Human Variation Research Articles

Microhomology-mediated end-joining Knock-In approaches to delete the allergenic domain of trout parvalbumin beta-1. Preliminary results in F0 animals and feedback

Background Gene editing techniques offer new opportunities to improve important traits in aquaculture. The allergenicity of fish flesh is a major problem in aquaculture. Parvalbumin (Parv) is the most prevalent fish allergen. For instance, in salmonids, a single parvalbumin beta-1 protein (parvb1) has been identified as an allergen in specific patients. Therefore, generating trout carrying two parvb1 alleles deleted from the allergenic peptide-encoding region could prevent allergies in these sensitive individuals. Methods Here, we describe the application of the Crispr/cas9 system in an attempt to delete parvb1 exon 2 encoding the allergenic peptide and, alternatively, to replace exon 2 of parvb1 with exon2 of parvalbumin beta-2 protein (parvb2,) which does not encode the allergenic peptide. Exon skipping and swapping were pursued through microhomology-mediated end-joining (MMEJ) knock-In using specifically designed double-stranded donor DNA. Results Genotyping of approximately 200 F0 fingerlings originating from eggs injected with donor DNA designed for exon 2 skipping led to the identification of only one animal carrying an allele lacking exon 2. Genotyping of approximately 150 fingerlings originating from eggs injected with donor DNA for exon 2 swapping did not result in any trout carrying the expected modified allele. Conclusions These preliminary results indicate the potential difficulties associated with the MMEJ KI experiments performed in farmed fish. Finally, new genomic techniques in aquaculture are further discussed in the context of lively debates taking place in the European parliament regarding a possible revision of the current law that determines the legal status of farm animals modified by genome editing. Gene editing, microhomology-mediated end-joining knock-in, parvalbumin, allergenicity, trout, and genetically modified organisms (GMOs).

Allergenic Potential of Common Hops (Humulus lupulus L.) in the Context of Cross-Reactions with Pollen Allergens

Background: Common hops (Humulus lupulus L.) play a key role in brewing, providing the bitterness, flavor, and aroma of beer, and are widely used in supplements for their antibacterial, anti-inflammatory, and antioxidant properties. However, despite their broad applications, the allergenic potential of common hops remains underexplored, particularly when compared to the closely related Humulus japonicus. This preliminary study aimed to investigate the allergenic potential of common hops and their potential cross-reactivity with common pollen allergens. Methods: The immunoreactivity of hop stalks, leaves, and cones was assessed using antibodies against major allergens from birch (Bet v1a), mugwort (Art v1), and timothy grass (Phl p5b), as well as three sera from pollen-allergic patients. Slot Blot analysis was performed using phosphate-buffered saline extracts from the stalks, leaves, and cones of three hop cultivars, while Western Blotting followed SDS-PAGE protein separation. Results: The results revealed significant immunoreactivity in native hop proteins, with diminished reactivity observed in denatured proteins. Cross-reactivity between hop proteins and major pollen allergens was confirmed, indicating that hop proteins may contribute to allergic sensitization in pollen-sensitive individuals. Conclusions: These findings underscore the potential allergenic risks associated with the consumption or exposure to hop-containing products.

Improved quality control of allergen products: Assessing the molecular allergen composition by mass spectrometry.

Natural allergen sources contain a variety of allergens, against which allergic subjects have developed individual sensitization profiles. Ideal allergen products for skin prick testing (SPT) and allergen immunotherapy (AIT) should contain the complete set of allergens of the respective allergen sources to cover all sensitization profiles. However, commercially available allergen products were shown to vary regarding their allergen composition. The qualitative allergen composition of different SPT and AIT products produced from pollen of grasses, birch, mugwort and from house dust mites was assessed by a consistent high-resolution liquid chromatography-coupled tandem mass spectrometry method (LC-MS/MS). All major, mid-tier and most minor allergens were detected in each of the investigated three batches of SPT and AIT products, demonstrating the completeness of the allergen composition and a high degree of batch-to-batch consistency. This is the first study using a single consistent high-resolution LC-MS/MS method to provide solid data on the qualitative allergen composition of SPT and AIT products manufactured from various common allergen sources. The applied method showed high reliability in qualitative batch-to-batch consistency testing and can be performed fast and with high throughput. High-resolution LC-MS/MS is applicable for process development and quality control to ensure market availability of allergen products corresponding to the composition of the respective natural allergen sources.

