Unlocking bacterial defense: Exploring the potent inhibition of NorA efflux pump by coumarin derivatives in Staphylococcus aureus.

The occurrence of bacterial resistance has been increasing, compromising the treatment of various infections. The high virulence of Staphylococcus aureus allows for the maintenance of the infectious process, causing many deaths and hospitalizations. The MepA and NorA efflux pumps are transporter proteins responsible for expelling antimicrobial agents such as fluoroquinolones from the bacterial cell. Coumarins are phenolic compounds that have been studied for their diverse biological actions, including against bacteria. A pharmacokinetic in silico characterization of compounds C10, C11, C13, and C14 was carried out according to the principles of Lipinski's Rule of Five, in addition to searching for similarity in ChemBL and subsequent search for publications in CAS SciFinder. All compounds were evaluated for their in vitro antibacterial and modulatory activity against standard and multidrug-resistant Gram-positive and Gram-negative strains. The effect of coumarins C9, C10, C11, C13, and C14 as efflux pump inhibitors in Staphylococcus aureus strains was evaluated using the microdilution method (MepA or NorA) and fluorimetry (NorA). The behavior of coumarins regarding the efflux pump was determined from their interaction properties with the membrane and coumarin-protein using molecular docking and molecular dynamics simulations. Only the isolated coumarin compound C13 showed antibacterial activity against standard strains of Staphylococcus aureus and Escherichia coli. However, the other tested coumarins showed modulatory capacity for fluoroquinolone and aminoglycoside antibacterials. Compounds C10, C13, and C14 were effective in reducing the MIC of both antibiotics for both multidrug-resistant strains, while C11 potentiated the effect of norfloxacin and gentamicin for Gram-positive and Gram-negative bacteria and only norfloxacin for Gram-negative. Only coumarin C14 produced synergistic effects when associated with ciprofloxacin in MepA-carrying strains. All tested coumarins have the ability to inhibit the NorA efflux pump present in Staphylococcus aureus, both in reducing the MIC and inducing increased ethidium bromide fluorescence emission in fluorimetry. The findings of this study offer an atomistic perspective on the potential of coumarins as active inhibitors of the NorA pump, highlighting their specific mode of action mainly targeting protein inhibition. In molecular docking, it was observed that coumarins are capable of interacting with various amino acid residues of the NorA pump. The simulation showed that coumarin C10 can cross the bilayer; however, the other coumarins interacted with the membrane but were unable to cross it. Coumarins demonstrated their potentiating role in the effect of norfloxacin through a dual mechanism: efflux pump inhibition through direct interaction with the protein (C9, C10, C11, and C13) and increased interaction with the membrane (C10 and C13). In the context of pharmacokinetic prediction studies, the studied structures have a suitable chemical profile for possible oral use. We suggest that coumarin derivatives may be an interesting alternative in the future for the treatment of resistant bacterial infections, with the possibility of a synergistic effect with other antibacterials, although further studies are needed to characterize their therapeutic effects and toxicity.

Effects of different temperature-humidity indexes on milk traits of Holstein cows: A 10-year retrospective study.

Test-day records (n = 723,091) collected between 2012 and 2021 from 43,015 Holstein cows at 157 farms located in northern Italy were used to study the effects of heat load on milk production and composition a posteriori. The data consisted of milk yield (kg/d), traditional gross composition traits, somatic cell score (SCS), differential somatic cell count (%), milk ß-hydroxybutyrate (BHB, mmol/L), milk urea (mg/dL), and milk fatty acid composition (g/100 g of milk). Test-day records were then associated with their relative temperature-humidity indexes (THI) calculated using historical environmental data registered by weather stations. Indexes were created using either yearly or summer THI data. The yearly indexes included the average daily THI (adTHI) and the maximum daily THI (mdTHI) measured throughout the whole year, and the summer indexes focused on 3 mo only (June-August) and included the average daily summer THI (adTHIs), the maximum daily summer THI (mdTHIs), and the average daily THI of the hottest 4 h of the day (adTHI4h; 1200-1600 h). All indexes had significant effects on the majority of milk traits analyzed, with, in particular, adTHI and mdTHI being highly significant in explaining the variation of all traits. Milk yield started to decline at a higher THI compared with protein and fat content. The reduction in fat ceased in the elevated THI experienced during the summer months, as demonstrated by adTHIs, mdTHIs, and adTHI4h. The cows had a tendency for increased BHB concentration with elevated THI, suggesting a greater risk of negative energy balance in presence of heat stress. Furthermore, the concentration of the de novo fatty acids C14:0 and C16:0 was reduced in higher THI, reflecting altered mammary gland activity upon elevated heat load and stress. Milk SCS tended to increase with higher adTHIs, mdTHIs, and adTHI4h. The use of yearly indexes is recommended when investigating the effects of heat load on milk composition, whereas summer indexes are suggested when investigating traits influenced by extreme conditions, such as SCS and milk yield. With global temperatures expected to further rise in the upcoming decades, early and easy identification of cows or herds suffering from heat stress, such as through changes in milk composition, is crucial for timely intervention. Adapting measures to mitigate such effects of elevated THI on milk yield and composition is a necessity for the dairy industry to prevent detrimental impacts on dairy production.

