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Cocoa bean shell is one of the main by-products of chocolate manufacturing and possesses several compounds with biofunctionalities. It can function as an antibacterial agent, and its action is mostly reported against Streptococcus mutans. However, only a few studies have investigated the cocoa bean shell compounds responsible for this activity. This study aimed to evaluate several extracts of cocoa bean shells from different geographical origins and cocoa varieties and estimate their antimicrobial properties against different fungal and bacterial strains by determining their minimal inhibitory concentration. The results demonstrated antimicrobial activity of cocoa bean shell against one of the tested strains, S. mutans. Cocoa bean shell extracts were further analysed via LC-HRMS for untargeted metabolomic analysis. LC-HRMS data were analysed (preprocessing and statistical analyses) using the Workflow4Metabolomics platform. The latter enabled us to identify possible compounds responsible for the detected antimicrobial activity by comparing the more and less active extracts. Active extracts were not the most abundant in polyphenols but contained higher concentrations of two metabolites. After tentative annotation of these metabolites, one of them was identified and confirmed to be 7-methylxanthine. When tested alone, 7-methylxanthine did not display antibacterial activity. However, a possible cocktail effect due to the synergistic activity of this molecule along with other compounds in the cocoa bean shell extracts cannot be neglected. In conclusion, cocoa bean shell could be a functional ingredient with benefits for human health as it exhibited antibacterial activity against S. mutans. However, the antimicrobial mechanisms still need to be confirmed. [ABSTRACT FROM AUTHOR]

To fight the rising resistance of microorganisms to antibiotics, a strategy followed by several researchers is to focus on natural compounds, such as essential oils, as a source of potent antibacterial compounds. These last decades, hundreds of original papers have been written about microbiological assays that prove the antibacterial activity of essential oils and their use in the medical field. But can we really compare all the data available in the literature when the raw material, the microbiological assays, and/or the strains are different from one article to another? This review will point out the differences and the inadequate practices found in published articles that tested 2 lesser-studied essential oils–Spanish lavender and the ajowan–by the broth dilution method against Staphylococcus aureus , a human pathogenic bacterium. Many pitfalls were found in the literature, for example, a variable chemical composition rarely underlined by the authors, unidentified strains or clinical strains used without a related antibiogram, a lack of quality controls, and the assertion of questionable positive results. At last, some general guidelines that should be followed by every scientific researcher will be discussed. [ABSTRACT FROM AUTHOR]

Cocoa bean shell is one of the main by-products of chocolate manufacturing and possesses several compounds with biofunctionalities. It can function as an antibacterial agent, and its action is mostly reported against Streptococcus mutans. However, only a few studies have investigated the cocoa bean shell compounds responsible for this activity. This study aimed to evaluate several extracts of cocoa bean shells from different geographical origins and cocoa varieties and estimate their antimicrobial properties against different fungal and bacterial strains by determining their minimal inhibitory concentration. The results demonstrated antimicrobial activity of cocoa bean shell against one of the tested strains, S. mutans. Cocoa bean shell extracts were further analysed via LC-HRMS for untargeted metabolomic analysis. LC-HRMS data were analysed (preprocessing and statistical analyses) using the Workflow4Metabolomics platform. The latter enabled us to identify possible compounds responsible for the detected antimicrobial activity by comparing the more and less active extracts. Active extracts were not the most abundant in polyphenols but contained higher concentrations of two metabolites. After tentative annotation of these metabolites, one of them was identified and confirmed to be 7-methylxanthine. When tested alone, 7-methylxanthine did not display antibacterial activity. However, a possible cocktail effect due to the synergistic activity of this molecule along with other compounds in the cocoa bean shell extracts cannot be neglected. In conclusion, cocoa bean shell could be a functional ingredient with benefits for human health as it exhibited antibacterial activity against S. mutans. However, the antimicrobial mechanisms still need to be confirmed. [ABSTRACT FROM AUTHOR]

