The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity.

Obesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic and inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts metabolic and immune signaling leading to metabolic endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the gut barrier but also exert metabolic and immunomodulatory effects via G protein-coupled receptor binding and epigenetic regulation. SCFAs are emerging as potential agents to counteract dysbiosis-induced epigenetic changes, specifically targeting metabolic and inflammatory genes through DNA methylation, histone acetylation, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). To assess whether SCFAs can effectively interrupt the detrimental cascade of obesity and inflammation, this review aims to provide a comprehensive overview of the current evidence for their clinical application. The review emphasizes factors influencing SCFA production, the intricate connections between metabolism, the immune system, and the gut microbiome, and the epigenetic mechanisms regulated by SCFAs that impact metabolism and the immune system.

A WORLDWIDE ENIGMA STUDY ON EPILEPSY-RELATED GRAY AND WHITE MATTER COMPROMISE ACROSS THE ADULT LIFESPAN.

Objectives: Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. Methods: We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. Results: In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. Conclusions: This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

Value of high-speed videoendoscopy as an auxiliary tool in differentiation of benign and malignant unilateral vocal lesions.

PURPOSE: The study aimed to assess the relevance of objective vibratory parameters derived from high-speed videolaryngoscopy (HSV) as a supporting tool, to assist clinicians in establishing the initial diagnosis of benign and malignant glottal organic lesions. METHODS: The HSV examinations were conducted in 175 subjects: 50 normophonic, 85 subjects with benign vocal fold lesions, and 40 with early glottic cancer; organic lesions were confirmed by histopathologic examination. The parameters, derived from HSV kymography: amplitude, symmetry, and glottal dynamic characteristics, were compared statistically between the groups with the following ROC analysis. RESULTS: Among 14 calculated parameters, 10 differed significantly between the groups. Four of them, the average resultant amplitude of the involved vocal fold (AmpInvolvedAvg), average amplitude asymmetry for the whole glottis and its middle third part (AmplAsymAvg; AmplAsymAvg_2/3), and absolute average phase difference (AbsPhaseDiffAvg), showed significant differences between benign and malignant lesions. Amplitude values were decreasing, while asymmetry and phase difference values were increasing with the risk of malignancy. In ROC analysis, the highest AUC was observed for AmpAsymAvg (0.719; p < 0.0001), and next in order was AmpInvolvedAvg (0.70; p = 0.0002). CONCLUSION: The golden standard in the diagnosis of organic lesions of glottis remains clinical examination with videolaryngoscopy, confirmed by histopathological examination. Our results showed that measurements of amplitude, asymmetry, and phase of vibrations in malignant vocal fold masses deteriorate significantly in comparison to benign vocal lesions. High-speed videolaryngoscopy could aid their preliminary differentiation noninvasively before histopathological examination; however, further research on larger groups is needed.

Diversity of Binge-Eating Disorder Symptoms Is Associated with Anxiety about Getting Fat Rather Than Body Image: A Clinical Study of Women in Poland.