Burden of disease and costs for the Unified Health System in Brazil due to diseases whose alcohol consumption is a necessary cause: an ecological study.

OBJECTIVE: This study aimed to quantify the health and economic impacts of alcohol consumption in Brazil for 2019. STUDY DESIGN: Ecological study using secondary data sources. METHODS: We calculated the disease burden using estimates from the Global Burden of Disease study, which incorporated data from health surveys and hospital records. Costs were estimated based on direct expenses recorded in the Hospital and Outpatient Information System of the Unified Health System, with data by sex, age group, cause, and Federative Units. RESULTS: Alcohol consumption was a necessary cause for 30,355 deaths and approximately 1.69 million disability-adjusted life years in Brazil, representing 2.2% and 2.6% of the national totals, respectively. The impact was more pronounced among men, in the Northeast region and within the 40- to 64-year-old age group. The total costs attributed to these outcomes reached approximately Int$43.1 million, with hospital admissions accounting for 94.16% of these expenses. CONCLUSION: In 2019, alcohol consumption had a significant impact on both the health of Brazilians and the expenses of the health system. As a preventable risk factor, alcohol consumption necessitates effective intersectoral strategies to mitigate its burden.

HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review.

BACKGROUND: The aim was to evaluate the frequency, clinicopathological features, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign HPV-related epithelial lesions of the oropharynx over the last 25 years. Moreover, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. MATERIAL AND METHODS: A cross-sectional study analyzed OP-SCC, squamous papilloma, verruca vulgaris, and condyloma accuminatum, diagnosed from 1997 to 2021. HPV status of OP-SCC was determined by immunohistochemistry and "in situ" hybridization. Bivariate statistics were performed (p≤0.05). For the literature review, MEDLINE/PubMed, Web of Science, EMBASE, and Scopus were searched. Two independent reviewers assessed the studies for eligibility. RESULTS: Cross-sectional: 211 OP-SCC (63.0%) and 124 benign lesions (37.0%) were included. OP-SCC frequency increased gradually over time, whereas benign lesions had steady trends. OP-SCC affected more males (n= 171; 81.0%), though the relative frequency in females rose over time. Smoking (n= 127; 60.2%) was common in OP-SCC. Nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors had similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (n= 32; 26.7%) women (n= 71; 57.3%), in the soft palate (n=101; 81.5%). LITERATURE REVIEW: 32 studies were included, and in 60% of them, HPV frequency in OP-SCC was less than 25%. CONCLUSIONS: OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency over the evaluated period.

Prevalence of basilar artery dolichoectasia in patients with acute ischemic stroke or transient ischemic attack in a single center of Spain. / Prevalencia de la dolicoectasia de la arteria basilar en pacientes con ictus isquémico agudo o ataque isquémico transitorio en un centro español.

INTRODUCTION: Basilar artery dolichoectasia (BADE) refers to abnormal enlargement or displacement of the basilar artery (BA). The previously reported prevalence of BADE among patients with stroke is 0.3 to 33.1%, however, it might vary among studied populations. We aim is to determine the prevalence of BADE in patients presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) in a Stroke Unit in a single center in Spain. PATIENTS AND METHODS: Patients 50 years old or older presenting with AIS or TIA were eligible for inclusion. Demographic and clinical data were prospectively collected. Two neuroradiologists, blind to each other, assessed BA morphology. RESULTS: Among 126 patients, 34.1% fulfilled the criteria for BADE (ectasia or dolichosis). BADE was associated with advanced age (p = 0.04). Patients with fetal-type circle of Willis presented smaller BA diameters (2.9 ± 0.1 vs. 3.5 ± 0.1; p < 0.001), whereas patients with lacunar strokes presented a greater diameter than other stroke subtypes (3.8 ± 0.3 mm vs. 3.3 ± 0.1 mm; p = 0.04). DISCUSSION AND CONCLUSIONS: In this single-center study of patients presenting with AIS or TIA, the prevalence of BADE (ectasia or dolichosis) is high. Further studies focusing on Spaniards should confirm our results.

