Uptake Process Research Articles

Lack of involvement of CD63 and CD9 tetraspanins in the extracellular vesicle content delivery process

Extracellular vesicles (EVs) are thought to mediate intercellular communication by transferring cargoes from donor to acceptor cells. The EV content-delivery process within acceptor cells is still poorly characterized and debated. CD63 and CD9, members of the tetraspanin family, are highly enriched within EV membranes and are respectively enriched within multivesicular bodies/endosomes and at the plasma membrane of the cells. CD63 and CD9 have been suspected to regulate the EV uptake and delivery process. Here we used two independent assays and different cell models (HeLa, MDA-MB-231 and HEK293T cells) to assess the putative role of CD63 and CD9 in the EV delivery process that includes uptake and cargo delivery. Our results suggest that neither CD63, nor CD9 are required for this function.

Highly reusable bentonite clay@biochar@Fe3O4 nanocomposite for Hg(II) removal from synthetic and real wastewater.

The present research investigates the performance of bentonite clay@biochar@Fe3O4 nanocomposite in removing mercury ions (Hg2+) from aqueous media. The physical and structural properties of bentonite clay@biochar@Fe3O4 were determined using Brunauer-Emmett-Teller (BET), vibrating-sample magnetometer (VSM), transmission electron microscopy (TEM), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and Raman analyses. The highest uptake efficiency of Hg2+ was obtained at pH 6, Hg2+ concentration of 10 mg/L, contact time of 80 min, and the composite dose of 1.5 g/L. Under these conditions, the uptake efficiency of bentonite clay@biochar@Fe3O4 and bentonite clay was obtained as 98.78% and 97.67%, respectively, which are remarkable values. Also, the qmax values in Hg2+ removal using bentonite clay@biochar@Fe3O4 and bentonite clay were obtained as 66.66 and 60.98 mg/g, respectively. Moreover, the uptake process of Hg2+ ions using bentonite clay@biochar@Fe3O4 nanocomposite and bentonite was spontaneous, physical, favorable, and exothermic. Besides, the impact of various divalent ions such as Co2+, Cu2+, Pb2+, Ni2+, and Zn2+ on the removal efficiency of Hg2+ was studied. The results showed that Co2+ and Zn2+ ions have the highest and lowest interference effect in Hg2+ removal, respectively. Also, the reusability of both adsorbents showed that they have high stability and can be used for at least 5 cycles with high uptake efficiency. Additionally, the removal efficiency of chemical oxygen demand (COD), biochemical oxygen demand (BOD5), Hg2+, As3+, and As5+ from real wastewater using bentonite clay@biochar@Fe3O4 was obtained as 37.5%, 28.9%, 65%, 60.5%, and 50%, respectively, indicating its remarkable performance.

Experimental and Numerical Investigation into the Effect of Water Uptake on the Capacitance of an Organic Coating.

Water uptake by organic coating systems used for corrosion prevention on airframes is one of the principal contributors to the loss of barrier properties of the coating. We used equivalent circuit analyses of electrochemical impedance spectroscopy (EIS) data to track changes in coating layer capacitance for a two-layer coating system consisting of an epoxy primer and polyurethane topcoat immersed in NaCl solutions with different concentrations and temperatures. The capacitance curve exhibited two different response regions, consistent with the "two-stage kinetics" mechanisms for water uptake by the polymers. We tested several numerical diffusion models of water sorption and found the most successful to be one that varied the diffusion coefficient as a function of polymer type and immersion time and accounted for physical aging processes in the polymer. We employed the Brasher mixing law along with the water sorption model to estimate the coating capacitance as a function of water uptake. The predicted capacitance of the coating was found to be consistent with the capacitance obtained from the EIS data, which is consistent with theories that water uptake occurs via initial rapid transport followed by a much slower aging process. Thus, both these water uptake processes need to be considered when making EIS measurements to assess the state of a coating system.

Mechanism of Tumor-Platelet Communications in Cancer.

