Can (Natural) deep eutectic systems increase the efficacy of ocular therapeutics?

The eye is one of the most complex organs in the human body, with a unique anatomy and physiology, being divided into anterior and posterior segments. Ocular diseases can occur in both segments, but different diseases affect different segments. Glaucoma and cataracts affect the anterior segment, while macular degeneration and diabetic retinopathy occur in the posterior segment. The easiest approach to treat ocular diseases, especially in the anterior segment, is through the administration of topical eye drops, but this route presents many constraints, namely precorneal dynamic and static ocular barriers. On the other hand, the delivery of drugs to the posterior segment of the eye is far more challenging and is mainly performed by the intravitreal route. However, it can lead to severe complications such as retinal detachment, endophthalmitis, increased intraocular pressure and haemorrhage. The design of new drug delivery systems for the anterior segment is very challenging, but targeting the posterior one is even more difficult and little progress has been made. In this review we will discuss various strategies including the incorporation of additives in the formulations, such as viscosity, permeability, and solubility enhancers, namely based on Deep eutectic systems (DES). Natural deep eutectic systems (NADES) have emerged to solve several problems encountered in pharmaceutical industry, regarding the pharmacokinetic and pharmacodynamic properties of drugs. NADES can contribute to the design of advanced technologies for ocular therapeutics, including hydrogels and nanomaterials. Here in, we revise some applications of (NA)DES in the development of new drug delivery systems that can be translated into the ophthalmology field.

Spatio-temporal dynamics of early somite segmentation in the chicken embryo.

During vertebrate embryo development, the body is progressively segmented along the anterior-posterior (A-P) axis early in development. The rate of somite formation is controlled by the somitogenesis embryo clock (EC), which was first described as gene expression oscillations of hairy1 (hes4) in the presomitic mesoderm of chick embryos with 15-20 somites. Here, the EC displays the same periodicity as somite formation, 90 min, whereas the posterior-most somites (44-52) only arise every 150 minutes, matched by a corresponding slower pace of the EC. Evidence suggests that the rostral-most somites are formed faster, however, their periodicity and the EC expression dynamics in these early stages are unknown. In this study, we used time-lapse imaging of chicken embryos from primitive streak to somitogenesis stages with high temporal resolution (3-minute intervals). We measured the length between the anterior-most and the last formed somitic clefts in each captured frame and developed a simple algorithm to automatically infer both the length and time of formation of each somite. We found that the occipital somites (up to somite 5) form at an average rate of 75 minutes, while somites 6 onwards are formed approximately every 90 minutes. We also assessed the expression dynamics of hairy1 using half-embryo explants cultured for different periods of time. This showed that EC hairy1 expression is highly dynamic prior to somitogenesis and assumes a clear oscillatory behaviour as the first somites are formed. Importantly, using ex ovo culture and live-imaging techniques, we showed that the hairy1 expression pattern recapitulates with the formation of each new pair of somites, indicating that somite segmentation is coupled with EC oscillations since the onset of somitogenesis.

Advances and challenges in the diagnosis and management of left ventricular noncompaction in adults: A literature review.

In the realm of cardiovascular health, isolated left ventricular noncompaction (LVNC) stands out for its distinct morphological features and the clinical challenges it presents, particularly in adults. This literature review explores the intricacies of LVNC, aiming to unravel its epidemiological spread, diagnostic hurdles, and therapeutic strategies. Despite technological advancements in cardiac imaging that have improved the recognition of LVNC, a significant gap persists alongside a fragmented understanding of its pathogenesis. The studies scrutinized reveal a broad spectrum of prevalence rates influenced by diverse diagnostic tools and demographic variables. This variation underscores the complexity of accurately identifying LVNC and the resultant implications for clinical management. The review succinctly addresses the need for precise guidelines to navigate the diagnosis of LVNC and outlines the imperative for tailored clinical management approaches that cater to the wide array of patient presentations, from asymptomatic cases to those with severe cardiac dysfunction. By highlighting the critical gaps in current literature-namely the absence of standardized diagnostic criteria and a comprehensive pathogenic model-the review sets the stage for future research directions. These endeavors are essential for enhancing diagnostic accuracy, refining management protocols, and ultimately improving patient outcomes in this complex subset of cardiomyopathy, thus contributing significantly to the advancement of cardiovascular medicine.