In their narratives: academic socialization in the experience of sensory processing sensitivity among university students

IntroductionWhile much of the worldwide contemporary research on sensory processing sensitivity (SPS) and environmental sensitivity (ES) has relied on the participation of university students, there remains a significant gap in understanding the academic social experiences of those scoring high in SPS (i.e., highly sensitive individuals).MethodsTo address this gap, this exploratory study aimed to investigate in detail students’ academic socialization through their narratives. We conducted nine interviews with Italian university students who self-identified as highly sensitive.ResultsThrough thematic reflexive analysis, we identified and analyzed 6 themes (with subthemes and versions of subthemes) concerning their self-definitions, their university experience (in classroom, before, during, and after exams), and socialization with peers and teachers.DiscussionAfter 20 years of research on SPS, this study integrates the relevant literature into the field of social psychology and academic socialization, emphasizing the importance of understanding SPS within real-life educational contexts and considering highly sensitive students’ perspectives on their resources and challenges in attending university. By contributing to the emerging qualitative literature on SPS and ES, this study provides practical implications for educators and policymakers seeking to foster inclusive learning environments for all students.

Tracking the Spread of Pollen on Social Media Using Pollen-Related Messages From Twitter: Retrospective Analysis.

Allergy disorders caused by biological particles, such as the proteins in some airborne pollen grains, are currently considered one of the most common chronic diseases, and European Academy of Allergy and Clinical Immunology forecasts indicate that within 15 years 50% of Europeans will have some kind of allergy as a consequence of urbanization, industrialization, pollution, and climate change. The aim of this study was to monitor and analyze the dissemination of information about pollen symptoms from December 2006 to January 2022. By conducting a comprehensive evaluation of public comments and trends on Twitter, the research sought to provide valuable insights into the impact of pollen on sensitive individuals, ultimately enhancing our understanding of how pollen-related information spreads and its implications for public health awareness. Using a blend of large language models, dimensionality reduction, unsupervised clustering, and term frequency-inverse document frequency, alongside visual representations such as word clouds and semantic interaction graphs, our study analyzed Twitter data to uncover insights on respiratory allergies. This concise methodology enabled the extraction of significant themes and patterns, offering a deep dive into public knowledge and discussions surrounding respiratory allergies on Twitter. The months between March and August had the highest volume of messages. The percentage of patient tweets appeared to increase notably during the later years, and there was also a potential increase in the prevalence of symptoms, mainly in the morning hours, indicating a potential rise in pollen allergies and related discussions on social media. While pollen allergy is a global issue, specific sociocultural, political, and economic contexts mean that patients experience symptomatology at a localized level, needing appropriate localized responses. The interpretation of tweet information represents a valuable tool to take preventive measures to mitigate the impact of pollen allergy on sensitive patients to achieve equity in living conditions and enhance access to health information and services.

Interactions of genes with alcohol consumption affect insulin sensitivity and beta cell function.

