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Leader–follower modalities and other asymmetric interactions that drive the collective motion of organisms are often quantified using information theory metrics like transfer or causation entropy. These metrics are difficult to accurately evaluate without a much larger number of data than is typically available from a time series of animal trajectories collected in the field or from experiments. In this paper, we use a generalized leader–follower model to argue that the time-separated mutual information between two organism positions can serve as an alternative metric for capturing asymmetric correlations that is much less data intensive and more accurately estimated by popular k-nearest neighbor algorithms than transfer entropy. Our model predicts a local maximum of this mutual information at a time separation value corresponding to the fundamental reaction timescale of the follower organism. We confirm this prediction by analyzing time series trajectories recorded for a pair of golden shiner fish circling an annular tank.

Design alternatives for traditional infrastructure are often compared in terms of expected–and often narrowly defined–costs and benefits to justify the selected plan. Taking a broader life cycle perspective in the benefit-cost evaluation process helps account for potentially rare, indirect, or accruing project benefits. Natural infrastructure design alternatives are generally difficult to compare to conventional alternatives due to their distinctly different costs and benefits. Natural infrastructure differs from conventional infrastructure in terms of performance and benefit development over time, lifespan, materials, intensity of intervention needs, and social and environmental benefits. This paper presents a life cycle framework that expands conventional life cycle analysis to capture other important and relevant aspects of natural and conventional infrastructure, enabling a more complete and equitable comparison of project costs and benefits. The framework consists of four dimensions: risk mitigation performance (e.g., traditional benefit of flood risk management), co-benefits, financial costs (life cycle cost analysis), and environmental costs (life cycle assessment). The framework takes current benefit cost analysis practice for both infrastructure types into account, is informed by existing life cycle evaluation methods and tools and is responsive to the unique needs and characteristics of natural infrastructure. Components of this framework have been advanced elsewhere, including in business product management, asset management, building code development, environmental certifications, ecosystem goods and services accounting, and others, but are generally not developed for natural infrastructure. Our proposed framework provides a roadmap for development of supporting resources to conduct life cycle evaluation for natural infrastructure. Systematically grasping the temporal flow of costs and benefits of natural infrastructure, in comparison to conventional flood risk management projects, will be important as societies address vast infrastructure needs in the face of climate change.

Abstract Functionalized multi-walled carbon nanotubes (MWCNT) have become the focus of increased research interest, particularly in their application as tools in different areas, such as the biomedical field. Despite the benefits associated with functionalization of MWCNT, particularly in overcoming issues relating to solubility, several studies have demonstrated that these functionalized nanoparticles display different toxicity profiles. For this study, we aim to compare NR8383 cells responses to three well-characterized MWCNT with varying functional groups. This study employed cytotoxicity assays, transcriptomics and proteomics to assess their toxicity using NR8383 rat alveolar macrophages as an in vitro model. The study findings indicated that all MWCNT altered ribosomal protein translation, cytoskeleton arrangement and induced pro-inflammatory response. Only functionalized MWCNT alter mTOR signaling pathway in conjunction with increased Lamtor gene expression. Furthermore, the type of functionalization was also important, with cationic MWCNT activating the transcription factor EB and inducing autophagy while the anionic MWCNT altering eukaryotic translation initiation factor 4 (EIF4) and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling pathway as well as upregulation Tlr2 gene expression. This study proposes that MWCNT toxicity mechanisms are functionalization dependent and provides evidence that inflammatory response is a key event of carbon nanotubes toxicity.

Introduction: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent. Methods: The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have. Results: Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation. Discussion: Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal.

Titanium dental implants have common clinical applications due to their biocompatibility, biophysical and biochemical characteristics. Although current titanium is thought to be safe and beneficial for patients, there are several indications that it may release toxic metal ions or metal nanoparticles from its alloys into the surrounding environment, which could lead to clinically relevant complications including toxic reactions as well as immune dysfunctions. Hence, an adequate selection and testing of medical biomaterial with outstanding properties are warranted. This study was designed to explore the biocompatibility of smooth titanium-niobium alloy (S_TiNb) versus smooth titanium commercially pure (S_TiCp)—a reference in implantology. All experiments were performed in vitro using human osteoblast-like SaOs-2 and monocyte THP-1 cell lines as models. Cell adhesion and growth morphology were determined by scanning electron microscopy, while cell viability was evaluated using WST-1 assay. Because niobate anions or niobium nanoparticles can be released from implants during biomaterial-cell interaction, potential immunotoxicity of potassium niobate (KNbO3) salt was evaluated by examining both metabolic activity and transcriptomic profiling of treated THP-1 monocytes. The main findings of this study are that S_TiCp and S_TiNb discs do not show an impact on the proliferation and viability of SaOs-2 cells compared to polystyrene surfaces, whereas a significant decrease in THP-1 cells’ viability and metabolic activity was observed in the presence of S_TiNb discs compared to the control group. However, no significant changes were found neither at the metabolic activity nor at the transcriptomic level of THP-1 monocytes exposed to KNbO3 salt, suggesting that niobium has no effect on the immune system. Overall, these data imply a possible toxicity of S_TiNb discs toward THP-1 cells, which may not be directly related to niobium but perhaps to the manufacturing process of titanium-niobium alloy. Thus, this limitation must be overcome to make titanium alloy an excellent material for medical applications.