BACKGROUND: Anxiety about gaining weight is strongly related to body image. Evidence indicates that body dissatisfaction is a strong predictor of eating disorder development. Although not included in DSM-V diagnostic criteria, body image dissatisfaction, and concern are clearly relevant also for individuals with binge-eating disorder (BED). Weight gain anxiety is associated with psychopathological behaviors, but existing research in this area is primarily focused on bulimia nervosa and anorexia nervosa. The goal of this present study was to investigate body image and body mass anxiety in people with BED. METHODS: Women diagnosed with BED (n = 105) aged 18 to 66 were surveyed using the questionnaire developed by the authors evaluating the presence of BED symptoms based on DSM-V criteria, and two other instruments: the Body Esteem Scale (BES), and the Body Mass Anxiety Scale (BMAS-20). Statistical analyses were conducted to examine the correlations of BED with body image and body mass anxiety (Pearson's r), to test differences between groups with greater and lesser BED symptom diversity (Student's t-test or the Mann-Whitney U test), and to assess differences among mild-, moderate- and severe-BED groups (ANOVA with a post-hoc test). RESULTS: A medium positive relationship was found between anxiety about getting fat (AGF) and the diversity of BED, measured as the number of BED symptoms. A larger number of BED symptoms was shown to be associated with a higher level of AGF. However, no significant differences in AGF levels were observed among BED-severity groups, specified with the frequency of binge eating episodes. No correlations were found between BED and body image. There were also no significant differences in body image between groups with a larger and a smaller number of BED symptoms. The only significant difference in body image observed among BED-severity groups was the level of weight concern. People with mild BED displayed a higher level of weight concern than those with severe BED. CONCLUSIONS: Women who binge eat experience high levels of AGF. In the present study, AGF was primarily associated with the number of BED symptoms and not the rate of recurrence of binge-eating episodes. The frequency of BED episodes, however, was linked with weight concern. On the other hand, the hypothesized relationship between disturbed body image and BED was not confirmed. The findings indicate that anxiety about getting fat should be viewed as one of the psychological costs incurred by women experiencing BED symptoms, and it should be mentioned in the next DSM version.

Possibility of Using Different Calcium Compounds for the Manufacture of Fresh Acid Rennet Cheese from Goat's Milk.

Calcium can be added to cheese milk to influence the coagulation process and to increase cheese yield. Calcium compounds used in the dairy industry show substantial differences in their practical application. Therefore, this study aimed to evaluate the potential use of 0, 5, 10, 15, and 20 mg Ca 100 g-1 of milk in the form of calcium gluconate, lactate, and carbonate as alternatives to calcium chloride in manufacturing fresh acid rennet cheese from high-pasteurized (90 °C, 15 s) goat's milk. The pH value of the cheese was reduced most strongly by the addition of increasing doses of calcium lactate (r = -0.9521). Each cheese sample showed increased fat content with the addition of calcium. Only calcium chloride did not reduce protein retention from goat's milk to cheese. The addition of 20 mg Ca 100 g-1 of milk in the form of gluconate increased cheese yield by 4.04%, and lactate reduced cheese yield by 2.3%. Adding each calcium compound to goat's milk significantly increased Ca and P levels in the cheese (p ≤ 0.05). The highest Ca levels were found in cheese with the addition of 20 mg Ca 100 g-1 of milk in the form of lactate. In all groups, similar contents of Mn, Mo, and Se were found. Calcium addition significantly affected cheese hardness, while higher calcium concentrations increased hardness. Carbonate caused the greatest increase in the cohesiveness of cheese. The addition of calcium compounds increased the adhesiveness and springiness of cheese compared to controls. The cheese with calcium chloride had the highest overall acceptability compared to the other cheese samples. The addition of calcium carbonate resulted in a lower score for appearance and consistency, and influenced a slightly perceptible graininess, sandiness, and stickiness in its consistency, as well as provided a slightly perceptible chalky taste.

High-Speed Videoendoscopy Enhances the Objective Assessment of Glottic Organic Lesions: A Case-Control Study with Multivariable Data-Mining Model Development.

The aim of the study was to utilize a quantitative assessment of the vibratory characteristics of vocal folds in diagnosing benign and malignant lesions of the glottis using high-speed videolaryngoscopy (HSV). METHODS: Case-control study including 100 patients with unilateral vocal fold lesions in comparison to 38 normophonic subjects. Quantitative assessment with the determination of vocal fold oscillation parameters was performed based on HSV kymography. Machine-learning predictive models were developed and validated. RESULTS: All calculated parameters differed significantly between healthy subjects and patients with organic lesions. The first predictive model distinguishing any organic lesion patients from healthy subjects reached an area under the curve (AUC) equal to 0.983 and presented with 89.3% accuracy, 97.0% sensitivity, and 71.4% specificity on the testing set. The second model identifying malignancy among organic lesions reached an AUC equal to 0.85 and presented with 80.6% accuracy, 100% sensitivity, and 71.1% specificity on the training set. Important predictive factors for the models were frequency perturbation measures. CONCLUSIONS: The standard protocol for distinguishing between benign and malignant lesions continues to be clinical evaluation by an experienced ENT specialist and confirmed by histopathological examination. Our findings did suggest that advanced machine learning models, which consider the complex interactions present in HSV data, could potentially indicate a heightened risk of malignancy. Therefore, this technology could prove pivotal in aiding in early cancer detection, thereby emphasizing the need for further investigation and validation.

