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Research that directs the way stakeholders act and how they collaborate is essential when addressing complex environmental challenges in the field of sustainability science. For example, researchers attempting to manage Prosopis invasions through biological control in South Africa have historically faced challenges from stakeholders. In this study, we illustrate the importance of stakeholder engagement and social learning by outlining the collaborative efforts of various stakeholders to promote effective, integrative and sustainable management of Prosopis invasions in the Northern Cape, South Africa. Through a community of practice approach, stakeholders worked together over the past half-decade in an attempt to develop a National Strategy for Prosopis management and improve its control. This strategy aimed not only to emphasise the need for integration of biomass use (aimed at offsetting the costs of mechanical clearing and necessary herbicide use) but also to underscore the significance of biocontrol alongside other management approaches. Stakeholders also identified that adequate farm-scale planning is necessary to provide a sense of purpose and assist in monitoring of progress. We worked alongside land managers and experts to develop such plans. The engagement of local champions played a crucial role in facilitating collaboration and learning among stakeholders, emphasising the significance of inclusive approaches in addressing complex sustainability challenges. In addition, we gained an understanding of how to develop the community of practice to enhance collaboration that ensures the implementation of plans to better manage Prosopis. Our findings underscore the necessity of meaningful stakeholder engagement and collaboration in effective invasive species management. By promoting understanding and involvement of diverse stakeholders, initiatives can have a greater impact in addressing broader sustainability issues. Significance: Our findings highlight the fundamental role of stakeholder collaboration in addressing environmental challenges (e.g. biological invasions), promoting sustainability and fostering social learning. Collaboration facilitates exchange of knowledge, promotes social learning and allows stakeholders to make informed decisions when addressing sustainability issues. Collaborative approaches promote the effectiveness of a community of practice in managing Prosopis invasions in South Africa. Local champions played a pivotal role in facilitating collaboration, bridging communication gaps and promoting inclusive approaches. Sustained stakeholder engagement, transdisciplinary collaborations, effective biological control and market development for biomass products will be essential to improve the sustainable management of Prosopis.

Aims. The main objective of this study was to determine the sensitivity of abdominal ultrasonography (US) in patients with isoattenuating pancreatic carcinoma and to compare the frequency of secondary signs on abdominal US and endoscopic ultrasonography (EUS) in these tumours. Methods. Twenty-four patients with histologically or cytologically verified isoattenuating pancreatic carcinoma who underwent abdominal US, contrast-enhanced CT and EUS of the pancreas as part of the diagnostic workup were included in this retrospective study. The sensitivity of abdominal US in detecting the isoattenuating pancreatic carcinoma was investigated and the frequency of secondary signs of isoattenuating pancreatic carcinoma on abdominal US and EUS was compared. Results. In 5 of 24 patients (21%) with isoattenuating pancreatic carcinoma, a hypoechogenic pancreatic lesion was directly visualised on abdominal US. Secondary signs were present on US in 21 patients (88%). These included dilatation of the common bile duct and/or intrahepatic bile ducts in 19/24 (79%), dilatation of the pancreatic duct in 3/24 (13%), abnormal contour/inhomogeneity of the pancreas in 1/24 (4%), and atrophy of the distal parenchyma in 1/24 (4%). Pancreatic duct dilatation was observed more frequently on EUS than on abdominal US (P=0.002). For other secondary signs, there was no significant difference in their detection on abdominal US and EUS (P=0.61-1.00). Conclusion. Abdominal US is capable of detecting secondary signs of isoattenuating pancreatic carcinoma with high sensitivity and has the potential to directly visualise these tumours.

Intraspecific variation in sex pheromones is a driver of reproductive isolation and speciation in insects. The False Codling Moth (FCM) Thaumatotibia leucotreta (Lepidoptera: Tortricidae) is a quarantine pest endemic to sub-Saharan Africa (SSA). The currently available precision control measures for FCM use female sex pheromone components to lure males into traps. However, the existing data on the composition of the female sex pheromone, especially the isomer ratios of the main pheromone component (E/Z)-8-dodecenyl acetate, are inconsistent for populations in SSA. This inconsistency led to speculation about possible reproductive isolation between geographically separated FCM populations and the potential need for local adjustment of pheromone-based FCM control tools. This, however, requires a comparative evaluation of geographic variation in FCM sexual communication and inter-population mating compatibility. We therefore investigated genetic isolation and mating compatibility between five geographically isolated FCM populations in South Africa and analysed the ratio of (E)- and (Z)-8-dodecenyl acetate in females from these populations. The five studied populations were found to form three genetically distinct groups with high genetic distances between each other. Mating compatibility tests showed that mating is possible across these groups, however, males preferred females of their own population when given choices; without a choice, males successfully mated with and transferred spermatophores to females from all other populations. The ratio of (E)- and (Z)-8-dodecenyl acetate was similar (c. 4:1) across the populations, indicating that this main female pheromone component does not cause the observed intra-population mating preferences. It remains to be investigated if qualitative/quantitative variation in other sex pheromone components influences intra-population recognition in South African FCM, providing a base for the development of regionally-specific lures for area-wide control programmes.

Abstract Background Causative genetic variants cannot yet be found for many disorders with a clear heritable component, including chronic fatigue disorders like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These conditions may involve genes in difficult-to-align genomic regions that are refractory to short read approaches. Structural variants in these regions can be particularly hard to detect or define with short reads, yet may account for a significant number of cases. Long read sequencing can overcome these difficulties but so far little data is available regarding the specific analytical challenges inherent in such regions, which need to be taken into account to ensure that variants are correctly identified. Research into chronic fatigue disorders faces the additional challenge that the heterogeneous patient populations likely encompass multiple aetiologies with overlapping symptoms, rather than a single disease entity, such that each individual abnormality may lack statistical significance within a larger sample. Better delineation of patient subgroups is needed to target research and treatment. Methods We use nanopore sequencing in a case of unexplained severe fatigue to identify and fully characterise a large inversion in a highly homologous region spanning the AKR1C gene locus, which was indicated but could not be resolved by short-read sequencing. We then use GC–MS/MS serum steroid analysis to investigate the functional consequences. Results Several commonly used bioinformatics tools are confounded by the homology but a combined approach including visual inspection allows the variant to be accurately resolved. The DNA inversion appears to increase the expression of AKR1C2 while limiting AKR1C1 activity, resulting in a relative increase of inhibitory GABAergic neurosteroids and impaired progesterone metabolism which could suppress neuronal activity and interfere with cellular function in a wide range of tissues. Conclusions This study provides an example of how long read sequencing can improve diagnostic yield in research and clinical care, and highlights some of the analytical challenges presented by regions containing tandem arrays of genes. It also proposes a novel gene associated with a novel disease aetiology that may be an underlying cause of complex chronic fatigue. It reveals biomarkers that could now be assessed in a larger cohort, potentially identifying a subset of patients who might respond to treatments suggested by the aetiology.