Introduction: Pragmatic trials in comparative effectiveness research assess the effects of different treatment, therapeutic, or healthcare options in clinical practice. They are characterized by broad eligibility criteria and large sample sizes, which can lead to an unmanageable number of participants, increasing the risk of bias and affecting the integrity of the trial. We describe the development of a sampling strategy tool and its use in the PREPARE trial to circumvent the challenge of unmanageable work flow. Methods: Given the broad eligibility criteria and high fracture volume at participating clinical sites in the PREPARE trial, a pragmatic sampling strategy was needed. Using data from PREPARE, descriptive statistics were used to describe the use of the sampling strategy across clinical sites. A Chi-square test was performed to explore whether use of the sampling strategy was associated with a reduction in the number of missed eligible patients. Results: 7 of 20 clinical sites (35%) elected to adopt a sampling strategy. There were 1539 patients excluded due to the use of the sampling strategy, which represents 30% of all excluded patients and 20% of all patients screened for participation. Use of the sampling strategy was associated with lower odds of missed eligible patients (297/4545 (6.5%) versus 341/3200 (10.7%) p

Medical imaging has relied on ultrasound (US) as an exploratory method for decades. Nonetheless, in cell biology, the numerous US applications are mainly in the research and development phase. In this review, we report the main effects on human or mammal cells of US induced by bulk or surface acoustic waves (SAW). At low frequencies, bulk US can lead to cell death. Under specific intensities and exposure times, however, cell proliferation and migration can be enhanced through cytoskeleton fluidization (a reorganization of the actin filaments and microtubules). Cavitation phenomena, frequencies of resonance close to those of the biological compounds, and mechanical transfers of energy from the acoustic pressure could explain those biological outcomes. At higher frequencies, no cavitation is observed. However, USs of high frequency stimulate ionic channels and increase cell permeability and transfection potency. Surface acoustic waves are increasingly exploited in microfluidics, especially for precise cell manipulations and cell sorting. With applications in diagnosis, infection, cancer treatment, or wound healing, US has remarkable potential. More mechanotransduction studies would be beneficial to understand the distinct roles of temperature rise, acoustic streaming and mechanical and electrical stimuli in the field.

Nanoparticle toxicity assessments have moved closer to physiological conditions while trying to avoid the use of animal models. An example of new in vitro exposure techniques developed is the exposure of cultured cells at the air–liquid interface (ALI), particularly in the case of respiratory airways. While the commercially available VITROCELL® Cloud System has been applied for the delivery of aerosolized substances to adherent cells under ALI conditions, it has not yet been tested on lung surfactant and semi-adherent cells such as alveolar macrophages, which are playing a pivotal role in the nanoparticle-induced immune response. Objectives: In this work, we developed a comprehensive methodology for coating semi-adherent lung cells cultured at the ALI with aerosolized surfactant and subsequent dose-controlled exposure to nanoparticles (NPs). This protocol is optimized for subsequent transcriptomic studies. Methods: Semi-adherent rat alveolar macrophages NR8383 were grown at the ALI and coated with lung surfactant through nebulization using the VITROCELL® Cloud 6 System before being exposed to TiO2 NM105 NPs. After NP exposures, RNA was extracted and its quantity and quality were measured. Results: The VITROCELL® Cloud system allowed for uniform and ultrathin coating of cells with aerosolized surfactant mimicking physiological conditions in the lung. While nebulization of 57 μL of 30 mg/mL TiO2 and 114 μL of 15 mg/mL TiO2 nanoparticles yielded identical cell delivered dose, the reproducibility of dose as well as the quality of RNA extracted were better for 114 μL.

There are many studies concerning titanium dioxide (TiO2) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification and validation of common markers under different exposure conditions are relevant for the development of smart and quick nanotoxicity tests. In this work, cell viability was assessed in vitro by WST-1 and LDH assays after the exposure of NR8383 cells to TiO2 NP sample. To evaluate in vitro gene expression profile, NR8383 cells were exposed to TiO2 NP during 4 h at 3 cm2 of TiO2 NP/cm2 of cells or 19 μg/mL, in two settings—submerged cultures and ALI. For the in vivo study, Fischer 344 rats were exposed by inhalation to a nanostructured aerosol at a concentration of 10 mg/m3, 6 h/day, 5 days/week for 4 weeks. This was followed immediately by gene expression analysis. The results showed a low cytotoxic potential of TiO2 NP on NR8383 cells. Despite the absence of toxicity at the doses studied, the different exposures to TiO2 NP induce 18 common differentially expressed genes (DEG) which are involved in mitosis regulation, cell proliferation and apoptosis and inflammation transport of membrane proteins. Among these genes, we noticed the upregulation of Ccl4, Osm, Ccl7 and Bcl3 genes which could be suggested as early response biomarkers after exposure to TiO2 NP. On the other hand, the comparison of the three models helped us to validate the alternative ones, namely submerged and ALI approaches.

The aims of the current study were to prepare chitosan nanoparticles (CNPs) and to evaluate its protective role alone or in combination with quercetin (Q) against AFB1-induce cytotoxicity in rats. Male Sprague-Dawley rats were divided into 12 groups and treated orally for 4 weeks as follow: the control group, the group treated with AFB1 (80 μg/kg b.w.) in corn oil, the groups treated with low (140 mg/kg b.w.) or high (280 mg/kg b.w.) dose of CNPs, the group treated with Q (50 mg/kg b.w.), the groups treated with Q plus the low or the high dose of CNPs and the groups treated with AFB1 plus Q and/or CNPs at the two tested doses. The results also revealed that administration of AFB1 resulted in a significant increase in serum cytokines, Procollagen III, Nitric Oxide, lipid peroxidation and DNA fragmentation accompanied with a significant decrease in GPx I and Cu–Zn SOD-mRNA gene expression. Q and/or CNPs at the two tested doses overcome these effects especially in the group treated with the high dose of CNPs plus Q. It could be concluded that CNPs is a promise candidate as drug delivery enhances the protective effect of Q against the cytogenetic effects of AFB1 in high endemic areas.

The aim of this study was to prepare Eudragit Retard L (Eudragit RL) nanoparticles (ENPs) and to determine their properties, their uptake by the human THP-1 cell line in vitro and their effect on the hematological parameters and erythrocyte damage in rats. ENPs showed an average size of 329.0 ± 18.5 nm, a positive zeta potential value of +57.5 ± 5.47 mV and nearly spherical shape with a smooth surface. THP-1 cell lines could phagocyte ENPs after 2 h of incubation. In the in vivo study, male Sprague-Dawley rats were exposed orally or intraperitoneally (IP) with a single dose of ENP (50 mg/kg body weight). Blood samples were collected after 4 h, 48 h, one week and three weeks for hematological and erythrocytes analysis. ENPs induced significant hematological disturbances in platelets, red blood cell (RBC) total and differential counts of white blood cells (WBCs) after 4 h, 48 h and one week. ENP increased met-Hb and Co-Hb derivatives and decreased met-Hb reductase activity. These parameters were comparable to the control after three weeks when administrated orally. It could be concluded that the route of administration has a major effect on the induction of hematological disturbances and should be considered when ENPs are applied for drug delivery systems.