To fight the rising resistance of microorganisms to antibiotics, a strategy followed by several researchers is to focus on natural compounds, such as essential oils, as a source of potent antibacterial compounds. These last decades, hundreds of original papers have been written about microbiological assays that prove the antibacterial activity of essential oils and their use in the medical field. But can we really compare all the data available in the literature when the raw material, the microbiological assays, and/or the strains are different from one article to another? This review will point out the differences and the inadequate practices found in published articles that tested 2 lesser-studied essential oils–Spanish lavender and the ajowan–by the broth dilution method against Staphylococcus aureus , a human pathogenic bacterium. Many pitfalls were found in the literature, for example, a variable chemical composition rarely underlined by the authors, unidentified strains or clinical strains used without a related antibiogram, a lack of quality controls, and the assertion of questionable positive results. At last, some general guidelines that should be followed by every scientific researcher will be discussed. [ABSTRACT FROM AUTHOR]

Applied to health, literacy enhances the capacity to make the decisions that are necessary for autonomous health management. With this position paper, we intend to defend the thesis that the conditions for creating a national strategy for health literacy in Portugal along the life course are strengthened by the modernization of the National Health Service (SNS). First, we conducted a scope review on health literacy, and then we collected data on the National Strategy for Health Literacy and the different actions around it. The Literacy Program in Health and Care Integration, aligned with the modernization program of the National Health Service “SNS + Proximidade,” has been developed based on a life course approach. On the other hand, the National Strategy for Health Literacy, in addition to encompassing different dimensions of health literacy, from the individual and community level to the health systems, also presents strategic opportunities for intervention in contexts associated with different determinants of health. The digital Health Literacy Library of the SNS Portal is the first tool to integrate this strategy, being a digital repository of resources to support the promotion of health literacy, accessible at all times. These resources include interactive digital health books and the “My Health Journal,” encouraging people to organize their health information and take control of their health throughout their lives. The strategy also includes plans to bring these resources to people in various everyday contexts, such as public libraries, schools, and day centers, enabling their activation. At the same time, the digital modernization of the SNS allows health information to be made available in the Citizen Area of the SNS Portal, for example, by facilitating each citizen’s access to their health information in a confidential way. The entire process of implementing the health literacy strategy is dynamic and aims to encourage all citizens to participate in its construction and evaluation, and consequently in its adaptation and continuous improvement.

The eastern north coast of Greenland is considered to be highly sensitive to the ongoing Arctic warming, but there is a general lack of data on modern conditions and in particular on the modern distribution of climate and environmental proxies to provide a baseline and context for studies on past variability. Here we present a detailed investigation of 11 biogenic proxies preserved in surface sediments from the remote High Arctic Wandel Sea shelf, the entrance to the Independence, Hagen, and Danmark fjords. The composition of organic matter (organic carbon, C:N ratios, δ13C, δ15N, biogenic silica, and IP25) and microfossil assemblages revealed an overall low primary production dominated by benthic diatoms, especially at the shallow sites. While the benthic and planktic foraminiferal assemblages underline the intrusion of chilled Atlantic waters into the deeper parts of the study area, the distribution of organic‐walled dinoflagellate cysts is controlled by the local bathymetry and sea ice conditions. The distribution of the dinoflagellate cyst Polarella glacialismatches that of seasonal sea ice and the specific biomarker IP25, highlighting the potential of this species for paleo sea ice studies. The information inferred from our multiproxy study has important implications for the interpretation of the biogenic‐proxy signal preserved in sediments from circum‐Arctic fjords and shelf regions and can serve as a baseline for future studies. This is the first study of its kind in this area. A new multiproxy reference baseline is provided for assessing past changes in High Arctic fjord and shelf environmentsCysts of the ice‐dwelling dinoflagellate Polarella glacialisare tightly connected with seasonal sea ice and show promise as new paleo sea‐ice proxyBenthic diatoms and ice algae are the main primary producers in the shallower sites, whereas heterotrophic dinoflagellates and benthic foraminifera are indicative of Atlantic water intrusion and dominate at the deeper sites

