Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. The main risks considered in this study are infections by West Nile virus, dengue virus and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of Public Health, which is responsible for issuing guidelines to mitigate the risks associated with products of human origin and for supporting public health policy decisions, are briefly outlined. The aim of this review is also to contribute to the standardization of recommendations at international level in areas with the same viral epidemiology.

Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease, for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKIs became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40-60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon re-treatment, indicating TKI discontinuation is safe. However, there is still a gap in the understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it ex-amines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, defined by progressive deterioration of the peripheral nerves. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility. This suggests that trafficking defects may be a common underlying mechanism in CMT. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the challenges and opportunities to this “impaired mobility” model of the disease.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies constitute the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments remain elusive. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and results in a lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are currently under clinical and preclinical investigation, and a broad array of therapeutic agents and their corresponding mechanisms have been discussed in this review. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, has been appraised. Each of these gene therapies has the potential for substantial advancements in future research.

Most police Mental Health Act (Section 136) detentions in England and Wales relate to suicide prevention. Despite attempts to reduce detention rates, numbers have risen almost continually. Although Section 136 has been subject to much academic and public policy scrutiny, the topic of individuals being detained on multiple occasions remains under-researched and thus poorly understood. A mixed methods study combined six in-depth interviews with people who had experienced numerous suicidal crises and police intervention, with detailed police and mental health records. A national police survey provided wider context. Consultants with lived experience of complex mental health problems jointly analysed interviews. Repeated detention is a nationally recognised issue. In South East England it almost exclusively relates to suicide or self-harm and accounts for a third of all detentions. Females are detained with the highest frequencies. The qualitative accounts revealed complex histories of unresolved trauma that had catastrophically damaged interviewee’s relational foundations, rendering them disenfranchised from services and consigned to relying on police intervention in repeated suicidal crises. A model is proposed that offers a way to conceptualise the phenomenon of repeated detention, highlighting that long-term solutions to sustain change are imperative, as reactive-only responses can perpetuate crisis cycles.

In recent years, it has become common for individuals to juggle employment and unpaid care work. This is just as true for the England-based academic workforce, our focus in this article. We discuss how, in the context of English HE, support for carers is enacted and negotiated through policies and practices of care. Our focus on academics with a diverse range of caring responsibilities is unusual insofar as the literature on care in academia is overwhelmingly concerned with parents, usually mothers. The article is informed primarily by critical and post-structuralist feminist perspectives. We draw on a corpus of 47 interviews conducted with academics representing a broad range of caring responsibilities, subjects, and positions. A thematic analysis reveals how carers’ relationship with the provision and policies of care support at institutional level is characterised by ambiguity. On the one hand, participants approve of societal and institutional policy support for carers. On the other hand, they are often reluctant to position themselves as the beneficiary of such policies, expressing instead a general preference for support from outside the workplace or for workplace-based inter-individual and informal care arrangements. This resistance is particularly noticeable in the case of participants with caring responsibilities other than the parenting of healthy, able-bodied children and of those whose gender, class, racial, or sexual identity do not conform with the figure of the ‘ideal academic’, contributing to their othering in the academic realm. These findings have significant implications for policies supporting carers, pointing to the need for greater visibility and recognition of caring responsibilities in academia, especially in terms of their diverse identities.

The expression "Follow the water" is used in order to recognize inside the universe, life as it exists on Earth. It is shown here that the expression "Follow the water in its high-subcritical state" can be used in order to recognize the components of life which form prior to the emergence of life. This specific state of water leaves signatures inside the minerals which are produced during high-subcritical water/rock interaction.

Regeneration is crucial for forest continuity in natural and managed stands. Analyzing intra-annual dynamics improves the understanding between growth and climate, identifying survival thresholds. The objective was to determine microclimate constraints (rainfall, air and soil temperatures) over Nothofagus antarctica regeneration growing at closed, open, and edge forests in Patagonia. We measured stand characteristics (forest structure, understory, soil properties, animal use), microclimate, and daily growth of regeneration using dendrometers (n = 6) during two growing seasons. We found significant differences in the studied variables (e.g. overstory, light, soil, understory, animal use). These changes defined microclimate across overstory gradient (e.g. soil moisture), influencing the daily growth across seasons (lag, exponential, stationary). Rainfall influenced more than temperature. Daily growth in closed forests indicating shrinkage (-0.0082 mm day-1 without rain, and -0.0008 mm day-1 with 0.0-0.2 mm day-1 rainfall), while above 0.2 mm day-1 rainfall, growth always increased. Open forests presented shrinkage during days without rain (-0.0051 mm day-1), showing positive growths according rainfall. Edge forests always presented positive daily growths. The resilience of regeneration under these changed conditions was related with overstory. Main outputs indicated that regeneration was vulnerable during non-rainy days, suggesting the needs of long-term monitoring to develop better silvicultural proposals.

The purpose of this study is to characterize atmospheric pollution and its sources in two West African urban sites during the dry season (January 2009 in Bamako, Mali, and December 2009 in Dakar, Senegal). Particulate Matter (PM) source apportionment was performed using Principal Component Analysis (PCA) and Positive Matrix Factorization (PMF). Carbonaceous components, water-soluble inorganic compounds, and trace elements were analyzed from PM (TSP, PM10, and PM2.5) samples. The measured PM2.5 and PM10 concentrations were 5 to 10 times and 3 to 8 times higher than the 2005 WHO 24-hour standards, respectively. PCA and PMF analyses identify five sources in both cities. The sources contributing to aerosol concentrations (PM2.5 - PM10) in Bamako are motor vehicles (20-13%), solid fuel combustion (16-13%), crustal dust (24-30%), resuspended road dust (26-30%) and secondary aerosols (10-16%). During the sampling period in Bamako, dust was the most prevalent source, accounting for 63% of the total PM10 mass. In Dakar, the main identified sources were motor vehicles (28-19%), mineral dust (16-25%), industries and oil burn-ing (11-10%), sea salts (15-20%), and resuspended road particles (21-29%). The findings also indicate that anthropogenic emissions contribute significantly to the PM2.5 fraction, implying that populations are highly exposed to fine particles.

Anthropomorphism is a natural tendency in humans, but it is also influenced by many characteristics of the observer (the human) and the observed entity (here, the animal species). This study asked participants to complete an online questionnaire about three videos showing epimeletic behaviours in three animal species. In the videos, an individual (a sparrow, an elephant and a macaque, respectively) displayed behaviours towards an inanimate conspecific that suddenly regained consciousness at the end of the footage. A fourth video showed a robot dog being kicked by an engineer to demonstrate its stability. Each video was followed by a series of questions designed to evaluate the degree of anthropomorphism of participants, from mentaphobia (no attribution of intentions and beliefs, whatever the animal species) to full anthropomorphism (full attribution of intentions and beliefs by animals, to the same extent as in humans) and to measure how far the participants had correctly assessed each situation in terms of biological reality (current scientific knowledge of each species). There is a negative correlation (about 61%) between the mental states attributed to animals by humans to animals and the real capability of animals. The heterogeneity of responses proved that humans display different forms of anthropomorphism, from rejecting all emotional or intentional states in animals to considering animals to show the same intentions as humans. However, the scores participants attributed to animals differed according to the species shown in the video and to human sociodemographic characteristics. Understanding the potential usefulness of these factors can lead to better relationships with animals and encourage a positive view of human-robot interactions. Indeed, reflective or critical anthropomorphism can increase our humanity.

In this study, we asked participants to answer an online questionnaire about videos showing animal epimeletic behaviours: an individual (a sparrow, an elephant and a macaque) displayed behaviours towards an inanimate conspecific who suddenly got back to conscious at the end of the footage. A fourth video showed a dog-robot kicked by an engineer to demonstrate its stability. After each video, questions were asked to score the degree of anthropomorphism of participants, from mentophobia (no attribution whatever the species) to full anthropomorphism and to measure how close participants are to biological reality (actual scientific knowledge). A first important result is that there is a negative correlation (about 61%) between the anthropomorphism score (AS) and the biological reality one (BRS) showing a wrong statement. The heterogeneity of responses proved that all levels of anthropomorphism are covered from mentaphobia to full anthropomorphism. However, the scores participants attributed to animals differ according to the species shown in the video and to human characteristics. Understanding how one can play with these factors can conduct to better relationships with animals as encourage human-robot interactions. Finally, such reflective anthropomorphism can lead to an increase of human empathy and sociality, finally increasing our humanity.

