Detection and Quantitative Analysis of Two Independent Binding Modes of a Small Ligand Responsible for DC-SIGN Clustering

DC-SIGN (dendritic cell-specific ICAM-3 grabbing non-integrin) is a C-type lectin receptor (CLRs) present, mainly in dendritic cells (DCs), as one of the major pattern recognition receptors (PRRs). This receptor has a relevant role in viral infection processes. Recent approaches aiming to block DC-SIGN have been presented as attractive anti-HIV strategies. DC-SIGN binds mannose or fucose-containing carbohydrates from viral proteins such as the HIV envelope glycoprotein gp120. We have previously demonstrated that multivalent dendrons bearing multiple copies of glycomimetic ligands were able to inhibit DC-SIGN-dependent HIV infection in cervical explant models. Optimization of glycomimetic ligands requires detailed characterization and analysis of their binding modes because they notably influence binding affinities. In a previous study we characterized the binding mode of DC-SIGN with ligand 1, which shows a single binding mode as demonstrated by NMR and X-ray crystallography. In this work we report the binding studies of DC-SIGN with pseudotrisaccharide 2, which has a larger affinity. Their binding was analysed by TR-NOESY and STD NMR experiments, combined with the CORCEMA-ST protocol and molecular modelling. These studies demonstrate that in solution the complex cannot be explained by a single binding mode. We describe the ensemble of ligand bound modes that best fit the experimental data and explain the higher inhibition values found for ligand

Effect of liposomal formulation of ascorbic acid on corneal permeability

Ascorbic acid (AA) has a pivotal role in corneal wound healing via stimulating the biosynthesis of highly organized extracellular matrix components, but its rapid degradation and low corneal permeability limits its therapeutic effects. In this paper, we present the pharmacokinetic properties of a liposomal-based formulation of AA in terms of corneal permeation. Chemical stability, shelf-life, and drug release rate of lyophilized liposome (AA-LLipo) formulation was determined in comparison to free-form of AA solution using high-performance liquid chromatography (HPLC) and rapid equilibrium dialysis. In vitro transcorneal permeability was studied using a parallel artificial membrane permeability assay (PAMPA). Ex vivo permeation was examined on AA-LLipo-treated porcine cornea by determining the AA content on the ocular surface, in the cornea as well as in the aqueous humor using HPLC, and by Raman-mapping visualizing the AA-distribution. Our results showed that the liposomal formulation improved the chemical stability of AA, while drug release was observed with the same kinetic efficiency as from the free-form of AA solution. Both corneal-PAMPA and porcine corneal permeability studies showed that AA-LLipo markedly improved the corneal absorption kinetics of AA, thus, increasing the AA content in the cornea and aqueous humor. AA-LLipo formulation could potentially increase the bioavailability of AA in corneal tissues

Impacts of Forest Fire on Understory Species Diversity in Canary Pine Ecosystems on the Island of La Palma

Forest fires are drivers of spatial patterns and temporal dynamics of vegetation and biodiversity. On the Canary Islands, large areas of pine forest exist, dominated by the endemic Canary Island pine, Pinus canariensis C. Sm. These mostly natural forests experience wildfires frequently. P. canariensis is well-adapted to such impacts and has the ability to re-sprout from both stems and branches. In recent decades, however, anthropogenically caused fires have increased, and climate change further enhances the likelihood of large forest fires. Through its dense, long needles, P. canariensis promotes cloud precipitation, which is an important ecosystem service for the freshwater supply of islands such as La Palma. Thus, it is important to understand the regeneration and vegetation dynamics of these ecosystems after fire. Here, we investigated species diversity patterns in the understory vegetation of P. canariensis forests after the large 2016 fire on the southern slopes of La Palma. We analyzed the effect of fire intensity, derived from Sentinel-2 NDVI differences, and of environmental variables, on species richness (alpha diversity) and compositional dissimilarity (beta diversity). We used redundancy analysis (dbRDA), Bray–Curtis dissimilarity, and variance partitioning for this analysis. Fire intensity accounted for a relatively small proportion of variation in alpha and beta diversity, while elevation was the most important predictor. Our results also reveal the important role of the endemic Lotus campylocladus ssp. hillebrandii (Christ) Sandral & D.D.Sokoloff for understory diversity after fire. Its dominance likely reduces the ability of other species to establish by taking up nutrients and water and by shading the ground. The mid-to long-term effects are unclear since Lotus is an important nitrogen fixer in P. canariensis forests and can reduce post-fire soil erosion on steep slopes

Effect of a two-year national quality improvement program on surgical checklist implementation