Schizophrenia is associated with numerous abnormalities, including imbalances in all hormonal axes, among which steroids play a major role. Steroidomic studies therefore represent a promising tool for early diagnosis and appropriate treatment of schizophrenia. A total of 51 adult male schizophrenics aged 27 (22, 34) years (shown as median with quartiles) and 16 healthy controls (HCs) aged 28 (25, 32) years were enrolled into this study. Our results showed the effective differentiation of men with schizophrenia from controls based on steroidomic profiles. We also found an altered metabolic pathway from pregnenolone and its sulfate (PREG/S) to cortisol in schizophrenics with several metabolic bottlenecks such as lower PREG levels due to increased PREG sulfation and/or suppressed PREGS desulfation and attenuated conversion of 17-hydroxy-PREG to 17-hydroxy-progesterone, as well as the results suggestive of suppressed CYP11B1 activity. In contrast, steroid molar ratios suggested two counterregulatory steps involving increased conversion of PREG/S to 17-hydroxy-PREG/S and decreased conversion of cortisol to cortisone, which may maintain unchanged basal cortisol levels but may not ensure a sufficient cortisol response to stress. Our data also indicated a trend to higher 7α-, 7β-, and 16α-hydroxylation that may counteract the autoimmune complications and proinflammatory processes accompanying schizophrenia. Finally, a possible suppression of HSD17B3 activity was suggested, resulting in decreased circulating testosterone levels with increased androstenedione levels.

The emotion of disgust protects individuals against pathogens, and it has been found to be elevated during pregnancy. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. This study aimed to assess the association between steroids and disgust sensitivity in pregnancy. Using a prospective longitudinal design, we analyzed blood serum steroid concentrations and measured disgust sensitivity via text-based questionnaires in a sample of 179 pregnant women during their first and third trimesters. We found positive correlations between disgust sensitivity and the levels of C19 steroids (including testosterone) and its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Additionally, positive correlations were observed with 5α/β-reduced C19 steroid metabolites in both trimesters. In the first trimester, disgust sensitivity was positively associated with 17-hydroxypregnanolone and with some estrogens. In the third trimester, positive associations were observed with cortisol and immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our findings show that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, with steroids which may be related to potential maternal-anxiety-related symptoms. This study highlights the complex relationship between hormonal changes and disgust sensitivity during pregnancy.

Aims. Sufficient visibility of the mucosa during upper endoscopy is crucial for successful diagnosis, especially for early neoplastic lesions. Data documenting the effect of administration of mucolytic solution prior to gastroscopy in order to improve mucosal visibility are limited in Europe. The aim of the study was to assess the score of mucosal visibility in the upper gastrointestinal tract after administration of the mucolytic solution defined by us. Patients and Methods. This is a monocentric, double-blind, randomized study involving 134 patients indicated for diagnostic upper endoscopy. Patients were randomly assigned to one of three arms, with mucolytic solution (100 mL water + 400 mg N-acetylcysteine + 20 mg simethicone), without the solution , and with 100 mL pure water. During the examination, 11 photographs were taken in defined areas. The visibility score was given by the sum of the score 0-5 from 5 defined localities evaluated by a blinded endoscopist and subsequently by two blinded endoscopists. Other parameters monitored were examination time and a semiquantitative evaluation of residual gastric fluid. Results. The basic characteristics of the group (sex, age, indications for examination) were comparable between arms. The visibility score was similar in all arms - 17.4 ± 1.9 vs. 17.0 ± 2.0 vs. 17.6 ± 1.8 (P=0.32). The examination time and the amount of residual fluid in the stomach were comparable in all arms. Conclusions. Administration of the mucolytic solution in our study did not increase the mucosal visibility score in the esophagus, stomach and duodenum. Trial Registration: ClinicalTrials.gov, NCT02967094.

Steroid hormones have diverse roles in pregnancy; some help stabilise pregnancy and influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies. To date, only a few studies have performed a very limited steroid analysis in multiple pregnancies. Our teams investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group, and a control singleton pregnancies group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35 + 3 to 39 + 3 weeks, while it was 38 + 1 to 41 + 1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies. Results demonstrate differences in the steroidome between singleton and twin pregnancies. These were based on the presence of two placentae and two foetal adrenal glands, both with separate enzymatic activity. Since every newborn was delivered by caesarean section, analysis was not negatively influenced by changes in the steroid metabolome associated with the spontaneous onset of labour.

The objective of the study was to determine the effects of inferior alveolar nerve transection on inorganic components in mandibular molars of the rat. We used 26 male laboratory rats of the Wistar strain for the study, age 7–9 weeks. The rats were divided in three groups. The control group (intact) included 6 rats. The surgery was performed under general anesthesia. The experimental group included (group with the nerve transected on the left) included 12 rats. The sham group (group with the nerve prepared without transection) included 8 rats. The animals were sacrificed after 4 weeks. Molars from the left and right sides of the mandible were extracted. Element content levels were determined using inductively coupled plasma mass spectrometry. The following elements were determined in all samples: magnesium (Mg), sodium (Na), potassium (K), calcium (Ca), zinc (Zn), and strontium (Sr). The nerve transection caused: a reduction of the contents of Ca and Sr in the mandibular molars; an increase in the contents of Mg and Zn; a difference arrangement of both sides for Na. The surgery approach itself caused a decrease in the contents of Na and K in the experimental and sham groups; the difference in K in M3 between the left and right sides disappeared due to the surgery. Our results have confirmed the hypothesis of inferior alveolar nerve transection having an effect on inorganic components in mandibular molars in the rat.

OBJECTIVES/GOALS: Scholarly achievement metrics are essential for academic researchers since they are used for promotion and funding opportunities. Our objective was to create awareness among pilot project PIs about how these scholarly activities are evaluated and about the need for continuous auto-evaluation. METHODS/STUDY POPULATION: NIH-sponsored Clinical & Translational Research (CTR) infrastructure grants are a critical mechanism to increase scholarly activity. The Pilot Project Program Core (PPP) of The Alliance IDeA-CTR created a weighted metrics system to evaluate activities including presentations, publications, promotion, honors, & community service. We used the revised evidence-based medicine pyramid to develop the metric instrument. Pilot project PIs received the metric table and met quarterly with a PPP member to discuss progress. The top PIs were acknowledged during the Alliance Research Day with a platform presentation and a monetary award for research expenses or travel to scientific meetings. RESULTS/ANTICIPATED RESULTS: During our first 2 pilot project calls (2020-2022) the PPP funded 7 one-year pilot projects for ($50,000 each). We had a total of 10 PIs, 2 of the projects were MPI. Seven PIs were early or new stage investigators (ESI/NSI). Using the productivity award metric we had a total of 33 presentations, 10 publications, 12 events of community service, and 2 external grant funding. These are significant outcomes considering the pandemics impact on clinical & translational research. A total of 3 awards were given, one award per year for funding and an overall award. The activity was well received by the PIs who actively participated in the tracking of their scholarly activities using the metric. DISCUSSION/SIGNIFICANCE: Productivity metrics are crucial for the career development of ESI and NSI by raising awareness regarding the importance of scholarly activities in their career. This activity will help them track their productivity in an ongoing manner while becoming independent researchers.