Alcohol consumption has complex effects on diabetes and metabolic disease, but there is widespread heterogeneity within populations and the specific reasons are unclear. Genetic factors may play a role and warrant exploration. The aim of this study was to elucidate genetic variants modulating the impact of alcohol consumption on insulin sensitivity and pancreatic beta cell function within populations presenting normal glucose tolerance (NGT). We recruited 4194 volunteers in Nanjing, 854 in Jurong and an additional 5833 in Nanjing for Discovery cohorts 1 and 2 and a Validation cohort, respectively. We performed an OGTT on all participants, establishing a stringent NGT group, and then assessed insulin sensitivity and beta cell function. Alcohol consumption was categorised as abstinent, light-to-moderate (<210 g per week) or heavy (≥210 g per week). After excluding ineligible individuals, an exploratory genome-wide association study identified potential variants interacting with alcohol consumption in 1862 NGT individuals. These findings were validated in an additional cohort of 2169 NGT individuals. Cox proportional hazard regression was further employed to evaluate the effect of the interaction between the potential variants and alcohol consumption on the risk of type 2 diabetes within the UK Biobank cohort. A significant correlation was observed between drinking levels and insulin sensitivity, accompanied by a consequent inverse relationship with insulin resistance and beta cell insulin secretion after adjusting for confounding factors in NGT individuals. However, no significant associations were noted in the disposition indexes. The interaction of variant rs56221195 with alcohol intake exhibited a pronounced effect on the liver insulin resistance index (LIRI) in the discovery set, corroborated in the validation set (combined p=1.32 × 10-11). Alcohol consumption did not significantly affect LIRI in rs56221195 wild-type (TT) carriers, but a strong negative association emerged in heterozygous (TA) and homozygous (AA) individuals. The rs56221195 variant also significantly interacts with alcohol consumption, influencing the total insulin secretion index INSR120 (the ratio of the AUC of insulin to glucose from 0 to 120 min) (p=2.06 × 10-9) but not disposition index. In the UK Biobank, we found a significant interaction between rs56221195 and alcohol consumption, which was linked to the risk of type 2 diabetes (HR 0.897, p=0.008). Our findings reveal the effects of the interaction of alcohol and rs56221195 on hepatic insulin sensitivity in NGT individuals. It is imperative to weigh potential benefits and detriments thoughtfully when considering alcohol consumption across diverse genetic backgrounds.

Effect of CAT gene polymorphism on sensitivity of human lymphocytes to genotoxic effect of organochlorine pesticide in vitro

Introduction. Over recent decades, toxicogenetic studies have focused on the issues of genome instability under the action of genotoxicants, taking into account biomarkers of sensitivity. The question about the genotoxic potential of chlorpyrifos remains open, since both positive and negative effects have been revealed in various tests. The aim of the study is the investigation of sensitivity of donor peripheral blood lymphocytes to chlorpyrifos in vitro and evaluation of the contribution of polymorphism of antioxidant defense system genes (CAT (rs1001179), SOD2 (rs4880)) to the response of human cells to the action of genotoxicant. Materials and methods. The DNA damaging effect of chlorpyrifos was assessed on lymphocytes from fifty two donors using DNA-comet assay with metabolic activation (+S9) and without it (–S9). The study of cytotoxic effects of chlorpyrifos on human lymphocytes was carried out using an automatic fluorescent cell analyzer ADAMII LS. Results. Chlorpyrifos had a pronounced cytotoxic effect on lymphocytes in most donors in the absence of metabolic activation system. With increasing concentration of the pesticide in the medium and time of cultivation, the viability of lymphocytes decreased, and the proportion of cells in late apoptosis and necrosis increased. Positive genotoxic effects were found on the cells of 33 donors (-S9). In the presence of the S9, mild but statistically significant effects were detected only on cells from 2 donors. % DNA values in the comet tail after exposure to the pesticide varied for cells from different donors. In the absence of metabolic activation, a statistically significant increase in the level of DNA damage was found in cells of individuals with genotype AA (homozygote for the minor allele) for the CAT G262A catalase gene (rs1001179), compared with homozygote for the dominant GG allele. Limitations. The genotoxicity of chlorpyryfos was studied in vitro. Conclusion. The results of the study shown cytotoxic and genotoxic effects of chlorpyrifos. The sensitivity of lymphocytes from different donors to the pesticide was found to be significantly different. The association of the level of DNA damage under exposure of chlorpyrifos in vitro with the G262A polymorphism of the catalase gene was found. The research also confirms the possibility of using a model test-system with peripheral blood lymphocytes to assess the potential genetic risk for humans and to study the contribution of gene polymorphism to individual sensitivity to the action of genotoxicants.