Thrombosis is one of the main complications in cancer patients often leading to mortality. However, the mechanisms underlying platelet hyperactivation are poorly understood. Murine and human platelets were isolated and treated with small extracellular vesicles (sEVs) from various cancer cell lines. The effects of these cancer-sEVs on platelets were evaluated both in vitro and in vivo using various approaches, including the detection of cancer-sEV-specific markers in murine platelets and patient samples, measurement of platelet activation and thrombosis assays. Signaling events induced by cancer-sEVs and leading to platelet activation were identified, and the use of blocking antibodies to prevent thrombosis was demonstrated. We demonstrate that platelets very effectively take up sEVs from aggressive cancer cells. The process of uptake is fast, proceeds effectively in circulation in mice, and is mediated by the abundant sEV membrane protein-CD63. The uptake of cancer-sEVs leads to the accumulation of cancer cell-specific RNA in platelets in vitro and in vivo. The human prostate cancer-sEV-specific RNA marker PCA3 is detected in platelets of ~70% of prostate cancer patients. This was markedly reduced after prostatectomy. In vitro studies showed that platelet uptake of cancer-sEVs induces strong platelet activation in a CD63-RPTPα (receptor-like protein tyrosine phosphatase alpha)-dependent manner. In contrast to physiological agonists ADP and thrombin, cancer-sEVs activate platelets via a noncanonical mechanism. Intravital studies demonstrated accelerated thrombosis both in murine tumor models and in mice that received intravenous injections of cancer-sEVs. The prothrombotic effects of cancer-sEVs were rescued by blocking CD63. Tumors communicate with platelets by means of sEVs, which deliver cancer markers and activate platelets in a CD63-dependent manner leading to thrombosis. This emphasizes the diagnostic and prognostic value of platelet-associated cancer markers and identifies new pathways for intervention.

Theoretical Analyses of Turgor Pressure during Stress Relaxation and Water Uptake, and after Changes in Expansive Growth Rate When Water Uptake Is Normal and Reduced.

Turgor pressure provides the force needed to stress and deform the cell walls of plants, algae, and fungi during expansive growth. However, turgor pressure plays another subtle but equally important role in expansive growth of walled cells: it connects the two biophysical processes of water uptake and wall deformation to ensure that the volumetric rates of water uptake and enlargement of the cell wall chamber are equal. In this study, the role of turgor pressure as a 'connector' is investigated analytically by employing validated and established biophysical equations. The objective is to determine the effect of 'wall loosening' on the magnitude of turgor pressure. It is known that an increase or decrease in turgor pressure and/or wall loosening rate increases or decreases the expansive growth rate, respectively. Interestingly, it is shown that an increase in the wall loosening rate decreases the turgor pressure slightly, thus reducing the effect of wall loosening on increasing the expansive growth rate. Other analyses reveal that reducing the rate of water uptake results in a larger decrease in turgor pressure with the same increase in wall loosening rate, which further reduces the effect of wall loosening on increasing the expansive growth rate.

Interactions and Covariation of Ecological Drivers Control CO2 Fluxes in an Alpine Peatland

Peatland ecosystems are a highly effective long-term carbon sink. However, the CO2 fluxes could be substantially altered by climate changes and the fate of carbon stored in these ecosystems is still uncertain. Currently, most studies concerning the carbon fluxes in peatlands were performed at high latitude sites, where these ecosystems are more widely distributed compared to temperate regions, where peatlands are less frequent and, in addition to climate pressure, increasingly threatened by human activities. However, the information we have on these peatlands is very scarce. To fill this knowledge gap, we studied CO2 fluxes in an alpine peatland, through light and dark incubations. Using the natural variation in ecological conditions, we identified the main drivers of CO2 fluxes, considering in particular their interactions and covariation. Ecosystem respiration and gross primary production were primarily stimulated by the lowering of the water table and the amount of photosynthetic radiation, respectively, whereas net ecosystem CO2 exchange showed greater variation along the growing season. The influence on CO2 fluxes of the interactions between the drivers investigated, including soil temperature and moisture as well as vegetation type and plant functional diversity, was found to be of pivotal importance. Finally, a substantial part of the variation in CO2 emission and uptake processes was regulated by the joint variation of atmospheric and edaphic factors. To understand and predict the CO2 dynamics of alpine peatlands, it is necessary to consider the interplays among ecological factors, especially in relation to the expected changes in climate and vegetation.