Quantitative Proteomics Reveal That CB2R Agonist JWH-133 Downregulates NF-κB Activation, Oxidative Stress, and Lysosomal Exocytosis from HIV-Infected Macrophages.

HIV-associated neurocognitive disorders (HAND) affect 15-55% of HIV-positive patients and effective therapies are unavailable. HIV-infected monocyte-derived macrophages (MDM) invade the brain of these individuals, promoting neurotoxicity. We demonstrated an increased expression of cathepsin B (CATB), a lysosomal protease, in monocytes and post-mortem brain tissues of women with HAND. Increased CATB release from HIV-infected MDM leads to neurotoxicity, and their secretion is associated with NF-κB activation, oxidative stress, and lysosomal exocytosis. Cannabinoid receptor 2 (CB2R) agonist, JWH-133, decreases HIV-1 replication, CATB secretion, and neurotoxicity from HIV-infected MDM, but the mechanisms are not entirely understood. We hypothesized that HIV-1 infection upregulates the expression of proteins associated with oxidative stress and that a CB2R agonist could reverse these effects. MDM were isolated from healthy women donors (n = 3), infected with HIV-1ADA, and treated with JWH-133. After 13 days post-infection, cell lysates were labeled by Tandem Mass Tag (TMT) and analyzed by LC/MS/MS quantitative proteomics bioinformatics. While HIV-1 infection upregulated CATB, NF-κB signaling, Nrf2-mediated oxidative stress response, and lysosomal exocytosis, JWH-133 treatment downregulated the expression of the proteins involved in these pathways. Our results suggest that JWH-133 is a potential alternative therapy against HIV-induced neurotoxicity and warrant in vivo studies to test its potential against HAND.

How Can Deep Eutectic Systems Promote Greener Processes in Medicinal Chemistry and Drug Discovery?

Chemists in the medicinal chemistry field are constantly searching for alternatives towards more sustainable and eco-friendly processes for the design and synthesis of drug candidates. The pharmaceutical industry is one of the most polluting industries, having a high E-factor, which is driving the adoption of more sustainable processes not only for new drug candidates, but also in the production of well-established active pharmaceutical ingredients. Deep eutectic systems (DESs) have emerged as a greener alternative to ionic liquids, and their potential to substitute traditional organic solvents in drug discovery has raised interest among scientists. With the use of DESs as alternative solvents, the processes become more attractive in terms of eco-friendliness and recyclability. Furthermore, they might be more effective through making the process simpler, faster, and with maximum efficiency. This review will be focused on the role and application of deep eutectic systems in drug discovery, using biocatalytic processes and traditional organic chemical reactions, as new environmentally benign alternative solvents. Furthermore, herein we also show that DESs, if used in the pharmaceutical industry, may have a significant effect on lowering production costs and decreasing the impact of this industry on the quality of the environment.

Food environment of bus terminals in the Rio de Janeiro metropolitan region.

PURPOSE: To describe and analyze the healthiness of formal and informal food establishments in bus terminals of the metropolitan region of the state of Rio de Janeiro. METHOD: An audit was conducted in 156 formal and 127 informal food establishments located in 14 bus terminals of the five most populous cities of the metropolitan region of Rio de Janeiro. Proportions of types of establishments and means (95%CI) of food availability indicators in formal and informal settings were calculated. For the formal setting, prices, proportions of accepted payment methods, days and hours of operation, and food categories with displayed advertising were described. RESULTS: The healthiness of food establishments in bus terminals was low (less than 36%). On average, ultra-processed food subgroups were 250% more available for purchase than fresh or minimally processed food. Purchasing food at these places was convenient because several forms of payment were available, and the opening hours of the establishments followed the peaks of movement. In addition, 73.3% of the advertising referred to ultra-processed drinks, and the cost-benefit of buying ultra-processed food was better than fresh or minimally processed food. CONCLUSION: The food environment of bus terminals in the metropolitan region of Rio de Janeiro promotes unhealthy eating. Regulatory public policies should focus on initiatives to limit the wide availability and advertising of ultra-processed food in spaces of great circulation of people.