TITLE: Prevalencia de la dolicoectasia de la arteria basilar en pacientes con ictus isquémico agudo o ataque isquémico transitorio en un centro español.Introducción. La dolicoectasia de la arteria basilar (DEAB) es un término que se refiere a la dilatación o elongación anormal de la arteria basilar (AB). La prevalencia de DEAB notificada hasta la fecha en pacientes con ictus es del 0,3 al 33,1%; sin embargo, puede variar entre poblaciones. Se propuso determinar la prevalencia de DEAB en pacientes con ictus isquémico agudo (IIA) o ataque isquémico transitorio (AIT) en una unidad de ictus de España. Pacientes y métodos. Se consideró a pacientes de 50 años o más con IIA o AIT para ser incluidos. La información demográfica y clínica se obtuvo de forma prospectiva. Dos neurorradiólogos evaluaron la morfología de la AB de forma independiente. Resultados. De 126 pacientes, el 34,1% cumplió los criterios de DEAB (ectasia o dolicosis). La DEAB se asoció a mayor edad (p = 0,04). Los pacientes con la variante fetal del polígono de Willis presentaron menor diámetro de la AB (2,9 ± 0,1 frente a 3,5 ± 0,1; p < 0,001), mientras que pacientes con ictus lacunar presentaron diámetros mayores de la AB que otros subtipos de ictus (3,8 ± 0,3 mm frente a 3,3 ± 0,1 mm; p = 0,04). Discusión y conclusiones. En este estudio de centro único de pacientes con IIA o AIT, la prevalencia de DEAB (ectasia o dolicosis) fue alta. Estudios futuros enfocados en población española podrían confirmar nuestros resultados.

Acute amnestic syndrome in fornix lesions: a systematic review of reported cases with a focus on differential diagnosis.

Introduction: Acute amnestic syndrome is an uncommon clinical presentation of neurological disease. Differential diagnosis encompasses several syndromes including Wernicke-Korsakoff and transient global amnesia (TGA). Structural lesions of the fornix account for a minority of cases of acute amnestic syndromes. Etiology varies from iatrogenic injury to ischemic, inflammatory, or neoplastic lesions. A prompt diagnosis of the underlying pathology is essential but challenging. The aim of this review is to systematically review the existing literature regarding cases of acute amnestic syndrome associated with non-iatrogenic lesions of the fornix. Methods: We performed a systematic literature search on PubMed, Scopus, and Web of Science up to September 2023 to identify case reports and case series of patients with amnestic syndrome due to fornix lesions. The systematic review was conducted according to PRISMA guidelines. The research was limited to articles written in English. Cases of fornix damage directly ascribable to a surgical procedure were excluded. Results: A total of 52 publications reporting 55 cases were included in the review. Focusing on acute/subacute onset, vascular etiology was highly prevalent, being responsible for 78% of cases, 40/55 (74%) of which were due to acute ischemic stroke. The amnestic syndrome was characterized by anterograde amnesia in all patients, associated with retrograde amnesia in 27% of cases. Amnesia was an isolated presentation in most cases. Up to two thirds of patients had persistent memory deficits of any severity at follow-up. Discussion: Acute amnestic syndrome can be rarely caused by fornix lesions. In most cases of acute/subacute presentation, the etiology is ischemic stroke, mainly caused by strokes involving the subcallosal artery territory. The differential diagnosis is challenging and a distinction from common mimics is often difficult on a clinical basis. A high index of suspicion should be maintained to avoid misdiagnosis and provide adequate acute treatment to patients with time-dependent disease, also employing advanced neuroimaging. More research is needed to better understand the outcome and identify prognostic factors in patients with amnestic syndrome due to fornix lesions.

Does the age of milk affect its mid-infrared spectrum and predictions?

Milk of dairy species commonly undergo standardized official analyses, these that may require chemical preservation and transportation to a certified laboratory. In this context, storage duration is an important factor that can potential affect both milk chemical analyses and its mid-infrared spectrum. We analysed milk samples at different time points/ages to assess repeatability and reproducibility of mid-infrared predicted traits (e.g., fat and protein). Using spectral data, we also evaluated the ability of spectroscopy coupled with chemometrics to discriminate samples according to their age. Although the main components of milk remained consistently reproducible across age (days), changes in the spectrum due to sample aging and deterioration of the matrix were detectable. Using a discriminant analysis, we achieved a classification accuracy of 77% in validation. Predicting milk age using mid-infrared spectra is feasible, allowing for sample monitoring within circuits where maximum reliability is needed, e.g., bulk or individual milk samples for legal/official use or payment systems.

