Unravelling the structure of CO2 in silica adsorbents: an NMR and computational perspective.

This comprehensive review describes recent advancements in the use of solid-state NMR-assisted methods and computational modeling strategies to unravel gas adsorption mechanisms and CO2 speciation in porous CO2-adsorbent silica materials at the atomic scale. This work provides new perspectives for the innovative modifications of these materials rendering them more amenable to the use of advanced NMR methods.

Molecular and structural basis of the dual regulation of the polycystin-2 ion channel by small-molecule ligands.

Mutations in the PKD2 gene, which encodes the polycystin-2 (PC2, also called TRPP2) protein, lead to autosomal dominant polycystic kidney disease (ADPKD). As a member of the transient receptor potential (TRP) channel superfamily, PC2 functions as a non-selective cation channel. The activation and regulation of the PC2 channel are largely unknown, and direct binding of small-molecule ligands to this channel has not been reported. In this work, we found that most known small-molecule agonists of the mucolipin TRP (TRPML) channels inhibit the activity of the PC2_F604P, a gain-of-function mutant of the PC2 channel. However, two of them, ML-SA1 and SF-51, have dual regulatory effects, with low concentration further activating PC2_F604P, and high concentration leading to inactivation of the channel. With two cryo-electron microscopy (cryo-EM) structures, a molecular docking model, and mutagenesis results, we identified two distinct binding sites of ML-SA1 in PC2_F604P that are responsible for activation and inactivation, respectively. These results provide structural and functional insights into how ligands regulate PC2 channel function through unusual mechanisms and may help design compounds that are more efficient and specific in regulating the PC2 channel and potentially also for ADPKD treatment.

Rural communities experience higher radon exposure versus urban areas, potentially due to drilled groundwater well annuli acting as unintended radon gas migration conduits.

Repetitive, long-term inhalation of radioactive radon gas is one of the leading causes of lung cancer, with exposure differences being a function of geographic location, built environment, personal demographics, activity patterns, and decision-making. Here, we examine radon exposure disparities across the urban-to-rural landscape, based on 42,051 Canadian residential properties in 2034 distinct communities. People living in rural, lower population density communities experience as much as 31.2% greater average residential radon levels relative to urban equivalents, equating to an additional 26.7 Bq/m3 excess in geometric mean indoor air radon, and an additional 1 mSv/year in excess alpha radiation exposure dose rate to the lungs for occupants. Pairwise and multivariate analyses indicate that community-based radon exposure disparities are, in part, explained by increased prevalence of larger floorplan bungalows in rural areas, but that a majority of the effect is attributed to proximity to, but not water use from, drilled groundwater wells. We propose that unintended radon gas migration in the annulus of drilled groundwater wells provides radon migration pathways from the deeper subsurface into near-surface materials. Our findings highlight a previously under-appreciated determinant of radon-induced lung cancer risk, and support a need for targeted radon testing and reduction in rural communities.

Dysglycemia Shapes Visceral Adipose Tissue's Response to GIP, GLP-1 and Glucagon in Individuals with Obesity.

Visceral adipose tissue (VAT) metabolic fingerprints differ according to body mass index (BMI) and glycemic status. Glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon are gut-associated hormones that play an important role in regulating energy and glucose homeostasis, although their metabolic actions in VAT are still poorly characterized. Our aim was to assess whether GLP-1, GIP and glucagon influence the VAT metabolite profile. To achieve this goal, VAT harvested during elective surgical procedures from individuals (N = 19) with different BMIs and glycemic statuses was stimulated with GLP-1, GIP or glucagon, and culture media was analyzed using proton nuclear magnetic resonance. In the VAT of individuals with obesity and prediabetes, GLP-1 shifted its metabolic profile by increasing alanine and lactate production while also decreasing isoleucine consumption, whereas GIP and glucagon decreased lactate and alanine production and increased pyruvate consumption. In summary, GLP-1, GIP and glucagon were shown to distinctively modulate the VAT metabolic profile depending on the subject's BMI and glycemic status. In VAT from patients with obesity and prediabetes, these hormones induced metabolic shifts toward gluconeogenesis suppression and oxidative phosphorylation enhancement, suggesting an overall improvement in AT mitochondrial function.