The global burden of antimicrobial resistance is on the rise, resulting in higher morbidity and mortality in our communities. The spread of antimicrobial resistance in the environment and development of resistant microbes is a challenge to the control of antimicrobial resistance. Approaches, such as antimicrobial stewardship programmes, and enhanced surveillance, have been devised to curb its spread. However, particularly in lower- and middle-income countries, the overall extent of antimicrobial resistance, and knowledge on on-going surveillance, stewardship or investigation efforts, re often poorly understood. This study aimed to look at the efforts that have been undertaken to combat antimicrobial resistance in Uganda as a means of establishing an overview of the situation, to help inform future decisions. We conducted a systematic literature review of the PubMed database to assess the efforts that have been done in Uganda to investigate and combat antimicrobial resistance. A search combining keywords associated with antimicrobial resistance were used to look up relevant studies between 1995 and 2020 on surveillance of antimicrobial resistance in Uganda, and susceptibility of microbes to different drugs. The search yielded 430 records, 163 of which met the inclusion criteria for analysis. The studies were categorized according to country and region, the type of antimicrobial resistance, context of the study, study design and outcome of the study. Antibacterial resistance and antimalarial resistance had the most published studies while antiviral and antifungal resistance each were represented by very few studies. Most studies were conducted in humans and hospital settings, with very few in veterinary and One Health contexts. The results from our work can inform public health policy on antimicrobial stewardship as it contributes to understanding the status of antimicrobial resistance surveillance in Uganda, and can also help to guide future research efforts. Notably, a One Health approach needs to be followed with re-spect to surveillance of antimicrobial resistance to better understand the mechanisms of resistance transfer across the human-animal–environment interface, including additional investigation in antiviral and antifungal resistance.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

Introduction: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders routinely screened for. Referenced publications insist on the importance of adequate screening but the proper course of action has yet to be defined. Aim of study: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. Material and methods: We led a semi structured interview with professionals included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient’s initial demand or lack thereof and the baby’s importance within, mindful of mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. Conclusion: HCPs need to enable patients’ trust on a personal and an institutional level. As well as empowering the patient in the moment and respecting their values and choices, HCPs also convey the stability of the institution that has to become a reference of refuge and assistance for patients from their pregnancy onwards.

Concrete is the most utilized construction material worldwide. In the marine environment, it is subject to chemical degradation through reactions with chloride (the most important ion), sulfate and magnesium ions in seawater and to biodeterioration resulting from biological (initially microbiological) activities, principally acid production. These two types of corrosion are reviewed and the failure of attempts to predict the degree of deterioration resulting from each is noted. Chemical (abiotic) corrosion is greatest in the splash zone of coastal constructions, while phenomenological evidence suggests that biodeterioration is greatest in tidal zones. There have been no comparative experiments to determine the rates and types of microbial biofilm formation in these zones. Both chemical and microbiological concrete deterioration are complex and have not been successfully modeled. The interaction between abiotic corrosion and biofilm formation is considered. EPS can maintain surface hydration, potentially reducing abiotic corrosion. The early marine biofilm contains relatively specific bacterial colonizers, including cyanobacteria and proteobacteria; these change over time, producing a generic concrete biofilm, but adhesion of microorganisms to concrete in the oceans is little investigated. The colonization of artificial reefs is briefly discussed. Concrete appears to be a relatively prescriptive substrate, with modifications necessary to increase colonization for the required goal of increasing biological diversity.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

Wearable antennas are increasingly vital in modern healthcare, facilitating continuous monitoring and communication for medical purposes. These antennas are integrated into wearable devices, allowing for the transmission and reception of vital health data, such as heart rate, body temperature, and blood pressure, to medical professionals or monitoring systems in real time. This instantaneous data transmission enables timely interventions, thus improving the quality of healthcare services. This review aims to comprehensively synthesize recent research from reputable databases, focusing on the functionality and effectiveness of wearable antennas in medical applications. The primary objectives of each study were categorized, including antenna design and integration, the performance of medical wearable antenna technology, safety considerations in wearable antenna biomedicine, and the use of antennas in clinical applications and their impact. This synthesis provides valuable insights for researchers and practitioners aiming to develop and deploy wearable antennas in medical settings, ultimately enhancing healthcare delivery and patient outcomes.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

Although research has long established that the interaction with the natural environment is associated with better overall health and well-being outcomes, the Western model mainly focuses on treating the symptoms. In Aotearoa-New Zealand, the Indigenous Māori have long demonstrated significantly more negative health outcomes than non-Māori. Little research has examined the causes compared to Western populations or the role of the natural environment in health outcomes for Māori. An exploration of rongoā Māori (traditional healing system) was conducted to ascertain the importance of landscape in the process of healing. Eight rongoā healers or practitioners took part in semi-structured narrative interviews from June to November 2020. Transcribed interviews were analysed using an interpretative phenomenological analysis and Kaupapa Māori techniques. The findings show how rongoā is underpinned by a complex set of cultural values and beliefs, drawing from the connection to wairua (spirit), tinana (body), tikanga and whakaora (customs and healing), rākau (plants), whenua (landscape) and whānau (family). Incorporating such constructs into the landscape can foster our understanding of health and well-being and its implications for conceptualising therapeutic environments and a culturally appropriate model of care for Māori and non-Māori communities.

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity. As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was done in four patients, and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Leptospirosis is a worldwide zoonotic disease, most common in tropical and rural settings. It's a public health problem in most of the French tropical overseas territories. The primary objective of this study was to describe severe forms of leptospirosis admitted to the intensive care unit (ICU) on Mayotte, a French island in the Indian Ocean. The secondary objective was to compare the characteristics of these patients with those admitted to the ICU in other French tropical territories and in mainland France. We conducted a retrospective study among adult patients admitted to the ICU of Mayotte hospital between 2009 and 2017. The diagnosis mainly relied on a positive PCR in blood or urine samples. The results were compared to the similar and available studies carried out in mainland France and in the other French tropical overseas territories. On the study period, 55 patients were admitted in the ICU for leptospirosis (18% of the leptospirosis admitted in the hospital). Among them, 45 (82%) were male and the median age was 44 years (25-75 IQR: 33-55). The median time between first symptoms and ICU admission was 3.5 days (2-5). The median duration for antibiotic treatment, hospital stay, and ICU stay were 7 days (7-8), 9 days (6-13) and 5 days (3-9) respectively. The main acute organ impairments were acute renal failure (87%), followed by circulatory failure (58%), acute liver failure (45%) and neurological failure (22%). The most frequently used supportive cares were: vaso-active drugs (56%) and renal replacement (56%), and mechanical ventilation (27%). The case-fatality rate was low (5%). Genotype identification could be performed on 19 patients’ isolates. The strain L. borgpetersenii serogroup Mini cgMLST CG78 was predominant (n=14), followed by L. interrogans serogroup Pyrogenes cgMLST CG 81 (n=4). No L. interrogans serogroup Icterohemorrhagiae was identified. We publish here the first series of severe patients admitted in the ICU in Mayotte, a French island with a high incidence rate of leptospirosis but with original strain specificities. Despite very severe clinical pictures, mortality remains rather low.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change.

Abstract: This comprehensive review seeks to deepen our comprehension of the African plant Momordica balsamina L. by elucidating its therapeutically important molecules and micronutrient composition. Commonly referred to as the balsam apple, this plant species is extensively harnessed for its diverse therapeutic potentials across its various organs including leaves, fruits, roots, and stems. Numerous bioactive molecules have been isolated or identified within this plant, notably encompassing polyphenols, flavonoids, terpenes, and carotenoids. These compounds exhibit a wide array of biological activities, ranging from antioxidative, anti-inflammatory, anti-diabetic, anti-carcinogenic, to anti-malarial properties, among others. Furthermore, the leaves of Momordica balsamina L. stand out for their abundant micronutrients, proteins, and amino acids. This investigation aims to shed light not only on the botanical characteristics of the Momordica balsamina plant and its potential applications in traditional medicine, but also on its chemical composition, biological functionalities, and physicochemical attributes, thus accentuating its nutritional advantages. Nonetheless, an intriguing avenue presents itself for the exploration of strategies to conserve this species, delve deeper into its potential within the cosmetics industry, and innovate methodologies for the synthesis or biosynthesis of these bioactive molecules.

State legitimacy and effectiveness could be seen by the way to deliver welfare to citizens to mitigate social grievances, that could eventually lead to conflicts (Kivimäki, 2021). Social security systems in Maghreb countries are quite similar in their architecture and aims to provide social insurance to all the workers in the labor market. However, they suffer from the same main problem: the low rate of enrollment of workers. Many workers (employees and self-employed) work informally without any social security coverage. The issue of whether informal jobs are chosen voluntarily by workers or as a strategy of last resort is controversial. Many authors recognize that the informal sector is heterogeneous and it is made up of workers who voluntary choose it and others who are pushed inside because of entry barriers to the formal sector (Günther & Launov, 2012). Using the SAHWA survey and discrete choice models, this article confirms the heterogeneity of the informal labor market in three Maghreb countries: Algeria, Morocco, and Tunisia. Furthermore, this article highlights the profiles of workers who voluntarily choose informality, which is missing from previous studies. Finally, this article proposes policy recommendations in order to extend social security to informal workers and to include them in the formal labour market.

Understanding molecular mechanisms of neurological disorders is required for development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, the treatments tailored for individual patients may be suggested. The vitamins-responsive neurological disorders are induced by deficiencies in the vitamin-dependent processes. The deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot-Marie-Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5’-phosphate, PLP). Alleviation of such disorders by administration of the lacking vitamin or its derivative calls upon a better introduction of the mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease, compared to the control subjects, are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting therapeutic potential of vitamin B3. Thus, improved diagnostics of the underlying causes of the CMT disease may allow the patients with the vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives or pharmacological forms.

