Noninvasive transcranial brain stimulation in central post-stroke pain: A systematic review.

BACKGROUND: The aim of this systematic review is to analyze the efficacy of noninvasive brain stimulation (NBS) in the treatment of central post-stroke pain (CPSP). METHODS: We included randomized controlled trials testing the efficacy of transcranial magnetic stimulation (TMS) or transcranial direct current stimulation versus placebo or other usual therapy in patients with CPSP. Articles in English, Portuguese, Spanish, Italian, and French were included. A bibliographic search was independently conducted on June 1, 2022, by two authors, using the databases MEDLINE (PubMed), Embase (Elsevier), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and Web of Science Core Collection. The risk of bias was assessed using the second version of the Cochrane risk of bias (RoB 2) tool and the certainty of the evidence was evaluated through Grading of Recommendations Assessment, Development and Evaluation. RESULTS: A total of 2,674 records were identified after removing duplicates, of which 5 eligible studies were included, involving a total of 119 patients. All five studies evaluated repetitive TMS, four of which stimulated the primary motor cortex (M1) and one stimulated the premotor/dorsolateral prefrontal cortex. Only the former one reported a significant pain reduction in the short term, while the latter one was interrupted due to a consistent lack of analgesic effect. CONCLUSION: NBS in the M1 area seems to be effective in reducing short-term pain; however, more high-quality homogeneous studies, with long-term follow-up, are required to determine the efficacy of this treatment in CSPS.

Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2ß did not differ between groups (p > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.

ZooTraits: An R shiny app for exploring animal trait data for ecological and evolutionary research.

Animal trait data are scattered across several datasets, making it challenging to compile and compare trait information across different groups. For plants, the TRY database has been an unwavering success for those ecologists interested in addressing how plant traits influence a wide variety of processes and patterns, but the same is not true for most animal taxonomic groups. Here, we introduce ZooTraits, a Shiny app designed to help users explore and obtain animal trait data for research in ecology and evolution. ZooTraits was developed to tackle the challenge of finding in a single site information of multiple trait datasets and facilitating access to traits by providing an easy-to-use, open-source platform. This app combines datasets centralized in the Open Trait Network, raw data from the AnimalTraits database, and trait information for animals compiled by Gonçalves-Souza et al. (2023, Ecology and Evolution 13, e10016). Importantly, the ZooTraits app can be accessed freely and provides a user-friendly interface through three functionalities that will allow users to easily visualize, compare, download, and upload trait data across the animal tree of life-ExploreTrait, FeedTrait, and GetTrait. By using ExploreTrait and GetTrait, users can explore, compare, and extract 3954 trait records from 23,394 species centralized in the Open Traits Network, and trait data for ~2000 species from the AnimalTraits database. The app summarizes trait information for numerous taxonomic groups within the Animal Kingdom, encompassing data from diverse aquatic and terrestrial ecosystems and various geographic regions worldwide. Moreover, ZooTraits enables researchers to upload trait information, serving as a hub for a continually expanding global trait database. By promoting the centralization of trait datasets and offering a platform for data sharing, ZooTraits is facilitating advancements in trait-based ecological and evolutionary studies. We hope that other trait databases will evolve to mirror the approach we have outlined here.

HIV and AIDS in the state of Paraná, Brazil, 2007-2022: trends and spatiotemporal distribution.

OBJECTIVE: The aim of this study was to analyze the spatiotemporal evolution of the incidence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in the state of Paraná, Brazil. METHODS: An ecological study with an analytical component of time series analysis was conducted in the state of Paraná from 2007 to 2022. The data source was the Notifiable Diseases Information System. To study the trend, the Prais-Winsten generalized linear regression model was used by decomposing the time series, and for spatial analysis, the Moran's index was applied. RESULTS: The total sample consisted of 50,676 HIV/AIDS records. The incidence rate showed an increasing trend, with an average growth of 2.14% [95% confidence interval - 95%CI 1.16-3.13] per month. From 2007 to 2014 and from 2015 to 2022, the average number of cases in the state was 105.64 and 159.20 per 100,000 inhabitants, respectively, with significant variation among municipalities. Spatial clusters of high risk persisted in the metropolitan region, the capital, and coastal areas, and a new cluster was observed in the northern region of the state. CONCLUSION: The incidence rates of HIV/AIDS showed an upward trend over time. The number of cases varied considerably in some municipalities, especially in the coastal region. Spatial analysis revealed geospatial patterns of high risk in the main metropolitan areas of Paraná: Curitiba (including the coastal area), Londrina, and Maringá, which share characteristics such as a high degree of urbanization and ongoing economic development.