GLP-1 Increases Circulating Leptin Levels in Truncal Vagotomized Rats.

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut-brain vagal pathway.

Ecotoxicological impacts of metals in single and co-exposure on mussels: Comparison of observable and predicted results.

Used in high-tech and everyday products, mercury (Hg), cobalt (Co), and nickel (Ni) are known to be persistent and potentially toxic elements that pose a serious threat to the most vulnerable ecosystems. Despite being on the Priority Hazardous Substances List, existing studies have only assessed the individual toxicity of Co, Ni and Hg in aquatic organisms, with a focus on the latter, ignoring potential synergistic effects that may occur in real-world contamination scenarios. The present study evaluated the responses of the mussel Mytilus galloprovincialis, recognized as a good bioindicator of pollution, after exposure to Hg (25 µg/L), Co (200 µg/L) and Ni (200 µg/L) individually, and to the mixture of the three metals at the same concentration. The exposure lasted 28 days at 17 ± 1 °C, after which metal accumulation and a set of biomarkers related to organisms' metabolic capacity and oxidative status were measured. The results showed that the mussels could accumulate metals in both single- and co-exposure conditions (bioconcentration factors between 115 and 808) and that exposure to metals induced the activation of antioxidant enzymes. Although Hg concentration in organisms in the mixture decreased significantly compared to single exposure (9.4 ± 0.8 vs 21 ± 0.7 mg/kg), the negative effects increased in the mixture of the three elements, resulting in depletion of energy reserves, activation of antioxidants and detoxification enzymes, and cellular damage, with a hormesis response pattern. This study underscores the importance of risk assessment studies that include the effects of the combination of pollutants and demonstrates the limitations of applying models to predict metal mixture toxicity, especially when a hormesis response is given by the organisms.

The diverse effects of pathogenic point mutations on ion channel activity of a gain-of-function polycystin-2.

Autosomal dominant polycystic kidney disease is caused by mutations in PKD1 or PKD2 genes. The latter encodes polycystin-2 (PC2, also known as TRPP2), a member of the transient receptor potential ion channel family. Despite most pathogenic mutations in PKD2 being truncation variants, there are also many point mutations, which cause small changes in protein sequences but dramatic changes in the in vivo function of PC2. How these mutations affect PC2 ion channel function is largely unknown. In this study, we systematically tested the effects of 31 point mutations on the ion channel activity of a gain-of-function PC2 mutant, PC2_F604P, expressed in Xenopus oocytes. The results show that all mutations in the transmembrane domains and channel pore region, and most mutations in the extracellular tetragonal opening for polycystins domain, are critical for PC2_F604P channel function. In contrast, the other mutations in the tetragonal opening for polycystins domain and most mutations in the C-terminal tail cause mild or no effects on channel function as assessed in Xenopus oocytes. To understand the mechanism of these effects, we have discussed possible conformational consequences of these mutations based on the cryo-EM structures of PC2. The results help gain insight into the structure and function of the PC2 ion channel and the molecular mechanism of pathogenesis caused by these mutations.

Regular Voluntary Running is Associated with Increased Tumor Vascularization and Immune Cell Infiltration and Decreased Tumor Growth in Mice.

Tumors present dysfunctional vasculature that limits blood perfusion and hinders immune cells delivery. We aimed to investigate if regular voluntary running promotes tumor vascular remodelling, improves intratumoral immune cells infiltration and inhibits tumor growth. Tumors were induced in C57BL/6 male mice (n=28) by subcutaneous inoculation in the dorsal region with a suspension of RM1 cells (1.5×105 cells/500 µL PBS) and randomly allocated into two groups: sedentary (n=14) and voluntarily exercised on a wheel (n=14). Seven mice from each group were sacrificed 14 and 28 days after cells' inoculation to evaluate tumor weight, microvessel density, vessels' lumen regularity and the intratumoral quantity of NKG2D receptors, CD4+and CD8+T cells, by immunohistochemistry. The statistical inference was done through a two-way ANOVA. Exercised mice developed smaller tumors at 14 (0.17±0.1 g vs. 0.48±0.2 g, p<0.05) and 28 (0.92±0.7 g vs. 2.09±1.3 g, p<0.05) days, with higher microvessel density (21.20±3.2 vs. 15.86±4.0 vessels/field, p<0.05), more regular vessels' lumen (1.06±0.2 vs. 1.43±0.2, p<0.05), and higher CD8+T cells (464.95±48.0 vs. 364.70±49.4 cells/mm2, p<0.01), after 28 days. NKG2D expression was higher in exercised mice at 14 (263.27±25.8 cells/mm2, p<0.05) and 28 (295.06±56.2 cells/mm2, p<0.001) days. Regular voluntary running modulates tumor vasculature, increases immune cells infiltration and attenuates tumor growth, in mice.

