Nanoemulsion of Minthostachys verticillata essential oil. In-vitro evaluation of its antibacterial activity

Infectious diseases constitute a problem of great importance for animal and human health, as well as the increasing bacterial resistance to antibiotics. In this context, medicinal plants emerge as an effective alternative to replace the use antibiotics. The essential oil (EO) of Minthostachys verticillata (Griseb.) Epling (Lamiaceae) has demonstrated a strong antimicrobial activity. However, its instability and hydrophobicity under normal storage conditions are limitations to its use. Nanoemulsion technology is an excellent way to solubilize, microencapsulate, and protect this compound. This study aimed to obtain a nanoemulsion based on M. verticillata EO and evaluate its antibacterial activity against Staphylococcus aureus. The EO was obtained by steam distillation. Identification and quantification of their components were determined by GC-MS revealing that the dominated chemical group was oxygenated monoterpenes. Nanoemulsions (NE) were characterized by measuring pH, transmittance, separation percentage, release profile, and morphology. The effect of NE on the growth of S. aureus and cyto-compatibility was also evaluated. The results showed that NE containing a higher percentage of tween 20 exhibited higher stability with an approximated droplet size of 10 nm. The effect of encapsulation process was evaluated by GC-MS revealing that the volatile components in EO were no affected. After 24 h, 74.24 ± 0.75% of EO was released from NE and the antibacterial activity of EO was enhanced considerably by its encapsulation. The incubation of S. aureus with the NE and pure EO, show a bacterial growth inhibition of 58.87% ± 0.99 and 46.72% ± 3.32 (p < 0.05), respectively. In addition, nanoemulsión did not cause toxicity to porcine and equine red blood cells. The results obtained showed that NE could be a potential vehicle for M. verticillata EO with promissory properties to emerge as a tool for developing advanced therapies to control and combat infections.EEA Marcos JuárezFil: Cecchini, María Eugenia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Físico-Químicas y Naturales. Departamento de Microbiología e Inmunología. Laboratorio de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biotecnología Ambiental y Salud. Universidad Nacional de Río Cuarto. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Paoloni, C. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria. Departamento de Anatomía Animal. Laboratorio de Biotecnología Animal; ArgentinaFil: Campra, Noelia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Físico-Químicas y Naturales. Departamento de Microbiología e Inmunología. Laboratorio de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biotecnología Ambiental y Salud. Universidad Nacional de Río Cuarto. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Picco, Natalia. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria. Departamento de Anatomía Animal. Laboratorio de Biotecnología Animal; ArgentinaFil: Grosso, M. Carolina. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria. Departamento de Anatomía Animal. Laboratorio de Biotecnología Animal; ArgentinaFil: Soriano Perez, María Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Alustiza, Fabrisio Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Cariddi, Noelia. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas, Físico-Químicas y Naturales. Departamento de Microbiología e Inmunología. Laboratorio de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biotecnología Ambiental y Salud. Universidad Nacional de Río Cuarto. Instituto de Biotecnología Ambiental y Salud; ArgentinaFil: Bellingeri, Romina. Universidad Nacional de Río Cuarto. Facultad de Agronomía y Veterinaria. Departamento de Anatomía Animal. Laboratorio de Biotecnología Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. Universidad Nacional de Río Cuarto. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; Argentin

Langmuir-Blodgett monolayers holding a wound healing active compound and its effect in cell culture. A model for the study of surface mediated drug delivery systems

Langmuir and Langmuir-Blodgett films holding a synthetic bioinspired wound healing active compound were used as drug-delivery platforms. Palmitic acid Langmuir monolayers were able to incorporate 2-methyltriclisine, a synthetic Triclisine derivative that showed wound healing activity. The layers proved to be stable and the nanocomposites were transferred to solid substrates. Normal human lung cells (Medical Research Council cell strain 5, MRC-5) were grown over the monomolecular Langmuir-Blodgett films that acted as a drug reservoir and delivery system. The proliferation and migration of the cells were clearly affected by the presence of 2-methyltriclisine in the amphiphilic layers. The methodology is proposed as a simple and reliable model for the study of the effects of bioactive compounds over cellular cultures.EEA Marcos JuárezFil: Fernández, Luciana. Universidad Nacional de Río Cuarto. Departamento de Física y Departamento de Química; ArgentinaFil: Fernández, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reviglio, Ana Lucía. Universidad Nacional de Río Cuarto. Departamento de Física y Departamento de Química; ArgentinaFil: Reviglio, Ana Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Heredia, Daniel A. Universidad Nacional de Río Cuarto. Departamento de Física y Departamento de Química; Argentina.Fil: Heredia, Daniel A. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morales, Gustavo M. Universidad Nacional de Río Cuarto. Departamento de Física y Departamento de Química; ArgentinaFil: Morales, Gustavo M. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Santo, Marisa. Universidad Nacional de Río Cuarto. Departamento de Física y Departamento de Química; ArgentinaFil: Santo, Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Otero, Luis. Universidad Nacional de Río Cuarto. Departamento de Física y Departamento de Química; ArgentinaFil: Otero, Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alustiza, Fabrisio Eduardo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Liaudat, Ana Cecilia. Universidad Nacional de Río Cuarto. Departamento de Biología Molecular; ArgentinaFil: Bosch, Pablo. Universidad Nacional de Río Cuarto. Departamento de Biología Molecular; ArgentinaFil: Larghi, Enrique L. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Bracca, Andrea B.J. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Kaufman, Teodoro S. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentin

The short-term mortality fluctuation data series, monitoring mortality shocks across time and space.