Muscle mass, strength and physical function are known to decline with age. This is associated with the development of geriatric syndromes including sarcopenia and frailty. These conditions are associated with disability, falls, longer hospital stay, higher readmission rates, institutionalisation, osteoporosis, and death. Moreover, they are associated with reduced quality of life, as well as substantial costs to health services around the world. Dietary protein is essential for skeletal muscle function. Older adults have shown evidence of anabolic resistance, where greater amounts of protein are required to stimulate muscle protein synthesis and therefore require higher daily amounts of dietary protein. Research shows that resistance exercise has the most beneficial effect on preserving skeletal muscle. A synergistic effect has been noted when this is combined with dietary protein, yet studies in this area lack consistency. This is due, in part, to the variation that exists within dietary protein, in terms of dose, quality, source, amino acid composition and timing. Research has targeted participants that are replete in dietary protein with negative results. Inconsistent measures of muscle mass, muscle function, physical activity and diet are used. This review attempts to summarise these issues, as well as introduce the possible role of the gut microbiome and its metabolome in this area.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

Heparins, Unfractionated or Low Molecular Weight, are permanently at the spotlight of both clinical indications and laboratory monitoring. An accurate drug dosage is necessary for an effi-cient and safe therapy. The one-stage anti-FXa kinetics’ assays are the most widely and universally used with full automation for large series, without needing exogenous Antithrombin. WHO in-ternational standards are available for UFH and LMWH, but external quality assessment surveys still report a high inter-assay variability. This heterogeneity results from: assay formulation, designed without or with dextran sulfate to measure all heparin in blood circulation; calibrators for testing UFH or LMWH with the same curve; and automation parameters. The various factors which impact heparin measurements are reviewed, and we share our experience to optimize assays for completely testing plasma heparin. Evidence is provided on the usefulness of low molecular weight dextran sulfate to mobilize all drug present in blood circulation. Other key factors concern adjustment of assay conditions to obtain fully superimposable calibration curves for UFH and LMWH, and automation parameters. The study is illustrated by the performances of the various anti-FXa assays used for testing heparin on UFH or LMWH treated patients’ plasmas and obtained using citrate or CTAD anticoagulants. Comparable results are obtained only when CTAD anti-coagulant is used. Using citrate UFH is underestimated in the absence of dextran sulfate. Heparin calibrators, adjustment of automation parameters and data treatment contribute to other smaller differences.

We report the treatment of a 21-year-old female Covid-19 patient by a novel combination of minocycline and a guanosine-restricted diet. Minocycline is an antibiotic with well documented broad spectrum anti-viral effects, including evidence of activity against SARS-CoV-2. Deprivation of guanosine has been documented as an effective anti-viral modality in vitro and in animal models, and specific in vitro activity against CoV-SARS-2 has been reported. The patient's symptoms resolved rapidly.

The German Constitutional Court’s climate verdict provides a re-interpretation of liberal- democratic core concepts and is highly relevant for liberal constitutional law in general – including EU and international law. The verdict accepts human rights as intertemporal and globally applicable; it applies the precautionary principle to these rights and frees them from the misleading causality debate. However, the court fails to address the most important violations of human rights, and it categorised climate policy as a greater threat to freedom than climate change. And the court does not make it clear that the Paris 1.5-degree limit implies a radically smaller carbon budget. Furthermore, little attention has so far been paid to the fact that the ruling implies an obligation for more EU climate protection, especially since most emissions are regulated supranationally. To be effective, the EU emissions trading system demands a reform, which should go well beyond the existing EU proposals to enable societal transformation to sustainability.

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

The morphology and maturation process of gonads of 70 Burmeister´s porpoises, with body lengths ranging 135–183 cm (n= 34 females) and 64.5-182 cm (n= 36 males) were described. Samples were collected in six ports of central and northern Peru in 1987-1999. In the field, females were classified as immature, mature (resting, lactating, pregnant) and males as immature, pubescent and mature based on, respectively, the presence of ovarian corpora and the relative quantity of semen in cut epididymides. The ovaries of P. spinipinnis are ovoid or bean-shaped and flattened, with corpora modifying surface appearance. In the laboratory, ovaries were examined macro- and microscopically, measured, weighed and sliced in 1-3 mm sections. The number of corpora ovarica (lutea, albicantia, atretica) found in each ovary as well as their macroscopic and microscopic characteristics were documented in some detail. The follicles, their oocytes and nucleus were measured. Follicular development in P. spinipinnis is predominantly left-sided, but occurs in both ovaries in 16.3% of females, mainly in those with numerous corpora. Macroscopically, several corpora atretica with luteinization had characteristics similar to those of corpora albicantia, making microscopic determination essential. Inconclusive evidence of recent ovulation was found in January. Two of three immature females showed good follicular development in March and April. The body length at 50% sexual maturity in females was estimated at 152.7 cm. There was no evidence of reproductive senescence. The testes of P. spinipinnis are elongated and cylindrical. Of the 36 males examined macroscopically, 7 were immature, 5 pubescent and 24 mature. The histological analysis determining the presence and abundance of Sertoli cells, spermatogonia, spermatocytes, spermatids and spermatozoa, the relative amount of interstitial tissue, the elongation and mean diameter of the seminiferous tubules and the relative size of the lumen allowed to confidently determine sexual maturity status. The field evaluation of maturity based on the presence of sperm in the epididymides is a useful but, in 8.3% of cases, not exact method. For males the body length at 50% sexual maturity was estimated at 157 cm. No histological evidence of male reproductive seasonality was found. Spermatogenesis was perceptible year-round and tubule diameters had non-specific variations for each month.

Eating disorders (EDs) are serious, life-threatening psychiatric conditions associated with physical and psychosocial impairments, as well as high morbidity and mortality. Given the chronic refractory nature of EDs and the paucity of evidence-based treatments, there is a pressing need to identify novel approaches for this population. The noncompetitive N-methyl-D-aspartate receptor (NMDAr) antagonist, ketamine, has recently been approved for treatment-resistant depression, exerting rapid and robust antidepressant effects. It is now being investigated for several new indications, including obsessive-compulsive, post-traumatic, and substance use disorder; and shows transdiagnostic potential for EDs, particularly among clinical non-responders. As such, the aim of this review is to examine contemporary findings on the treatment of EDs with ketamine, whether used as a primary, adjunctive, or combination psychopharmacotherapy. Avenues for future research are also discussed. Overall, results are encouraging and point to therapeutic value, yet are limited to case series and reports on anorexia nervosa. Further empirical work is thus needed to explore ketamine efficacy across ED subgroups; establish safety profiles and optimize dosing; and develop theory-driven, targeted treatment strategies at the individual patient level.

Chronic pain is a source of major alterations in quality of life. It represents significant costs for health systems, and reduces the competitiveness of the working population. Vulnerability can drive the incidence of chronic pain, through its influence on modifiable risk factors, and reduced utilization of health care systems. But vulnerability can also be the consequence of a chronic pain: illness can push people into precariousness. We analysed the factors associated with pain intensity among vulnerable persons with a chronic condition, in five European countries (N=1,364). Pain was, among the whole set of variables, the main predictor of sleep problems, fatigue, depression, self-perceived health, physical and mental quality of life. This is in line with other studies showing the major impact of pain on an individual’s health and life. Multivariable analyses, adjusting for the whole set of variables, showed that women had more intense pain, as well as participants with a lower education level. These results confirm the social component in the complex etiology of pain and clearly plaid in favor of integrated care, taking into account individual characteristics and environment.

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from ethyl acetate soluble fraction of Acacia auriculiformis stem bark. Column chromatography, gel filtration and NMR spectroscopy were used to purified and characterized betulin from the extract. Betulin which is a known inducer of apoptosis was screened against a panel of 16 disease-related protein kinases. Betulin was shown to inhibit Abelson murine leukemia viral oncogene homolog 1 (ABL1) kinase, casein kinase 1epsilon (CK1epsilon), glycogen synthase kinase 3alpha/β (GSK-3alpha/β), Janus kinase 3 (JAK3), NIMA Related Kinase 6 (NEK6) and vascular endothelial growth factor receptor 2 kinase (VEGFR2) and with activity in µM range. The effect of betulin on the cell viability of doxorubicin-resistant K562R chronic myelogenous leukemia cells was then verified to underline its putative use as anti-cancer compound. Betulin was shown to modulate the mitogen-activated protein (MAP) kinase pathway similarly to imatinib mesylate, a well-known inhibitor of ABL1 kinase. The interaction of betulin and ABL1 was studied by molecular docking showing an interaction of the inhibitor with the ATP binding pocket. Altogether, these data demonstrate that betulin is a multi-target inhibitor of protein kinases, an activity that can contribute to the anticancer properties of the natural compound and notably for treatment of leukemia.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

Pesticides have a vital contribution to the agricultural industry in Australia. However, pesticide applications may not always selective to its target organism. Exposure to pesticide has been associated with negative impacts to human health. One of the ways to reduce pesticide risk to the population and the environment is through government regulations. To put Australia pesticide regulations into perspective, comparisons were made between Australia and other nation’s pesticides regulations. The EU pesticide regulatory system was chosen for comparison with the Australian’s in the aspect of protecting the population from pesticide exposure. The comparison showed that the assessment to authorize a pesticide in Australia is based on the risk while in the EU, the assessment is based on the hazard of the pesticide. A registered active substance in Australia can be authorized for use indefinitely unless it is nominated for reconsideration while the period of registration of an active substance in the EU lasts for 10 years. In addition, no routine systematic chemical residue surveys are conducted in Australia for food commodities. The results highlight areas for improvement in the Australian pesticide regulatory system from the perspective of controlling undue exposure among the general population.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

Objective: In this pilot study, we described the gross motor development of infants aged 4 to 24 months with congenital heart disease (CHD) and assessed through a systematic develop­mental screening programme, with individualised motor interventions. Methods: Thirty infants who had cardiac repair underwent gross motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results: Based on AIMS, 80% of 4-month-old infants had a delay in gross motor development and required physical therapy. Gross motor abilities significantly improved by 24 months. Infants who benefited from regular physiotherapy tended to show better improvement in motor scores. Conclusion: Our study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in those at-risk. Further research is needed to assess the effectiveness of systematic developmental screening and individualized inter­vention programmes at identifying at risk patients, and their impact on developmental outcomes.

