Association of synthetic anthelmintics and natural monoterpenes against Haemonchus contortus

The resistance of Haemonchus contortus to synthetic anthelmintics is an increasing concern and different strategies are being evaluated. The present trial studied the in vitro effect of the association of synthetic compound and natural monoterpene on eggs and larvae of H. contortus. The monoterpenes carvacrol, thymol, r-carvone, s-carvone, citral and p-cymene, and the synthetic antihelmintic ivermectin, and albendazole were used. Egg Hatch Test (EHT) and Larval Migration Inhibition Test (LMIT) were performed. The lowest efficient concentration of monoterpenes in EHT (≤ 11% of efficacy) and LMIT (≤ 18% of efficacy) was used in association with different concentration of synthetic compound. The IC50 and Synergism Rate (SR) were calculated. The highest efficiency of monoterpenes in EHT was obtained with r-carvone (IC50 = 0.25 mg/mL) and s-carvone (IC50 = 0.79 mg/mL) and in the LMIT with r-carvone (IC50 = 0.60 mg/mL). The best association was observed in the EHT with albendazol (thymol SR: 2.9 and r-carvone SR: 1.6) and ivermectin (citral SR: 1.9 and carvacrol SR:1.7). No synergistic effect was obtaining using the LMIT. The combination of synthetic compound and natural monoterpenes could be positive to gastrointestinal nematodes control: However this strategy should be carefully analysed due to the possibility of antagonic effects among the different compounds.Fil: Costa Junior, Livio. Universidade Federal do Maranhao; BrasilFil: Silva, Carolina R.. Universidade Federal do Maranhao; BrasilFil: Macedo, Sara R. D.. Universidade Federal do Maranhao; BrasilFil: Campos, Nagilla R. C. L.. Universidade Federal do Maranhao; BrasilFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina26th Conference World Association for the Advancement of Veterinary ParasitologyKuala LumpurMalasiaWorld Association for the Advancement of Veterinary Parasitolog

The impact of work clothing design on workers’ comfort

Physical and physiological comfort, at work and during leisure time, is important to human health and motivation. A growing number of jobs require workers to sit. Most clothes, except those intended for wheelchair users, were designed for walking or the standing position. Clothing designs should be user-oriented and meet users’ needs. Garment design should conform to body position and posture, not just shape and size. In this paper we present the ergometric impact of a new type of trousers designed to adapt to changes in position. Concentrations of compression forces, temperature and pressure were documented in an exploratory pilot study and contrasted to traditional designs. The new trousers showed significant decreases in compression force concentration, especially in and around the knees and waist. Most participants identified comfort as an important factor when purchasing a pair of trousers and that, for working purposes, they would prefer these special trousers rather than traditional designs.This work was financed by FEDER funds through the Competitive Factors Operational Program (COMPETE) and by national funds through FCT (Portuguese Foundation for Science and Technology) with the projects PEst- C/CTM/U10264/2013, ID/CEC/00319/2013, BD SFRH/BD/79762/2011, NORTE-07-0401-FEDER-031444 and NORTE-07-0402-FEDER-019152

Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.The influenza virus fusion process, whereby the virus fuses its envelope with the host endosome membrane to release the genetic material, takes place in the acidic late endosome environment. Acidification triggers a large conformational change in the fusion protein, hemagglutinin (HA), which enables the insertion of the N-terminal region of the HA2 subunit, known as the fusion peptide, into the membrane of the host endosome. However, the mechanism by which pH modulates the molecular properties of the fusion peptide remains unclear. To answer this question, we performed the first constant-pH molecular dynamics simulations of the influenza fusion peptide in a membrane, extending for 40 µs of aggregated time. The simulations were combined with spectroscopic data, which showed that the peptide is twofold more active in promoting lipid mixing of model membranes at pH 5 than at pH 7.4. The realistic treatment of protonation introduced by the constant-pH molecular dynamics simulations revealed that low pH stabilizes a vertical membrane-spanning conformation and leads to more frequent contacts between the fusion peptide and the lipid headgroups, which may explain the increase in activity. The study also revealed that the N-terminal region is determinant for the peptide's effect on the membrane.This work was financially supported by FCT—Fundação para a Ciência e a Tecnologia, Portugal, through projects PTDC/QUI-BIQ/114774/2009, PTDC/CCI-BIO/28200/2017 and Pest-OE/EQB/LA0004/2011. This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT—Fundação para a Ciência e a Tecnologia. DL was supported by FCT post-doc fellowship SFRH/BPD/92537/2013.info:eu-repo/semantics/publishedVersio

Impact of functional flours from pineapple by-products on human intestinal microbiota