Antimony isotope fractionation and the key controls in the soil profiles of an antimony smelting area

The controlling factors of antimony migration and transformation in soil profiles are still unclear. Antimony isotopes might be a useful tool to trace it. In this paper, antimony isotopic compositions of plant and smelter-derived samples, and two soil profiles were measured for the first time. The δ123Sb values of the surface and bottom layers of the two soil profiles varied in 0.23‰−1.19‰ and 0.58‰−0.66‰, respectively, while δ123Sb of the smelter-derived samples varied in 0.29‰−0.38‰. The results show that the antimony isotopic compositions in the soil profiles are affected by post-depositional biogeochemical processes. The enrichment and loss of light isotopes at 0–10 cm and 10–40 cm layers of the contrasted soil profile may be controlled by plant uptake process. The loss and enrichment of heavy isotopes in the 0–10 cm and 10–25 cm layers of the antimony from smelting source in the polluted soil profile may be controlled by the adsorption process, while the enrichment of light isotopes in the 25–80 cm layer may be related to the reductive dissolution process. The conclusion emphasizes that the promotion of the Sb isotope fractionation mechanism will play a crucial role in understanding the migration and transformation behaviors of Sb in soil systems.

Intracellular Monitoring by Dendritic Cells – a New Way to Stay Informed – From Simple Scavenger to Active Gatherer.

Abstract The ability of dendritic cells (DCs) to acquire antigen from their environment is critical for the induction of an adaptive immune response and the maintenance of tolerance. Despite its importance, it is tacitly assumed that DCs acquire antigen by scavenging extracellular material via endocytosis or macropinocytosis. Here, using labeled RNA and time lapse imaging, we observe DCs siphoning material directly from live neighboring keratinocytes. This contact dependent mechanism of antigen uptake – which we term intracellular monitoring– accounts for a large percentage of RNA transferred to DCs, and cannot be blocked by inhibitors of known antigen uptake processes. It is exclusive to DCs, as other cell types do not efficiently siphon RNA from neighboring cells, and common among most DCs subsets tested. Langerhans cells with a conditional gene deletion can successfully overcome their deficiency by siphoning RNA and protein from their neighbors, but only if the deleted protein is expressed in the donating cell. Such behavior reframes our understanding of DCs from mere scavengers to highly informed supervisors with extensive access to the cytosol of surrounding cells. Intracellular monitoring may therefore play important roles in the maintenance of tolerance, defense against infection, and detection of cancerous cells.

A model of zinc dynamics evoked by intense stimulation at the cleft of hippocampal mossy fiber synapses.

Zinc is a transition metal that is particularly abundant in the mossy fibers of the hippocampal CA3 area. Despite the large number of studies about the zinc role in mossy fibers, the action of zinc in synaptic mechanisms is only partly known. The use of computational models can be a useful tool for this study. In a previous work, a model was developed to evaluate zinc dynamics at the mossy fiber synaptic cleft, following weak stimulation, insufficient to evoke zinc entry into postsynaptic neurons. For intense stimulation, cleft zinc effluxes must be considered. Therefore, the initial model was extended to include postsynaptic zinc effluxes based on the Goldman-Hodgkin-Katz current equation combined with Hodgkin and Huxley conductance changes. These effluxes occur through different postsynaptic escape routes, namely L- and N-types voltage-dependent calcium channels and NMDA receptors. For that purpose, various stimulations were assumed to induce high concentrations of cleft free zinc, named as intense (10μM), very intense (100μM) and extreme (500μM). It was observed that the main postsynaptic escape routes of cleft zinc are the L-type calcium channels, followed by the NMDA receptor channels and by N-type calcium channels. However, their relative contribution for cleft zinc clearance was relatively small and decreased for higher amounts of zinc, most likely due to the blockade action of zinc in postsynaptic receptors and channels. Therefore, it can be concluded that the larger the zinc release, the more predominant the zinc uptake process will be in the cleft zinc clearance.

