Sleep patterns are associated with cardiometabolic risk factors in nine-year-old Swedish children.

AIM: Sleep duration and bedtime may play a role in children's cardiometabolic health, but research is lacking. This study examined associations between sleep patterns and cardiometabolic risk factors in Swedish nine-year-olds. METHODS: This cross-sectional study used data from three studies, where identical outcome measures were conducted in 411 nine-year-olds, 51% boys, between 2016 and 2020. Sleep was assessed with wrist-worn accelerometers and sleep journals. Children were grouped based on meeting the sleep guidelines of 9-11 h and going to bed early or late based on the median bedtime. Analysis of covariance was used to examine associations between sleep patterns and cardiometabolic risk factors. RESULTS: Meeting sleep guidelines and going to bed early were associated with lower metabolic syndrome score (-0.15 vs. 0.42, p = 0.029), insulin resistance (0.30 vs. 0.60, p = 0.025) and insulin levels (6.80 vs. 8.87 mIU/L, p = 0.034), compared with their peers who did not meet the guidelines and went to bed later. When adjusting for total sleep time, analyses still showed associations with the metabolic syndrome score (-0.19 vs. 0.50, p = 0.011). CONCLUSION: The findings indicate that good sleep patterns could help mediate positive overall cardiometabolic health in children.

Effects of a concurrent exercise training program on low back and sciatic pain and pain disability in late pregnancy.

OBJECTIVE: The aim of the present study was to explore the influence of a concurrent exercise (aerobic + resistance) training program, from the 17th gestational week (g.w.) until birth on low back and sciatic pain, and pain disability. A total of 93 pregnant women divided into exercise (n = 49) and control (n = 44) groups followed a 60-min, 3 days/week, concurrent exercise training. METHODS: Low back and sciatic pain were measured with a Visual Analogic Scale (VAS). The disability resulting from pain was assessed with the Oswestry Disability Index (ODI). Measures were performed at the 16th and 34th g.w. RESULTS: The exercise group increased 21.9 mm less the VAS low back (between-group differences (B): 95% CI: -33.6 to -10.2; p < 0.001) and 12.9 mm less the VAS sciatica score (between-group differences: 95% CI (B): -21.8 to -4.0; p = 0.005) than the control group. Regarding the ODI questionnaire, the exercise group increased 0.7, 0.5, and 0.7 less than the control group in pain while sleeping (between-group differences (B): 95% CI: -1.4 to -0.01; p = 0.025), pain while lifting weight (between-group differences (B): 95% CI: -0.9 to -0.01; p = 0.016), and limitations of the social life due to pain (between-group differences(B): 95% CI: -1.3 to -0.06; p = 0.032). Furthermore, the exercise group suffered 6.9% less pain than the control group in the ODI total score (between-group differences (B): 95% CI: -13.9 to 0.053; p = 0.052). CONCLUSION: This concurrent exercise training program adapted to pregnant women improved pain compared to controls.

Insights into the reduction of antibiotic-resistant bacteria and mobile antibiotic resistance genes by black soldier fly larvae in chicken manure.

The increasing prevalence of antibiotic-resistant bacteria (ARB) from animal manure has raised concerns about the potential threats to public health. The bioconversion of animal manure with insect larvae, such as the black soldier fly larvae (BSFL, Hermetia illucens [L.]), is a promising technology for quickly attenuating ARB while also recycling waste. In this study, we investigated BSFL conversion systems for chicken manure. Using metagenomic analysis, we tracked ARB and evaluated the resistome dissemination risk by investigating the co-occurrence of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and bacterial taxa in a genetic context. Our results indicated that BSFL treatment effectively mitigated the relative abundance of ARB, ARGs, and MGEs by 34.9%, 53.3%, and 37.9%, respectively, within 28 days. Notably, the transferable ARGs decreased by 30.9%, indicating that BSFL treatment could mitigate the likelihood of ARG horizontal transfer and thus reduce the risk of ARB occurrence. In addition, the significantly positive correlation links between antimicrobial concentration and relative abundance of ARB reduced by 44.4%. Moreover, using variance partition analysis (VPA), we identified other bacteria as the most important factor influencing ARB, explaining 20.6% of the ARB patterns. Further analysis suggested that antagonism of other bacteria on ARB increased by 1.4 times, while nutrient competition on both total nitrogen and crude fat increased by 2.8 times. Overall, these findings provide insight into the mechanistic understanding of ARB reduction during BSFL treatment of chicken manure and provide a strategy for rapidly mitigating ARB in animal manure.