Social animals are capable of enhancing their awareness by paying attention to their neighbors, and prey found in groups can also confuse their predators. Both sides of these sensory benefits have long been appreciated, yet less is known of how the perception of events from the perspectives of both prey and predator can interact to influence their encounters. Here we examined how a visual sensory mechanism impacts the collective motion of prey and, subsequently, how their resulting movements influenced predator confusion and capture ability. We presented virtual prey to human players in a targeting game and measured the speed and accuracy with which participants caught designated prey. As prey paid more attention to neighbor movements their collective coordination increased, yet increases in prey coordination were positively associated with increases in the speed and accuracy of attacks. However, while attack speed was unaffected by the initial state of the prey, accuracy dropped significantly if the prey were already organized at the start of the attack, rather than in the process of self-organizing. By repeating attack scenarios and masking the targeted prey's neighbors we were able to visually isolate them and conclusively demonstrate how visual confusion impacted capture ability. Delays in capture caused by decreased coordination amongst the prey depended upon the collection motion of neighboring prey, while it was primarily the motion of the targets themselves that determined capture accuracy. Interestingly, while a complete loss of coordination in the prey (e.g., a flash expansion) caused the greatest delay in capture, such behavior had little effect on capture accuracy. Lastly, while increases in collective coordination in prey enhanced personal risk, traveling in coordinated groups was still better than appearing alone. These findings demonstrate a trade-off between the sensory mechanisms that can enhance the collective properties that emerge in social animals and the individual group member's predation risk during an attack.

Artificial barriers have become ubiquitous features in freshwater ecosystems and they can significantly impact a region's biodiversity. Assessing the risk faced by fish forced to navigate their way around artificial barriers is largely based on assays of individual swimming behavior. However, social interactions can significantly influence fish movement patterns and alter their risk exposure. Using an experimental flume, we assessed the effects of social interactions on the amount of time required for juvenile palmetto bass (Morone chrysops × M. saxatilis) to navigate downstream past an artificial barrier. Fish were released either individually or in groups into the flume using flow conditions that approached the limit of their expected swimming stamina. We compared fish swimming behaviors under solitary and schooling conditions and measured risk as the time individuals spent exposed to the barrier. Solitary fish generally turned with the current and moved quickly downstream past the barrier, while fish in groups swam against the current and displayed a 23-fold increase in exposure time. Solitary individuals also showed greater signs of skittish behavior than those released in groups, which was reflected by larger changes in their accelerations and turning profiles. While groups displayed fission-fusion dynamics, inter-individual positions were highly structured and remained steady over time. These spatial patterns align with theoretical positions necessary to reduce swimming exertion through either wake capturing or velocity sheltering, but diverge from any potential gains from channeling effects between adjacent neighbors. We conclude that isolated performance trials and projections based on individual behaviors can lead to erroneous predictions of risk exposure along engineered structures. Our results also suggest that risk perception and behavior may be more important than a fish's swimming stamina in artificially modified systems.

Summary: Background: Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label reflecting the nutrient profile of foods. It has been implemented in several European countries on a voluntary basis, pending the revision of the European labeling regulation. Hence, scientific evidence is needed regarding the ability of the nutrient profile underlying the Nutri-Score (uNS-NPS, 2023-updated version) to characterize healthier foods. Our objective was therefore to study the prospective association between the nutritional quality of diet characterized by the uNS-NPS and the risk of cardiovascular diseases in a large European population. Methods: Our analyses included 345,533 participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC, 1992–2010, 7 European countries). Food intakes were assessed at baseline using country-specific dietary questionnaires. The uNS-NPS was calculated as a continuous scale for each food, based on its 100 g content of energy, sugars, saturated fatty acids, salt, fibre, and protein and percentage content of fruit, vegetables, and pulses. A dietary index was derived at the individual level (uNS-NPS DI: energy-weighted mean of uNS-NPS scores of all foods consumed by a participant). Cardiovascular events during follow-up were retrieved using country-specific methods (self-report, registry data). Multi-adjusted Cox models were computed. Findings: Overall, 16,214 first cardiovascular events were reported (median follow-up: 12.3 years; 4,103,133 person-years). The consumption of foods with a higher uNS-NPS score (reflecting a lower overall nutritional quality of diet) was associated with higher risks of total cardiovascular events (Hazards Ratio (HR) for an increment of 1 standard deviation: 1.03 (95% Confidence Interval 1.01–1.05)), especially myocardial infarction (HR = 1.03 (1.01–1.07)), and stroke (HR = 1.04 (1.01–1.07)). Interpretation: In this large prospective study among European adults, a higher risk of cardiovascular diseases (total and several subtypes) was observed in individuals consuming a diet with a lower nutritional value, as graded by the uNS-NPS score. This brings new evidence on the relevance of the updated nutrient profile underlying the Nutri-Score to characterize foods with a healthier nutrient profile. Funding: EPIC-CVD was supported by EU FP7, ERC, UK MRC, British Heart Foundation, and UK NIHR.

Abstract Background Ageing leads to altered immune responses, resulting in higher susceptibility to certain infections in the elderly. Immune ageing is a heterogeneous process also associated with inflammaging, a low-grade chronic inflammation. Altered cytotoxic T cell responses and cytokine storm have previously been described in severe COVID-19 cases, however the parameters responsible for such immune response failures are not well known. The aim of our study was to characterize CD8+ T cells and cytokines associated with ageing, in a cohort of patients aged over 70 years stratified by COVID-19 severity. Results One hundred and four patients were included in the study. We found that, in older people, COVID-19 severity was associated with (i) higher level of GM-CSF, CXCL10 (IP-10), VEGF, IL-1β, CCL2 (MCP-1) and the neutrophil to lymphocyte ratio (NLR), (ii) increased terminally differentiated CD8+T cells, and (ii) decreased early precursors CD8+ T stem cell-like memory cells (TSCM) and CD27+CD28+. The cytokines mentioned above were found at higher concentrations in the COVID-19+ older cohort compared to a younger cohort in which they were not associated with disease severity. Conclusions Our results highlight the particular importance of the myeloid lineage in COVID-19 severity among older people. As GM-CSF and CXCL10 were not associated with COVID-19 severity in younger patients, they may represent disease severity specific markers of ageing and should be considered in older people care.