The role of necroscopy and autopsy investigations in the diagno-sis and risk management of infections related to public health care: forensic and medico legal implications.

Background: Healthcare-associated infections (HAIs) represent the most frequent adverse event in healthcare systems around the world. From a forensic point of view, HAIs show various legal implications. Therefore, it is essential in cases of death or injury from a suspected nosocomial infection that the infection itself, the source and the method of contamination are correctly diagnosed in order to evaluate any profiles of professional liability. Methods: This study combined a minireview of the scientific literature using the Pubmed search engine, the website of the Higher Institute of Health and the member states information sessions on infection prevention and control (IPC). Discussion: Despite the significant impact that HAIs have on healthcare systems, their severity is often not fully understood by healthcare professionals, leading to insufficient responses. In the autopsy setting, the diagnosis of these infections is not always simple due to the risk of post-mortem contamination determined by the endogenous bacterial flora. In the forensic field, the medical examiner during the autopsy can use various diagnostic techniques and investigative tools to identify the infection. Some usefulpp approaches include: 1) Macroscopic examination of the organs; 2) Histopathological investiga-tions; 3) Microbiological analyzes with the performance of swabs; 4) Immunofluorescence tests for the detection of antigens or antibodies on biological liquids; 5) Molecular tests. The choice of methods will depend on the nature of the suspected infection and the availability of diagnostic resources.

The effect of first-lactation calving season, milk production, and morphology on the survival of Simmental cows.

Longevity in dairy and dual-purpose cattle is a complex trait which depends on many individual and managerial factors. The purpose of the present study was to investigate the survival (SURV) rate of Italian Simmental dual-purpose cows across different parities. Data of this study referred to 2 173 primiparous cows under official milk recording that calved between 2002 and 2020. Only cows linearly classified for type traits, including muscularity (MU) and body condition score (BCS) were kept. Survival analysis was carried out, through the Cox regression model, for different pairwise combinations of classes of milk productivity MU, BCS, and calving season. Herd-year of first calving was also considered in the model. SURV (0 = culled; 1 = survived) at each lactation up to the 6th were the dependent variables, so that, for example, SURV2 equal to 1 was attributed to cows that entered the 2nd lactation. Survival rates were 98, 71, 63, 56, and 53% for 2nd, 3rd, 4th, 5th, and 6th lactation, respectively. Results revealed that SURV2 was not dependent on milk yield, while in subsequent parities, low-producing cows were characterized by higher SURV compared to high-producing ones. Additionally, cows starting the lactation in autumn survived less (47.38%) than those starting in spring (53.49%), suggesting that facing the late gestation phase in summer could increase the culling risk. The present study indicates that SURV in Italian Simmental cows is influenced by various factors in addition to milk productivity. However, it is important to consider that in this study all first-calving cows culled before the linear evaluation - carried out between mid- and late lactation in this breed - were not accounted for. Finding can be transferred to other dual-purpose breeds, where the cows' body conformation and muscle development - i.e. meat-related features - are often considered as important as milk performance by farmers undertaking culling decisions.

Urothelial carcinoma in a mule.

Equine bladder neoplasms are rare. This report aimed to describe the clinical signs and treatment of urothelial carcinoma (UC) in a mule. Cystoscopy of a 20-year-old female mule with a one-week history of hematuria and anemia revealed vascular congestion in the mucosa and an intraluminal, pedunculated mass in the dorsal bladder region. Histopathological examination revealed UC. Initial therapy consisted of four weekly cystoscopic guided injections of fluorouracil. At the fourth chemotherapy session, a paler and more friable tumor mass was observed. Consequently, we opted to surgically remove it during cystoscopy. Following mass excision, patient comfort, gross appearance of urine, and the hematocrit returned to normal. Repeat cystoscopy examinations revealed no gross appearance of tumor recurrence 18 months after treatment. Bladder neoplasms clinically resemble urolithiasis and cystitis and should be considered a differential diagnosis in cases of anemia and hematuria.

Depression and cognition are associated with lipid dysregulation in both a multigenerational study of depression and the National Health and Nutrition Examination Survey.