Nitrospirillum viridazoti sp. nov., an Efficient Nitrogen-Fixing Species Isolated from Grasses.

A group of Gram-negative plant-associated diazotrophic bacteria belonging to the genus Nitrospirillum was investigated, including both previously characterized and newly isolated strains from diverse regions and biomes, predominantly in Brazil. Phylogenetic analysis of 16S rRNA and recA genes revealed the formation of a distinct clade consisting of thirteen strains, separate from the formally recognized species N. amazonense (the closest species) and N. iridis. Comprehensive taxonomic analyses using the whole genomes of four strains (BR 11140T = AM 18T = Y-2T = DSM 2788T = ATCC 35120T, BR 11142T = AM 14T = Y-1T = DSM 2787T = ATCC 35119T, BR 11145 = CBAmC, and BR 12005) supported the division of these strains into two species: N. amazonense (BR 11142 T and BR 12005) and a newly proposed species (BR 11140 T and BR 11145), distinct from N. iridis. The phylogenomic analysis further confirmed the presence of the new Nitrospirillum species. Additionally, MALDI-TOF MS analysis of whole-cell mass spectra provided further evidence for the differentiation of the proposed Nitrospirillum species, separate from N. amazonense. Analysis of chemotaxonomy markers (i.e., genes involved in fatty acid synthesis, metabolism and elongation, phospholipid synthesis, and quinone synthesis) revealed that the new species highlights high similarity and evolutionary convergence with other Nitrospirillum species. This new species exhibited nitrogen fixation ability in vitro, it has similar NifHDK protein phylogeny position with the closest species, lacked denitrification capability, but possessed the nosZ gene, enabling N2O reduction, distinguishing it from the closest species. Despite being isolated from diverse geographic regions, soil types, and ecological niches, no significant phenotypic or physiological differences were observed between the proposed new species and N. amazonense. Based on these findings, a new species, Nitrospirillum viridazoti sp. nov., was classified, with the strain BR 11140T (DSM 2788T, ATCC 35120T) designated as the type strain.

Sensitive detection of pathological seeds of α-synuclein, tau and prion protein on solid surfaces.

Prions or prion-like aggregates such as those composed of PrP, α-synuclein, and tau are key features of proteinopathies such as prion, Parkinson's and Alzheimer's diseases, respectively. Their presence on solid surfaces may be biohazardous under some circumstances. PrP prions bound to solids are detectable by ultrasensitive real-time quaking-induced conversion (RT-QuIC) assays if the solids can be immersed in assay wells or the prions transferred to pads. Here we show that prion-like seeds can remain detectable on steel wires for at least a year, or even after enzymatic cleaning and sterilization. We also show that contamination of larger objects with pathological seeds of α-synuclein, tau, and PrP can be detected by simply assaying a sampling medium that has been transiently applied to the surface. Human α-synuclein seeds in dementia with Lewy bodies brain tissue were detected by α-synuclein RT-QuIC after drying of tissue dilutions with concentrations as low as 10-6 onto stainless steel. Tau RT-QuIC detected tau seeding activity on steel exposed to Alzheimer's disease brain tissue diluted as much as a billion fold. Prion RT-QuIC assays detected seeding activity on plates exposed to brain dilutions as extreme as 10-5-10-8 from prion-affected humans, sheep, cattle and cervids. Sampling medium collected from surgical instruments used in necropsies of sporadic Creutzfeldt-Jakob disease-infected transgenic mice was positive down to 10-6 dilution. Sensitivity for prion detection was not sacrificed by omitting the recombinant PrP substrate from the sampling medium during its application to a surface and subsequent storage as long as the substrate was added prior to performing the assay reaction. Our findings demonstrate practical prototypic surface RT-QuIC protocols for the highly sensitive detection of pathologic seeds of α-synuclein, tau, and PrP on solid objects.