In-Well Degassing of Monitoring Wells Completed in Gas-Charged Aquifers.

Total dissolved gas pressure (PTDG ) measurements are useful to measure accurate in situ dissolved gas concentrations in groundwater, but challenged by in-well degassing. Although in-well degassing has been widely observed, its cause(s) are not clear. We investigated the mechanism(s) by which gas-charged groundwater in a recently pumped well becomes degassed. Vertical PTDG and dissolved gas concentration profiles were monitored in the standing water column (SWC) of a groundwater well screened in a gas-charged aquifer for 7 days before and 15 days after pumping. Prior to pumping, PTDG values remained relatively constant and below calculated bubbling pressure (PBUB ) at all depths. In contrast, significant increases in PTDG were observed at all depths after pumping was initiated, as fresh groundwater with elevated in situ PTDG values was pumped through the well screen. After pumping ceased, PTDG values decreased to below PBUB at all depths over the 15-day post-pumping period, indicating well degassing was active over this time frame. Vertical profiles of estimated dissolved gas concentrations before and after pumping provided insight into the mechanism(s) by which in-well degassing occurred in the SWC. During both monitoring periods, downward mixing of dominant atmospheric and/or tracer gases, and upwards mixing of dominant groundwater gases were observed in the SWC. The key mechanisms responsible for in-well degassing were (i) bubble exsolution when PTDG exceeded PBUB as gas-charged well water moves upwards in the SWC during recovery (i.e., hydraulic gradient driven convection), (ii) microadvection caused by the upward migration of bubbles under buoyancy, and (iii) long-term, thermally driven vertical convection.

Obesity-Related Genes Expression in Testes and Sperm Parameters Respond to GLP-1 and Caloric Restriction.

Aim: Calorie restriction (CR) diets and glucagon-Like Peptide-1 (GLP-1) analogs are known to alter energy homeostasis with the potential to affect the expression of obesity-related genes (ORGs). We hypothesized that CR and GLP-1 administration can alter ORGs expression in spermatozoa and testes, as well as the sperm parameters implicated in male fertility. Materials and Methods: Six-week-old adult male Wistar rats (n = 16) were divided into three groups, submitted either to CR (n = 6, fed with 30% less chow diet than the control rats), GLP-1 administration (n = 5, 3.5 pmol/min/kg intraperitoneal) for 28 days, or used as controls (n = 5, fed ad libitum). Selected ORGs expression, namely the fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), glucosamine-6-phosphate deaminase 2 (GNPDA2), and transmembrane protein 18 (TMEM18) were evaluated in testes and spermatozoa by a quantitative polymerase chain reaction (qPCR). Results: CR resulted in lower body weight gain and insulin resistance, but a higher percentage of sperm head defects. GLP-1 administration, despite showing no influence on body weight or glucose homeostasis, resulted in a lower percentage of sperm head defects. CR and GLP-1 administration were associated with a higher expression of all ORGs in the testes. Under CR conditions, the genes FTO and TMEM18 expression in the testes and the MC4R and TMEM18 transcripts abundance in sperm were positively correlated with the spermatozoa oxidative status. The abundance of FTO and TMEM18 in the spermatozoa of rats under CR were positively correlated with sperm concentration, while the testes' TMEM18 expression was also positively correlated with sperm vitality and negatively correlated with insulin resistance. Testes GNPDA2 expression was negatively correlated with sperm head defects. Conclusions: CR and GLP-1 administration results in higher ORGs expression in testes, and these were correlated with several alterations in sperm fertility parameters.

The effect of ocean warming on accumulation and cellular responsiveness to cobalt in Mytilus galloprovincialis.