Palynological analyses of sediment core MSM343310 from Disko Bugt (68°38′861°N, 53°49′493°W) document decadal‐ to centennial‐scale variability of sea surface conditions during the last ~3,600 years. Dinocyst fluxes (>104cysts/cm2yr−1) indicate a very high productivity. Dinocyst assemblages dominated by Islandinium minutum, Brigantediniumspp., Islandinium? cezare, and the cyst of Pentapharsodinium daleisuggest low surface salinity and marked shifts in summer sea surface temperature. The application of the modern analog technique to dinocyst assemblages, using an updated reference data set with new sites from the West Greenland margin, led to reconstruct decadal‐centennial‐scale variations in sea surface salinity and temperature, in phase with the δ18O variations in the Camp Century ice core. At ~1.5 ka BP, the seasonal sea ice cover records an important regime change, from winter‐only sea ice to more unstable conditions marked by successive cooling pulses with sea ice cover of up to 8 months/yr. The data suggest a close relationship between hydrographic conditions and regional climate over Greenland. Our record shows variations with a mean 200 years periodicity until ~2 ka BP, which supports the hypothesis of climate variations driven by solar variability. After 1.5 ka BP, our data show a variability characterized by a 60–70 year periodicity, which suggests linkages with the Atlantic Multidecadal Oscillation and southwestward migration of the atmospheric polar front. The most recent part of the record, from ~1900 CE to 2007 CE, is characterized by assemblages reflecting warmer surface conditions and reduced sea ice cover. Sea surface salinity changes are used as indicators of fresh‐meltwater events and sea ice cover as a diagnostic feature of regional climateChanging sea surface conditions from Disko Bugt are closely related with regional climate over GreenlandA marked change in surface waters at about 1.5 ka BP corresponds to enhanced sea ice cover and the onset of unstable conditions

Background Gastric mucosa-associated lymphoid tissue lymphoma (gMALT) and gastric adenocarcinoma (GC) are long-term complications of chronic Helicobacter pylori(HP) gastritis. Treatment of HP infection induces remission in most patients with gMALT. Endoscopic follow-up is not currently endorsed after complete remission. However, the risk of GC in these patients is unclear.Objective The objective of this study is to estimate GC risk in gMALT patients.Methods The National Cancer Institute Surveillance, Epidemiology and End Results 13 (SEER) database-Nov 2014 Sub (1992–2012) was used to identify adult patients diagnosed with gMALT between 1992 and 2012. The standardized incidence ratio of second primary GC after a latency period of 12 months was calculated and compared to a reference SEER cohort of identical age, sex and time period. The risk of GC in these patients was also stratified by latency period (five years) and age.Results We identified 2195 cases of gMALT lymphoma, and 20 (0.91%) of them subsequently developed GC with a relative risk (RR) of 4.32 (95% CI 2.64–6.67) compared to the American population. The median latency time was five years and the risk was maintained afterward (RR 4.92, 95% CI 2.45–8.79). When stratified by age group the risk was highest for the 45–64 group (RR 14.04, 95% CI 5.64–28.93).Conclusion gMALT lymphoma is associated with an increased risk of metachronous gastric adenocarcinoma. The risk is still present after more than five years of follow-up. Further studies may clarify the most adequate follow-up strategy.

Streptococcus agalactiaeis associated with an increasing burden of invasive disease. Its recognition as an agent of toxic shock-like syndrome can prevent casualties.Toxic shock syndrome is a rare life-threatening disease. The raising of new etiologic agent identification and antimicrobial therapy resistance poses new questions. We report a rare case of Streptococcus agalactiaetoxic shock–like syndrome and a literature review focusing on the presentation, current therapeutic challenges, and future approaches.

The 2016 World Health Assembly endorsed the elimination of hepatitis B virus (HBV) infection as a public health threat by 2030; existing therapies and prophylaxis measures make such elimination feasible, even in the absence of a virological cure. We aimed to estimate the national, regional, and global prevalence of HBV in the general population and among children aged 5 years and younger, as well as the rates of diagnosis, treatment, prophylaxis, and the future burden globally.

