Large environmental changes reduce valence-dependent belief updating.

When updating beliefs, humans tend to integrate more desirable information than undesirable information. In stable environments (low uncertainty and high predictability), this asymmetry favors motivation towards action and perceived self-efficacy. However, in changing environments (high uncertainty and low predictability), this process can lead to risk underestimation and increase unwanted costs. Here, we examine how people (n = 388) integrate threatening information during an abrupt environmental change (mandatory quarantine during the COVID-19 pandemic). Given that anxiety levels are associated with the magnitude of the updating belief asymmetry; we explore its relationship during this particular context. We report a significant reduction in asymmetrical belief updating during a large environmental change as individuals integrated desirable and undesirable information to the same extent. Moreover, this result was supported by computational modeling of the belief update task. However, we found that the reduction in asymmetrical belief updating was not homogeneous among people with different levels of Trait-anxiety. Individuals with higher levels of Trait-anxiety maintained a valence-dependent updating, as it occurs in stable environments. On the other hand, updating behavior was not associated with acute anxiety (State-Anxiety), health concerns (Health-Anxiety), or having positive expectations (Trait-Optimism). These results suggest that highly uncertain environments can generate adaptive changes in information integration. At the same time, it reveals the vulnerabilities of individuals with higher levels of anxiety to adapt the way they learn.

Critical behavior of cascading failures in overloaded networks.

While network abrupt breakdowns due to overloads and cascading failures have been studied extensively, the critical exponents and the universality class of such phase transitions have not been discussed. Here, we study breakdowns triggered by failures of links and overloads in networks with a spatial characteristic link length ζ. Our results indicate that this abrupt transition has features and critical exponents similar to those of interdependent networks, suggesting that both systems are in the same universality class. For weakly embedded systems (i.e., ζ of the order of the system size L) we observe a mixed-order transition, where the order parameter collapses following a long critical plateau. On the other hand, strongly embedded systems (i.e., ζ≪L) exhibit a pure first-order transition, involving nucleation and the growth of damage. The system's critical behavior in both limits is similar to that observed in interdependent networks.

Low-Density Lipoproteins Increase Proliferation, Invasion, and Chemoresistance via an Exosome Autocrine Mechanism in MDA-MB-231 Chemoresistant Cells.

Dyslipidemias involving high concentrations of low-density lipoproteins (LDLs) increase the risk of developing triple-negative breast cancer (TNBC), wherein cholesterol metabolism and protein translation initiation mechanisms have been linked with chemoresistance. Doxorubicin (Dox) treatment, a member of the anthracycline family, represents a typical therapeutic strategy; however, chemoresistance remains a significant challenge. Exosomes (Exs) secreted by tumoral cells have been implicated in cell communication pathways and chemoresistance mechanisms; the content of exosomes is an outcome of cellular cholesterol metabolism. We previously induced Dox resistance in TNBC cell models, characterizing a variant denominated as variant B cells. Our results suggest that LDL internalization in parental and chemoresistant variant B cells is associated with increased cell proliferation, migration, invasion, and spheroid growth. We identified the role of eIF4F translation initiation factor and the down-regulation of tumor suppressor gene PDCD4, an inhibitor of eIF4A, in chemoresistant variant B cells. In addition, the exomes secreted by variant B cells were characterized by the protein content, electronic microscopy, and cell internalization assays. Critically, exosomes purified from LDL-treated variant B cell promoted cell proliferation, migration, and an increment in lactate concentration. Our results suggest that an autocrine phenomenon induced by exosomes in chemoresistant cells may induce modifications on signaling mechanisms of the p53/Mdm2 axis and activation of p70 ribosomal protein kinase S6. Moreover, the specific down-regulated profile of chaperones Hsp90 and Hsp70 secretion inside the exosomes of the chemoresistant variant could be associated with this phenomenon. Therefore, autocrine activation mediated by exosomes and the effect of LDL internalization may influence changes in exosome chaperone content and modulate proliferative signaling pathways, increasing the aggressiveness of MDA-MB-231 chemoresistant cells.

Therapeutic potential of LINS01 histamine H3 receptor antagonists as antineoplastic agents for triple negative breast cancer.

