In Silico Molecular Modeling of Four New Afatinib Derived Molecules Targeting the Inhibition of the Mutated Form of BCR-ABL T315I.

Four afatinib derivatives were designed and modeled. These derivatives were compared to the known tyrosine-kinase inhibitors in treating Chronic Myeloid Leukemia, i.e., imatinib and ponatinib. The molecules were evaluated through computational methods, including docking studies, the non-covalent interaction index, Electron Localization and Fukui Functions, in silico ADMET analysis, QTAIM, and Heat Map analysis. The AFA(IV) candidate significantly increases the score value compared to afatinib. Furthermore, AFA(IV) was shown to be relatively similar to the ponatinib profile when evaluating a range of molecular descriptors. The addition of a methylpiperazine ring seems to be well distributed in the structure of afatinib when targeting the BCR-ABL enzyme, providing an important hydrogen bond interaction with the Asp381 residue of the DFG-switch of BCR-ABL active site residue and the AFA(IV) new chemical entities. Finally, in silico toxicity predictions show a favorable index, with some molecules presenting the loss of the irritant properties associated with afatinib in theoretical predictions.

Genetic architecture of congenital hypogonadotropic hypogonadism: insights from analysis of a Portuguese cohort.

STUDY QUESTION: What is the contribution of genetic defects in Portuguese patients with congenital hypogonadotropic hypogonadism (CHH)? SUMMARY ANSWER: Approximately one-third of patients with CHH were found to have a genetic cause for their disorder, with causal pathogenic and likely pathogenic germline variants distributed among 10 different genes; cases of oligogenic inheritance were also included. WHAT IS KNOWN ALREADY: CHH is a rare and genetically heterogeneous disorder characterized by deficient production, secretion, or action of GnRH, LH, and FSH, resulting in delayed or absent puberty, and infertility. STUDY DESIGN SIZE DURATION: Genetic screening was performed on a cohort of 81 Portuguese patients with CHH (36 with Kallmann syndrome and 45 with normosmic hypogonadotropic hypogonadism) and 263 unaffected controls. PARTICIPANTS/MATERIALS SETTING METHODS: The genetic analysis was performed by whole-exome sequencing followed by the analysis of a virtual panel of 169 CHH-associated genes. The main outcome measures were non-synonymous rare sequence variants (population allele frequency <0.01) classified as pathogenic, likely pathogenic, and variants of uncertain significance (VUS). MAIN RESULTS AND THE ROLE OF CHANCE: A genetic cause was identified in 29.6% of patients. Causal pathogenic and likely pathogenic variants were distributed among 10 of the analysed genes. The most frequently implicated genes were GNRHR, FGFR1, ANOS1, and CHD7. Oligogenicity for pathogenic and likely pathogenic variants was observed in 6.2% of patients. VUS and oligogenicity for VUS variants were observed in 85.2% and 54.3% of patients, respectively, but were not significantly different from that observed in controls. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: The identification of a large number of VUS presents challenges in interpretation and these may require reclassification as more evidence becomes available. Non-coding and copy number variants were not studied. Functional studies of the variants were not undertaken. WIDER IMPLICATIONS OF THE FINDINGS: This study highlights the genetic heterogeneity of CHH and identified several novel variants that expand the mutational spectrum of the disorder. A significant proportion of patients remained without a genetic diagnosis, suggesting the involvement of additional genetic, epigenetic, or environmental factors. The high frequency of VUS underscores the importance of cautious variant interpretation. These findings contribute to the understanding of the genetic architecture of CHH and emphasize the need for further studies to elucidate the underlying mechanisms and identify additional causes of CHH. STUDY FUNDING/COMPETING INTERESTS: This research was funded by the Portuguese Foundation for Science and Technology (grant numbers PTDC/SAU-GMG/098419/2008, UIDB/00709/2020, CEECINST/00016/2021/CP2828/CT0002, and 2020.04924.BD) and by Sidra Medicine-a member of the Qatar Foundation (grant number SDR400038). The authors declare no competing interests.

