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Introduction: Tuberous sclerosis complex (TSC) is a neurocutaneous disease with a high incidence of epilepsy and damaging effects on cognitive development. To understand the mechanisms leading to abnormal cognitive development, diffusion tensor imaging (DTI) techniques have begun to be used in recent years. The present study is the first to investigate differences in the microstructure and integrity of white matter tracts in adult patients with TSC and with and without epilepsy. Method: A total of 37 patients with TSC (18 with epilepsy, median age 36 years; 19 without epilepsy, median age 35 years) without intellectual disability and autism spectrum disorder were included in the study. The control group (median age 34 years) comprised 37 individuals without psychiatric or neurodevelopmental disorders and neurological and cardiovascular diseases, diabetes, or addictions. A magnetic resonance imaging (MRI) DTI sequence was applied. Results: There were differences in the average values of DTI parameters between patients with TSC and epilepsy and patients with TSC but without epilepsy in five white matter bands. When comparing the average values of DTI parameters between patients with TSC and epilepsy and healthy controls, we found differences in 15 of 20 analysed white matter fibres. White matter tracts in patients with TSC and epilepsy had more abnormalities than in patients with TSC but without epilepsy. The former group presented abnormalities in longer white matter fibres, especially in the left hemisphere. However, the latter group presented abnormalities in more medial and shorter white matter fibres. Conclusion: This DTI study documents the changes in the brain white matter of patients with TSC associated with the presence of epilepsy.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

The agri-food industry is a source of various substrates - plants as well as plant and animal residues or waste, which can be recycled. Determining the yield of agri-food waste processing products that can be obtained from them, as well as estimating the local availability of a given raw material allows for the selection of appropriate substrates that guarantee both their effective production and their continuous supply. The presented article includes a review of scientific reports on the acquisition of bioactive substances, substrates for the production of activated carbon and materials for use in construction from waste from the agri-food industry. Moreover, the article discusses the economic aspects of agri-food waste in terms of bioeconomy.

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00–17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL—the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Introduction: Tuberous sclerosis complex (TSC) is a neurocutaneous disease with a high incidence of epilepsy and damaging effects on cognitive development. To understand the mechanisms leading to abnormal cognitive development, diffusion tensor imaging (DTI) techniques have begun to be used in recent years. The present study is the first to investigate differences in the microstructure and integrity of white matter tracts in adult patients with TSC and with and without epilepsy. Method: A total of 37 patients with TSC (18 with epilepsy, median age 36 years; 19 without epilepsy, median age 35 years) without intellectual disability and autism spectrum disorder were included in the study. The control group (median age 34 years) comprised 37 individuals without psychiatric or neurodevelopmental disorders and neurological and cardiovascular diseases, diabetes, or addictions. A magnetic resonance imaging (MRI) DTI sequence was applied. Results: There were differences in the average values of DTI parameters between patients with TSC and epilepsy and patients with TSC but without epilepsy in five white matter bands. When comparing the average values of DTI parameters between patients with TSC and epilepsy and healthy controls, we found differences in 15 of 20 analysed white matter fibres. White matter tracts in patients with TSC and epilepsy had more abnormalities than in patients with TSC but without epilepsy. The former group presented abnormalities in longer white matter fibres, especially in the left hemisphere. However, the latter group presented abnormalities in more medial and shorter white matter fibres. Conclusion: This DTI study documents the changes in the brain white matter of patients with TSC associated with the presence of epilepsy. [ABSTRACT FROM AUTHOR]

Forests provide a wide range of ecosystem services, and ecosystem models can be applied to assess the contribution of different forest management strategies to climate mitigation and adaptation. Complex model output and trade-offs between environmental, economic, and social sustainability dimensions are difficult to convey. To facilitate stakeholder communication, we developed composite indicators based on ten ecosystem service indicators obtained from ecosystem model simulations representing 19 forestry management strategies across three ecoregions and climate scenario projections in Sweden. Eight alternative composites were generated around a central framework addressing sustainability aspects in terms of wood production, preservation of biodiversity, climate change mitigation and adaptation (risk management). A combination of principal component analysis, exploratory factor analysis, Cronbach’s coefficient alpha, and hierarchical cluster analysis was applied to account for the statistical relationships between indicators. Z-score normalization was superior to min-max normalization in capturing differences among management strategies. Two weighting schemes were applied, based on policy prioritizations between sub-components that reflected 1) current policy with an equal emphasis on production and biodiversity, and 2) a stronger focus on nature protection. Equal emphasis generated a larger range of scores (76.0 ± 21.2) than the focus on nature protection (32.0 ± 5.8), as the latter would provide less production benefits and thereby fewer trade-offs between production and other aspects. The final scores of the 19 management strategies fell within a variance boundary of each other, showing their contribution to different policy targets and the usefulness of combining strategies at the landscape level. The composites displayed agreement across regions and scenarios. They indicated that a shift from even-aged conifer monocultures towards a combination of continuous cover, broadleaf-mixture, and unmanaged would work well for balancing goals under changing climate conditions.