We explore the possibility to create hybrid quantum systems that combine ultracold atoms with graphene membranes. We investigate a setup in which a cold atom cloud is placed close to a free-standing sheet of graphene at distances of a few hundred nanometers. The atoms then couple strongly to the graphene membrane via Casimir-Polder forces. Temporal changes in the atomic state of the atomic cloud changes the Casimir-Polder interaction, thereby leading to the creation of a back-action force in the graphene sheet. This setup provides a controllable way to engineer ripples in a graphene sheet with cold atoms. [ABSTRACT FROM AUTHOR]

The Casimir-Polder interaction of ground-state and excited atoms with graphene is investigated with the aim to establish whether graphene systems can be used as a shield for vacuum fluctuations of an underlying substrate. We calculate the zero-temperature Casimir-Polder potential from the reflection coefficients of graphene within the framework of the Dirac model. For both doped and undoped graphene we show limits at which graphene could be used effectively as a shield. Additional results are given for AB-stacked bilayer graphene. [ABSTRACT FROM AUTHOR]

Casimir-Polder interactions between an atom and a macroscopic body are typically regarded as being due to the exchange of virtual photons. This is strictly true only at zero temperature. At finite temperatures, real-photon exchange can provide a significant contribution to the overall dispersion interaction. Here, we describe a resonant two-photon process between an atom and a planar interface. We derive a second-order effective Hamiltonian to explain how atoms can couple resonantly to the surface polariton modes of the dielectric medium. This leads to second-order energy exchanges which we compare with the standard nonresonant Casimir-Polder energy. [ABSTRACT FROM AUTHOR]

LundholmN., RibeiroS., AndersenT.J., KochT., GodheA., EkelundF. andEllegaardM. 2011. Buried alive – germination of up to a century-old marine protist resting stages. Phycologia50: 629–640. DOI: 10.2216/11-16.1We report on the survival and germination of up to a century-old marine protist resting stages naturally preserved in sediments from Koljö Fjord on the west coast of Sweden. This work has focused on germination of dinoflagellate cysts, but diatom resting stages were also observed. We record the longest known survival of dormant dinoflagellate cells. We individually isolated more than 1200 cysts of the three most abundant dinoflagellate taxa: Pentapharsodinium dalei, Lingulodinium polyedrumand Scrippsiellaspp. Germination success decreased with core depth, and all successful germinations took place within the first 2 wk of incubation. Pentapharsodinium daleihad the highest germination success rate, with a maximum of up to 80% in 28-yr-old sediment, and could successfully germinate from core sediments dated to 1920 ± 12. Scrippsiellaspp. cysts with cell contents occurred down to c.90-yr-old sediment and could germinate from down to ca. 40-yr-old sediments, with a maximum germination rate of 50–60% in recent sediments. Cysts of L. polyedrumgerminated frequently down to 20 yr and rarely to c.80 yr, with a maximum of 20–50% germination success in recent sediments. Cyst isolation under cooled conditions rather than at room temperature resulted in a significantly higher germination success in P. dalei, while no effect was observed for L. polyedrum. The time elapsed since slicing of the core affected survival of L. polyedrumcysts negatively, most likely due to the effect of oxygen. The long-term survival potential of benthic resting stages that we report here has important implications, as viable resting stages accumulated in bottom sediments can be transported back to the water column by, for example, bioturbation and human-mediated sediment dredging. Hence, the sediment may to a higher degree than previously considered play a role as seed bank. This is important in a changing climate and might have particularly severe impacts in the case of harmful species.