Abstract Background Increased oxidative/dicarbonyl stress and chronic inflammation are considered key pathophysiological mediators in the progression of complications in obesity and type 2 diabetes (T2D). Lifestyle and diet composition have a major impact. In this study, we tested the effects of a vegan (V) and a conventional meat containg (M) meal, matched for energy and macronutrients, on postprandial oxidative and dicarbonyl stress, inflammatory markers and appetite hormones. Methods A randomised crossover design was used to evaluate T2D, obese with normal glucose tolerance and control participants (n = 20 in each group), with serum concentrations of analytes determined at 0, 120 and 180 min. Repeated-measures ANOVA was used for statistical analysis. Results In T2D subjects, we observed decreased postprandial concentrations of oxidised glutathione (p ˂ 0.001) and increased glutathione peroxidase activity (p = 0.045) after the V-meal consumption, compared with the M-meal. In obese participants, V-meal consumption increased postprandial concentrations of reduced glutathione (p = 0.041) and decreased methylglyoxal concentrations (p = 0.023). There were no differences in postprandial secretion of TNFα, MCP-1 or ghrelin in T2D or obese men, but we did observe higher postprandial secretion of leptin after the V-meal in T2D men (p = 0.002) compared with the M-meal. Conclusions The results show that a plant-based meal is efficient in ameliorating the postprandial oxidative and dicarbonyl stress compared to a conventional energy- and macronutrient-matched meal, indicating the therapeutic potential of plant-based nutrition in improving the progression of complications in T2D and obese patients. Registered under ClinicalTrials.gov Identifier No. NCT02474147.

Epidemiological studies suggest an association between Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

The shape of the glycemic curve during the oral glucose tolerance test (OGTT), interpreted in the correct context, can predict impaired glucose homeostasis. Our aim was to reveal information inherent in the 3 h glycemic trajectory that is of physiological relevance concerning the disruption of glycoregulation and complications beyond, such as components of metabolic syndrome (MS). Methods: In 1262 subjects (1035 women, 227 men) with a wide range of glucose tolerance, glycemic curves were categorized into four groups: monophasic, biphasic, triphasic, and multiphasic. The groups were then monitored in terms of anthropometry, biochemistry, and timing of the glycemic peak. Results: Most curves were monophasic (50%), then triphasic (28%), biphasic (17.5%), and multiphasic (4.5%). Men had more biphasic curves than women (33 vs. 14%, respectively), while women had more triphasic curves than men (30 vs. 19%, respectively) (p < 0.01). Monophasic curves were more frequent in people with impaired glucose regulation and MS compared to bi-, tri-, and multiphasic ones. Peak delay was the most common in monophasic curves, in which it was also most strongly associated with the deterioration of glucose tolerance and other components of MS. Conclusion: The shape of the glycemic curve is gender dependent. A monophasic curve is associated with an unfavorable metabolic profile, especially when combined with a delayed peak.

Introduction: The study is aimed to analyze the interplay among the physical balance level, physical activities realization, anthropometric determinants and psychosocial indices in relation to gender and age of seniors 65+. Methods: The participants comprised 500 seniors in age 65+ (234 males and 266 females) participated voluntarily in the research. For data collection we used methods of the “Medical anamnesis”, “Tinetti Balance Assessment Tool”, “Health Survey SF-36”. For statistics analyses the multivariate regression with reduction of dimensionality and orthogonal projection to latent structure was used. Results: Analyzed disabilities “Depression”, “Type 2 diabetes mellitus”, “Hypertension” and “Vertigo” significantly negatively interplay with the Tinneti summary balance score in both genders. Results of the anthropometric parameters of female seniors, in a contrast to the male seniors parameters, proved that body high and muscle mass correlate significantly positively with the performance of the Tinneti summary balance test (p

Steroid sulfation and desulfation participates in the regulation of steroid bioactivity, metabolism and transport. The authors focused on sulfation and desulfation balance in three neurodegenerative diseases: Alzheimer´s disease (AD), Parkinson´s disease (PD), and multiple sclerosis (MS). Circulating steroid conjugates dominate their unconjugated counterparts, but unconjugated steroids outweigh their conjugated counterparts in the brain. Apart from the neurosteroid synthesis in the central nervous system (CNS), most brain steroids cross the blood-brain barrier (BBB) from the periphery and then may be further metabolized. Therefore, steroid levels in the periphery partly reflect the situation in the brain. The CNS steroids subsequently influence the neuronal excitability and have neuroprotective, neuroexcitatory, antidepressant and memory enhancing effects. They also exert anti-inflammatory and immunoprotective actions. Like the unconjugated steroids, the sulfated ones modulate various ligand-gated ion channels. Conjugation by sulfotransferases increases steroid water solubility and facilitates steroid transport. Steroid sulfates, having greater half-lives than their unconjugated counterparts, also serve as a steroid stock pool. Sulfotransferases are ubiquitous enzymes providing massive steroid sulfation in adrenal zona reticularis and zona fasciculata.. Steroid sulfatase hydrolyzing the steroid conjugates is exceedingly expressed in placenta but is ubiquitous in low amounts including brain capillaries of BBB which can rapidly hydrolyze the steroid sulfates coming across the BBB from the periphery. Lower dehydroepiandrosterone sulfate (DHEAS) plasma levels and reduced sulfotransferase activity are considered as risk factors in AD patients. The shifted balance towards unconjugated steroids can participate in the pathophysiology of PD and anti-inflammatory effects of DHEAS may counteract the MS.