Bioavailability of Macroelements from Synbiotic Sheep's Milk Ice Cream.

To determine the potential bioavailability of macroelements (Ca, Mg, P, K), probiotic ice cream samples (Lactaseibacillus paracasei L-26, Lactobacillus casei 431, Lactobacillus acidophilus LA-5, Lactaseibacillus rhamnosus and Bifidobacterium animalis ssp. lactis BB-12) from sheep's milk with inulin, apple fiber and inulin, or apple fiber and control samples were submitted to in vitro digestion in the mouth, stomach and small intestine. The bioavailability of calcium in the ice cream samples ranged from 40.63% to 54.40%, whereas that of magnesium was 55.64% to 44.42%. The highest bioavailability of calcium and magnesium was shown for the control samples. However, adding 4% inulin reduced the bioavailability of calcium by about 3-5% and magnesium only by about 5-6%. Adding 4% apple fiber reduced the bioavailability of calcium by as much as 6-12% and magnesium by 7-8%. The highest bioavailability of calcium was determined in ice cream with L. paracasei, and the highest bioavailability of magnesium was determined in ice cream with L. casei. The bioavailability of phosphorus in ice cream ranged from 47.82% to 50.94%. The highest bioavailability of phosphorus (>50%) was in sheep ice cream fermented by B. animalis. In the control ice cream, the bioavailability of potassium was about 60%. In ice cream with inulin, the bioavailability of potassium was lower by 3-4%, and in ice cream with apple fiber, the bioavailability of potassium was lower by up to 6-9%. The bioavailability of potassium was significantly influenced only by the addition of dietary fiber. The results of the study confirmed the beneficial effect of bacteria on the bioavailability of Ca, Mg and P.

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence.

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

mTOR/α-ketoglutarate signaling: impact on brain cell homeostasis under ischemic conditions.

The multifunctional molecules mechanistic target of rapamycin (mTOR) and α-ketoglutarate (αKG) are crucial players in the regulatory mechanisms that maintain cell homeostasis in an ever-changing environment. Cerebral ischemia is associated primarily with oxygen-glucose deficiency (OGD) due to circulatory disorders. Upon exceeding a threshold of resistance to OGD, essential pathways of cellular metabolism can be disrupted, leading to damage of brain cells up to the loss of function and death. This mini-review focuses on the role of mTOR and αKG signaling in the metabolic homeostasis of brain cells under OGD conditions. Integral mechanisms concerning the relative cell resistance to OGD and the molecular basis of αKG-mediated neuroprotection are discussed. The study of molecular events associated with cerebral ischemia and endogenous neuroprotection is relevant for improving the effectiveness of therapeutic strategies.

Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies.