An archaeobotanical and stable isotope approach to changing agricultural practices in the NW Mediterranean region around 4000 BC.

It has recently been observed, that a change in the crop spectrum happened during the so-called Middle Neolithic in France at ca. 4000 BC. An agricultural system based on free-threshing cereals (naked wheat and naked barley) seems to shift to one based on glume wheats. This is a major change for traditional farmers and this paper aims to shed light on its possible causes. Here we describe the results of new investigations in a key area for the understanding of this process: the NW Mediterranean arch, where free-threshing cereals are the main cultivars since ca. 5100 BC. New data confirm that the shift towards glume wheats is also observed in some sites of the NE of the Iberian Peninsula and that among the glume wheats that spread at ca. 4000 BC we should not only consider emmer and einkorn but also Timopheevi's wheat. Stable isotope analyses indicate no major decrease in soil fertility or alterations in local precipitation regimes. The agricultural change may be the result of a combination of the spread of damaging pests for free-threshing cereals and presumably new networks being developed with the North-eastern part of Italy and the Balkans.

Postpandemic Rebound in Noninvasive Group a Streptococcal Disease is not Synchronous with Winter RSV and Influenza Epidemics.

An increase in invasive group A Streptococcus infections was reported in 2022, associated with intense respiratory virus circulation. We describe a marked increase of noninvasive group A Streptococcus infections. Although the rise coincided with epidemics of respiratory syncytial virus and influenza, it continued after detection of these viruses fell to low levels, suggesting that other factors have contributed to this epidemiologic change.

Comparison of green solvents for the revalorization of orange by-products: Carotenoid extraction and in vitro antioxidant activity.

Orange peels contain a considerable number of bioactive compounds such as carotenoids, that can be used as ingredients in high-value products. The aim of this study was to compare orange peel extracts obtained with different green solvents (vegetable oils, fatty acids, and deep eutectic solvents (DES)). In addition, the chemical characterization of a new hydrophobic DES formed by octanoic acid and l-proline (C8:Pro) was performed. The extracts were compared in terms of carotenoid extraction, antioxidant activity by three methods, color, and environmental impact. The results confirmed that the mixture of C8:Pro is a DES and showed the highest carotenoid extraction (46.01 µg/g) compared to hexane (39.28 µg/g). The antioxidant activity was also the highest in C8:Pro (2438.8 µM TE/mL). Finally, two assessment models were used to evaluate the greenness and sustainability of the proposed extractions. These results demonstrated the potential use of orange peels in the circular economy and industry.

Food environment of bus terminals in the Rio de Janeiro metropolitan region / Ambiente alimentar de terminais rodoviários da região metropolitana do Rio de Janeiro

ABSTRACT PURPOSE To describe and analyze the healthiness of formal and informal food establishments in bus terminals of the metropolitan region of the state of Rio de Janeiro. METHOD An audit was conducted in 156 formal and 127 informal food establishments located in 14 bus terminals of the five most populous cities of the metropolitan region of Rio de Janeiro. Proportions of types of establishments and means (95%CI) of food availability indicators in formal and informal settings were calculated. For the formal setting, prices, proportions of accepted payment methods, days and hours of operation, and food categories with displayed advertising were described. RESULTS The healthiness of food establishments in bus terminals was low (less than 36%). On average, ultra-processed food subgroups were 250% more available for purchase than fresh or minimally processed food. Purchasing food at these places was convenient because several forms of payment were available, and the opening hours of the establishments followed the peaks of movement. In addition, 73.3% of the advertising referred to ultra-processed drinks, and the cost-benefit of buying ultra-processed food was better than fresh or minimally processed food. CONCLUSION The food environment of bus terminals in the metropolitan region of Rio de Janeiro promotes unhealthy eating. Regulatory public policies should focus on initiatives to limit the wide availability and advertising of ultra-processed food in spaces of great circulation of people.