Oxidative-stress and long-term hepatotoxicity: comparative study in Upcyte human hepatocytes and hepaRG cells.

Drug-induced liver injury (DILI) is one of the most common and serious adverse drug reactions and a major cause of drug development failure and withdrawal. Although different molecular mechanisms are implicated in DILI, enhanced ROS levels have been described as a major mechanism. Human-derived cell models are increasingly used in preclinical safety assessment because they provide quick and relatively inexpensive information in early stages of drug development. We have analyzed and compared the phenotype and functionality of two liver cell models (Upcyte human hepatocytes and HepaRG cells) to demonstrate their suitability for long-term hepatotoxicity assessments and mechanistic studies. The transcriptomic and functional analysis revealed the maintenance of phase I and phase II enzymes, and antioxidant enzymes along time in culture, although the differences found between both test systems underlie the differential sensitivity to hepatotoxins. The evaluation of several mechanisms of cell toxicity, including oxidative stress, by high-content screening, demonstrated that, by combining the stable phenotype of liver cells and repeated-dose exposure regimes to 12 test compounds at clinically relevant concentrations, both Upcyte hepatocytes and HepaRG offer suitable properties to be used in routine screening assays for toxicological assessments during drug preclinical testing.

The "Historical Materials BAG": A New Facilitated Access to Synchrotron X-ray Diffraction Analyses for Cultural Heritage Materials at the European Synchrotron Radiation Facility.

The European Synchrotron Radiation Facility (ESRF) has recently commissioned the new Extremely Brilliant Source (EBS). The gain in brightness as well as the continuous development of beamline instruments boosts the beamline performances, in particular in terms of accelerated data acquisition. This has motivated the development of new access modes as an alternative to standard proposals for access to beamtime, in particular via the "block allocation group" (BAG) mode. Here, we present the recently implemented "historical materials BAG": a community proposal giving to 10 European institutes the opportunity for guaranteed beamtime at two X-ray powder diffraction (XRPD) beamlines-ID13, for 2D high lateral resolution XRPD mapping, and ID22 for high angular resolution XRPD bulk analyses-with a particular focus on applications to cultural heritage. The capabilities offered by these instruments, the specific hardware and software developments to facilitate and speed-up data acquisition and data processing are detailed, and the first results from this new access are illustrated with recent applications to pigments, paintings, ceramics and wood.

Psychosocial impact of the COVID-19 pandemic on patients with inflammatory bowel disease in Spain. A post lockdown reflection.

OBJECTIVES: This multicenter cross-sectional study was conducted to assess the psychosocial impact of COVID-19 on patients with inflammatory bowel disease (IBD) in Spain during lockdown and the first wave of the pandemic. PATIENTS AND METHODS: A self-report questionnaire that integrated the Spanish version of the Depression, Anxiety and Stress Scale-21 items (DASS-21) and the Perceived Stress Questionnaire (PSS) was designed to gather sociodemographic data and information related to the effects of lockdown on the lives of IBD patients. Twelve IBD units invited their patients to answer the anonymous online survey between the 1st July and the 25th August 2020. RESULTS: Of the 693 survey participants with IBD, 67% were women and the mean age was 43 (SD 12). Sixty-one percent had ulcerative colitis, 36% Crohn's disease and 3% indeterminate colitis. DASS-21 scores indicate that during lockdown the estimated prevalence of depression was 11% [95% CI 8.2-13%], anxiety 20% [95% CI 17 to 23%] and stress 18% [95% CI 8.2-13%]. Multivariate analysis showed that the perceived high risk of COVID-19 infection because of having IBD and maladaptation to government measures to reduce the spread of disease doubled the risk of anxiety and stress during lockdown. CONCLUSIONS: In the short-term, lockdown during the COVID-19 pandemic seemed to have an impact on the already affected mental health of our IBD patients in Spain.

