Magnetic resonance elastography (MRE) has revealed sexual dimorphism in brain stiffness in healthy individuals and multiple sclerosis (MS) patients. In the animal model of MS, experimental autoimmune encephalomyelitis (EAE), we showed previously that inflammation-induced brain softening was associated with alterations of the extracellular matrix (ECM). However, it remained unclear whether the brain ECM presents sex-specific properties that can be visualized by MRE. Therefore, we aimed here at quantifying sexual dimorphism in brain viscoelasticity in association with ECM changes in healthy and inflamed brains. Multifrequency MRE was applied to the midbrain of healthy and EAE mice of both sexes to quantitatively map regional stiffness. To define differences in brain ECM composition, gene expression of the key basement membrane components laminin (Lama4, Lama5), collagen (Col4a1, Col1a1) and fibronectin (Fn1) was investigated by RT-qPCR. We showed that the healthy male cortex expressed less Lama4, Lama5, Col4a1 but more Fn1 (all p < 0.05) than the healthy female cortex, which was associated with 9% softer properties (p = 0.044) in that region. At peak EAE, cortical softening was similar in both sexes compared to healthy tissue, with an 8% difference remaining between males and females during EAE (p < 0.001). Cortical Lama4, Lama5 and Col4a1 expression increased 2 to 3-fold in EAE in both sexes while Fn1 decreased only in males (all p < 0.05). No significant sex differences in stiffness were detected in other brain regions. In conclusion, sexual dimorphism in the ECM composition of cortical tissue in the mouse brain is reflected by in vivo stiffness measured with MRE and should be considered in future studies by sex-specific reference values.

Covid-19 fatality rates of 0.37% (Gangelt, Germany) and 0.17% (Santa Clara, USA) have been reported, estimated from serological studies. We show that the two confidence intervals strongly overlap when the uncertainty in the number of deaths is taken into account, so that the two investigations may be regarded as representative of the same population (tentatively: “Western society with no overload of the Health Care System during the pandemic”). Combining the results, the Covid-19 fatality rate is estimated to be found with 95% confidence in the range [0.1%; 0.3%].

Rapid SARS-CoV-2 self-tests have the potential to expand access to COVID-19 testing and improve community-level case detection, particularly in resource-constrained countries such as Kenya. However, prior to their introduction, their acceptability must be assessed. This qualitative study explored key decision-takers’ values towards SARS-CoV-2 self-testing in Kenya. Healthcare workers, representatives of civil society, and potential implementors from Mombasa and Taita-Taveta were selected as decision-takers. Semi-structured interviews and focus group discussions were used to collect data on their values towards self-testing. A thematic analysis approach was applied. Most informants considered that the Kenyan public is equipped to accept and use self-testing safely as an approach to help to reduce workload at public healthcare facilities, and know one’s COVID-19 status in a private manner. The informants emphasized the need to provide counselling to end-users, to support those needing to self-isolate, and to engage different civil society stakeholders in information provision on self-testing. Fear of stigma and of forced isolation were noted as potential deterrents to self-testing uptake for some individuals. In conclusion, there is high acceptability of self-testing in Kenya among decision-takers. However, enhanced education, counselling, and addressing deterrents to testing would be helpful to ensure effective use of SARS-CoV-2 self-testing in Kenya.

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.

About 70% of children and adolescents with cerebral palsy experience gait impairments which affect their autonomy and well-being. Robotic-assisted gait training using the Lokomat is particu-larly promising for rehabilitation as it provides a standardized environment favoring the massive repetition of the movement, in which physical demands are low on the therapist and high training loads can be achieved. As no guidelines exist regarding training protocols and Lokomat settings, the goal of this study was to review the literature on Lokomat-assisted gait therapy and possibly make training recommendations. The twelve studies reviewed reported both positive and null effects of Lokomat training on gait. Half of the studies combined Lokomat with other types of training and only five used a control intervention to assess its benefit. Overall, training was administered 1-5 times per week for 20-60 minutes, over 1-12 weeks. Although Lokomat settings were not always described, progressively decreasing body-weight support and guidance, while increasing treadmill speed appear to be prioritized. The variety of training protocols and settings used did not allow pooling of the studies to assess effects of interventions on gait parameters in children and adoles-cents with cerebral palsy. This review highlights the need for homogenization of interventions so that clear guidelines can emerge and be applied in rehabilitation centers.

In the context of seismic risk, studying the characteristics of urban soils and of the built environment means adopting a holistic vision of the city taking a step forward compared to the current microzonation approach. Based on this principle, CLARA WebGIS aims to collect, organise, and disseminate the available information on soils and buildings in the urban area of Matera. The geodatabase is populated with i) 488 downloadable geological, geotechnical, geophysical, surveys; ii) geological, geomorphological, and seismic homogeneous microzones maps and iii) a new Digital Surface Model. The CLARA WebGIS (https://smartcities-matera-clara.imaa.cnr.it/) is the first publicly available database reporting for the whole urban area the spatial distribution of the fundamental frequencies for soils and the overlying 4043 buildings, along with probability levels of soil-building resonance. The WebGIS is addressed to a broad target of end users (local government, engineers, and geologists, etc.) as a support to the implementation of seismic risk mitigation strategies in terms of urban planning, seismic retrofitting, and management of post-earthquake crises. We recommend that the database be managed by local administrators, who would also have the task of deciding on future developments and continuous updating as new data becomes available.

Disrupted biological function, manifesting through the hallmarks of aging, poses as one of the largest threats to healthspan and risk of disease development, such as metabolic disorders, cardiovascular ailments, and neurodegeneration. In recent years, numerous geroprotectors, senolytics, and other nutraceuticals have emerged as potential disruptors of aging and may be viable interventions in the immediate state of human longevity science. In this review, we focus on the decrease of nicotinamide adenine dinucleotide (NAD+) with age and the supplementation of NAD+ precursors, such as nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), in combination with other geroprotective compounds to restore youthful NAD+ levels. Furthermore, these geroprotectors may enhance the efficacy of NMN supplementation while concurrently providing their own numerous health benefits. By analyzing the prevention of NAD+ degradation through inhibition of CD38 or supporting protective downstream agents of SIRT1, we provide a potential framework of the CD38/NAD+/SIRT1 axis through which geroprotectors may enhance the efficacy of NMN supplementation and reduce the risk of age-related diseases, thereby potentiating healthspan in humans.

Macrophage Migration Inhibitory Factors (MIF) are pivotal cytokines/chemokines for vertebrate immune systems. MIFs are typically soluble single-domain proteins that are conserved across plant, fungal, protist, and metazoan kingdoms but their functions have not been determined in most phylogenetic groups. Here we describe an atypical multidomain MIF protein. The marine dinoflagellate Lingulodinium polyedra produces a transmembrane protein with an extra-cytoplasmic MIF domain, which localizes to cell wall-associated membranes and vesicular bodies. This protein is also present in the membranes of extracellular vesicles accumulating at the secretory pores of the cells. Upon exposure to biotic stress, L. polyedra exhibits reduced expression of the MIF gene and reduced abundance of the surface-associated protein. These findings indicate that the transmembrane MIF may contribute to intercellular communication and/or interactions between free-living organisms in multispecies planktonic communities and raise the question of possible analogies in MIF functions between cells of metazoan organisms and protist communities.

Mutations in KRT1 (keratin 1) or KRT10 (keratin 10) underlie a spectrum of diseases known as keratinopathic ichthyoses. Epidermolytic ichthyosis (EI) is caused by heterozygous missense mutations in the genes KRT1 or KRT10, mutations in the gene KRT2 (keratin 2) lead to superficial epidermolytic ichthyosis, and congenital reticular ichthyosiform erythroderma is caused by frameshift mutations in the genes KRT10 or KRT1, which lead to the phenomenon of revertant mosaicism. Epidermolytic ichthyosis is also present in a mosaic pattern known as epidermolytic (acantholytic) nevus, isolated or diffuse. In the latter case, gonadic involvement is possible, leading to a rare pedigree in which a parent with diffuse epidermolytic nevus (linear EI) gives birth to a child affected by EI. We present here an update on the phenotypic presentations of keratinopathic ichthyoses and their molecular mechanisms.

We have evaluated the antihypertensive effect of several flavonoid extracts in the spontaneous hypertensive rat model (SHR). Treatments were carried out for 6 and 12 weeks in two groups of SHR rats which received Apigenin, Lemon Extract, Grapefruit + Bitter Orange (GBO) extracts and Cocoa extract. Captopril was used as a positive control in the SHR group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts significantly reduced the elevated blood pressure of the SHR6 animals, but none of the extracts was effective in the SHR12 group. Apigenin, LE, GBO and captopril also ameliorated nitric oxide-dependent and independent aortic vascular relaxation and elevated plasma and urinary excretion of nitrites, only in the SHR6 group. Kidney and urinary TBARS were also significantly reduced by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12 group and all the flavonoids studied reduced urinary TBARS excretion and proteinuria. Vascular abnormalities such as lumen/wall ratio in coronary arteries and thoracic aorta were moderately improved by these treatments in the SHR6 group. In conclusion, the flavonoids included in this study, especially apigenin, LE and GBO improved vascular vasodilatory function of young adult SHRs but only the GBO-treated rats benefited from a reduction in BP. These extracts may be used as functional food ingredients with a moderate therapeutic benefit, especially in the early phases of arterial hypertension.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

N-palmitoylethanolamine (PEA) is an endocannabinoid-like compound first encountered within lipid fractions of specific foods and has intrigued researchers since the 1950s due to its therapeutic effects. This study aims to explore the therapeutic promise held by PEA as an anti-inflammatory and immunomodulatory agent. Therapeutic impact of PEA reverberates across diverse physiological systems, as the central nervous system, gastrointestinal tract, vascular network, digestive and respiratory system. Additionally, it was effective in pain management, reduction of inflammation and immune responses. These attributes have fostered collaborations targeting conditions such as Alzheimer's disease, multiple sclerosis, cerebral ischemia, neuroinflammation, general inflammation, pain, coagulopathy, steatohepatitis, and acute lung injury. PEA operates both independently and in synergy with other compounds, like paracetamol, luteolin, and oxymetazoline. This efficacy stems from its interactions with pivotal targets including PPARα, PPAR-δ, PPAR-γ, CB1, CB2, GPR55, and TRPV1. Additionally, PEA exerts a direct influence on the inflammatory cascade, orchestrating precise adjustments in immune responses. Numerous animal studies have elucidated the inherent potential of PEA. Nevertheless, the imperative of reinforcing clinical investigation is evident. This review notably underscores the pivotal necessity for methodologically rigorous clinical trials to definitively establish the translational efficacy of PEA in ameliorating diverse inflammatory pathologies within the human milieu.

1) Background: we have evaluated the antihypertensive effect of several flavonoid extracts in a rat model of arterial hypertension caused by chronic administration (6 weeks) of the nitric oxide synthesis inhibitor, L-NAME. 2) Methods: Sprague Dawley rats received L-NAME alone or L-NAME plus flavonoid-rich vegetal extracts (Lemon, Grapefruit + Bitter Orange, and Cocoa) or purified flavonoids (Apigenin and Diosmin) for 6 weeks. 3) Results: L-NAME treatment resulted in a marked elevation of blood pressure, and treatment with Apigenin, Lemon Extract, and Grapefruit + Bitter Orange extracts significantly reduced the elevated blood pressure of these animals. Apigenin and some of these flavonoids also ameliorated nitric oxide-dependent and independent aortic vasodilation and elevated nitrite urinary excretion. End-organ abnormalities such as cardiac infarcts, hyaline arteriopathy and fibrinoid necrosis in coronary arteries and aorta were improved by these treatments, reducing the end-organ vascular damage. 4) Conclusions: the flavonoids included in this study, specially apigenin, may be used as functional food ingredients with potential therapeutic benefit in arterial hypertension.

Perinatal mortality is a major issue in laboratory mouse breeding. We compared a counting method using daily checks (DAILY_CHECK) with a method combining daily checks with detailed video analyses to detect cannibalisms (VIDEO_TRACK) for estimating the number of C57BL/6 pups born, died and weaned in 193 litters from trios with (TRIO-OVERLAP) or without (TRIO-NO_OVERLAP) the presence of another litter. Linear mixed models were used at litter level. To understand if cannibalism was associated with active killing (infanticide), we analysed VIDEO_TRACK recordings of 109 litters from TRIO-OVERLAP, TRIO-NO_OVERLAP or SOLO (single dams). We used Kaplan-Meier method and logistic regression at pup level. For DAILY_CHECK, the mean litter size was 35% smaller than for VIDEO_TRACK (P&lt;0.0001) and the number of dead pups was twice lower (P&lt;0.0001). The risk of pup loss was higher for TRIO-OVERLAP than TRIO-NO_OVERLAP (P&lt;0.0001). A high number of pup losses occurred between birth and the first cage checking. Analyses of VIDEO_TRACK data indicated that pups were clearly dead at the start of most of the cannibalism events and infanticide was rare. As most pups die and disappear before the first cage check, many breeding facilities are likely to be unaware of their real rates of mouse pup mortality.