RibeiroS., LundholmN., AmorimA. andEllegaardM. 2010. Protoperidinium minutum(Dinophyceae) from Portugal: cyst–theca relationship and phylogenetic position on the basis of single-cell SSU and LSU rDNA sequencing. Phycologia49: 48–63. DOI: 10.2216/09-11.1Round brown spiny cysts are common elements of Recent and Quaternary dinoflagellate cyst records and are often used to infer past climate conditions. Echinidiniumand Islandinium, two cyst-based genera composed of round brown spiny cysts, are believed to have affinities within the Protoperidiniaceae. However, their biological counterparts are still virtually unknown. In this study, we examined the cyst–theca relationship of an Echinidinium-like cyst isolated from recent sediments of the Portuguese coast. The cysts (25–34 µm) had an intercalary theropylic archeopyle and numerous processes (4–9 µm) with tapered stems and minutely expanded tips. Germinated cells were identified as Protoperidinium minutumon the basis of theca morphology and tabulation. This taxon has a complicated taxonomic history and most likely represents a complex of species with very similar thecae but different cyst morphologies. To provide a first step in elucidating the phylogeny of P. minutumand its evolutionary relationship among the Protoperidiniaceae, we undertook the first molecular study of this taxon on the basis of small-subunit (SSU) and large-subunit (LSU) ribosomal (r)DNA genetic sequences obtained through single-cell polymerase chain reaction. On the basis of SSU rDNA analysis, P. minutumformed a clade together with the Diplopsaloideae, not grouping together with the other Protoperidiniumspecies. LSU rDNA-based phylogenies indicate P. minutumas early divergent within the Protoperidiniaceae. The evolutionary significance of round brown spiny cysts produced by P. minutum-like species and diplopsalids is discussed.

Design of dual antagonists for the chemokine receptors CCR2 and CCR5 will be greatly facilitated by knowledge of the structural differences of their binding sites. Thus, we computationally predicted the binding site of the dual CCR2/CCR5 antagonist N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzohepten-8-yl] carbonyl]amino]benzyl]tetrahydro-2H-pyran-4-aminium (TAK-779), and a CCR2-specific antagonist N-(carbamoylmethyl)-3-trifluoromethyl benzamido-parachlorobenzyl 3-aminopyrrolidine (Teijin compound 1) in an ensemble of predicted structures of human CCR2 and CCR5. Based on our predictions of the protein-ligand interactions, we examined the activity of the antagonists for cells expressing thirteen mutants of CCR2 and five mutants of CCR5. The results show that residues Trp982.60and Thr2927.40contribute significantly to the efficacy of both TAK-779 and Teijin compound 1, whereas His1213.33and Ile2636.55contribute significantly only to the antagonistic effect of Teijin compound 1 at CCR2. Mutation of residues Trp862.60and Tyr1083.32adversely affected the efficacy of TAK-779 in antagonizing CCR5-mediated chemotaxis. Y49A1.39and E291A7.39mutants of CCR2 showed a complete loss of CCL2 binding and chemotaxis, despite robust cell surface expression, suggesting that these residues are critical in maintaining the correct receptor architecture. Modeling studies support the hypothesis that the residues Tyr491.39, Trp982.60, Tyr1203.32, and Glu2917.39of CCR2 form a tight network of aromatic cluster and polar contacts between transmembrane helices 1, 2, 3, and 7.

Background: Chemokines play an important role in host defense coordinating the migration of immune cells. They do this by activating G-protein-coupled receptors and these proteins have attracted a huge investment in research and development by the pharmaceutical industry with the promise of new therapeutics for treating inflammatory diseases. Objective: Here, we provide a brief perspective of the in vitroassays that have been used in drug discovery for identifying potent and specific chemokine receptor antagonists. We outline the complexity of the chemokine system, give a historical perspective on the in vitroassays and types of assays used at different stages of discovery, followed by several examples of successes and failures in the clinic. Conclusion: We discuss the rationale for continuing, after several failures, targeting chemokine receptors and how screening may change with the increasing evidence of dimerization of chemokine receptors.