Abstract Objective To investigate autonomic nervous system activity measured by brain–heart interactions in comatose patients after cardiac arrest in relation to the severity and prognosis of hypoxic–ischemic brain injury. Methods Strength and complexity of bidirectional interactions between EEG frequency bands (delta, theta, and alpha) and ECG heart rate variability frequency bands (low frequency, LF and high frequency, HF) were computed using a synthetic data generation model. Primary outcome was the severity of brain injury, assessed by (i) standardized qualitative EEG classification, (ii) somatosensory evoked potentials (N20), and (iii) neuron‐specific enolase levels. Secondary outcome was the 3‐month neurological status, assessed by the Cerebral Performance Category score [good (1–2) vs. poor outcome (3–4–5)]. Results Between January 2007 and July 2021, 181 patients were admitted to ICU for a resuscitated cardiac arrest. Poor neurological outcome was observed in 134 patients (74%). Qualitative EEG patterns suggesting high severity were associated with decreased LF/HF. Severity of EEG changes were proportional to higher absolute values of brain‐to‐heart coupling strength (p

Background: Despite advances in asthma treatments, severe asthma exacerbation (SAE) remains a life-threatening condition in adults, and there is a lack of data derived from adult patients admitted to intensive care units (ICUs) for SAE. The current study investigated changes in adult patient characteristics, management, and outcomes of SAE over a 20-year period in 40 ICUs in the greater Paris area. Methods: In this retrospective observational study, admissions to 40 ICUs in the greater Paris area for SAE from January 1, 1997, to December 31, 2016 were analyzed. The primary outcome was the proportion of ICU admissions for SAE during 5-year periods. Secondary outcomes were ICU and hospital mortality, and the use of mechanical ventilation and catecholamine. Multivariate analysis was performed to assess factors associated with ICU mortality. Results: A total of 7049 admissions for SAE were recorded. For each 5-year period, the proportion decreased over time, with SAE accounting for 2.84% of total ICU admissions (n=2841) between 1997 and 2001, 1.76% (n=1717) between 2002 and 2006, 1.05% (n=965) between 2007 and 2011, and 1.05% (n=1526) between 2012 and 2016. The median age was 46 years (interquartile range [IQR]: 32–59 years), 55.41% were female, the median Simplified Acute Physiology Score II was 20 (IQR: 13–28), and 19.76% had mechanical ventilation. The use of mechanical ventilation remained infrequent throughout the 20-year period, whereas the use of catecholamine decreased. ICU and hospital mortality rates decreased. Factors associated with ICU mortality were renal replacement therapy, catecholamine, cardiac arrest, pneumothorax, acute respiratory distress syndrome, sepsis, and invasive mechanical ventilation (IMV). Non-survivors were older, had more severe symptoms, and were more likely to have received IMV. Conclusion: ICU admission for SAE remains uncommon, and the proportion of cases decreased over time. Despite a slight increase in symptom severity during a 20-year period, ICU and hospital mortality decreased. Patients requiring IMV had a higher mortality rate.

Abstract Genomic selection (GS) has become an increasingly popular tool in plant breeding programs, propelled by declining genotyping costs, an increase in computational power, and rediscovery of the best linear unbiased prediction methodology over the past two decades. This development has led to an accumulation of extensive historical datasets with genotypic and phenotypic information, triggering the question of how to best utilize these datasets. Here, we investigate whether all available data or a subset should be used to calibrate GS models for across-year predictions in a 7-year dataset of a commercial hybrid sunflower breeding program. We employed a multi-objective optimization approach to determine the ideal years to include in the training set (TRS). Next, for a given combination of TRS years, we further optimized the TRS size and its genetic composition. We developed the Min_GRM size optimization method which consistently found the optimal TRS size, reducing dimensionality by 20% with an approximately 1% loss in predictive ability. Additionally, the Tails_GEGVs algorithm displayed potential, outperforming the use of all data by using just 60% of it for grain yield, a high-complexity, low-heritability trait. Moreover, maximizing the genetic diversity of the TRS resulted in a consistent predictive ability across the entire range of genotypic values in the test set. Interestingly, the Tails_GEGVs algorithm, due to its ability to leverage heterogeneity, enhanced predictive performance for key hybrids with extreme genotypic values. Our study provides new insights into the optimal utilization of historical data in plant breeding programs, resulting in improved GS model predictive ability.

Introduction: Liquefied petroleum gas (LPG) is a clean cooking fuel that emits less household air pollution (HAP) than polluting cooking fuels (e.g. charcoal, wood). While switching from polluting fuels to LPG can reduce HAP and improve health, the impact of ‘stacking’ (concurrent use of polluting fuels and LPG) on adverse health symptoms (e.g. headaches, eye irritation, cough) among female cooks is uncertain. Methods: Survey data from the CLEAN-Air(Africa) study was collected on cooking patterns and health symptoms over the last 12 months (cough, wheezing, chest tightness, shortness of breath, eye irritation, headaches) from approximately 400 female primary cooks in each of three peri‑urban communities in sub-Saharan Africa: Mbalmayo, Cameroon; Obuasi, Ghana; and Eldoret, Kenya. Random effects Poisson regression, adjusted for socioeconomic and health-related covariates, assessed the relationship between primary and secondary cooking fuel type and self-reported health symptoms. Results: Among 1,147 participants, 10 % (n = 118) exclusively cooked with LPG, 45 % (n = 509) stacked LPG and polluting fuels and 45 % (n = 520) exclusively cooked with polluting fuels. Female cooks stacking LPG and polluting fuels had significantly higher odds of shortness of breath (OR 2.16, 95 %CI:1.04–4.48) compared with those exclusively using LPG. In two communities, headache prevalence was 30 % higher among women stacking LPG with polluting fuels (Mbalmayo:82 %; Eldoret:65 %) compared with those exclusively using LPG (Mbalmayo:53 %; Eldoret:33 %). Women stacking LPG and polluting fuels (OR 2.45, 95 %CI:1.29–4.67) had significantly higher odds of eye irritation than women cooking exclusively with LPG. Second-hand smoke exposure was significantly associated with higher odds of chest tightness (OR 1.92, 95 % CI:1.19–3.11), wheezing (OR 1.76, 95 % CI:1.06–2.91) and cough (OR 1.78, 95 %CI:1.13–2.80). Conclusions: In peri‑urban sub-Saharan Africa, women exclusively cooking with LPG had lower odds of several health symptoms than those stacking LPG and polluting fuels. Promoting a complete transition to LPG in these communities may likely generate short-term health benefits for primary cooks.

