Pathogenic Potential of a PCK1 Gene Variant in Cytosolic PEPCK Deficiency: A Compelling Case Study.

BACKGROUND Cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) deficiency is an extremely rare autosomal recessive inherited error of metabolism in which gluconeogenesis is impaired, resulting in life-threatening episodes of hypoglycemia and metabolic acidosis. The diagnosis of gluconeogenesis disorders is challenging. In the diagnostic pathway, the molecular test plays a paramount role. CASE REPORT The aim of the paper is to present the case report of a girl with recurrent episodes of severe hypoglycemia, in whom molecular diagnosis enabled the confirmation of PEPCK - C deficiency. The patient experienced 4 episodes of severe hypoglycemia. Most of them were accompanied by hyperlacticaemia, metabolic acidosis, and elevated liver enzymes. All of the metabolic decompensations were triggered by infectious agents. The episodes resolved after continuous infusion of high-dose glucose. Due to the recurrent character of the disease, a genetic condition was suspected. The differential diagnosis included metabolic and endocrinological causes of hypoglycemia. Two variants in the PCK1 gene were detected: c.265G>A p.(Glu89Lys) in exon 3 and c.925G>A p.(Gly309Arg) in exon 6. As c.925G>A p.(Gly309Arg) is a known pathogenic variant, the second variant was first described in June 2023 in the ClinVar database and described as "with unknown clinical significance". CONCLUSIONS According to the clinical symptoms observed in the presented case, the variant c.265G>A p.(Glu89Lys) in PCK1 gene should be considered likely pathogenic. We suggest considering molecular diagnostics in every patient presented with recurrent, severe hypoglycemia with accompanying liver damage as most accurate, feasible, and reliable method.

Do children with asymptomatic ventricular preexcitation have similar quality of life as healthy children?

BACKGROUND: To our knowledge, no studies have assessed quality of life (QoL) in asymptomatic children with a preexcitation electrocardiogram pattern. AIM: To evaluate the QoL of children with asymptomatic Wolff-Parkinson-White (WPW) syndrome. METHODS: This study involved QoL assessment of 31 children with asymptomatic preexcitation and 82 healthy children using the WHOQOL-BREF and the Pediatric Arrhythmia Related Score (PARS), a specific questionnaire that we have developed, which is related to patients' feelings and observations concerning arrhythmia. RESULTS: There were no significant differences between the two groups in all the measured domains; however, there were significant differences regarding general satisfaction with their health condition (P = 0.01). There were no differences in general satisfaction with the QoL, but WPW children more often experienced palpitations than the control group (P <0.001) and were more likely to feel sad (P = 0.046) and nervous (P = 0.04) compared to healthy children. CONCLUSIONS: The children with WPW were more dissatisfied with their health compared to healthy children. Although both groups of children had similar levels of satisfaction with their QoL, some areas of physical and psychological parameters of QoL were worse in WPW children. The PARS questionnaire is a useful tool as a disease-specific QoL instrument, which supplements the general questionnaire and aids in clinical practice and decision-making.

Comparison of Eating Habits, Body Composition and Densitometric Parameters between Subjects with Normal Cognitive Function and Mild Cognitive Impairment: An Observational Study.

The role of nutrition in the ageing process of the brain is pivotal. Therefore, the study aimed to compare eating habits, body composition and densitometric parameters between subjects with normal cognitive function (NCF) and mild cognitive impairment (MCI). A total of 95 subjects with NCF (74% of women) and 95 individuals with MCI (77% of women) aged 50-70 years were studied. Densitometric parameters were evaluated using dual-energy X-ray absorptiometry methods. Eating habits were assessed using the food frequency questionnaire and 3-day diary records, and advanced glycation end products (AGEs) intake was calculated. Significant differences between groups were detected for the %fat in the right arm (NCF vs. MCI: 38.4 (30.4-46.8) vs. 43.5 (35.5-49.2)%, p = 0.0407). Moreover, the MCI group had a significantly lower intake of calcium (p = 0.0010), phosphor (p = 0.0411), vitamins B2 (p = 0.0138) and B12 (p = 0.0024) compared to the NCF group, with both groups also differing in the frequency of butter (p = 0.0191) and fermented milk beverages (p = 0.0398) intake. Analysis restricted to women showed significant differences between groups in right arm %fat, VAT mass, calcium, vitamins B2, B12, butter and fermented milk products intake, while in men, differences were detected in the intake of calcium, iodine, vitamin B1, water and AGEs. In conclusion, subjects with NCF and MCI have comparable densitometric variables but differ significantly in some body composition parameters and the intake of some food groups and nutrients.