The polyphagous shot hole borer (PSHB) beetle is a recent invader in South Africa. Together with its fungal symbiont, Fusarium euwallaceae, it can rapidly kill highly susceptible host plants. Its impact is most profound in urban areas, but it has also been found infesting important forestry, agricultural crop and native species. Since its first detection in 2012, PSHB has spread to all but one province in the country. The beetle–fungus complex has several biological traits that enhance its anthropogenically mediated dispersal, establishment and survival in novel environments – factors that have likely facilitated its rapid spread across the country. We review the history of the PSHB invasion in South Africa, its taxonomic status and the reasons for its rapid spread. We highlight its potential impact and challenges for its management. Finally, we provide an updated distribution map and list of confirmed host plants in South Africa. Of the 130 plant species identified as hosts, 48 of these (19 indigenous and 29 introduced) are reproductive hosts able to maintain breeding PSHB populations. These reproductive hosts may succumb to beetle infestations and act as ‘pest-amplifiers’. The economic impact on urban forests, plantation forestry and agricultural crops may be severe, but the ecological impact of PSHB invasion in native ecosystems should not be underestimated. Significance: • We provide an updated host list and distribution map for South Africa of the globally significant tree pest, the polyphagous shot hole borer (PSHB, Euwallacea fornicatus). The South African PSHB invasion represents the largest outbreak of this pest in its global invaded range. PSHB was confirmed to infest 130 plant species in urban, agricultural, and native ecosystems in South Africa, including 44 previously unreported hosts. Impact in South Africa is in its infancy but will likely be substantial to local economies and ecosystems. Mitigation has proven difficult, but numerous research projects have been initiated throughout the country.

Background: Anorexia nervosa (AN) is a life-threatening illness with poor treatment outcomes. Although transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method, its effect in patients with AN remains unclear.Objective: This study investigated changes in maladaptive eating behavior, body mass index (BMI), and depression after 10 sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC).Methods: In this double-blind, randomized controlled trial, 43 inpatients with AN were divided to receive either active (n = 22) or sham (n = 21) tDCS over the left DLPFC (anode F3/cathode Fp2, 2 mA for 30 min). All patients filled the Eating Disorder Examination Questionnaire (EDE-Q) and Zung Self-Rating Depression Scale (ZUNG), and their BMI was measured. These values were obtained repeatedly in four stages: (1) before tDCS treatment, (2) after tDCS treatment, (3) in the follow-up after 2 weeks, and (4) in the follow-up after 4 weeks.Results: Primary outcomes (EDE-Q) based on the ANOVA results do not show any between-group differences either after the active part of the study or in the follow-up. Secondary analysis reveals a reduction in some items of EDE-Q. Compared with sham tDCS, active tDCS significantly improved self-evaluation based on body shape (p < 0.05) and significantly decreased the need of excessive control over calorie intake (p < 0.05) in the 4-week follow-up. However, the results do not survive multiple comparison correction. In both sham and active groups, the BMI values improved, albeit not significantly.Conclusion: We did not observe a significant effect of tDCS over the left DLPFC on complex psychopathology and weight recovery in patients with AN. tDCS reduced the need to follow specific dietary rules and improved body image evaluation in patients with AN. Tests with a larger sample and different positions of electrodes are needed.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03273205.

Vitamin D is no longer considered an agent only affecting calcium phosphate metabolism. A number of studies over the past few years have demonstrated its role in immunomodulation and its influence on the development and functioning of the brain and nervous system. In the current epidemiological crisis caused by coronavirus disease 2019 (COVID-19), the immunoprotective role of vitamin D has been discussed by some authors regarding whether it contributes to protection against this serious disease or whether its use does not play a role. Non-standard approaches taken by laboratories in examining the serum levels of the vitamin D metabolite calcidiol have contributed to inconsistent results. We examined the serum of 60 volunteers in the spring and autumn of 2021 who declared whether they were taking vitamin D at the time of sampling. Furthermore, the tested participants noted whether they had experienced COVID-19. A newly developed liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was used to measure calcidiol levels. The analysis of variance (ANOVA) model of Statgraphics Centurion 18 statistical software from Statgraphics Technologies was used for calculations. The results of this study showed that those who took vitamin D suffered significantly less often from COVID-19 than those who did not take vitamin D.

Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.

Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.

In the European energy market, the community energy sector is earmarked to make a significant contribution to the transition from fossil fuels to sustainable sources. Based on the diffusion of innovation model, large-scale development of community energy requires that the concept and the success of existing energy communities be widely communicated to potential participants and that user confidence be developed over time. In this paper, we present the architecture, design, prototyping, and testing of a digital support platform, co-designed with EU-wide energy communities, to support this process. The platform has been designed to engage early-stage or ongoing groups to progress projects and to connect and share experiences with other communities. This “community of communities” creates the necessary communication channel defined in the Diffusion of Innovation model. A transactional architecture for such a platform is outlined with clear links to all community energy actors. Based on this architecture, a prototype one-stop-shop (OSS) implementation is presented. Feedback gathered and lessons learned from beta testing with a representative group of end-users are outlined. The OSS architecture shows potential as a communications channel to expand the community energy concept and as a monitoring tool to track the progress of the energy community sector.

The equilibrium and reciprocal actions among appetite-stimulating (orexigenic) and appetite-suppressing (anorexigenic) signals synthesized in the gut, brain, microbiome and adipose tissue (AT), seems to play a pivotal role in the regulation of food intake and feeding behavior, anxiety, and depression. A dysregulation of mechanisms controlling the energy balance may result in eating disorders such as anorexia nervosa (AN) and bulimia nervosa (BN). AN is a psychiatric disease defined by chronic self-induced extreme dietary restriction leading to an extremely low body weight and adiposity. BN is defined as out-of-control binge eating, which is compensated by self-induced vomiting, fasting, or excessive exercise. Certain gut microbiota-related compounds, like bacterial chaperone protein Escherichia coli caseinolytic protease B (ClpB) and food-derived antigens were recently described to trigger the production of autoantibodies cross-reacting with appetite-regulating hormones and neurotransmitters. Gut microbiome may be a potential manipulator for AT and energy homeostasis. Thus, the regulation of appetite, emotion, mood, and nutritional status is also under the control of neuroimmunoendocrine mechanisms by secretion of autoantibodies directed against neuropeptides, neuroactive metabolites, and peptides. In AN and BN, altered cholinergic, dopaminergic, adrenergic, and serotonergic relays may lead to abnormal AT, gut, and brain hormone secretion. The present review summarizes updated knowledge regarding the gut dysbiosis, gut-barrier permeability, short-chain fatty acids (SCFA), fecal microbial transplantation (FMT), blood-brain barrier permeability, and autoantibodies within the ghrelin and melanocortin systems in eating disorders. We expect that the new knowledge may be used for the development of a novel preventive and therapeutic approach for treatment of AN and BN.