The Impact of Excessive Fructose Intake on Adipose Tissue and the Development of Childhood Obesity.

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.

Use of Trichoderma in the Production of Forest Seedlings.

Forest production has great relevance in the Brazilian economy, characterized by several production sectors, including the production of seedlings. With the focus on maximizing the capacity of survival, development, and adaptation of seedlings, Trichoderma is highlighted as a potentially useful genus of microorganisms for promoting growth and higher product quality. In this sense, this review aims to describe the main mechanisms of fungi action in forest seedlings' production. The different species of the genus Trichoderma have specific mechanisms of action, and the current scenario points to more advances in the number of species. The interaction process mediated by different mechanisms of action begins in the communication with plants, from the colonization process. After the interaction, chemical dialogues allow the plant to develop better because, from colonization, the forest seedlings can maximize height and increase shoot and root development. Fungi promote solubilization and availability of nutrients to seedlings, which show numerous benefits to the development. The use of beneficial microorganisms, such as fungi of the genus Trichoderma, has become a sustainable strategy to enhance seedling development, reducing the use of agrochemicals and industrial fertilizers.

Challenges in adapting a stroke unit in a middle-income country: warning about costs and underfunding to achieve the Brazilian Ministry of Health's benchmark.

Background: Since the implementation of the stroke care line in Brazil, the relationship (adequacy) of costs spent during hospitalization with the Brazilian Ministry of Health indicators for a stroke unit have not yet been analyzed. Aims: This study aimed to assess the adequacy of a comprehensive stroke center for key performance indicators and analyze the costs involved in hospitalization. We verified the association between stroke severity at admission and care costs during hospitalization. Methods: A retrospective medical chart review of 451 patients was performed using semiautomatic electronic data from a single comprehensive stroke center in Brazil between July 2018 and January 2020. Clinical and resource utilization data were collected, and the mean acute treatment cost per person was calculated. The Kruskal-Wallis test with Dunn's post-test was used to compare the total costs between stroke types and reperfusion therapies. A robust linear regression test was used to verify the association between stroke severity at hospital admission and the total hospitalization costs. Good adequacy rates were observed for several indicators. Results: Data from 451 patients were analyzed. The stroke unit had good adaptation to key performance indicators, but some critical points needed revision and improvement to adapt to the requirements of the Ministry of Health. The average total cost of the patient's stay was the USD 2,637.3, with the daily hospitalization, procedure, operating room, and materials/medication costs equating to USD 2,011.1, USD 220.7, USD 234.1, and USD 98.8, respectively. There was a positive association between the total cost and length of hospital stay (p < 0.001). Conclusion: The stroke unit complied with most of the main performance indicators proposed by the Brazilian Ministry of Health. Underfunding of the costs involved in the hospitalization of patients was verified, and high costs were associated with the length of stay, stroke severity, and mechanical thrombectomy.

To what extent does frailty mediate the association between age and the outcomes of brain reperfusion following acute ischemic stroke?

Objective: We evaluated the extent to which frailty mediated the association between age, poor functional outcomes, and mortality after acute ischemic stroke when patients were treated with brain reperfusion (thrombolytic therapy and/or thrombectomy). Materials and methods: This retrospective cohort study included patients diagnosed with ischemic stroke who had undergone intravenous cerebral reperfusion therapy and/or mechanical thrombectomy. We created a mediation model by analyzing the direct natural effect of an mRS score > 2 and death on age-mediated frailty according to the Frailty Index. Results: We enrolled 292 patients with acute ischemic stroke who underwent brain reperfusion. Their mean age was 67.7 ± 13.1 years. Ninety days after the stroke ictus, 54 (18.5%) participants died, and 83 (28.4%) lived with moderate to severe disability (2 < mRS < 6). In the mediation analysis of the composite outcome of disability (mRS score > 2) or death, frailty accounted for 28% of the total effect of age. The models used to test for the interaction between age and frailty did not show statistically significant interactions for either outcome, and the addition of the interaction did not significantly change the direct or indirect effects, nor did it improve model fit. Conclusion: Frailty mediated almost one-third of the effect of age on the composite outcome of disability or death after acute ischemic stroke.