The aims of this work were to evaluate the expression of histamine H3 receptor (H3R) in triple negative breast cancer (TNBC) samples and to investigate the antitumoral efficacy and safety of the LINS01 series of H3R antagonists, through in silico, in vitro, and in vivo approaches. Antitumor activity of LINS01009, LINS01010, LINS01022, LINS01023 was assayed in vitro in 4T1 and MDA-MB-231 TNBC cells (0.01-100 µM), and in vivo in 4T1 tumors orthotopically established in BALB/c mice (1 or 20 mg/kg). Additionally, H3R expression was assessed in 50 human TNBC samples. We have described a higher H3R mRNA expression in basal-like/TNBC tumors vs. matched normal tissue using TCGA Pan-Cancer Atlas data, and a higher H3R expression in human tumor samples vs. peritumoral tissue evidenced by immunohistochemistry associated with poorer survival. Furthermore, while all the essayed compounds showed antitumoral properties, LINS01022 and LINS01023 exhibited the most potent antiproliferative effects by: i) inducing cell apoptosis and suppressing cell migration in 4T1 and MDA-MB-231 TNBC cells, and ii) inhibiting cell growth in paclitaxel-resistant 4T1 cells (potentiating the paclitaxel antiproliferative effect). Moreover, 20 mg/kg LINS01022 reduced tumor size in 4T1 tumor-bearing mice, exhibiting a safe toxicological profile and potential for druggability estimated by ADME calculations. We conclude that the H3R is involved in the regulation of TNBC progression, offering promising therapeutic potential for the novel LINS01 series of H3R antagonists.

Benefits and trade-offs of replacing inorganic fertilizer by organic substrate in crop production: A global meta-analysis.

Replacing inorganic fertilizer with organic substrate contributes to sustainable agricultural production capacity. However, the effects of organic substitution regimes (OSR) on global crop productivity, soil carbon (C) and nitrogen (N) losses and biofertility as function of environmental variables have not been systematically quantified. Here, we have conducted a meta-analysis of these effects using field data (211 papers with 852 observations) collected around the world. Results indicated that OSR increased crop productivity (3.04 %) and soil biofertility (soil qMBC, qMBN, microbial richness, Shannon and functionality by 11.4 %, 21.1 %, 10.2 %, 3.95 %, and 38.5 %, respectively), and reduced soil N losses (N2O emissions, NH3 volatilization and soil N leaching by 26.5 %, 26.1 %, and 33.8 %, respectively), but increased CO2 emissions (19.4 %), and paddy fields CH4 emissions (41.2 %). N rate was an important factor influencing crop productivity and soil biofertility response to OSR, and crop productivity and soil biofertility had a greater positive response at moderate substitution rates in acid soil and long-term trials, but full substitution significantly decreased crop yield. Furthermore, the increase in soil biofertility and crop yield saturated in ~10-14 and ~ 22 years after organic substrate input. The emissions of CO2, CH4, and N2O significantly increased with increasing substitution rates, while the opposite was true for N leaching. The NH3 volatilization response to OSR presented a positive effect in acidic and coarse texture soil. OSR was more beneficial in mitigating soil C and N loss response (except CO2 emissions) in uplands compared to paddy fields. Therefore, implementation of OSR requires site-specific strategies to better achieve a balance between increasing crop production and reducing environmental benefits. Given that the OSR improvement varies depending on environmental variables, we propose a predictive model to initially assess the potential for OSR improvement. This study will provide scientific guidance on the reasonable application of organic substrate in agroecosystems.

IQGAP1 and NWASP promote human cancer cell dissemination and metastasis by regulating ß1-integrin via FAK and MRTF/SRF.

Attachment of circulating tumor cells to the endothelial cells (ECs) lining blood vessels is a critical step in cancer metastatic colonization, which leads to metastatic outgrowth. Breast and prostate cancers are common malignancies in women and men, respectively. Here, we observe that ß1-integrin is required for human prostate and breast cancer cell adhesion to ECs under shear-stress conditions in vitro and to lung blood vessel ECs in vivo. We identify IQGAP1 and neural Wiskott-Aldrich syndrome protein (NWASP) as regulators of ß1-integrin transcription and protein expression in prostate and breast cancer cells. IQGAP1 and NWASP depletion in cancer cells decreases adhesion to ECs in vitro and retention in the lung vasculature and metastatic lung nodule formation in vivo. Mechanistically, NWASP and IQGAP1 act downstream of Cdc42 to increase ß1-integrin expression both via extracellular signal-regulated kinase (ERK)/focal adhesion kinase signaling at the protein level and by myocardin-related transcription factor/serum response factor (SRF) transcriptionally. Our results identify IQGAP1 and NWASP as potential therapeutic targets to reduce early metastatic dissemination.