Theoretical Study of CH4 and CO2 Separation by IRMOFs.

Porous materials such as isoreticular metal-organic frameworks (IRMOFs) can be applied in several areas that explore the physical adsorption. An area that has gained prominence is fuel gas storage, as it provides the storage of a large amount of gas at low pressure and the purification of combustible gas due to the selectivity of the different chemical environments of its pores. IRMOFs represent an ideal study group due to their wide range of pore sizes resulting from the use of different organic ligands. In this context, exploring IRMOFs that adsorb more efficiently stands out, mainly for optimizing the ligand, pressure, and temperature. This work focused on the adsorption and separation of CH4 and CO2 using various IRMOFs. The results suggest that IRMOF-6 is the most suitable for separation and purification and that enhanced purification occurs when the temperature is reduced and the system pressure is increased. This better performance is associated with the higher adsorption energies for this MOF, with CO2 being higher than CH4, which tends to become even more evident when the system pressure increases.

Mapping functional traces of opioid memories in the rat brain.

Addiction to psychoactive substances is a maladaptive learned behaviour. Contexts surrounding drug use integrate this aberrant mnemonic process and hold strong relapse-triggering ability. Here, we asked where context and salience might be concurrently represented in the brain during retrieval of drug-context paired associations. For this, we developed a morphine-conditioned place preference protocol that allows contextual stimuli presentation inside a magnetic resonance imaging scanner and investigated differences in activity and connectivity at context recall. We found context-specific responses to stimulus onset in multiple brain regions, namely, limbic, sensory and striatal. Differences in functional interconnectivity were found among amygdala, lateral habenula, and lateral septum. We also investigated alterations to resting-state functional connectivity and found increased centrality of the lateral septum in a proposed limbic network, as well as increased functional connectivity of the lateral habenula and hippocampal 'cornu ammonis' 1 region, after a protocol of associative drug-context. Finally, we found that pre- conditioned place preference resting-state connectivity of the lateral habenula and amygdala was predictive of inter-individual conditioned place preference score differences. Overall, our findings show that drug and saline-paired contexts establish distinct memory traces in overlapping functional brain microcircuits and that intrinsic connectivity of the habenula, septum, and amygdala likely underlies the individual maladaptive contextual learning to opioid exposure. We have identified functional maps of acquisition and retrieval of drug-related memory that may support the relapse-triggering ability of opioid-associated sensory and contextual cues. These findings may clarify the inter-individual sensitivity and vulnerability seen in addiction to opioids found in humans.

Branched-Chain Amino Acids, Alanine, and Thyroid Function: A Cross-Sectional, Nuclear Magnetic Resonance (NMR)-Based Approach from ELSA-Brasil.

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs-leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson's coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism.

Development of a Global Physical Literacy (GloPL) Action Framework: Study protocol for a consensus process.

BACKGROUND: The holistic concept of physical literacy (PL) has gained growing attention in recent research, policy, and practice. Many important policy documents of the physical activity and educational fields (e.g., Global Action Plan on Physical Activity 2018-2030 by the World Health Organization, UNESCO's Quality Physical Education guidelines for policymakers) have specified PL. However, a clear framework for action is needed, as most initiatives across the world are fragmented, lack a prospective orientation, can benefit from conceptual clarification, and are not linked to effective translation into practice. Therefore, we aim to consensually develop a Global Physical Literacy (GloPL) Action Framework to define goals and principles (asking what is needed) as well as actions and ways (asking how these can be achieved) to move PL forward. MATERIALS AND METHODS: We apply a three-stage group Delphi technique involving three representation groups: (a) geographical representatives to achieve global coverage of perspectives; (b) representatives of special thematic interest reflecting prominent gaps of current PL activities; and (c) representatives of societies from the broad field of physical activity and health to facilitate dissemination. The process will begin with an individual pre-Delphi exercise, in which experts generate initial ideas for the framework, followed by a four-eye document analysis to derive themes for the discussion. Subsequently, the experts will meet face-to-face in three online rounds to discuss and prioritize the themes. Interspersed formal voting with pre-defined agreement thresholds (via descriptive statistics) will inform the inclusion of themes within the final framework. CONCLUSIONS: A global consensus on goals, principles, actions, and ways for the development of PL has the potential to provide a largely accepted roadmap for future activities in research, policy, and practice. The co-production approach will help disseminate the GloPL Action Framework and benefit work in relevant application fields of physical activity and health worldwide.