Solid fractions from pineapple stems and peels are constituted by structural carbohydrates coupled with dietary fibre, simple sugars, but also vitamins and polyphenols, which together can have potential effects on human health. The present studies report for the first time the bioavailability and bioaccessibility of pineapple by-products fractions throughout simulated gastrointestinal tract, evaluates prebiotic potential and in vitro human microbiota fermentation. The pineapple flours promoted the human faeces fermentation through growth of beneficial strains, being corroborated by the decrease of simple sugars and the production of healthy organic acids (acetic, propionic and butyric acids) - well known short chain fatty acids. On the other hand, a high phenolic compounds content was release through flours digestion, developing an antioxidant environment within human gut. Thus, was possible to conclude that pineapple flour promoted a positive modulation in the overall system, proving a synergetic interaction of dietary fibre and polyphenols upon human microbiota.This work wasfinancially supported by BiValBi - Biotechnologies toValorise the regional Biodiversity in Latin America, in the funding project FP7-PEOPLE-2013-IRSES PEOPLE Marie Curie Program through project reference PIRSES-GA-2013-611493. We would like to thank thescientific collaboration of CBQF under the FCT–Fundação para aCiência e a Tecnologia with project Multibiorefinery–Multi-purposestrategies for the valorisation of a wide range of agroforestry by-pro-ducts andfisheries: A step forward in the creation of an integratedbiorefinery, (POCI-01-0145-FEDER-0066), project UID/Multi/50016/2013 and by PhD grant SFRH/BD/104074/2014 to Débora Campos.info:eu-repo/semantics/publishedVersio

Factor structure and proposed scoring revision of the ThreeDimensional Psychological Pain Scale

Abstract: The development of psychometrically sound measures to assess mental pain are important because research has consistently demonstrated a robust relationship to suicide risk. The current research evaluated the Three-Dimensional Psychological Pain Scale (TDPPS) structure, a suicide-relevant measure intended to articulate pain into affective, cognitive, and behavioral facets. As the first Western study to evaluate the TDPPS structure with non-Chinese respondents, six samples comprising 1,627 adults participated. Neither confirmatory factor analyses nor exploratory structural equation modeling supported the hypothesized three-dimensional structure of the TDPPS but, instead, identified two dimensions: pain escape and pain emotions. Scales based on these two dimensions demonstrated replicability in crossvalidation and score internal consistency reliability. Furthermore, validity for scores on these two scales was confirmed through moderate associations with another pain measure and scales of suicidal behavior and depression. Findings extend knowledge of TDPPS’s structure of psychological pain and suggest a scale scoring revision

A Ketogenic Diet Improves Cognition and Has Biochemical Effects in Prefrontal Cortex That Are Dissociable From Hippocampus

Age-related cognitive decline has been linked to a diverse set of neurobiological mechanisms, including bidirectional changes in proteins critical for neuron function. Importantly, these alterations are not uniform across the brain. For example, the hippocampus (HPC) and prefrontal cortex (PFC) show distinct patterns of dysfunction in advanced age. Because higher cognitive functions require large–scale interactions across prefrontal cortical and hippocampal networks, selectively targeting an alteration within one region may not broadly restore function to improve cognition. One mechanism for decline that the PFC and HPC share, however, is a reduced ability to utilize glucose for energy metabolism. Although this suggests that therapeutic strategies bypassing the need for neuronal glycolysis may be beneficial for treating cognitive aging, this approach has not been empirically tested. Thus, the current study used a ketogenic diet (KD) as a global metabolic strategy for improving brain function in young and aged rats. After 12 weeks, rats were trained to perform a spatial alternation task through an asymmetrical maze, in which one arm was closed and the other was open. Both young and aged KD-fed rats showed resilience against the anxiogenic open arm, training to alternation criterion performance faster than control animals. Following alternation testing, rats were trained to perform a cognitive dual task that required working memory while simultaneously performing a bi-conditional association task (WM/BAT), which requires PFC–HPC interactions. All KD-fed rats also demonstrated improved performance on WM/BAT. At the completion of behavioral testing, tissue punches were collected from the PFC for biochemical analysis. KD-fed rats had biochemical alterations within PFC that were dissociable from previous results in the HPC. Specifically, MCT1 and MCT4, which transport ketone bodies, were significantly increased in KD-fed rats compared to controls. GLUT1, which transports glucose across the blood brain barrier, was decreased in KD-fed rats. Contrary to previous observations within the HPC, the vesicular glutamate transporter (VGLUT1) did not change with age or diet within the PFC. The vesicular GABA transporter (VGAT), however, was increased within PFC similar to HPC. These data suggest that KDs could be optimal for enhancing large-scale network function that is critical for higher cognition

Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis.