Evaluation by community health agents of the attributes of Primary Health Care for fighting leprosy: a cross-sectional study

OBJECTIVE: To evaluate whether the attributes of Primary Healthcare are present in leprosy control actions in Londrina from Community Health Workers' (CHW) perspectives. METHOD: Observational and evaluative study. Data collection occurred between January and March 2020 in Londrina, Paraná, using the questionnaire "Primary Care Assessment Tool (PCATool) - Hansen's disease - CHW version" and a population-based census of 246 CHWs from 52 Primary Healthcare Units. The analyses used a cutoff point (≥ 6.6), central tendency, and dispersion measures. One-way ANOVA and Tukey's post hoc tests were used to analyze differences. Results: The general performance towards the primary healthcare attributes were evaluated as strong (mean = 6.95 / SD = 1.08) and the essential score (mean = 7.39 / SD = 1.0). On the other hand, the derived score was evaluated as poor (mean = 6.07 / sd = 1.06). Concerning the Access attribute, the rural zone had a lower score than the urban (mean = 4.47 / SD = 1.63). Conclusion: The study highlights issues that can be improved, such as first contact access, catalog of services offered to leprosy patients, information provided to the community, professional training, and differences in PHC performance between urban and rural regions.

Implantable SDF-1α-loaded silk fibroin hyaluronic acid aerogel sponges as an instructive component of the glioblastoma ecosystem: Between chemoattraction and tumor shaping into resection cavities.

In view of inevitable recurrences despite resection, glioblastoma (GB) is still an unmet clinical need. Dealing with the stromal-cell derived factor 1-alpha (SDF-1α)/CXCR4 axis as a hallmark of infiltrative GB tumors and with the resection cavity situation, the present study described the effects and relevance of a new engineered micro-nanostructured SF-HA-Hep aerogel sponges, made of silk fibroin (SF), hyaluronic acid (HA) and heparin (Hep) and loaded with SDF-1α, to interfere with the GB ecosystem and residual GB cells, attracting and confining them in a controlled area before elimination. 70 µm-pore sponges were designed as an implantable scaffold to trap GB cells. They presented shape memory and fit brain cavities. Histological results after implantation in brain immunocompetent Fischer rats revealed that SF-HA-Hep sponges are well tolerated for more than 3 months while moderately and reversibly colonized by immuno-inflammatory cells. The use of human U87MG GB cells overexpressing the CXCR4 receptor (U87MG-CXCR4+) and responding to SDF-1α allowed demonstrating directional GB cell attraction and colonization of the device in vitro and in vivo in orthotopic resection cavities in Nude rats. Not modifying global survival, aerogel sponge implantation strongly shaped U87MG-CXCR4+ tumors in cavities in contrast to random infiltrative growth in controls. Overall, those results support the interest of SF-HA-Hep sponges as modifiers of the GB ecosystem dynamics acting as "cell meeting rooms" and biocompatible niches whose properties deserve to be considered toward the development of new clinical procedures. STATEMENT OF SIGNIFICANCE: Brain tumor glioblastoma (GB) is one of the worst unmet clinical needs. To prevent the relapse in the resection cavity situation, new implantable biopolymer aerogel sponges loaded with a chemoattractant molecule were designed and preclinically tested as a prototype targeting the interaction between the initial tumor location and its attraction by the peritumoral environment. While not modifying global survival, biocompatible SDF1-loaded hyaluronic acid and silk fibroin sponges induce directional GB cell attraction and colonization in vitro and in rats in vivo. Interestingly, they strongly shaped GB tumors in contrast to random infiltrative growth in controls. These results provide original findings on application of exogenous engineered niches that shape tumors and serve as cell meeting rooms for further clinical developments.