Introduction: Cannabis use has a high prevalence in young youth and is associated with poor psychosocial outcomes. Such outcomes have been ascribed to the impact of cannabis exposure on the developing brain. However, findings from individual studies of volumetry in youth cannabis users are equivocal. Objectives: Our primary objective was to systematically review the evidence on brain volume differences between young cannabis users and nonusers aged 12-26 where profound neuromaturation occurs, accounting for the role of global brain volumes (GBVs). Our secondary objective was to systematically integrate the findings on the association between youth age and volumetry in youth cannabis users. Finally, we aimed to evaluate the quality of the evidence. Materials and Methods: A systematic search was run in three databases (PubMed, Scopus, and PsycINFO) and was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We run meta-analyses (with and without controlling for GBV) of brain volume differences between young cannabis users and nonusers. We conducted metaregressions to explore the role of age on volumetric differences. Results: Sixteen studies were included. The reviewed samples included 830 people with mean age 22.5 years (range 14-26 years). Of these, 386 were cannabis users (with cannabis use onset at 15-19 years) and 444 were controls. We found no detectable group differences in any of the GBVs (intracranium, total brain, total white matter, and total gray matter) and regional brain volumes (i.e., hippocampus, amygdala, orbitofrontal cortex, and total cerebellum). Age and cannabis use level did not predict (standardized mean) volume group differences in metaregression. We found little evidence of publication bias (Egger's test p>0.1). Conclusions: Contrary to evidence in adult samples (or in samples mixing adults and youth), previous single studies in young cannabis users, and meta-analyses of brain function in young cannabis users, this early evidence suggests nonsignificant volume differences between young cannabis users and nonusers. While prolonged and long-term exposure to heavy cannabis use may be required to detect gross volume alterations, more studies in young cannabis users are needed to map in detail cannabis-related neuroanatomical changes.

Synthesis of Current Knowledge of the Morphology of the Larval Stages of Paederinae (Coleoptera; Staphylinidae), with a First Insight into the Mature Larva of Pseudomedon Mulsant & Rey, 1878, in the Light of a New Systematic Division.

This is the first morphological description of the mature larva (L2) of the genus Pseudomedon, belonging to the tribe Lathrobiini and subtribe Medonina. Detailed illustrations of its structural features are provided. Based on earlier published and new data, 10 and 18 diagnostic larval morphological characters for Paederinae and Pseudomedon, respectively, are proposed. In the light of the new tribal system established for the subfamily Paederinae and based on the current knowledge (including Pseudomedon) concerning the larval morphology of these staphylinids, a comparative analysis of the traits at different taxonomic levels was carried out: intertribal-between Lathrobiini and Paederini sensu nov., intersubtribal (Lathrobiini)-between Medonina and Lathrobiina, and intrasubtribal for Medonina. As a consequence, 12 intertribal, 2 intersubtribal and 3 intrasubtribal distinguishing features were selected. These features, appearing on the head, antennae and mouthparts of the larvae, confirm the validity of the recent proposals to alter the systematics of these staphylinids at higher taxonomic levels. Our proposed practical identification key to Paederinae larvae at the generic level is a synthesis of the current knowledge of Paederinae larvae, including new data. The work also gives a thorough review of the literature and the state of knowledge of the morphology of Paederinae larvae.

Impact of COVID-19 on Head and Neck Cancer Advancement Measured by Increasing Numbers of Urgent Dyspnea Cases-What Could Be Improved in the Event of Subsequent Pandemics?

The COVID-19 pandemic has altered all aspects of the healthcare system's organization and impacted patients with head and neck cancer (HNC) who have experienced delayed diagnosis and treatment. The pandemic resulted in the admission of patients with severe dyspnea and a need for tracheotomy due to extremely advanced HNC. This study's objective was to evaluate the clinical characteristics of two multi-center cohorts, "pre-COVID-19" and "COVID-19", of HNC patients admitted as emergencies for dyspnea. The therapeutic activity of HNC patients in four University Departments of Otolaryngology was studied over two time periods: September-February 2019/2020 and 2020/2021. A group of 136 HNC patients who underwent a tracheotomy in two-time cohorts, pre-COVID-19 (N = 59) and COVID-19 (N = 77), was analyzed. The mean tracheotomies incidence proportion was 1.82 (SD: 1.12) for the pre-COVID-19 and 3.79 (SD: 2.76) for COVID-19 period. A rise in the occurrence of emergency dyspnea was observed in the COVID-19 cohort, and the greatest increase was seen in the centers with the highest limitations on planned surgeries. In the pre-COVID-19 period, 66% of patients presented with symptoms for more than a month in comparison to 78% of patients in the COVID-19 period (p = 0.04). There was a higher incidence of laryngeal and laryngopharyngeal cancer in the COVID-19 period (63% vs. 75%, respectively). The number of tracheotomies performed under general anesthesia dropped in favor of local anesthesia during COVID-19 (64% vs. 56%, respectively) due to extremely advanced HNC. In the COVID-19 cohort, most patients received a telemedicine consultation (N = 55, 71%) in comparison to the pre-COVID-19 period (N = 14, 24%). Reorganization of the referral system, adjustment of treatment capacity for an increased number of HNC, and a reserve for more extensive resection and reconstruction surgeries should be made in the profile of otorhinolaryngological departments, ensuring future HNC treatment is not hampered in case of a new pandemic wave.