Maternal-Foetal/Infant Interactions-Gut Microbiota and Immune Health.

In recent years, the number of scientific publications on the role of intestinal microbiota in shaping human health, as well as the occurrence of intestinal dysbiosis in various disease entities, has increased dynamically. However, there is a gap in comprehensively understanding the factors influencing a child's gut microbiota. This review discusses the establishment of gut microbiota and the immunological mechanisms regulating children's microbiota, emphasising the importance of prioritising the development of appropriate gut microbiota in a child from the planning stages of pregnancy. The databases PubMed, Web of Sciences, Cochrane, Scopus and Google Scholar were searched to identify relevant articles. A child's gut microbiota composition is influenced by numerous factors, such as diet during pregnancy, antibiotic therapy, the mother's vaginal microbiota, delivery method, and, later, feeding method and environmental factors. During pregnancy, the foetus naturally acquires bacterial strains from the mother through the placenta, thereby shaping the newborn's immune system. Inappropriate maternal vaginal microbiota may increase the risk of preterm birth. Formula-fed infants typically exhibit a more diverse microbiota than their breastfed counterparts. These factors, among others, shape the maturation of the child's immune system, impacting the production of IgA antibodies that are central to cellular humoral immune defence. Further research should focus on identifying specific microbiota-immune system interactions influencing a child's immune health and developing personalised treatment strategies for immune-related disorders.

Exploring the paradoxical nature of cold temperature mortality in Europe.

While low winter temperatures are associated with increased mortality, this phenomenon has been suggested to be most severe in regions with seemingly mild winters. The study aimed to establish a temperature-based formula that could elucidate the previously ambiguous regional differences in vulnerability to low temperature. European weekly mortality data (2000-2019) were matched with meteorological data to determine for each region vulnerability to temperature decrease and the optimal temperature with lowest mortality. Regression models were developed to generalize and explain these findings considering regional temperature characteristics. Optimal temperature could be predicted based on local average summer temperature (R2 = 85.6%). Regional vulnerability to temperature decrease could be explained by combination of winter and summer temperatures (R2 = 86.1%). Regions with warm winters and cold summers showed the highest vulnerability to decrease of temperature during winter. Contrary to theories about economic disparities Eastern Europe exhibited resistance comparable to Scandinavia. The southern edges of Europe demonstrated serious low temperature vulnerability to decreased temperatures, even if temperature was relatively high around 20 °C. This suggests that the observed connection primarily reflects the modulation of the length of respiratory virus infection seasons by climate conditions, counterbalanced by varying levels of acquired immunity and the presence of heatwaves eliminating the most frail individuals. Thus, relatively low vulnerability and a flat mortality cycle in countries with harsh climates paradoxically imply the presence of threats throughout the whole year.

Pediatric endoscopy in times of pandemic: A nationwide retrospective analysis.

BACKGROUND: Gastrointestinal endoscopy is a procedure that carries an increased risk of transmission of SARS-CoV-2 infection to medical staff. In patients, COVID-19 is a risk factor for adverse events of medical procedures. This study analyzed the real-life risk of, and factors contributing to, infection transmission to endoscopic personnel, and possible adverse events of the endoscopy procedure and anesthesia in children with COVID-19. METHODS: Nationwide retrospective analysis of medical records of children with confirmed SARS-CoV-2 infection who underwent gastrointestinal endoscopy in Poland between February 2020 and February 2022. RESULTS: Fifty-eight patients were included in the analysis, 35% of whom had COVID-19 symptoms at the time of endoscopy. The dominant indications for endoscopy were foreign body or corrosive substance ingestion and gastrointestinal bleeding. Nine cases of virus transmission were registered among endoscopic personnel. In all of these cases, the endoscopy team was unaware of the patient's infection (p < 0.01), although symptoms were present in 78% of the children. Lack of use of personal protective equipment was the strongest predictor of SARS-CoV-2 transmission (p < 0.01). The risk of infection was not statistically significantly dependent on the method of anesthesia, intubation or the type of endoscopy. No statistically significant correlation was found between symptomatic infection and adverse events of endoscopy or anesthesia occurrence. There was one reported anesthesia-related adverse event involving extubation difficulties due to worsening respiratory infection symptoms. CONCLUSIONS: The risk of transmitting SARS-CoV-2 to endoscopic personnel during procedures in children is low and depends on compliance with infection prevention and control measures. Performing gastrointestinal endoscopy in children with COVID-19 does not appear to be associated with an increased risk of adverse events.