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

There has been a growing interest in incorporating psychological and neuroscientific knowledge about the development of cognitive functions in educational policies and academic practices. In this paper, we argue that the current knowledge about the interactions between these functions and their neurodevelopmental characteristics should also be considered in order to develop practices that could be better suited to pupils depending on their age. To facilitate this, we review current neuroscientific knowledge on the competitive interactions between two neural circuitry underlying distinct learning functions, their developmental trajectories and how they are linked to other functions such as cognitive control. The incorporation of this knowledge in education could help improve academic outcomes.

Our wellbeing is greatly influenced by our childhood and adolescence, and the relationships that we form during those phases of our development. The human-dog bond started thousands of years ago. The higher prevalence of dog ownership around the world, especially in households including children along with the growing number of people studying dogs most likely explain the growing literature focusing on child-dog interactions. We review the potential effects of child-dog interactions on the physical, mental, and social wellbeing of both species. A scoping search of the SCOPUS database found several hundred documents meeting selection criteria. It allowed us to define the numerous ways in which children and dogs can interact, be it neutral (e.g., sharing a common area), positive (e.g., petting), or negative (e.g., biting). Then, we found evidence for an association between interacting with dogs during childhood and an array of health and mental benefits like stress relief and the development of empathy. Walking a dog and playing with one are perfect physical activity opportunities. Additionally, interacting with a dog can help lower stress and may have a role in the development of empathy. Nonetheless, a number of detrimental outcomes have also been identified in both humans and dogs. Children are the most at-risk population regarding dog bites and dog-borne zoonoses, which may lead to a subsequent fear of dogs or even death. Moreover, pet bereavement is generally inevitable when living with a canine companion and should not be trivialized. In terms of dogs, children sometimes take part in caretaking behaviors toward them which include going on walks. They are opportunities for dogs to relieve themselves outside, but also to exercise and socialize. In contrast, a lack of physical activity can lead to the onset of obesity. Dogs may present greater levels of stress when in the presence of children. Finally, the welfare of assistance, therapy, and free-roaming dogs remains underexplored. Overall, the study of the effects, positive as well as negative, on both species still requires further development. We call for more longitudinal studies and hope for cross-cultural research in the future in order to better understand the impact child-dog interactions might have.

Rapid industrialization, urbanization, and population explosion in sub-Saharan Africa escalate environmental Lead levels with subsequent elevation of blood Lead levels in children. Nutrition status, age, and genetics govern one’s susceptibility to Lead toxicity. This study expounded this susceptibility by relating blood Lead levels, d-aminolevulinic acid dehydratase enzyme activity (ALAD), and genetic variations of proteins that code for ALAD enzyme in urban children of Uganda. Spectrophotometric analysis for blood Lead (BL), hemoglobin levels, and determination d-levels aminolevulinic acid dehydratase enzyme activity of the blood samples from 198 children were performed prior to a polymerase chain reaction and restriction fragment length digestion for ALAD polymorphism was done. Up to 99.5% of samples coded for the ALAD1 allele whereas 0.05% coded for ALAD2. Genotypes ALAD2-2 members had elevated BLL (mean 14.1 µg/dL) and reduced ALAD enzyme activity compared to others. This, therefore, implies that the majority of children hoard BL which may affect them later in life.

Due to the continuing high suicide rates among young men, there is a need to understand help-seeking behaviour and engagement with tailored suicide prevention interventions. The aim of this study was to compare help-seeking among younger and older men who attended a therapeutic centre for men in a suicidal crisis. In this case series study, data were collected from 546 men who were referred into a community-based therapeutic service in North West England. Of the 546 men, 337 (52%) received therapy; 161 (48%) were aged between 18 and 30 years (mean age 24 years, SD=3.4). Analyses included baseline differences, symptom trajectories for the CORE-34 Clinical Outcome Measure (CORE-OM) and engagement with the therapy. For the CORE-OM there was a clinically significant reduction in mean scores between assessment and discharge (p<0.001) for both younger and older men. At initial assessment, younger men were less affected by entrapment (46% v 62%; p=.02), defeat (33% v 52%; p=.01), not engaging in new goals (38% v 47%; p=.02), and positive attitudes towards suicide (14% v 18%; p=.001) than older men. At discharge assessment, older men were significantly more likely to have an absence of positive future thinking (15% v 8%; p=0.03), have less social support (45% v 33%; p=.02) and feelings of entrapment (17% v 14%; p=.02) than younger men. Future research needs to assess the long-term effects of help-seeking using a brief psychological intervention for young men in order to understand whether the effects of the therapy are sustainable over a period of time following discharge from the service.

This single case study aims to address a gap in literature regarding the establishment of microenterprises for people with physical disability in Vietnam. Semi-structured interviews were conducted with seven people with physical disability including the Director of a non-government organisation supporting six entrepreneurs with physical disability who were engaged in teaching English to school aged children after school. Data was analysed utilising Lingelbach, De La Vina and Asel’s (2005) three characteristics that improve probability of entrepreneurial success in developing countries. This framework aided in examining the approach of establishing microenterprises by the non-government organisation. The entrepreneurs with physical disability reported earnings above average wages and feeling empowered by participating in the microenterprises. These feelings of empowerment were reportedly associated with greater independence, increased self-efficacy and a confidence in planning for their futures.

Biological technologies are fundamentally unlike any other because biology evolves. Bioengineering therefore requires novel design methodologies with evolution at their core. Knowledge about evolution is currently applied to the design of biosystems ad hoc. Unless we have a unified engineering theory of evolution, we will neither be able to meet evolution’s potential as a design tool, nor understand or limit its unintended consequences on our designs. Our concept of the evotype offers a conceptual framework for engineering the evolutionary potential of biosystems. We show how a biosystem’s evolutionary properties might be rationally designed by engineering aspects of genetic variation, designed function, and natural selection. This idea could apply to all biosystems – from individual proteins to communities of whole-cells or even entire ecosystems – whether the goal is to direct evolution in the design process, or to limit its impacts during application. These principles could even be used beyond the realm of bioengineering to design entirely synthetic evolving auto-adaptive technologies.

Pharmaceutical poisoning is a significant global public health concern, causing approximately 190,000 deaths yearly. This scoping review aims to comprehensively map the available literature on pharmaceutical poisoning and compare patterns between high-income countries (HICs) and low-middle-income countries (LMICs). A systematic search was performed across the following databases: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL. Studies included were from 1st January 2011 to 31st December 2020, in English, with full text available. Seventy-nine articles were included in the study; 21 were from LMICs and 58 were from HICs. The toxic exposure was largely intentional (77%) in LMICs and accidental (68%) in HICs. Drugs acting on the nervous system were responsible for 95% of toxicities worldwide with analgesics accounting for the largest subtherapeutic group in both LMICs (40%) and HICs (58%). Notable statistics were that HICs accounted for 99% of opioid overdoses, and LMICs accounted for 19% of anti-epileptic-induced toxicities. Overall, the medical outcomes of poisonings were generally worse in LMICs. The review provides possible interventions to target specific geographic locations, based on the trends identified, to reduce the burden worldwide. Many gaps within the literature were recognised, calling for more robust analytical research.

Due to the continuing high suicide rates among young men, there is a need to understand help-seeking behaviour and engagement with tailored suicide prevention interventions. The aim of this study was to explore help-seeking behaviour and engagement for young men aged 18 to 30 years who attended a therapeutic centre for men in a suicidal crisis. In this prospective cohort study, data were collected from 546 men who were referred into a community-based therapeutic service in North West England. Of the 546 men, 337 (52%) received therapy; 161 (48%) were aged between 18 and 30 years (mean age 24 years, SD=3.4). One third (n=54; 34%) of the men were seen within 48 hours of their referral. Analyses included baseline differences, symptom trajectories for the CORE-34 Clinical Outcome Measure (CORE-OM) and engagement with the therapy. For the CORE 34 there was a clinically significant reduction in mean scores between assessment and discharge (p<0.001), with all outcomes demonstrating a large effect size. Future research needs to assess the long-term effects of help-seeking using a brief psychological intervention for young men in order to understand whether the effects of the therapy are sustainable over a period of time following discharge from the service.