Sheep Milk Symbiotic Ice Cream: Effect of Inulin and Apple Fiber on the Survival of Five Probiotic Bacterial Strains during Simulated In Vitro Digestion Conditions.

We conducted a study to determine the survival of bacterial cells under in vitro digestion. For this purpose, ice cream mixes were prepared: control, with 4% inulin, 2.5% inulin and 1.5% apple fiber and 4% apple fiber. Each inoculum (pH = 4.60 ± 0.05), containing 9 log cfu g-1 bacteria, at 5% (w/w) was added to the ice cream mixes (Lacticaseibacilluscasei 431, Lactobacillus acidophilus LA-5, Lacticaseibacillus paracasei L-26, Lacticaseibacillusrhamnosus, Bifidobacterium animalis ssp. lactis BB-12) and fermentation was carried out to pH 4.60 ± 0.05. The in vitro digestion method simulated the stages of digestion that occur in the mouth, stomach and small intestine under optimal controlled conditions (pH value, time and temperature). At each stage of digestion, the survival rate of probiotic bacteria was determined using the plate-deep method. As expected, in the oral stage, there was no significant reduction in the viability of the probiotic bacteria in any ice cream group compared to their content before digestion. In the stomach stage, Bifidobacterium animalis ssp. lactis BB-12 strain had the highest viable counts (8.48 log cfu g-1) among the control samples. Furthermore, a 4% addition of inulin to ice cream with Bifidobacterium BB-12 increased gastric juice tolerance and limited strain reduction by only 16.7% compared to the number of bacterial cells before digestion. Regarding ice cream samples with Bifidobacterium BB-12, replacing part of the inulin with apple fiber resulted in increased survival at the stomach stage and a low reduction in the bacterial population of only 15.6% compared to samples before digestion. At the stomach stage, the positive effect of the addition of inulin and apple fiber was also demonstrated for ice cream samples with Lacticaseibacilluscasei 431 (9.47 log cfu g-1), Lactobacillus acidophilus LA-5 (8.06 log cfu g-1) and Lacticaseibacillus paracasei L-26 (5.79 log cfu g-1). This study showed the highest sensitivity to simulated gastric stress for ice cream samples with Lacticaseibacillusrhamnosus (4.54 log cfu g-1). Our study confirmed that the 4% addition of inulin to ice cream increases the survival rate of L. casei and Bifidobacterium BB-12 in simulated intestinal juice with bile by 0.87 and 2.26 log cfu g-1, respectively. The highest viable count in the small intestine stage was observed in ice cream with L. acidophilus. The addition of inulin increased the survival of L. rhamnosus by 10.8% and Bifidobacterium BB-12 by about 22% under conditions of simulated in vitro digestion compared to their control samples. The survival rates of L. casei and L. paracasei were also highly affected by the 4% addition of apple fiber, where the increase under gastrointestinal passage conditions was determined to range from 7.86-11.26% compared to their control counterparts. In comparison, the lowest survival rate was found in the control ice cream with L. rhamnosus (47.40%). In our study at the intestinal stage, only five ice cream groups: a sample with 4% inulin and L. acidophilus, a control sample with Bifidobacterium BB12, a sample with 2.5% inulin and 1.5% apple fiber with Bifidobacterium BB12, a control sample with L. rhamnosus, a sample with 4% fiber and L. rhamnosus reported bacterial cell counts below 6 log cfu g-1 but higher than 5 log cfu g-1. However, in the remaining ice cream groups, viable counts of bacterial cells ranged from 6.11 to 8.88 log cfu g-1, ensuring a therapeutic effect. Studies have clearly indicated that sheep milk ice cream could provide a suitable matrix for the delivery of probiotics and prebiotics and contribute to intestinal homeostasis. The obtained results have an applicative character and may play an essential role in developing new functional sheep milk ice cream.