A first determination of the strong coupling αS\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha _S$$\\end{document} at approximate N3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{N}^3$$\\end{document}LO order in a global PDF fit

We present the first determination of the value of the strong coupling via a simultaneous global fit of the proton parton distribution functions (PDFs) at approximate N3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{N}^3$$\\end{document}LO (aN3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{N}^3$$\\end{document}LO) order in QCD. This makes use of the MSHT global PDF fitting framework, and in particular the recent theoretical advances t l;;mhat allow a PDF fit to now be performed at this order. The value of the strong coupling is found to be αS(MZ2)(aN3LO)=0.1170±0.0016\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\alpha _{S}(M_Z^2)(\\mathrm{aN^3LO}) = 0.1170 \\pm 0.0016$$\\end{document}. This is in excellent agreement with the NNLO value of αS(MZ2)(NNLO)=0.1171±0.0014\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ \\alpha _{S}(M_Z^2)(\ extrm{NNLO}) = 0.1171 \\pm 0.0014$$\\end{document}, indicating that good perturbative convergence has been found. The resulting uncertainties, calculated using the MSHT dynamic tolerance procedure, are somewhat larger, but more accurate, at aN3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{N}^3$$\\end{document}LO, due to the missing higher order theoretical uncertainties that are included at this order, but not at NNLO. We in addition present a detailed breakdown of the individual dataset sensitivity to the value of the strong coupling, with special focus on the impact of fitting dijet rather than inclusive jet data. This choice is found to have a non-negligible impact, but with overall good consistency found, especially at aN3\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ extrm{N}^3$$\\end{document}LO.

8045 A Case Report of Primary Adrenal Insufficiency Due to a Novel Pathogenic Variant in NR0B1 (Dax 1) Gene

Abstract Disclosure: M.N. Lemos: None. G.D. Martins: None. J.R. Cicogna: None. N.M. Scalissi: None. J.V. Lima-Jr: None. Background: X-linked adrenal hypoplasia congenita caused by a pathogenic variant in NR0B1/DAX-1 is a rare inherited disorder. Patients with adrenal hypoplasia congenita are usually diagnosed with primary adrenal insufficiency in infancy or early childhood and usually present hypogonadotropic hypogonadism during adolescence. Clinical Case: Our male patient first presented with adrenal crisis at the age of 11 years, managed with glucocorticoids (prednisolone) and mineralocorticoids (fludrocortisone) in a local hospital at Bahia state, Brazil. He was referred to our reference service in Sao Paulo at the age of 14, in regular use of those medications. In this time, he brought some laboratorial analysis from the time of diagnosis, and it showed hyponatremia (sodium 99 mEq/L; NR 135 - 150) and hyperkalemia (potassium 6,7 mEq/L; NR 3,5 - 5), ACTH 23,2 pg/mL (NR &amp;lt; 45) and basal cortisol 6,6 mcg/dL (NR 5 - 18). In addition, we had from this time some additional laboratorial data from our admissional analysis, that found S-DHEA 10,1 mcg/dL (NR: 23,8 - 267,7), total testosterone 472 ng/dL (NR: 240 - 816), FSH 3,05 mUI/L (NR: &amp;lt; 10), LH 2,63 mUI/L (NR: &amp;lt;10), aldosterone 1,9 ng/dL (NR: 5 - 23) and renin &amp;gt; 500µIU/mL (NR: 2,8 - 39,9). Over the years, he started to present hyperpigmented skin lesions, due to primary adrenal insufficiency, resulting in great psychological suffering. We have screened hypogonadism many times during follow-up, but it was never found. The Genetics analysis by next generation sequence (NGS) identified in homozygosity, in gene NR0B1 (DAX1) on X chromosome, a variant of normality (chrX:30.309.248 C&amp;gt;T) were amino acid tryptophan was replaced by a stop codon. The patient does not have any brother, no other similar cases in the family and their parents deny consanguinity. Our case differs from others previously described because of the absence of associated hypogonadism, which is very common in NR0B1 variants. Clinical lesson/Conclusion: This case report shows that the absence of hypogonadism does not exclude the possibility of primary adrenal insufficiency caused by NR0B1(DAX 1) gene variants, and encourages genetic testing to patients living with this disease. Presentation: 6/2/2024