Brain-gut microbiota interactions are intensively studied in connection with various neurological and psychiatric diseases. While anorexia nervosa (AN) pathophysiology is not entirely clear, it is presumably linked to microbiome dysbiosis. We aimed to elucidate the gut microbiota contribution in AN disease pathophysiology. We analyzed the composition and diversity of the gut microbiome of patients with AN (bacteriome and mycobiome) from stool samples before and after renourishment, and compared them to healthy controls. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in stool samples by MS and NMR, respectively. Biochemical, anthropometric, and psychometric profiles were assessed. The bacterial alpha-diversity parameter analyses revealed only increased Chao 1 index in patients with AN before the realimentation, reflecting their interindividual variation. Subsequently, core microbiota depletion signs were observed in patients with AN. Overrepresented OTUs (operation taxonomic units) in patients with AN taxonomically belonged to Alistipes, Clostridiales, Christensenellaceae, and Ruminococcaceae. Underrepresented OTUs in patients with AN were Faecalibacterium, Agathobacter, Bacteroides, Blautia, and Lachnospira. Patients exhibited greater interindividual variation in the gut bacteriome, as well as in metagenome content compared to controls, suggesting altered bacteriome functions. Patients had decreased levels of serotonin, GABA, dopamine, butyrate, and acetate in their stool samples compared to controls. Mycobiome analysis did not reveal significant differences in alpha diversity and fungal profile composition between patients with AN and healthy controls, nor any correlation of the fungal composition with the bacterial profile. Our results show the changed profile of the gut microbiome and its metabolites in patients with severe AN. Although therapeutic partial renourishment led to increased body mass index and improved psychometric parameters, SCFA, and neurotransmitter profiles, as well as microbial community compositions, did not change substantially during the hospitalization period, which can be potentially caused by only partial weight recovery.

The aim of our study was to address the potential for improvements in thyroid cancer detection in routine clinical settings using a clinical examination, the American College of Radiology Thyroid Imaging Reporting and Database System (ACR TI-RADS), and fine-needle aspiration cytology (FNAC) concurrently with molecular diagnostics. A prospective cohort study was performed on 178 patients. DNA from FNA samples was used for next-generation sequencing to identify mutations in the genes BRAF, HRAS, KRAS, NRAS, and TERT. RNA was used for real-time PCR to detect fusion genes. The strongest relevant positive predictors for malignancy were the presence of genetic mutations (p < 0.01), followed by FNAC (p < 0.01) and ACR TI-RADS (p < 0.01). Overall, FNAC, ACR TI-RADS, and genetic testing reached a sensitivity of up to 96.1% and a specificity of 88.3%, with a diagnostic odds ratio (DOR) of 183.6. Sensitivity, specificity, and DOR decreased to 75.0%, 88.9%, and 24.0, respectively, for indeterminate (Bethesda III, IV) FNAC results. FNA molecular testing has substantial potential for thyroid malignancy detection and could lead to improvements in our approaches to patients. However, clinical examination, ACR TI-RADS, and FNAC remained relevant factors.

A systematic review and meta-analysis of studies demonstrated a relationship between sex and balance determinants in seniors; however, no study has focused on sex-related differences in static and dynamic balance performance after a physical intervention as primary interest. The aim was to investigate sex differences in the static and dynamic balance performance after a 4-week physical intervention based on yoga in seniors 65+ years of age. Five-hundred participants (234 males, 266 females) were assessed with the Tinetti Balance Assessment Tool in pre-and post-testing. The experimental group (122 males, 140 females) underwent the intervention, while the control group (112 males, 126 females) ran their usual daily program. ANCOVA model was used for the statistical evaluation of the results. No sex differences were found in balance performance after a short-term physical intervention in seniors 65+ years of age. At the same time, a significant positive shift was demonstrated in performance in both static and dynamic balance.

Background The effect of fat tissue on a developing individual is fundamentally different from the effect on an adult. Several changes caused by obesity during sexual maturation have an irreversible and severe negative effect (lower fertility, reduced final height, type 2 diabetes mellitus) even for those who have subsequently lost weight. Our study was focused on monitoring the skeletal structure substantially influenced by sex hormones—the pelvis. The adult pelvis is strongly sexually dimorphic, which is not the case for the juvenile pelvis; skeletal differences between sexes are not so prominent and start to manifest with the onset of puberty. Evidence from animal models and case studies of treatment of gender dysphoria suggests that estrogens have a stimulatory effect on the growth plates present on the pelvis, leading to morphological change. Male obesity, especially in puberty, is connected with hypogonadism, manifesting in low levels of testosterone, and high levels of estrogens. The goal of our study was to evaluate the influence of obesity during adolescence on the morphology of the adult pelvis in the context of androgen and estrogen status. Sample and Methods Our sample consists of 238 individuals (144 females, 94 males) observed after an 8 year follow-up (mean age during enrollment 15.2 years, follow-up 23.3 years). Anthropometry and body composition using bioimpedance analysis (BIA) were obtained. During the follow-up, saliva samples from male participants were also collected to estimate testosterone and estradiol levels using the salivary ELISA kit (Salimetrics LLC, State College, PA, USA). Results The body fat (percentage of body fat estimated using BIA) was strongly positively associated with relative pelvic breadths in adulthood (males r = 0.64; females r = 0.56, both with p < 0.001). Adulthood pelvic breadth was a highly sensitive (0.81) and specific (0.74) retrospective marker of obesity during adolescence. The complex regression model (with reduction of dimensionality) including testosterone, estradiol to testosterone ratio and body fat (adolescent and adulthood) was able to describe 54.8% variability of pelvic breadth among males. Discussion We observed that adults with a history of obesity from adolescence tend to have a wider dimension of the bony pelvis in adulthood. Based on the parameters of the adult pelvis, the history of obesity can be determined with satisfactory sensitivity and specificity (

Background/Aims: IgA nephropathy is associated with aberrant O-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended. Methods: The relationship between the corticosteroid therapy and serum levels of IgA, aberrantly O-glycosylated IgA1, IgA-containing immune complexes and their mesangioproliferative activity was analyzed in IgA nephropathy patients and disease and healthy controls. Results: Prednisone therapy significantly reduced proteinuria and levels of serum IgA, galactose-deficient IgA1, and IgA-IgG immune complexes in IgA nephropathy patients and thus reduced differences in all of the above parameters between IgAN patients and control groups. A moderate but not significant reduction of mesangioproliferative potential of IgA-IgG immune complexes and IgA sialylation was detected. Conclusion: The prednisone therapy reduces overall aberrancy in IgA1 O-glycosylation in IgA nephropathy patients, but the measurement of IgA1 parameters does not allow us to predict the prednisone therapy outcome in individual patients.