Nutrient Combinations Sensed by L-Cell Receptors Potentiate GLP-1 Secretion.

Obesity is a risk factor for cardiometabolic diseases. Nutrients stimulate GLP-1 release; however, GLP-1 has a short half-life (<2 min), and only <10-15% reaches the systemic circulation. Human L-cells are localized in the distal ileum and colon, while most nutrients are absorbed in the proximal intestine. We hypothesized that combinations of amino acids and fatty acids potentiate GLP-1 release via different L-cell receptors. GLP-1 secretion was studied in the mouse enteroendocrine STC-1 cells. Cells were pre-incubated with buffer for 1 h and treated with nutrients: alpha-linolenic acid (αLA), phenylalanine (Phe), tryptophan (Trp), and their combinations αLA+Phe and αLA+Trp with dipeptidyl peptidase-4 (DPP4) inhibitor. After 1 h GLP-1 in supernatants was measured and cell lysates taken for qPCR. αLA (12.5 µM) significantly stimulated GLP-1 secretion compared with the control. Phe (6.25-25 mM) and Trp (2.5-10 mM) showed a clear dose response for GLP-1 secretion. The combination of αLA (6.25 µM) and either Phe (12.5 mM) or Trp (5 mM) significantly increased GLP-1 secretion compared with αLA, Phe, or Trp individually. The combination of αLA and Trp upregulated GPR120 expression and potentiated GLP-1 secretion. These nutrient combinations could be used in sustained-delivery formulations to the colon to prolong GLP-1 release for diminishing appetite and preventing obesity.

The Antioxidant and Neuroprotective Potential of Leaves and Inflorescences Extracts of Selected Hemp Varieties Obtained with scCO2.

Cannabis sativa, a versatile plant with numerous varieties, holds promising potential for a wide range of biological activity. As raw materials for research, we chose leaves and inflorescences of hemp varieties such as Bialobrzeskie, Henola, and Tygra, which are cultivated mainly for their fibers or seeds. The choice of extraction is a key step in obtaining the selected compositions of active compounds from plant material. Bearing in mind the lipophilic nature of cannabinoids, we performed supercritical carbon dioxide (scCO2) extraction at 50 °C under 2000 (a) and 6000 PSI (b). The cannabinoid contents were determined with the use of the HPLC-DAD method. The antioxidant capabilities were assessed through a series of procedures, including the DPPH, ABTS, CUPRAC, and FRAP methods. The capacity to inhibit enzymes that play a role in the progression of neurodegenerative diseases, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase was also studied. The dominant cannabinoids in the extracts were cannabidiol (CBD) and cannabidiolic acid (CBDA). The highest concentration of eight cannabinoids was detected in the Tygra inflorescences extract (b). The most notable antioxidant properties were provided by the Tygra inflorescences extract (b). Nonetheless, it was the Henola inflorescences extract (b) that demonstrated the most efficient inhibition of AChE and BChE, and tyrosinase was inhibited the most significantly by the Bialobrzeskie inflorescences extract (b). Multidimensional comparative analysis enrolled all assays and revealed that the Henola inflorescences extract (b) showed the most substantial neuroprotective potential.

Pasteurella Multocida Infection in Humans.