The study examines the relationship between corporate social responsibility (CSR) and the corporate life cycle (CLC) of the Chinese pharmaceutical listed companies for the duration of 2010 to 2018. The firm cash flow pattern is used as a proxy for the CLC. The study results indicate that the relationship between CSR and CLC is positive and linear in all the phases of the CLC including, the introduction, growth and maturity stage. Although the relationship is smaller and more significant at the maturity phase. The research further shows that investors incorporating social responsibilities values play a key role in the firm cash flow performance (CFP) across all the firm stages. Whilst, employees espousing social responsibility tenets can only improve CFP in the decline or shakeout stages. Likewise, embedding CSR into the customers group only improves CFP at the maturity stage. Applying the lag effects lead to the same study results. The finding for the bi-directional causality indicates that although CSR can positively influence CFP, CFP is ultimately more associated with the firm unobservable characteristics rather than performance attributed to CSR. On the whole, our study results point to positive causality between CSR and CFP across all the firm life stages and the CSR has a mediating effect on each life cycle.

Data on helminth parasites and epizoites is presented for the long-beaked and short-beaked common dolphins from the Southeast Pacific. Sampling in 1985-2000 was conducted mainly at six fishing ports in Peru and Ecuador where cetaceans were landed. From a total of 473 common dolphins sampled, we identified helminths including three species of Trematoda: Nasitrema globicephalae, Pholeter gastrophilus and Braunina cordiformis; three species of Nematoda, which includes Anisakis spp., Crassicauda sp. and Halocercus sp.; and two cestodes Tetrabothrius forsteri and Clistobothrium delphini (formerly Phyllobothrium delphini). No acanthocephalans were observed. No statistically significant sexual and ontogenetic variation in helminth prevalence was detected after which samples were pooled. The highest prevalence in the long-beaked common dolphin (n=440) was observed for N. globicephalae (96.3%) in cranial sinuses, Crassicauda sp. (83.3%) in mammary glands, Crassicauda sp. (78.8%) infesting the cranial sinuses, followed by Cl. delphini (28.6%) in the blubber and P. gastrophilus and B. cordiformis (20.4%) in the digestive tract. Although comparative testing was unfeasible due to minimal samples of short-beaked common dolphin (n=33), several of the same helminth species were found, but not N. globicephalae nor B. cordiformis. No cyamids were encountered while pseudo-stalked barnacles Xenobalanus globicipitis were common. No new (global) helminth host records are revealed for common dolphins, but this study presents a first checklist of parasites separately for the Southeast Pacific long-beaked and short-beaked common dolphins. Future work should include exhaustive laboratory-based necropsies, enhanced sampling of the short-beaked form, focus on intermediate hosts and parasitic pathology, including potential human health impact from consumption of small cetaceans.

Post-translational modifications (PTMs) represent a cornerstone in the complexity of the proteome, significantly contributing to diversifying protein structure and function. PTMs can significantly influence protein function, stability, localization, and interactions with other molecules. Therefore, it is important when choosing a protein expression system to ensure the precise incorporation of PTMs during protein synthesis, which is paramount for producing biologically active proteins. Cell-free protein synthesis (CFPS) system has emerged as a powerful protein synthesis platform and research toolkit in synthetic biology. The open nature of the system allows the reaction environment to be tailored to any protein of interest to promote specific PTMs, thus allowing for the production of a protein with the desired modifications. This review presents various PTMs achieved in the CFPS systems, providing insights into the current challenges, successes, and future prospects.

Milk and dairy foods are naturally rich sources of a wide range of nutrients, and when consumed according to recommended intakes contribute essential nutrients across all stages of the life cycle. Since then, seminal studies recommendations with respect to intake of saturated fat have been consistent and clear; limit total fat intake to 30% or less total dietary energy, with a specific recommendation for intake of saturated fat to less than 10% of total dietary energy. However, recent work has re-opened the debate on intake of saturated fat in particular, with suggestions that recommended intakes be considered not at a total fat intake within the diet, but at a food specific level. A large body of evidence exists examining the impact of dairy consumption on markers of metabolic health, both at a total dairy intake and also at a food level, with mixed findings to date, but suggests that the impact of saturated fat intake on health differs both across food groups and even between foods within the same good group such as dairy. Milk and dairy foods contain a range of nutrients and bioactive components in different levels, housed within very different food structures. The interaction of the overall food structure and the nutrients describes the concept of the ‘food matrix effect’ which has been well documented for dairy foods. Studies show that nutrients from different dairy food sources can have different effects on health and for this reason, they should be considered individually rather than grouped as a single food category in epidemiological research. This review examines the current evidence from randomised controlled trials and meta-analyses, with respect to dairy, milk, yoghurt and cheese on aspects of metabolic health, and summarises some of the potential mechanisms for these findings.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Over the past 150 million years, the Chilean Atacama Desert has been transformed into one of the most inhospitable landscapes by geophysical changes, which makes it an ideal Mars analog that has been explored for decades. However, two heavy rainfalls that occurred in the Atacama in 2015 and 2017 provide a unique opportunity to study the response of resident extremophiles to rapid environmental change associated with excessive water and salt shock. Here we combine mineral/ salt composition measurements, amendment cell culture experiments, and next-generation sequencing analyses to study the variations in salts and microbial communities along a latitudinal aridity gradient of the Atacama Desert. In addition, we examine the reshuffling of Atacama microbiomes after the two rainfall events by comparing with previous researches. Analysis of microbial community composition revealed that soils within the southern arid desert were consistently dominated by Actinobacteria, Proteobacteria, Acidobacteria, Planctomycetes, Chloroflexi, Bacteroidetes, Gemmatimonadetes, and Verrucomicrobia. Intriguingly, the hyperarid microbial consortia exhibited a similar pattern to the more southern desert. Salts at the shallow subsurface were dissolved and leached down to a deeper layer, challenging indigenous microorganisms with the increasing osmotic stress. Microbial viability was found to change with aridity and rainfall events. This study sheds light on the structure of xerophilic, halophilic, and radioresistant microbiomes from the hyperarid northern desert to the less arid southern transition region, as well as their response to changes in water availability. Our findings may infer similar events that happened on the wetter early Mars.

In a context of increasingly necessary energy transition, precise modelling of profiles for low-voltage (LV) network consumers is crucial to enhance hosting capacity. Typically, load curves for these consumers are estimated through measurement campaigns conducted by Distribution System Operators (DSO) for a representative subset of customers or through the aggregation of load curves from household appliances within a residence. With the instrumentation of smart meters becoming more common, a new approach to modelling profiles for residential customers is proposed to make the most of the measurements from these meters. The disaggregation model estimates the load profile of customers on a low-voltage network by disaggregating the load curve measured at the secondary substation level. By utilizing only the maximum power measured by Linky smart meters, along with the load curve of the secondary substation, this model can estimate the daily profile of customers. For 48 secondary substations in our dataset, the model obtained an average symmetric mean average percentage error (SMAPE) error of 4.91% in reconstructing the load curve of the secondary substation from the curves disaggregated by the model. This methodology can allow the estimation of the daily consumption behaviors of the low-voltage customers. In this way, we can safely envision solutions that enhance the grid hosting capacity.

Bacterial collections are invaluable tools for microbiologists. However, their practical use is compromised by imprecise taxonomical assignation of bacterial strains. This is particularly true for soft rotting plant pathogens of the Pectobacterium genus. To solve this difficulty, we analyzed the taxonomic status of 265 Pectobacterium strains deposited at CIRM-CFBP collection from 1944 to 2020. This collection gathered Pectobacterium strains isolated in 27 countries from 32 plant species representing 17 botanical families or from non-host environments. MLSA approach completed by genomic analysis of 15 strains was performed to update the taxonomic status of these 265 strains. Results showed that the CIRM-CFBP Pectobacterium collection harboured at least one strain of each species to the exception of P. polonicum. Yet, 6 strains could not be assigned to any of the described species and may represent at least two new species. Surprisingly, the P. versatile species, recently described in 2019, is the most prevalent species among CIRM-CFBP strains. Analysis of P. versatile strains revealed that this species is endemic all over the world on various host plants and environments. At the opposite, other species gathered strains isolated from only one botanical family or exclusively from fresh water environment. Our work also revealed new host plants for several Pectobacterium spp.

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

The development and generalization of Digital Volume Correlation (DVC) on X-ray computed tomography data highlight the issue of long term storage. The present paper proposes a new model-free method for pruning the DVC data. The size of the remaining sampled data can be user-defined, depending on the needs concerning storage space. The data pruning procedure is deeply linked to hyper-reduction techniques. The DVC data of a resin-bonded sand tested in uniaxial compression is used as an illustrating example. The relevance of the pruned data is tested afterwards for model calibration. A new Finite Element Model Updating (FEMU) technique coupled with an hybrid hyper-reduction method is used to successfully calibrate a constitutive model of the resin bonded sand with the pruned data only.

The rise in prevalence of obesity in women of reproductive age in both developed and developing countries might propagate intergenerational cycles of detrimental effects on metabolic health, contributing to substantial economic burden on society. Placental lipid metabolism might be disrupted by maternal obesity, which possibly affects the life-long health of the offspring. Here, we investigated placental lipid metabolism and handling from women with pre-gestational obesity as a sole pregnancy complication and compared to placental responses of lean women. Open profile and targeted lipidomics were used to assess placental lipids and oxidized products of docosahexahenoic acid (DHA), neuroprostanes, and arachidonic acid (AA), isoprostanes. Placental fatty acid transporters FABP1, FABP3 and endothelial lipase protein were measured. Despite no signs of overall alterations in lipid content, increased contents of DHA, AA, DHA-derived neuroprostanes and AA-derived isoprostanes and decreased content of FABP1 protein were found in placentas from obese women. Multivariate analyses suggested that these oxidised fatty acids are associated with maternal and placental inflammation and also with birth weight. These results might shed light on the molecular mechanisms associated with altered fatty acid metabolism and lipid handling in maternal pre-gestational obesity, placing these oxidized fatty acids as novel mediators of placental function.