When Implementing the Presynch-11/Ovsynch Reproductive Management Program, the Fertility of Lactating Dairy Cows Improved When They Received Timed Artificial Insemination Compared with the Inclusion of Estrus Detection.

Artificial insemination 12 h following observed standing estrus is a standard estimate of the fertility levels of cattle. The main objective of this study was to determine if controlling ovarian development with a fertility program could alter the fertility of lactating dairy cows. Lactating dairy cows (n = 1356) 60-66 days in milk (DIM) were randomly assigned to receive timed AI following Presynch-11/Ovsynch (Presynch-11) or a combination of estrus detection and timed AI using the Presynch-11/Ovsynch program (Estrus + TAI). Cows in standing estrus, following the first two cloprostenol sodium (CLO) injections, in the Estrus + TAI group were artificially inseminated using the AM/PM rule. Cows in this group that were not observed in standing estrus received Ovsynch and TAI beginning 11 d after the second CLO injection. Cows in the Presynch-11 group received two injections of 500 µg CLO 14 d apart but were not observed for estrus. The first GnRH (100 µg) of Ovsynch was administered 11 d following the second CLO injection. All cows in the Presynch-11-Ovsynch group received TAI following Ovsynch. Cows in this treatment were then assigned randomly to receive either CLO or dinoprost 7 d following the first GnRH of Ovsynch. The final GnRH of Ovsynch was administered 56 h later and TAI 16 h after the final GnRH. Pregnancies/AI (P/AI) were greater (p < 0.001) for the Presynch-11 group compared with the Estrus + TAI group (45 vs. 31%). Primiparous cows had greater fertility following observed standing estrus compared with multiparous cows. Days in milk at the first AI were greater (p < 0.01) in the Presynch-11 group vs. the Estrus + TAI group (98 vs. 80) but less variable (p < 0.01). The range of DIM at the first AI was 95 to 101 in the Presynch-11 group and 60 to 101 in the Estrus + TAI group. Within the Presynch-11 group, there were no differences in the rate of luteolysis or P/AI for the prostaglandin type at the final PGF2α of Ovsynch. Multiparous cows treated with Presynch-11 had >60% chance of pregnancy compared with multiparous cows receiving AI following standing estrus. In summary, lactating dairy cows receiving timed AI following the Presynch-11/Ovsynch program had improved fertility compared with a group of cows that received AI following standing estrus or, if not observed in estrus, timed AI. This comparison indicated that controlling ovarian development with GnRH and PGF2α positively impacted the fertility of lactating dairy cows.

Focal alveolar hemorrhage following guide-wire progression into the pulmonary arterial circulation during fibrin sheath angioplasty and catheter exchange: Case report.

Central venous catheters are a frequently used vascular access for hemodialysis. Fibrin sheath formation is a common complication and is associated with catheter malfunction. Although fibrin sheath angioplasty with catheter exchange is a frequently employed procedure, it can be associated with mechanical complications. An important technical step in this procedure is progression of the guide-wire into the inferior vena cava. Focal alveolar hemorrhage is a very rare complication of this procedure. We report a case of a 70-year old patient on dual antiplatelet therapy who underwent fibrin sheath angioplasty with guide-wire catheter exchange and experienced focal alveolar hemorrhage presenting as hemoptysis and acute type 1 respiratory failure. Progression of the guide-wire into the pulmonary circulation and antithrombotic therapy played a significant role in the development of this complication. This report aims to call attention to a poorly described and potentially serious yet avoidable complication of fibrin sheath angioplasty with guide-wire catheter exchange.