HIV and AIDS in the state of Paraná, Brazil, 2007-2022: trends and spatiotemporal distribution / HIV e AIDS no Estado do Paraná, Brasil, 2007-2022: tendência e distribuição espaçotemporal

ABSTRACT Objective: The aim of this study was to analyze the spatiotemporal evolution of the incidence rates of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in the state of Paraná, Brazil. Methods: An ecological study with an analytical component of time series analysis was conducted in the state of Paraná from 2007 to 2022. The data source was the Notifiable Diseases Information System. To study the trend, the Prais-Winsten generalized linear regression model was used by decomposing the time series, and for spatial analysis, the Moran's index was applied. Results: The total sample consisted of 50,676 HIV/AIDS records. The incidence rate showed an increasing trend, with an average growth of 2.14% [95% confidence interval - 95%CI 1.16-3.13] per month. From 2007 to 2014 and from 2015 to 2022, the average number of cases in the state was 105.64 and 159.20 per 100,000 inhabitants, respectively, with significant variation among municipalities. Spatial clusters of high risk persisted in the metropolitan region, the capital, and coastal areas, and a new cluster was observed in the northern region of the state. Conclusion: The incidence rates of HIV/AIDS showed an upward trend over time. The number of cases varied considerably in some municipalities, especially in the coastal region. Spatial analysis revealed geospatial patterns of high risk in the main metropolitan areas of Paraná: Curitiba (including the coastal area), Londrina, and Maringá, which share characteristics such as a high degree of urbanization and ongoing economic development.

RESUMO Objetivo: Este estudo teve como objetivo analisar a evolução espaçotemporal das taxas de incidência do vírus da imunodeficiência humana (HIV) e da síndrome da imunodeficiência adquirida (AIDS) no estado do Paraná, Brasil. Métodos: Foi realizado um estudo ecológico com componente analítico de séries temporais e análise espacial no estado do Paraná, de 2007 a 2022. A fonte de dados foi o Sistema de Informação de Agravos de Notificação. Para estudar a tendência, foi utilizado o modelo de regressão linear generalizada de Prais-Winsten por meio da decomposição de séries temporais e, para a análise espacial, foi aplicado o Índice de Moran. Resultados: A amostra total foi composta de 50.676 registros de HIV/AIDS. A taxa de incidência apresentou tendência crescente, com crescimento médio de 2,14% (intervalo de confiança de 95% — IC95% 1,16-3,13) ao mês. Nos períodos de 2007 a 2014 e 2015 a 2022, a média de casos no estado foi de 105,64 e 159,20 a cada 100 mil habitantes, respectivamente, com importantes variações entre os municípios. Agrupamentos espaciais de alto risco permaneceram na região metropolitana à capital e litoral e um novo agrupamento foi observado à região norte do estado. Conclusão: As taxas de incidência do HIV/AIDS apresentaram tendência temporal crescente. O número de casos variou substancialmente em alguns municípios, principalmente naqueles localizados na região litorânea. A análise espacial revelou padrões geoespaciais de alto risco nas principais regiões metropolitanas do Paraná: Curitiba (abrange o litoral), Londrina e Maringá, as quais compartilham características como elevado grau de urbanização e constante desenvolvimento econômico.

Proposition of In silico Pharmacophore Models for Malaria: A Review.

In the field of medicinal chemistry, the concept of pharmacophore refers to the specific region of a molecule that possesses essential structural and chemical characteristics for binding to a receptor and eliciting biological activity. Understanding the pharmacophore is crucial for drug research and development, as it allows the design of new drugs. Malaria, a widespread disease, is commonly treated with chloroquine and artemisinin, but the emergence of parasite resistance limits their effectiveness. This study aims to explore computer simulations to discover a specific pharmacophore for Malaria, providing new alternatives for its treatment. A literature review was conducted, encompassing articles proposing a pharmacophore for Malaria, gathered from the "Web of Science" database, with a focus on recent publications to ensure up-to-date analysis. The selected articles employed diverse methods, including ligand-based and structurebased approaches, integrating molecular structure and biological activity data to yield comprehensive analyses. Affinity evaluation between the proposed pharmacophore and the target receptor involved calculating free energy to quantify their interaction. Multiple linear regression was commonly utilized, though it is sensitive to multicollinearity issues. Another recurrent methodology was the use of the Schrödinger package, employing tools such as the Phase module and the OPLS force field for interaction analysis. Pharmacophore model proposition allows threedimensional representations guiding the synthesis and design of new biologically active compounds, offering a promising avenue for discovering therapeutic agents to combat Malaria.