RESUMO OBJETIVO Descrever e analisar a saudabilidade dos estabelecimentos com venda formal e informal de alimentos em terminais rodoviários da região metropolitana do Rio de Janeiro. MÉTODOS Realizou-se auditoria em 156 estabelecimentos formais e 127 pontos informais de venda de alimentos localizados em 14 terminais rodoviários das cinco cidades mais populosas da região metropolitana do Rio de Janeiro. Foram calculadas proporções de tipos de estabelecimentos e médias (IC95%) de indicadores de disponibilidade de alimentos nos ambientes formal e informal. Para o ambiente formal, foram descritos preços, proporções das formas de pagamento aceitas, dias e horários de funcionamento e categorias de alimentos com propaganda exposta. RESULTADOS A saudabilidade dos pontos de venda de alimentos nos terminais rodoviários era baixa (inferior a 36%). Em média, estavam disponíveis para compra 250% mais subgrupos de alimentos ultraprocessados do que in natura ou minimamente processados. Adquirir comida nesses locais era conveniente porque diversas formas de pagamento estavam disponíveis e os horários de funcionamento dos estabelecimentos acompanhavam os picos de movimentação. Além disso, 73,3% das propagandas se referiam a bebidas ultraprocessadas e o custo-benefício da compra de alimentos ultraprocessados era melhor que o de alimentos in natura ou minimamente processados. CONCLUSÃO O ambiente alimentar dos terminais rodoviários da região metropolitana do Rio de Janeiro promove uma alimentação não saudável. Políticas públicas de regulação devem se concentrar em iniciativas que limitem a ampla disponibilidade e publicidade de alimentos ultraprocessados nesses espaços de grande circulação de pessoas.

Plasmacytoid Dendritic Cells, the Expression of the Stimulator of Interferon Genes Protein (STING) and a Possible Role of Th17 Immune Response in Cervical Lesions Mediated by Human Papillomavirus.

Human papillomavirus (HPV) is a virus with a DNA structure that specifically targets squamous epithelial cells. In individuals with a healthy immune system, HPV infection is typically resolved naturally, leading to spontaneous regression. However, when the viral genetic material integrates into the host DNA, it can disrupt the immune response and eventually give rise to neoplastic manifestations. Remarkably, HPV infection appears to activate a protein called Stimulator of Interferon genes (STING), which contributes to the infiltration of Treg Foxp3 + cells. This cellular response acts as a predisposing factor in patients with HPV, potentially exacerbating the progression of the infection. The STING is versatile in different circumstances and can play a role in the immune response as an anti-tumour therapeutic target in HPV-related carcinogenesis. The function of Th17 cells is ambiguous, depending on the microenvironment in the tumour. In this study, 46 biopsies of the uterine cervix of human immunodeficiency virus (HIV) positive patients were divided into three groups: I-cervicitis (10); II-low-grade intraepithelial neoplasia (26); III-moderate or severe intraepithelial neoplasia (10) and it was performed an immunohistochemical technique with the specific antibodies to HPV, CD123, STING and IL17. Immunostained cells were quantified and statistically analysed. Antigens of HPV were detected in the cervical intraepithelial neoplasia (CIN) groups and were absent in cervicitis group. The expression of CD123 was positive in 10.87% of the casuistic, with no statistical difference among groups. STING was present in the three groups. Group 1 presented an area fraction that varied from 3 to 20%, group 2 presented a variation of 3-23% and group 3 presented an area fraction between 4 and 12%. Cells expressing IL17 were present in three groups, more frequent in cervicitis. Considering that the casuistic is composed of women carrying HIV, this infectious agent could influence the numerical similarities of the cells studied among three groups, even in the absence of HPV.