Cobalt (Co) is among the hazardous substances identified in aquatic environments. Industrialization and population growth have also contributed to climate change, namely in what concerns ocean temperature rise. The aim of the present study was to evaluate the influence of temperature rise on the impacts caused by Co on Mytilus galloprovincialis. To this end, mussels were exposed for 28 days to 17 °C and 21 °C, without and with 200 µg L-1 of Co. Results showed no significant differences in Co bioaccumulation by the organisms between temperatures. A significant interaction between temperature and Co contamination was observed in terms of oxidative damage, detoxification capacity, and neurotoxicity, with a synergistic effect particularly evident in terms of biotransformation enzymes' activity. The obtained results point out that population survival and distribution may be limited in the long term, highlighting the need for future research on the combined effects of both stressors.

Free-Phase Gas Detection in Groundwater Wells via Water Pressure and Continuous Field Parameters.

Detection of free-phase gas (FPG) in groundwater wells is critical for accurate assessment of dissolved gas concentrations and the occurrence of FPG in the subsurface, with consequent implications for understanding groundwater contamination and greenhouse gas emissions. However, identifying FPG is challenging during routine groundwater monitoring and there is poor agreement on the best approach to detect the occurrence of FPG in groundwater. In this study, laboratory experiments in a water column were designed to mimic nonflowing and flowing conditions in a groundwater well to evaluate how the presence of FPG affects water pressure and commonly used continuous field parameters. The laboratory results were extrapolated to interpret field data at an abandoned exploration well with episodic release of free-gas CO2 . The FPG effect on water pressure varied between flowing and nonflowing wells, and depending on whether the FPG was above or below the sensor. Electrical conductivity values were decreased and/or behaved erratically when FPG was present in the water column. Findings from this study have shown that the combined measurement of water pressure, electrical conductivity, and total dissolved gas pressure can provide information about the occurrence of FPG in groundwater wells. Measurement of these parameters at different depths can also provide information about relative depths and amounts of FPG within the well water column. This approach can be used for long-term monitoring of groundwater gases, managing gas-locking in production wells with gassy groundwater, and measuring fugitive greenhouse gas emissions from groundwater wells.

Applying the Human Appropriation of Net Primary Production framework to map provisioning ecosystem services and their relation to ecosystem functioning across the European Union.

Human intervention on land enhances the supply of provisioning ecosystem services, but also exerts pressures on ecosystem functioning. We utilize the Human Appropriation of Net Primary Production (HANPP) framework to assess these relations in European agriculture, for 220 NUTS2 regions. We put a particular focus on individual land system components, i.e. croplands, grasslands, and livestock husbandry and relate associated biomass flows to the potential net primary productivity NPP. For the reference year 2012, we find that 469 g dm/m2/yr (38% of NPPpot) of used biomass were harvested on total agricultural land, and that one tonne of annually harvested biomass is associated with 1.67 tonnes dry matter (dm) of HANPP, ranging from 0.8 to 8.1 tonnes dry matter (dm) across all regions. EU livestock systems are a large consumer of these provisioning ecosystem services, and invoking higher HANPP flows than current HANPP on cropland and grassland within the EU, even exceeding the potential NPP in one fifth of all NUTS2 regions. NPP remaining in ecosystems after provisioning society with biomass is essential for the functioning of ecosystems and is 563 g dm/m2/yr or 46% of NPPpot on all agricultural land. We conclude from our analysis that the HANPP framework provides useful indicators that should be integrated in future ecosystem service assessments.

Global process-based characterization factors of soil carbon depletion for life cycle impact assessment.

Regionalization of land use (LU) impact in life cycle assessment (LCA) has gained relevance in recent years. Most regionalized models are statistical, using highly aggregated spatial units and LU classes (e.g. one unique LU class for cropland). Process-based modelling is a powerful characterization tool but so far has never been applied globally for all LU classes. Here, we propose a new set of spatially detailed characterization factors (CFs) for soil organic carbon (SOC) depletion. We used SOC dynamic curves and attainable SOC stocks from a process-based model for more than 17,000 world regions and 81 LU classes. Those classes include 63 agricultural (depending on 4 types of management/production), and 16 forest sub-classes, and 1 grassland and 1 urban class. We matched the CFs to LU elementary flows used by LCA databases at country-level. Results show that CFs are highly dependent on the LU sub-class and management practices. For example, transformation into cropland in general leads to the highest SOC depletion but SOC gains are possible with specific crops.

