies costs vary widely by county in New York State, and were associated with human population size and methods used by counties to estimate costs. Rabies cost variability must be considered in developing estimates of possible ORV-related cost savings. Costs of PEPs and specimen preparation/shipments, as well as the costs of pet vaccination provided by this study may be valuable for development of more realistic scenarios in economic modelling of ORV costs versus benefits

Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis

Introduction: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. Methods and Results: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%–39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%–57%). Recipient age (odds ratio 1.02, 95% CI 1.01–1.04) and prior sternotomy (OR 1.57, 95% CI 0.99–2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. Conclusions: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT