Long-lasting Changes Research Articles

Germination improvement of fenugreek seeds with cold plasma: Exploring long-lasting effects of surface modification

Pre-sowing cold plasma (CP) treatment of seeds is a proven method for enhancing seed germination and plant growth. This paper presents a study on the long-lasting effects of CP treatment on fenugreek (Trigonella foenum-graecum) seeds to elucidate the basic mechanism of plasma action and pave the way for future field experiments. The seeds were subjected to short-duration treatments (10 and 20 s) using the kINPen 11 plasma jet and then stored for 3 months before sowing. After this period, the treated seeds exhibited higher germination efficiency, and the resulting seedlings were longer and more vigorous compared to normal seedlings. The improvement in germination was particularly noticeable for a treatment time of 20 s. Although we observed the age-related hydrophobic recovery, the plasma-treated seeds consistently showed better wettability than the control group. However, no direct correlation was found between wettability and germination improvement. Scanning electron microscopy (SEM) analysis revealed increased surface roughness and microstructuring of the outer layers of the seed coat after plasma treatment, while X-ray photoelectron spectroscopy (XPS) indicated an increase in the O/C ratio, as well as the presence of calcium and potassium. These findings suggest that the argon plasma etched the uppermost layer of the seed coat, leading to structural changes. It is suspected that the observed faster germination and growth of plasma-treated seeds is seeds due to these long-lasting changes in the seed coat structure, which may disrupt its tissues and open access to the interior of the seed. Under appropriate conditions, this facilitates an increase in the metabolic activity of the embryo. Such a mechanism can be considered as plasma scarification of the seed. This study highlights the potential of cold plasma technology as a viable and simple strategy for improving seed germination and plant growth in the long term, with important implications for the agricultural sector.

Machine Learning Technology for EEG-Forecast of the Blood-Brain Barrier Leakage and the Activation of the Brain's Drainage System during Isoflurane Anesthesia.

Anesthesia enables the painless performance of complex surgical procedures. However, the effects of anesthesia on the brain may not be limited only by its duration. Also, anesthetic agents may cause long-lasting changes in the brain. There is growing evidence that anesthesia can disrupt the integrity of the blood-brain barrier (BBB), leading to neuroinflammation and neurotoxicity. However, there are no widely used methods for real-time BBB monitoring during surgery. The development of technologies for an express diagnosis of the opening of the BBB (OBBB) is a challenge for reducing post-surgical/anesthesia consequences. In this study on male rats, we demonstrate a successful application of machine learning technology, such as artificial neural networks (ANNs), to recognize the OBBB induced by isoflurane, which is widely used in surgery. The ANNs were trained on our previously presented data obtained on the sound-induced OBBB with an 85% testing accuracy. Using an optical and nonlinear analysis of the OBBB, we found that 1% isoflurane does not induce any changes in the BBB, while 4% isoflurane caused significant BBB leakage in all tested rats. Both 1% and 4% isoflurane stimulate the brain's drainage system (BDS) in a dose-related manner. We show that ANNs can recognize the OBBB induced by 4% isoflurane in 57% of rats and BDS activation induced by 1% isoflurane in 81% of rats. These results open new perspectives for the development of clinically significant bedside technologies for EEG-monitoring of OBBB and BDS.

PSV-8 Early Life Adversity Impacts Intestinal Epithelial Development and Stem Cells Activities in Pigs

Abstract Early life adversity significantly impacts organ development and predisposes animals towards greater risk of diseases later in life. In the previous research in pigs, long lasting intestinal barrier dysfunctions have been found to be associated with early weaning stress. However, the underlying mechanism is not fully elucidated. Intestinal epithelial functions are associated with the number and maturation of multicellular components, including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells (EEC). Intestinal epithelial stem cells (IESC) give rise to the whole epithelium within 5 to 7 days. Such rapid turnover rate allows intestinal adaptation to stress conditions. We hypothesized that the early life stress impacted stem cells activities which would contribute to the long-lasting post-stress functional changes in intestinal epithelium. The objective of the present study is to evaluate the epithelium component cells and IESC proliferation and differentiation activities in an early weaning stress model in pigs. Piglets (n = 18) were obtained from commercial litters and were pair-weaned at the age of d 15 (early weaning, EW) and d 26 (late weaning, LW). Piglets were co-housed and raised under the same conditions. At the age of d 35, ileal tissues were isolated and fixed for morphological measurements. Intestinal crypts were isolated and cultured in the Matrigel matrix to form enteroids. The proliferation activities of IESCs were measured by enteroids morphology; differentiation capacity was measured by quantification of epithelial cell markers with and without chemicals-induced enteroids differentiation. Gene expressions and (or) staining of specific markers for IESCs (Olfm4, BMI1), enterocytes (ALP1), goblet cells (Muc2), Paneth cells (LYZ), and EECs (ChgA) in ileal tissue and ileal enteroids were also quantified. Data were analyzed by the student’s t-test. Our results showed that EW significantly (P < 0.05) reduced ileal villus width and crypt fission rate, while no changes were found on villus height and crypt depth compared with LW control. The alterations of ileal epithelium components in EW pigs were indicated by significantly fewer number of EECs, greater number of the goblet cells, and reduced ALP1 marker expression. The enteroids formation and budding rates were both significantly suppressed in EW pigs, which indicated a reduced IESC proliferating activity. In the fully developed enteroids, gene expressions of LYZ, ALP1, BMI1, Olfm4, and Hes1 were least in EW, but Muc2 expression was greater compared with control. In the differentiation culture media, the enteroids from EW pigs exhibited significantly enhanced potential for goblet cell differentiation but reduced capacity for enterocyte differentiation compared with LW pigs. Overall, the results indicate that early weaning stress affects the programming and activity of IESCs, which leads to an altered epithelium cell population and intestinal functions. Further understanding of mechanisms regulating IESCs activity will shed light on novel strategies mitigating stress-associated intestinal dysfunctions.

Cocaine intake correlates with risk-taking behavior and affects estrous cycling in female Sprague-Dawley rats.

Navigating complex decisions and considering their relative risks and rewards is an important cognitive ability necessary for survival. However, use of and dependence on illicit drugs can result in long-lasting changes to this risk/reward calculus in individuals with substance use disorder. Recent work has shown that chronic exposure to cocaine causes long-lasting increases in risk taking in male and female rats, but there are still significant gaps in our understanding of the relationship between cocaine use and changes in risk taking. For example, it is unclear whether the magnitude of cocaine intake dictates the extent to which risk taking is altered. To address this, male and female Sprague-Dawley rats underwent cocaine (or sucrose) self-administration and, following a period of abstinence, were trained and tested in a rodent model of risky decision making. In this behavioral task, rats made discrete-trial choices between a lever associated with a small food reward (i.e., "safe" option) and a lever associated with a larger food reward accompanied by a variable risk of footshock delivery (i.e., "risky" option). Surprisingly, and in contrast to prior work in Long-Evans rats, there were no effects of cocaine self-administration on choice of the large, risky reward (i.e., risk taking) during abstinence in males or females. There was, however, a significant relationship between cocaine intake and risk taking in female rats, with greater intake associated with greater preference for the large, risky reward. Relative to their sucrose counterparts, female rats in the cocaine group also exhibited irregular estrous cycles, characterized by prolonged estrus and/or diestrus phases. Collectively, these data suggest that there may be strain differences in the effects of cocaine on risk taking and highlight the impact that chronic cocaine exposure has on hormonal cyclicity in females. Future work will focus on understanding the neural mechanisms underlying cocaine's intake-dependent effects on risk taking in females, and whether this is directly related to cocaine-induced alterations in neuroendocrine function.

Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes.

Postoperative immunosuppression has been recognized as an important driver of surgery-related morbidity and mortality. It is characterized by lymphocyte depression and impaired monocyte capability to present foreign antigens to T-cells via Major Histocompatibility Complex, Class II (MHC-II) molecules. In patients with postoperative abdominal sepsis, we previously detected a persisting differential binding of the CCCTC-Binding Factor (CTCF), a superordinate regulator of transcription, inside the MHC-II region with specific impact on human leucocyte antigen (HLA) gene expression. In this prospective exploratory study, we investigated to which extent major surgery affects the MHC-II region of circulating CD14+-monocytes. In non-immunocompromised patients undergoing elective major abdominal surgery, a postoperative loss of monocyte HLA-DR surface receptor density was accompanied by a decline in the transcription levels of the classical MHC-II genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1. The surgical event decreased the expression of the transcriptional MHC-II regulators CIITA and CTCF and led to a lower CTCF enrichment at an intergenic sequence within the HLA-DR subregion. During the observation period, we found a slow and only incomplete restoration of monocyte HLA-DR surface receptor density as well as a partial recovery of CIITA, HLA-DRA and HLA-DRB1 expression. In contrast, transcription of HLA-DPA1, HLA-DPB1, CTCF and binding of CTCF within the MHC-II remained altered. In circulating monocytes, major surgery does not globally affect MHC-II transcription but rather induces specific changes in the expression of selected HLA genes, followed by differential recovery patterns and accompanied by a prolonged reduction of CTCF expression and binding within the MHC-II region. Our results hint toward a long-lasting impact of a major surgical intervention on monocyte functionality, possibly mediated by epigenetic changes that endure the life span of the individual cell.

Integrin α3 is required for high-frequency repetitive transcranial magnetic stimulation-induced glutamatergic synaptic transmission in mice with ischemia.

Repetitive transcranial magnetic stimulation (rTMS) is an effective therapy in post-stroke motor recovery. However, the underlying mechanisms of rTMS regulates long-lasting changes with synaptic transmission and glutamate receptors function (including AMPARs or NMDARs) remains unclear. Mice were received 10-Hz rTMS treatment once daily on the third day after photothrombotic (PT) stroke for 18 days. Motor behaviors and the Western blot were used to evaluate the therapeutic efficacy of 10-Hz rTMS in the mice with PT model. Moreover, we used wild-type (WT) and NEX-α3-/- mice to further explore the 10-Hz rTMS effect. We found that 10-Hz rTMS improved the post-stroke motor performance in the PT mice. Moreover, the levels of AMPAR, vGlut1, and integrin α3 in the peri-infarct were significantly increased in the rTMS group. In contrast, 10-Hz rTMS did not induce these aforementioned effects in NEX-α3-/- mice. The amplitude of AMPAR-mediated miniature excitatory postsynaptic currents (EPSCs) and evoked EPSCs was increased in the WT + rTMS group, but did not change in NEX-α3-/- mice with rTMS. In this study, 10-Hz rTMS improved the glutamatergic synaptic transmission in the peri-infract cortex through effects on integrin α3 and AMPARs, which resulted in motor function recovery after stroke.

Size-dependent and sex-specific negative effects of micro- and nano-sized polystyrene particles in the terrestrial invertebrate model Drosophila melanogaster

Microplastic pollution is believed to be one of the most widespread and long-lasting changes on a global scale. Our understanding that microplastics significantly impact terrestrial systems and are a global change stressor continues to grow. In the present study, we investigated the negative effect of long-term (28 days of exposure in food) polystyrene particles of micro (1.0–1.9 µm, 0.4–0.6 µm) and nano (0.04–0.06 µm) scale, in low doses, on the fruit fly – representing a common, globally distributed terrestrial invertebrate, and a model species in many fields. Our observations involved such parameters as ingestion and transfer of particles, survival, reproduction, changes in ultrastructure and tissue and cell responses in midgut epithelium (the place of direct contact with plastic), ovary, and testis in adults, and transgenerational effects in larvae. These observations may indicate possible toxic effects of the tested substances, even in low doses, that can be expected in other taxa, in terrestrial ecosystems. We observed a negative impact of polystyrene particles on the fruit fly survival, midgut, ovary, and testis, involving ultrastructural alterations, such as autophagy and/or ultimately necrosis in the midgut, triggering oxidative stress and activating processes of antioxidative protection. Despite the changes, midgut function and reproduction were not altered – spermatogenesis and oogenesis proceeded normally. The effect was size-dependent – the smaller the polystyrene particles were, the more substantial was the impact they caused. Ultrastructural changes and studied parameters, i.e., generation of ROS (overproduction of which generates oxidative stress), total glutathione concentration (involved in defense against ROS, acting in distinct pathways), and total antioxidant concentration (the oxidative defense system) showed the highest levels after exposure to the smallest nanoparticles, and vice versa. The effect was also sex-dependent, with male flies being more sensitive. Negative effects in males were more substantial and more prominent, even after contact with larger particles, compared to females. The smaller particles (0.4–0.6 µm, 0.04–0.06 µm) were transferred to the ovary and accumulated in the oocytes. In this case, a transgenerational negative effect was detected in larvae. It was characterized by size-dependent alterations, with smaller particles triggering higher levels of ROS and cellular oxidative response. Only the largest particles (1.0–1.9 µm) did not pass into the gonad and did not alter the larvae. These observations together demonstrated that polystyrene particles of micro- and nanoscale, even in a low dose, can induce numerous negative effects on terrestrial invertebrates.

Effects of Using Websites on Physical Activity and Diet Quality for Adults Living With Chronic Health Conditions: Systematic Review and Meta-Analysis.

Adults with chronic health conditions need support to manage modifiable risk factors such as physical inactivity and poor diet. Disease-specific websites with health information on physical activity and diet quality may be effective in supporting adults in managing their chronic illnesses. The primary aim of this review was to determine whether using websites with health information can lead to improvements in physical activity levels or diet quality in adults with chronic health conditions. Randomized controlled trials evaluating the effectiveness of website use on levels of physical activity or diet quality in adults with chronic health conditions were included. MEDLINE, Embase, CINAHL, and the Physiotherapy Evidence Database were searched from the earliest available record until February 2023. Data for outcomes measuring physical activity levels; diet quality; and, where reported, self-efficacy and quality of life were independently extracted by 2 reviewers. The risk of bias was assessed using the Physiotherapy Evidence Database scale, and the overall certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Where values were presented as the same unit of measure, postintervention scores were pooled for meta-analysis to yield an overall mean difference (MD). A standardized MD (SMD) was calculated for the pooled data in which different units for the same outcome were used. Individual trial data were described in cases where the data of trials could not be pooled. A total of 29 trials (N=6418 participants) across 8 different disease groups with intervention periods ranging from 4 weeks to 12 months were included in the analysis. There was moderate-certainty evidence that using websites with health information increased levels of moderate to vigorous physical activity (MD=39 min/wk, 95% CI 18.60-58.47), quality of life (SMD=0.36, 95% CI 0.12-0.59), and self-efficacy (SMD=0.26, 95% CI 0.05-0.48) and high-certainty evidence for reduction in processed meat consumption (MD=1.1 portions/wk, 95% CI 0.70-1.58) when compared with usual care. No differences were detected in other measures of diet quality. There was no increased benefit for website users who were offered additional support. The use of websites for risk factor management has the potential to improve physical activity levels, quality of life, and self-efficacy as well as reduce processed meat consumption for adults living with chronic health conditions when compared with usual care. However, it remains unclear whether using websites leads to meaningful and long-lasting behavior change. PROSPERO CRD42021283168; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=283168.

Interrelated effects of age and parenthood on whole-brain controllability: protective effects of parenthood in mothers.

Controllability is a measure of the brain's ability to orchestrate neural activity which can be quantified in terms of properties of the brain's network connectivity. Evidence from the literature suggests that aging can exert a general effect on whole-brain controllability. Mounting evidence, on the other hand, suggests that parenthood and motherhood in particular lead to long-lasting changes in brain architecture that effectively slow down brain aging. We hypothesize that parenthood might preserve brain controllability properties from aging. In a sample of 814 healthy individuals (aged 33.9 ± 12.7 years, 522 females), we estimate whole-brain controllability and compare the aging effects in subjects with vs. those without children. We use diffusion tensor imaging (DTI) to estimate the brain structural connectome. The level of brain control is then calculated from the connectomic properties of the brain structure. Specifically, we measure the network control over many low-energy state transitions (average controllability) and the network control over difficult-to-reach states (modal controllability). In nulliparous females, whole-brain average controllability increases, and modal controllability decreases with age, a trend that we do not observe in parous females. Statistical comparison of the controllability metrics shows that modal controllability is higher and average controllability is lower in parous females compared to nulliparous females. In men, we observed the same trend, but the difference between nulliparous and parous males do not reach statistical significance. Our results provide strong evidence that parenthood contradicts aging effects on brain controllability and the effect is stronger in mothers.

Physicians’ Compliance With Order Entry Forms for Intravenous Pantoprazole in a Tertiary Care Hospital

The widespread inappropriate use of intravenous (IV) pantoprazole, due to its high cost, is a substantial issue. To improve its rational use, an order entry form (OEF) based on the institutional guideline, was implemented. Physicians were required to fill an OEF upon administration of IV pantoprazole. We aimed to evaluate the compliance of physicians as well as the accuracy of filled OEFs six months after the implementation. The study was conducted in a tertiary care teaching hospital in Tehran. Chart review was performed for all patients with an IV pantoprazole order. IV pantoprazole OEFs received by the hospital pharmacy for these patients were evaluated in terms of quantity and quality (e.g., completeness, accuracy of filled items, etc.). Only for 270 (62%) patients, OEFs were received by the hospital pharmacy. Indications were specified in 199 (73.5%) forms, and their agreement with the forms filled by the researcher was 37.8%. The most frequent indication specified in OEFs was stress ulcer prophylaxis (40.7%). IV pantoprazole administration was rational only in 15.9% of cases. The emergency ward had the highest frequency of orders (57.9%), while having the lowest fill rate (56.7%) among the wards with the highest number of orders. The disagreement between the researcher and the OEFs regarding the need for IV medication was 39.5%. This study demonstrated that the compliance of physicians with the accurate completion of OEFs was suboptimal. It seems that for long-lasting changes in IV pantoprazole utilization patterns, barriers should be determined, and additional methods such as ongoing educational seminars or feedback might be needed along with OEF.

Advances in proteomics: characterization of the innate immune system after birth and during inflammation.

Proteomics is the characterization of the protein composition, the proteome, of a biological sample. It involves the large-scale identification and quantification of proteins, peptides, and post-translational modifications. This review focuses on recent developments in mass spectrometry-based proteomics and provides an overview of available methods for sample preparation to study the innate immune system. Recent advancements in the proteomics workflows, including sample preparation, have significantly improved the sensitivity and proteome coverage of biological samples including the technically difficult blood plasma. Proteomics is often applied in immunology and has been used to characterize the levels of innate immune system components after perturbations such as birth or during chronic inflammatory diseases like rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In cancers, the tumor microenvironment may generate chronic inflammation and release cytokines to the circulation. In these situations, the innate immune system undergoes profound and long-lasting changes, the large-scale characterization of which may increase our biological understanding and help identify components with translational potential for guiding diagnosis and treatment decisions. With the ongoing technical development, proteomics will likely continue to provide increasing insights into complex biological processes and their implications for health and disease. Integrating proteomics with other omics data and utilizing multi-omics approaches have been demonstrated to give additional valuable insights into biological systems.

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes.

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.

Funding and financing the zero emissions journey: urban visions from the 100 Climate-Neutral and Smart Cities Mission

Cities play a critical role in delivering emission-free futures, yet the financial capacities, together with the unprecedented estimated capital requirements represent substantial barriers to climate action. In this study, we use data collected through the European Mission on 100 Climate-Neutral and Smart Cities to investigate how 362 ambitious, yet differently prepared cities are fostering climate investment, under three aspects of (i) financial readiness, (ii) financial proactiveness, and (iii) financial innovation. On one hand, according to their self-assessment, over 70% of the cities have not yet estimated—not even roughly—the total investment needed to become climate neutral and the majority (i) have experience in financing only a few specific climate projects, (ii) are ill-equipped to tap capital markets, (iii) have developed only marginally co-financing with the private sector, and (iv) have taken no steps to establish an investor-ready pipeline of projects contributing to climate neutrality. On the other hand, cities are at the forefront of financial innovation, creating blueprints and business models that are being tested under a learning-by-doing approach, creating deep and long-lasting transformative change, and establishing coordinating mechanisms with new critical players. In this context, current financial management, regulation, and institutional arrangements are key barriers to unlocking access to financing and creating an enabling environment for investment at the city level. The different levels of maturity in terms of financial readiness and institutional arrangements are discussed as the catalysers of climate financing at the city level.

Exploring the pathologist's role in understanding COVID-19: from pneumonia to long-COVID lung sequelae.

The crucial role of pathologists in enhancing our understanding of SARS-CoV-2-related disease, from initial pneumonia manifestations to persistent long COVID lung symptoms, is the focus of this review. Pathological explorations have offered unprecedented insights into the early stages of severe COVID-19, shedding light on the interplay between the virus and subsequent complications, thereby shaping clinical approaches. Growing interest is directed to residual lung abnormalities of COVID-19 survivors. Although various radiological studies reported long-lasting pulmonary changes (e.g., ground glass opacities, reticulations, and bronchiectasis), the true incidence of pulmonary fibrosis and corresponding pathological findings in these patients remains largely unknown. There are a few high-impact and knowledgeable works on late complications in COVID-19 survivors, several coming from explant or autopsy cases, and rare cases from in vivo sampling. The study of biopsy samples has further deepened our knowledge of the aftermath of COVID-19 on lung tissue, uncovering alterations at the cellular level and shifts in vascular and epithelial dynamics. Despite the substantial progress made, future research is needed to devise a uniform strategy for interpreting lung biopsies, with a focus on leveraging advanced tools such as molecular and digital pathology techniques, along with artificial intelligence.

Extrapyramidal Side Effects with Chronic Atypical Antipsychotic Can Be Predicted by Labeling Pattern of FosB and phosphoThr34-DARPP-32 in Nucleus Accumbens.

Extrapyramidal side effects (EPS) can be induced by neuroleptics that regulate the expression of transcription factor FosB and dopaminergic mediator DARPP-32 in the striatum. However, the long-term neurobiological changes in striatal projection neurons resulting from a cumulative dosage of typical and atypical antipsychotics are poorly understood. The present study aimed to determine the differential and long-lasting changes in FosB distribution and DARPP-32 phosphorylation in the striatum and nucleus accumbens (NAc) associated with chronic antipsychotic-induced EPS. Male C57Bl/6J mice received daily injections of Olanzapine (Olz, 15 mg/kg), Clozapine (Clz, 20 mg/kg), or Haloperidol (Hal, 1 mg/kg), for a period of 11 weeks with a 4-day withdrawal period before the last dosage. Catalepsy for detection of EPS, along with open-field and rotarod tests, were assessed as behavioral correlates of motor responses. Additionally, FosB and phosphorylated-DARPP-32 immunohistochemistry were examined in striatal regions after treatment. All antipsychotics produced catalepsy and reduced open-field exploration, such as impaired rota-rod performance after Olz and Hal. The washout period was critical for Clz-induced side effects reduction. Both Olz and Clz increased FosB in NAc Shell-region, and phosphoThr34-DARPP-32 in NAc. Only Clz reduced phosphoThr75-DARPP-32 in the dorsal striatum and showed FosB/phosphoThr34-Darpp-32-ir in the NAc Core region. This study provides evidence that atypical antipsychotics such as Olz and Clz also give rise to EPS effects frequently associated with a cumulative dosage of typical neuroleptics such as Hal. Nevertheless, FosB/phosphoThr34-Darpp-32-ir in the NAc Core region is associated with hypokinetic movements inhibition.

Research governance for change: funding project-based measures in the field of responsible research and innovation (RRI) and their potential for organisational learning

PurposeThis paper aims to look at the implementation of project-funded research governance and its potential to induce organisational learning on responsible research and innovation (RRI). This paper analysed what types of organisational learning and change can take place within organisations of an Europe-funded project and to what extent. This paper examined whether and how change occurs and how it is shaped and co-produced with other orderings.Design/methodology/approachThe paper is based on materials and evidence collected while working on the internal evaluation of a Horizon 2020-funded project. Analysis of the results of the mixed methods evaluation design was used to characterise occurrences of organisational learning and change.FindingsThe authors identified different forms of learning (single-loop learning, double-loop learning, reflexive and reflective learning and situational learning). The extent of learning that could lead to long-lasting organisational change was limited. This was due to the project-based and organisational design, the key-based definition of RRI and the indeterminacy of what constitutes learning and change – both at the level of funding and performing the project. For organisational change to occur, the authors argue for governance mechanisms based on reflexive learning that consider a range of structural conditions and measures.Originality/valueOrganisational learning plays an important role in change processes, which has so far been given too little consideration concerning the governance and implementation of RRI through project-based funding. The authors argue for a restructuring of governance and funding mechanisms to create more space for reflexivity and learning.

Being friendly: paced mating for the study of physiological, behavioral, and neuroplastic changes induced by sexual behavior in females.

Paced mating in rats is an experimental condition that allows the evaluation of sexual behavior in a way that closely resembles what occurs in seminatural and natural conditions enabling the female to control the rate of the sexual interaction. In conventional non-paced mating tests, females cannot escape from male approaches, which may lead to an unrewarding overstimulation. Paced mating is an alternative laboratory procedure that improves animal welfare and has a higher ethological relevance. The use of this procedure contributed to the identification of physiological and behavioral factors that favor reproduction. Paced mating includes motivational and behavioral components differentiating quantitative and qualitative characteristics that are critical for the induction of the rewarding properties of mating. These positive consequences ensure that the behavior will be repeated, favoring the species' survival. Sexual reward is an immediate consequence of paced mating, mediated mainly by the endogenous opioid system. Paced mating also induces long-lasting neuroplastic changes, including gene expression, synthesis of proteins, and neurogenesis in sex-relevant brain areas. The interest in paced mating is growing since the complexity of its elements and consequences at different levels in a laboratory setting resembles what occurs in natural conditions. In this review, we analyze the classic studies and recent publications demonstrating the advantages of using paced mating to evaluate different aspects of sexual behavior in females.

Gut microbiota alterations induced by intensive chemotherapy in acute myeloid leukaemia patients are associated with gut barrier dysfunction and body weight loss

Acute myeloid leukaemia (AML) chemotherapy has been reported to impact gut microbiota composition. In this study, we investigated using a multi -omics strategy the changes in the gut microbiome induced by AML intense therapy and their association with gut barrier function and cachectic hallmarks. 10 AML patients, allocated to standard induction chemotherapy (SIC), were recruited. Samples and data were collected before any therapeutic intervention (T0), at the end of the SIC (T1) and at discharge (T4). Gut microbiota composition and function, markers of inflammation, metabolism, gut barrier function and cachexia, as well as faecal, blood and urine metabolomes were assessed. AML patients demonstrated decreased appetite, weight loss and muscle wasting during hospitalization, with an incidence of cachexia of 50%. AML intensive treatment transiently impaired the gut barrier function and led to a long-lasting change of gut microbiota composition characterized by an important loss of diversity. Lactobacillaceae and Campylobacter concisus were increased at T1 while Enterococcus faecium and Staphylococcus were increased at T4. Metabolomics analyses revealed a reduction in urinary hippurate and faecal bacterial amino acid metabolites (bAAm) (2-methylbutyrate, isovalerate, phenylacetate). Integration using DIABLO revealed a deep interconnection between all the datasets. Importantly, we identified bacteria which disappearance was associated with impaired gut barrier function (Odoribacter splanchnicus) and body weight loss (Gemmiger formicilis), suggesting these bacteria as actionable targets. AML intensive therapy transiently impairs the gut barrier function while inducing enduring alterations in the composition and metabolic activity of the gut microbiota that associate with body weight loss. NCT03881826, https://clinicaltrials.gov/ct2/show/NCT03881826.

Psilocybin-Assisted Therapy: A scoping review of participants’ and facilitators’ experiences in qualitative studies

There has been a surge in research on Psilocybin-Assisted Therapy (PAT) over the past three decades. PAT has yielded positive results across clinical trials and demonstrated efficacy in treating various mental disorders. However, limited qualitative research exists that explores peoples’ experiences of PAT. This study aims to review the current literature on the experiences of individuals that have participated in PAT, as well as individuals that have facilitated PAT. This study aims to increase our understanding of PAT to guide and improve therapeutic effectiveness. A scoping review was conducted from English language studies published in peer-reviewed journals. Searches were conducted from PsycInfo, CINAHL, PubMed, Web of Science, and Cochrane Library databases. Inclusion criteria were qualitative studies involving PAT that were conducted between January 1990 and December 2022; articles published in peer-reviewed journals; and psychedelic practitioners’ experiences of facilitating PAT. In total, 13 articles were extracted to be included in the review. Articles were published between 2017 and 2021, and were divided into (1) Participant Studies (10) and (2) Facilitator Studies (3). Six themes were identified: the influence of set and setting; PAT was personalised and meaningful; PAT can be highly emotive; transcendental experiences; reduction of symptoms and long-lasting changes; and boundaries and responsibility. The literature revealed numerous interrelated therapeutic elements that may have contributed to a meaningful experience during PAT. This may play a role in attaining long-lasting positive therapeutic outcomes. The studies were varied and highlighted the usefulness of further exploring PAT.

Environmental enrichment improves hippocampus-dependent spatial learning in female C57BL/6 mice in novel IntelliCage sweet reward-based behavioral tests.

The IntelliCage is an automated home-cage system that allows researchers to investigate the spontaneous behavior and learning abilities of group-housed mice. The IntelliCage enables us to increase the standardization and reproducibility of behavioral outcomes by the omission of experimenter-mouse interactions. Although the IntelliCage provides a less stressful environment for animals, standard IntelliCage protocols use controlled water access as the motivational driver for learning. To overcome possible water restrictions in slow learners, we developed a series of novel protocols based on appetitive learning, in which mice had permanent access to plain water but were additionally rewarded with sweetened water upon solving the task. C57BL/6NCrl female mice were used to assess the efficacy of these sweet reward-based protocols in a series of learning tasks. Compared to control mice tested with standard protocols, mice motivated with a sweet reward did equal to or better in operant performance and place learning tasks. Learning of temporal rules was slower than that in controls. When faced with a combined temporal x spatial working memory task, sweet-rewarded mice learned little and chose plain water. In a second set of experiments, the impact of environmental enrichment on appetitive learning was tested. Mice kept under enriched environment (EE) or standard housing (SH) conditions prior to the IntelliCage experiments performed similarly in the sweet-rewarded place learning task. EE mice performed better in the hippocampus-dependent spatial working memory task. The improved performance of EE mice in the hippocampus-dependent spatial working memory task might be explained by the observed larger volume of their mossy fibers. Our results confirm that environmental enrichment increases complex spatial learning abilities and leads to long-lasting morphological changes in the hippocampus. Furthermore, simple standard IntelliCage protocols could easily be adapted to sweet rewards, which improve animal welfare by removing the possibility of water restriction. However, complex behavioral tasks motivated by sweet reward-based learning need further adjustments to reach the same efficacy as standard protocols.