Pregnanolone glutamate (PA-G) is a neuroactive steroid that has been previously demonstrated to be a potent neuroprotective compound in several biological models in vivo. Our in vitro experiments identified PA-G as an inhibitor of N-methyl-D-aspartate receptors and a potentiator of γ-aminobutyric acid receptors (GABAARs). In this study, we addressed the hypothesis that combined GABAAR potentiation and NMDAR antagonism could afford a potent anticonvulsant effect. Our results demonstrated the strong age-related anticonvulsive effect of PA-G in a model of pentylenetetrazol-induced seizures. PA-G significantly decreased seizure severity in 12-day-old animals, but only after the highest dose in 25-day-old animals. Interestingly, the anticonvulsant effect of PA-G differed both qualitatively and quantitatively from that of zuranolone, an investigational neurosteroid acting as a potent positive allosteric modulator of GABAARs. Next, we identified 17-hydroxy-pregnanolone (17-OH-PA) as a major metabolite of PA-G in 12-day-old animals. Finally, the administration of PA-G demonstrated direct modulation of unexpected neurosteroid levels, namely pregnenolone and dehydroepiandrosterone sulfate. These results suggest that compound PA-G might be a pro-drug of 17-OH-PA, a neurosteroid with a promising neuroprotective effect with an unknown mechanism of action that may represent an attractive target for studying perinatal neural diseases.

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM− women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM− women (n = 33), in weeks 24–28, 30–36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

The high penetration of photovoltaic (PV) systems and fast communications networks increase the potential for PV inverters to support the stability and performance of microgrids. PV inverters in the distribution network can work cooperatively and follow centralized and decentralized control commands to optimize energy production while meeting grid code requirements. However, there are older autonomous inverters that have already been installed and will operate in the same network as smart controllable ones. This paper proposes a decentralized optimal control (DOC) that performs multi-objective optimization for a group of PV inverters in a network of existing residential loads and autonomous inverters. The interaction of independent DOC groups in the same network is considered. The limit of PV inverter power factor is included in the control. The DOC is done by the power flow calculation and an autoregression prediction model for estimating maximum power point and loads. Overvoltage caused by prediction errors resulting in non-optimal commands from the DOC is avoided by switching to autonomous droop control (ADC). The DOC and ADC operate at different time scales to take account of communication delays between PV inverters and decentralized controller. The simulation of different scenarios of network control has proved the effectiveness of the control strategies.

The aging of human populations, including those in Europe, is an indisputable fact. The challenge for the future is not simply prolonging human life at any cost or by any means but rather extending self-sufficiency and quality of life. Even in the most advanced societies, the eternal questions remain. Who will take care of the older generations? Will adult children’s own circumstances be sufficient to support family members as they age? For a range of complex reasons, including socioeconomic conditions, adult children are often unable or unwilling to assume responsibility for the care of older family members. For this reason, it is imperative that aging adults maintain their independence and self-care for as long as possible. Movement is an important part of self-sufficiency. Moreover, movement has been shown to improve patients’ clinical status. At a time when the coronavirus pandemic is disrupting the world, older people are among the most vulnerable. Our paper explores current knowledge and offers insights into the significant benefits of movement for the elderly, including improved immunity. We discuss the biochemical processes of aging and the counteractive effects of exercise and endogenous substances, such as vitamin D.

Objective: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). Methods: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. Results: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. Conclusion: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.

Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia nervosa (BN) and anorexia nervosa. BN is characterized by binge eating, self-induced vomiting or excessive exercise.Approach: To test the hypothesis that treatment with OLB together with exercise vs. exercise alone would induce feedback action of GH, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and leptin on ghrelin in Czech women with BN and in healthy-weight Czech women (HW). The lipolysis rate (as glycerol release) in subcutaneous abdominal AT was assessed with microdialysis. At an academic medical center, 12 BN and 12 HW (the control group) were randomized to OLB 500 mg 1 h before a single exercise bout (45 min, 2 W/kg of lean body mass [LBM]) once a week vs. identical placebo over a total of 2 weeks. Blood plasma concentrations of GH, PP, PYY, leptin, ghrelin, FFA, glycerol, and concentrations of AT interstitial glycerol were estimated during the test by RIA utilizing 125I-labeled tracer, the electrochemiluminescence technique (ECLIA) or colorimetric kits.Results: OLB administration together with short-term exercise significantly increased plasma GH (P < 0.0001), PP (P < 0.0001), PYY, and leptin concentrations and significantly decreased plasma ghrelin (P < 0.01) concentrations in both groups, whereas short-term exercise with placebo resulted in plasma ghrelin (P < 0.05) decrease exclusively in BN. OLB administration together with short-term exercise significantly lowered local subcutaneous abdominal AT interstitial glycerol (P < 0.0001) to a greater extent in BN.Conclusion: OLB-induced suppression of plasma ghrelin concentrations together with short-term exercise and after the post-exercise recovering phase suggests a potential negative co-feedback of GH, PP, PYY, and leptin on ghrelin secretion to a greater extent in BN. Simultaneously, the exercise-induced elevation in AT interstitial glycerol leading to a higher inhibition of peripheral lipolysis by OLB in BN.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT03338387

(1) Background. The aim was to define typical features of isoattenuating pancreatic carcinomas on computed tomography (CT) and endosonography and determine the yield of fine-needle aspiration endosonography (EUS-FNA) in their diagnosis. (2) Methods. One hundred and seventy-three patients with pancreatic carcinomas underwent multiphase contrast-enhanced CT followed by EUS-FNA at the time of diagnosis. Secondary signs on CT, size and location on EUS, and the yield of EUS-FNA in isoattenuating and hypoattenuating pancreatic cancer, were evaluated. (3) Results. Isoattenuating pancreatic carcinomas occurred in 12.1% of patients. Secondary signs of isoattenuating pancreatic carcinomas on CT were present in 95.2% cases and included dilatation of the pancreatic duct and/or the common bile duct (85.7%), interruption of the pancreatic duct (76.2%), abnormal pancreatic contour (33.3%), and atrophy of the distal parenchyma (9.5%) Compared to hypoattenuating pancreatic carcinomas, isoattenuating carcinomas were more often localized in the pancreatic head (100% vs. 59.2%; p < 0.001). In ROC (receiver operating characteristic) analysis, the optimal cut-off value for the size of isoattenuating carcinomas on EUS was ≤ 25 mm (AUC = 0.898). The sensitivity of EUS-FNA in confirmation of isoattenuating and hypoattenuating pancreatic cancer were 90.5% and 92.8% (p = 0.886). (4) Conclusions. Isoattenuating pancreatic head carcinoma can be revealed by indirect signs on CT and confirmed with high sensitivity by EUS-FNA.

Background and aims. Patients with intrahepatic cholestasis of pregnancy (ICP) benefit from ursodeoxycholic acid (UDCA) treatment. Since there is still certain reluctance to use UDCA in pregnant women, mainly due to warnings in the official SPC information in respective drug leaflets, our objective was to assess the efficacy and safety of UDCA during pregnancy.Material and methods. Our retrospective multicentric study was performed on 191 consecutive pregnant women with ICP treated with UDCA. Any maternal and/or fetal complications of the UDCA treatment were searched for; healthy pregnant women (n = 256) served as controls.Results. The UDCA treatment improved liver disease status in the majority of the affected women (86.1%). This treatment was well tolerated, with only negligible skin reactions (0.5%) and mild diarrhea (4.7%). No complications attributable to UDCA treatment were detected during the fetal life, delivery, or the early neonatal period.Conclusion. We confirmed the good efficacy and safety of UDCA treatment in pregnancy for both mothers and fetuses/neonates.