We performed for the first time to our knowledge fully ab initio molecular dynamics simulations of additive tribochemistry in boundary lubrication conditions. We consider an organophosphourus additive that has been experimentally shown to reduce friction in steel-on-steel sliding contacts thanks to the tribologically-induced formation of an iron phosphide tribofilm. The simulations allow us to observe in real time the molecular dissociation at the sliding iron interface under pressure and to understand the mechanism of iron phosphide formation. We discuss the role played by the mechanical stress by comparing the activation times for molecular dissociation observed in the tribological simulations at different applied loads with that expected on the basis of the dissociation barrier.

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

Manual material handling (MMH) significantly impacts worker health and productivity, often leading to musculoskeletal disorders (MSDs) primarily in the lower back. As a novel assistive technology, exoskeletons may serve as ergonomic tools to mitigate these work-related MSDs. It is essential to examine exoskeletons from the users’ perspectives before their widespread implementation in occupational settings. This study investigates the effectiveness of a passive back-support exoskeleton (BExo) in reducing perceived physical exertion and improving ergonomic safety in manufacturing context. Twenty-two college students were recruited to perform MMH tasks in a controlled lab environment, both with and without the BExo, followed by completing a survey questionnaire on various aspects of the BExo. Using ANOVA, the study analyzed biomechanical exertion across various body parts and tasks. The findings indicate that the BExo substantially alleviates discomfort in the low back, shoulders and knees, thereby, enhancing ergonomic posture and reducing fatigue. These results underscore the potential of passive exoskeletons to boost workers’ safety and efficiency, providing valuable insights for future ergonomic strategies in industrial setting.

Our study clarified what is the same or not between Tier 1(Tokyo) and Tier 2(Kansai) metropolitan areas on shrinking cities problems. Both of metropolitan areas will dramatically decrease the Housing Asset Value (HAV) where areas of bedroom communities are located. On the other hand, compared to Tokyo, Kansai has been hit by decline at a faster pace. This raises the question of whether Kansai will be more or less impoverished by the deflation of the HAV. According to our results, Kansai municipalities should expect the HAV losses of 38% by 2045, but the HAV losses would be higher in the northern suburbs of Osaka. Kansai has to face the effects of the HAV deflation faster than Tokyo. But Tokyo has a neck of higher residential land price, the income multiplier of the HAV per household is about 4. The HAV deflation hits more severe problems for elderly households in Tokyo. Considering our study, Tier 2 metropolitan area is much faster effects of the HAV deflation, but Tier 1 metropolitan area has more serious social problem than Tier 2. Hence, there are different problems of different natures rather than which one is more severely affected by the deflation of the HAV.

We present a compact optical head design for wide-range and low noise displacement sensing using deep frequency modulation interferometry. The on-axis beam topology is realised in a quasi-monolithic component and relies on cube beamsplitters and beam transmission through perpendicular surfaces to keep angular alignment constant when operating in air or vacuum, which leads to the generation of ghost beams that can limit the phase readout linearity. We investigate the coupling of these beams into the non-linear phase readout scheme of DFMI and demonstrate adjustments of the phase estimation algorithm to reduce this effect. This is done through a combination of balanced detection and the inherent orthogonality of beat signals with different relative time-delays in deep frequency modulation interferometry that is a unique feature not available for heterodyne, quadrature or homodyne interferometry.

The EU has set the ambitious target of raising the share of EU energy consumption produced from renewable resources to 32% by 2030 with a target of climate neutrality by 2050. The aim of this paper is to assess the role of biomass usage in the context of these targets. The paper identifies progress made between 2013–2022 by focusing on a selection of EU countries. The largest bio-energy increments of 130PJ, 77PJ and 60PJ were reported for Poland, Sweden, and the Nether-lands. This study valuates the crucial role in co-generation and heat in EU regions, with biomass usage between 55-80% of the combined heat and power (CHP) energy in Nordic countries. The future perspectives for bioenergy based on EU policies, biomass resources and technical issues were addressed. The EU possess around 9% of the global biomass supply, ensuring a certain level of biomass resource dependence. Thus, the biomass usage demand in energy production, non-energy sectors and transport is expected to rise leading to increments of 13%-76% on biomass imports. It appears that bioenergy development is mostly limited by economic issues and uneven support for bioenergy in different EU countries as well as environmental issues. The study shows a promising and sustainable potential of bioenergy in the EU as a renewable energy source while minimizing negative impacts on the environment and the economy. By 2050, liquid biofuels are likely to be increasingly used in the transport sector. Non-energy sector usage of biomass is still in an early stage of development, except for the pulp and paper industry, and significant use of biomass in non-energy sectors seems unlikely in the near future.

Exopolysaccharides-EPS are long-chain biopolymer with branched, recurring unit of sugars and non-carbohydrate constituents connected to exterior of cells. Rhizobial, a legume nodulating organism is capable of producing EPS. This study investigated the characteristics’ of some Rhizobium EPS and their effects in shelf life extension of some Musa spp. Rhizobial-EPS was produced using yeast extract mineral medium purified by standard methods. The EPS was characterized to determine functional group, thermal stability, chemical compounds and the monosaccharide component using Fourier Transform Infra-red, Spectroscopy, thermogravimetric Analysis (TGA), Gas Chromatography–Mass Spectrometry and HPLC and their bio-preservative property on post-harvest quality of plantain and different banana was done. The Rhizobial-EPS functional groups were hydroxyl, carboxyl, amine, methyl and ethers associated with polysaccharides. Pentadecanoic acid, octadecanoic acid, oleic acid and heptacosanoic acid, and varied concentration of monosaccharides were detected in the exopolysaccharides. The TGA of the EPS shows a constant loss in weight with two quasi-sharp alterations and almost steady plateau. The EPS coated samples had the lowest weight loss across the samples and as such edible coating was effective in delaying weight loss. The weight loss of Musa paradisiaca (plantain) coated with (EPSA obtained from USDA 110), (EPSB USDA 532C) and (EPSC S2) at the first day were 314 and 314.5g. The initial weight loss of coated and uncoated Musa sp. (Apple Banana), Musa acuminata (Lady Finger), and Musa balbisiana (Cooking Banana), ranged from 72 – 72.7g, 96 – 97g and 95 – 98g respectively. The total sugar of EPS Coated Musa sp. ranges from 0.381 – 0.528mg/L, 0.392 – 0.576 mg/L and 0.41 – 0.598 mg/L at days 1, 2 and 3 respectively. The highest Titratable acidity and pH was observed in EPS coated sample. The results obtained from this study proves that EPS solution is a valuable product for fruit preservation and viable for commercial applications.

Zika virus (ZIKV), without a vaccine or no effective treatment approved as yet, have globally spread since the past century. The infection caused by ZIKV in humans has changed progressively from mild to subclinical in the last years, causing epidemics with greater infectivity, tropism towards new tissues, and other related symptoms as a product of various emergent ZIKV-host cell interactions. However, it is still unknown why or how the RNA genome structure impacts those interactions in differential evolutionary origin strains. Moreover, genomic comparison of ZIKV strains from the sequence-based phylogenetic analysis is well known, but differences from RNA structure comparisons are less known. Thus, in order to understand the RNA genome variability of lineages of various geographic distributions better, 412 complete genomes in a phylogenomic scanning were used for studying the conservation of structured RNAs. We found specific genomic regions, which highlight their patterns of conserved RNA structures at the level of inter-geographical comparisons. We have proposed these structures as candidates for further experimental validation to establish their potential role in vital functions of the viral cycle of ZIKV and their possible associations with the singularities of different outbreaks that occurred in specific geographic regions.

Tropical storm Nate, which was a powerful hurricane prior to landfall along the Alabama coast, traversed north towards our instrumented site in Hunstville, AL. The rain bands lasted 18 h and the 2D-video disdrometer (2DVD) captured the event which was shallow and indicative of pure warm rain processes. Measurements of raindrop size, shape and velocity distributions are quite rare in pure warm rain and are expected to differ from cold rain processes. In particular, asymmetric shapes due to drop oscillations and their impact on polarimetric radar signatures in warm rain have not been studied so far. Recently, the 2DVD data has been used for 3D reconstruction of asymmetric raindrop shapes but their fraction (relative to the more common oblate shapes) in warm rain has yet to be ascertained. Here we compute the scattering matrix drop-by-drop using Computer Simulation Technology integral equation solver for drop sizes>2.5 mm. From the scattering matrix elements, the polarimetric radar observables are simulated by integrating over 1 minute consecutive segments of the event. These simulated values are compared with dual-polarized C-band radar data located at 15 km range from the 2DVD site to evaluate the contribution of the asymmetric drop shapes.

The study proposes planning independent children's mobility through geoinformation technologies for listening to children. This research assumes that children’s values and expectations must be considered in city planning. A bibliographic review identifies 15 indicators which make spaces safe and attractive for children to circulate and play. Thematic maps of the indicators are prepared, integrated by Multicriteria Analysis by Weights of Evidence, according to the hierarchical importance of each variable. The definition of weights considers the opinion of children and technicians. Consultation with children is carried out by Mapping Volunteers (VGI), Consultation on Hierarchy, Geodesign of Ideas for the area and Artistic Workshop. In the technical study, the query applies the Delphi method. It uses the VGI – Volunteered Geographic Information – web-based platform, where children record places of topophilia and topophobia, while technicians map the presence of 15 indicators. The set of information is made available on a web-based platform of SDI – Spatial Data Infrastructure, in which there are resources for a Geodesign workshop when ideas for the area are elaborated through negotiation and co-creation. The product is a transformation design for the area through urban design and parameterisation of uses.

We seek to examine effective collaboration when engaging in value cocreation with the customer for mobile financial services in EMs. Our study is a motivation for multi-stakeholder engagement in value cocreation with financial inclusion of all consumers including marginalized populations. Furthermore, our work discovers that social sustainability is a product of social creativity and results in financial inclusion. We apply a qualitative descriptive methodology utilizing exemplars from extant research and phenomenology to analyze the data from the contexts of Ghana and Kenya. The results show that value is co-created for mobile financial services in networks in emerging markets when actors integrate resources for social and environmental sustainability as essential elements for mobile financial inclusion.

In recent years, the role of non-coding RNAs (ncRNAs) in regulating cell physiology has begun to be better understood. Recent discoveries in viral molecular biology have revealed that such cellular functions are disturbed during viral infections mainly due to host cell ncRNAs, cellular factors, and virus-derived ncRNAs. Apart from the interplay between those molecules, other interactions derive from the specific folding of RNA virus genomes. These fulfill canonical regulation functions such as replication, translation, and viral packaging. In some cases, folds serve as precursors of small viral RNAs whose biogenesis is not yet clearly understood. Since ncRNAs and RNA viral genomes modulate complex molecular and cellular processes in viral infections, a new taxonomy is being proposed here overarching three main categories, considering the current information about ncRNA interactions in some well-known viral infections. The first category shows examples of host ncRNAs associated with the trigger of the immune response under viral infections. The second category describes interactions between the virus and host ncRNAs. The last category shows how the shape of the RNA viral genome is essential in processing RNAs derived from viruses. Finally, we introduce evidence of how these three categories can also work as a framework in order to organize known interactions of ncRNAs and cellular factors under DENV infection. This new taxonomy of interactions provides a comprehensive framework for organizing the ncRNA regulatory roles in the context of viral interactions and an RNA world.

The neural crest, a unique cell population originating from the primitive neural field, has a multi-systemic and structural contribution to vertebrate development. At the cephalic level, the neural crest generates most of the skeletal tissues encasing the developing forebrain and provides the prosencephalon with functional vasculature and meninges. Over the last decade, we have demonstrated that the cephalic neural crest (CNC) exerts an autonomous and prominent control on forebrain and sense organs development. The present paper reviews the primary mechanisms by which CNC can orchestrate vertebrate encephalization. Demonstrating the role of the CNC as an exogenous source of patterning for the forebrain provides a novel conceptual framework with profound implications for understanding neurodevelopment. From a biomedical standpoint, these data suggest that the spectrum of neurocristopathies is broader than expected and that some neurological disorders may stem from CNC dysfunctions.