Increased susceptibility to kainate-induced seizures in a mouse model of tuberous sclerosis complex: Importance of sex and circadian cycle.

OBJECTIVE: Comorbidity of epilepsy and autism in tuberous sclerosis complex 2 (TSC2) is very frequent, but the link between these conditions is still poorly understood. To study neurological problems related to autism, the scientific community has been using an animal model of TSC2, Tsc2+/- mice. However, it is still unknown whether this model has the propensity to exhibit increased seizure susceptibility. Further, the importance of sex and/or the circadian cycle in this biological process has never been addressed. This research aimed to determine whether male and female Tsc2+/- mice have altered seizure susceptibility at light and dark phases. METHODS: We assessed seizure susceptibility and progression in a Tsc2+/- mouse model using the chemical convulsant kainic acid (KA), a potent agonist of the AMPA/kainate class of glutamate receptors. Both male and female animals at adult age were evaluated during non-active and active periods. Seizure severity was determined by integrating individual scores per mouse according to a modified Racine scale. Locomotor behavior was monitored during control and after KA administration. RESULTS: We found increased seizure susceptibility in Tsc2+/- mice with a significant influence of sex and circadian cycle on seizure onset, progression, and behavioral outcomes. While, compared to controls, Tsc2+/- males overall exhibited higher susceptibility independently of circadian cycle, Tsc2+/- females were more susceptible during the dark and post-ovulatory phase. Interestingly, sexual dimorphisms related to KA susceptibility were always reported during light phase independently of the genetic background, with females being the most vulnerable. SIGNIFICANCE: The enhanced susceptibility in the Tsc2 mouse model suggests that other neurological alterations, beside brain lesions, may be involved in seizure occurrence for TSC. Importantly, our work highlighted the importance of considering biological sex and circadian cycle for further studies of TSC-related epilepsy research. PLAIN LANGUAGE SUMMARY: Tuberous sclerosis complex (TSC) is a rare genetic disorder. It causes brain lesions and is linked to epilepsy, intellectual disability, and autism. We wanted to investigate epilepsy in this model. We found that these mice have more induced seizures than control animals. Our results show that these mice can be used in future epilepsy research for this disorder. We also found that sex and time of day can influence the results. This must be considered in this type of research.

Effectiveness of two scrub methods with different chlorhexidine combinations for surgical field antisepsis in cats.

Objective: Assessing effectiveness of circular (CM) and linear (LM) scrub methods using 3 different combinations of chlorhexidine in surgical field antisepsis in cats. Animals and procedure: Surgical field antisepsis was applied with 2 scrub methods (CM and LM) and 3 different chlorhexidine combinations (A1, A2, and A3) in 51 female cats undergoing ovariectomy. Sterile swabs collected from the surgical field pre- and post-antisepsis were inoculated in the laboratory and colony-forming units (CFU/mL) were quantified. Results: Following the application of antisepsis, the number of positive samples decreased in all groups (P < 0.05) when using both CM and LM, except for CM in the A1 group (P = 0.063). The CFU/mL counts also decreased after antisepsis with both CM and LM in all groups (P < 0.05). A high reduction in CFU/mL counts was observed after antisepsis with both CM and LM in all groups, but no significant differences were observed between the 2 scrub methods (P > 0.05). Conclusion and clinical relevance: Surgical field antisepsis in cats with CM and LM scrub methods, using 2% chlorhexidine combined with 70% ethyl or 70% isopropyl alcohol, or 1% chlorhexidine combined with 70% ethyl alcohol, can effectively reduce the bacterial load on the skin.