Influence of the degree of adherence to the mediterranean diet and its components on cardiometabolic risk during pregnancy. The GESTAFIT project.

BACKGROUND AND AIMS: Studies regarding dietary patterns and cardiometabolic risk markers during pregnancy are scarce. The aim of the present study was to analyse whether different degrees of adherence to the Mediterranean diet (MD) and the MD components were associated with cardiometabolic markers and a clustered cardiometabolic risk during pregnancy. METHODS AND RESULTS: This study comprised 119 pregnant women from the GEStation and FITness (GESTAFIT) project. Dietary habits were assessed with a food frequency questionnaire at the 16th and 34th gestational weeks (g.w.). The Mediterranean Diet Score was employed to assess MD adherence. The following cardiometabolic markers were assessed: pre-pregnancy body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglycerides and high-density lipoprotein cholesterol (HDL-C). A greater MD adherence was associated with a better cardiometabolic status in cross-sectional (16th g.w. and 34th g.w.) and prospective analyses (MD adherence at the 16th g.w. and cardiometabolic markers at the 34th g.w.; SBP, DBP and HDL-C; all, p < 0.05). Participants with the highest MD adherence (Tertile 3) had a lower clustered cardiometabolic risk than those with the lowest MD adherence (Tertile 1) at the 16th and 34th g.w. (both, p < 0.05). A higher intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts were associated with a lower cardiometabolic risk during pregnancy (all, p < 0.05). CONCLUSION: A higher MD adherence, a greater intake of fruits, vegetables and fish and a lower intake of refined cereals and red meat and subproducts showed a cardioprotective effect throughout gestation.

Objectively measured sedentary time and physical activity levels in Spanish pregnant women. Factors affecting the compliance with physical activity guidelines.

The aims of this cross-sectional study were to describe objectively measured sedentary time (ST) and physical activity (PA) levels in Spanish pregnant women, to analyze the degree of compliance with PA guidelines during the early second trimester of pregnancy and to explore sociodemographic and clinical factors associated with meeting these PA guidelines. One hundred and thirty-four Caucasian pregnant women were recruited between October 2015 and October 2017 to participate in this study. Triaxial accelerometers were used to analyze ST andPA levels for seven consecutive valid days. Womenspent512 ± 92.1 minutes daily in sedentary behaviors, and 85 ± 108.2 minutes in moderate-to-vigorous physical activity (MVPA) in bouts of at least 10 minutes. They walked on average 7436 ± 2410steps per day. Only 22% of the study sample complied with the PA guidelines. Having an University degree was related with threefold higher odds of compliance with the PA guidelines (95% confidence interval: 0.096-0.913, p < .05). Binary logistic regressions showed that being primiparous was associated with fivefold higher odds of compliance with the PA guidelines (95% confidence interval 1.658-18.039, respectively, p < .01). Maternal age, BMI, marital status, working status, and previous miscarriages were not associated with compliance with PA guidelines. Pregnant women spent more than a third of the day in sedentary behaviors and the compliance with PA guidelines was less than desirable. Finally, not having an university degree or having children could be factors related to lower odds of compliance with these guidelines, and therefore require special attention from healthcare professionals.

[VIG-Express: Consensus on an express multidimensional/geriatric assessment system in Catalonia]. / VIG-Express: Consenso de un sistema de valoración multidimensional/geriátrica rápida en Cataluña.