Use of the surgical checklist in Switzerland is still incomplete and unsatisfactory. A national improvement program was developed and conducted in Switzerland to implement and improve the use of the surgical safety checklists. The aims of the implementation program were to implement comprehensive and correct checklist use in participating hospitals in every patient and in every surgical procedure; and to improve safety climate and teamwork as important cultural context variables. 10 hospitals were selected for participation in the implementation program. A questionnaire assessing use, knowledge, and attitudes towards the checklist and the Safety Climate Survey were conducted at two measurement occasions each in October/November 2013 and January/February 2015. Significant increases emerged for frequency of checklist use (F(1,1001)=340.9, p<0.001), satisfaction (F(1,1232)=25.6, p<0.001), and knowledge(F(1,1294)=184.5, p<0.001). While significant differences in norms (F(1,1284)=17.9, p<0.001) and intentions (F(1,1284)=7.8, p<0.01) were observed, this was not the case for attitudes (F(1,1283)=.8, n.s.) and acceptance (F(1,1284)=0.1, n.s.). Significant differences for safety climate and teamwork emerged in the present study (F(1,3555)=11.8, p<0.001 and F(1,3554)=24.6, p<0.001, respectively). However, although statistical significance was reached, effects are very small and practical relevance is thus questionable. The results of the present study suggest that the quality improvement program conducted by the Swiss Patient Safety Foundation in 10 hospitals led to successful checklist implementation. The strongest effects were seen in aspects concerning behaviour and knowledge specifically related to checklist use. Less impact was achieved on general cultural variables safety climate and teamwork. However, as a trend was observable, these variables may simply need more time in order to change substantially

Assessing the potential replacement of laurel forest by a novel ecosystem in the steep terrain of an Oceanic Island

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. T. Biological invasions are a major global threat to biodiversity and often affect ecosystem services negatively. They are particularly problematic on oceanic islands where there are many narrow-ranged endemic species, and the biota may be very susceptible to invasion. Quantifying and mapping invasion processes are important steps for management and control but are challenging with the limited resources typically available and particularly difficult to implement on oceanic islands with very steep terrain. Remote sensing may provide an excellent solution in circumstances where the invading species can be reliably detected from imagery. We here develop a method to map the distribution of the alien chestnut (Castanea sativa Mill.) on the island of La Palma (Canary Islands, Spain), using freely available satellite images. On La Palma, the chestnut invasion threatens the iconic laurel forest, which has survived since the Tertiary period in the favourable climatic conditions of mountainous islands in the trade wind zone. We detect chestnut presence by taking advantage of the distinctive phenology of this alien tree, which retains its deciduousness while the native vegetation is evergreen. Using both Landsat 8 and Sentinel-2 (parallel analyses), we obtained images in two seasons (chestnuts leafless and in-leaf, respectively) and performed image regression to detect pixels changing from leafless to in-leaf chestnuts. We then applied supervised classification using Random Forest to map the present-day occurrence of the chestnut. Finally, we performed species distribution modelling to map the habitat suitability for chestnut on La Palma, to estimate which areas are prone to further invasion. Our results indicate that chestnuts occupy 1.2% of the total area of natural ecosystems on La Palma, with a further 12–17% representing suitable habitat that is not yet occupied. This enables targeted control measures with potential to successfully manage the invasion, given the relatively long generation time of the chestnut. Our method also enables research on the spread of the species since the earliest Landsat images

Patterns in recent and Holocene pollen accumulation rates across Europe - the Pollen Monitoring Programme Database as a tool for vegetation reconstruction

The collection of modern, spatially extensive pollen data is important for the interpretation of fossil pollen assemblages and the reconstruction of past vegetation communities in space and time. Modern datasets are readily available for percentage data but lacking for pollen accumulation rates (PARs). Filling this gap has been the motivation of the pollen monitoring network, whose contributors monitored pollen deposition in modified Tauber traps for several years or decades across Europe. Here we present this monitoring dataset consisting of 351 trap locations with a total of 2742 annual samples covering the period from 1981 to 2017. This dataset shows that total PAR is influenced by forest cover and climate parameters, which determine pollen productivity and correlate with latitude. Treeless vegetation produced PAR values of at least 140 grains cm−2 yr−1. Tree PAR increased by at least 400 grains cm−2 yr−1 with each 10 % increase in forest cover. Pollen traps situated beyond 200 km of the distribution of a given tree species still collect occasional pollen grains of that species. The threshold of this long-distance transport differs for individual species and is generally below 60 grains cm−2 yr−1. Comparisons between modern and fossil PAR from the same regions show similar values. For temperate taxa, modern analogues for fossil PARs are generally found downslope or southward of the fossil sites. While we do not find modern situations comparable to fossil PAR values of some taxa (e.g. Corylus), CO2 fertilization and land use may cause high modern PARs that are not documented in the fossil record. The modern data are now publicly available in the Neotoma Paleoecology Database and aid interpretations of fossil PAR data.publishedVersio

Is 'Opt-Out HIV Testing' a real option among pregnant women in rural districts in Kenya?