Chronic dysregulation of peripheral lipids has been found to be associated with depression and cognition, but their interaction has not been investigated. Growing evidence has highlighted the association between peripheral lipoprotein levels with depression and cognition with inconsistent results. We assessed the association between peripheral lipids, depression, and cognition while evaluating their potential interactions using robust clinically relevant predictors such as lipoprotein levels and chronic medical disorders that dysregulate lipoproteins. We report an association between peripheral lipids, depression, and cognition, suggesting a common underlying biological mechanism driven by lipid dysregulation in two independent studies. Analysis of a longitudinal study of a cohort at high or low familial risk for major depressive disorder (MDD) (n = 526) found metabolic diseases, including diabetes, hypertension, and other cardiovascular diseases, were associated with MDD and cognitive outcomes. Investigating a cross-sectional population survey of adults in the National Health and Nutrition Examination Survey 2011-2014 (NHANES) (n = 2377), depression was found to be associated with high density lipoprotein (HDL) and cognitive assessments. In the familial risk study, medical conditions were found to be associated with chronic lipid dysregulation and were significantly associated with MDD using the structural equation model. A positive association between chronic lipid dysregulation and cognitive scores was found in an exploratory analysis of the familial risk study. In a complementary study, analysis of NHANES revealed a positive association of HDL levels with cognition. Further analysis of the NHANES cohort indicated that depression status mediated the interaction between HDL levels and cognitive tests. Importantly, the protective effect of HDL on cognition was absent in those with depressive symptoms, which may ultimately result in worse outcomes leading to cognitive decline. These findings highlight the potential for the early predictive value of medical conditions with chronic lipid dyshomeostasis for the risk of depression and cognitive decline.

Quantum biochemical analysis of the TtgR regulator and effectors.

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs by numerous mechanisms, active efflux of the drugs is a critical concern. A single species of efflux pump can produce a simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC: a tripartite resistance-nodulation-division (RND) efflux pump implicated in the intrinsic antibiotic resistance in Pseudomonas putida DOT-T1E. The expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. In this context, by employing quantum chemistry methods based on the Density Functional Theory (DFT) within the Molecular Fragmentation with Conjugate Caps (MFCC) approach, we investigate the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical computational results show the: [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most relevant amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve the understanding of the binding mechanism of effectors and facilitate the development of new chemicals targeting TtgR, helping in the battle against the rise of resistance to antimicrobial drugs. These advances are crucial in the ongoing fight against rising antimicrobial drug resistance, providing hope for a future where healthcare-associated infections can be more beneficially treated.

The allelopathic effects of aqueous Talinum triangulare (jacq.) willd extracts on the development of Lactuca sativa L. seedlings.

Plants that produce allelopathic compounds against weeds have emerged as a potential solution for the development of ecologically correct bioherbicides. Talinum triangulare is noteworthy in this regard, as its phytochemical composition encompasses flavonoids, alkaloids and other metabolites that can be used to develop inhibitory weed growth solutions. Lactuca sativa (lettuce) has been widely applied as a bioindicator species for bioherbicides and several chemicals, animal waste, water and soil quality, and atmospheric contamination, among others. In this context, this study aimed to assess the potential allelopathic effect of aqueous T. triangulare extracts on the development of L. sativa seedlings. A completely randomized design employing a 2x4 factorial scheme (shoot and root extracts) x the concentration of each extract (0, 2.5, 5, 7.5%) was applied, comprising four replications. Lactuca sativa seeds were sown on germitest papers soaked with the extracts in a germination chamber at 20°C. Physiological seed evaluations comprising the germination test, where normal and abnormal seedlings are counted on the seventh day after sowing, first normal seedling counts on the fourth day after sowing, and seedling and root length measurements. At the end of the germination test, L. sativa seedlings were separated for morphoanatomical characterizations and chlorophyll a fluorescence analyses. The T. triangulare extracts significantly influenced L. sativa root growth, with shoot extract exposure leading to more abnormal plants and lower root lengths at increasing concentrations and compared to the root extract. Root extract exposure led to evident cellular changes and lower non-photochemical quenching and unregulated dissipation quantum yields at a 5% exposure dose compared to shoot extract exposure. These findings suggest that both aqueous T. triangulare root and shoot extracts from 5% exposure doses exhibit high potential as bioherbicides, acting directly on plant structure, anatomy, quality, size and physiology.

Link between supercurrent diode and anomalous Josephson effect revealed by gate-controlled interferometry.

In Josephson diodes the asymmetry between positive and negative current branch of the current-phase relation leads to a polarity-dependent critical current and Josephson inductance. The supercurrent nonreciprocity can be described as a consequence of the anomalous Josephson effect -a φ0-shift of the current-phase relation- in multichannel ballistic junctions with strong spin-orbit interaction. In this work, we simultaneously investigate φ0-shift and supercurrent diode efficiency on the same Josephson junction by means of a superconducting quantum interferometer. By electrostatic gating, we reveal a direct link between φ0-shift and diode effect. Our findings show that spin-orbit interaction in combination with a Zeeman field plays an important role in determining the magnetochiral anisotropy and the supercurrent diode effect.

Genomic insights into the expansion of carbapenem-resistant Klebsiella pneumoniae within Portuguese hospitals.