OBJECTIVE: To reach a consensus on an rapid multidimensional/geriatric assessment (RMGA) tool for all health and social professionals of Catalonia as a shared and universal system to assess patients with multimorbidities, frailty, complexity or advanced conditions. DESIGN: Three-phase consensus of professionals, combining in-person sessions with telematics. LOCATION: Catalonia. PARTICIPANTS: A group of 27 interdisciplinary professionals from different care settings. METHOD: The Design Thinking methodology for an initial consensus on the characteristics of the RMGA tool (Phase 1) has been combined with the Lean Startup methodology to create a new RMGA tool (Phase 2), and then tested in a group of patients (Phase 3). RESULTS: In Phase 1, a consensus was reached that the perfect RMGA tool should allow for an ad hoc assessment of patients, be fast and flexible (<10 min), identify altered dimensions using trigger questions and facilitate the diagnosis of the condition (ideally quantified). In Phase 2, a prototype of a new RMGA tool containing 15 + 2 questions (VIG-Express) was developed, which was then tested in 35 patients in Phase 3. CONCLUSIONS: Based on preliminary results, the VIG-Express tool seems to facilitate a simple, rapid multidimensional assessment and the customization of interventions, as well as provide a unique look and shared narrative between professionals from different care settings. More studies will be required to corroborate these findings.

Cuff-assisted versus cap-assisted colonoscopy for adenoma detection: results of a randomized study.

BACKGROUND: The adenoma detection rate (ADR) is the most important marker of colonoscopy quality. Devices to improve adenoma detection have been developed, such as the Endocuff and transparent cap. The aim of the current study was to examine whether there was a difference in ADR between Endocuff-assisted (EAC) and cap-assisted colonoscopy (CAC). METHODS: A randomized prospective trial was conducted. Eligible patients included adults ≥ 18 years referred because of symptoms, surveillance, or colonoscopies as part of the Bowel Cancer Screening Programme (BCSP). The primary outcome measure was ADR. Secondary outcomes included mean number of adenomas, mean number of polyps, polyp detection rate, cecal intubation rate, and time to cecal intubation. Procedural measures, device removal rate, and adverse events were also recorded. RESULTS: A total of 711 patients (51.1 % men; median age 63 years) were included, of whom 357 patients were randomized to EAC and 354 patients to CAC. In the intention-to-treat analysis, the ADR was similar in both groups: EAC 50.4 % (95 % confidence interval [CI] 45.1 - 55.7) vs. CAC 50.6 % (95 %CI 45.2 - 55.9). Similar results were obtained in the per-protocol analysis: EAC 51.6 % (95 %CI 46.2 - 57) vs. CAC 51.4 % (95 %CI 46 - 56.8). There were no differences between the two devices in ADR according to the mean number of adenomas and polyps per procedure, polyp detection rate, cecal intubation rate, and time to cecal intubation. Device removal rate and adverse events were also similar. CONCLUSION: In this randomized study, no differences in ADR were found between Endocuff- and cap-assisted colonoscopy.

Long-term and mechanistic evaluation of drug-induced liver injury in Upcyte human hepatocytes.

Drug-induced liver injury (DILI) constitutes one of the most frequent reasons of restricted-use warnings as well as withdrawals of drugs in postmarketing and poses an important concern for the pharmaceutical industry. The current hepatic in vivo and in vitro models for DILI detection have shown clear limitations, mainly for studies of long-term hepatotoxicity. For this reason, we here evaluated the potential of using Upcytes human hepatocytes (UHH) for repeated-dose long-term exposure to drugs. The UHH were incubated with 15 toxic and non-toxic compounds for up to 21 days using a repeated-dose approach, and, in addition to conventional examination of effects on viability, the mechanisms implicated in cell toxicity were also assessed by means of high-content screening. The UHH maintained the expression and activity levels of drug-metabolizing enzymes for up to 21 days of culture and became more sensitive to the toxic compounds after extended exposures, showing inter-donor differences which would reflect variability among the population. The assay also allowed to detect the main mechanisms implicated in the toxicity of each drug as well as identifying special susceptibilities depending on the donor. UHH can be used for a long-term repeated detection of DILI at clinically relevant concentrations and also offers key mechanistic features of drug-induced hepatotoxicity. This system is therefore a promising tool in preclinical testing of human relevance that could help to reduce and/or replace animal testing for drug adverse effects.

Association of self-reported physical fitness with pain during pregnancy: The GESTAFIT Project.