The biological rhythm is a fundamental aspect of an organism, regulating many physiological processes. This study focuses on the analysis of the molecular basis of circadian rhythms and its impact on the functioning of the liver. The regulation of biological rhythms is carried out by the clock system, which consists of the central clock and peripheral clocks. The central clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus and is regulated by signals received from the retinal pathway. The SCN regulates the circadian rhythm of the entire body through its indirect influence on the peripheral clocks. In turn, the peripheral clocks can maintain their own rhythm, independent of the SCN, by creating special feedback loops between transcriptional and translational factors. The main protein families involved in these processes are CLOCK, BMAL, PER and CRY. Disorders in the expression of these factors have a significant impact on the functioning of the liver. In such cases lipid metabolism, cholesterol metabolism, bile acid metabolism, alcohol metabolism, and xenobiotic detoxification can be significantly affected. Clock dysfunctions contribute to the pathogenesis of various disorders, including fatty liver disease, liver cirrhosis and different types of cancer. Therefore understanding circadian rhythm can have significant implications for the therapy of many liver diseases, as well as the development of new preventive and treatment strategies. [ABSTRACT FROM AUTHOR]

Numerous physiological processes occurring in the digestive system are subject to circadian rhythms, which are regulated by the endogenous biological clock. The motor activity of the small intestine, large intestine, and rectum operates in a 24-hour system, with significant differences between day and night periods. It is primarily correlated with the time of meals, hormone secretion rhythms, and other activities undertaken by the organism. In recent years, numerous scientific reports have emerged about the fundamental role of circadian rhythms in the proper functioning of the gut microbiota. In addition, the microbiota and its metabolites also influence the host's daily cycles, which affects the overall state of their organism. The aim of this review is to outline the mechanisms of action and interactions between biological rhythms, gut motility, and the functioning of the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: The efficacy of SARS-CoV-2 vaccination among kidney transplant recipients (KTR) is low. The main goal of this study was to analyze factors that may influence the humoral response to vaccination. Methods: We analyzed the titer magnitude of IgG antibodies directed against spike (S)-SARS-CoV-2 antigen after the second dose of the mRNA vaccine in 142 infection naïve KTR (83 men, i.e., 58.4%) with a median age (IQR) of 54 (41–63), and 36 respective controls without chronic kidney disease. mRNA-1273 or BNT162b2 were applied in 26% and 74% of KTR, respectively. Results: S-specific immune response (seroconversion) was seen in 73 (51.41%) of KTR, and in all controls 36 (100%). Independent predictors of no response were elder age, shorter transplantation vintage, and a more than two-drug immunosuppressive protocol. In subgroup analyses, the seroconversion rate was highest among KTR without MMF/MPS treatment (70%), treated with no more than two immunosuppressants (69.2%), treated without corticosteroid (66.7%), younger patients aged

Kidney transplantation is the treatment of choice for end-stage kidney diseases. Unfortunately, kidney allograft recipients rarely develop tolerance or accommodation and require life-long immunosuppression. Among many other regulatory mechanisms, CD5+ B lymphocytes (mainly B-1a) seem to be involved in the process of allograft acceptance. These cells are the major source of natural, low-affinity antibodies, which are polyreactive. Thus, we hypothesized that CD5+ B cells could be referred to as a biomarker in those patients who developed accommodation towards kidney allotransplant. In this study, 52 low-immunized kidney transplant recipients were evaluated for transplant outcome up to 8 y post-transplant. The follow up included anti-HLA antibodies, B cells phenotype and cytokines. We have identified a cohort of recipients who produced alloantibodies (Abs+), which was associated with increased levels of CD5+ B cells, mainly during the first year after transplantation but also later on. Importantly, creatinine levels were comparable between Abs+ and Abs− allorecipients at 2 years after the transplantation and graft survival rate was comparable between these groups even eight years post-transplant. So, it seems that despite the presence of alloantibodies the graft function was sustained when the level of CD5+ B cells was increased. Targeting CD5+ B cells may be a valuable therapeutic option to increase transplant success. The phenotype can be also tried as a biomarker to increase the effectiveness of individualized post-transplant treatments.