Application of Calcium Citrate in the Manufacture of Acid Rennet Cheese Produced from High-Heat-Treated Goat's Milk from Spring and Autumn Season.

The stability of milk proteins is affected by changes in the pH value of milk, the heating temperature, and the addition of calcium compounds or chelating agents, which can cause alterations in calcium distribution. The purpose of this study was to determine the potential of the use of calcium citrate to manufacture fresh acid rennet cheese from high-temperature-pasteurized goat's milk (90 °C, 15 s) from the spring and autumn season and the effect of the calcium dose used on the physicochemical and organoleptic properties of the cheese. Autumn milk was found to be a richer source of total solids, confirming the effect of the production season on milk quality. The applied doses of calcium did not cause the denaturation of goat milk proteins and allowed pasteurization to take place at 90 °C for 15 s. The addition of calcium citrate resulted in a significant increase in the pH value of milk and cheese compared to the control sample. Adding 15 and 20 mg of Ca 100 g-1 to milk as citrate had the most beneficial effect on increasing protein retention in cheese in both seasons, showing a rise from 1.33% to 2.40%. The production season significantly influenced the cheese yield. The control goat cheese from the autumn season showed a 6.85% higher yield compared to the spring cheese. An increase in cheese yield was also observed as the calcium dose of milk increased. The content of micro- and microelements in cheese was affected by the production season. The addition of calcium citrate to milk resulted in a significant increase in the calcium content of cheese-from 120.83 to 147.45 mg 100 g-1 in the spring season and from 130.66 to 151.21 mg 100 g-1 in the autumn season. Increasing the dose of calcium increased the hardness of cheese samples by 1.37 N in the spring and 0.90 N in the autumn. The organoleptic evaluation showed that adding calcium to milk did not significantly affect the organoleptic characteristics of goat cheese.

Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression.

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.

Health-Promoting Nature of Lactococcus lactis IBB109 and Lactococcus lactis IBB417 Strains Exhibiting Proliferation Inhibition and Stimulation of Interleukin-18 Expression in Colorectal Cancer Cells.

Lactic acid bacteria (LAB) are Gram-positive bacteria which are considered for use as adjuvant therapeutics in management of various disease ailments, including obesity, irritable bowel syndrome, lactose intolerance and cancer. To investigate the possible use of Lactococcus lactis strains from our collection in treatment of gastrointestinal cancer, we tested them for the ability to arrest proliferation of human colorectal adenocarcinoma cells (Caco-2). Results of the BrdU assay showed that the anti-proliferative activity of L. lactis cells is strain-specific. We found that particularly, two strains, L. lactis IBB109 and L. lactis IBB417, exhibited the most potent inhibitory effect. Moreover, both strains triggered interleukin 18 gene expression, normally inhibited in Caco-2 (cancer) cells. To examine the probiotic potential of the two strains, we tested them for bile salts and acid tolerance, as well as adhesion properties. Both isolates exhibited probiotic potential-they survived in the presence of 0.3% bile salts and tolerated exposure to low pH and osmotic stress. Notably, we found that L. lactis IBB417 displayed better adherence to mucus and Caco-2 cells than L. lactis IBB109. Additionally, by microdilution tests we confirmed that both strains are sensitive to all nine antibiotics of human and veterinary importance listed by the European Food Safety Authority. Finally, by in silico investigations of whole genome sequencing data, we revealed the genetic features of L. lactis IBB109 and L. lactis IBB417 that can be associated with functional (e.g., adhesion and carbohydrate metabolic genes) and safety (e.g., virulence and antibiotic resistance) aspects of the strains, confirming their health-promoting potential.