Although hundreds of keV in energy gain have already been demonstrated in dielectric laser accelerators (DLAs), there remains challenge in creating structures that can confine electrons for multiple millimeters. We focus here on dual gratings with single sided drive, which have experimentally demonstrated energy modulation numerous times. Using a FTDT simulation to find the fields within various DLA structures and correlating these results with particle tracking simulation, we look at the impact of teeth height and width, as well as gap and offset, on the performance of these structures. We find a tradeoff between electron throughput and acceleration, but that for any given grating geometry there is a gap and offset that will allow some charge acceleration. For our 780 nm laser wavelength, this results in a 1200 nm optimal gap size for most gratings.

The aim of this paper is to provide a new perspective on the conditions for the multiple dimensions of concerns, and to understand why some wind power projects run smoothly while others lead to unexpected outcomes due to local resistance. The paper described how multiple community concerns about wind power project planning can be described using conflict management theory and by using different procedures to handle tangible and intangible concerns. Policy recommendations are given on how: to minimise overflowing and the risk of the conflicts; to avoid “boxing” community concerns in categories; to give more attention to the intangible and less calculable concerns; to secure appropriate and early planning with proactive involvement of local communities.

Research on microglia in Down syndrome (DS) has shown that microglial activation, increased inflammatory gene expression, and oxidative stress occur at different ages in DS brains. However, most studies resulted in simplistic definitions of microglia as quiescent or active, ignoring potential intermediate states. However, a recent work on microglial cells in young DS brains indicated that those evolve through different intermediate activation phenotypes before reaching a full activated state. Here we used single nucleus RNA sequencing, to examine how trisomy affects microglial states in the Ts65Dn mouse model of DS. Despite no substantial changes in the proportion of glial populations, differential expression analysis revealed cell type-specific gene expression changes, most notably in astroglia, microglia, and oligodendroglia. Focusing on microglia, we identified differential expression of genes associated with different microglial states, including disease-associated microglia (DAMs), activated response microglia (ARMs), and human Alzheimer’s disease microglia (HAMs), in trisomic microglia. Furthermore, pseudotime analysis reveals a unique reactivity profile in Ts65Dn microglia, with fewer in a homeostatic state and more in an intermediate aberrantly reactive state than in euploid microglia. This comprehensive understanding of microglial transcriptional dynamics sheds light on potential pathogenetic mechanisms but also possible avenues for therapy for neurodevelopmental disorders.

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed .

Geoethics is a field of knowledge currently in full development. Researchers in geoethics are pri-marily concerned with the anthropogenic interaction with the Earth system. Due to its nature, ge-oethics holds particular importance in sustainable development due to its nature as it aims to promote ethical human behaviour that does not negatively impact the Earth system. In the present research, we implemented an intervention program addressing various issues related to the sus-tainability of the Earth system, such as the exploitation of geological resources, the management of geological risks, and the conservation and promotion of geopatrimony. The intervention program was applied to higher education students in the geosciences field. A sample of 90 students from various geosciences courses completed an initial questionnaire, revealing limited knowledge about geoethics. This study resorted to mixed-method research involving interviews with some students who volunteered (n=52). The results showed that after applying the intervention programme most students had developed a deeper understanding of the topics addressed and recognised the con-tributions this scientific area can make to sustainable development. Additional research in geoethics education is essential to foster the integration of geoethics into the curricula of higher education institutions.

"Hidden hunger", the deficiency of important mineral micronutrients, affects more than 2 billion people globally. Adolescence is unquestionably a period of nutritional risk, given the high nutritional requirements for growth and development, erratic or capricious diets and the increased consumption of snacks. This study applied the rational food design approach to obtain micronutrient-dense biscuits by combining chickpea and rice flours to achieve an optimal nutritional profile, crunchy texture and appealing flavour. The perception of 33 adolescents of the suitability of such biscuits as a mid-morning snack was examined. Four biscuits were formulated, with different ratios of chickpea and rice flours (CF:RF): G100:0, G75:25, G50:50 and G25:75. Nutritional content, baking loss, acoustic-texture and sensory analyses were carried out. On average, the mineral content of biscuits with the CF:RF ratio of 100:0 doubled compared with the 25:75 formula. The dietary reference values for iron, potassium and zinc reached 100% in the biscuits with CF:RF ratios of 50:50, 75:25 and 100:0, respectively. The analysis of mechanical properties revealed that samples G100:0 and G75:25 were harder than the others. Sample G100:0 showed the highest sound pressure level (Smax). Sensory analysis showed that increasing the proportion of CF in the formulation augments the grittiness, hardness, chewiness and crunchiness. Most of the adolescents (72.7%) were habitual snack consumers; 52% awarded scores ≥ 6 to biscuit G50:50 for its overall quality, 24% described its flavour as "biscuit" and 12% as "nutty". However, 55% of the participants could not pinpoint any dominant flavour. In conclusion, it is possible to design nutrient-dense snacks that meet the micronutrient requirements and sensory expectations of adolescents by combining flours naturally rich in micronutrients.

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS endowed with signalling properties are mainly produced by NADPH oxidases at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differs in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetics processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function as well as pharmacological strategies have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways.

The aim of this study was to evaluate the psychometric evidence of the original and brief version of the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) in Spanish in a sample of 245 Peruvian adolescents and adults (mean age = 21.04 years, SD = 3.07, 47.8% male and 52.2% female), selected by non-probabilistic convenience sampling. Additionally, the Coronavirus Anxiety Scale and the Satisfaction with Life Scale were applied. Confirmatory Factor Analysis, internal consistency reliability methods, hierarchical sequence of variance models and Graded Response Model were used. Results indicate that both versions of the SCSRFQ showed robust psychometric properties: adequate unidimensional structure, adequate difficulty and discrimination parameters, and significant relationships with the measures of fear of COVID-19 and satisfaction with life. The original version of the SCSRFQ showed evidence of strict measurement invariance by gender and age; whereas the short version showed strict invariance by gender and configural invariance by age. Both versions showed acceptable reliability indices. In conclusion, the original and brief versions of the SCSRFQ show evidence of psychometric indicators that support their use to assess the strength of religious faith

With rising rates of human obesity, the study aimed to determine the relationship between maternal diet-induced obesity and offspring morphometrics and behaviour in mice. Pregnant and lactating female mice fed a diet high in fat and sugar (HFHS) commonly consumed by human populations showed decreased food, calorie, and protein intake but increased adiposity at the expense of lean mass. The pre-weaning body weight of HFHS offspring was reduced for the first postnatal week but not thereafter with HFHS female offspring having higher body weights by weaning, due to continuing higher fractional growth rates. Post-weaning, there were minor differences in offspring food and protein intake. Maternal diet, however, affected fractional growth rate and total body fat content of male but not female HFHS offspring. Maternal diet did not affect offspring locomotor activity or social behaviour in either sex. Both male and female HFHS offspring displayed reduced anxiety-related behaviours with sex differences in particular aspects of the elevated plus maze task. In the novel object recognition task, performance was impaired in male but not female HFHS offspring. Collectively, the findings demonstrate that maternal obesity alters the growth, adiposity, and behaviour of male and female offspring, with sex-specific differences.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

The chemistry and electrochemistry basic fields have been active since the last two decades of the past century studying how surface modification of electrodes by coating with conductive films enhances their activity and performance. In the light of the development of alternative sustainable ways of energy storage and carbon dioxide conversion by electrochemical processes, these research studies have jumped in the 21st century to more applied fields such as chemical engineering, energy and environmental science and engineering. The huge amount of literature on experimental works dealing with the development of CO2 electroreduction processes addresses electrocatalyst development. Membranes can help understanding and controlling the mass transport limitations of current electrodes and reactors designs. The present bibliometric review addresses the papers published in the 21st century regarding membrane coated electrodes and electrocatalysts to enhance electrochemical reactor performance and viability with a special focus on the urgent issue of carbon dioxide capture and utilization.

We report here a giant microfossil resembling the conidium of an ascomycete fungus (cf. Alternaria alternata). The specimen is preserved in stromatolitic black chert of the Gunflint Iron Formation (Paleoproterozoic Eon, Orosirian Period, ca. 1.9-2.0 Ga) of southern Ontario, Canada, and the rock that provided the thin section may have been collected by Elso Barghoorn as part of the original discovery of the Gunflint microbiota. The large size of the fossil sets it apart from other, tiny by comparison, Gunflint microfossils. The fossil is 200 microns in length and has cross walls. Individual cells are 30-46 microns in greatest dimension. The apical ‘spore’ is cap-shaped, and has partly separated from the rest of the structure. Cloulicaria gunflintensis gen. nov. sp. nov. may provide early evidence for eukaryotes (fungi) in the fossil record, and may also represent the earliest evidence for asexual reproduction in a eukaryote by means of mitospores.

Speleothem oxygen isotope records from the Caribbean, Central, and North America reveal climatic controls that include orbital variation, deglacial forcing related to ocean circulation and ice sheet retreat, and the influence of local and remote sea surface temperature variations. Here, we review these records and the global climate teleconnections they suggest following the recent publication of the Speleothem Isotopes Synthesis and Analysis (SISAL) database. We find that low-latitude records generally reflect changes in precipitation, whereas higher latitude records are sensitive to temperature and moisture source variability. Tropical records suggest precipitation variability is forced by orbital precession and North Atlantic Ocean circulation driven changes in atmospheric convection on long timescales, and tropical sea surface temperature variations on short timescales. On millennial timescales, precipitation seasonality in southwestern North America is related to North Atlantic climate variability. Great Basin speleothem records are closely linked with changes in Northern Hemisphere summer insolation. Although speleothems have revealed these critical global climate teleconnections, the paucity of continuous records precludes our ability to investigate climate drivers from the whole of Central and North America for the Pleistocene through modern. This underscores the need to improve spatial and temporal coverage of speleothem records across this climatically variable region.

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.

The first FDA-approved drugs were small, chemically-manufactured and highly active molecules with possible off-target effects. After this first successful wave of small drugs, biotechnology allowed the development of protein-based medicines such as antibodies. Conventional antibodies bind a specific protein and are becoming increasingly important in the therapeutic landscape. A very prominent class of biologicals are the anti-TNF drugs that are applied in several inflammatory diseases that are characterized by dysregulated TNF levels. Marketing of TNF inhibitors revolutionized the treatment of diseases such as Crohn’s disease. However, these inhibitors also have undesired effects, some of them directly associated with the inherent nature of this drug class such as immunogenicity, whereas others are linked with their mechanism of action. Recently, researchers tried to design innovative drugs with reduced side effects aiming to make them more effective and safer. Molecules with more specificity e.g. that target one specific TNF format or receptor, or that neutralize the TNF signaling pathway in specific cells, are generated. Alternatively, TNF-directed biologicals without the typical antibody structure are manufactured. Here, we review the complications related to the use of conventional TNF inhibitors, together with the anti-TNF alternatives and the different (neurodegenerative) diseases that might benefit from selective approaches.

In most econometrics literature, the Autoregressive Distributed Lag (ARDL) model is often applied in many economic analyses to study short and long run relationships. This is because ARDL model can deal with economic variables that are integrated of different order (I(0), I(1) or combination of both) and also it is robust where there is single long-run relationship between the underlying variables in a simple sample size. This study applied the ARDL model to examine the contributions of commercial Banks to GDP growth in Nigeria. To achieve this, annual data covering 1981 to 2015 for loans and advances, savings, lending rates and GDP of Financial Institutions were collected from CBN bulletin. The ADF test revealed that the variables are I(1) except for lending rate which was of I(0) order. The ARDL(1,1,1,2) model revealed that loans and advances, and lending rates are significantly positively related to GDP in Nigeria but savings was not significant in the model. The model revealed some evidence of short run relationships while the ecm(-1) was -0.6156 (P-value=0.0038<0.05) which means that the rate of the speed of adjustment to equilibrium is 61.56% annually. The estimated model is free from serial correlation, multicollinearity, heteroscedasticity while the model is stable and the residuals are normally distributed. The study recommends that savings and savings culture should be encouraged in Nigeria since economic theory states that savings and investment are related in any economic development.