Teacher feedback literacy, feedback regimes and iterative change: towards enhanced value in feedback processes

ABSTRACT This paper discusses teacher capacities for implementing learning-focused feedback processes within the social contexts of feedback regimes. Data are derived from longitudinal interviews carried out with six recipients of an award for good feedback practice; supplemented by documentary analysis of feedback artefacts; and an interview with the key instigator of the feedback award. Key elements of teacher feedback literacy are highlighted: designing feedback processes for student uptake; reflecting upon students’ responses to feedback; and iterative refinement of practices over time on the basis of cumulative experience. Engaging reflectively with students’ struggles with feedback potentially encourages teachers to adjust practices in the direction of learning-focused feedback processes, indicative of reflective feedback literacy. Broader social contexts in which feedback processes are enacted, including disciplinary and workload-related factors, are influenced by the feedback regimes that hold practices in place. Feedback regimes underpin the social practice of feedback in highlighting routines and procedures facilitating or constraining learning-focused feedback processes. Change elements of salience, congruence and value cast light on prospects for structural refinements to feedback regimes. A value perspective on change envisages making feedback practices satisfying for teachers as well as useful for students.

Value of implementation science and hybrid implementation research designs for nursing education research: A discussion paper

IntroductionNursing education research is complex and contextualized. The evaluation and impact of educational innovations on students, educators, and educational outcomes are influenced by the complexity of environments. Most interventional research in nursing is designed and implemented without considering the behavioral and contextual issues affecting educational innovations, uptake and change processes, and outcomes. Implementation science has emerged as a valuable methodology for designing and conducting interventional research that has the potential to translate evidence and innovations quickly into practice. PurposeThis paper aims to explore the value of implementation science theories, models, and frameworks and hybrid designs for interventional nursing education research and illustrate how these can be used in nursing education research. MethodsA brief overview of implementation science, the various types of theories, models and frameworks and Hybrid designs are provided. Illustrative examples demonstrating the incorporation of these methodologies in interventional nursing education research are provided. ResultsA brief overview of implementation and its key concepts namely context, implementation strategies, fidelity, outcomes, adaptation, and sustainability is provided. Three types of hybrid designs are discussed with examples in nursing education research. DiscussionThe implications of implementation science for nursing education research are: a) Accelerating uptake of innovations to improve educational outcomes, b) targeting systematic change in individual and organizational behaviour and c) ensuring the sustainability of teaching and learning innovations. ConclusionIncorporating implementation science in nursing education research can optimize the uptake of educational innovations in practice in a sustainable manner. Nurse educators should equip themselves with implementation science skills and develop competencies to enhance the delivery of effective and quality nursing education.

Current Progress and Future Prospect of Wheat Genetics Research towards an Enhanced Nitrogen Use Efficiency.

To improve the yield and quality of wheat is of great importance for food security worldwide. One of the most effective and significant approaches to achieve this goal is to enhance the nitrogen use efficiency (NUE) in wheat. In this review, a comprehensive understanding of the factors involved in the process of the wheat nitrogen uptake, assimilation and remobilization of nitrogen in wheat were introduced. An appropriate definition of NUE is vital prior to its precise evaluation for the following gene identification and breeding process. Apart from grain yield (GY) and grain protein content (GPC), the commonly recognized major indicators of NUE, grain protein deviation (GPD) could also be considered as a potential trait for NUE evaluation. As a complex quantitative trait, NUE is affected by transporter proteins, kinases, transcription factors (TFs) and micro RNAs (miRNAs), which participate in the nitrogen uptake process, as well as key enzymes, circadian regulators, cross-talks between carbon metabolism, which are associated with nitrogen assimilation and remobilization. A series of quantitative genetic loci (QTLs) and linking markers were compiled in the hope to help discover more efficient and useful genetic resources for breeding program. For future NUE improvement, an exploration for other criteria during selection process that incorporates morphological, physiological and biochemical traits is needed. Applying new technologies from phenomics will allow high-throughput NUE phenotyping and accelerate the breeding process. A combination of multi-omics techniques and the previously verified QTLs and molecular markers will facilitate the NUE QTL-mapping and novel gene identification.