Translation and linguistic validation into Spanish of the Owner-Reported Outcome Measure "Liverpool Osteoarthritis in Dogs".

Introduction: Assessing chronic pain in dogs has been greatly favoured by the development of Owner-Reported Outcome Measures. Among them, the Liverpool Osteoarthritis in Dogs (LOAD) has been widely used for this purpose. Most of these tools have been written in English and its use by non English natives requires not only translation but also linguistic validation for use by veterinarians and owners. For its use, the LOAD has not undergone translation into Spanish and the objective was to generate a linguistically validated Spanish translation of the LOAD. Methods: Following the World Health Organisation and the International Society for Pharmacoeconomics and Outcomes Research published guidelines, the original LOAD English version underwent analysis and translation by two native linguists proficient in the target language. Both translations were then reviewed by a third native linguist to identify potential disparities and establish a cohesive translation (reconciliation). Subsequently, an independent linguist, fluent in both English and the target language, conducted the back translation. Finally, the research team compared the original and back translated versions to pinpoint and resolve any significant differences. Following the creation of the translated version, a cognitive debriefing was conducted to assess the questionnaire within the target population. Results: A total of 89 surveys were distributed to dog owners of varying ages, genders, and socioeconomic backgrounds. Although there were some suggestions and comments, and some adjustments were made, all respondents found the survey to be clear, achieving a linguistic validation of the Spanish LOAD.

Implementation of a Bleeding Management Algorithm in Liver Transplantation: A Pilot Study.

Objectives: The aims of the study were to compare the consumption of blood products before and after the implementation of a bleeding management algorithm in patients undergoing liver transplantation and to determine the feasibility of a multicentre, randomized study. Background: Liver transplantation remains the only curative therapy for patients with end-stage liver disease, but it carries a high risk of surgical bleeding. Materials and Methods: Retrospective study of patients treated before (group 1) and after (group 2) implementation of a haemostatic algorithm guided by viscoelastic testing, including use of lyophilized coagulation factor concentrates (prothrombin complex and fibrinogen concentrates). Primary outcome was the number of units of blood products transfused in 24 h after surgery. Secondary outcomes included hospital stay, mortality, and cost. Results: Data from 30 consecutive patients was analysed; 14 in group 1 and 16 in group 2. Baseline data were similar between groups. Median total blood product consumption 24 h after surgery was 33 U (IQR: 11-57) in group 1 and 1.5 (0-23.5) in group 2 (p = 0.028). Significantly fewer units of red blood cells, fresh frozen plasma, and cryoprecipitate were transfused in group 2 versus group 1. There was no significant difference in complications, hospital stay, or in-hospital mortality between groups. The cost of haemostatic therapy was non-significantly lower in group 2 versus group 1 (7,400 vs. 15,500 USD; p = 0.454). Conclusion: The haemostatic management algorithm was associated with a significant reduction in blood product use during 24 h after liver transplantation. This study demonstrated the feasibility and provided a sample size calculation for a larger, randomized study.

Salvadoran Celastraceae Species as a Source of Antikinetoplastid Quinonemethide Triterpenoids.

Chagas disease and leishmaniasis are among the most widespread neglected tropical diseases, and their current therapies have limited efficacy and several toxic side effects. The present study reports the chemical and antikinetoplastid profiles of extracts from five Salvadoran Celastraceae species against the Trypanosoma cruzi epimastigotes stage and Leishmania amazonensis and Leishmania donovani promastigote forms. The phytochemical profile evinced the presence of flavonoids, tannins, sterols, and triterpenes as the main components in all plant species, whereas quinonemethide triterpenoids (QMTs) were restricted to the root bark of the studied species. Antikinetoplastid evaluation highlights the root bark extracts from Zinowewia integerrima, Maytenus segoviarum, and Quetzalia ilicina as the most promising ones, exhibiting higher potency against T. cruzi (IC50 0.71-1.58 µg/mL) and L. amazonensis (IC50 0.38-2.05 µg/mL) than the reference drugs, benznidazole (IC50 1.81 µg/mL) and miltefosine (IC50 2.64 µg/mL), respectively. This potent activity was connected with an excellent selectivity index on the murine macrophage J774A.1 cell line. These findings reinforce the potential of QMTs as antikinetoplastid agents for the development of innovative phytopharmaceuticals and the plant species under study as a source of these promising lead compounds.