Pasteurella multocida (P. multocida) is an immobile, anaerobic, Gram-negative coccobacillus fermenting bacterium. This pathogen is commonly prevalent in the upper airways of healthy pets, such as cats and dogs, but was also confirmed in domestic cattle, rabbits, pigs, birds, and various wild animals. Infection in humans occurs as a result of biting, scratching, or licking by animals and contact with nasopharyngeal secretions. Inflammation at the site of infection develops within the first day from the injury. It is usually confined to the skin and subcutaneous tissue but, in particular situations, may spread to other organs and manifest as a severe systemic infection. Careful history-taking and microbiological confirmation of the infection enable diagnosis and appropriate treatment. Any wound resulting from an animal bite should be disinfected. The preferred and highly effective treatment against local P. multocida infection is penicillin or its derivatives. The prognosis for P. multocida infections depends on the infected site and the patient's comorbidities.

To vaccinate or to isolate? Establishing which intervention leads to measurable mortality reduction during the COVID-19 Delta wave in Poland.

Background: During the Delta variant COVID-19 wave in Poland there were serious regional differences in vaccination rates and discrepancies in the enforcement of pandemic preventive measures, which allowed us to assess the relative effectiveness of the policies implemented. Methods: Creating a model that would predict mortality based on vaccination rates among the most vulnerable groups and the timing of the wave peak enabled us to calculate to what extent flattening the curve reduced mortality. Subsequently, a model was created to assess which preventive measures delayed the peak of infection waves. Combining those two models allowed us to estimate the relative effectiveness of those measures. Results: Flattening the infection curve worked: according to our model, each week of postponing the peak of the wave reduced excess deaths by 1.79%. Saving a single life during the Delta wave required one of the following: either the vaccination of 57 high-risk people, or 1,258 low-risk people to build herd immunity, or the isolation of 334 infected individuals for a cumulative period of 10.1 years, or finally quarantining 782 contacts for a cumulative period of 19.3 years. Conclusions: Except for the most disciplined societies, vaccination of high-risk individuals followed by vaccinating low-risk groups should have been the top priority instead of relying on isolation and quarantine measures which can incur disproportionately higher social costs. Our study demonstrates that even in a country with uniform policies, implementation outcomes varied, highlighting the importance of fine-tuning policies to regional specificity.

The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis.

Folic acid might improve endothelial function, but the results are inconclusive. This systematic review evaluated the effect of folic acid supplementation on endothelial parameters and arterial stiffness in adults. The study protocol was registered with the PROSPERO database (CRD42021290195). The PubMed, Web of Sciences, Cochrane and Scopus databases were searched to identify English-language randomised controlled trials of the effect of folate supplementation on arterial stiffness and endothelial function markers in adults. There were significant differences between the effect of folic acid and placebo on flow-mediated dilation (random-effects model, standardized mean differences (SMD): 0.888, 95% confidence interval (CI): 0.447, 1.329, p < 0.001) and monocyte chemotactic protein 1 (random-effects model, SMD: -1.364, 95% CI: -2.164, -0.563, p < 0.001), but there was no significant difference in the central pulse wave velocity (fixed-effects model, SMD: -0.069, 95% CI: -0.264, 0.125, p = 0.485) and peripheral pulse wave velocity (fixed-effects model, SMD: -0.093, 95% CI: -0.263, 0.077, p = 0.284). In conclusion, folic acid might have a favourable effect on endothelial function but may not affect arterial stiffness. Further studies are needed to confirm these results.

The Effect of Conjugated Linoleic Acid Supplementation on Densitometric Parameters in Overweight and Obese Women-A Randomised Controlled Trial.

Background and Objectives: Conjugated linoleic acid (CLA) can improve bone health in animals, yet the effects on humans have not been consistent. Therefore, this parallel randomised controlled trial aimed to assess the effect of CLA supplementation on bone mineral density (BMD) and content (BMC) in overweight or obese women. Materials and Methods: The study population included 74 women who were divided into the CLA (n = 37) and control (n = 37) groups. The CLA group received six capsules per day containing approximately 3 g of cis-9, trans-11 and trans-10, cis-12 CLA isomers in a 50:50 ratio. The control group received the same number of placebo capsules that contained sunflower oil. BMC and BMD at total body, lumbar spine (L1-L4), and femoral neck were measured before and after a three-month intervention. Results: The comparison of BMC and BMD for the total body, lumbar spine (L1-L4), and femoral neck before and after the intervention showed no differences between the groups. However, a within-group analysis demonstrated a significant increase in BMC (p = 0.0100) and BMD (p = 0.0397) at lumbar spine (L1-L4) in the CLA group. Nevertheless, there were no significant differences between the CLA and placebo groups in changes in all analysed densitometric parameters. Conclusions: Altogether, three-month CLA supplementation in overweight and obese women did not improve bone health, although the short intervention period could have limited our findings, long-term intervention studies are needed. The study protocol was registered in the German Clinical Trials Register database (ID: DRKS00010462, date of registration: 4 May 2016).