Efficacité de deux méthodes de désinfection avec différentes combinaisons de chlorhexidine pour l'antisepsie du champ opératoire chez le chat. Objectif: Évaluation de l'efficacité des méthodes de désinfection par mouvements circulaires (CM) et linéaires (LM) utilisant 3 combinaisons différentes de chlorhexidine dans l'antisepsie du champ opératoire chez le chat. Animaux et procédure: Une antisepsie chirurgicale sur le terrain a été appliquée avec 2 méthodes de désinfection (CM et LM) et 3 combinaisons différentes de chlorhexidine (A1, A2 et A3) chez 51 chattes subissant une ovariectomie. Des écouvillons stériles prélevés sur le champ opératoire avant et après l'antisepsie ont été inoculés en laboratoire et les unités formant des colonies (UFC/mL) ont été quantifiées. Résultats: À la suite de l'application de l'antisepsie, le nombre d'échantillons positifs a diminué dans tous les groupes (P < 0,05) lors de l'utilisation à la fois de CM et de LM, à l'exception du CM dans le groupe A1 (P = 0,063). Le nombre d'UFC/mL a également diminué après antisepsie avec CM et LM dans tous les groupes (P < 0,05). Une forte réduction du nombre d'UFC/mL a été observée après antisepsie avec CM et LM dans tous les groupes, mais aucune différence significative n'a été observée entre les 2 méthodes de désinfection (P > 0,05). Conclusion et pertinence clinique: L'antisepsie chirurgicale sur le terrain chez les chats avec les méthodes de désinfection CM et LM, utilisant 2 % de chlorhexidine combinée à 70 % d'alcool éthylique ou 70 % d'alcool isopropylique, ou 1 % de chlorhexidine combinée à 70 % d'alcool éthylique, peut réduire efficacement la charge bactérienne sur la peau.(Traduit par Dr Serge Messier).

Clinical Difficulties Related to Direct Composite Restorations: A Multinational Survey.

AIMS: Composite materials are widely used in dentistry for direct tooth restorations. However, they are highly sensitive to the working technique employed during the restorative procedure. Even minor procedural errors can have a significant impact on the quality including the longevity of the restoration. Hence the aim of this study was to determine the material preferences and analyse the clinical problems associated with direct composite restorations in a cohort of dentists. METHODS: A 20-item online questionnaire was created in English and administered 1830 general dentists and specialists in 13 countries. The first section of the questionnaire included four questions to elicit demographic data, and the second section comprised 16 questions focused on material preferences for conservative restorations, durability of composite restorations, and the most challenging stages the dentists faced during the composite restorative procedures. RESULTS: Respondents decided most often to use composite materials for the tooth restorations (OR 997.4, 95% CI 233.8-4254.8, P value <.001). Most respondents indicated that the durability of composite restorations was approximately 7 to 10 years (41.5%). Among the factors affecting durability, maintenance of a dry cavity was the most often reported reason (47.1%) and the foremost challenge faced by dentists (61.0%) during the composite restorative procedures. CONCLUSIONS: Our study confirmed that resin-based composites are the most popular material for direct restoration in many countries. Although working with this material is difficult and involves multiple steps, maintaining a dry cavity during bonding, and material application may affect the therapeutic success and durability of these restorations. Clinicians need to be attentive to this issue and be prepared to adapt their decision-making and consider opting for alternative restorative materials, if appropriate.

The Erasmus+ EUMOVE project-a school-based promotion of healthy lifestyles to prevent obesity in European children and adolescents.

The aim of this study was to describe the goals, activities, and methods of EUMOVE project in developing a set of resources targeting both primary and secondary schools that allow the entire educational community to promote healthy lifestyles (HL). The EUMOVE project is an Erasmus+ program based in the Creating Active Schools (CAS) framework. The project lasted 3 years and was developed by 14 academic and non-governmental institutions from Spain, Portugal, France, Italy, and the UK. EUMOVE was divided into three phases. In the first phase, several work packages were carried out aimed to ensure the coordination/management of the project activities. In the second phase, seven educational resources strengthened by rigorous scientific research were developed to promote HL from schools. During the last phase, all the resources were disseminated through scientific seminars, workshops with families and teachers, and the online promotion by the non-governmental institutions of each country. The EUMOVE project developed and promoted a smartphone APP, video/activity repository of physically active lessons, active break virtual platform, learning units, and parent/teachers/school-leaders' guidelines to promote physical activity, active commuting, active school playgrounds, healthy diet, and sleep habits. To our knowledge, EUMOVE is the first European project to provide a set of practical tools based on scientific evidence to help schools or future school-wide interventions implement a paradigm shift based on the CAS framework for the promotion of HL. Future research will need to investigate the implementation, effectiveness, and scalability of this proposal.