Alterations induced by Colomerus vitis on the structural and physiological leaf features of two grape cultivars.

Vitis vinifera is cultivated worldwide for its high nutritional and commercial value. More than 60 grape cultivars are cultivated in Chile. Two of these, the país and the corinto cultivars, are the oldest known and widely used for the preparation of traditional homemade drinks and consumption as table grapes. These two grape cultivars are affected by Colomerus vitis, an eriophyid mite which establishes on their leaves and forms erinea, where the mite and its offspring obtain shelter and food. Although C. vitis has a cosmopolitan distribution, few studies of its impact on the structure and physiology of affected plants have been reported. Herein we aimed to evaluate the impact of C. vitis infection on the structural and physiological leaf performance of the two grape cultivars. The results showed tissue hyperplasia and cell hypertrophy in the epidermis, with an overproduction of trichomes and emergences in the abaxial epidermis in both cultivars. The anatomical changes were similar between the país and corinto cultivars, but they were proportionally greater in the país, where the area affected by the erinea were greater. No significant changes were detected in the photosynthetic pigment content; however, there was an increase in the total soluble sugars content in the erineum leaves of the país cultivar. Higher contents of anthocyanins and total phenols, as well as the presence of the pinocembrin in the corinto cultivar, which was less affected by C. vitis, could also indicate some resistance to mites' attack, which should be investigated in future studies.

Bio-guided isolation of aromatic abietane diterpenoids from Salvia canariensis as biopesticides in the control of phytopathogenic fungi.

BACKGROUND: Biofungicides arise as a promising alternative to the indiscriminate use of harmful synthetic fungicides in crop management. RESULTS: The present study reports the bio-guided fractionation of an endemic plant from the Canary Islands, Salvia canariensis against the phytopathogens, Alternaria alternata, Botrytis cinerea, and Fusarium oxysporum. This procedure allowed identifying a series of diterpenoids with an abietane skeleton (1-5), which exhibited remarkable activity against the phytopathogenic fungi assayed. Their structures were established by means of spectroscopic and spectrometric methods, as well as comparison with reported data. Compounds 2 (carnosic acid), 4 (11-acetoxy carnosic acid) and 5 (11,12-diacetoxy carnosic acid) showed significant mycelium growth inhibition (%GI > 50 at 0.1 mg/mL concentration) on all the assayed fungi, and with a potency also higher than the positive control, Fosbel-Plus, a fungicide commonly used in agriculture. A preliminary structure-activity relationship is also discussed. CONCLUSIONS: These findings underline the aromatic abietane diterpenoids as promising eco-friendly alternatives to conventional fungicides to use in integrated pest management. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

New information on paleopathologies in non-avian theropod dinosaurs: a case study on South American abelisaurids.

Studies on pathological fossil bones have allowed improving the knowledge of physiology and ecology, and consequently the life history of extinct organisms. Among extinct vertebrates, non-avian dinosaurs have drawn attention in terms of pathological evidence, since a wide array of fossilized lesions and diseases were noticed in these ancient organisms. Here, we evaluate the pathological conditions observed in individuals of different brachyrostran (Theropoda, Abelisauridae) taxa, including Aucasaurus garridoi, Elemgasem nubilus, and Quilmesaurus curriei. For this, we use multiple methodological approaches such as histology and computed tomography, in addition to the macroscopic evaluation. The holotype of Aucasaurus shows several pathognomonic traits of a failure of the vertebral segmentation during development, causing the presence of two fused caudal vertebrae. The occurrence of this condition in Aucasaurus is the first case to be documented so far in non-tetanuran theropods. Regarding the holotype of Elemgasem, the histology of two fused vertebrae shows an intervertebral space between the centra, thus the fusion is limited to the distal rim of the articular surfaces. This pathology is here considered as spondyloarthropathy, the first evidence for a non-tetanuran theropod. The microstructural arrangement of the right tibia of Quilmesaurus shows a marked variation in a portion of the outer cortex, probably due to the presence of the radial fibrolamellar bone tissue. Although similar bone tissue is present in other extinct vertebrates and the cause of its formation is still debated, it could be a response to some kind of pathology. Among non-avian theropods, traumatic injuries are better represented than other maladies (e.g., infection, congenital or metabolic diseases, etc.). These pathologies are recovered mainly among large-sized theropods such as Abelisauridae, Allosauridae, Carcharodontosauridae, and Tyrannosauridae, and distributed principally among axial elements. Statistical tests on the distribution of injuries in these theropod clades show a strong association between taxa-pathologies, body regions-pathologies, and taxa-body regions, suggesting different life styles and behaviours may underlie the frequency of different injuries among theropod taxa.