Episcopic imaging using techniques such as High Resolution Episcopic Microscopy (HREM) and its variants, allows biological samples to be visualized in three dimensions over a large field of view. Quantitative analysis of episcopic image data is undertaken using a range of methods. In this systematic review, we look at trends in quantitative analysis of episcopic images and discuss avenues for further research. Papers published between 2011 and 2022 were analyzed for details about quantitative analysis approaches, methods of image annotation and choice of image processing software. It is shown that quantitative processing is becoming more common in episcopic microscopy and that manual annotation is the predominant method of image analysis. Our meta-analysis highlights where tools and methods require further development in this field, and we discuss what this means for the future of quantitative episcopic imaging, as well as how annotation and quantification may be automated and standardized across the field.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

Combining the Job Demands-Resourses model and the Work Adjustment theory, this research aims to create a theoretical model that considers Leader-Member Exchange (LMX) and Work Adjustment as protective factors, capable of reducing job exhaustion and turnover intention. A convenience sample of 257 Italian employees filled an online self-report questionnaire. A sequential mediation model was tested, which showed that the relationship between LMX and turnover intention is mediated by Work Adjustment and Job Exhaustion. The results show that the higher the LMX, the higher the work adjustment of the workers and the less they will perceive job exhaustion and, consequently, intent to leave the organisation. With a view to primary prevention, the aim was to investigate possible protective factors at work and the risk factors to look out for in order to move in the direction of preventing a malaise phenomenon before it develops with the aim of promoting wellbeing in organisations.

Creative thinking is increasingly recognised as an essential ability that should be part of school curricula. Given the move towards online learning and assessment, we investigate whether mathematical creativity can be assessed at-scale in the Numbers game, an arithmetic game in Math Garden, a popular online math practice platform. In the Numbers game, a generalisation of the 24 Game, children are asked to figure out how to compute a target number using basic arithmetic operations and a given set of numbers. We argue that creative thinking is required when the search space is complex, and propose that the base-pattern, i.e., the sequence of the operations needed to solve a Numbers game item, indicates search space complexity. We then demonstrate that items with disordered base-patterns are more likely to require mathematical creativity to figure out. Specifically, our analysis shows that for items with only one solution sequence, those with disordered base-patterns are more difficult and take longer to solve compared to items with ordered base-patterns. For items where multiple solution sequences are possible, nine times out of ten children choose ordered over disordered base-patterns. We conclude that the Numbers game has potential for assessing mathematical creativity at-scale.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

This study assesses attitudes of young adults' (18-30 years old) consumption on local and traditional products in7 European countries. A clustered sample (n=836) from natives of Greece, Bulgaria, Romania, Slovenia, Croatia, Denmark and France was collected, by distributing questionnaires through social media and university mail services. Sample was examined by implementing Principal Component Analysis (PCA) in three different samples; overall and two subgroups, Eastern and Western European countries. Six major factors revealed: consumer behavior, health issues, cost, influence from media and close environment and availability on store. As a result, young adults have a positive attitude to local and traditional food products but they express insecurity for health issues. Cost factor influences less people from Eastern European countries than those from the overall sample (3rd and 5th factor accordingly). Influence of close environment is a different factor in Eastern countries comparing to Western ones that it common with influence from media. Females and older people (25-30 years old) doubt less about TFPs, while media have high influence on consumers’ decisions. Aim of this survey is to create consumer profiles of young adults and create different promotion strategies of local and traditional products among the two groups of countries.

Conservation of wildlife depends on precise and unbiased knowledge on the abundance and distribution of species. It is challenging to choose appropriate methods to obtain a sufficiently high detectability and spatial coverage matching the species characteristics and spatiotemporal use of the landscape. In remote regions, such as in the Arctic, monitoring efforts are often resource-intensive and there is a need for cheap and precise alternative methods. Here, we compare an uncrewed aerial vehicle (UAV; quadcopter) pilot-survey of the non-gregarious Svalbard reindeer to traditional population abundance surveys from ground and helicopter to investigate whether UAVs can be an efficient alternative technology. We found that the UAV survey underestimated reindeer abundance compared to the traditional abundance surveys when used at management relevant spatial scales. Observer variation in reindeer detection on UAV imagery was influenced by the RGB greenness index and mean blue channel. In future studies, we suggest to test long-range fixed-wing UAVs to increase the sample size of reindeer and area coverage and incorporate detection probability in animal density models from UAV imagery. In addition, we encourage focus on more efficient post-processing techniques, including automatic animal object identification with machine learning and analytical methods that account for uncertainties.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

As AI models become more and more common in business and even in our daily lives, it is important to understand what the carbon impact of these models is. Recent papers have shown that this impact can be quite great, i.e., the training of a single high-end model can result in emissions of more than 500t of CO2eq. In this paper we discuss the factors that influence the carbon footprint of AI models, explore what impact different decisions have, and show how the footprint can be reduced. We also examine the footprint of different models to give a guideline on how urgent action is for different organizations.

Social and spatial characteristics of a population often interact to influence health outcomes, suggesting a need to jointly analyze both to offer useful insights in community health. However, researchers have used either social or spatial analyses to examine community-based health issues and inform intervention programs. We propose a combined socio-spatial analytic approach to develop a social network with spatial weights and a spatial statistic with social weights, and apply them to an ongoing study of mental and physical well-being of rural Latino immigrants in North Florida, USA. We demonstrate how this approach can be used to calculate measures, such as social network centrality, support contact dyads, and spatial kernel density based on a health survey data. Findings reveal that the integrated approach accurately reflected interactions between social and spatial elements, and identified community members (who) and locations (where) that should be prioritized for community-based health interventions.

Maternal obesity is increasingly prevalent and is associated with elevated morbidity and mortality rates in both mothers and children. As the interface between the mother and fetus, the placenta has mediates the impact of the maternal environment on fetal development. Most of the literature data on the effects of maternal obesity on placental functions do not exclude potential confounding factors like metabolic diseases (e.g. gestational diabetes). Moreover, it is now clear that the placental response to maternal environment depends on the fetal sex. In this context, we reviewed how maternal obesity (in the absence of gestational diabetes) affects the human placenta in terms of (i) endocrine function, (ii) morphological characteristics, (iii) nutrient exchanges and metabolism, (iv) inflammatory/immune status, (v) oxidative stress, and (vi) transcriptome, with a focus on fetal sex specificities. A better understanding of sex-specific placental responses to maternal obesity is crucial for improving pregnancy outcomes and the health of mothers and children.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with complex carcinogenesis. Although there has been significant progress in the treatment of HCC over the past decades, drug resistance to chemotherapy remains a major obstacle in its successful management. In this study we were able to reduce chemoresistance in cisplatin-resistant HepG2 cells by either silencing the expression of transglutaminase type 2 (TG2) using siRNA or by pre-treatment of cells with the TG2 enzyme inhibitor cystamine. Further analysis revealed that, whereas the full-length TG2 isoform (TG2-L) was almost completely cytoplasmic in its distribution, the majority of the short TG2 isoform (TG2-S) was membrane-associated in both parental and chemoresistant HepG2 cells. Following induction of cisplatin toxicity in non-chemoresistant parental cells, TG2-S together with cisplatin quickly relocated to the cytosolic fraction. Conversely, no cytosolic relocalisation of TG2-S or nuclear accumulation cisplatin was observed following identical treatment of chemoresistant cells, where TG2-S remained predominantly membrane-associated. This suggests that deficient subcellular relocalisation of TG2-S from membranous structures into the cytoplasm may limit the apoptic response to cisplatin toxicity in chemoresistant cells. Structural analysis of TG2 revealed the presence of binding motifs for interaction of TG-S with the membrane scaffold protein LC3/LC3 homologue that could contribute to a novel mechanism of chemotherapeutic resistance in HepG2 cells.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

Pieron's and Chocholle’s seminal psychophysical work predicts that human response time to information relative to visual contrast and/or sound frequency decreases when contrast intensity or sound frequency increases. The goal of this study is to bring to the fore the ability of individuals to use visual contrast intensity and sound frequency in combination for faster perceptual decisions of relative depth (“nearer”) in planar (2D) object configurations on the basis of physical variations in luminance contrast. Computer controlled images with two abstract patterns of varying contrast intensity, one on the left and one on the right, preceded or not by a pure tone of varying frequency, were shown to healthy young humans in controlled experimental sequences. Their task (two-alternative forced-choice) was to decide as quickly as possible which of two patterns, the left or the right one, in a given image appeared to “stand out as if it were nearer” in terms of apparent (subjective) visual depth. The results show that the combinations of varying relative visual contrast with sounds of varying frequency exploited here produced an additive effect on choice response times in terms of facilitation, where a stronger visual contrast combined with a higher sound frequency produced shorter forced-choice response times. This new effect is predicted by cross-modal audio-visual probability summation.