Professional activity, gender and disease-related emotions: The impact on parents' experiences in caring for children with phenylketonuria.

Introduction: Clinical management of rare diseases often fails to acknowledge the challenges faced by caregivers. Whilst management of phenylketonuria (PKU) may not be considered as dire as other conditions, most studies primarily concentrate on clinical issues, dietary adherence, or the quality of life of the PKU patients, leaving caregivers in the background. The aim of the study was to evaluate the psychosocial effects of PKU on family caregivers. Methods: Between October 30th, 2022 and February 28th, 2023, we collected data from caregivers of children with PKU using an anonymous, self-administered, computer-assisted online questionnaire. The survey was distributed among to patients during their regular visits to five Polish PKU treatment centers. Results: A total of 159 Polish caregivers of children with PKU completed the survey. This research shows that while women caregivers were more likely to be unemployed due to their responsibilities for childcare (50.3% compared to 0% for men), and men caregivers were more likely to be employed full-time (93.8% compared to 40.6% for women), the former reported higher emotional engagement in caregiving (88.1% vs 56.3% respectively). Significantly, unemployed mothers reported higher levels of loneliness, helplessness, and emotional control problems, and lacked psychological/emotional support more often than employed mothers. This research also shows a statistically significant positive correlation between mothers' education level and financial situation (p < 0.05) and education level and professional activity (p < 0.01). Additionally, a significant positive correlation was found between perceived financial situation and feeling of happiness (p < 0.001), and between financial situation and professional activity (p < 0.001). Finally, a significant positive correlation was observed between feeling of happiness and professional activity (p < 0.05). Conclusions: According to our findings, there is a link between subjective happiness, financial situation, and professional activity among female caregivers. The relationship between these factors goes beyond just the income earned from work. The results of our study imply that there could even be a therapeutic advantage for working mothers. It is crucial to recognize the emotional difficulties that employed mothers may experience while taking care of a child with PKU, and to provide them with the necessary assistance and resources to meet their needs. Additionally, our results may provide a foundation for redefining the support system for caregivers in Poland.

Multidirectional Effects of Red Clover (Trifolium pratense L.) in Support of Menopause Therapy.

Red clover is a raw material of interest primarily due to its isoflavone content. However, other groups of compounds may affect the pleiotropic biological effects of this raw material. It is used to alleviate menopausal symptoms, but the fact that there are many varieties of this plant that can be grown makes it necessary to compare the biological activity and phytochemical composition of this plant. Also of interest are the differences between the leaves and flowers of the plant. The aim of this study was to evaluate the properties of the leaves and flowers of six clover varieties-'Tenia', 'Atlantis', 'Milena', 'Magellan', 'Lemmon' and 'Lucrum'-with respect to their ability to inhibit α-glucosidase, lipase, collagenase and antioxidant activity. Therefore, the contents of polyphenols and the four main isoflavones-genistein, daidzein, biochanin and formononetin-were assessed. The study was complemented by testing for permeability through a model membrane system (PAMPA). Principal component analysis (PCA) identified a relationship between activity and the content of active compounds. It was concluded that antioxidant activity, inhibition of glucosidase, collagenase and lipase are not correlated with isoflavone content. A higher content of total polyphenols (TPC) was determined in the flowers of red clover while a higher content of isoflavones was determined in the leaves of almost every variety. The exception is the 'Lemmon' variety, characterized by high isoflavone content and high activity in the tests conducted.

Pancreatic Involvement in the Course of Inflammatory Bowel Disease in Children-A Multi-Center Study.