Integrating sEMG and IMU Sensors in an e-Textile Smart Vest for Forward Posture Monitoring: First Steps.

Currently, the market for wearable devices is expanding, with a growing trend towards the use of these devices for continuous-monitoring applications. Among these, real-time posture monitoring and assessment stands out as a crucial application given the rising prevalence of conditions like forward head posture (FHP). This paper proposes a wearable device that combines the acquisition of electromyographic signals from the cervical region with inertial data from inertial measurement units (IMUs) to assess the occurrence of FHP. To improve electronics integration and wearability, e-textiles are explored for the development of surface electrodes and conductive tracks that connect the different electronic modules. Tensile strength and abrasion tests of 22 samples consisting of textile electrodes and conductive tracks produced with three fiber types (two from Shieldex and one from Imbut) were conducted. Imbut's Elitex fiber outperformed Shieldex's fibers in both tests. The developed surface electromyography (sEMG) acquisition hardware and textile electrodes were also tested and benchmarked against an electromyography (EMG) gold standard in dynamic and isometric conditions, with results showing slightly better root mean square error (RMSE) values (for 4 × 2 textile electrodes (10.02%) in comparison to commercial Ag/AgCl electrodes (11.11%). The posture monitoring module was also validated in terms of joint angle estimation and presented an overall error of 4.77° for a controlled angular velocity of 40°/s as benchmarked against a UR10 robotic arm.

Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

BACKGROUND: Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. METHODS: We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. RESULTS: A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). CONCLUSION: Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Structural Design, Anticancer Evaluation, and Molecular Docking of Newly Synthesized Ni(II) Complexes with ONS-Donor Dithiocarbazate Ligands.

The current article reports the investigation of three new Ni(II) complexes with ONS-donor dithiocarbazate ligands: [Ni(L1)PPh3] (1), [Ni(L2)PPh3] (2), and [Ni(L2)Py] (3). Single-crystal X-ray analyses revealed mononuclear complexes with a distorted square planar geometry and the metal centers coordinated with a doubly deprotonated dithiocarbazate ligand and coligand pyridine or triphenylphosphine. The non-covalent interactions were investigated by the Hirshfeld surface and the results revealed that the strongest interactions were π⋅⋅⋅π stacking interactions and non-classical hydrogen bonds C-H···H and C-H···N. Physicochemical and spectroscopic methods indicate the same structures in the solid state and solution. The toxicity effects of the free ligands and Ni(II) complexes were tested on the human breast cancer cell line MCF-7 and non-malignant breast epithelial cell line MCF-10A. The half-maximal inhibitory concentration (IC50) values, indicating that the compounds were potent in inhibiting cell growth, were obtained for both cell lines at three distinct time points. While inhibitory effects were evident in both malignant and non-malignant cells, all three complexes demonstrated lower IC50 values for malignant breast cell lines than their non-malignant counterparts, suggesting a stronger impact on cancerous cell lines. Furthermore, molecular docking studies were performed showing the complex (2) as a promising candidate for further therapeutic exploration.

Rhizosphere-xylem sap connections in the olive tree microbiome: implications for biostimulation approaches.