Gut microbiota affects progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg Lpps /L, but not 0.25 and 1mg Lpps/L significantly alleviated RA symptoms in CIA DBA/1OOaHsd mice. Arthritis index (AI) was also reduced in CAIA mice. In CIA protected group, colon Ligilactobacillus murinus, caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher caecal and colon E. coli and lower caecal L.murinus. Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA protected mice triggered by LPS secreted higher Il-10 than control ones. However, higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs recruitment. Labeled bacteria with Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16h post-gavage but not in Peyer’s patches and spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24h. FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.

Combined awareness about the power and limitations of bioinformatics and molecular biology enables advanced research based on high-throughput data. Despite an increasing demand for scientists with a combined background in both fields, the education in dry lab and wet lab is often separated. This work describes an example of integrated education with focus on genomics and transcriptomics. Participants learn computational and molecular biology methods in the same practical course. Peer-review is applied as a teaching method to foster cooperative learning of students with heterogeneous backgrounds. Evaluation results indicate acceptance and appreciation of this approach.

Introduction: This population-based retrospective cohort study assesses rates of adverse events (AEs) involving cerebral thromboembolism (CTE) after COVID-19 vaccines. Methods: Data were collected from the U.S. Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) Vaccine Adverse Event Reporting System (VAERS) database from January 1, 1990 to December 31, 2023. CTE AEs after COVID-19 vaccines were compared to those after influenza vaccines and after all other vaccines using proportional reporting ratio (PRR) analysis by time. Results: There are 5137 cerebral thromboembolism AEs reported in the 3 years (36 months) after COVID-19 vaccines compared to 52 AEs for the influenza vaccines over the past 34 years (408 months) and 282 AEs for all other vaccines (excluding COVID-19) over the past 34 years (408 months). The PRR’s are significant when comparing AEs by time from COVID-19 vaccines to that of the influenza vaccines (p < 0.0001) or to that of all other vaccines (p < 0.0001). The CTE AEs PRR by time (95% confidence intervals) for the COVID-19 vaccine AEs vs influenza AEs is 1120 (95% confidence interval (723-1730), p < 0.0001) and for COVID-19 vaccines vs all others is 207 (95% confidence interval (144-296), p < 0.0001). Cerebral venous thromboembolism AEs are female predominant with a female/male odds ratio of 1.63 (95% confidence interval (1.52-1.74), p < 0.0001). Conversely, cerebral arterial thromboembolism has a nonsignificant male preponderance. Cerebral venous thromboembolism is far more common than cerebral arterial thromboembolism over 36 months with an odds ratio (OR) of 14.8 (95% confidence interval 14.0-15.5, p < 0.0001). Atrial fibrillation, the most common identifiable cause of cerebral arterial thromboembolism, occurs far more commonly after the COVID-19 as compared to all other vaccines with a PRR of 123 (95% CI 88.3-172, p < 0.0001) Conclusions: There is an alarming breach in the safety signal threshold concerning cerebral thrombosis AEs after COVID-19 vaccines compared to that of the influenza vaccines and even when compared to that of all other vaccines. An immediate global moratorium on the use of COVID-19 vaccines is necessary with an absolute contraindication in women of reproductive age.

Local air quality is a major concern for the population regularly exposed to high levels of air pollution. The airport, mainly due to its aircraft engines activities during taxiing and take off, is often submitted to heterogeneous but important concentrations of NOx and PM. The study suggests an innovative approach to determine the air traffic impact on air quality at the scale of the airport, its runways and terminals, in order to be able to locate the persistent high concentrations spots. The pollutants concentrations at 10 m resolution and 1 s time step are calculated in order to identify the most affected areas of an airport platform. A real day of air traffic on a regional airport is simulated, using real data as aircraft trajectories (from radar streams). In order to estimate the aircraft emissions, the Air Transport Systems Evaluation Infrastructure (IESTA) is used. Regarding local air quality, IESTA relies on the non-hydrostatic meso-scale atmospheric model Meso-NH using grid-nesting capabilities with 3 domains, for this study. The detailed cartography of the airport distinguishes between grassland, parking and terminals, allowing to compute exchanges of heat, water and momentum between the different types of surfaces and the atmosphere as well as the interactions with the building using a drag force. The dynamic parameters like wind, temperature, turbulent kinetic energy and pollutants concentration are computed at 10 m resolution over the 2 × 4 km airport domain. The pollutants are considered in this preliminary study as passive tracers, without chemical reactions. This preliminary study aims at proving the feasibility of high scale modelling over an airport with state of the art physical models.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labour, and preeclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This review summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidenced-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

The prefabricated houses supply in Chile was analyzed from web platforms, public market, social media, and Internal Revenue Service, using indicators according to regulatory compliance, complexity, and sustainability attributes, which are essential in advancing to industrialization, and climate change adaptability. The 80% is concentrated in construction, and manufacturing companies, 83% of them are legally registered,with the capacity of meeting technical requirements. To delve deeper into this, 54% has low level, 35% medium level, and 11% high level. The sustainability was measured in 5 levels: 2.7% (1), 37,5% (2), 58,6% (3), 1,1% (4) and 0% (5), which is the highest one. This attribute was determined as the weakest one. The proposed evaluation, based on indicators by attribute, is objective and relevant to consideration since there is still a lack of capacity to supply the housing deficit, and there is not attributes associated to security in habitability to address the climate change, and environment threats, with a lack of action by the state to promote this productive sector, therefore focusing more in provide products, than taking responsibility of the site, not advancing to become a real state agency, which could be improved if management, and regulation were incorporated.

Development of effective treatments for high-grade glioma (HGG) is hampered by 1) the blood-brain barrier (BBB), 2) an infiltrative growth pattern, 3) rapid development of therapeutic resistance, and, in many cases, 4) dose-limiting toxicity due to systemic exposure. Convec-tion-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and in-crease therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.

Over the last 15 years, the advent of high-throughput ‘omics’ techniques has revealed the multiple roles and interactions occurring among hosts, their microbial partners and their environment. This microbiome revolution has radically changed our views of biology, evolution and individuality. Sitting at the interface between a host and its environment, the microbiome is a relevant yet understudied compartment for ecotoxicology research. Various recent works confirm that the microbiome reacts to and interacts with contaminants, with consequences for hosts and ecosystems. In this paper, we thus advocate for the development of a “microbiome-aware ecotoxicology” of organisms. We emphasize its relevance and discuss important conceptual and technical pitfalls associated with study design and interpretation. We identify topics such as functionality, quantification, temporality, resilience, interactions and prediction as major challenges and promising venues for microbiome research applied to ecotoxicology.

The impact of sex in the development of long-term toxicities affecting the quality of life of cancer survivors has not been investigated experimentally. To address this issue, a series of neurologic and cardiologic endpoints were used to investigate sex-based differences triggered by paclitaxel treatment and radiotherapy exposure. Male and female WT mice were treated with Paclitaxel (150 and 300 mg/kg) administered weekly over 6 weeks or exposed to 19 Gy cardiac irradiation. Cohorts were analyzed for behavioral and neurobiologic endpoints to assess systemic toxicity of paclitaxel or cardiovascular endpoints to assess radiotherapy toxicity. Interestingly, female WT mice exhibited enhanced tolerance compared to male WT mice regardless of the treatment regimen. To provide insight into the possible sex-specific protective mechanisms, rhoB deficient animals and elderly mice (22 months) were used with a focus on the possible contribution of sex hormones including estrogen. RhoB deficiency and advanced age had no impact on neurocognitive impairment induced by Paclitaxel but reversed the cardioprotection was observed in females after radiotherapy. Conversely, rhoB deficiency protected males from radiation toxicity. In sum, rhoB was identified as a molecular determinant driving estrogen dependent cardioprotection in female mice, whereas neuroprotection was not sex-hormone dependent. To our knowledge, this study revealed for the first time sex- and organ-specific responses to paclitaxel and radiotherapy.

The potential for transmission of the SARS-CoV-2 virus during minimally invasive gynaecological procedures, such as hysteroscopy or laparoscopy, on the reproductive tract of patients with COVID-19 is not known. We examined existing data for prevalence of virus in the reproductive tract and other bodily fluids.

DIEP-based breast reconstruction necessitates wide undermining at the abdominal donor-site, creating large wound areas. Flap harvesting is usually conducted using electrosurgical dissection devices. This study sought to compare the clinical outcomes in patients after using the PEAK PlasmaBlade (PPB) versus monopolar electrocautery (MPE). This retrospective cohort study included 128 patients with DIEP-based breast reconstruction. Patient characteristics as well as information on the postoperative course were collected and a comparative evaluation was conducted. The MPE group exhibited significantly (p* = 0.0324) higher abdominal drainage volume (351.11 ± 185.96 ml) compared to the PPB group (279.38 ± 183.38 ml). Subgroup analysis demonstrated that PPB significantly reduced postoperative wound fluid in patients with BMI > 30 kg/m² (p* = 0.0284), without prior neoadjuvant chemotherapy (p** = 0.0041), and among non-smokers (p = 0.0046). Furthermore, postoperative pain was significantly (p**** < 0.0001) lower in the PPB cohort. This study confirms the non-inferiority of the PEAK PlasmaBlade to conventional electrocautery for abdominal flap harvesting. The PPB demonstrated advantages, notably reduced drainage volume and lower postoperative pain levels. Recognizing patient subsets that benefit more from the PPB highlights the importance of personalized device selection based on patient characteristics.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

In addition to absorbing nitrogen from the soil, legumes have the ability to use atmospheric N2 through symbiotic nitrogen fixation. Therefore, legumes have developed mechanisms regulating nodulation in response to the amount of nitrate in the soil; in the presence of high nitrate concentrations, nodulation is inhibited while low nitrate concentrations stimulate nodulation and nitrogen fixation. This allows the legumes to switch from soil nitrogen acquisition to symbiotic nitrogen fixation. Recently, a particular interest has been given to the nitrate transporters, such as NPF or NRT2, having a role in the functioning of nodules. Nitrate transporters of the two model plants, Lotus japonicus and Medicago truncatula, shown to have a positive and/or a negative role in nodule functioning, depending on nitrate concentration, are presented in this review. Also, by exploiting available genomic and transcriptomic data in the literature we have identified the complete PsNPF family in Pisum sativum (69 sequences previously described and 21 new that we have annotated) and putative nitrate transporters candidate for playing a role in nodule functioning in P. sativum.