The coexistence of inflammatory bowel disease (IBD) with pancreatic pathology is rare in children. A retrospective analysis of data from 1538 children diagnosed with IBD in 2014-2021 was conducted to determine the frequency and causes of pancreatitis and asymptomatic hyperlipasemia (HL) or hyperamylasemia (HA) in this group of patients. Among the 176 children (11.4%) with pancreatic involvement (PI), acute pancreatitis (AP) was diagnosed in 77 children (43.8%), and HA or HL was observed in 88 children (50.0%). Only a few patients were diagnosed with autoimmune or chronic pancreatitis (6.2%). PI was observed at the time of the IBD diagnosis in 26.1% of the cases. A total of 54.5% of the patients had moderate to severe IBD, and 96% had colonic involvement at the time of diagnosis of PI. Idiopathic PI was the most common (57%), followed by drug-induced PI (37%) and azathioprine (AZA). In patients with AZA-induced AP, the successful introduction of 6-mercaptopurine (6-MP) to therapy was noted in 62.5% of the children. Our results suggest that routine monitoring of pancreatic enzymes in patients with IBD should be performed, especially after the initiation of the AZA treatment. The presence of transient HA/HL in IBD does not necessarily indicate pancreatic pathology.

The clinical phenotype with gastrostomy and abdominal wall infection in a pediatric patient with Takenouchi-Kosaki syndrome due to a heterozygous c.191A > G (p.Tyr64Cys) variant in CDC42: a case report.

The CDC42 (cell division cycle homolog 42) gene product, Cdc42 belongs to the Rho GTPase family which plays a pivotal role in the regulation of multiple cellular functions, including cell cycle progression, motility, migration, proliferation, transcription activation, and reactive oxygen species production. The Cdc42 molecule controls various tissue-specific functional pathways underpinning organogenesis as well as developmental integration of the hematopoietic and immune systems. Heterozygous c.191A>G (p.Tyr64Cys) pathogenic variants in CDC42 cause Takenouchi-Kosaki syndrome characterized by a spectrum of phenotypic features comprising psychomotor developmental delay, sensorineural hearing loss, growth retardation, facial dysmorphism, cardiovascular and urinary tract malformations, camptodactyly, accompanied by thrombocytopenia and immunodeficiency of variable degree. Herein, we report a pediatric patient with the Takenouchi-Kosaki syndrome due to a heterozygous p.Tyr64Cys variant in CDC42 manifesting as a congenital malformation complex accompanied by macrothrombocytopenia, poor specific antibody response, B and T cell immunodeficiency, and low serum immunoglobulin A level. We also suggst that feeding disorders, malnutrition, and a gastrointestinal infection could be a part of the phenotypic characteristics of Takenouchi-Kosaki syndrome supporting the hypothesis of immune dysregulation and systemic inflammation occurring in the p.Tyr64Cys variant in CDC42.

Lower respiratory infection in humans caused by pasteurella multocida.

BACKGROUND: Pasteurella (P.) multocida commonly occurs in the upper respiratory tract of healthy domestic pets, especially cats and dogs. People become infected by biting, scratching or direct contact with the animal's saliva. Inflammation develops in the wound and limits itself to the skin and subcutaneous tissue. P. multocida may cause respiratory tract infections and severe life-threatening complications. The study aimed to identify the lower respiratory infection in humans caused by P. multocida, to determine the potential source of infection and the associated symptoms, comorbidities and applied treatment. MATERIALS AND METHODS: Between January 2010 and September 2021, 14,258 patients underwent 16,255 routine flexible video bronchoscopy (FVB), and the same number of bronchoalveolar lavage fluid (BALF) samples for microbiological examination were taken. RESULTS: Microbiological examinations of the BALF only allowed the identification of six patients with P. multocida infection. All persons reported multiple scratches or bites and licking or kissing by their pets in the past. Productive cough with expectoration of mucopurulent discharge was the predominant symptom. CONCLUSIONS: A lower respiratory infection caused by P. multocida is not common in humans. It should be considered particularly in elderly patients with underlying diseases and exposure to cats and dogs.

Transcriptomic Context of RUNX3 Expression in Monocytes: A Cross-Sectional Analysis.