Automatic sleep spindles identification and classification with multitapers and convolution.

Sleep spindles are isolated transient surges of oscillatory neural activity present during sleep stages 2 and 3 in the nonrapid eye movement (NREM). They can indicate the mechanisms of memory consolidation and plasticity in the brain. Spindles can be identified across cortical areas and classified as either slow or fast. There are spindle transients across different frequencies and power, yet most of their functions remain a mystery. Using several electroencephalogram (EEG) databases, this study presents a new method, called the "spindles across multiple channels" (SAMC) method, for identifying and categorizing sleep spindles in EEGs during the NREM sleep. The SAMC method uses a multitapers and convolution (MT&C) approach to extract the spectral estimation of different frequencies present in sleep EEGs and graphically identify spindles across multiple channels. The characteristics of spindles, such as duration, power, and event areas, are also extracted by the SAMC method. Comparison with other state-of-the-art spindle identification methods demonstrated the superiority of the proposed method with an agreement rate, average positive predictive value, and sensitivity of over 90% for spindle classification across the three databases used in this paper. The computing cost was found to be, on average, 0.004 seconds per epoch. The proposed method can potentially improve the understanding of the behavior of spindles across the scalp and accurately identify and categories sleep spindles.

Nonlinear Reduction in Hyperautofluorescent Ring Area in Retinitis Pigmentosa.

PURPOSE: To report baseline dimension of the autofluorescent (AF) ring in a large cohort of retinitis pigmentosa (RP) patients and to evaluate models of ring progression. DESIGN: Cohort study. PARTICIPANTS: Four hundred and forty-five eyes of 224 patients with clinical diagnosis of RP. METHODS: Autofluorescent rings from near-infrared AF (NIRAF) and short-wavelength AF (SWAF) imaging modalities in RP eyes were segmented with ring area and horizontal extent extracted from each image for cross-sectional and longitudinal analyses. In longitudinal analysis, for each eye, ring area, horizontal extent, and natural logarithm of the ring area were assessed as the best dependent variable for linear regression by evaluating R2 values. Linear mixed-effects modeling was utilized to account for intereye correlation. MAIN OUTCOME MEASURES: Autofluorescent ring size characteristics at baseline and ring progression rates. RESULTS: A total of 439 eyes had SWAF imaging at baseline with the AF ring observed in 206 (46.9%) eyes. Mean (95% confidence interval) of ring area and horizontal extent were 7.85 (6.60 to 9.11) mm2 and 3.35 (3.10 to 3.60) mm, respectively. In NIRAF, the mean ring area and horizontal extent were 7.74 (6.60 to 8.89) mm2 and 3.26 (3.02 to 3.50) mm, respectively in 251 out of 432 eyes. Longitudinal analysis showed mean progression rates of -0.57 mm2/year and -0.12 mm/year in SWAF using area and horizontal extent as the dependent variable, respectively. When ln(Area) was analyzed as the dependent variable, mean progression was -0.07 ln(mm2)/year, which equated to 6.80% decrease in ring area per year. Similar rates were found in NIRAF (area: -0.59 mm2/year, horizontal extent: -0.12 mm/year and ln(Area): -0.08 ln(mm2)/year, equated to 7.75% decrease in area per year). Analysis of R2 showed that the dependent variable ln(Area) provided the best linear model for ring progression in both imaging modalities, especially in eyes with large overall area change. CONCLUSIONS: Our data suggest that using an exponential model to estimate progression of the AF ring area in RP is more appropriate than the models assuming linear decrease. Hence, the progression estimates provided in this study should provide more accurate reference points in designing clinical trials in RP patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A meta-analysis of hairy vetch as a previous cover crop for maize.

