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Emerging evidence suggests a potential association between “leaky gut syndrome” and low-grade systemic inflammation in individuals with psychiatric disorders, such as schizophrenia. Gut dysbiosis could increase intestinal permeability, allowing the passage of toxins and bacteria into the systemic circulation, subsequently triggering immune-reactive responses. This study delves into understanding the relationship between plasma markers of intestinal permeability and symptom severity in schizophrenia. Furthermore, the influence of lifestyle habits on these intestinal permeability markers was determined.
Methods
Biomarkers of intestinal permeability, namely lipopolysaccharide-binding protein (LBP), lipopolysaccharides (LPS), and intestinal fatty acid binding protein (I-FABP), were analyzed in 242 adult schizophrenia patients enrolled in an observational, cross-sectional, multicenter study from four centers in Spain (PI17/00246). Sociodemographic and clinical data were collected, including psychoactive drug use, lifestyle habits, the Positive and Negative Syndrome Scale to evaluate schizophrenia symptom severity, and the Screen for Cognitive Impairment in Psychiatry to assess cognitive performance.
Results
Results revealed elevated levels of LBP and LPS in a significant proportion of patients with schizophrenia (62% and 25.6%, respectively). However, no statistically significant correlation was observed between these biomarkers and the overall clinical severity of psychotic symptoms or cognitive performance, once confounding variables were controlled for. Interestingly, adherence to a Mediterranean diet was negatively correlated with I-FABP levels (beta = −0.186, t = −2.325, p = 0.021), suggesting a potential positive influence on intestinal barrier function.
Conclusions
These findings underscore the importance of addressing dietary habits and promoting a healthy lifestyle in individuals with schizophrenia, with potential implications for both physical and psychopathological aspects of the disorder.
End members and species defined with permissible ranges of composition are presented for the true micas, the brittle micas and the interlayer-cation-deficient micas. The determination of the crystallochemical formula for different available chemical data is outlined, and a system of modifiers and suffixes is given to allow the expression of unusual chemical substitutions or polytypic stacking arrangements. Tables of mica synonyms, varieties, ill-defined materials and a list of names formerly or erroneously used for micas are presented. The Mica Subcommittee was appointed by the Commission on New Minerals and Mineral Names (“Commission”) of the International Mineralogical Association (IMA). The definitions and recommendations presented were approved by the Commission.
Most frequently felt needs in dementia concern maintaining self-management and participation in meaningful activities. E-health interventions may support these aspects of social health but few have undergone large-scale evaluations. The effectiveness of the FindMyApps intervention, an app selection tool and tablet training, designed to support people to find and use tablet apps that meet their needs and interests, was evaluated.
Methods:
A non-blinded, single-centre, randomized controlled trial and process evaluation were conducted in the Netherlands between January 2020 and November 2022. Participants were community-dwelling people with mild dementia (MMSE <26 and >17) or mild cognitive impairment, and their informal caregivers. FindMyApps was compared with digital care as usual (normal tablet computer and general advice). Data regarding primary outcomes (self-management and social participation of the person with dementia, sense of competence of the caregiver) and secondary outcomes (including quality of life) were collected with standardized instruments at baseline and after a three months intervention period. ANCOVAs were conducted on post-test outcome measures, corrected for baseline scores, to investigate group differences.
Results:
Data collection was completed in November 2022 and analyses are underway. Of 150 dyads randomized, 128 completed the three-month follow-up (64 experimental, 64 control). Results of ANCOVAs investigating the effect and effect size of FindMyApps on the primary and secondary outcomes at three months, will be reported, as well as results of post-hoc analyses that explored the effect on outcomes of: previous tablet experience and education level of participants; observed use of the FindMyApps app; and reported adherence to recommended frequency of tablet use.
Discussion and conclusions:
Results of this study will indicate whether FindMyApps is an effective intervention for supporting social health of people with mild dementia and MCI. Comparisons with previous studies of FindMyApps and other digital interventions for social health in dementia will be drawn and implications for professionals, concerning implementation of FindMyApps, and for researchers regarding further development, translation and evaluation of FindMyApps discussed. Finally, establishing feasibility and utility of randomized controlled trials in this field, the results of this study will set the bar for future evaluations of eHealth interventions in general.