Carbapenem-resistant Klebsiella pneumoniae (CR-KP) are a public health concern, causing infections with a high mortality rate, limited therapeutic options and challenging infection control strategies. In Portugal, the CR-KP rate has increased sharply, but the factors associated with this increase are poorly explored. In order to address this question, phylogenetic and resistome analysis were used to compare the draft genomes of 200 CR-KP isolates collected in 2017-2019 from five hospitals in the Lisbon region, Portugal. Most CR-KP belonged to sequence type (ST) 13 (29%), ST17 (15%), ST348 (13%), ST231 (12%) and ST147 (7%). Carbapenem resistance was conferred mostly by the presence of KPC-3 (74%) or OXA-181 (18%), which were associated with IncF/IncN and IncX plasmids, respectively. Almost all isolates were multi-drug resistant, harbouring resistance determinants to aminoglycosides, beta-lactams, trimethoprim, fosfomycin, quinolones and sulphonamides. In addition, 11% of isolates were resistant to colistin. Colonizing and infecting isolates were highly related, and most colonized patients (89%) reported a previous hospitalization. Moreover, among the 171 events of cross-dissemination identified by core genome multi-locus sequence typing data analysis (fewer than five allelic differences), 41 occurred between different hospitals and 130 occurred within the same hospital. The results suggest that CR-KP dissemination in the Lisbon region results from acquisition of carbapenemases in mobile genetic elements, influx of CR-KP into the hospitals by colonized ambulatory patients, and transmission of CR-KP within and between hospitals. Prudent use of carbapenems, patient screening at hospital entry, and improvement of infection control are needed to decrease the burden of CR-KP infection in Portugal.

Hancornia speciosa serum latex fraction: a non-allergenic biomaterial / Fração soro do látex de Hancornia speciosa: um biomaterial não alergênico

Abstract Plant-derived products can assist in the healing process of dermal wounds. It has been demonstrated that Hancornia speciosa latex present angiogenic, osteogenic, anti-inflammatory, and antioxidant activities. Then, it could contribute to the wound healing process. However, natural products in contact with skin may cause dermatitis. The objective of this work was to evaluate the allergic and irritant potential of H. speciosa serum fraction latex using in vitro assays. The obtained results showed that the H. speciosa serum fraction latex has a slightly irritant potential and is not cytotoxic neither allergenic for human cells. Moreover, we identified a remarkable low amount of proteins in this material in comparison to Hevea brasiliensis latex. This result could explain the non-allergenic potential of H. speciosa serum fraction latex because proteins present in latex are the main responsible for allergy. This biomaterial could be used as a non-allergenic source for development of new medicines.

Resumo Produtos derivados de plantas podem auxiliar no processo de cicatrização de feridas cutâneas. Foi demonstrado que o látex de Hancornia speciosa apresenta atividades angiogênicas, osteogênicas, antiinflamatórias e antioxidantes. Então, este biomaterial pode contribuir para o processo de cicatrização de feridas. No entanto, produtos naturais em contato com a pele podem causar dermatites. O objetivo deste trabalho foi avaliar o potencial alérgico e irritante do látex da fração soro de H. speciosa por meio de ensaios in vitro. Os resultados obtidos mostraram que o látex da fração do soro de H. speciosa possui um potencial pouco irritante e não é citotóxico nem alergênico para células humanas. Além disso, foi identificado uma notável baixa quantidade de proteínas neste material em comparação ao látex de Hevea brasiliensis. Esse resultado poderia explicar o potencial não alergênico do látex da fração soro de H. speciosa, pois as proteínas presentes no látex são as principais responsáveis ​​pela alergia. Este biomaterial pode ser utilizado como fonte não alergênica para desenvolvimento de novos medicamentos.

Hancornia speciosa serum latex fraction: a non-allergenic biomaterial / Fração soro do látex de Hancornia speciosa: um biomaterial não alergênico

Plant-derived products can assist in the healing process of dermal wounds. It has been demonstrated that Hancornia speciosa latex present angiogenic, osteogenic, anti-inflammatory, and antioxidant activities. Then, it could contribute to the wound healing process. However, natural products in contact with skin may cause dermatitis. The objective of this work was to evaluate the allergic and irritant potential of H. speciosa serum fraction latex using in vitro assays. The obtained results showed that the H. speciosa serum fraction latex has a slightly irritant potential and is not cytotoxic neither allergenic for human cells. Moreover, we identified a remarkable low amount of proteins in this material in comparison to Hevea brasiliensis latex. This result could explain the non-allergenic potential of H. speciosa serum fraction latex because proteins present in latex are the main responsible for allergy. This biomaterial could be used as a non-allergenic source for development of new medicines.