Despite many calls to reduce or eliminate the use of mechanical restraint, it is still widely used in many countries. Studies using patient interviews have a very clear message: Patients experience mechanical restraint as the most humiliating intervention. There seems to be a lack of alternatives with violent patients. We developed a method using 30 kg bags, originally designed for fitness purposes, to be attached to a patient's wrist or ankle under 1:1 supervision. The method was tested with 10 experienced nurses and de-escalation trainers. A video was made and presented to six outpatients who had previously experienced mechanical restraint. All participants were interviewed. Transcribed interviews were analysed using qualitative content analysis. All participants approved of the method as a milder and less humiliating alternative to mechanical restraint. Nurses' main concerns were the risk of falls and the use of the bags as a weapon. The latter could be controlled by using an additional bag. Patients were generally positive, especially if there was a history of abuse. The method should be further developed to replace at least part of mechanical restraints. As with all ‘milder means‘, care should be taken to really replace restraint and not to introduce additional coercion.

A critical aspect of coronary heart disease (CHD) care and secondary prevention is ensuring patients have access to evidence-based information. The purpose of this review is to summarise the guiding principles, content, context and timing of information and education that is beneficial for supporting people with CHD and potential communication strategies including digital interventions. We conducted a scoping review involving searching four databases (Web of Science, PubMed, CINAHL, Medline) for articles published from January 2000 to August 2022. Literature was identified through title and abstract screening by expert reviewers. Evidence was synthesised according to the review aims. Results demonstrated that information-sharing, decision-making, goal-setting, positivity and practicality are important aspects of secondary prevention and should be patient-centred and evidenced based with consideration of patient need and preference. Initiation and duration of education is highly variable between and within people, but hence communication and support should be regular and ongoing. In conclusion, text messaging programs, smartphone applications and wearable devices are examples of digital health strategies that facilitate education and support for patients with heart disease. There is no one size fits all approach that suits all patients at all stages and hence flexibility and a suite of resources and strategies is optimal.

Researchers have been exploring seaweed to reduce methane (CH4) emissions from livestock. This study aimed to investigate the potential of a red alga, Bonnemaisonia hamifera, as an alternative to mitigate CH4 emissions. B. hamifera, harvested from the West coast of Sweden, was used in an in vitro experiment using a fully automated gas production system. The experiment was a ran-domized complete block design consisting of a 48-h incubation that included a control (grass si-lage) and B. hamifera inclusions at 2.5%, 5.0% and 7.5% of grass silage OM mixed with buffered rumen fluid. Predicted in vivo CH4 production and total gas production were estimated by ap-plying a set of models to the gas production data and in vitro fermentation characteristics were evaluated. The results demonstrated that the inclusion of B. hamifera reduced (P = 0.01) predicted in vivo CH4 and total gas production, and total gas production linearly decreased (P = 0.03) with higher inclusion of B. hamifera. The molar proportion of propionate increased (P = 0.03) while isovalerate decreased (P = 0.04) with inclusion of B. hamifera. There was a tendency for increased (0.06 ≤ P ≤ 0.10) total volatile fatty acid production, as well as lower proportions of butyrate, isobutyrate, and 2-methylbutyrate. Chemical analyses revealed that B. hamifera had moderate concentrations of polyphenols. The iodine content was low and there was no detectable bromo-form, suggesting quality advantages over Asparagopsis taxiformis. Additionally, B. hamifera exhib-ited antioxidant activity comparable to the positive control Resveratrol. The findings of this study indicated that B. hamifera harvested from temperate waters in Sweden possesses capacity to mitigate CH4 in vitro.

As overeating, overweight and obesity remain public health concerns, it is crucial to design satiety-enhancing foods that suppress appetite and lower snack intake. Existing research identifies oro-sensory targets to promote satiation and satiety within the “satiety cascade” yet it remains unclear as to whether it is ‘chewing’ or ‘oral lubrication’ that might amplify satiation signals.Here we have combined techniques from experimental psychology, food material science and mechanical engineering to measure the role of chewing and lubrication using novel, model foods as preloads on subjective appetite and intake of a salty snack. Three mint flavoured hydrogels were engineered to vary in their texture (fracture stress) and lubrication (inverse of friction coefficient) properties, and a control group received a mint tea. Results showed that snack intake was suppressed by 32% after eating the low chewing/high lubricating preload as compared to the high chewing/low lubricating preload (p<0.05). No other significant effects were found for snack intake. Hunger ratings decreased from t1 to t3 (p<0.05), however differences between conditions were subtle and not significant. Thus, this proof-of-concept study demonstrates that manipulating oral lubrication is a promising new construct to reduce snack intake that merits future research in the oro-sensory satiety domain.

In this review, we provide an overview of the current knowledge on the different sexual systems and sex determining mechanisms in bivalves, with a focus on the various epigenetic and genetic factors that may be involved. The final section of the review provides recent discoveries on sex-specific mitochondrial genes in bivalves possessing the unconventional system of doubly uniparental inheritance of mitochondria (which is found in several members of the orders Mytiloida, Unionoida, Veneroida and Nuculanoida). The genes involved in this developmental pathway could represent the first sex determination system in animals in which mitochondrially-encoded genes are directly involved.

The Covid-19 pandemic and the initial focus on handwashing measures have again highlighted the importance of water access as an essential service in protecting human health. Yet, especially in southern cities, uneven geographies of water access – often mediated by fragmented and unequal infrastructure systems – may hamper the fight against infectious diseases. The spread of SARS-CoV-2 presented a dilemma for water providers as well as residents in water-deprived urban areas as they had to adhere to new hygiene standards and requirements, despite limited access to basic water infrastructure. Therefore, a deeper understanding of pandemic urban waterscapes – the infrastructure and governance systems as well as everyday practices and technologies – is necessary for ongoing debates on (post-) pandemic or zoonotic cities. In our paper, we focus on changes in urban (water) governance and government water projects in Nairobi since early 2020. We show that Covid-19 has contributed to changes in Nairobi’s waterscape but only in conjunction with recent changes in the city’s overall governance structure. However, if these waterscape changes lead to greater equity in water access, and if they have helped to curb the spread of SARS-CoV-2, is more than questionable.

As a result of the growing demand for foods with reduced animal protein content, many new alternative diets are now emerging. Nevertheless, recent studies have shown that the Western population is unprepared for drastic changes and is disinclined to accept foods based on alternative proteins. However, hybrid products might become a good transitional offer. This study used a desirability-based mixture design to model hybrid spreadable cheese analogues (SCAs). The design combined the dairy protein (MPC), Tenebrio molitor (IF) and faba bean (FBP) flours. Nine SCAs with different MPC/FBP/IF ratios were formulated, representing 0, 50 and 100% MPC replacement (7.1% of the formula). Incorporating the IF negatively impacted the desirable texture properties. The FBP flour improved the texture (achieving increased firmness and stickiness and decreased spreadability), but only when combined with MPC. Changing the MPC/FBP/IF ratio affected the colour of SCAs. Sensory analysis showed that hybrid SCAs (≤ 50% MPC) had a more characteristic cheesy flavour than the commercial plant-based reference, and sample C2 had a texture profile similar to the dairy reference. Samples containing IF showed a better flavour profile than the products without IF. The SCAs had higher protein and lower saturated fat, starch and sugar con-tent than commercial analogues.This study demonstrates that the inclusion of alternative proteins can be effective as a strategy to reduce dairy protein content in hybrid product formulations.

Severe COVID-19 is a major cause of morbidity and mortality worldwide, especially to those with co-morbidities, the elderly and the immunocompromised. However, the molecular determinants critical for severe COVID-19 progression remain to be fully elucidated. Meta-analysis of transcriptomic RNAseq and single-cell sequencing datasets comparing between severe and mild COVID-19 patients have demonstrated that the early expansion of myeloid-derived suppressor cells (MDSCs) could a key feature of severe COVID-19 progression. Besides serving as potential early prognostic biomarkers for severe COVID-19 progression, several studies have also indicated the functional roles of MDSCs in severe COVID-19 pathogenesis and possibly even long COVID. Given the potential links between MDSCs and severe COVID-19, we examined the existing literature summarizing the characteristics of MDSCs, the evidence of MDSCs in facilitating severe COVID-19 pathogenesis and discuss the potential therapeutic avenues that can be explored to reduce the risk and burden of severe COVID-19. We also provide a web app where users can visualise the temporal changes of specific genes or MDSC-related gene sets during severe COVID-19 progression and disease resolution at https://temporal-severe-covid.streamlit.app/, based on our previous study described by Ong et al., 2021.

The severity of the global COVID-19 pandemic, with a high transmission rate, 2.6-4.7% lethality and a huge economic impact, poses an urgent need for efficient medical treatments and vaccines. Currently, there are only non-specific treatments to assist the patients in acute respiratory distress during the inflammatory step following the preliminary infection by SARS-CoV-2. Clinical trials of drug repurposing were quickly launched at the international level. Specific treatments such as the transfusion of plasma from patients who have recovered into infected patients or the use of specific inhibitors of the viral RNA-polymerase complex are promising strategies to block infection. To complete the therapeutic arsenal, we believe that the opportunity of targeting the SARS-CoV-2 genome by RNA therapy should be deeply investigated. In the present paper, we propose to design specific antisense oligonucleotides targeting transcripts encoding viral proteins associated to replication and transcription of SARS-CoV-2, aiming to block infection. We designed antisense oligonucleotides targeting the genomic 5’ untranslated region (5’-UTR), open reading frames 1a and 1b (ORF1a and ORF1b) governing expression of the replicase/transcriptase complex, and the gene N encoding the nucleoprotein that is genome-associated. To maximize the probability of efficiency, we predicted the antisense oligonucleotides by using two design methods: i) conventional antisense oligonucleotides with 100% phosphorothioate modifications (ASO); ii) antisense locked nucleic acids GapmeR. After binding the viral RNA target, the hetero-duplexes antisense oligonucleotide-RNA are cleaved by RNAse H1. Nine potent ASO candidates were found and we selected five of them targeting ORF1a (3), ORF1b (1) and N (1). Nine GapmeR candidates were predicted with excellent properties and we retained four of them targeting 5’-UTR (1), ORF1a (3), ORF1b (1) and N (1). The most potent GapmeR candidate targets the 5’-UTR, a key genomic domain with multiple functions in the viral cycle. By this open publication, we are pleased to share these in silico results with the scientific community in hopes of stimulating innovation in translational research in order to fight the unprecedented COVID-19 pandemic. These antisense oligonucleotide candidates should be now experimentally evaluated.

Eastern boundary upwelling systems feature strong zonal gradients of physical and biological ocean properties between cool, productive coastal oceans and warm, oligotrophic subtropical gyres. Zonal currents and jets (striations) are therefore likely to contribute to the transport of water properties between coastal and open oceanic regions. Multi-sensor satellite data are used to characterize the signatures of striations in sea surface temperature (SST), salinity (SSS), and chlorophyll-a (Chl-a) in subtropical eastern North/South Pacific (ENP/ESP) upwelling systems. In the ENP, tracers exhibit striated patterns extending up to ~2500 km offshore. Striations in SST and SSS are highly correlated with quasi-zonal jets, suggesting that these jets contribute to SST/SSS mesoscale patterns via zonal advection. Chl-a striations are collocated with sea surface height (SSH) bands, a possible result of mesoscale eddy trains trapping nutrients and forming striated signals. In the ESP, striations are only found in SST and coincide with SSH bands, consistently with quasi-zonal jets located outside major zonal tracer gradients. An interplay between large-scale SST/SSS advection by the quasi-zonal jets, mesoscale SST/SSS advection by the large-scale meridional flow and eddy advection may explain the persistent ENP hydrographic striations. These results underline the importance of quasi-zonal jets for surface tracer structuring at the mesoscale.

Emerin is a nuclear envelope protein that contributes to genome organization and cell mechanics. Through its N-terminal LEM-domain, emerin interacts with the DNA-binding protein Barrier-to-Autointegration (BAF). Emerin also binds to members of the Linker of the Nucleoskeleton and Cytoskeleton (LINC) complex. Mutations in the gene encoding emerin are responsible for the majority of cases of X-linked Emery-Dreifuss Muscular Dystrophy (X-EDMD). Most of these mutations lead to an absence of emerin. A few missense and short deletion mutations in the disordered region of emerin are also associated with X-EDMD. More recently, missense and short deletion mutations P22L, ∆K37 and T43I were discovered in emerin LEM-domain, associated with isolated atrial cardiac defects (ACD). Here we reveal which defects, at both molecular and cellular levels, are elicited by these LEM-domain mutations. Whereas DK37 mutation impairs correct folding of the LEM-domain, P22L and T43I have no impact on the 3D structure of emerin. Surprisingly, all three mutants bind to BAF, albeit with a weaker affinity in the case of DK37. In human myofibroblasts derived from a patient’s fibroblasts, emerin ∆K37 is correctly localized at the inner nuclear membrane, but is present at a significantly lower level, indicating that this mutant is abnormally degraded. Moreover, SUN2 is reduced, and cells are defective in producing actin stress fibers when grown on a stiff substrate and after cyclic stretches. Altogether, our data suggest that the main effect of mutation DK37 is to perturb emerin function within the LINC complex in response to a mechanical stress.