Amidst the strong demand for wood-based products, and the clamor of environmental consciousness, more functional and green solutions arise to meet both of these goals. Pursuant to this, the study looked into the potential of a bio-waste taken from Cocos nucifera tree known as phellem—the tree’s outermost skin made of dead tissues, to be a main component of a new construction material. This study builds on existing research showing phellem is impermeable, buoyant, elastic, has a slow burn rate, and repels water during precipitation, which supports the hypothesis that phellem may be a potential substitute material for dry wall boards. To test this, three (3) formulations were developed as experimental setups to test the physico-mechanical properties of coconut palm phellem (COPAP): Formulation A (40% COPAP and 60% cement); Formulation B ( 25% COPAP and 75% cement); and lastly, Formulation C that was (10% COPAP and 90% cement). The study tested (1) which among these formulations exhibited the best physico-mechanical properties, then it (2) compared the formulations with common dry wall products available in the market, and subsequently, (3) identified the possible architectural applications of COPAP board as a new building material. Of the three setups, Formulation C exhibited the best physico-mechanical properties in terms of compressive and flexural strength, fire resistivity, and water absorption. It fared better than the particle board in terms of compressive strength, better than wafer and particle board in fire resistivity, performed best in the water absorption test, and was almost equivalent in flexural strength to fiber cement board. With these findings, the study concluded that COPAP board can be used for projects that entail a high number of interior partitions, such as offices, BPO firms and commercial stalls in shopping malls, etc. The findings were conclusive only for interior applications, as the results clearly suggest that the COPAP boards are not load-bearing. Future investigations may explore and assess other properties of COPAP boards like thermal and sound insulation, resistance to rot and other properties that may prove its competitive advantage as a construction material.

The new NICE guideline for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), published in October 2021, makes significant changes in treatment recommendations. It acknowledges the complexity of this chronic medical condition, which always impacts quality of life and can be profoundly disabling, recognising the prejudice and stigma that people with ME/CFS often experience in the absence of any specific diagnostic test. The guideline outlines steps for accurate diagnosis, recognising post-exertional malaise as a core symptom; importantly, ME/CFS can now be diagnosed after just 3 months in a bid to improve long-term health outcomes. It recommends the need for individual, tailored management by a multi-disciplinary team, ensuring that the wellbeing of the individual is paramount. The guideline makes clear that any programme based on fixed incremental increases in physical activity or exercise, for example graded exercise therapy (GET), should not be offered as a treatment for ME/CFS and emphasises that cognitive behavioural therapy (CBT) should only be offered as a supportive intervention. Because of the rigorous methodology required by NICE Committee review and the inclusion of the testimony of people with lived experience as committee members, this guideline will influence the future diagnosis and management of ME/CFS in the UK and beyond.

Proper regulation of microtubules (MTs) is critical for the execution of diverse cellular processes, including mitotic spindle assembly and chromosome segregation. There are a multitude of cellular factors that regulate the dynamicity of MTs and play critical roles in mitosis. Members of the Kinesin-8 family of motor proteins act as MT-destabilizing factors to control MT length in a spatially and temporally regulated manner. In this review, we focus on recent advances in our understanding of the structure and function of the Kinesin-8 motor domain, and the emerging contributions of the C-terminal tail of Kinesin-8 proteins to regulate motor activity and localization.

Chironomus riparius is a well-established model organism in various fields such as ecotoxicology and ecology, and therefore environmental preferences, ecological interactions and metabolic traits are well-studied. With the recent publication of a high-quality draft genome, as well as different population genetic parameters such as mutation and recombination rate, the species can be used as an alternative to the Drosophila models in experimental population genomics or molecular ecology. To facilitate access to this promising experimental model species for a wider range of researchers, we describe experimental methods to first create and sustain long term cultures of C. riparius and then use them to perform repeatable and comparable experiments for various research questions.

Mechanistic models have been used for centuries to describe complex interconnected processes, including biological ones. As the scope of these models has widened, so have their computational demands. This complexity can limit their suitability when running many simulations or when real-time results are required. Surrogate machine learning models can be used to approximate the behaviour of complex mechanistic models, and once built, their computational demands are several orders of magnitude lower. This paper provides an overview of the relevant literature, both from an applicability and a theoretical perspective. For the latter, the paper focuses on the design and training of the underlying machine learning models. Application-wise, we show how machine learning surrogates have been used to approximate different mechanistic models. We present a perspective on how these approaches can be applied to models representing biological processes with potential industrial applications (e.g., metabolism and whole-cell modelling) and show why surrogate machine learning models may hold the key to making the simulation of complex biological models possible using a typical desktop computer.

Gelatinization of starch content in pet foods can be impacted by several factors including moisture, retention time, and ingredients used. Starch gelatinization has been associated with digestibility but isn’t well studied using ingredients common in non-traditional canine diets. The objective of this research was to examine the impacts of dietary ingredient profile (traditional vs non-traditional) and assess impacts to total starch content and starch gelatinization. Traditional diets (n = 10) utilizing meat-based ingredients including chicken, chicken by-product meal, meat and bone meal and plant-based ingredients including rice, barley, oats, and corn were examined in comparison with non-traditional diets (n = 10) utilizing meat-based ingredients including alligator, buffalo, venison, kangaroo, squid, quail, rabbit, rabbit and salmon along with plant-based ingredients including tapioca, peas, chickpeas, lentils, potato, and pumpkin. Representative samples were collected via grab sample technique (5 samples/diet) and were assessed for total starch content as well as percent starch gelatinization. Difference between ingredient type was assessed using a Students t-test in SAS 9.4. Significance was set at P < 0.05. Distribution of total starch content based on ingredient type (traditional vs non-traditional) revealed that mean total starch content was higher in traditional diets as compared to non-traditional diets (P <0.0001). Conversely, starch gelatinization was found to be higher in non-traditional diets (P < 0.0001). Total starch content and total gelatinized starch had a strong negative correlation (P < 0.01) in traditional diets, though no correlation was observed in non-traditional diets. This negative correlation indicates a decrease in total gelatinized starch associated with increased total starch content. These novel data reveal important differences between starch content and gelatinization and could impact manufacturing processes for ingredient types as well as feeding recommendations. Unpredicted variation between ingredient formulations could potentially lead to decreased digestibility and absorption and may result in nutrient deficiencies.

Avian necrotic enteritis is an enteric disease of broiler chickens caused by certain pathogenic strains of Clostridium perfringens in combination with predisposing factors. A vaccine offering complete protection against the disease has not yet been commercialized. In a previous study, we produced five recombinant proteins predicted to be surface-exposed and unique to necrotic enteritis-causing C. perfringens and the immunogenicity of these potential vaccine candidates was assessed in broiler chickens. In the current work, the relative contribution of the antibodies raised by these putative antigens to protect broiler chickens was evaluated using an experimental necrotic enteritis induction model. Additionally, the link between the immune response elicited and the gut microbiota profiles in immunized birds subjected to infection with virulent C. perfringens was studied. ELISA results showed that the IgY antibody titers in vaccinated birds on days 21 and 33 were significantly higher than those on days 7 and 14 and those in birds receiving the adjuvant alone, while the relative contribution of the specific immunity attributed to these antibodies could not be precisely determined using this experimental NE induction model. Besides, 16S rRNA gene amplicon sequencing showed that immunization of birds with recombinant proteins had a low impact on the chicken caecal microbiota.

Significant amounts of anthropogenic radionuclides were introduced in ocean waters following nuclear atmospheric tests and development of the nuclear industry. Dispersion of artificial dissolved radionuclides has been extensively measured for decades over the European continental shelf. The radionuclide measurement and release fluxes databases provided here represent an exceptional opportunity to validate dispersion hydrodynamic models. MARS hydrodynamic model have been applied at different scales to reproduce in realistic conditions the measured dispersion. Specific methods have been developed to obtain qualitative and quantitative results and perform model/measurement comparisons. Model validation concerns short to large scales with dedicated surveys following the dispersion: it was performed within two and three dimensions framework and from minutes and hours following a release up to several years. Results are presented concerning the dispersion of radionuclides in marine systems deduced from standalone measurements, or according to model comparisons. It allows characterising dispersion over the continental shelf, pathways, transit times, budgets and source terms. This review exhibits the main features retained from the point of view of radiotracers, hydrodynamic models and model/measurement methods with perspectives of applications in other areas or oceanographic domains.