AIMS: To explore the association of self-reported physical fitness with bodily, lumbar and sciatic pain, and pain disability during pregnancy. METHODS: The present study sample comprised 159 pregnant women (32.9 ± 4.7 years old). Self-reported physical fitness was assessed with the International Fitness Scale (IFIS), where higher scores indicate greater physical fitness. Bodily pain was assessed with the 36-Item Short Form Health Survey (SF-36), where higher scores indicate lower pain. Lumbar and sciatic pain were measured with a visual analogue scale (VAS). The Oswestry Disability Index (ODI) questionnaire was employed to assess the disability resulting from pain. Measures were assessed at 16th and 34th gestational weeks (g. w.). RESULTS: Pregnant women showed low-moderate pain during pregnancy course. Most of them showed medium self-reported overall physical fitness. At 16th g. w., greater self-reported overall physical fitness and cardiorespiratory fitness were associated with less bodily and lumbar pain, and pain disability (all, P < 0.05). Greater muscular strength was associated with less bodily pain and pain disability (both, P < 0.05). Greater speed-agility was associated with less bodily pain (P < 0.01) and less pain disability (P < 0.05). Self-reported flexibility was not associated with any outcome (P > 0.05). At 34th g. w., greater overall physical fitness and its components were associated with less bodily and sciatic pain (all, P < 0.05). CONCLUSION: Greater self-reported overall physical fitness and its components are associated with less bodily, lumbar and sciatic pain, and reduced pain disability during pregnancy. Future studies are needed to explore whether increasing physical fitness before and during pregnancy could decrease pain in this relevant stage.

Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury.

Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify metabolic phenotypes with increased susceptibility to DILI. To this end, HepG2 cells with different expression levels of specific drug-metabolism enzymes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, GSTM1 and UGT2B7) were exposed to nine drugs with reported hepatotoxicity. A panel of pre-lethal mechanistic parameters (mitochondrial superoxide production, mitochondrial membrane potential, ROS production, intracellular calcium concentration, apoptotic nuclei) was used. Significant differences were observed according to the level of expression and/or the combination of several drug-metabolism enzymes in the cells created ad hoc according to the enzymes implicated in drug toxicity. Additionally, the main mechanisms implicated in the toxicity of the compounds were also determined showing also differences between the different types of cells employed. This screening tool allowed to mimic the variability in drug metabolism in the population and showed a highly efficient system for predicting human DILI, identifying the metabolic phenotypes associated with increased DILI risk, and indicating the mechanisms implicated in their toxicity.

Cost of Hospitalizations due to Exacerbation in Patients with Non-Cystic Fibrosis Bronchiectasis.

BACKGROUND: Knowing the cost of hospitalizations for exacerbation in bronchiectasis patients is essential to perform cost-effectiveness studies of treatments that aim to reduce exacerbations in these patients. OBJECTIVES: To find out the mean cost of hospitalizations due to exacerbations in bronchiectasis patients, and to identify factors associated with higher costs. METHODS: Prospective, observational, multicenter study in adult bronchiectasis patients hospitalized due to exacerbation. All expenses from the patients' arrival at hospital to their discharge were calculated: diagnostic tests, treatments, transferals, home hospitalization, admission to convalescence centers, and hospitals' structural costs for each patient (each hospital's tariff for emergencies and 70% of the price of a bed for each day in a hospital ward). RESULTS: A total of 222 patients (52.7% men, mean age 71.8 years) admitted to 29 hospitals were included. Adding together all the expenses, the mean cost of the hospitalization was EUR 5,284.7, most of which correspond to the hospital ward (86.9%), and particularly to the hospitals' structural costs. The adjusted multivariate analysis showed that chronic bronchial infection by Pseudomonas aeruginosa, days spent in the hospital, and completing the treatment with home hospitalization were factors independently associated with a higher overall cost of the hospitalization. CONCLUSIONS: The mean cost of a hospitalization due to bronchiectasis exacerbation obtained from the individual data of each episode is higher than the cost per process calculated by the health authorities. The most determining factor of a higher cost is chronic bronchial infection due to P. aeruginosa, which leads to a longer hospital stay and the use of home hospitalization.