Effect of Magnetic Water Treatment on the Growth, Nutritional Status, and Yield of Lettuce Plants with Irrigation Rate

Climate change is causing an increase in dry spells, altering rainfall patterns and soil moisture, and affecting water and nutrient plant uptake, which inevitably affects vegetable production. To mitigate this issue, some technologies that allow the maintenance of the ideal soil moisture for the uptake process are being investigated. Considering this, we hypothesize that the use of water treated with a magnetic field can increase water use efficiency in lettuce crop production. Thus, the present study aimed to evaluate the effect of the irrigation rate of magnetically treated water on biomass accumulation and nutrient uptake by lettuce plants. An experiment was conducted in a randomized block design with a 2 × 5 factorial arrangement of two water sources (conventional water and magnetically treated water) and five irrigation application rates to replace crop evaporation: 25, 50, 75, 100, and 125%, with five replicates. The use of magnetically treated water increased the concentrations of nitrogen and phosphorus in leaves, meaning that it induced higher nitrogen assimilation, leading to increases in agronomical characteristics (leaf number, fresh and dry shoot weight, fresh and dry root weight). The conclusions of this study showcase that magnetically treated water has beneficial effects on lettuce plants, improving their nutritional status and yield. Moreover, the results presented can lead to an increase in water use efficiency, thus optimizing irrigation management.

Catalytic activity of a new Cd (II) complex in the peroxidation of cyclohexane and the resulting CdO nanoparticles in the removal of Congo red

A new coordination complex of [Cd (2,2′‐bipyridine)(dipic) (H2O)2]. 7H2O (dipic2− = pyridine 2,6‐dicarboxylate) was synthesized under hydrothermal conditions. The crystal structure of Cd complex was characterized by X‐ray diffraction. The results confirmed that the coordination geometry of Cd2+ is a distorted pentagonal bipyramid. The complex was evaluated as a catalyst for the peroxidation of cyclohexane. The oxidation reaction was performed under mild conditions by hydrogen peroxide at room temperature. In the absence of HNO3, Cd complex exhibits a maximum yield of 31%. CdO nanoparticles were synthesized through thermal analysis of Cd complex and identified by various techniques. The ability of CdO nanoparticles was investigated for the removal of Congo red (CR). The effects of contact time, adsorbent dosage, and pH were evaluated using batch method. Studies have shown that the uptake process is pseudo‐second order. Also, the adsorption isotherm can be well fitted by the Langmuir model, while this process is spontaneous.

Adsorption Studies on the Removal of Anionic and Cationic Dyes from Aqueous Solutions Using Discarded Masks and Lignin.

The carbon materials derived from discarded masks and lignin are used as adsorbent to remove two types of reactive dyes present in textile wastewater: anionic and cationic. This paper introduces the results of batch experiments where Congo red (CR) and Malachite green (MG) are removed from wastewater onto the carbon material. The relationship between adsorption time, initial concentration, temperature and pH value of reactive dyes was investigated by batch experiments. It is discovered that pH 5.0-7.0 leads to the maximum effectiveness of CR and MG removal. The equilibrium adsorption capacities of CR and MG are found to be 232.02 and 352.11 mg/g, respectively. The adsorption processes of CR and MG are consistent with the Freundlich and Langmuir adsorption models, respectively. The thermodynamic processing of the adsorption data reveals the exothermic properties of the adsorption of both dyes. The results show that the dye uptake processes follow secondary kinetics. The primary adsorption mechanisms of MG and CR dyes on sulfonated discarded masks and alkaline lignin (DMAL) include pore filling, electrostatic attraction, π-π interactions and the synergistic interactions between the sulphate and the dyes. The synthesized DMAL with high adsorption efficiency is promising as an effective recyclable adsorbent for adsorbing dyes, especially MG dyes, from wastewater.