7449 A Genome-wide CRISPR Screen Identifies Drivers of Impaired Glucose Uptake in Human Insulin Resistance

Abstract Disclosure: N. Haider: None. Y. Lee: None. P. Yi: None. C.R. Kahn: None. Insulin resistance is a major risk factor in the development of type 2 diabetes (T2D), and metabolic syndrome. Although 25% of people within the general non-diabetic population are insulin resistant, the primary underlying cause of insulin resistance remains elusive. In this study, we have used induced pluripotent stem cells (iPSC) derived from non-diabetic humans at both ends of the insulin sensitivity spectrum, i.e., the top 20% of insulin resistance vs. the top 20% of insulin sensitive, as well as individuals with T2D to model human insulin resistance. We find that iPSCs differentiated into myoblasts (iMyos) from T2D and non-diabetic individuals in the highest quintile of insulin resistance (I-Res) show impaired insulin signaling and defective insulin-stimulated glucose uptake, as compared to iMyos from the insulin sensitive individuals (I-Sen), indicating that these cells in vitro mirror the alterations seen in vivo in a cell autonomous manner. To uncover the primary upstream drivers that contribute to the impaired glucose uptake associated with insulin resistance, we conducted a genome-wide loss-of-function screen using a CRISPR-based approach to identify genes that positively or negatively regulated glucose uptake in I-Res and T2D iMyos. Knockdown of ∼525 genes show effect to rescue the impaired glucose uptake in both I-Res and T2D iMyos, i.e., were negative regulators of glucose uptake. We hypothesized that important negative regulators of glucose uptake might be over-expressed at the protein level in I-Res and T2D iMyos and crossing the iMyos proteomics data with the CRISPR screen revealed 8 top candidates that are increased at the protein level and whose knockdown rescued glucose uptake in I-Res and T2D iMyos. These included candidates associated with cytoskeleton changes, protein kinases, transmembrane transport, mitochondrial and nuclear proteins. In summary, iPSC derived myoblasts from patients with insulin resistance and T2D mirror defects in glucose uptake observed in vivo. Combining CRISPR screening and global proteomics, we have identified important upstream regulators of insulin resistance in humans. Presentation: 6/2/2024

Introducing the concept of acoustic personalised environmental control systems (Acoustic PECS) within the framework of IEA EBC Annex 87

The availability of systems that can locally adjust environmental parameters holds the potential to enhance building occupant satisfaction by considering individual sensitivities, expectations, and needs. To this aim, Personalised Environmental Control Systems (PECS) are being studied as solutions that can provide individually controlled environments in the immediate surroundings of an occupant, without affecting directly the entire space and other occupants' environment. The concept has been primarily developed to address individual control of the thermal environment and perceived air quality, as in chairs with heating/cooling functions and desks equipped with personalized ventilation systems. By extending the concept of PECS to the acoustic domain, a framework on Acoustic PECS is here introduced and exemplified. The study builds on ongoing research within the IEA EBC - Annex 87, dedicated to investigating the Energy and Indoor Environmental Quality Performance of Personalised Environmental Control Systems.

Radiosensitivity in individuals with tuberous sclerosis complex

Benign tumors, but rarely cancer, are common in patients with tuberous sclerosis complex (TSC). Blood samples from patients undergoing treatment for TSC at our institution were analyzed for their individual sensitivity to ionizing radiation. Blood samples were collected from 13 adult patients with TSC. The samples were irradiated ex vivo and analyzed by 3-color fluorescence in situ hybridization. In each patient, aberrations were analyzed in 200 metaphases of chromosomes 1, 2, and 4 and scored as breaks. Radiosensitivity was determined by mean breaks per metaphase (B/M) and compared to both healthy donors and oncologic patients. The radiosensitivity (B/M) of the TSC patient cohort (n = 13; female: 46.2%, B/M: 0.48 ± 0.11) was clearly increased compared to healthy individuals of similar age (n = 90; female: 54.4%; B/M: 0.40 ± 0.09; p = 0.001). There was no difference compared to age-matched oncological patients (n = 78; female: 67.9%; B/M 0.49 ± 0.14; p = 0.246). Similarly, the proportion of radiosensitive (B/M > 0.5) and distinctly radiosensitive individuals (B/M > 0.6) was increased in the TSC and oncological patient cohorts (TSC: 30.8% and 7.7%, oncological patients: 46.2% and 14.1%) compared to the healthy individuals (11.1% and 2.2%). Although patients with TSC develop mostly benign and rarely malignant tumors, they are similarly sensitive to radiation as patients with malignant tumors.