G870A Polymorphic Variants of CCND1 Gene and Cyclin D1 Protein Expression as Prognostic Markers in Laryngeal Lesions.

CCND1 gene encodes Cyclin D1 protein, the alternations and overexpression of which are commonly observed in human cancers. Cyclin D1 controls G1-S transition in the cell cycle. The aim of the study was to assess utility of the genotyping and protein expression in predicting the susceptibility of transformation from normal tissue to precancerous laryngeal lesions (PLLs) and finally to laryngeal cancer (LC). Four hundred and thirty-five patients (101 with LC, 100 with PLLs and 234 healthy volunteers) were enrolled in the study. Cyclin D1 expression was examined by immunohistochemistry and G870A polymorphism of gene CCND1 by PCR-RFLP technique. We confirmed association between the A allele and risk of developing LC from healthy mucosa (p = 0.006). Significantly higher expression of Cyclin D1 was observed in LC compering with PLLs (p < 0.0001) and we found that it could be a predictive marker of shorter survival time. To sum up, in the study population CCND1 gene polymorphism A870G and Cyclin D1 expression have a significant impact on the risk of developing PLLs and LC, and, therefore, Cyclin D1 could be a useful marker for the prediction of survival time in LC, whereas CCND1 gene polymorphism does not have a direct impact on patients' outcome.

Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy.

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Developing lactic acid bacteria starter cultures for wholemeal rye flour bread with improved functionality, nutritional value, taste, appearance and safety.

Starter cultures composed of lactic acid bacteria (LAB) were developed based on the genotypic and phenotypic characterisation of isolates belonging to dominant groups of bacteria in spontaneous rye wholemeal sourdoughs. Combinations of strains have been evaluated on an industrial scale in the sourdough fermentation process. Wholemeal rye bread was prepared using sourdoughs obtained with 3 new starter cultures, and compared to bread made using the commercial culture (LV2). All newly developed cultures used for the preparation of wholemeal rye bread allowed to obtain better quality products as compared to the LV2 based bread. The best results were obtained when the culture containing Lactiplantibacillus plantarum 2MI8 and exopolysaccharide (EPS)-producing Weissella confusa/cibaria 6PI3 strains was applied. The addition of yeast during sourdough breads production, especially the one prepared from mentioned above starter culture, significantly improved their organoleptic properties, their volume and crumb moisture was increased, and also the crumb acidity and hardness was reduced. Fermentation of rye wholemeal dough, especially without the yeast addition, resulted in a significant reduction in the content of higher inositol phosphates as compared to the applied flour, which is associated with improved bioavailability of minerals. The results of this study prove that the investigated new starter cultures can be successfully applied in wholemeal rye bread production.

mTOR/α-ketoglutarate-mediated signaling pathways in the context of brain neurodegeneration and neuroprotection.

Cerebral disorders are largely associated with impaired cellular metabolism, despite the regulatory mechanisms designed to ensure cell viability and adequate brain function. Mechanistic target of rapamycin (mTOR) signaling is one of the most crucial factors in the regulation of energy homeostasis and its imbalance is linked with a variety of neurodegenerative diseases. Recent advances in the metabolic pathways' modulation indicate the role of α-ketoglutarate (AKG) as a major signaling hub, additionally highlighting its anti-aging and neuroprotective properties, but the mechanisms of its action are not entirely clear. In this review, we analyzed the physiological and pathophysiological aspects of mTOR in the brain. We also discussed AKG's multifunctional properties, as well as mTOR/AKG-mediated functional communications in cellular metabolism. Thus, this article provides a broad overview of the mTOR/AKG-mediated signaling pathways, in the context of neurodegeneration and endogenous neuroprotection, with the aim to find novel therapeutic strategies.