Knowledge graphs have become a common approach for knowledge representation. Yet, the application of graph methodology is elusive due to the sheer number and complexity of knowledge sources. In addition, semantic incompatibilities hinder efforts to harmonize and integrate across these diverse sources. As part of The Biomedical Translator Consortium, we have developed a knowledge graph–based question-answering system designed to augment human reasoning and accelerate translational scientific discovery: the Translator system. We have applied the Translator system to answer biomedical questions in the context of a broad array of diseases and syndromes, including Fanconi anemia, primary ciliary dyskinesia, multiple sclerosis, and others. A variety of collaborative approaches have been used to research and develop the Translator system. One recent approach involved the establishment of a monthly “Question-of-the-Month (QotM) Challenge” series. Herein, we describe the structure of the QotM Challenge; the six challenges that have been conducted to date on drug-induced liver injury, cannabidiol toxicity, coronavirus infection, diabetes, psoriatic arthritis, and ATP1A3-related phenotypes; the scientific insights that have been gleaned during the challenges; and the technical issues that were identified over the course of the challenges and that can now be addressed to foster further development of the prototype Translator system. We close with a discussion on Large Language Models such as ChatGPT and highlight differences between those models and the Translator system.
Diets and dietary constituents that we consume have a considerable impact on disease risk. Intriguingly these effects may be modulated to some extent by sex. Lack of female representation in nutritional studies as well as a lack of stratification by sex has and continues to limit our understanding of these sex × diet interactions. Here we provide an overview of the current and available literature describing how exposure to certain dietary patterns (Western-style diet, Mediterranean diet, vegetarian/vegan, ketogenic diet) and dietary constituents (dietary fibre, PUFA and plant bioactive) influences disease risk in a sex-specific manner. Interestingly, these sex differences appear to be highly disease-specific. The identification of such sex differences in response to diet stresses the importance of sex stratification in nutritional research.
Systems Engineering (SE) is becoming increasingly relevant in industrial application since more stakeholders are involved in engineering activities. To implement SE, companies have to adapt existing engineering processes and methods. This adaption requires knowledge about new methods as well as their integration into the engineering activities. In order to ensure goal-oriented identification of methods for different SE activities in this contribution an action field profile and the Systems Engineering Method Matrix are proposed. The development of both tools is driven by the assumption that most SE activities and methods can be described based on the artefacts the deliver. In order to get feedback about the proposed tools, semi-structured interviews with two industry partners were conducted, focussing on the tool's usability. These interviews underline the basic usability of the tools and their support to identify SE activities to be supported by (new) methods. Moreover, requirements for further development and adaption are derived from the interviews.
The stable core, an inner model of the form $\langle L[S],\in , S\rangle $ for a simply definable predicate S, was introduced by the first author in [8], where he showed that V is a class forcing extension of its stable core. We study the structural properties of the stable core and its interactions with large cardinals. We show that the $\operatorname {GCH} $ can fail at all regular cardinals in the stable core, that the stable core can have a discrete proper class of measurable cardinals, but that measurable cardinals need not be downward absolute to the stable core. Moreover, we show that, if large cardinals exist in V, then the stable core has inner models with a proper class of measurable limits of measurables, with a proper class of measurable limits of measurable limits of measurables, and so forth. We show this by providing a characterization of natural inner models $L[C_1, \dots , C_n]$ for specially nested class clubs $C_1, \dots , C_n$, like those arising in the stable core, generalizing recent results of Welch [29].
There has been growing interest in the vertical integration of physicians and hospitals during the past decade, as evidenced by multiple literature reviews and research investigations.1 Historically, physicians operated small firms that provided “physicians’ services” to patients who sometimes used facilities provided by separate hospital firms at which many physicians would have “privileges.” This interest in combining the two types of organizations culminated in a December 2020 issue of Health Services Research devoted to the topic that expressed surprise (and disappointment) that integration is not “a miracle cure”.2 Just months earlier, two of the major proponents of vertical integration published a study in the August issue of Health Affairs that came to a similar, “startling” conclusion: the financial integration of physicians and hospitals (e.g., via employment) had no impact on their clinical integration (and perhaps none on quality).