Exercise intensities and metabolic health: Targeting blood glucose, insulin, and C-peptide levels in adults with prediabetes in the postprandial state

ObjectiveExercise improves postprandial glycemia and insulin sensitivity in individuals with prediabetes, but the optimal intensity for this metabolic regulation remains unclear. The current study explored the impact of various exercise intensities on blood glucose, insulin, and C-peptide levels in prediabetic individuals to identify the optimal intensity for improving these metabolic indicators. MethodsIn this crossover study, 25 individuals with prediabetes participated in exercise sessions at four different intensities 50 %, 60 %, 70 %, and 80 % of their predicted maximum heart rate using a treadmill. Each session lasted 30 min, including a 5-min warm-up and 5-min cool-down period. Blood samples were collected at four time points: during fasting, immediately before exercise, and 30 and 60 min post-exercise. These samples were analyzed for glucose, insulin, and C-peptide levels. The effects of exercise intensity on these parameters were evaluated using repeated measures analysis of variance (ANOVA), with post hoc tests conducted to determine specific differences between the intensities. ResultsThe participants had an average age of 34.88 years, mean height of 170 cm, and body mass index of 30.34 kg/m2. A significant reduction in insulin and glucose levels post-exercise was observed at 70 % intensity (p ≤ 0.001). Despite high fasting blood glucose levels (110–115 mg/dL), significant reductions were noted at 30 and 60 min post-exercise (p ≤ 0.001). Insulin levels approached near baseline at 70 % intensity, from fasting (26.74 ± 20.83) to 60 min post-exercise (28.47 ± 20.79), indicating a positive response at this intensity. C-peptide levels also showed significant changes, with 70 % intensity exercise bringing them closest to fasting levels by 60 min post-exercise. ConclusionThis study highlights the importance of exercise intensities in enhancing metabolic parameters in individuals with prediabetes. Specifically, 70 % of the predicted maximum heart rate was beneficial, optimizing insulin sensitivity and potentially reducing the risk of progressing from prediabetes to diabetes.

A 3-Week Ketogenic Diet Increases Skeletal Muscle Insulin Sensitivity in Individuals With Obesity: A Randomized Controlled Crossover Trial.

A ketogenic diet (KD) can induce weight loss and improve glycemic regulation, potentially reducing the risk of developing type 2 diabetes. To elucidate the underlying mechanisms behind these beneficial effects of a KD, we investigated the impact of a KD on organ-specific insulin sensitivity (IS) in skeletal muscle, liver, and adipose tissue. We hypothesized that a KD would increase IS in skeletal muscle. The study included 11 individuals with obesity who underwent a randomized, crossover trial with two three-week interventions: 1) KD and 2) standard diet. Skeletal muscle IS was quantified as the increase in glucose disposal during a hyperinsulinemic-euglycemic clamp (HEC). Hepatic IS and adipose tissue IS were quantified as the relative suppression of endogenous glucose production (EGP) and the relative suppression of palmitate flux during the HEC. The KD led to a 2.2 kg weight loss, increased insulin-stimulated glucose disposal, whereas the relative suppression of EGP during the HEC was similar. In addition, the KD decreased insulin-mediated suppression of lipolysis. In conclusion, a KD increased skeletal muscle IS in individuals with obesity.

Diagnostic value of combined detection of serum neuron-specific enolase and homocysteine in patients with coronary atherosclerosis.

The aim of this paper was to investigate the diagnostic significance and severity assessment of serum neuron-specific enolase (NSE) combined with homocysteine (Hcy) for patients with coronary atherosclerosis (coronary artery disease, CAD). Two hundred sixty-three patients with coronary artery disease were selected as the research group, and 400 healthy individuals who underwent physical examination during the same period were taken as the control group. Electrochemiluminescence immunoassay and biochemical analyzer were employed to detect the serum NSE and Hcy levels of all subjects. The diagnostic value of combined and individual serum NSE and Hcy detection for the combined group was analyzed using the ROC curve. The serum NSE (19.91±9.98 vs. 11.17±2.35) and Hcy levels (15.76±5.37 vs. 10.17±3.71) in the research group were significantly higher than those in the control group, with a statistically significant difference (P<0.05). The serum NSE (16.67±4.02 vs. 18.63±5.49 vs. 20.29±5.87) and Hcy levels (13.28±2.49 vs. 15.56±2.67 vs. 16.66±3.94) gradually increased across groups A, B, and C, and inter-group comparisons showed statistically significant differences (P<0.05). The AUC value of combined serum NSE and Hcy detection for CAD patients was higher (0.879 vs. 0.724 vs. 0.827) than individual NSE and Hcy testing. The specificity of Hcy for the diagnosis of CAD was the highest, reaching 90.3%. The sensitivity of combined NSE and Hcy (82.9%) was higher than the individual testing sensitivity of the two groups. The combined detection of serum NSE and Hcy has high diagnostic efficacy for CAD and provides reference value in assessing the severity of the disease.