Adipose Tissue Epigenetic Profile in Obesity-Related Dysglycemia - A Systematic Review.

Background: Obesity is a major risk factor for dysglycemic disorders, including type 2 diabetes (T2D). However, there is wide phenotypic variation in metabolic profiles. Tissue-specific epigenetic modifications could be partially accountable for the observed phenotypic variability. Scope: The aim of this systematic review was to summarize the available data on epigenetic signatures in human adipose tissue (AT) that characterize overweight or obesity-related insulin resistance (IR) and dysglycemia states and to identify potential underlying mechanisms through the use of unbiased bioinformatics approaches. Methods: Original data published in the last decade concerning the comparison of epigenetic marks in human AT of individuals with metabolically unhealthy overweight/obesity (MUHO) versus normal weight individuals or individuals with metabolically healthy overweight/obesity (MHO) was assessed. Furthermore, association of these epigenetic marks with IR/dysglycemic traits, including T2D, was compiled. Results: We catalogued more than two thousand differentially methylated regions (DMRs; above the cut-off of 5%) in the AT of individuals with MUHO compared to individuals with MHO. These DNA methylation changes were less likely to occur around the promoter regions and were enriched at loci implicated in intracellular signaling (signal transduction mediated by small GTPases, ERK1/2 signaling and intracellular trafficking). We also identified a network of seven transcription factors that may play an important role in targeting DNA methylation changes to specific genes in the AT of subjects with MUHO, contributing to the pathogeny of obesity-related IR/T2D. Furthermore, we found differentially methylated CpG sites at 8 genes that were present in AT and whole blood, suggesting that DMRs in whole blood could be potentially used as accessible biomarkers of MUHO. Conclusions: The overall evidence linking epigenetic alterations in key tissues such AT to metabolic complications in human obesity is still very limited, highlighting the need for further studies, particularly those focusing on epigenetic marks other than DNA methylation. Our initial analysis suggests that DNA methylation patterns can potentially discriminate between MUHO from MHO and provide new clues into why some people with obesity are less susceptible to dysglycemia. Identifying AT-specific epigenetic targets could also lead to novel approaches to modify the progression of individuals with obesity towards metabolic disease. Systematic Review Registration: PROSPERO, identifier CRD42021227237.

Visceral Adipose Tissue Displays Unique Metabolomic Fingerprints in Obesity, Pre-Diabetes and Type 2 Diabetes.

Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (1H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals' health status.

Can the recycling of europium from contaminated waters be achieved through living macroalgae? Study on accumulation and toxicological impacts under realistic concentrations.

Europium (Eu) strategic importance for the manufacturing industry, high economic value and high supply risk, categorizes it as critical raw material. Due to anthropogenic contamination, Eu levels in ecosystems have been growing, which opens opportunities for innovation: its recovery and recycling from contaminated water as element source - circular economy. In this pioneering study, six widely available living marine macroalgae (Ulva intestinalis, Ulva lactuca, Gracilaria sp., Osmundea pinnatifida, Fucus vesiculosus and Fucus spiralis) were characterized (water content and specific surface area) and evaluated in the pre-concentration and recovery of Eu from contaminated seawater, under different relevant contamination scenarios (10, 152 and 500 µg L-1). U. lactuca and Gracilaria sp. (3 g L-1, fresh weight) proved to be the most effective in removing Eu, reaching up to 85% in 72 h, while the highest Eu enrichment was observed in U. intestinalis biomass, up to 827 µg g-1 (bioconcentration factor of 1800), which is higher than Eu levels in common apatite ores. The effect of Eu exposure on macroalgae growth rate and organism biochemical performance (LPO, SOD, GPx and GSTs) was also evaluated for the first time, to the best of our knowledge. Although no cellular damage was recorded, findings revealed toxicity and defence mechanisms activation, emphasizing the need of further studies on the potential risks associated with the presence of this emerging contaminant in aquatic ecosystems.

Regular Voluntary Running Inhibits Androgen-Independent Prostate Cancer Growth in Mice.