Studies on the time course of ACTH- or insulin-induced hypoglycemia stimulating adrenal androgens are usually limited to dehydroepiandrosterone and/or its sulphate. Our data on dehydroepiandrosterone (DHEA) and its hydroxylated metabolites clearly show that measurements of DHEA and its sulphate (DHEAS) are valuable markers of the integrity of the HPA (hypothalamus-pituitary-adrenal) axis. Assessments of HPA function should rely on measurements of baseline and/or stimulated serum cortisol concentrations, and C19 Δ5-steroids may provide additional information. The art of stimulation of 7- and 16-hydroxylated metabolites of DHEA can help our understanding of the formation sequence of these compounds.

High penetration levels of renewable energy generation in the distribution network require voltage regulation to avoid excessive voltage at generating nodes. To effectively control the network and optimize network hosting capacity, the distribution system operator must have an efficient model for power flow analysis. This paper presents the formulas and steps to express the power flow analysis equations of an unbalanced 3-phase network in matrix form suited to programmed solutions. A benchmark MATLAB/Simulink network with unbalanced distribution lines, photovoltaic inverters, and loads is built to verify the matrix model. To demonstrate the application of the model, the control of reverse energy flow from the photovoltaic inverters to keep the voltage in the network below the regulated level is simulated. Two decentralized control algorithms are applied in the network, including an on/off and a multi-objective constrained optimization controller. The detailed construction of the optimization problem for the 3-phase network in matrix form, which is consistent with the power flow calculation, is described. Simulation with the control methods over a day shows that the total active power of the on/off and optimized controllers deliver 41.92% and 99.39% of the available solar power, respectively, while maintaining the network node voltages within limits.

Eight women of reproductive age with normal body mass index were given 5 standardised meals, and their hormonal milieu was determined during the course of the day. Plasma from 12 withdrawals was analysed for dehydroepiandrosterone and its 7- and 16-hydroxylated metabolites. Overall, there was a maximum in the levels of steroid hormones in the morning, followed by decreases throughout the day. There was also an additional significant decrease found for dehydroepiandrosterone and its 7α-hydroxyderivative in association with the consumption of main meals, but not for the 7β-isomer or 16α-hydroxyderivative.

The influence of steroid hormones on food intake is well described. However, there are only a few studies on the effect of food intake on steroid levels. The study involved eight non-smoker women (average age 29.48 ± 2.99 years; average BMI 21.3 ± 1.3 kg/m2); they did not use any kind of medication affecting steroidogenesis. We analysed the influence of four various stimuli on the levels of steroid hormones and melatonin. During their follicular phase of menstrual cycle, each woman had an oral glucose tolerance test (OGTT), intravenous glucose tolerance test (IVGTT), a standard breakfast and psyllium (a non-caloric fibre). Cortisol declined during each test, which is a physiological decline in the morning hours. In all tests (except of the application of the non-caloric fibre, psyllium), however, this decline was modified. After the standard breakfast there was an increase in cortisol at 40th minute. The OGTT and IVGTT tests led to a plateau in cortisol levels. Testosterone levels and those of other steroid hormones showed no relationships to tested stimulations. Oral and intravenous glucose have influenced physiological decline of melatonin levels. During the IVGTT test, melatonin levels started to increase at 20th minute, reaching a maximum at 40th minute. The OGTT test led to a delayed increase in melatonin levels, compared to IVGTT. Despite the fact that we performed the tests in the morning hours, when steroid hormone levels physiologically start to change due to their diurnal rhythm, we still found that food intake influences some of the hormone levels.

BACKGROUND:Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved. METHODS:In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses. RESULTS:Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p

Smoking represents the most widespread substance dependence in the world. Nicotine alters women hormonal homeostasis. Women smokers have higher testosterone and lower estradiol levels throughout life compared to non-smokers. We monitored the effect of smoking discontinuation on steroid spectrum with 25 postmenopausal women smokers. They had been examined before discontinuation of smoking and after 6, 12, 24 and 48 weeks of abstinence. Blood was collected to determine steroid spectrum (measured by GC-MS), luteinizing hormone, follicle stimulating hormone and sex hormone binding globulin (measured by IRMA). Repeated measures ANOVA model was used for evaluation of the data. In postmenopausal women, an increase in testosterone, dihydrotestosterone, dehydroepiandrosterone and other androgens occurred. Neither nicotine replacement therapy nor weight changes nor age play a role in androgen level increase. The higher androgens levels correlated with failure in smoking cessation. Women smokers have higher androgen levels, which might play a role in smoking dependence development. Women successful in smoking cessation, compared to the non-successful ones, have lower androgen levels initially and also after smoking discontinuation.

Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland’s role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.

Diminished postprandial secretion of incretins and insulin represents one of the key pathophysiological mechanisms behind type 2 diabetes (T2D). We tested the effects of two energy- and macronutrient-matched meals: A standard meat (M-meal) and a vegan (V-meal) on postprandial incretin and insulin secretion in participants with T2D. A randomized crossover design was used in 20 participants with T2D. Plasma concentrations of glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), amylin, and gastric inhibitory peptide (GIP) were determined at 0, 30, 60, 120, and 180 min. Beta-cell function was assessed with a mathematical model, using C-peptide deconvolution. Repeated-measures ANOVA was used for statistical analysis. Postprandial plasma glucose responses were similar after both test meals (p = 0.64). An increase in the stimulated secretion of insulin (by 30.5%; 95% CI 21.2 to 40.7%; p < 0.001), C-peptide (by 7.1%; 95% CI 4.1 to 9.9%; p < 0.001), and amylin (by 15.7%; 95% CI 11.8 to 19.7%; p < 0.001) was observed following consumption of the V-meal. An increase in stimulated secretion of GLP-1 (by 19.2%; 95% CI 12.4 to 26.7%; p < 0.001) and a decrease in GIP (by −9.4%; 95% CI −17.3 to −0.7%; p = 0.02) were observed after the V-meal. Several parameters of beta-cell function increased after the V-meal, particularly insulin secretion at a fixed glucose value 5 mmol/L, rate sensitivity, and the potentiation factor. Our results showed an increase in postprandial incretin and insulin secretion, after consumption of a V-meal, suggesting a therapeutic potential of plant-based meals for improving beta-cell function in T2D.