Background: The use of hairy vetch (Vicia villosa Roth.) as cover crop is increasing worldwide. Hairy vetch can contribute as a nitrogen (N) source with potential to impact subsequent high N demanding cereals such as maize (Zea mays L.). Contrasting literature results emphasize the need for a global synthesis analysis to quantify changes in maize yield after hairy vetch. Objectives: A meta-analysis was conducted to i) quantify maize yield response to hairy vetch as previous crop, ii) explore hairy vetch influence on fertilized and non-N fertilized maize yields, and iii) assess the tillage and environment factors on maize yield response to hairy vetch. Methods: The global systematic search yielded 23 publications selected by the following criteria, i) hairy vetch dry matter at the end of the season, ii) maize grain yield, and iii) experimental design with (Mzhv) and without (Mzcontrol) hairy vetch treatments. Information such as N fertilization for maize, N accumulation in hairy vetch, organic matter, and tillage before maize sowing were recorded. Hairy vetch effects (effect size) were expressed as a ratio (percentage of grain yield variation in Mzhv/Mzcontrol). Results: Under non-N fertilization (n = 9), results revealed hairy vetch had mostly a positive effect, ranging from 13 to 45% (n = 6). In contrast, N-fertilized maize (n = 20) showed a high chance of neutral effects (n = 12), moderate probability of positive yield impact (7 to 38%, n = 6), and a low likelihood of negative effects (-32 and -17%, n = 2). Notably, maize yields improved by 21-25% when the N accumulation in hairy vetch ranged from 95 to 150 kg ha-1 and N rate from 0 to 120 kg ha-1. Non-N-fertilized maize exhibited a 14% increase in response in no-till systems and a 31% increase with conventional tillage. Conclusion: This study summarizes potential benefits of hairy vetch preceding maize. Yet, the heterogeneous outcomes deserve further exploration in terms of environment and management factors.

Immune Predictors of Response after Bacillus Calmette-Guérin Treatment in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) has been the standard of care for the treatment of high-risk, non-muscle-invasive bladder cancer (NMIBC) for decades, but 49.6% of high-risk and very-high-risk patients will experience progression to muscle-invasive disease in five years. Furthermore, cytology and cystoscopy entail a high burden for both patients and health care systems due to the need for very long periods of follow-up. Subsequent adjuvant treatment using intravesical immunotherapy with BCG has been shown to be effective in reducing tumor recurrence and progression, but it is not free of severe adverse effects that ultimately diminish patients' quality of life. Because not all patients benefit from BCG treatment, it is of paramount importance to be able to identify responders and non-responders to BCG as soon as possible in order to offer the best available treatment and prevent unnecessary adverse events. The tumor microenvironment (TME), local immune response, and systemic immune response (both adaptive and innate) seem to play an important role in defining responders, although the way they interact remains unclear. A shift towards a proinflammatory immune response in TME is thought to be related to BCG effectiveness. The aim of this review is to collect the most relevant data available regarding BCG's mechanism of action, its role in modulating innate and adaptive immune responses and the secretion of certain cytokines, and their potential use as immunological markers of response; the aim is also to identify promising lines of investigation.

Gentamicincoated tibial nail is an effective prevention method for fracture-related infections in open tibial fractures.

Fracture-related infection (FRI) is a common complication following open tibia fracture (OTF), especially in patients with high-energy trauma or comorbidities. The use of gentamicin-coated nail (GCN) has been proposed as a local adjuvant to prevent FRI in high-risk patients. HYPOTHESIS: The incidence of FRI is expected to be lower in OTF treated with a GCN, alongside with no detrimental effects on fracture healing time. OBJECTIVES: This study aimed to evaluate the effectiveness of GCNs as a definitive fixation method and prophylaxis for FRI in OTFs. Secondary outcomes included non-union rates and time to healing. METHODS: The study design was a mixed cohort, including a prospective group of patients treated with GCN (Expert Tibial Nail PROtect™, Depuy Synthes, Johnson&Johnson Company Inc, New Jersey, USA) and a retrospectively evaluated group treated with non-gentamicin-coated nail (NGCN). Patients with at least 12 months of follow-up were included. The treatment protocol consisted of timely administration of antibiotics, surgical debridement, and early soft-tissue coverage. Exclusion criteria included protocol infringement, traumatic amputation, and loss of follow-up. Statistical analysis was performed using Stata v14.0, with a significance level of p < 0.05. RESULTS: The study included 243 patients, 104 in GCN group and 139 NGCN group. External Fixator use was higher in the NGCN group, but this did not significantly affect the FRI rate. GCN use was associated with a significantly lower incidence of FRI (2.88% GCN group vs. 15.83% NGCN group, OR 0.16, p < 0.01). Furthermore, GCN use was found to be a protective factor against tibial non-union (OR 0.41, p = 0.03). There were no adverse effects attributed to locally administered gentamycin. The NGCN cohort had a higher incidence of polytrauma, although the difference was not statistically significant. A longer time to heal as well as more FRI and Non-union according to the progression in Gustilo-Anderson classification was observed in the GCN group. CONCLUSION: Our findings suggest that GCN is an effective prophylactic method to reduce the risk of FRI in open tibial fractures at 12-month follow-up, as well as, probably derived from this protective effect, leading to lower fracture consolidation times when compared with cases treated without GCN.