Produtos derivados de plantas podem auxiliar no processo de cicatrização de feridas cutâneas. Foi demonstrado que o látex de Hancornia speciosa apresenta atividades angiogênicas, osteogênicas, antiinflamatórias e antioxidantes. Então, este biomaterial pode contribuir para o processo de cicatrização de feridas. No entanto, produtos naturais em contato com a pele podem causar dermatites. O objetivo deste trabalho foi avaliar o potencial alérgico e irritante do látex da fração soro de H. speciosa por meio de ensaios in vitro. Os resultados obtidos mostraram que o látex da fração do soro de H. speciosa possui um potencial pouco irritante e não é citotóxico nem alergênico para células humanas. Além disso, foi identificado uma notável baixa quantidade de proteínas neste material em comparação ao látex de Hevea brasiliensis. Esse resultado poderia explicar o potencial não alergênico do látex da fração soro de H. speciosa, pois as proteínas presentes no látex são as principais responsáveis pela alergia. Este biomaterial pode ser utilizado como fonte não alergênica para desenvolvimento de novos medicamentos.

Hancornia speciosa serum latex fraction: a non-allergenic biomaterial

Abstract Plant-derived products can assist in the healing process of dermal wounds. It has been demonstrated that Hancornia speciosa latex present angiogenic, osteogenic, anti-inflammatory, and antioxidant activities. Then, it could contribute to the wound healing process. However, natural products in contact with skin may cause dermatitis. The objective of this work was to evaluate the allergic and irritant potential of H. speciosa serum fraction latex using in vitro assays. The obtained results showed that the H. speciosa serum fraction latex has a slightly irritant potential and is not cytotoxic neither allergenic for human cells. Moreover, we identified a remarkable low amount of proteins in this material in comparison to Hevea brasiliensis latex. This result could explain the non-allergenic potential of H. speciosa serum fraction latex because proteins present in latex are the main responsible for allergy. This biomaterial could be used as a non-allergenic source for development of new medicines.

Resumo Produtos derivados de plantas podem auxiliar no processo de cicatrização de feridas cutâneas. Foi demonstrado que o látex de Hancornia speciosa apresenta atividades angiogênicas, osteogênicas, antiinflamatórias e antioxidantes. Então, este biomaterial pode contribuir para o processo de cicatrização de feridas. No entanto, produtos naturais em contato com a pele podem causar dermatites. O objetivo deste trabalho foi avaliar o potencial alérgico e irritante do látex da fração soro de H. speciosa por meio de ensaios in vitro. Os resultados obtidos mostraram que o látex da fração do soro de H. speciosa possui um potencial pouco irritante e não é citotóxico nem alergênico para células humanas. Além disso, foi identificado uma notável baixa quantidade de proteínas neste material em comparação ao látex de Hevea brasiliensis. Esse resultado poderia explicar o potencial não alergênico do látex da fração soro de H. speciosa, pois as proteínas presentes no látex são as principais responsáveis pela alergia. Este biomaterial pode ser utilizado como fonte não alergênica para desenvolvimento de novos medicamentos.

Osmoprotection in Salvia hispanica L. seeds under water stress attenuators / Osmoproteção em sementes de Salvia hispanica L. sob atenuadores do estresse hídrico

Salvia hispanica cultivation is recent in Brazil and occurs in the off-season, when there is lower water availability in the soil. Water deficit is one of the abiotic factors that most limit germination for compromising the sequence of metabolic events that culminate with seedling emergence. Several attenuating substances have been used to mitigate the effects resulting from this stress and give higher tolerance to the species. Thus, the objective of this study was to evaluate the action of different agents as water stress attenuators in the germination and accumulation of organic compounds in S. hispanica seedlings. The treatments consisted of pre-soaking the seeds for 4 hours in salicylic acid (1 mM.L-1), gibberellic acid (0.4 mM.L-1), distilled water and control treatment (without soaking). The seeds were germinated at osmotic potentials of 0.0, -0.1, -0.2, -0.3 and -0.4 MPa, using PEG 6000 as an osmotic agent. The variables germination percentage, germination speed index, shoot and primary root lengths, total dry mass, proline, total soluble sugars and total free amino acids were analyzed. Salicylic acid and gibberellic acid led to the best results among the attenuators tested, increasing germination, length, dry mass and biochemical components of S. hispanica seedlings under water deficit. Therefore, salicylic and gibberellic acids are efficient in mitigating water stress in S. hispanica seeds up to the potential of -0.4 MPa.