Consumers, public officials, and even managers of health care and insurance are unhappy about care quality, access, and costs. This book shows that is because efforts to do something about these problems often rely on hope or conjecture, not rigorous evidence of effectiveness. In this book, experts in the field separate the speculative from the proven with regard to how care is rendered, how patients can be in control, how providers should be paid, and how disparities can be reduced – and they also identify the issues for which evidence is currently missing. It provides an antidote to frustration and a clear-eyed guide for forward progress, helping health care and insurance innovators make better decisions on deciding whether to go ahead now based on current evidence, to seek and wait for additional evidence, or to move on to different ideas. It will be useful to practitioners in hospital systems, medical groups, and insurance organizations and can also be used in executive and MBA teaching.
Recent studies have shown that the low seismicity of northern Germany is characterized by fault activity caused by the decay of the Late Pleistocene (Weichselian) ice sheet. Several faults and fault systems show evidence of neotectonic activity, all of which are oriented parallel to the margin of the Pleistocene ice sheets. The timing of fault movements implies that the seismicity in northern Germany is likely induced by varying lithospheric stress conditions related to glacial isostatic adjustment, and the faults thus can be classified as glacially induced faults. For the Osning, Harz Boundary and Schaabe faults, this is supported by numerical simulation of glacial isostatic adjustment-related stress field changes. Glacial isostatic adjustment is also a likely driver for the historical and parts of the recent fault activity. Glacial isostatic adjustment is also described for the Alps, but it is difficult to clearly distinguish between reactivation of faults in the foreland of the Alps due to the Alpine collision and glacial isostatic adjustment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
Aims
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Method
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Results
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
Conclusions
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Background: For the rising number of people living with dementia, cost-effective community-based interventions to support psychosocial care are needed. The FindMyApps program helps people with dementia and their caregivers learn to use tablet computers and find user-friendly apps that facilitate self-management and engagement in meaningful activities. This definitive trial builds on previous feasibility pilot trials of FindMyApps and further evaluates cost-effectiveness.
Method: This is a protocol for a non-blinded randomized controlled trial (RCT) with two arms (intervention and usual care). 150 dyads (person with dementia and their carer) will be recruited. Participants must be resident in the community, with a diagnosis of Mild Cognitive Impairment or mild dementia (Mini Mental-State Examination 17-26, or Global Deterioration Scale 3-4. Dyads will be randomly assigned in equal proportions to receive either the FindMyApps intervention (experimental arm) or usual care (control arm). Primary outcomes measured at 3 months will be: patient self-management and social participation; caregiver sense of competence. Data will be collected through questionnaires filled in by the researcher (patient outcomes) or participants themselves (carer outcomes). In addition to a main effect analysis, a cost-effectiveness analysis will take place. In line with Medical Research Council (MRC) guidance for the evaluation of complex interventions, a process analysis will be undertaken, to identify factors that may influence trial outcomes. Semi-structured interviews and remotely collected data regarding use of the FindMyApps app will support the process analysis.
Result: Results of this study are expected in 2022. The study will be adequately powered to detect at least a moderate effect size of the intervention with respect to the primary outcomes.
Conclusion: This study will investigate the effectiveness and cost-effectiveness of the FindMyApps intervention. The results of the study will provide strong evidence to support or oppose scaling up implementation of the intervention. This is also an example of how the MRC framework for the evaluation of complex interventions can be implemented in practice. In a field which is often criticized for a lack of high quality evidence, randomized controlled trials should be applied more frequently designed for the robust and transparent evaluation of digital tools and technologies.
Several dietary factors have been extensively investigated for associations with risk of breast cancer, but to date unequivocal evidence only exists for alcohol consumption. We sought to systematically evaluate the association between 92 dietary factors and breast cancer risk using a nutrient-wide association study approach. Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression with age as the time scale and adjustment for potential confounders, was used to quantify the association between each food or nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to evaluate in the independent replication cohort, the Netherlands Cohort Study (NLCS). During a median follow-up time of 15 years, 10,979 incident invasive breast cancers were identified in the women from the EPIC study. Six foods and nutrients were associated with risk of breast cancer when controlling the FDR at 0.05. Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% confidence interval (CI) 1.03–1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03–1.06 and 1.04, 95% CI 1.02–1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94–0.98; 0.96, 95% CI 0.94–0.99; and 0.96, 95% CI 0.95–0.98, respectively). When evaluated in the NLCS (2368 invasive breast cancer cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk of breast cancer in the NLCS. Our findings confirm the well-established increased risk of breast cancer associated with alcohol consumption, and suggest that higher intake of dietary fibre, and possibly fruit and carbohydrates, might be associated with reduced breast cancer risk.