The runt-related transcription factor 3 (RUNX3) regulates the differentiation of monocytes and their response to inflammation. However, the transcriptomic context of RUNX3 expression in blood monocytes remains poorly understood. We aim to learn about RUNX3 from its relationships within transcriptomes of bulk CD14+ cells in adults. This study used immunomagnetically sorted CD14+ cell gene expression microarray data from the Multi-Ethnic Study of Atherosclerosis (MESA, n = 1202, GSE56047) and the Correlated Expression and Disease Association Research (CEDAR, n = 281, E-MTAB-6667) cohorts. The data were preprocessed, subjected to RUNX3-focused correlation analyses and random forest modeling, followed by the gene ontology analysis. Immunity-focused differential ratio analysis with intermediary inference (DRAIMI) was used to integrate the data with protein-protein interaction network. Correlation analysis of RUNX3 expression revealed the strongest positive association for EVL (rmean = 0.75, pFDR-MESA = 5.37 × 10-140, pFDR-CEDAR = 5.52 × 10-80), ARHGAP17 (rmean = 0.74, pFDR-MESA = 1.13 × 10-169, pFDR-CEDAR = 9.20 × 10-59), DNMT1 (rmean = 0.74, pFDR-MESA = 1.10 × 10-169, pFDR-CEDAR = 1.67 × 10-58), and CLEC16A (rmean = 0.72, pFDR-MESA = 3.51 × 10-154, pFDR-CEDAR = 2.27 × 10-55), while the top negative correlates were C2ORF76 (rmean = -0.57, pFDR-MESA = 8.70 × 10-94, pFDR-CEDAR = 1.31 × 10-25) and TBC1D7 (rmean = -0.55, pFDR-MESA = 1.36 × 10-69, pFDR-CEDAR = 7.81 × 10-30). The RUNX3-associated transcriptome signature was involved in mRNA metabolism, signal transduction, and the organization of cytoskeleton, chromosomes, and chromatin, which may all accompany mitosis. Transcriptomic context of RUNX3 expression in monocytes hints at its relationship with cell growth, shape maintenance, and aspects of the immune response, including tyrosine kinases.

Effects of infant feeding with goat milk formula or cow milk formula on atopic dermatitis: protocol of the randomised controlled Goat Infant Formula Feeding and Eczema (GIraFFE) trial.

INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin condition significantly affecting quality of life. A small randomised trial showed an approximately one-third lower incidence of AD in goat milk formula-fed compared with cow milk formula-fed infants. However, due to limited statistical power, AD incidence difference was not found to be significant. This study aims to explore a potential risk reduction of AD by feeding a formula based on whole goat milk (as a source of protein and fat) compared with a formula based on cow milk proteins and vegetable oils. METHODS AND ANALYSIS: This two-arm (1:1 allocation), parallel, randomised, double-blind, controlled nutritional trial shall enrol up to 2296 healthy term-born infants until 3 months of age, if parents choose to start formula feeding. Ten study centres in Spain and Poland are participating. Randomised infants receive investigational infant and follow-on formulas either based on whole goat milk or on cow milk until the age of 12 months. The goat milk formula has a whey:casein ratio of 20:80 and about 50% of the lipids are milk fat from whole goat milk, whereas the cow milk formula, used as control, has a whey:casein ratio of 60:40 and 100% of the lipids are from vegetable oils. The energy and nutrient levels in both goat and cow milk formulas are the same. The primary endpoint is the cumulative incidence of AD until the age of 12 months diagnosed by study personnel based on the UK Working Party Diagnostic Criteria. The secondary endpoints include reported AD diagnosis, measures of AD, blood and stool markers, child growth, sleep, nutrition and quality of life. Participating children are followed until the age of 5 years. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethical committees of all participating institutions. TRIAL REGISTRATION NUMBER: NCT04599946.

Methodological Changes in the Field of Paleogenetics.

Paleogenetics has significantly changed since its inception almost forty years ago. Initially, molecular techniques available to the researchers offered minimal possibilities for ancient DNA analysis. The subsequent expansion of the scientific tool cabinet allowed for more remarkable achievements, combined has with the newfound popularity of this budding field of science. Finally, a breakthrough was made with the development of next-generation sequencing (NGS) technologies and the update of DNA isolation protocols, through which even very fragmented aDNA samples could be used to sequence whole genomes. In this paper, we review the achievements made thus far and compare the methodologies utilized in this field of science, discussing their benefits and challenges.