The diagnosis and the pathology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) remain under debate. However, there is a growing body of evidence for an autoimmune component in ME/CFS caused by the Epstein-Barr virus (EBV) and other viral infections. In this work, we took advantage of a large public dataset on the IgG antibodies to 3,054 EBV peptides to understand whether these immune responses could be used as putative biomarkers for disease diagnosis and triggers of pathological autoimmunity in ME/CFS patients using healthy controls (HCs) as a comparator cohort. We then aimed at predicting disease status of study participants using a Super Learner algorithm targeting an accuracy of 85% when splitting data into train and test datasets. When we compared data of all ME/CFS patients or data of a subgroup of these patients with non-infectious or unknown disease trigger to the dataset of HC, we could not find an antibody-based classifier that would meet the desired accuracy in the test dataset. In contrast, we could identify a 26-antibody classifier that could distinguish ME/CFS patients with an infectious disease trigger from HCs with 100% and 90% accuracies on the train and test sets, respectively. We finally performed a bioinformatic analysis of the EBV peptides associated with these 26 antibodies. We found no correlation between the importance metric of the selected antibodies in the classifier and the maximal sequence homology between human proteins and each EBV peptide recognized by these antibodies. In conclusion, these 26 antibodies against EBV have an effective potential for disease diagnosis of a subset of patients, but they are less likely to trigger pathological autoimmune responses that could explain the pathogenesis of ME/CFS.

(1) Background: In Eugenia Stipitata Mac Vaugh (Arazá), there is an abundance of flavonoids, carotenoids, and phenolic acids, which are bioactive compounds with antioxidant, anticarcinogenic, antimicrobial, anti-inflammatory, antispasmodic, antiulcer, and cardiovascular disease prevention benefits. Therefore, the aim of this review is to compile the compounds that have been identified in the fruit and gather information about secondary metabolites to establish their potential preventive and therapeutic effects; (2) Methods: a literature search was conducted in repositories and databases such as Science Direct, Scopus, PubMed, Web of Science, Agriculture Collection Gale, SAGE, OXFORD University, DOAJ, among others. Articles identifying and quantifying bioactive compounds present in Arazá were included; (3) Results: Five studies meeting the inclusion criteria were incorporated, resulting in the compilation of 82 compounds, of which 24 were identified and quantified, while 58 were solely identified. This review was able to identify and report the concentration, and in some cases, the quantity, of phenolic compounds with antioxidant and anti-inflammatory capabilities present in Arazá; (4) Conclusions: With this scope, it was possible to obtain a more comprehensive understanding of the fruit's potential to potentially enhance health aspects, thereby providing greater prominence and added value to this product, allowing for more frequent inclusion in the diets of consumers, and even enabling exportation.

Despite the important role that the GH/IGF-I axis plays in vascular homeostasis, these kind of growth factors barely appear in articles addressing the neovascularization process. Currently, the vascular endothelium has turned to be considered as an authentic gland of internal secretion due to the wide variety of released factors and functions with local effect, including the paracrine/autocrine production of GH or IGF-I, for which the endothelium has specific receptors. In this comprehensive review, it will be described the evidence involving these proangiogenic hormones in arteriogenesis dealing with the arterial occlusion and making of them a potential therapy. It will be analyzed all those elements triggering the local and systemic production of GH/IGF-I and their possible role both in physiological and pathological conditions. The whole evidence will be combined with important data from the GHAS trial, in which GH or placebo were administrated to patients suffering from critical limb ischemia with no option for revascularization. We postulate that GH, alone or in combination, should be considered as a promising therapeutic agent for helping in the approach of the ischemic disease.

Since smart cities aim at becoming self-monitoring and self-response systems, their deployment relies on close resource monitoring through large-scale urban sensing. The subsequent gathering of massive amounts of data makes essential the development of event filtering mechanisms that enable the selection of what is relevant and trustworthy. Due to the rise of mobile event producers, location information has become a valuable filtering criterion as it not only offers extra information on the event described but also enhances trust on the producer. Implementing mechanisms that validate the quality of location information becomes then imperative. The lack of such strategies in cloud architectures compels the adoption of new communication schemes for IoT-based urban services. To serve the demand for location verification in urban event-based systems (DEBS), we have designed three different fog architectures that combine proximity and cloud communication. Moreover, we have successfully assessed their performance using network simulations with realistic urban traces.

Mammals have two insulin-like growth factors (IGF) that are key mediators of somatic growth, of tissue differentiation and cellular responses to stress. Thus, the mechanisms that regulate the bioavailability of IGFs are important in both normal and aberrant development. IGF-I levels are primarily controlled via the growth hormone-IGF axis, in response to nutritional status, and also reflect metabolic diseases and cancer. One mechanism that controls IGF bioavailablity is the binding of circulating IGF to a number of binding proteins that keep IGF in a stable, but receptor non-binding state. But even before IGF is released from the cells that produce it, it undergoes an obligatory association with a ubiquitous chaperone protein, GRP94. This binding is required for secretion of a properly folded, mature IGF. This chapter reviews the known aspects of the interaction and highlights the specificity issues yet to be determined. The IGF-GRP94 interaction provides a potential novel mechanism of idiopathic short stature, involving the obligatory chaperone and not just IGF gene expression. It also provides a novel target for cancer treatment, as GRP94 activity can be either inhibited or enhanced.

This study aimed to assess the microbiological quality of set of fruits and vegetables sold on stalls in the streets and open markets of Dakar, the capital city of Senegal. Samples purchased in seven sites were analyzed to isolate E. coli, Salmonella spp. and Vibrio spp. Some primary samples with a positive microbiological culture were subjected to DNA extraction and subsequent metagenomic analysis. A total of 240 fresh fruit and vegetable samples were collected including lettuce (n=40), tomatoes (n=40), mango slices (n=40), onion slices (n=40), mint leaves (n=40), strawberries and grapes (respectively n=20). Of these samples, 50.83% (122/240) and 60.41% (145/240) was contaminated with Escherichia coli and Vibrio spp. respectively, while Salmonella was not isolated in any product. Levels of contamination with both E. coli (1.3 103 to 6 106 CFU/g) and Vibrio spp. (4.55 102 to 8.73 106 CFU/g) were significantly above the thresholds acceptable for human consumption. The most contaminated samples were lettuce with a prevalence of 98% (39/40) for E. coli and for Vibrio spp. followed by mint leaves with 100% (40/40) and 93% (37/40) of the samples containing for E. coli and Vibrio spp. respectively. Out of 46 samples sequenced, metagenomic analysis revealed high contamination rates for E. coli, Vibrio spp. and Salmonella spp. with 100%, 67.39% and 93.47% of prevalence respectively. On the other hand, the alpha diversity analysis shows a high bacterial diversity in lettuce and mint leaf samples while beta diversity analysis highlighted the presence of two major clusters. Our results stress the need of a surveillance system that extends this investigation to a national scale while increasing the number of sampling sites and products analyzed.

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided bra-chial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 ml kg-1), and eight received lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 minute-1). Rescue analgesia was provided with Fentanyl IV. Carprofen was administered at the end of surgery. Post-operative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered accord-ing to pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to no rabbits in BPB. How-ever, rabbits in both groups had similar pain scores and there was no difference in administration of postoperative analgesia. There were no significant differences in food intake or faeces produc-tion over 18 hours, and no significant differences in distance travelled, or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively both groups were comparable.

Background: Vascular inflammation plays a crucial role in peripheral arterial disease (PAD), although the role of the mediators involved has not yet been properly defined. The aim of this work is to investigate gene expression and plasma biomarkers in chronic limb-threating ischemia (CLTI). Methods: Using patients from the GHAS trial, both blood and ischemic muscle samples were obtained to analyze plasma markers and mRNA expression, respectively. Statistical analy-sis was performed by using univariate (Spearman, t-Student, X2) and multivariate (multiple lo-gistic regression) tests. Results: 35 patients were available at baseline (29 for mRNA expression). Baseline characteristics (mean): Age:71.4±12.4 (79.4% male); TNF-α:10.7±4.9; hs-CRP:1.6±2.2; Neutrophil-to-lymphocyte ratio (NLR):3.5±2.8. Plasma TNF-α was found elevated (≥8.1) in 68.6% of patients, while high hs-CRP (≥0.5) in 60.5%. Diabetic patients with high level of inflammation showed significantly higher levels of NOX4 expression at baseline (p=0.0346). Plasma TNF-α had a negative correlation with eNOS expression (-0.5, p=0.015) and hs-CRP with VEGF-A (-0.63, p=0.005). The expression of NOX4 was parallel to that of plasma TNF-α (0.305, p=0.037), especial-ly in DM. Cumulative mortality at 12-month was related to NLR ≥3 (p=0.019) and TNF-α ≥8.1 (p=0.048). The best cut-off point for NLR to predict mortality was 3.4. Conclusions: NOX4 and TNF-α are crucial for the development and complications of lower limb ischemia, especially in DM. hs-CRP could have a negative influence on angiogenesis too. NLR and TNF-α represent suita-ble markers of mortality in CLTI. These results are novel because they connect muscle gene expres-sion and plasma information in patients with advanced PAD, deepening the search of new and ac-curate targets for this condition.

The threat of antimicrobial resistance to society is compounded by a relative lack of new clinically effective licensed therapies reaching patients over the past three decades. This has been particularly problematic within antifungal drug development leading to a rise in fungal infection rates and associated mortality. This paper highlights the potential of an ultrashort peptide, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFKK-OH), encompassing hydrogel-forming and antifungal properties within a single peptide motif, thus overcoming formulation (e.g. solubility, drug loading) issues associated with many current employed highly hydrophobic antifungals. A range of fungal susceptibility (colony counts) and cell cytotoxicity (MTS cell viability, LIVE/DEAD staining® with fluorescent microscopy, haemolysis) assays were employed. Scanning electron microscopy confirmed the nanofibrous architecture of our self-assembling peptide, existing as a hydrogel at concentrations of 1% w/v and above. Broad-spectrum activity was demonstrated against a range of fungi clinically relevant to infection (Aspergillus niger, Candida glabrata, Candida albicans, Candida parapsilosis and Candida dubliniensis) with greater than 4 log10 CFU/mL reduction at concentrations of 0.5% w/v and above. We hypothesise antifungal activity is due to targeting of anionic components present within fungal cell membranes resulting in membrane disruption and cell lysis. NapFFKK-OH demonstrated reduced toxicity against mammalian cells (NCTC 929, ARPE-19) suggesting increased selectivity for fungal cells. However, further studies relating to safety for systemic administration is required, given the challenges toxicity has presented in the wider context of antimicrobial peptide drug development. Overall this study highlights the promise of NapFFKK-OH hydrogels, particularly as a topical formulation for the treatment of fungal infections relating to the skin and eyes, or as a hydrogel coating for the prevention of biomaterial related infection.