Short- and long-term effects of oral vancomycin on the human intestinal microbiota.

BACKGROUND: Oral vancomycin remains the mainstay of therapy for severe infections produced by Clostridium difficile, the most prevalent cause of healthcare-associated infectious diarrhoea in developed countries. However, its short- and long-term effects on the human intestinal microbiota remain largely unknown. METHODS: We utilized high-throughput sequencing to analyse the effects of vancomycin on the faecal human microbiota up to 22 weeks post-antibiotic cessation. The clinical relevance of the observed microbiota perturbations was studied in mice. RESULTS: During vancomycin therapy, most intestinal microbiota genera and operational taxonomic units (OTUs) were depleted in all analysed subjects, including all baseline OTUs from the phylum Bacteroidetes. This was accompanied by a vast expansion of genera associated with infections, including Klebsiella and Escherichia/Shigella. Following antibiotic cessation, marked differences in microbiota resilience were observed among subjects. While some individuals recovered a microbiota close to baseline composition, in others, up to 89% of abundant OTUs could no longer be detected. The clinical relevance of the observed microbiota changes was further demonstrated in mice, which developed analogous microbiota alterations. During vancomycin treatment, mice were highly susceptible to intestinal colonization by an antibiotic-resistant pathogen and, upon antibiotic cessation, a less-resilient microbiota allowed higher levels of pathogen colonization. CONCLUSIONS: Oral vancomycin induces drastic and consistent changes in the human intestinal microbiota. Upon vancomycin cessation, the microbiota recovery rate varied considerably among subjects, which could influence, as validated in mice, the level of susceptibility to pathogen intestinal colonization. Our results demonstrate the negative long-term effects of vancomycin, which should be considered as a fundamental aspect of the cost-benefit equation for antibiotic prescription.

Advantageous use of HepaRG cells for the screening and mechanistic study of drug-induced steatosis.

Only a few in vitro assays have been proposed to evaluate the steatotic potential of new drugs. The present study examines the utility of HepaRG cells as a cell-based assay system for screening drug-induced liver steatosis. A high-content screening assay was run to evaluate multiple toxicity-related cell parameters in HepaRG cells exposed to 28 compounds, including drugs reported to cause steatosis through different mechanisms and non-steatotic compounds. Lipid content was the most sensitive parameter for all the steatotic drugs, whereas no effects on lipid levels were produced by non-steatotic compounds. Apart from fat accumulation, increased ROS production and altered mitochondrial membrane potential were also found in the cells exposed to steatotic drugs, which indicates that all these cellular events contributed to drug-induced hepatotoxicity. These findings are of clinical relevance as most effects were observed at drug concentrations under 100-fold of the therapeutic peak plasmatic concentration. HepaRG cells showed increased lipid overaccumulation vs. HepG2 cells, which suggests greater sensitivity to drug-induced steatosis. An altered expression profile of transcription factors and the genes that code key proteins in lipid metabolism was also found in the cells exposed to drugs capable of inducing liver steatosis. Our results generally indicate the value of HepaRG cells for assessing the risk of liver damage associated with steatogenic compounds and for investigating the molecular mechanisms involved in drug-induced steatosis.

LC-MS untargeted metabolomic analysis of drug-induced hepatotoxicity in HepG2 cells.

Hepatotoxicity is the number one cause for agencies not approving and withdrawing drugs for the market. Drug-induced human hepatotoxicity frequently goes undetected in preclinical safety evaluations using animal models. Human-derived in vitro models represent a common alternative to in vivo tests to detect toxic effects during preclinical testing. Most current in vitro toxicity assays rely on the measurement of nonspecific or low sensitive endpoints, which result in poor concordance with human liver toxicity. Therefore, making more accurate predictions of the potential hepatotoxicity of new drugs remains a challenge. Metabolomics, whose aim is to globally assess all the metabolites present in a biological sample, may represent an alternative in the search for sensitive sublethal markers of drug-induced hepatotoxicity. To this end, a comprehensive LC-MS-based untargeted metabolite profiling analysis of HepG2 cells, exposed to a set of well-described model hepatotoxins and innocuous compounds, was performed. It allowed to determine meaningful metabolic changes triggered by a toxic insult and gave a first estimation of the main toxicity-related pathways. Based on these metabolic patterns, a partial least squares-discriminant analysis model, able to discriminate between nontoxic and hepatotoxic compounds, was constructed. The approach described herein may provide an alternative for animal testing in preclinical stages of drug development and a controlled experimental approach to gain a better understanding of the underlying causes of hepatotoxicity.