INTRODUCTION: Benefits of regular physical exercise were demonstrated as preventive and coadjuvant nonpharmacological anticancer therapy. However, the role of exercise in modulating prostate cancer behavior has yet to be established. METHODS: Prostate tumors were induced in C57BL/6 male mice (n = 28) by subcutaneous inoculation of a suspension of murine androgen-independent RM1 cells (1.5 × 105 cells/500 µL phosphate-buffered saline) in the dorsal region. Mice were randomly allocated into 2 study groups: sedentary tumor-induced (n = 14) and exercised tumor-induced (n = 14). Exercise consisted of voluntary running in wheeled cages. Mice (n = 7 per group) were sacrificed either 14 or 28 days after cell inoculation to evaluate tumor weight and percentage of area occupied by immunohistochemistry stained cells for Ki-67 and TdT-mediated dUTP-biotin nick end labeling, used as surrogate markers of cell proliferation and apoptosis, respectively. RESULTS: Compared with sedentary tumor-induced mice, the tumors developed by exercised tumor-induced mice were significantly smaller at 14 days (0.17 [0.12] g vs 0.48 [0.24] g, P < .05) and at 28 days (0.92 [0.73] g vs 2.09 [1.31] g, P < .05), with smaller Ki-67 and greater TdT-mediated dUTP-biotin nick end-labeling stained areas (P < .05). CONCLUSION: These results suggest that regular voluntary running inhibits prostate cancer cell growth by reducing cell proliferation and enhancing apoptosis.

Use of flash glucose monitoring for post-bariatric hypoglycaemia diagnosis and management.

Our aim was to assess the potential of flash glucose monitoring (FGM) for diagnostic workup of suspected post-bariatric hypoglycaemia (PBH). Patients (N = 13) with suspected PBH underwent a food and symptoms diary (FSD) record along with FGM over 14 days. Targeted data analysis confirmed the occurrence of low glucose events in parallel to meal-triggered symptoms. Glycaemic variability, as assessed by Mean Absolute Glucose change (MAG change), was increased, while a higher risk of glycaemic excursions towards both hyper and hypoglycaemia (ADRRFGMGT) was observed in those with more frequent and severe hypoglycaemia. The herein described hypoglycaemia risk index (LBGIFGMGT) with a cut-off value of 4.6 showed to have 100% sensitivity and 100% specificity for PBH. This pilot proof-of-concept study highlighted that FSD coupled with FGM followed by targeted data analysis, provides relevant insights towards PBH diagnosis and grading in a user-friendly and easy to implement study protocol. Furthermore, LBGIFGMGT demonstrated to be an excellent index for PBH diagnosis. The unexpected improvement of glucose profile noticed along the monitoring time also unravels a possible application for PBH management.

Food systems in a zero-deforestation world: Dietary change is more important than intensification for climate targets in 2050.

Global food systems contribute to climate change, the transgression of planetary boundaries and deforestation. An improved understanding of the environmental impacts of different food system futures is crucial for forging strategies to sustainably nourish a growing world population. We here quantify the greenhouse gas (GHG) emissions of global food system scenarios within a biophysically feasible "option space" in 2050 comprising all scenarios in which biomass supply - calculated as function of agricultural area and yields - is sufficient to cover biomass demand - derived from human diets and the feed demand of livestock. We assessed the biophysical feasibility of 520 scenarios in a hypothetical no-deforestation world. For all feasible scenarios, we calculate (in) direct GHG emissions related to agriculture. We also include (possibly negative) GHG emissions from land-use change, including changes in soil organic carbon (SOC) and carbon sinks from vegetation regrowth on land spared from food production. We identify 313 of 520 scenarios as feasible. Agricultural GHG emissions (excluding land use change) of feasible scenarios range from 1.7 to 12.5 Gt CO2e yr-1. When including changes in SOC and vegetation regrowth on spare land, the range is between -10.7 and 12.5 Gt CO2e yr-1. Our results show that diets are the main determinant of GHG emissions, with highest GHG emissions found for scenarios including high meat demand, especially if focused on ruminant meat and milk, and lowest emissions for scenarios with vegan diets. Contrary to frequent claims, our results indicate that diets and the composition and quantity of livestock feed, not crop yields, are the strongest determinants of GHG emissions from food-systems when existing forests are to be protected.