Physical ageing effect on water uptake and adhesion of epoxy coatings by EIS and the blister test

In a previous work, it was shown that the physical ageing of organic coatings had a strong effect onto the water uptake process, leading to lower water uptake values at saturation. The service life of an organic coating can be related to the water content at saturation, that may induce corrosion of the substrate, but also to the adhesion that prevents direct contact between the substrate and the aggressive environment. In this work, the effect of physical ageing onto water uptake and adhesion of epoxy coatings onto aluminium is then investigated.A model epoxy coating (DGEBA/Jeffamine230) was applied onto aluminium panels and fully cured using adequate thermal cycles. Different amounts of physical ageing were created by controlling the cooling of the systems and measured thanks to modulated differential scanning calorimetry (MDSC). The coated panels were then immersed in sodium chloride solution (30 g.L − 1) at different ageing temperatures. The water uptake was calculated using EIS thanks to the Brasher and Kingsbury relation and the diffusion coefficients were evaluated using the dual-Fick diffusion model.For different values of physical ageing and different amounts of water uptake, the adhesion was evaluated using the blister test method. The obtained results allow to discuss the effect of physical ageing onto the water uptake content and the adhesion of organic coatings.

Hollow polyphosphazene microcapsule with rigid-flexible coupling cationic skeletons for highly efficient and selective adsorption of anionic dyes from water

An amino-rich hollow polyphosphazene microcapsule with rigid-flexible coupling cationic skeleton (HTCM) was facilely prepared by one-step polycondensation from hexachlorocyclotriphosphazene and tetraethylenepentamine. The systematic adsorption studies for six single dye systems and three binary mixed dye systems showed that HTCM possessed a highly-efficient and selective adsorption behavior towards anionic dyes from water. Especially, the adsorption capacity of HTCM towards methyl orange (MO) at equilibrium reached 1009.66 mg g−1 at 25 °C, and the relative separation factors of anionic dye MO for three cationic dyes (methylene blue, Crystal violet and Rhodamine B) was up to 124.22, 124.87 and 136.35, respectively. The adsorption rate of MO onto HTCM was very rapid, attaining 68.6 % of adsorption equilibrium capacity for MO within the first 30 min. The adsorption kinetics, isotherm and thermodynamic analysis revealed that the uptake behavior of HTCM towards MO obeyed pseudo-second-order kinetic model, intraparticle diffusion model and Langmuir model, and the uptake process was spontaneous and endothermic. As verified from FT-IR and XPS analysis for HTCM before and after MO adsorption, the adsorption mechanism of HTCM for MO involved electrostatic interaction and hydrogen bonding. The present study promises the potential of HTCM for highly selective separation of anionic dyes from wastewater.

Intracellular bioaccumulation of the rare earth element Gadolinium in ciliate cells resulting in biogenic particle formation and excretion

Ciliates are abundant unicellular organisms capable of resisting high concentrations of metal ions in the environment caused by various anthropogenic activities. Understanding the cellular pathways involved in resistance to and detoxification of elements is required to predict the impact of ciliates on environmental element cycles. Here, we investigated the so far unknown process of tolerance, cellular uptake and bioaccumulation of the emerging rare earth element gadolinium (Gd) in the common ciliate Tetrahymena pyriformis. Gd treatment results in the intracellular formation and excretion of biogenic Gd-containing particles. This cellular process effectively removes dissolved Gd from the organic growth medium by 53.37% within 72 h. Based on light and electron microscopic observations, we postulate a detoxification pathway: Cells take up toxic Gd3+ ions from the medium by endocytosis, process them into stable Gd-containing particles within food vacuoles, and exocytose them. Stable biogenic particles can be isolated, which are relatively homogeneous and have a diameter of about 3 µm. They consist of the elements Gd, C, O, P, Na, Mg, K, and Ca. These findings broaden the view of metal ion accumulation by protists and are of relevance to understand environmental elemental cycles and may inspire approaches for metal recovery or bioremediation.