AIMS: Climate change is endangering olive groves. Farmers are adapting by exploring new varieties of olive trees and examining the role of microbiomes in plant health.The main objectives of this work were to determine the primary factors that influence the microbiome of olive trees and to analyze the connection between the rhizosphere and endosphere compartments. METHODS AND RESULTS: The rhizosphere and xylem sap microbiomes of two olive tree varieties were characterized by next-generation 16S rRNA amplicon sequencing, and soil descriptors were analyzed. Bacterial communities in the rhizosphere of olive trees were more diverse than those found in the xylem sap. Pseudomonadota, Actinobacteriota, Acidobacteriota, and Bacillota were the dominant phyla in both compartments. At the genus level, only very few taxa were shared between soil and sap bacterial communities. CONCLUSIONS: The composition of the bacteriome was more affected by the plant compartment than by the olive cultivar or soil properties, and a direct route from the rhizosphere to the endosphere could not be confirmed. The large number of plant growth-promoting bacteria found in both compartments provides promising prospects for improving agricultural outcomes through microbiome engineering.

Can a Sacrococcygeal Epidural of 0.25% Bupivacaine Prevent the Activation of the Sympathetic Nervous System during Feline Ovariectomy?

The ovariectomy (OVE) procedure can trigger somatosensory and visceral peritoneal nociception. Sacrococcygeal epidural (ScE) anesthesia may complement or replace systemic analgesia used for feline OVE, reducing opioid consumption and their related undesirable adverse effects and consequently reducing or completely blocking the sympathetic nervous system activation during this procedure. The present study aimed to evaluate the activation of the sympathetic nervous system resulting from adding an ScE injection of bupivacaine 0.25% (0.3 mL kg-1) in feline OVE and identify whether this translates to hemodynamic variables stability. A Parasympathetic Tone Activity (PTA) monitor was applied given that it performs analysis of heart rate variability (HRV) detecting changes in sympathetic and parasympathetic tone, making it a good tool for detecting activation of the sympathetic nervous system during the study. Two groups of animals were evaluated in five perioperative times, namely, the control group (CG) (n = 18) with systemic analgesia alone and the sacrococcygeal epidural group (ScEG) (n = 20) with 0.25% bupivacaine combined with systemic analgesia. Thirty-eight female cats were selected. All animals assigned to CG and ScEG were premedicated with dexmedetomidine (20 µg kg-1 IM) and methadone (0.2 mg kg-1 IM). General anesthesia was induced with propofol IV ad effectum and maintained with isoflurane in 100% oxygen. Heart rate, non-invasive systolic and median blood pressure, respiratory rate, and instantaneous parasympathetic tone activity were recorded. Compared to systemic analgesia alone (CG), sacrococcygeal epidural (ScEG) reduced the rise of common hemodynamic variables but did not prevent sympathetic nervous system activation.

Wood inspired biobased nanocomposite films composed of xylans, lignosulfonates and cellulose nanofibers for active food packaging.

The growing concerns on environmental pollution and sustainability have raised the interest on the development of functional biobased materials for different applications, including food packaging, as an alternative to the fossil resources-based counterparts, currently available in the market. In this work, functional wood inspired biopolymeric nanocomposite films were prepared by solvent casting of suspensions containing commercial beechwood xylans, cellulose nanofibers (CNF) and lignosulfonates (magnesium or sodium), in a proportion of 2:5:3 wt%, respectively. All films presented good homogeneity, translucency, and thermal stability up to 153 °C. The incorporation of CNF into the xylan/lignosulfonates matrix provided good mechanical properties to the films (Young's modulus between 1.08 and 3.79 GPa and tensile strength between 12.75 and 14.02 MPa). The presence of lignosulfonates imparted the films with antioxidant capacity (DPPH radical scavenging activity from 71.6 to 82.4 %) and UV barrier properties (transmittance ≤19.1 % (200-400 nm)). Moreover, the films obtained are able to successfully delay the browning of packaged fruit stored over 7 days at 4 °C. Overall, the obtained results show the potential of using low-cost and eco-friendly resources for the development of sustainable active food packaging materials.

Corrigendum: Normative mice retinal thickness: 16-month longitudinal characterization of wild-type mice and changes in a model of Alzheimer's disease.

[This corrects the article DOI: 10.3389/fnagi.2023.1161847.].