O cultivo da Salvia hispanica é recente no Brasil e se dá no período de entressafra, quando há menor disponibilidade hídrica no solo. O déficit hídrico é um dos fatores abióticos que mais limitam a germinação por comprometer a sequência de eventos metabólicos que culminam com a emergência da plântula. Diversas substâncias atenuadoras têm sido empregadas com a finalidade de mitigar os efeitos resultantes desse estresse e conferir maior tolerância às espécies. Desse modo, objetivou-se avaliar a ação de diferentes agentes como atenuadores do estresse hídrico na germinação e acúmulo de compostos orgânicos em plântulas de S. hispanica. Os tratamentos consistiram na pré-embebição das sementes durante 4 horas em ácido salicílico (1 mM.L-1), ácido giberélico (0,4 mM.L-1), água destilada e o tratamento controle (sem embebição). As sementes foram germinadas sob os potenciais osmóticos 0,0, -0,1, -0,2, -0,3 e -0,4 MPa, utilizando PEG 6000 como agente osmótico. Analisaram-se as variáveis porcentagem de germinação, índice de velocidade de germinação, comprimento da parte aérea e da raiz primária, massa seca total, prolina, açúcares solúveis totais e aminoácidos livres totais. O ácido salicílico e o ácido giberélico apresentaram os melhores resultados, dentre os atenuadores testados, incrementando a germinação, o comprimento, a massa seca e os componentes bioquímicos de plântulas de S. hispanica sob déficit hídrico. Logo, os ácidos salicílico e giberélico são eficientes na mitigação do estresse hídrico em sementes de S. hispanica até o potencial -0,4 MPa.

Osmoprotection in Salvia hispanica L seeds under water stress attenuators / Osmoproteção em sementes de Salvia hispanica L sob atenuadores do estresse hídrico

Salvia hispanica cultivation is recent in Brazil and occurs in the off-season, when there is lower water availability in the soil. Water deficit is one of the abiotic factors that most limit germination for compromising the sequence of metabolic events that culminate with seedling emergence. Several attenuating substances have been used to mitigate the effects resulting from this stress and give higher tolerance to the species. Thus, the objective of this study was to evaluate the action of different agents as water stress attenuators in the germination and accumulation of organic compounds in S. hispanica seedlings. The treatments consisted of pre-soaking the seeds for 4 hours in salicylic acid (1 mM.L-¹), gibberellic acid (0.4 mM.L-¹), distilled water and control treatment (without soaking). The seeds were germinated at osmotic potentials of 0.0, -0.1, -0.2, -0.3 and -0.4 MPa, using PEG 6000 as an osmotic agent. The variables germination percentage, germination speed index, shoot and primary root lengths, total dry mass, proline, total soluble sugars and total free amino acids were analyzed. Salicylic acid and gibberellic acid led to the best results among the attenuators tested, increasing germination, length, dry mass and biochemical components of S. hispanica seedlings under water deficit. Therefore, salicylic and gibberellic acids are efficient in mitigating water stress in S. hispanica seeds up to the potential of -0.4 MPa.

O cultivo da Salvia hispanica é recente no Brasil e se dá no período de entressafra, quando há menor disponibilidade hídrica no solo. O déficit hídrico é um dos fatores abióticos que mais limitam a germinação por comprometer a sequência de eventos metabólicos que culminam com a emergência da plântula. Diversas substâncias atenuadoras têm sido empregadas com a finalidade de mitigar os efeitos resultantes desse estresse e conferir maior tolerância às espécies. Desse modo, objetivou-se avaliar a ação de diferentes agentes como atenuadores do estresse hídrico na germinação e acúmulo de compostos orgânicos em plântulas de S. hispanica. Os tratamentos consistiram na pré-embebição das sementes durante 4 horas em ácido salicílico (1 mM.L-¹), ácido giberélico (0,4 mM.L-¹), água destilada e o tratamento controle (sem embebição). As sementes foram germinadas sob os potenciais osmóticos 0,0, -0,1, -0,2, -0,3 e -0,4 MPa, utilizando PEG 6000 como agente osmótico. Analisaram-se as variáveis porcentagem de germinação, índice de velocidade de germinação, comprimento da parte aérea e da raiz primária, massa seca total, prolina, açúcares solúveis totais e aminoácidos livres totais. O ácido salicílico e o ácido giberélico apresentaram os melhores resultados, dentre os atenuadores testados, incrementando a germinação, o comprimento, a massa seca e os componentes bioquímicos de plântulas de S. hispanica sob déficit hídrico. Logo, os ácidos salicílico e giberélico são eficientes na mitigação do estresse hídrico em sementes de S. hispanica até o potencial -0,4 MPa.