Diffuse type of gastric cancer (GC) has an increasing prevalence worldwide, especially in Western countries, is usually diagnosed at advanced stages, and has no efficacious treatment options. Epidemiological studies have reported an increased mortality from GC after occupational exposure to well-studied pro-carcinogen that are metabolically activated by Cyp P450 enzymes through aryl hydrocarbon receptor (AhR). Substantial studies support the involvement of AhR in gastric carcinogenesis. However, little is known about the role of AhR in diffuse GC, as compared to intestinal GC. In a cohort of 29 gastric tumors, we described a significantly increased AhR protein and mRNA expression levels in GCs, independently of subtypes and clinical parameters. AhR and RhoA mRNA expression were correlated in diffuse GC. Further, our study characterized how AhR affects gene expression in diffuse GC. Using qRT-PCR, we compared the expression levels of AhR, Cyp1A1 and Cyp1B1 to the expression of genes in a panel previously described. In diffuse GC, Cyp1A1 expression correlated with genes involved in IGF signalling, EMT (VIM), migration (MMP2). In an in vitro assay using the poorly differentiated KATOIII epithelial cell line, two well-known ligands for AhR (TCDD and BaP) induced mRNA expression of CYP1A1, IL1b, as well as UGT1, NQO1 and AhRR to a lower extent. We also observed a strong increase in Cyp1B1 expression in diffuse GC, along with a lower TCDD-increased Cyp1B1 expression as compared to Cyp1A1 in KATOIII cells, and immunostaining in stromal cells. In intestinal GC, Cyp1B1 inversely correlated with several genes including IDO1 (generating endogenous kynurenin-e AhR ligand). Our data provide evidence for a major role of AhR in GC, as an environmental xenobiotics receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support continued efforts to clarify the identities of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

MicroRNAs are small non-coding RNAs, which contribute to the regulation of many physiolog-ical and pathological processes. Conventionally, miRNAs perform their activity in the cyto-plasm, where they regulate gene expression by interacting in a sequence-specific manner with mature messenger RNAs. Recent studies point to the presence of mature miRNAs in the nucleus. This review summarizes current findings regarding the molecular activities of nuclear miRNAs. These molecules can regulate gene expression at the transcriptional level by directly binding DNA on the promoter or the enhancer of regulated genes. MiRNAs recruit to these regions dif-ferent protein complexes, resulting both in activation or repression of transcription, through a number of molecular mechanisms. Haematopoiesis is presented as a paradigmatic biological process whereby nuclear miRNAs possess a relevant regulatory role. Nuclear miRNAs may af-fect gene expression also acting on nuclear mRNA processing and on the biogenesis of miRNA themselves by regulating pri-miRNA maturation. Overall, nuclear miRNAs are biologically ac-tive molecules that can be critical for the fine tuning of gene expression and deserve further studies in a number of physiological and pathological conditions

There is no doubt that seagrass beds constitute one of the most productive ecosystems in shallow coastal waters. Despite this, picoplankton in seagrass ecosystems has received relatively little attention. The purpose of this study was to compare picoplankton growth and mortality rates between seagrass and unvegetated habitats using chamber incubations. We tested two main hypotheses: (i) incubation with seagrass would result in higher bacterial growth rates due to increased DOM release from seagrass photosynthesis, and (ii) Synechococcus spp. would be lower in the presence of seagrass due to competition for inorganic nutrients. Our results showed bacterial growth rates of 2.31 and 2.44 d–1 without and with seagrass, respectively. In seagrass chambers, bacterial growth was higher than that in non-seagrass chambers, suggesting that organic carbon coming from the seagrass community may support bacterial production. Furthermore, we observed a negative Synechococcus spp. growth rate (-0.9 d–1) in the seagrass treatment, likely reflecting nutrient competition with the seagrass. Small-scale chambers proved to be a useful tool for studying the factors controlling spatial and temporal patterns of picoplankton across different habitats. Furthermore, future studies should examine picoplankton growth over a wider range of spatial scales in seagrass beds and adjacent unvegetated sediment.

Cognitive impairment in older adults is associated with poor gait performance, physical decline, falls and poor quality of life. This paper analyzes the feasibility and efficacy of a tango-based in-tervention in older people with cognitive impairment living in nursing homes. A multicenter study, with pre and post-test, was carried out. Intervention attendance, well-being, physical abilities (Short Physical Performance Battery), walking performance, functional capacities (Katz Index), and quality of life (Quality of Life in Alzheimer’s Disease) were assessed. Fifty-four participants (84.9 ± 6.7 years, Mini Mental State Examination 14.5 ± 7.4) completed the protocol. Intervention attendance was 92%, and the mean subjective well-being after each session was 4.5 ± 0.5 (on a five-point scale). Statistically significant improvement was found in the quality of life (p = 0.030). Non statistically significant changes were found in walking performance, physical abilities, or in functional capacities. The study shows feasibility and suggests evidence for the effects of Tango therapy on well-being and quality of life. Further studies are necessary to contrast these findings and to verify the role of Tango interventions as a holistic approach to prevent functional decline in older people with cognitive impairment.

The clinical application of Phentolamine Mesylate (PM) as an anaesthetic reversal agent has been documented in paediatric patients and in conservative dentistry, but no studies have been found in implant surgery. A prospective randomised study was conducted in 60 patients eligible for mandibular implant treatment, randomly divided between the Control Group (CG) and Experimental Group (EG), who were administered PM. Haemodynamic changes, adverse effects and patient satisfaction were assessed. No statistically significant differences in haemodynamic changes and postoperative pain were found between CG and EG (p&lt;0.05), except for Systolic Blood Pressure (SBP) which increased slightly in EG, without posing a risk to the patient. There were no differences in the presence of adverse effects between the two groups, except in the CG which presented greater difficulty in chewing and biting (p&lt;0.05) and the EG with greater pain in the injection area (p=0.043). 83.3% of the EG patients would request PM again for future dental treatment. The use of PM offers an alternative in implant surgery, without increasing the risks and increasing the patient's quality of life.

Proteins are the main active molecules of Life. While natural proteins play many roles, as enzymes or antibodies for example, there is a need to go beyond the repertoire of natural proteins to produce engineered proteins that precisely meet application requirements, in terms of function, stability, activity or other protein capacities. Computational Protein Design aims at designing new proteins from first principles, using full-atom molecular models. However, the size and complexity of proteins require approximations to make them amenable to energetic optimization queries. These approximations make the design process less reliable and a provable optimal solution may fail. In practice, expensive libraries of solutions are therefore generated and tested. In this paper, we explore the idea of generating libraries of provably diverse low energy solutions by extending Cost Function Network algorithms with dedicated automaton-based diversity constraints on a large set of realistic full protein redesign problems. We observe that it is possible to generate provably diverse libraries in reasonable time and that the produced libraries do enhance the Native Sequence Recovery, a traditional measure of design methods reliability.

Several studies have already demonstrated the relationship between the loss of natural habitats and the incidence of diseases caused by vectors, such as dengue, which is an acute fever disease, considered a serious public health problem. The aim of the present study was to analyze the relationship between land use changes between 2009 and 2019 and the occurrence of dengue fever in 2015 and 2019 by municipality, using the state of Minas Gerais as a case study. For this, secondary data obtained from openly available sources were used. Natural vegetation cover data were obtained from the MAPBiomas platform and dengue occurrence data from the Ministry of Health, in addition to socioeconomic indicators from the Brazilian Institute for Geography and Statistics. Between 2015 and 2019, 1,255,731 cases of dengue were recorded throughout the state of Minas Gerais, ranging from 0 to 227 per thousand inhabitants between municipalities. The occurrence of dengue was distributed throughout all regions of Minas Gerais, affected by climatic and socioeconomic aspects. In general, municipalities with net loss of natural vegetation, predominantly located in the Cerrado biome, had the highest number of dengue cases in the studied period. Despite the significant positive relationship between these two variables, three of the eight socioeconomic parameters analyzed also affected the occurrence of dengue: population density, human development index (both positively) and Gini inequality index (negatively). These results indicate that, contrary to expectations, municipalities with better social conditions had more dengue cases. Our study indicates that natural vegetation is, directly or indirectly, involved in the ecosystem service of dengue control, despite the occurrence of this disease being affected by multiple factors that interact in a complex way. Thus, policies towards reducing deforestation must be complemented by a continuous investment in public health policies and reduction of social inequalities to efficiently control dengue fever.

The concept of genetic improvement in relation to biological control involves the exploitation of natural genetic variation for the benefit of existing biological control agents (BCAs). Despite recent calls for this process to be adopted in biological control research, there is no clear overview of the current state of research into genetic variation within a biological control context, including quantifiable estimates such as narrow-sense heritability (h²). In this systematic review, we aim to determine the current state of research on the genetic variation of biological control traits in natural enemies. After the searching process, screening for papers that can deliver on our research question reduced the initial 2,927 search hits to only a mere 69 papers for data extraction. Of these, the majority (73.6%) did not report quantitative values for genetic variation. Extracting the traits measured in these papers, we categorized them according to two approaches; the first related to fitness components, and the second related to biological control importance. This systematic review highlights the need for more rigorous reporting of the quantitative values of genetic variation to enable the successful genetic improvement of biological control agents.

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 Smart Angel connected medical device allows ambulatory surgery patients to monitor their health by taking their own blood pressure and oxygen levels and by answering a health questionnaire from home. This preventive device must necessarily be "usable" by patients with different profiles. The objective of this article is, therefore, to better understand the links between certain characteristics of potential patients and usability. We conducted an experimental study involving thirty-six participants, investigating the effects of four patient characteristics (i.e. age, education, technophilia and health literacy) on usability measured in terms of effectiveness, efficiency, and satisfaction. The results show a moderate correlation between age, health literacy and usability. However, there is a weak correlation between technophilia and usability and no relationship between the level of education and usability. This study provides theoretical insights into the effects of user characteristics by means of personas in usability (ISO 9241-11).

The Surface Water and Ocean Topography (SWOT) mission, to be launched in 2021, will provide water surface elevations, slopes, and river width measurements for rivers wider than 100 m. In this study, synthetic SWOT data are assimilated in a regional hydrometeorological model in order to improve the dynamics of continental waters over the Garonne catchment, one of the major French catchments. The aim of this paper is to demonstrate that the sequential assimilation of SWOT-like river depths allows the correction of river bed roughness coefficients and thus simulated river depths. An extended Kalman Filter is implemented and the data assimilation strategy was applied to four experiments of gradually increasing complexity regarding observation and model error over the 1995-2000 period. With respect to a “true” river state, assimilating river depths allows the proper retrieval of constant and spatially distributed roughness coefficients with a root mean square error of 1 m1/3 s-1, and the estimation of associated river depths. It was also shown that river depth differences can be assimilated, resulting in a higher root mean square error for roughness coefficients with respect to the true river state. The last study shows how one can take into account more realistic sources of SWOT error measurements, in particular the importance of the estimation of the tropospheric water content in the process.

Background: The aim of this study was to design and analyze the content validity of an instrument to assess the risk of behaviors associated with the Chemsex phenomenon since there is currently no instrument with this objective. Method: Firstly, a bank of items identified from the literature was elaborated. Secondly, 50 experts with knowledge of the Chemsex phenomenon at the national level were contacted. A Delphi group was formed with them to carry out two rounds of item evaluation (comprehension and appropriateness) using a Likert scale of 1 to 5. To assess linguistic validity, the mean score of the item comprehension scores was used. The content validity index (CVI) and Aiken's V (VdA) were calculated for each item. A minimum value of CVI and VdA of 0.6 was established to include the items in the questionnaire. Results: In the first round of evaluation, 36 experts evaluated 114 items, of which 61 were selected. In a second round, 30 experts evaluated the 61 items selected, leaving the scale finally made up of 52 items. Conclusion: A questionnaire has been designed to assess the risk of behaviors associated with the Chemsex phenomenon. The items that make up the questionnaire have shown adequate content and linguistic validity, so this instrument can be considered valid. The Delphi method proved to be a useful technique for the proposed objective.

Background. The treatment of coronary stenosis relies on invasive high risk surgical assessment to generate the fractional flow reserve diagnostics index, a ratio of distal to proximal pressures in respect of coronary atherosclerotic plaque causing stenosis. Non-invasive methods are therefore a need of the times. This study proposes an extensible mathematical description of the coronary vasculature that permits rapid estimation of the coronary fractional flow reserve. Methods. By adapting an existing closed loop model of human coronary blood flow, the effects of large vessel stenosis and microvascular disease on fractional flow reserve were quantified. Several simula-tions generated flow and pressure information which was used to compute fractional flow re-serve under a spectrum of conditions including focal stenosis, diffuse stenosis, and microvascular disease. Sensitivity analysis stratified the influence of model parameters on the index. The model was simulated as coupled non-linear ordinary differential equations and numerically solved us-ing an implicit higher order method. Results. Large vessel stenosis affected fractional flow re-serve. The model predicts that the presence, rather than severity, of microvascular disease affect coronary flow deleteriously. Sensitivity analysis revealed that heart rate may not affect the index. Conclusions. The model provides a computationally inexpensive instrument for future in silico coronary blood flow investigations as well as clinical-imaging decision making. A combination of focal and diffuse stenosis appears to be essential in reducing the index. In addition to pressure measurements in the large epicardial vessels, diagnosis of microvascular disease is essential. The independence of the index with respect to heart rate suggests that computationally inexpensive steady state simulations may provide sufficient information to reliably compute the index.