The COVID-19 pandemic has revealed substantial coverage and quality gaps in existing international and national statistical monitoring systems. It is striking that obtaining timely, accurate, and comparable across countries data in order to adequately respond to unexpected epidemiological threats is very challenging. The most robust and reliable approach to quantify the mortality burden due to short-term risk factors is based on estimating weekly excess deaths. This approach is more reliable than monitoring deaths with COVID-19 diagnosis or calculating incidence or fatality rates affected by numerous problems such as testing coverage and comparability of diagnostic approaches. In response to the emerging data challenges, a new data resource on weekly mortality has been established. The Short-term Mortality Fluctuations (STMF, available at www.mortality.org ) data series is the first international database providing open-access harmonized, uniform, and fully documented data on weekly all-cause mortality. The STMF online vizualisation tool provides an opportunity to perform a quick assessment of the excess weekly mortality in one or several countries by means of an interactive graphical interface

Meta-analysis of functional neuroimaging and cognitive control studies in schizophrenia: preliminary elucidation of a core dysfunctional timing network

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile

Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk

Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin

OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps

Stone Age Yersinia pestis genomes shed light on the early evolution, diversity, and ecology of plague

The bacterial pathogenYersinia pestisgave rise to devastating outbreaks throughouthuman history, and ancient DNA evidence has shown it afflicted human populations asfar back as the Neolithic.Y. pestisgenomes recovered from the Eurasian Late Neolithic/Early Bronze Age (LNBA) period have uncovered key evolutionary steps that led to itsemergence from aYersinia pseudotuberculosis-like progenitor; however, the number ofreconstructed LNBA genomes are too few to explore its diversity during this criticalperiod of development. Here, we present 17Y. pestisgenomes dating to 5,000 to 2,500y BP from a wide geographic expanse across Eurasia. This increased dataset enabled usto explore correlations between temporal, geographical, and genetic distance. Ourresults suggest a nonflea-adapted and potentially extinct single lineage that persistedover millennia without significant parallel diversification, accompanied by rapid dis-persal across continents throughout this period, a trend not observed in other pathogensfor which ancient genomes are available. A stepwise pattern of gene loss provides fur-ther clues on its early evolution and potential adaptation. We also discover the presenceof theflea-adapted form ofY. pestisin Bronze Age Iberia, previously only identified inin the Caucasus and the Volga regions, suggesting a much wider geographic spread ofthis form ofY. pestis. Together, these data reveal the dynamic nature of plague’s forma-tive years in terms of its early evolution and ecology

Adiponectin, leptin, and IGF-1 are useful diagnostic and stratification biomarkers of NAFLD

[EN] Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome. Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics. Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p < 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p < 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p < 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p < 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p<0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p < 0.01). Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis.CR was funded by FEDER through the COMPETE program and by national funds through Fundação para a Ciência e a Tecnologia (PTDC/MED-FAR/29097/2017—LISBOA-01- 0145-FEDER-029097) and by European Horizon 2020 (H2020- MSCA-RISE-2016-734719). This work was also supported by Fundação para a Ciência e Tecnologia (PD/BD/135467/2017) and Portuguese Association for the Study of Liver/MSD 2017. JB was funded by Spanish Carlos III Health Institute (ISCIII) (PI15/01132, PI18/01075 and Miguel Servet Program CON14/00129 and CPII19/00008), co-financed by Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III (CIBERehd, Spain), La Caixa Scientific Foundation (HR17-00601), Fundación Científica de la Asociación Española Contra el Cáncer, and European Horizon 2020 (ESCALON project: H2020-SC1-BHC-2018-2020)

Adiponectin, Leptin, and IGF-1 Are Useful Diagnostic and Stratification Biomarkers of NAFLD

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease where liver biopsy remains the gold standard for diagnosis. Here we aimed to evaluate the role of circulating adiponectin, leptin, and insulin-like growth factor 1 (IGF-1) levels as non-invasive NAFLD biomarkers and assess their correlation with the metabolome.Materials and Methods: Leptin, adiponectin, and IGF-1 serum levels were measured by ELISA in two independent cohorts of biopsy-proven obese NAFLD patients and healthy-liver controls (discovery: 38 NAFLD, 13 controls; validation: 194 NAFLD, 31 controls) and correlated with clinical data, histology, genetic parameters, and serum metabolomics.Results: In both cohorts, leptin increased in NAFLD vs. controls (discovery: AUROC 0.88; validation: AUROC 0.83; p &lt; 0.0001). The leptin levels were similar between obese and non-obese healthy controls, suggesting that obesity is not a confounding factor. In the discovery cohort, adiponectin was lower in non-alcoholic steatohepatitis (NASH) vs. non-alcoholic fatty liver (AUROC 0.87; p &lt; 0.0001). For the validation cohort, significance was attained for homozygous for PNPLA3 allele c.444C (AUROC 0.63; p &lt; 0.05). Combining adiponectin with specific serum lipids improved the assay performance (AUROC 0.80; p &lt; 0.0001). For the validation cohort, IGF-1 was lower with advanced fibrosis (AUROC 0.67, p &lt; 0.05), but combination with international normalized ratio (INR) and ferritin increased the assay performance (AUROC 0.81; p &lt; 0.01).Conclusion: Serum leptin discriminates NAFLD, and adiponectin combined with specific lipids stratifies NASH. IGF-1, INR, and ferritin distinguish advanced fibrosis