The Pendjari Biosphere Reserve is one of the protected areas of Benin where biodiversity conservation policies intertwine with the economic development of local populations. It is located in the Atacora region in northern Benin, which has a high prevalence of poverty and food insecurity among households. Agriculture and livestock farming are the primary activities of the local communities in the villages surrounding the reserve. However, wild animals sometimes cause damage to people’s fields or livestock. To deal with the damage caused by wild animals, local populations have developed several mitigation measures that may not be effective, leading them into a vulnerable situation. Vulnerability is often associated with the impacts of natural disasters and their management, anticipation, and recovery. In the context of human–wildlife conflict, vulnerability refers to the level of risk farmers face from issues such as crop raiding, livestock depredation, and human injury caused by wildlife, as well as farmers’ ability to cope with such damage. To assess the vulnerability of households, we used the Livelihood Vulnerability Index (LVI). Data were collected from July to December 2019 through questionnaires and interviews. We surveyed 320 households to collect data on their socio-demographics, livelihoods, social networks, natural capital, food and water security, and the incidence and severity of human–wildlife conflicts. The results showed that farmers around the Pendjari Biosphere Reserve are highly sensitive to human–wildlife conflicts, with a low adaptive capacity, revealing their vulnerability. More precisely, farmers are vulnerable in terms of major components of the LVI such as water, food, social networks, and livelihoods. Conservation policies are expected to pay more attention to local populations’ vulnerability to human–wildlife conflicts in order to improve their tolerance towards wildlife and guarantee the success of conservation efforts.

Abstract Background The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. Methods Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. Results Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p

This paper edits and translates three unpublished Ethiopian texts in Ajami, Arabic, and Amharic from the 19th and 20th centuries that mention nostalgically the now vanished great medieval market of Gendabelo. The market appears in the 15th and 16th century documentation, both endogenous and exogenous to the Horn of Africa, in which it is described as one of the main breakbulk points for caravans linking the Red Sea coasts to the Ethiopian highlands. Located in the region of Ifāt, which was a powerful sultanate in the 14th century and, although it came under Christian rule in the early 15th century, continues to be inhabited by numerous Muslim communities to the present day, Gendabelo is not located. This article proposes a hypothesis of localization with the archaeological site of Asbari, based in particular on archaeological material (imported ceramics, glass, pearls, metal) collected during a visit in 2009 and with the help of the 19th c. Ajami poem.

Abstract Background Understanding drug use and behavior within the PWUD population is crucial to adapt harm reduction and prevention strategies, and provide improved addiction and medical treatment. However, in most countries such as France, the knowledge of drug use behaviors is likely biased as it originates from addiction centers which are attended by only an unknown proportion of PWUD. The objectives of this study were to describe drug use behavior in a population of active PWUD in the urban area of Montpellier, South of France. Methods We implemented a community-based respondent-driven sampling survey (RDSS), a validated strategy to obtain a representative sample of a population, to recruit PWUD in the city. Adult individuals reporting frequent psychoactive drug use other than cannabis, with confirmation by urine test, were eligible. Beside HCV and HIV testing, trained peers interviewed participants on their drug consumption and behavior using standardized questionnaires. Fifteen seeds launched the RDSS. Results During the 11 weeks of the RDSS, 554 actives PWUD were consecutively included. They were mostly men (78.8%), had a median age of 39 years, and only 25.6% had a stable living place. On average, participants consumed 4.7 (± 3.1) different drugs, and 42.6% smoked free-base cocaine. Unexpectedly, heroin and methamphetamine were consumed by 46.8% and 21.5% of participants, respectively. Among the 194 participants injecting drugs, 33% declared sharing their equipment. Conclusion This RDSS highlighted a high consumption of heroin, crack and methamphetamine in this PWUD population. These unexpected results can be explained by low attendance to addiction centers, the source of drug use reports. Despite free care and risk reduction equipment in the city, sharing was very frequent among injectors, challenging the current program of harm reduction.

Summary: Climate change has adversely affected maize productivity. Thereby, a holistic understanding of metabolic crosstalk among its organs is important to address this issue. Thus, we reconstructed the first multi-organ maize metabolic model, iZMA6517, and contextualized it with heat and cold stress transcriptomics data using expression distributed reaction flux measurement (EXTREAM) algorithm. Furthermore, implementing metabolic bottleneck analysis on contextualized models revealed differences between these stresses. While both stresses had reducing power bottlenecks, heat stress had additional energy generation bottlenecks. We also performed thermodynamic driving force analysis, revealing thermodynamics-reducing power-energy generation axis dictating the nature of temperature stress responses. Thus, a temperature-tolerant maize ideotype can be engineered by leveraging the proposed thermodynamics-reducing power-energy generation axis. We experimentally inoculated maize root with a beneficial mycorrhizal fungus, Rhizophagus irregularis, and as a proof-of-concept demonstrated its efficacy in alleviating temperature stress. Overall, this study will guide the engineering effort of temperature stress-tolerant maize ideotypes.