Important steps for PrEP uptake among adolescent men who have sex with men and transgender women in Brazil.

HIV Pre-exposure prophylaxis (PrEP) is an effective prevention tool, but there are still few studies about PrEP uptake among adolescents. We aimed to analyze the PrEP uptake process and factors associated with daily oral PrEP initiation among adolescent men who have sex with men (aMSM) and transgender women (aTGW) in Brazil. Baseline data from the first demonstration PrEP cohort study among aMSM and aTGW 15-19 years old (yo) ongoing in three large Brazilian cities (PrEP1519). After completing informed consent procedures, participants were enrolled in the cohort from February/2019 to February/2021. A socio-behavioral questionnaire was applied. Factors associated with PrEP initiation were assessed using a logistic regression model with adjusted prevalence ratios (aPR) and 95% confidence intervals (95%CI). Among recruited participants, 174 (19,2%) were aged 15-17 yo and 734 (80,8%) 18-19 yo. The rate of PrEP initiation was 78.2% and 77.4% for 15-17 yo and 18-19 yo, respectively. Factors associated with PrEP initiation were: black or mixed race (aPR 2.31; 95%CI: 1.10-4.84) among the younger adolescents 15-17 yo; experienced violence and/or discrimination due to their sexual orientation or gender identity (aPR 1.21; 95%CI: 1.01-1.46); transactional sex (aPR 1.32; 95%CI: 1.04-1.68); and having had between 2 to 5 sexual partners in the previous three months (aPR 1.39; 95%CI: 1.15-1.68) among those 18-19 yo. Unprotected receptive anal intercourse in the previous six months was associated with PrEP initiation in both age groups (aPR 1.98; 95%CI: 1.02-3.85 and aPR 1.45; 95%CI: 1.19-1.76 among 15-17 yo and 18-19 yo, respectively). The biggest challenge to promoting PrEP use for aMSM and aTGW was in the first steps of the PrEP uptake process. Once they were linked to the PrEP clinic, initiation rates were high.

Prolonged Ca2+ release refractoriness and T-tubule disruption as determinants of increased propensity to cardiac alternans in the hypertensive heart disease.

Cardiac alternans is a dynamical phenomenon linked to the genesis of severe arrhythmias and sudden cardiac death. It has been proposed that alternans is caused by alterations in Ca2+ handling by the sarcoplasmic reticulum (SR), in both the SR Ca2+ uptake and release processes. The hypertrophic myocardium is particularly prone to alternans, but the precise mechanisms underlying its increased vulnerability are not known. Mechanical alternans (intact hearts) and Ca2+ alternans (cardiac myocytes) were studied in spontaneously hypertensive rats (SHR) during the first year of age after the onset of hypertension and compared with age-matched normotensive rats. Subcellular Ca2+ alternans, T-tubule organization, SR Ca2+ uptake, and Ca2+ release refractoriness were measured. The increased susceptibility of SHR to high-frequency-induced mechanical and Ca2+ alternans appeared when the hypertrophy developed, associated with an adverse remodeling of the T-tubule network (6 mo). At the subcellular level, Ca2+ discordant alternans was also observed. From 6 mo of age, SHR myocytes showed a prolongation of Ca2+ release refractoriness without alterations in the capacity of SR Ca2+ removal, measured by the frequency-dependent acceleration of relaxation. Sensitizing SR Ca2+ release channels (RyR2) by a low dose of caffeine or by an increase in extracellular Ca2+ concentration, shortened refractoriness of SR Ca2+ release, and reduced alternans in SHR hearts. The tuning of SR Ca2+ release refractoriness is a crucial target to prevent cardiac alternans in a hypertrophic myocardium with an adverse T-tubule remodeling.