Natural Killer T Cell Diversity and Immunotherapy.

Invariant natural killer T cells (iNKTs), a type of unconventional T cells, share features with NK cells and have an invariant T cell receptor (TCR), which recognizes lipid antigens loaded on CD1d molecules, a major histocompatibility complex class I (MHC-I)-like protein. This interaction produces the secretion of a wide array of cytokines by these cells, including interferon gamma (IFN-γ) and interleukin 4 (IL-4), allowing iNKTs to link innate with adaptive responses. Interestingly, molecules that bind CD1d have been identified that enable the modulation of these cells, highlighting their potential pro-inflammatory and immunosuppressive capacities, as required in different clinical settings. In this review, we summarize key features of iNKTs and current understandings of modulatory α-galactosylceramide (α-GalCer) variants, a model iNKT cell activator that can shift the outcome of adaptive immune responses. Furthermore, we discuss advances in the development of strategies that modulate these cells to target pathologies that are considerable healthcare burdens. Finally, we recapitulate findings supporting a role for iNKTs in infectious diseases and tumor immunotherapy.

Macaronesian Plants as Promising Biopesticides against the Crop Pest Ceratitis capitata.

Ceratitis capitata is responsible for significant economic losses in the fruit production industry, and the market lacks biopesticides that are effective but also cheaper and less contaminating, with fewer negative impacts on the environment. In this regard, the present study suggests as potential options ethanolic extracts from several Macaronesian plants, which inhibit the oviposition and are toxic to C. capitata, and whose preparation involve a non-toxic solvent (i.e., ethanol), low energy expenditure and cheap apparatus (i.e., maceration at room temperature). Among the evaluated species, the extracts of Hedychium gardnerianum, Cistus symphytifolius and Salvia canariensis are the most active (50 mg/mL), revealing an increase in C. capitata adults' mortality from 21.15% to 27.41% after 72 h, a value statistically identical to azadirachtin (25.93%) at the recommended concentration (0.88 mg/mL). Considering the quantity and biomass available to prepare a biopesticide in the future, and the level of activity, the ethanolic extract of H. gardnerianum was fractionated and each fraction tested. The water fraction at 50 mg/mL proved to be more effective than the original extract, both in terms of mortality (57.69%), with LT50 = 72.5 h, and oviposition deterrence (83.43%), values statistically higher than those obtained by azadirachtin at 0.88 mg/mL. Analysis of this fraction by HPLC-MS/MS showed that it is mainly composed of glycosylated derivatives of quercetin and myricetin in addition to some triterpenes. These findings highlight some Macaronesian species, and in particular, the more polar fraction of H. gardnerianum ethanolic extract, as promising and ecological alternatives to conventional insecticides, for use in the integrated management of the C. capitata pest.

Inhibitory Activity of 4-Benzylidene Oxazolones Derivatives of Cinnamic Acid on Human Acetylcholinesterase and Cognitive Improvements in a Mouse Model.

We synthesized seven (Z)-benzylidene-2-(E)-styryloxazol-5(4H)-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 µM, showed an affinity (Ki) from 2 to 198 µM, and an IC50 from 9 to 246 µM. Molecular docking studies revealed that all binding moieties are involved in the non-covalent interactions with hAChE for all compounds. In addition, in silico pharmacokinetic analysis was carried out to predict the compounds' blood-brain barrier (BBB) permeability. The most potent inhibitor of hAChE significantly improved cognitive impairment in a modified Y-maze test (5 µmol/kg) and an Object Recognition Test (10 µmol/kg). Our results can help the rational design of hAChE inhibitors to work as potential candidates for treating cognitive disorders.