Stimulator of Interferon genes protein (STING) is versatile in different mechanisms in the immune response and may be a target in HPV-related carcinogenesis. Through immunohistochemistry it was detected IL17 in cervicitis and lesions with HPV. Also, CD123 + plasmacytoid cells seems to play a role both in cervicitis and lesions mediated by HPV.

Understanding the Relationship between Vaccine Supply Dead Space and Wasted COVID-19 Vaccine Doses.

INTRODUCTION: By July 2023, Brazil had administered approximately 540 million COVID-19 vaccine doses. This study aimed to quantify wasted doses resulting from dead space in vaccine supplies. METHODS: The vaccine supply was initially weighed, filled with distilled water, and expelled to simulate administration. Weighing it again after the application determined the dead space volume. Descriptive analyses calculated the waste rate/wasted dose count. RESULTS: The estimated total number of wasted vaccine doses using supplies with the lowest dead space was 62,097,338. CONCLUSIONS: Syringe dead space is a crucial factor in dose wastage, directly influencing the number of wasted doses.

International Pediatric COVID-19 Severity Over the Course of the Pandemic.

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear. Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children. Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded. Exposures: SARS-CoV-2 hospitalization during the stipulated time frame. Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy. Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children. Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Genomic Characterization of Salmonella Isangi: A Global Perspective of a Rare Serovar.

Salmonella Isangi is an infrequent serovar that has recently been reported in several countries due to nosocomial infections. A considerable number of reports indicate Salmonella Isangi multidrug resistance, especially to cephalosporins, which could potentially pose a risk to public health worldwide. Genomic analysis is an excellent tool for monitoring the emergence of microorganisms and related factors. In this context, the aim of this study was to carry out a genomic analysis of Salmonella Isangi isolated from poultry in Brazil, and to compare it with the available genomes from the Pathogen Detection database and Sequence Read Archive. A total of 142 genomes isolated from 11 different countries were investigated. A broad distribution of extended-spectrum beta-lactamase (ESBL) genes was identified in the Salmonella Isangi genomes examined (blaCTX-M-15, blaCTX-M-2, blaDHA-1, blaNDM-1, blaOXA-10, blaOXA-1, blaOXA-48, blaSCO-1, blaSHV-5, blaTEM-131, blaTEM-1B), primarily in South Africa. Resistome analysis revealed predicted resistance to aminoglycoside, sulfonamide, macrolide, tetracycline, trimethoprim, phenicol, chloramphenicol, and quaternary ammonium. Additionally, PMQR (plasmid-mediated quinolone resistance) genes qnr19, qnrB1, and qnrS1 were identified, along with point mutations in the genes gyrAD87N, gyrAS83F, and gyrBS464F, which confer resistance to ciprofloxacin and nalidixic acid. With regard to plasmids, we identified 17 different incompatibility groups, including IncC, Col(pHAD28), IncHI2, IncHI2A, IncM2, ColpVC, Col(Ye4449), Col156, IncR, IncI1(Alpha), IncFIB (pTU3), Col(B5512), IncQ1, IncL, IncN, IncFIB(pHCM2), and IncFIB (pN55391). Phylogenetic analysis revealed five clusters grouped by sequence type and antimicrobial gene distribution. The study highlights the need for monitoring rare serovars that may become emergent due to multidrug resistance.

Rescue of alveolar wall liquid secretion blocks fatal lung injury due to influenza-staphylococcal coinfection.