Micromobility has gained attention from policymakers, industry stakeholders, and academia; however, a comprehensive conceptualization of micromobility is still missing. Existing definitions are largely vehicle-centric: either listing modes or detailing vehicle characteristics. This paper addresses this gap by developing a ‘beyond vehicles’, multi-dimensional conceptualization of micromobility, accompanied by a novel socio-technical definition. Through a review of related concepts, combined with an analysis of the use and definitions of the term micromobility in publications, this study establishes a new conceptualization of micromobility. It incorporates human, social, and cultural dimensions, considers environmental, economic, infrastructure, vehicle technology, regulatory and policy aspects, and considerations for public health. Our definition of micromobility encompasses a wide range of mobility options typically used for shorter trips and manoeuvrable by an individual without motor assistance, at least for short distances. These modes are characterized by their ‘micro’ attributes, including low energy demand, environmental impact, and road space use relative to automobility. The conceptualization incorporates a range of micromobility modes, including fully human-powered (including walking), partially motor-assisted, and fully powered options. These modes typically operate at speeds not exceeding 25 to 32 kilometres per hour (or 45 km/h for faster options), weigh (typically substantially) below 350 kilograms and often yield significant (public) health benefits. Trip length is generally less than 15 kilometres, and daily distances under 80 kilometres. Importantly, our definition includes the practices, policies, cultures, and infrastructures that emerge around the use of micromobility options and shape their uptake. This proposed conceptualization significantly broadens the prevailing vehicle-focus in micromobility debates towards a socio-technical perspective. Embracing a widely accepted conceptualisation of micromobility would offer several advantages, including robust design standards, legislation, and evaluation metrics and methods. Additionally, this paper highlights the pivotal role micromobilities can play in transcending the limitations of automobility, towards more sustainable and equitable mobility futures.

Modal testing is a common step in aerostructure design, serving to validate the predicted natural frequencies and mode shapes obtained through computational methods. The strategic placement of sensors during testing is crucial to accurately measuring the intended natural frequencies. However, conventional methodologies for sensor placement are often time-consuming and involve iterative processes. This study explores the potential of machine learning techniques to enhance sensor selection methodologies. Three machine learning-based approaches are introduced and assessed, comparing their efficiency with established techniques. The evaluation of these methodologies is conducted using a numerical model of a beam to simulate real-world scenarios. The results offer insights into the efficacy of machine learning in optimizing sensor placement, presenting an innovative perspective on enhancing the efficiency and precision of modal testing procedures in aerostructure design.

In ancient Egyptian religion, psychostasis was the ceremony in which the deceased was judged before gaining access to the afterlife. This ritual was also known as the "weighing of the heart" or "weighing of the soul." The Egyptians believed that the heart, not the brain, was the seat of human wisdom, emotions, and memory. They were the first to recognize the cardiocentric nature of the body, identifying the heart as the center of the circulatory system. Aristotle (fourth century BC) considered the importance of the heart in human physiology in his philosophical analyses. For Galen (third century AD), the heart muscle was the site of the vital spirit, which regulated body temperature. Cardiology knowledge advanced significantly in the 15th century, coinciding with Leonardo da Vinci and Vesalius's pioneering anatomical and physiological studies. It was William Harvey, in the 17th century, who introduced the concept of cardiac circulation. Servet's research and Marcello Malpighi's discovery of arterioles and capillaries provided a more detailed understanding of circulation. Richard Lower emerged as the foremost pioneer of experimental cardiology in the late 17th century. He demonstrated the heart's neural control by tying off the vagus nerve. In 1753, Albrecht von Haller, a professor at Göttingen, was the first to discover the heart's automaticity and the excitation of muscle fibers. Towards the end of the 18th century, Antonio Scarpa challenged the theories of Albrecht von Haller and Johann Bernhard Jacob Behrends, who maintained that the myocardium possessed its own "irritability," on which the heartbeat depended and was independent of neuronal sensitivity. Instead, Scarpa argued that the heart required innervation to maintain life, refuting Galenic notions. In contemporary times, the study of cardiac innervation has regained prominence, particularly in understanding the post-acute sequelae of SARS-CoV-2 infection (PASC), which frequently involves cardiorespiratory symptoms and dysregulation of the intrinsic cardiac innervation. Recently, it has been recognized that post-acute sequelae of ARIs (acute respiratory infections) due to other pathogens can also be a cause of long-term vegetative and somatic symptoms. Understanding cardiac innervation and modulation can help to recognize and treat long COVID and long non-COVID-19 ARIs.

Hydrogels (gels) are attractive tools for tissue engineering and regenerative medicine due to their potential for drug delivery and ECM-like composition. In this study, we use rheology to characterize GelMA/alginate gels loaded with human platelet lysate (PL). We then characterize these gels from a physicochemical perspective and evaluate their ability to transport PL proteins, their pore size, and their rate of degradation. Finally, their biocompatibility is evaluated. We describe how alginate changes the mechanical behavior of the gels from elastic to viscoelastic after ionic (calcium-mediated) crosslinking. In addition, we positively report the release of PL proteins and relate it to the degradation profile of the gels and the biocompatibility of the gels. Thus, the developed gels represent attractive substrates for both cell studies and bioactive materials.

The objective of this paper is to estimate the trend of Total Ozone Column (TOC) over Togo. Multi Sensor Reanalysis-2 (MSR-2) TOC over the entire territory of Togo were used. Multiple Linear Regression (MLR) method has been applied to retrieve the interannual contributions of different forcings and the long term variability. It was found that the Annual Oscillation (AnO), the Quasi Biennial Oscillation at 30 mb (QBO30), the Solar Flux (SF), and the El Niño–Southern Oscillation (ENSO) have statistically significant influence on the interannual variability of the TOC. The strongest contribution (22 ± 1.4 DU) is allocated to the AnO while the weakest (< 1 DU) is attributed to the Semi-Annual Oscillations (SAnO). Before the peak year of Equivalent Effective Stratospheric Chlorine (EESC) in tropics in 1997 the trend is negative (- 0.3% ± 0.9% per decade) and is not statistically significant. After the peak year, a statistically significant positive trend is observed. The trend of TOC is 0.6% ± 0.2% per decade. The monthly TOC trend over Togo is positive and statistically significant during the rainy season (particularly during the monsoon period) except in April, unlike during the harmatan period (DJF) where the trend is not significant.

Bladder cancer is one of the most common malignant diseases in the urinary system and a highly aggressive neoplasm. The prognosis is not favourable usually and its evolution for particular patients is very difficult to find out. In this paper we propose a dynamic mathematical model that describes the bladder tumor growth and the immune response evolution. This model is customized for a single patient, determining appropriate model parameter values via model calibration. Due to the uncertainty of the tumor evolution, using the calibrated model parameters, we predict the tumor size and the immune response evolution over the next few months assuming three different scenarios: favourable, neutral and unfavourable. In the former, the cancer disappears; in the second a 5mm tumor is expected around the middle of August 2018; in the worst scenario, a 5mm tumor is expected around the end of May 2018. The patient has been cited around June 15th, 2018, to check the tumor size, if it exists.

Selenium (Se) is an essential trace element for the health and immunity of cattle. Double-muscled Belgian Blue cows are well known to be prone to nutritional deficiencies. Colostrum Se level is also a key factor to promote immunoglobulin intake in young calves. The main objectives of this study were to assess (1) the plasma and colostrum Se statuses of properly-supplemented Belgian-Blue cows on commercial farms and (2) the relationship between Se concentrations in plasma and colostrum. Secondary objectives were to assess relationships between plasma or colostrum Se concentrations and dietary Se supplementation as well as blood biomarkers. Blood and colostrum samples were collected from 49 Belgian Blue cows on 5 commercial farms in Belgium. They received 5 different rations with Se supplementation ranging from 0.5 to 2 ppm including 20% to 83% of organic form. Results showed that average Se concentration was 90 +- 15 µg/L in plasma and 79 +- 26 µg/L in colostrum, consistent with previous studies on well-supplemented cows. No relationship was observed between Se concentrations in plasma and colostrum, suggesting that colostrum Se testing would be a complementary indicator for improving calf Se supplementation. Relationships between plasma or colostrum Se and dietary Se or blood biomarkers emphasized the complexity of Se metabolism in observational studies under field conditions.

Mineral surfaces have been demonstrated to play a central role in prebiotic reaction, which are supposed to be at the basis of the origin of life. Among the various molecules proposed as precursors for these reactions, one of the most interesting is formamide. Formamide has been shown to be a pluripotent molecule, generating a wide distribution of relevant pre-biotic products. In particular, the outcomes of its reactivity are strongly related to the presence of mineral phases, acting as catalysts toward specific reaction pathways. Even if the mineral-products relationship has been deeply studied for a large pool of materials, the fundamental description of the formamide reactivity over the mineral surface at a microscopic level is missing in the literature. In particular, a key step of formamide chemistry at surfaces is its adsorption on the available interaction sites. This report aims to investigate the adsorption of formamide over a well-defined amorphous silica, chosen as model mineral surface. An experimental IR investigation of formamide adsorption has been carried out and its outcomes have been interpreted on the basis of first principles simulation of the process adopting a realistic model of the amorphous silica.

Machine learning approaches are currently used to understand or model complex physical systems. In general, a substantial number of samples must be collected to create a model with reliable results. However, collecting numerous data is often relatively time-consuming or expensive. Moreover, the problems of industrial interest tend to be more and more complex and depending on a high number of parameters. High dimensional problems intrinsically involve the need of large data amount through the curse of dimensionality. That is why, new approaches based on smart sampling techniques are investigated to minimize the number of samples to be given to train the model, such as Active Learning methods. Here, we propose a technique based on a combination of Fisher information matrix and of Sparse Proper Generalized Decomposition that enables the definition of a new Active Learning informativeness criterion in high dimensions. We provide examples proving the performances of this technique on a theoretical 5D polynomial function and on an industrial crash simulation application. The results prove that the proposed strategy over-perform the usual ones.

Pipefishes (Family Syngnathidae) are representative fishes in many European coastal areas asso-ciated with vegetal assemblages and other shallow habitats. The polyandrous pipefishes Syngnathus abaster and S. acus co-occur in Metruk Tuzla (Bargilya Wetland, Aegean Sea, Turkey), a protected but threatened wetland due to anthropogenic disturbances. Both species were sam-pled during the breeding season (April-2018 and June-2019) for the assessment of growth and trophic features revealed from stable isotope profiles (δ13C and δ15N) and gut content. Both species showed positive allometric growth, with similar length-weight relationships. The isotope approach indicated that both species occupy similar trophic niches, with mean δ13C and δ15N values of -17.0 ± 1.2 ‰ for δ13C and 13.2 ± 0.6 ‰ for δ15N in S. abaster, and -17.3 ± 1.2 ‰ for δ13C and 13.3 ± 0.7 ‰ for δ15N in S. acus. The niche area for all sex types (undifferentiated specimens, males and females) in S. acus was slightly broader than in S. abaster. The simulation analysis of the trophic position (TP) in both species agreed with the isotopic assessment (TP = 3.67 ± 0.61 in S. abaster and 3.46 ± 0.66 in S. acus). Despite the high trophic resemblance between S. abaster and S. acus, the gut content assessment revealed the large contribution of copepods (especially Calanipeda aquaedulcis) to the dietary regime in both pipefishes. However, while the diet in S. abaster seemed to be almost monospecific, cladocerans were also an important resource in S. acus. Hence, we suggest that potential inter-specific competition for dietary resources would be minimized likely due to the occupancy of different microhabitats, a hypothesis that needs to be confirmed by further research.

Agricultural landscapes are more and more characterized by intensification and habitat losses. Landscape composition and configuration are known to mediate insect abundance and richness. In the context of global insect decline, and despite 75% of crops being under insect’s dependence, there is still a gap of knowledge about the link between pollinators and aromatic crops. Fennel (Foeniculum vulgare) is an aromatic plant cultivated in South of France, for its essential oil which is of great economic interest. Using pan-traps, we investigated the influence of the surrounding habitats at landscape scale (semi-natural habitat proportion and vicinity, landscape configuration) and local scale agricultural practices (insecticides and patch size) on fennel-flower-visitor abundance and richness and their subsequent impact on fennel essential oil yield. We found that fennel may to be a generalist plant species. We did not find any effect of intense local management practices on insect abundance and richness. Landscape configuration and the proximity to semi-natural habitat were the main drivers of flying insect’s family richness. This richness positively influenced fennel essential oil yield. Maintaining a complex configuration of patches at the landscape scale are important to sustain insect diversity and crop yield.