PMTCT allows people living with HIV to actualize childbearing. However, it also complicates motherhood, as the medical consequences and public health implications of non-adherence to PMTCT service recommendations disrupt socio-cultural expectations of childbearing and parenthood. This thesis aimed to study childbearing and adherence to PMTCT interventions focusing on how women living with HIV realize motherhood in Kenya. We sought to answer how women on ART experience motherhood and how motherhood aggravate adherence to PMTCT services Methods: A quantitative cross sectional study (I) with a questionnaire survey conducted among pregnant women at their first visit to antenatal clinic to study consent to HIV testing and three qualitative studies analyzed with content analysis (II and IV) and narrative structuring (III) were included. Qualitative interviews were performed with women living with HIV who were pregnant, recently delivered and those actively planning a pregnancy to explore views and experiences when seeking a pregnancy (II), the reasoning and deciding about adherence to PMTCT (III) and how motherhood interferes with HIV treatment (IV). Results: ‘Striving for motherhood’ was the overriding theme describing the desire of women on ART to be parents while negotiating the challenges of living with HIV (IIV). Children improve women’s position in society and are a sign of a happy and fulfilled life (II-IV). Of 900 pregnant women surveyed at their first visit to antenatal care clinic, only 17% understood that HIV testing is optional (I). Making an informed decision to decline HIV testing was associated with knowing that testing was optional (OR=5.44, 95%CI 3.44-8.59), not having a stable relationship with the child’s father (OR=1.76, 95%CI 1.02-3.03), and not having discussed HIV testing with a partner before the ANC visit (OR=2.64 95%CI 1.79-3.86). Socio-economic affluence and residence influence behaviors such as no condom use, non-disclosure of HIV infection, use of traditional medicine simultaneously with ART, home delivery and stigma and discrimination from partners, family and community, all of which undermine adherence to PMTCT services (II-IV). Structural shortcomings in PMTCT result in the lack of antiretroviral HIV medicines, practice of mixed infant feeding and missed appointments (I, III, IV). Conclusion: Motherhood is achieved at the cost of striving to balance socio-cultural expectations of childbearing that also conceals their HIV infection at the cost of nonadherence to PMTCT recommendations. Being infected with HIV does not remove the desire of motherhood and related socio-cultural demands. It is important to acknowledge the significance childbearing among women infected with HIV to improve adherence. Women with chronic illness such as HIV-infection who are dependent on continuous medication and health check-ups struggle to balance the desire for children with the needs related to their illness and the expectations of being a ‘good mother’

Family History of Schizophrenia and Bipolar Disorder as Risk Factors for Autism

The clinical and etiological relation between autism spectrum disorders (ASD) and schizophrenia is unclear. The degree to which these disorders share a basis in etiology has important implications for clinicians, researchers, and those affected. Our objective was to determine if a family history of schizophrenia and/or bipolar disorder was a risk factor for ASD. We conducted a case-control evaluation of histories of schizophrenia or bipolar disorder in first-degree relatives of probands in three samples, population registers in Sweden, Stockholm County, and Israel. Probands met criteria for ASD, and affection status of parents and siblings for schizophrenia and bipolar disorder were established

Poor mental health and sexual risk behaviours in Uganda: A cross-sectional population-based study

<p>Abstract</p> <p>Background</p> <p>Poor mental health predicts sexual risk behaviours in high-income countries, but little is known about this association in low-income settings in sub-Saharan Africa where HIV is prevalent. This study investigated whether depression, psychological distress and alcohol use are associated with sexual risk behaviours in young Ugandan adults.</p> <p>Method</p> <p>Household sampling was performed in two Ugandan districts, with 646 men and women aged 18-30 years recruited. Hopkins Symptoms Checklist-25 was used to assess the presence of depression and psychological distress. Alcohol use was assessed using a question about self-reported heavy-episodic drinking. Information on sexual risk behaviour was obtained concerning number of lifetime sexual partners, ongoing concurrent sexual relationships and condom use.</p> <p>Results</p> <p>Depression was associated with a greater number of lifetime partners and with having concurrent partners among women. Psychological distress was associated with a greater number of lifetime partners in both men and women and was marginally associated (p = 0.05) with having concurrent partners among women. Psychological distress was associated with inconsistent condom use among men. Alcohol use was associated with a greater number of lifetime partners and with having concurrent partners in both men and women, with particularly strong associations for both outcome measures found among women.</p> <p>Conclusion</p> <p>Poor mental health is associated with sexual risk behaviours in a low-income sub-Saharan African setting. HIV preventive interventions should consider including mental health and alcohol use reduction components into their intervention packages, in settings where depression, psychological distress and alcohol use are common.</p

Crimean-Congo hemorrhagic fever: epidemiological trends and controversies in treatment

Crimean-Congo hemorrhagic fever (CCHF) virus has the widest geographic range of all tick-borne viruses and is endemic in more than 30 countries in Eurasia and Africa. Over the past decade, new foci have emerged or re-emerged in the Balkans and neighboring areas. Here we discuss the factors influencing CCHF incidence and focus on the main issue of the use of ribavirin for treating this infection. Given the dynamics of CCHF emergence in the past decade, development of new anti-viral drugs and a vaccine is urgently needed to treat and prevent this acute, life-threatening disease