Effectiveness of neurolysis as a treatment for complications of leprosy neuritis: a systematic review.

BACKGROUND: Complications of leprosy neuritis are considered serious and apparent, with the potential to disable and/or limit individuals. These complications affect not only a patient's physical functioning, but also their family and social lives, while directly impacting the ability to work and/or maintain financial independence, subsequently interfering with their overall quality of life. The present review, therefore, aimed to analyze the effectiveness of neurolysis as an alternative treatment for the complications associated with leprosy neuritis. METHODS: The present review was performed based on the Joanna Briggs Institute methodology, in an effort to answer the following research question: what is the effectiveness of neurolysis as a treatment for leprosy neuritis complications? This research question was defined using the patient-intervention-outcome (PIO) framework, where leprosy represents 'P', neurolysis for 'I', and neuropathic pain/motor function/sensorial function/physical disability/quality of life for 'O'. Randomized and non-randomized clinical trials and prospective observational cohort studies were included in the present review, with no time or date restrictions. RESULTS: The present review included 1 randomized clinical trial and 10 prospective studies, published between 1976 and 2020. All of the outcomes showed improvement, with relief from neuropathic pain being the primary finding. CONCLUSIONS: The evidence obtained in the present review suggested that neurolysis is an effective alternative for the treatment of physical disabilities, the recovery of sensory and motor function, the restoration of quality of life, and neuropathic pain relief.

Insights into Healthcare Professionals' Perceptions and Attitudes toward Nanotechnological Device Application: What Is the Current Situation in Glioblastoma Research?

Nanotechnology application in cancer treatment is promising and is likely to quickly spread worldwide in the near future. To date, most scientific studies on nanomaterial development have focused on deepening the attitudes of end users and experts, leaving clinical practice implications unexplored. Neuro-oncology might be a promising field for the application of nanotechnologies, especially for malignant brain tumors with a low-survival rate such as glioblastoma (GBM). As to improving patients' quality of life and life expectancy, innovative treatments are worth being explored. Indeed, it is important to explore clinicians' intention to use experimental technologies in clinical practice. In the present study, we conducted an exploratory review of the literature about healthcare workers' knowledge and personal opinions toward nanomedicine. Our search (i) gives evidence for disagreement between self-reported and factual knowledge about nanomedicine and (ii) suggests the internet and television as main sources of information about current trends in nanomedicine applications, over scientific journals and formal education. Current models of risk assessment suggest time-saving cognitive and affective shortcuts, i.e., heuristics support both laypeople and experts in the decision-making process under uncertainty, whereas they might be a source of error. Whether the knowledge is poor, heuristics are more likely to occur and thus clinicians' opinions and perspectives toward new technologies might be biased.

ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair.

To recognize DNA adducts, nucleotide excision repair (NER) deploys the XPC sensor, which detects damage-induced helical distortions, followed by engagement of TFIIH for lesion verification. Accessory players ensure that this factor handover takes place in chromatin where DNA is tightly wrapped around histones. Here, we describe how the histone methyltransferase ASH1L, once activated by MRG15, helps XPC and TFIIH to navigate through chromatin and induce global-genome NER hotspots. Upon UV irradiation, ASH1L adds H3K4me3 all over the genome (except in active gene promoters), thus priming chromatin for XPC relocations from native to damaged DNA. The ASH1L-MRG15 complex further recruits the histone chaperone FACT to DNA lesions. In the absence of ASH1L, MRG15 or FACT, XPC is misplaced and persists on damaged DNA without being able to deliver the lesions to TFIIH. We conclude that ASH1L-MRG15 makes damage verifiable by the NER machinery through the sequential deposition of H3K4me3 and FACT.

Effect of high pressure processing and water activity on pressure resistant spoilage lactic acid bacteria (Latilactobacillus sakei) in a ready-to-eat meat emulsion model.