A novel approach for intracellular 3D immuno-labeling for electron tomography.

Electron tomography (ET) is an indispensable high-resolution tool for three dimensional (3D) imaging in cell biology. When applied to immuno-labeled cells, ET can provide essential insights in both the cellular architecture and the dynamics. Current protocols for 3D immuno-labeling of intracellular antigens include permeabilization steps that cause random, extensive cell membrane disruption. This permeabilization results in a poor cell ultrastructure, limiting the usefulness of the specimens for high-resolution studies. Here we describe a novel method, based on a well-controlled permeabilization by targeted laser cell perforation, that allows for the 3D immuno-localization of cytoplasmic antigens in cultured cells. The approach is unique since it is applicable to both chemically and cryo-fixed cells and leads to a superior ultrastructural preservation for electron microscopy and tomography.

Stimulating the biofilm formation of Bacillus populations to mitigate soil antibiotic resistome during insect fertilizer application.

Antibiotic resistance in soil introduced by organic fertilizer application pose a globally recognized threat to human health. Insect organic fertilizer may be a promising alternative due to its low antibiotic resistance. However, it is not yet clear how to regulate soil microbes to reduce antibiotic resistance in organic fertilizer agricultural application. In this study, we investigated soil microbes and antibiotic resistome under black soldier fly organic fertilizer (BOF) application in pot and field systems. Our study shows that BOF could stimulate ARB (antibiotic resistant - bacteria) - suppressive Bacillaceae in the soil microbiome and reduce antibiotic resistome. The carbohydrate transport and metabolism pathway of soil Bacillaceae was strengthened, which accelerated the synthesis and transport of polysaccharides to form biofilm to antagonistic soil ARB, and thus reduced the antibiotic resistance. We further tested the ARB - suppressive Bacillus spp. in a microcosm assay, which resulted in a significant decrease in the presence of ARGs and ARB together with higher abundance in key biofilm formation gene (epsA). This knowledge might help to the development of more efficient bio-fertilizers aimed at mitigating soil antibiotic resistance and enhancing soil health, in particular, under the requirements of global "One Health".

Mediterranean Diet Adherence and Health-Related Quality of Life during Pregnancy: Is the Mediterranean Diet Beneficial in Non-Mediterranean Countries?

This study aimed to examine the association of Mediterranean diet (MD) adherence and MD components with health-related quality of life (HRQoL) in pregnant women from Spain and Sweden. A total of 138 pregnant women from Spain (age: 32.9 ± 4.6 years old) and 302 pregnant women from Sweden (age: 31.3 ± 4.1 years old) were included. MD adherence was assessed with the Mediterranean food pattern (i.e., a MD index) at the 14-16th gestational weeks. HRQoL was assessed with the Spanish and Swedish versions of the 36-item Short-Form Health Survey (SF-36 and RAND-36, respectively) at the 14-16th and 34-37th gestational weeks. A greater MD adherence was associated with better physical functioning, bodily pain, vitality, emotional role, and mental health in cross-sectional associations (2nd trimester) in the Spanish sample (all p < 0.05). Furthermore, a greater MD adherence was associated with lower bodily pain in both Spanish and Swedish samples (both p < 0.05) in the 3rd trimester. The associations of MD adherence with pain seem to be explained by a greater intake of fiber, fish, fruits, nuts, and legumes (all p < 0.05). A greater MD adherence, driven by a higher intake of fiber, fish, fruits, nuts, and legumes, was associated with lower pain throughout pregnancy in both Mediterranean and non-Mediterranean populations.