Gastrointestinal hormones are involved in regulation of glucose metabolism and satiety. We tested the acute effect of meal composition on these hormones in three population groups. A randomized crossover design was used to examine the effects of two energy- and macronutrient-matched meals: a processed-meat and cheese (M-meal) and a vegan meal with tofu (V-meal) on gastrointestinal hormones, and satiety in men with type 2 diabetes (T2D, n = 20), obese men (O, n = 20), and healthy men (H, n = 20). Plasma concentrations of glucagon-like peptide -1 (GLP-1), amylin, and peptide YY (PYY) were determined at 0, 30, 60, 120 and 180 min. Visual analogue scale was used to assess satiety. We used repeated-measures Analysis of variance (ANOVA) for statistical analysis. Postprandial secretion of GLP-1 increased after the V-meal in T2D (by 30.5%; 95%CI 21.2 to 40.7%; p < 0.001) and H (by 15.8%; 95%CI 8.6 to 23.5%; p = 0.01). Postprandial plasma concentrations of amylin increased in in all groups after the V-meal: by 15.7% in T2D (95%CI 11.8 to 19.6%; p < 0.001); by 11.5% in O (95%CI 7.8 to 15.3%; p = 0.03); and by 13.8% in H (95%CI 8.4 to 19.5%; p < 0.001). An increase in postprandial values of PYY after the V-meal was significant only in H (by 18.9%; 95%CI 7.5 to 31.3%; p = 0.03). Satiety was greater in all participants after the V-meal: by 9% in T2D (95%CI 4.4 to 13.6%; p = 0.004); by 18.7% in O (95%CI 12.8 to 24.6%; p < 0.001); and by 25% in H (95%CI 18.2 to 31.7%; p < 0.001). Our results indicate there is an increase in gut hormones and satiety, following consumption of a single plant-based meal with tofu when compared with an energy- and macronutrient-matched processed-meat meat and cheese meal, in healthy, obese and diabetic men.

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17). An age-adjusted linear model, receiver-operating characteristics (ROC), and multivariate regression (a method of orthogonal projections to latent structure, OPLS) were used for data evaluation. While aminotransferases, conjugates of pregnanediols, 17-hydroxypregnenolone and 5β-androstane-3α,17β-diol were higher in ICP patients, 20α-dihydropregnenolone, 16α-hydroxy-steroids, sulfated 17-oxo-C19-steroids, and 5β-reduced steroids were lower. The OPLS model including steroids measured by GC-MS and RIA showed 93.3% sensitivity and 100% specificity, while the model including steroids measured by GC-MS in a single sample aliquot showed 93.3% sensitivity and 94.1% specificity. A composite index including ratios of sulfated 3α/β-hydroxy-5α/β-androstane-17-ones to conjugated 5α/β-pregnane-3α/β, 20α-diols discriminated with 93.3% specificity and 81.3% sensitivity (ROC analysis). These new data demonstrating altered steroidogenesis in ICP patients offer more detailed pathophysiological insights into the role of steroids in the development of ICP.

The aim of this study was to test the effect of a plant-based dietary intervention on beta-cell function in overweight adults with no history of diabetes. Participants (n = 75) were randomized to follow a low-fat plant-based diet (n = 38) or to make no diet changes (n = 37) for 16 weeks. At baseline and 16 weeks, beta-cell function was quantified with a mathematical model. Using a standard meal test, insulin secretory rate was calculated by C-peptide deconvolution. The Homeostasis Model Assessment (HOMA-IR) index was used to assess insulin resistance while fasting. A marked increase in meal-stimulated insulin secretion was observed in the intervention group compared with controls (interaction between group and time, Gxt, p < 0.001). HOMA-IR index fell significantly (p < 0.001) in the intervention group (treatment effect −1.0 (95% CI, −1.2 to −0.8); Gxt, p = 0.004). Changes in HOMA-IR correlated positively with changes in body mass index (BMI) and visceral fat volume (r = 0.34; p = 0.009 and r = 0.42; p = 0.001, respectively). The latter remained significant after adjustment for changes in BMI (r = 0.41; p = 0.002). Changes in glucose-induced insulin secretion correlated negatively with BMI changes (r = −0.25; p = 0.04), but not with changes in visceral fat. Beta-cell function and insulin sensitivity were significantly improved through a low-fat plant-based diet in overweight adults.

The objective was to evaluate the effects of a hypoallergenic (HA) formula supplemented with prebiotic galacto-oligosaccharides on the severity of atopic manifestations. A randomised clinical trial was conducted. The control group was infants, fed with hypoallergenic formula and without supplementation. The duration of the study was six months. The primary outcome of the study was a difference in the severity of atopic dermatitis measured using SCORAD (Scoring Atopic Dermatitis) criteria. Secondary outcomes were anthropometry (length, weight, and head circumference), together with the tolerance and incidence of infections. Both groups showed a decrease of average SCORAD values, but no statistically significant difference between the evaluated groups was observed. There were no statistically significant differences in anthropometry, or the tolerance or incidence of infections. Although there is no evidence, that consumption of a hypoallergenic infant formula enriched with prebiotic galacto-oligosaccharides had any effect on SCORAD, it was safe and well tolerated.www.clinicaltrials.gov NCT 02077088.

The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses.In a randomized crossover study, 50 patients suffering from type 2 diabetes (T2D) and 50 healthy subjects underwent two 3-h meal tolerance tests. For statistical analyses, repeated-measures ANOVA was performed.The M-meal resulted in a higher postprandial increase in lipids in both groups (p

Abnormal postprandial elevation of plasma glucose and lipids plays an important role in the pathogenesis of diabetes and strongly predicts cardiovascular mortality. In patients suffering from type 2 diabetes (T2D) postprandial state is associated with oxidative stress, cardiovascular risk and, probably, with impairment of both secretion and the effect of gastrointestinal peptides. Evaluating postprandial changes of gastrointestinal hormones together with changes in oxidative stress markers may help to understand the mechanisms behind the postprandial state in diabetes as well as suggest new preventive and therapeutical strategies.A standard meal test has been used for monitoring the postprandial concentrations of gastrointestinal hormones and oxidative stress markers in patients with T2D (n = 50) compared to healthy controls (n = 50). Blood samples were drawn 0, 30, 60, 120 and 180 minutes after the standard meal.Both basal and postprandial plasma concentrations of glucose and insulin proved to be significantly higher in patients with T2D, whereas plasma concentrations of ghrelin showed significantly lower values during the whole meal test. In comparison with healthy controls, both basal and postprandial concentrations of almost all other gastrointestinal hormones and lipoperoxidation were significantly increased while ascorbic acid, reduced glutathione and superoxide dismutase activity were decreased in patients with T2D. A positive relationship was found between changes in GIP and those of glucose and immunoreactive insulin in diabetic patients (p