Performance of a BeO-based dosimetry system for proton and electron beam dose measurements

This study aims to evaluate the performance of the BeO-based myOSLchip system (RadPro International GmbH, Remscheid, Germany) for dosimetry of proton and electron radiotherapy beams. Although beryllium oxide (BeO) has been recognised as a promising material for luminescence dosimetry in radiotherapy, this research extends beyond material properties and examines the entire BeO-based dosimetry system, including the detector, holder, and readout components.Packages of myOSLchip detectors were irradiated either in a (70−230) MeV proton beam or in a 16 MeV electron beam. The readouts were carried out using the portable myOSLchip reader. In the electron beam, tests on the precision, dose response up to 100 Gy and dose-rate effects of the system were carried out. In the proton beam, the system was tested for its dose response (up to 10 Gy), fading, and linear energy transfer (LET) response.For proton irradiations, the myOSLchip BeO OSLDs exhibited stability within 2 % over 135 days, as well as a linear dose response in the tested range, (0.1−10) Gy. The efficiency showed a reduction for proton beams with LET values (for water) above 0.6 keV/μm, with up to 40 % loss in efficiency at 4 keV/μm. For the electron irradiations, they showed a linear dose–response up to 20 Gy and dose-rate independence, with a constant response at least up to 2.99×105 Gy s−1. Using individual chip sensitivity correction, the precision for a single chip was around 3.5% (standard deviation of the data of all chips) and for a package comprising four chips was 1.7% (standard deviation of the mean of the four chips).These findings suggest the myOSLchip system’s potential as a reliable alternative to existing dosimetry systems in clinical applications.

Contrast-enhanced endoscopic ultrasound for differential diagnosis of autoimmune pancreatitis: a meta-analysis.

Background and study aims To assess the diagnostic value of contrast-enhanced endoscopic ultrasound (CE-EUS) for autoimmune pancreatitis and other solid pancreatic masses. Patients and methods A systematic search of PubMed, Embase, and Web of Science was performed from inception to October 2022. We calculated individual and pooled sensitivities and specificities to determine the diagnostic ability of CE-EUS. In addition, we calculated I 2 to test for heterogeneity and explored the source of heterogeneity by meta-regression analysis. Results A total of 472 patients from seven eligible studies were included. The mean sensitivity and specificity of the Bivariate analysis were 0.84 (95% CI 0.71-0.92) and 0.95 (95% CI 0.84-0.99), respectively. The diagnostic advantage ratio was 107.91 (95% confidence interval [CI] 22.22-524.13), and the area under the summary receiver operating characteristics curve was 0.91 (95% CI 0.88-0.93). The overall heterogeneity of the studies is negligible (I 2 =0, 95% CI 0-100). However, notable heterogeneity was observed in the combined specificity ( P <0.01, I 2 =74.82) and diagnostic odds ratio ( P =0.05, I 2 =51.54). The heterogeneity in these aspects could be elucidated through sensitivity analysis. Conclusions Our analysis showed that CE-EUS is useful in identifying autoimmune pancreatitis. However, further large sample size, multicenter, prospective studies are needed to demonstrate its utility.

Freezing stress tolerance of benthic freshwater diatoms from the genus Pinnularia: Comparison of strains from polar, alpine, and temperate habitats.