Abstract Over the past 2 years, SARS-CoV-2 infection has resulted in numerous hospitalizations and deaths worldwide. As young intensivists, we have been at the forefront of the fight against the COVID-19 pandemic and it has been an intense learning experience affecting all aspects of our specialty. Critical care was put forward as a priority and managed to adapt to the influx of patients and the growing demand for beds, financial and material resources, thereby highlighting its flexibility and central role in the healthcare system. Intensivists assumed an essential and unprecedented role in public life, which was important when claiming for indispensable material and human investments. Physicians and researchers around the world worked hand-in-hand to advance research and better manage this disease by integrating a rapidly growing body of evidence into guidelines. Our daily ethical practices and communication with families were challenged by the massive influx of patients and restricted visitation policies, forcing us to improve our collaboration with other specialties and innovate with new communication channels. However, the picture was not all bright, and some of these achievements are already fading over time despite the ongoing pandemic and hospital crisis. In addition, the pandemic has demonstrated the need to improve the working conditions and well-being of critical care workers to cope with the current shortage of human resources. Despite the gloomy atmosphere, we remain optimistic. In this ten-key points review, we outline our vision on how to capitalize on the lasting impact of the pandemic to face future challenges and foster transformative changes of critical care for the better.

Introduction Delirium is a severe complication that is associated with short-term adverse events, prolonged hospital stay and neurological sequelae in survivors. Automated pupillometry is an easy-to-use device that allows for accurate objective assessment of the pupillary light responses in comatose patients in the intensive care unit (ICU). Whether automated pupillometry might predict delirium in critically ill patients is not known. We hypothesise that automated pupillometry could predict the occurrence of delirium in critically ill patients without primary brain injury, requiring more than 48 hours of invasive mechanical ventilation in the ICU.Methods and analysis The PupillOmetry for preDIction of DeliriUM in ICU (PODIUM) study is a prospective cohort study, which will be conducted in eight French ICUs in the Paris area. We aim to recruit 213 adult patients requiring invasive mechanical ventilation for more than 48 hours. Automated pupillometry (Neurological Pupil Index; NPi-200, Neuroptics) will be assessed two times per day for 7 days. Delirium will be assessed using the Confusion Assessment Method in ICU two times per day over 14 days in non-comatose patients (Richmond Agitation and Sedation Scale ≥−3).The predictive performances of the seven automated pupillometry parameters (ie, pupillary diameter, variation of the pupillary diameter, pupillary constriction speed, pupillary dilatation speed, photomotor reflex latency, NPi and symmetry of pupillary responses) measured to detect the delirium occurrence within 14 days will be the main outcomes. Secondary outcomes will be the predictive performances of the seven automated pupillometry parameters to detect complications related to delirium, ICU length of stay, mortality, functional and cognitive outcomes at 90 days.Ethics and dissemination The PODIUM study has been approved by an independent ethics committee, the Comité de Protection des Personnes (CPP) OUEST IV—NANTES (CPP21.02.15.45239 32/21_3) on 06 April 2021). Participant recruitment started on 15 April 2022. Results will be published in international peer-reviewed medical journals and presented at conferences.Trial registration number NCT05248035; clinicaltrials.gov.

IntroductionCognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made of Ambra grisea, Anamirta cocculus L., Conium maculatum, and Petroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04’s biological activity.MethodsIn the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neurons in vitro and mRNA expression of synaptophysin in the hippocampus.ResultsAdministration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experiments in vitro showed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain.DiscussionOur findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.

We introduce the Kendall multivariate quantiles, which are a transformation of orthant quantiles by the Kendall function. Each quantile is then a set of vectors with some advantageous properties, compared to the standard orthant quantile: i/ it in[1]duces a total order, ii/ the probability level of the quantile is consistent with the probability measure of the set of the dominated vectors, iii/ the multivariate quantiles based on the distribution function or on the survival function have vectors in common which conciliate both upper- and lower-orthant approaches. Definition and properties of the Kendall multivariate quantiles are illustrated using Archimedean copulas.

The humoral response is frequently dysfunctioning in autoimmunity with a frequent rise in total serum immunoglobulins, among which are found autoantibodies that may be pathogenic by themselves and/or propagate the inflammatory reaction. The infiltration of autoimmune tissues by antibody-secreting cells (ASCs) constitutes another dysfunction. The known high dependency of ASCs on the microenvironment to survive combined to the high diversity of infiltrated tissues implies that ASCs must adapt. Some tissues even within a single clinical autoimmune entity are devoid of infiltration. The latter means that either the tissue is not permissive or ASCs fail to adapt. The origin of infiltrated ASCs is also variable. Indeed, ASCs may be commonly generated in the secondary lymphoid organ draining the autoimmune tissue, and home at the inflammation site under the guidance of specific chemokines. Alternatively, ASCs may be generated locally, when ectopic germinal centers are formed in the autoimmune tissue. Alloimmune tissues with the example of kidney transplantation will also be discussed own to their high similarity with autoimmune tissues. It should also be noted that antibody production is not the only function of ASCs, since cells with regulatory functions have also been described. This article will review all the phenotypic variations indicative of tissue adaptation described so for at the level of ASC-infiltrating auto/alloimmune tissues. The aim is to potentially define tissue-specific molecular targets in ASCs to improve the specificity of future autoimmune treatments.

This study aims to detect the impact of preexfoliation corrosion on the efficiency of 2 mm thick 2024-T3 aluminum alloy friction stir spot welded (FSSW) joints. Five specimens of FSSW joints, welded with 620 r·min−1 rotational speed and a dwell time of 10 seconds, were immersed in an exfoliation corrosion solution for five different times: 10 h, 20 h, 30 h, 40 h, and 50 h. The tensile shear load for the noncorroded joint was 3.5 kN. The results showed that the degradation of mechanical properties increased with increasing exposure time, and the joint efficiency drop reached 62% for specimens exposed for 50 h to the corroded solution. As welded FSSW 2024-T3 AA joints exhibited a nugget debonding failure mode and a mixed-mode tensile-shear fracture, in the corroded specimens, only a shear fracture could be seen. The results were attributed to a reduction in the bonding area between the upper and lower sheets due to corrosion.