Secondary lung infection by inhaled Staphylococcus aureus (SA) is a common and lethal event for individuals infected with influenza A virus (IAV). How IAV disrupts host defense to promote SA infection in lung alveoli, where fatal lung injury occurs, is not known. We addressed this issue using real-time determinations of alveolar responses to IAV in live, intact, perfused lungs. Our findings show that IAV infection blocked defensive alveolar wall liquid (AWL) secretion and induced airspace liquid absorption, thereby reversing normal alveolar liquid dynamics and inhibiting alveolar clearance of inhaled SA. Loss of AWL secretion resulted from inhibition of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel in the alveolar epithelium, and airspace liquid absorption was caused by stimulation of the alveolar epithelial Na+ channel (ENaC). Loss of AWL secretion promoted alveolar stabilization of inhaled SA, but rescue of AWL secretion protected against alveolar SA stabilization and fatal SA-induced lung injury in IAV-infected mice. These findings reveal a central role for AWL secretion in alveolar defense against inhaled SA and identify AWL inhibition as a critical mechanism of IAV lung pathogenesis. AWL rescue may represent a new therapeutic approach for IAV-SA coinfection.

Ionic Levothyroxine Formulations: Synthesis, Bioavailability, and Cytotoxicity Studies.

Thyroid diseases affect a considerable portion of the population, with hypothyroidism being one of the most commonly reported thyroid diseases. Levothyroxine (T4) is clinically used to treat hypothyroidism and suppress thyroid stimulating hormone secretion in other thyroid diseases. In this work, an attempt to improve T4 solubility is made through the synthesis of ionic liquids (ILs) based on this drug. In this context, [Na][T4] was combined with choline [Ch]+ and 1-(2-hydroxyethyl)-3-methylimidazolium [C2OHMiM] + cations in order to prepare the desired T4-ILs. All compounds were characterized by NMR, ATR-FTIR, elemental analysis, and DSC, aiming to check their chemical structure, purities, and thermal properties. The serum, water, and PBS solubilities of the T4-ILs were compared to [Na][T4], as well as the permeability assays. It is important to note an improved adsorption capacity, in which no significant cytotoxicity was observed against L929 cells. [C2OHMiM][T4] seems to be a good alternative to the commercial levothyroxine sodium salt with promising bioavailability.

Using Natural Deep Eutectic Systems as Alternative Media for Ocular Applications.

The major goal of this work was to study the potential of natural deep eutectic systems (NADES) as new media for ocular formulations. In formulating eye drops, it is important to increase the retention time of the drug on the surface of eye; hence, due to their high viscosity, NADES may be interesting candidates for formulation. Different systems composed of combinations of sugars, polyols, amino acids, and choline derivatives were prepared and then characterized in terms of rheological and physicochemical properties. Our results showed that 5-10% (w/v) aqueous solutions of NADES have a good profile in terms of viscosity (0.8 to 1.2 mPa.s), osmolarity (412 to 1883 mOsmol), and pH (7.4) for their incorporation of ocular drops. Additionally, contact angle and refractive index were determined. Acetazolamide (ACZ), a highly insoluble drug used to treat glaucoma, was used as proof-of-concept. Herein, we show that NADES can increase the solubility of ACZ in aqueous solutions by at least up to 3 times, making it useful for the formulation of ACZ into ocular drops and thereby enabling more efficient treatment. The cytotoxicity assays demonstrated that NADES are biocompatible up to 5% (w/v) in aqueous media, promoting cell viability (above 80%) when compared to the control after 24 h incubation in ARPE-19 cells. Furthermore, when ACZ is dissolved in aqueous solutions of NADES, the cytotoxicity is not affected in this range of concentrations. Although further studies are necessary to design an optimal formulation incorporating NADES, this study shows that these eutectics can be powerful tools in the formulation of ocular drugs.

Morphometrics of waterlogged archaeological seeds give new insights into the domestication and spread of Papaver somniferum L. in Western Europe.