Diatoms are among the most important primary producers in alpine and polar freshwaters. Although temperate diatoms are sensitive to freezing, polar diatoms often exhibit more resistance. This is particularly true for members of the (predominantly terrestrial) Pinnularia borealis species complex. However, it remains unclear to what extent this resistance applies to other representatives of the genus. Here, we compare the freezing-stress tolerance of 11 freshwater, benthic strains representing different species of Pinnularia (including Caloneis) from polar, alpine, and temperate habitats. As vegetative cells, strains were exposed to freezing temperatures of -4, -10, -20, -40, -80, and -196°C. Survival was assessed by light microscopy and photosynthetic measurements. We observed vegetative cells to be sensitive to low freezing temperatures; only "mild" freezing was survived by all tested strains, and most tested strains did not survive treatments ≤-10°C. However, individual strain sensitivities appeared related to their original habitats. For example, polar and alpine strains better withstood "mild" and "moderate" freezing (-4 and -10°C, respectively); although temperate strains were significantly affected by the "mild" freezing treatment, polar and alpine strains were not. The -10°C treatment was survived exclusively by polar strains, and only P. catenaborealis survived all treatments. Interestingly, this species exhibited the lowest survival in the -10°C treatment, potentially implying some metabolic activity even at freezing temperatures. Thus, despite more extensive sampling throughout the genus and finer temperature scaling compared to previous studies, the remarkable freezing-stress tolerance of the P. borealis species complex remains unique within the genus.

Understanding the role of the human gut microbiome in overweight and obesity.

The gut microbiome may be related to the prevalence of overweight and obesity, but high interindividual variability of the human microbiome complicates our understanding. Obesity often occurs concomitantly with micronutrient deficiencies that impair energy metabolism. Microbiota composition is affected by diet. Host-microbiota interactions are bidirectional. We propose three pathways whereby these interactions may modulate the gut microbiome and obesity: (1) ingested compounds or derivatives affecting small intestinal transit, endogenous secretions, digestion, absorption, microbiome balance, and gut barrier function directly affect host metabolism; (2) substrate availability affecting colonic microbial composition and contact with the gut barrier; and (3) microbial end products affecting host metabolism. The quantity/concentration, duration, and/or frequency (circadian rhythm) of changes in these pathways can alter the gut microbiome, disrupt the gut barrier, alter host immunity, and increase the risk of and progression to overweight and obesity. Host-specific characteristics (e.g., genetic variations) may further affect individual sensitivity and/or resilience to diet- and microbiome-associated perturbations in the colonic environment. In this narrative review, the effects of selected interventions, including fecal microbiota transplantation, dietary calorie restriction, dietary fibers and prebiotics, probiotics and synbiotics, vitamins, minerals, and fatty acids, on the gut microbiome, body weight, and/or adiposity are summarized to help identify mechanisms of action and research opportunities.

Understanding the Relationship Between Attachment Orientation and Physical Activity Participation: An Exploratory Study.

Physical inactivity is recognized as a global health challenge. Attachment theory may provide insight into individual physical activity (PA) patterns, informing the development of PA interventions to promote the maintenance of behavior change. This study investigated the associations between attachment orientation and why and how individuals engage in PA. Given the association between attachment and sensory processing, this study also investigated the link between sensory processing and PA participation. Participants (N = 141) completed an online questionnaire that included the Modified Experiences of Close Relationships Scale and the Highly Sensitive Person Scale. The relationship between attachment orientation and sensory processing patterns, and preference for PA participation were analyzed using 2-sided independent t tests. Attachment avoidance, attachment anxiety, and sensory sensitivity were significantly related to participants' preference for PA participation in theoretically consistent ways. Avoidantly attached individuals were less likely to participate in PA as a form of social interaction (mean = 8.57, SD = 2.87, P = .005, d = 0.48). Anxiously attached individuals were more likely to participate in PA to support weight management (mean = 37.02, SD = 11.54, P = .01, d = -0.46) or if recommended by a health professional (mean = 43.55, SD = 12.45, P = .039, d = -0.88). Sensory sensitive individuals were more likely to participate in PA alone (mean = 124.11, SD = 19.23, P = .005, d = -0.510), and more likely to prefer light-intensity forms of PA (mean = 133.29, SD = 12.67, F3,123 = 5.49, P = .001). Findings highlight the potential value of considering an individual's attachment orientation and sensory processing patterns in the development of PA interventions. This may help to address the challenges of PA participation, by individually tailoring interventions to participants.