Abstract Background and Aim The efficacy and safety profiles of elbasvir–grazoprevir (EBR/GZR) has been established in more than 10 clinical trials. However, the characteristics of patients treated in routine clinical practice may differ. The present study was therefore designed to assess the real‐life effectiveness of EBR/GZR therapy in the general population and among subgroups with a high hepatitis C virus (HCV) prevalence in France. Methods The Zephyr study was designed as a French, multicentre, prospective, observational study on EBR/GZR use and effectiveness in current practice in chronic hepatitis C patients. These results are based on data regarding the adult patients who received at least one dose of EBR/GZR between December 2017 and June 2019 in 67 French hospitals and clinics. Results Overall, 478 patients were included. The Full Analysis Set corresponded to the 467 patients who met all the inclusion criteria and none of the exclusion criteria. Gender was balanced and the mean age was 55.7 ± 13.3 years. The patients were mainly treatment‐naive (89.5%) and infected with Genotype 1b (70.4%). Among the 75 patients with HCV Gt1a genotype, 56% had HCV RNA ≥ 800,000 IU/ml. F3–F4 fibrosis stage involved 24.2% of our population. Our subgroups were distributed among 110 migrants (23.6%), 58 (15.3%) using opioid agonist treatment, including people who inject drugs, 30 (6.8%) with chronic kidney disease Stages 3–5, 9 (1.9%) with an inherited blood disorder, and 4 (0.9%) coinfected with HIV. The remaining 269 (58.7%) were included in the general population subgroup. Overall, sustained virologic response 12 weeks after the end of treatment reached 98.0% and remained consistent among genotype, HCV RNA values, fibrosis stage, and the subgroup of interest. The rate of Alcohol Use Disorders Identification Test‐Consumption​​​ and Life Habit questionnaire completion was high at each visit, with data suggesting alcohol consumption decrease and an improvement in quality of life. Conclusions Using real‐world evidence data on a French population representative of HCV patients, we confirmed the results obtained during EBR/GZR development program.

Amiour et al. use a multi-year field trial evaluation and association mapping to determine if increased enzyme activity and native allelic variations at the GS1 loci in maize contribute to differences in grain yield. Overexpression of GS1 and polymorphisms in the corresponding loci were associated with kernel yield, indicating that GS1 expression can directly control kernel production and that GS1 has a potential lead in the production of high yielding maize hybrids depending on environmental conditions.

The agronomic potential of glutamate dehydrogenase 2 (GDH2) in maize kernel production was investigated by examining the impact of a mutation on the corresponding gene. Mu-insertion homozygous and heterozygous mutant lines lacking GDH2 activity were isolated and characterized at the biochemical, physiological and agronomic levels. In comparison to the wild type and to the homozygous ghd2 mutants, the heterozygous gdh2 mutant plants were characterized by a decrease in the root amino acid content, whereas in the leaves an increase of a number of phenolic compounds was observed. On average, a 30 to 40% increase in kernel yield was obtained only in the heterozygous gdh2 mutant lines when plants were grown in the field over two years. The importance of GDH2 in the control of plant productivity is discussed in relation to the physiological impact of the mutation on amino acid content, with primary carbon metabolism mostly occurring in the roots and secondary metabolism occurring in the leaves.

To meet the growing demand for fish in human nutrition, aquaculture is developing increasingly from marine fishery products (i.e. fish meal and fish oil). New environmentally sustainable protein and lipid resources are recommended for this sector and insects, particularly black soldier fly (BSF), Hermetia illucens (L. 1758), are considered as promising candidates for fish feed production. BSF larvae convert organic materials into high-valued protein and lipid, their nutritional composition is related to their diet and could therefore be manipulated. The key issue in fish nutrition will be the fatty acid composition of BSF larvae that are characterized by high saturated fatty acids (SFAs) level (>60%) with lack of essential polyunsaturated fatty acids. This study aimed to adjust the fatty acid profile of BSF larvae by manipulating their food on focusing on diet formulation with local oilseed cakes for essential ω3 fatty acid (ALA: α-linolenic acid, C18:3n3) enrichment. Selected populations (100 individuals/population) of 7 days old BSF larvae were reared on Chicken feed (CF) diets enriched with flax and rape cakes at six incorporation rates (10–20 − 40–60 − 80–100%), the CF was used as the control diet and all diets were tested in triplicate (n = 3). The first prepupae appeared from 15 rearing days on all diets with an average weight of 195 mg excepted for full oil cake diets showing longer prepupal collection time (7 days) and lower average weight (116 mg). Oil cakes incorporation shows an impact on the prepupae fatty acid profiles. The results show that progressive oil cakes diets incorporation decreased saturated fatty acids from 75.86 ± 0.34% to 56.10 ± 0.74%. Simultaneously, rape cake incorporation leads mainly to oleic acid (C18:1n-9) enrichment which not sought in fish nutrition and low ALA rate from 1.16 ± 0.25% to 2.42 ± 0.12% but Flax cake incorporation increase ALA enrichment up till 15.27 ± 0.02% favorable to fish needs allowing a potential increase BSF meal incorporation in fish feed. This research therefore presents a model of progressive prepupae oil enrichment from oilseed coproducts for application in fish feed.

As one of the top countries with the highest casualties per capita in road traffic accidents, Thailand needs to raise public awareness about the economic loss from road traffic crashes. This paper calculates the value of productivity loss due to road traffic accidents in Thailand in 2017. Extensive data collection and analyses enable to compute income losses over time in case of fatalities, permanent disabilities as well as major and minor injuries. The results reveal that, at the end of 2017, the total amount of productivity loss caused by road traffic accidents alone was approximately 121 billion Baht (45 billions for fatalities, 7 for disabilities, 67.5 for serious injuries and 1.5 for slight injuries), or close to 0.8% of the country's GDP, which is very significant. At-risk age groups are determined in each case and we see that the 16–25 age group is bearing the highest burden in all types of accidents. Future policies can then be targeted to types of casualties and to a specific public.