In this study, we report the first example of a nonpeptide chemokine receptor agonist, 2-{2-[4-(3-phenoxybenzyl)piperazin-1-yl]ethoxy}ethanol (ZK 756326), for the CC chemokine receptor CCR8. ZK 756326 inhibited the binding of the CCR8 ligand I-309 (CCL1), with an IC50 value of 1.8 µM. Furthermore, ZK 756326 was a full agonist of CCR8, dose-responsively eliciting an increase in intracellular calcium and cross-desensitizing the response of the receptor to CCL1. In addition, ZK 756326 stimulated extracellular acidification in cells expressing human CCR8. The ability of ZK 756326 to induce a response was receptor-specific and mediated through Gαi, because it could be blocked by treatment with pertussis toxin. The CCR8 agonist activated cells expressing murine CCR8, eliciting their chemotaxis and inducing phosphorylation of extracellular signal-regulated kinase ERK1/2. Like CCL1, ZK 756326 inhibited human immunodeficiency virus (HIV) fusion of cells expressing CD4 and CCR8. Finally, unlike mCCL1, ZK 756326 bound to and activated a form of mCCR8 that was mutated to eliminate O-linked sulfation at tyrosines 14 and 15. Therefore, ZK 756326 is most probably not binding in the same manner as CCL1 but can activate the switch mechanism involved in transducing signaling events. In summary, we have identified a nonpeptide agonist of CCR8. This compound may be useful in evaluating the physiological role of CCR8 in HIV infection, as well as in the general study of CCR8 biology without the constraints inherent to the use of protein agonists such as its natural ligand.

The basic and applied research efforts devoted to the development of DNA vaccines must be accompanied by manufacturing processes capable of being scaled up and delivering a clinical-grade product. This work describes a rapid process of this kind, based on hydrophobic interaction chromatography (HIC) for the production of milligram quantities of an experimental DNA rabies vaccine. Its properties and protective activity are tested in comparison with the same plasmid DNA purified with a commercial kit. The experimental DNA vaccine encoding the rabies virus glycoprotein was amplified in vivo in Escherichia coli. The plasmid was isolated by alkaline lysis, pre-purified and concentrated by isopropanol and (NH4)2SO4 precipitation, and purified by HIC and dialysis. Product quality was controlled by using high-performance liquid chromatography (HPLC), Southern slot blotting, agarose gel electrophoresis, the kinetic-QCL Limulus amoebocyte lysate assay, and protein assays. The expression of the rabies virus glycoprotein was tested in vitro in neuroblastoma cells. The production of rabies-virus-neutralising antibodies and the protection against an intracerebral virus challenge were tested in mice. One hundred and forty-two milligrams of the plasmid, with an HPLC purity greater than 99% were obtained from 4.5 l medium. Control analysis showed that the vaccine conforms to specifications in terms of impurities (endotoxins, genomic DNA, RNA, proteins). Furthermore, the final experimental vaccine induces rabies-virus-neutralising antibodies and protects mice against a rabies virus challenge. This study demonstrates that the method developed for the purification of milligram amounts of plasmid delivers an endotoxin-free, experimental rabies DNA vaccine, with protective activity similar to that obtained with the vaccine purified using a commercial kit. Copyright © 2001 John Wiley & Sons, Ltd.

We propose a scheme to actively cool the fundamental flexural (out-of-plane) mode of a graphene sheet via vacuum forces. Our setup consists of a cold-atom cloud placed close to a graphene sheet at distances of a few micrometers. The atoms couple to the graphene membrane via Casimir-Polder forces. By deriving a self-consistent set of equations governing the dynamics of the atomic gas and the flexural modes of the graphene, we show it is possible to cool graphene from room temperatures by actively (laser) cooling an atomic gas. By choosing the right set of experimental parameters we are able to cool a graphene sheet down to ~ 60 μK. [ABSTRACT FROM AUTHOR]

Effective population size (Ne) determines the rate of genetic drift and the relative influence of selection over random genetic changes. While free-living protist populations characteristically consist of huge numbers of cells (N), the absence of any estimates of contemporary Neraises the question whether protist effective population sizes are comparably large. Using microsatellite genotype data of strains derived from revived cysts of the marine dinoflagellate Pentapharsodinium daleifrom sections of a sediment record that spanned some 100 years, we present the first estimates of contemporary Nefor a local population in a free-living protist. The estimates of Neare relatively small, of the order of a few 100 individuals, and thus are similar in magnitude to values of Nereported for multicellular animals: the implications are that Neof P. daleiis of many orders of magnitude lower than the number of cells present (Ne/N∼ 10−12) and that stochastic genetic processes may be more prevalent in protist populations than previously anticipated.