Domesticated opium poppy Papaver somniferum L. subsp. somniferum probably originated in the Western Mediterranean from its possible wild progenitor, Papaver somniferum L. subsp. setigerum and spread to other European regions. Seeds of opium poppy have been identified in different European regions since the Early Neolithic (from the 6th millennium cal. BC onwards) period. However, until recently, the absence of morphological identification criteria has prevented the discrimination between wild and domestic morphotypes. New morphometric approaches to distinguish modern subspecies have been proven to be applicable to waterlogged archaeological remains, opening the possibility of understanding the process of domestication of the plant in both time and space. This paper applies seed outline analyses, namely elliptic Fourier transforms, combined with size and number of cells to archaeological waterlogged Papaver seeds throughout the Neolithic period in the NW Mediterranean and the surroundings of the Alps. Furthermore, one example from the Late Bronze Age (LBA) was added to see what kind of differences appeared during the >1000 years between the end of the Neolithic and the LBA. The aim of the study is to classify the archaeological seeds as domestic or wild morphotypes and observe morphometric changes in connection to geographical and chronological patterns that can explain the spread and domestication process(es) of this important crop. A total of 295 archaeological seeds coming from 10 waterlogged sites dating between 5300-2300 cal. BC (Neolithic), and one LBA site dating to 1070 cal. BC were analysed. The results indicate the presence of seeds, similar to the wild morphotype, in the Mediterranean sites and larger seeds, similar to the domestic morphotype, in the regions surrounding the Alps. The number of cells mainly increased during the Late Neolithic (3300 to 2300 cal. BC) and, finally, in the Late Bronze Age (ca. 1050-800 cal. BC), larger, morphologically domesticated seeds are clearly predominant. A change in the shape of the seeds is only clearly visible in the LBA material. Altogether our results suggest that opium poppy seeds show no sign of domestication in the early periods of the Neolithic, despite the fact that the plant was very probably already cultivated at that time in the western Mediterranean region.

Unusual carriage of virulence genes sasX/sesI/shsA by nosocomial Staphylococcus haemolyticus from Brazil.

Background: Staphylococcus haemolyticus is an emerging threat in the nosocomial environment but only some virulence factors are known. Materials & methods: The frequency of the sasX gene (or orthologues sesI/shsA), encoding an invasiveness-related surface-associated protein, in S. haemolyticus was detected in different hospitals in Rio de Janeiro. Results: 9.4% of strains were sasX/sesI/shsA-positive, some were in the context of the ΦSPß-like prophage and devoid of CRISPR systems, indicating potential transferability of their virulence genes. Gene sequencing evidenced that Brazilian S. haemolyticus harbored sesI, instead of the usual sasX, while S. epidermidis had sasX instead of sesI, suggesting horizontal acquisition. Conclusion: The contexts of Brazilian sasX/sesI/shsA favor transfer, which is alarming given the difficulty in treating infections caused by S. haemolyticus.

A Hydrophilic Sulfated Resveratrol Derivative for Topical Application: Sensitization and Anti-Allergic Potential.

Resveratrol (RSV), a naturally occurring metabolite, is widely used in skincare products, but its hydrophobicity impairs its own incorporation into cosmetic formulations. RSV-GS is a synthetic hydrophilic sulfated glycosylated derivative inspired by marine natural products that present a lower cytotoxicity than RSV while exhibiting similar levels of bioactivity. Herein, we predict the skin sensitization potential of this new compound using an in vitro approach based on the OECD 442E guideline. Furthermore, the anti-allergic potential of RSV-GS was also disclosed. The monocyte THP-1 cell line was stimulated with RSV and RSV-GS in the presence or absence of the extreme skin allergen 1-fluoro-2,4-dinitrobenzene (DNFB). The results demonstrated that RSV-GS alone (500 µM) evoked a relative fluorescence index (RFI) lower than the thresholds established by the OECD guideline for CD54 (200%) and CD86 (150%), indicating the absence of a skin sensitization potential. Interestingly, in the presence of the skin allergen DNFB, RSV-GS exhibited the ability to rescue the DNFB-induced maturation of THP-1 cells, with RFI values lower than those for RSV, suggesting the potential of RSV-GS to mitigate skin sensitization evoked by allergens and, consequently, allergic contact dermatitis. These results open new avenues for the use of RSV-GS as a safe and anti-allergic active cosmetic ingredient.