The main use of High Pressure Processing (HPP) in food processing is microorganism inactivation, and studies demonstrated that the characteristics of matrix and microorganisms can interfere on it. As the behavior of lactic acid bacteria exposed to different water activity (aw) levels in a meat product is still unclear, this study aimed to determine the effect of pressure, time, and aw to inactivate Latilactobacillus sakei, a pressure resistant lactic acid bacteria (LAB) in a meat emulsion model through a response surface methodology. The meat emulsion model was designed with adjusted aw (from 0.940 to 0.960) and was inoculated with a pressure resistant LAB and processed varying pressure (400-600 MPa) and time (180-480 s), following the Central Composite Rotational Design (CCRD). The inactivation of the microorganism ranged from 0.99 to 4.12 UFC/g depending on the applied condition. At studied conditions, according to the best fitting and most significant polynomial equation (R2 of 89.73 %), in a meat emulsion model, aw had no influenced on HPP inactivation on LAB (p > 0.05) and only pressure and holding time had significative impact on it. The results of experimental validation of the mathematical model were satisfactory, confirming the suitability of the model. The information obtained in the present study stands out the matrix, microorganism and process effects at HPP efficiency. The answers obtained support food processors in product development, process optimization and food waste reduction.

Plasmodium vivax infection alters the peripheral immunoregulatory network of CD4 T follicular cells and B cells.

Regulatory and effector cell responses to Plasmodium vivax, the most common human malaria parasite outside Africa, remain understudied in naturally infected populations. Here, we describe peripheral CD4+ T- and B-cell populations during and shortly after an uncomplicated P. vivax infection in 38 continuously exposed adult Amazonians. Consistent with previous observations, we found an increased frequency in CD4+ CD45RA- CD25+ FoxP3+ T regulatory cells that express the inhibitory molecule CTLA-4 during the acute infection, with a sustained expansion of CD21- CD27- atypical memory cells within the CD19+ B-cell compartment. Both Th1- and Th2-type subsets of CXCR5+ ICOShi PD-1+ circulating T follicular helper (cTfh) cells, which are thought to contribute to antibody production, were induced during P. vivax infection, with a positive correlation between overall cTfh cell frequency and IgG antibody titers to the P. vivax blood-stage antigen MSP119 . We identified significant changes in cell populations that had not been described in human malaria, such as an increased frequency of CTLA-4+ T follicular regulatory cells that antagonize Tfh cells, and a decreased frequency of circulating CD24hi CD27+ B regulatory cells in response to acute infection. In conclusion, we disclose a complex immunoregulatory network that is critical to understand how naturally acquired immunity develops in P. vivax malaria.

Bringing light onto the Raunkiæran shortfall: A comprehensive review of traits used in functional animal ecology.

Trait-based approaches elucidate the mechanisms underlying biodiversity response to, or effects on, the environment. Nevertheless, the Raunkiæran shortfall-the dearth of knowledge on species traits and their functionality-presents a challenge in the application of these approaches. We conducted a systematic review to investigate the trends and gaps in trait-based animal ecology in terms of taxonomic resolution, trait selection, ecosystem type, and geographical region. In addition, we suggest a set of crucial steps to guide trait selection and aid future research to conduct within and cross-taxon comparisons. We identified 1655 articles using virtually all animal groups published from 1999 to 2020. Studies were concentrated in vertebrates, terrestrial habitats, the Palearctic realm, and mostly investigated trophic and habitat dimensions. Additionally, they focused on response traits (79.4%) and largely ignored intraspecific variation (94.6%). Almost 36% of the data sets did not provide the rationale behind the selection of morphological traits. The main limitations of trait-based animal ecology were the use of trait averages and a rare inclusion of intraspecific variability. Nearly one-fifth of the studies based only on response traits conclude that trait diversity impacts ecosystem processes or services without justifying the connection between them or measuring them. We propose a guide for standardizing trait collection that includes the following: (i) determining the type of trait and the mechanism linking the trait to the environment, ecosystem, or the correlation between the environment, trait, and ecosystem, (ii) using a "periodic table of niches" to select the appropriate niche dimension to support a mechanistic trait selection, and (iii) selecting the relevant traits for each retained niche dimension. By addressing these gaps, trait-based animal ecology can become more predictive. This implies that future research will likely focus on collaborating to understand how environmental changes impact animals and their capacity to provide ecosystem services and goods.