Sentinel lymph node dissection (sLND) using a magnetometer and superparamagnetic iron oxide nanoparticles (SPIONs) as a tracer was successfully applied in prostate cancer (PCa). Radioisotope-guided sLND combined with extended pelvic LND (ePLND) achieved better node removal, increasing the number of affected nodes or the detection of sentinel lymph nodes outside the established ePLND template. We determined the diagnostic value of additional magnetometer-guided sLND after intraprostatic SPION-injection in high-risk PCa. This retrospective study included 104 high-risk PCa patients (PSA >20 ng/ml and/or Gleason score ≥8 and/or cT2c) from a prospective cohort who underwent radical prostatectomy with magnetometer-guided sLND and ePLND. The diagnostic accuracy of sLND was assessed using ePLND as a reference standard. Lymph node metastases were found in 61 of 104 patients (58.7%). sLND had a 100% diagnostic rate, 96.6% sensitivity, 95.6% specificity, 96.6% positive predictive value, 95.6% negative predictive value, 3.4% false negative rate, and 4.4% false positive rate (detecting lymph node metastases outside the ePLND template). These findings demonstrate the high sensitivity and additional diagnostic value of magnetometer-guided sLND, exceeding that of ePLND through the individualized extension of PLND or the detection of sentinel lymph nodes / lymph node metastases outside the established node template in high-risk PCa.

Chest X-ray (CXR) is the first tool globally employed to detect cardiopulmonary pathologies. These acquisitions are highly affected by scattered photons due to the large field-of-view required. Scatter in CXRs introduces background in the images, which reduces their contrast. We developed three deep learning-based models to estimate and correct the scatter contribution to CXRs. We used a Monte Carlo (MC) ray-tracing model to simulate CXRs from human models obtained from CT scans using different configurations (depending on the availability of dual-energy acquisitions). The simulated CXRs contained the separated contribution of direct and scattered X-rays in the detector. These simulated datasets were then used as the reference for the supervised training of several NN. Three NN models (single and dual energy) were trained with the MultiResUNet architecture. The performance of the NN models was evaluated on CXRs obtained with the MC code from chest CTs of patients affected by COVID-19. The results showed that the NN models were able to estimate and correct the scatter contribution to CXRs with an error &lt;5%, being robust to variations in the simulation setup and improving the contrast in soft tissue. The single-energy model was tested with real CXRs, providing robust estimations of the scatter-corrected CXRs.

The present research intents to study the evolution of the skin fatty acids and physiological disorders through cold storage in ‘Golden Delicious’ apples treated with 1-MCP and calcium. Harvested fruit were treated with calcium chloride (Ca), 1-MCP (MCP), Ca+MCP or no treatment (control) then subjected to cold storage at 0.5 ºC for 6 months. Fatty acids composition, Malondialdehyde (MDA) and the physiological disorders bitter pit (BP), superficial scald and diffuse skin browning (DSB) were measured at harvest and after storage plus 7 days shelf-life at room temperature ≈22 ºC. Palmitic acid decreased and linoleic acid increased through time, while oleic and stearic acids had few changes. Unsaturated/saturated fatty acids and MDA increased through time, despite Ca and Ca+MCP were related to lower MDA and lower BP and rotten fruit, after cold storage and shelf-life. In those treatments, the unsaturated/saturated fatty acids were higher, mainly due to higher linoleic acid and lower palmitic acids. Further research is needed to clarify the changes in membrane properties and the effect of some treatments in response to chilling injury through storage.

Meat-based diets are still the norm and vegans and vegetarians represent only a small minority of the population. A transition respectively behavioural change towards a diet with less meat can only occur with the adoption of a positive attitude towards dietary changes based on reasons and motivations. The main aim of this study is to validate the so-called meat attachment scale (MEAS) for Germany in order to analyse if this construct is a barrier towards a diet with less meat in this country. The findings show that the MEAS can be applied in Germany and a similar structure as reported for Spain and other countries could be found. Furthermore, a correlation analysis demonstrated that food neophobia and MEAS are not correlated with each other. That is, that meat attachment represents an independent and single predictor for trust in food (processing) technologies as e.g. plant-based proteins or cultured meat.

Cellular senescence is characterized by permanent proliferation and migration arrest, senescence-associated secretory phenotype (SASP), and oxidative stress. Senescent vascular smooth muscle cells (VSMCs) contribute to cardiovascular diseases and atherosclerotic plaque instability. To establish and characterize a model of replicative senescence (RS), human aortic VSMCs were serially passaged to represent different stages of RS such as young proliferating cells and old/senescent non-proliferating cells. More than 50% of old cells stained positive for the senescence-associated β-galactosidase compared to 20% of young cells. Old cells have a slower proliferation rate, a migratory activity reduced by 50%, but increased levels of TP53 and of cell cycle inhibitors p21/p16 expression, and accumulate in the G1 phase. Old cells showed a flattened appearance and enlarged and regular nuclei, and downregulation of the expression of LMNB1 and HMGB1. Old cells showed also an increased expression of SASP molecules (IL1β, IL6, IL8, and MMP3). Moreover, among a set of 12 manually selected long non-coding RNAs (lncRNAs), we detected significant upregulation of PURPL and NEAT1. We observed also increased levels of RRAD mRNA. The detection of novel molecular markers of senescence, such as RRAD, PURPL, and NEAT1, could be helpful for future studies on potential anti-aging factors.

(1) Background: Metabolic syndrome is associated with cardiovascular complications. Therefore, this study aims to establish cut points for the conicity index based on the components of the metabolic syndrome and to associate it with characteristics sociodemographic, food consumption and occupational factors in Brazilian rural workers; (2) Methods: Cross-sectional study carried out with farmers. The receiver operating characteristic curve was calculated and the cutoff points for the conicity index were identified by the area under the curve, sensitivity and specificity. The variables included in the binary logistic regression analysis were selected by considering p &lt; 0.20 in the bivariate test; (3) Results: The cut points were similar in females according to both criteria, resulting in a single cut-off of 1.269. In males, the cut points showed differences, resulting in 1.272 according to the NCEP-ATP III and 1.252 according to the IDF. We have shown that younger people, those who work more than 40 hours a week and the lowest contribution of culinary ingredients are associated with increased odds of abdominal obesity. While the consumption of the products they sell or produce decreases these chances; (4) Conclusions: The conicity index showed high discriminatory power for the identification of abdominal obesity in rural workers.

The yeast Saccharomyces cerevisiae is widely used in food and nonfood industries. During industrial fermentations yeast are exposed to fluctuations in oxygen concentration, osmotic pressure, pH, ethanol concentration, nutrient availability and temperature. Fermentation performance depends on the ability of different yeast strains to adapt to these changes. Suboptimal growth conditions trigger responses to these external stimuli to allow cellular homeostasis to be maintained. Stress-specific signaling pathways are activated to coordinate changes in tran-scription, translation, protein function, and metabolic fluxes while a transient arrest of growth and cell cycle progression occur. cAMP-PKA, HOG-MAPK and CWI signalling pathways are signal transduction pathways turned on during stress re-sponse. Comprehension of the mechanisms involved in the responses and in the adaptation to these stresses during fermentation is key to improving this industrial process. The scope of this review is to outline the advancement of knowledge about the cAMP-PKA signalling and the crosstalk of this pathway with the CWI and HOG-MAPK cascades in response to the environmental challenges heat and hy-perosmotic stress.

An essential metric for determining the efficacy of tuberculosis (TB) control programs is the evaluation of TB treatment outcomes. Assessing treatment outcomes is fundamental to facilitating the End TB Strategy set target. Clinic records from 457 patients with DR-TB were examined for data collection while 101 patients were followed up prospectively. Data were analyzed using Stata version 17.0. The odds ratio and 95% confidence interval were calculated to check the association between variables. P ≤ 0.05 was con-sidered statistically significant. Of the 427 participants, 65.8% had successful treatment whilst 34.2% had unsuccessful TB treatment. A total of 61.2% and 39% of the HIV-positive and HIV-negative participants had a successful TB treatment whilst 66% and 34% of both HIV-negative and positive participants had unsuccessful TB treatment. From 101 patients that were followed up, smokers had longer treatment outcomes compared to non-smokers. In the study with HIV/TB co-infection, men predominated. HIV and tuberculosis co-infection made therapy difficult with unfavorable effects on TB management. The treatment success rate (65.8%) is lower than the WHO threshold standard with a high proportion of patients lost to follow-up. The co-infection of tuberculosis and HIV resulted in undesirable treatment outcomes. Strengthening TB surveillance and control is recommended.

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation that is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD) including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion, however, that therapeutic approach leads to ischemic/reperfusion injury (IRI) often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.

With a low rate of new building construction and insufficient rate of existing building renovation, there is the need for stepping up the pace of building renovation with ambitious performance targets to achieve EU climate change policies. However, effective technologies alone cannot solve the low renovation rate of existing buildings in Europe that is hindering the reaching of EU-wide targets. A workshop was held at the Sustainable Place Conference 2018 to present successful experiences with an integrative approach from H2020 innovation actions (4RinEU, P2ENDURE, Pro-GET-OnE, MORE-CONNECT) aiming at improving building energy performance through deep renovation. This article presents the outcomes of the joint workshop and interactive discussion, by focusing on the different technical, financial and social added values, barriers and challenges in building renovation as well as on the identification of open questions to address future innovation opportunities.

Low 25 OH vitamin D (25(OH)D) in preterm infants is a risk factor of bronchopulmonary dysplasia (BPD), but increased supplementation failed to demonstrate beneficial effect on BPD. In neonatal animal models, deficiency and excessive vitamin D exposure have been associated with increased mortality and lung histological alterations evocative of BPD. Our hypothesis is that 25(OH)D levels ≥ 120nmol/L is also a risk factor for BPD or death. This retrospective single-center cohort study included all infants born <31 weeks gestational age without major malformation with at least a determination of 25(OH)D <36 weeks corrected age and no determination <50 nmol/L. Routine 25(OH)D determination was performed at 1 month and monthly thereafter. A total of 175 infants were included. Infants with BPD or who died had a significantly lower term and weight, but a similar frequency of 25(OH)D ≥120nmol/L (50.5% vs 43.9%, p=0.53). The logistic regression identified weight (OR 0.997, 95%CI [0.995-0.998]) and term (OR 0.737, 95%CI [0.551-0.975]) as significantly associated with BPD or death; the occurrence of excessive 25(OH)D was not significantly associated (OR 1.029, 95%CI [0.503-2.093]). The present study did not demonstrate any significant association between excessive 25(OH)D after one month of age and BPD or death.

Insect outbreaks are major drivers of natural disturbances in forest ecosystems. Outbreaks can have both direct and indirect effects on the composition of soil arthropod communities, through canopy opening, nutrient addition and predator-prey interactions. In this study, we aim to understand the effects of forest tent caterpillar (Malacosoma disstria; FTC) outbreaks on ant communities in both temperate and boreal forests in Canada. Using pitfall traps and Berlese funnels, we compared the ant communities as well as the surrounding arthropod communities between control and outbreak sites in boreal andboreal and temperate forests (in Québec, Canada). Using the Sørensen dissimilarity index, we determined the alpha and beta diversity of the ant community. Other arthropods collected in the traps were counted to evaluate the richness and abundance of potential prey for the ants and other potential predators of the FTC. We used an indicator species analysis to examine the species associated with sites defoliated by the outbreak. In the boreal forest, we found that FTC outbreaks caused decreases in species richness and increases in the evenness of ant communities in defoliated sites. In the boreal forest sites, species composition varied significantly between control and outbreak sites. This pattern was driven by the presence of other predators. We also saw no changes in beta diversity in the boreal forest but did see a significant decrease in the temperate forest between the outbreak sites and the control sites. A similar, but weaker pattern was observed in the temperate forest. Ant species in the boreal forest tended to exhibit a more marked preference for either control or previously defoliated sites than species in the temperate forest. Our study showed that disturbances like insect outbreaks can drive changes in the ant community. While we saw small effects of outbreaks, manipulation experiments using resource addition could help us validate the mechanisms behind these relationships.

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivatives 7a-l have been designed and synthesized via cyclocondensation reactions of pyrazolo-enaminone 5 with a series of arylidene malononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole (3). The structures of the target compounds 7a-l were investigated by spectral techniques and elemental analysis (IR, UV-Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the conjugate 7e was the most active towards many cell lines with EC50 values ranging between 9.1 and 13.5 µM, respectively. Moreover, in silico docking studies of 7e with six anticancer drug targets, i.e. DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX also was performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.