Gliomas are the most common primary tumours affecting the adult central nervous system and respond poorly to standard therapy. Myc is causally implicated in most human tumours and the majority of glioblastomas have elevated Myc levels. Using the Myc dominant negative Omomyc, we previously showed that Myc inhibition is a promising strategy for cancer therapy. Here, we preclinically validate Myc inhibition as a therapeutic strategy in mouse and human glioma, using a mouse model of spontaneous multifocal invasive astrocytoma and its derived neuroprogenitors, human glioblastoma cell lines, and patient-derived tumours both in vitro and in orthotopic xenografts. Across all these experimental models we find that Myc inhibition reduces proliferation, increases apoptosis and remarkably, elicits the formation of multinucleated cells that then arrest or die by mitotic catastrophe, revealing a new role for Myc in the proficient division of glioma cells

BARD1 Pathogenic Variants are Associated with Triple-Negative Breast Cancer in a Spanish Hereditary Breast and Ovarian Cancer Cohort

Only a small fraction of hereditary breast and/or ovarian cancer (HBOC) cases are caused by germline variants in the high-penetrance breast cancer 1 and 2 genes (BRCA1 and BRCA2). BRCA1-associated ring domain 1 (BARD1), nuclear partner of BRCA1, has been suggested as a potential HBOC risk gene, although its prevalence and penetrance are variable according to populations and type of tumor. We aimed to investigate the prevalence of BARD1 truncating variants in a cohort of patients with clinical suspicion of HBOC. A comprehensive BARD1 screening by multigene panel analysis was performed in 4015 unrelated patients according to our regional guidelines for genetic testing in hereditary cancer. In addition, 51,202 Genome Aggregation Database (gnomAD) non-Finnish, non-cancer European individuals were used as a control population. In our patient cohort, we identified 19 patients with heterozygous BARD1 truncating variants (0.47%), whereas the frequency observed in the gnomAD controls was 0.12%. We found a statistically significant association of truncating BARD1 variants with overall risk (odds ratio (OR) = 3.78; CI = 2.10-6.48; p = 1.16 x 10(-5)). This association remained significant in the hereditary breast cancer (HBC) group (OR = 4.18; CI = 2.10-7.70; p = 5.45 x 10(-5)). Furthermore, deleterious BARD1 variants were enriched among triple-negative BC patients (OR = 5.40; CI = 1.77-18.15; p = 0.001) compared to other BC subtypes. Our results support the role of BARD1 as a moderate penetrance BC predisposing gene and highlight a stronger association with triple-negative tumors

Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation

IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21lowCD38low). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies

Antipsychotic prescribing for vulnerable populations: a clinical audit at an acute Australian mental health unit at two-time points

Background: Antipsychotics are recognised as a critical intervention for schizophrenia and bipolar disorder. Guidelines globally endorse the routine practice of antipsychotic monotherapy, at the minimum effective dose. Even in treatmentresistant schizophrenia, clozapine use is endorsed before combining antipsychotics. This aim of this study was to review antipsychotic polytherapy alone, high-dose therapy alone, polytherapy and highdose prescribing patterns in adults discharged from an inpatient mental health unit at two time-points, and the alignment of this prescribing with clinical guideline recommendations. Additionally, associations with polytherapy and high-dose antipsychotic prescribing, including patient and clinical characteristics, were explored. Methods: A retrospective clinical audit of 400 adults (200 patients at two different time-points) discharged with at least one antipsychotic. Preliminary findings and education sessions were provided to physicians between Cohorts. Outcomes (polytherapy alone, high-dose therapy alone, polytherapy and high-dose therapy) were compared between study Cohorts using chi-squared and rank-sum tests. Associations between outcomes and covariates were assessed using multivariable logistic regression. Results: Most patients (62.5%) were discharged on a single antipsychotic within the recommended dose range. There was a clear preference for prescribing second generation antipsychotics, and in this respect, prescribing is aligned with current evidence-based guidelines. However, sub-optimal prescribing practices were identified for both Cohorts in relation to polytherapy and high-dose antipsychotic rates. Involuntary treatment, frequent hospitalisations and previous clozapine use significantly increased the risk of all three prescribing outcomes at discharge. Conclusions: In a significant minority, antipsychotic prescribing did not align with clinical guidelines despite increased training, indicating that the education program alone was ineffective at positively influencing antipsychotic prescribing practices. Further consideration should be given when prescribing antipsychotics for involuntary patients, people with frequent hospitalisations, and those who have previously trialled clozapine