Nitrogen (N) is one of the most limiting nutrients for cereal production, especially in wheat, which is one of the main crops cultivated globally. To achieve high yields, wheat requires a certain amount of nitrogen (N), as N deficiency can lead to a decrease in yield and thus reduce income for farmers. In contrast, excessive applications of N fertilizer can be detrimental to both terrestrial and aquatic environments. To optimize N fertilizer applications in wheat, a three-year field experiment was conducted to evaluate the impact of different N fertilization strategies on various N-related physiological and agronomic traits. Moreover, to optimize N utilization efficiency while maintaining crop productivity, a mixture of five winter wheat varieties was used to mitigate the possible impact of environmental constraints. These strategies were based on a simultaneous increase in N fertilization and N fertilizer fractionation at key stages of plant development in a soil conservation agriculture (SCA) system in which legumes were grown prior to the cultivation of the main crop. In this SCA system, we observed that 200 kgN·ha−1 was optimal for both N use efficiency (NUE) and aerial and grain biomass production. Moreover, we found that at this level of N fertilization, of the application strategies, a 40%/40%/20% split application at full tillering, at the first node, and at booting, respectively, appeared to be the best option for the highest plant productivity.

Abstract Background Household air pollution (HAP) is a recognised risk factor for many diseases, including respiratory diseases, cardiovascular/circulatory disorders, adverse pregnancy outcomes and cataracts. Population exposure to biomass fuels, including wood, varies among countries and from one fuel source to the other. This study aimed to investigate the different sources of HAP in peri-urban and rural communities in Cameroon. Methods A cross-sectional survey was conducted in a representative sample of households from the Dschang Health District (DHD) region. This included 848 homes in which a range of fuels for cooking including biomass (firewood, charcoal, sawdust), kerosene and liquefied petroleum gas (LPG) were used both indoors and outdoors. Results Of the study households, 651 (77%) reported exclusive use of firewood and 141 (17%) reported using more than one source of fuel. Exclusive use of firewood was greater in rural communities (94%) than in peri-urban communities (38%). In peri-urban communities, use of multiple fuels including LPG, wood, sawdust and kerosene, was more common (44.75%). A total of 25.03% of households in both peri-urban and rural communities reported using bottled gas (or liquified petroleum gas (LPG) for cooking. Motivations for choice of fuel included, affordability, availability, rapidity, and cultural factors. Conclusion Wood is the main cooking fuel in both peri-urban and rural communities in the Dschang Health District. Supporting households (especially those with limited resources) to adopt LPG equipment for cooking, and use in a more exclusive way is required to help reduce household air pollution.

Abstract Background Neuroinflammation has been implicated in the pathogenesis of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease association with exposure to repetitive head impacts (RHI) received though playing contact sports such as American football. Past work has implicated early and sustained activation of microglia as a potential driver of tau pathology within the frontal cortex in CTE. However, the RHI induced signals required to recruit microglia to areas of damage and pathology are unknown. Methods Postmortem brain tissue was obtained from 261 individuals across multiple brain banks. Comparisons were made using cases with CTE, cases with Alzheimer’s disease (AD), and cases with no neurodegenerative disease and lacked exposure to RHI (controls). Recruitment of Iba1+ cells around the CTE perivascular lesion was compared to non-lesion vessels. TMEM119 staining was used to characterize microglia or macrophage involvement. The potent chemoattractant CCL2 was analyzed using frozen tissue from the dorsolateral frontal cortex (DLFC) and the calcarine cortex. Finally, the amounts of hyperphosphorylated tau (pTau) and Aβ42 were compared to CCL2 levels to examine possible mechanistic pathways. Results An increase in Iba1+ cells was found around blood vessels with perivascular tau pathology compared to non-affected vessels in individuals with RHI. TMEM119 staining revealed the majority of the Iba1+ cells were microglia. CCL2 protein levels in the DLFC were found to correlate with greater years of playing American football, the density of Iba1+ cells, the density of CD68+ cells, and increased CTE severity. When comparing across multiple brain regions, CCL2 increases were more pronounced in the DLFC than the calcarine cortex in cases with RHI but not in AD. When examining the individual contribution of pathogenic proteins to CCL2 changes, pTau correlated with CCL2, independent of age at death and Aβ42 in AD and CTE. Although levels of Aβ42 were not correlated with CCL2 in cases with CTE, in males in the AD group, Aβ42 trended toward an inverse relationship with CCL2 suggesting possible gender associations. Conclusion Overall, CCL2 is implicated in the pathways recruiting microglia and the development of pTau pathology after exposure to RHI, and may represent a future therapeutic target in CTE.

Chronic Obstructive Pulmonary Disease (COPD) is a highly prevalent and debilitating respiratory condition, characterized by chronic airflow limitation, breathlessness, and other persistent respiratory symptoms. Critically, patients suffering from COPD often find themselves trapped in a vicious comorbidity cycle: while breathlessness and increased respiratory rate are known inducers of anxiety, the latter have been shown in turn to exacerbate breathlessness and chest discomfort. Hypnosis holds great potential for the simultaneous complementary management of anxiety and breathlessness in COPD. It is an inexpensive psychological intervention tailored to the patient’s own experience, convenient in terms of logistics and implementation. In this short qualitative review, we present hypnosis’ structural, cognitive, and neural fundamentals, and assess existing instances of hypnosis use in the treatment of anxiety, depression, and respiratory disease. We then discuss its potential as a tool for improving health-related quality of life and the self-management of COPD within (and beyond) pulmonary rehabilitation.

Abstract Long-range cortico-cortical functional connectivity has long been theorized to be necessary for conscious states. In the present work, we estimate long-range cortical connectivity in a series of intracranial and scalp EEG recordings experiments. In the two first experiments intracranial-EEG (iEEG) was recorded during four distinct states within the same individuals: conscious wakefulness (CW), rapid-eye-movement sleep (REM), stable periods of slow-wave sleep (SWS) and deep propofol anaesthesia (PA). We estimated functional connectivity using the following two methods: weighted Symbolic-Mutual-Information (wSMI) and phase-locked value (PLV). Our results showed that long-range functional connectivity in the delta-theta frequency band specifically discriminated CW and REM from SWS and PA. In the third experiment, we generalized this original finding on a large cohort of brain-injured patients. FC in the delta-theta band was significantly higher in patients being in a minimally conscious state (MCS) than in those being in a vegetative state (or unresponsive wakefulness syndrome). Taken together the present results suggest that FC of cortical activity in this slow frequency band is a new and robust signature of conscious states.