Kupffer cells dictate hepatic responses to the atherogenic dyslipidemic insult.

Apolipoprotein-B (APOB)-containing lipoproteins cause atherosclerosis. Whether the vasculature is the initially responding site or if atherogenic dyslipidemia affects other organs simultaneously is unknown. Here we show that the liver responds to a dyslipidemic insult based on inducible models of familial hypercholesterolemia and APOB tracing.

Early prediction of spontaneous preterm birth before 34 gestational weeks based on a combination of inflammation-associated plasma proteins.

Background: In order to identify and possibly offer prophylactic treatment to women at risk for preterm birth (PTB), novel prediction models for PTB are needed. Our objective was to utilize high-sensitive plasma protein profiling to investigate whether early prediction of spontaneous PTB (sPTB) before 34 gestational weeks (gw) was possible in a low-risk population.

Methods: A case-control study was conducted on 46 women with sPTB before 34 gw and 46 women with normal pregnancies and term deliveries.

Chemokine and cytokine profiles in preterm and term labor, in preterm prelabor rupture of the membranes, and in normal pregnancy.

The objective of this study was to investigate the immune mechanisms involved in preterm labor (PTL), preterm prelabor rupture of the membranes (PPROM), and normal pregnancies. The second objective was to explore immune profiles in PTL for association with early ( < 34 gestational weeks (gw)) or instant ( < 48 h) delivery. This prospective observational multi-center study included women with singleton pregnancies with PTL (n = 80) or PPROM (n = 40) before 34 gw, women with normal pregnancies scheduled for antenatal visits (n = 44), and women with normal pregnancies in active labor at term (n = 40).

TAILR (Nursing-Sensitive Events and Their Association With Individual Nurse Staffing Levels) Project: Protocol for an International Longitudinal Multicenter Study.

Background: Nursing-sensitive events (NSEs) are common, accounting for up to 77% of adverse events in hospitalized patients (eg, fall-related harm, pressure ulcers, and health care-associated infections). NSEs lead to adverse patient outcomes and impose an economic burden on hospitals due to increased medical costs through a prolonged hospital stay and additional medical procedures. To reduce NSEs and ensure high-quality nursing care, appropriate nurse staffing levels are needed.

Proteomics reveal biomarkers for diagnosis, disease activity and long-term disability outcomes in multiple sclerosis.

Sensitive and reliable protein biomarkers are needed to predict disease trajectory and personalize treatment strategies for multiple sclerosis (MS). Here, we use the highly sensitive proximity-extension assay combined with next-generation sequencing (Olink Explore) to quantify 1463 proteins in cerebrospinal fluid (CSF) and plasma from 143 people with early-stage MS and 43 healthy controls. With longitudinally followed discovery and replication cohorts, we identify CSF proteins that consistently predicted both short- and long-term disease progression.

No Baby to Bring Home: Perinatal Loss, Infertility, and Mental Illness-Overview and Recommendations for Care.

Purpose Of Review: Update readers on the state of the research on mental health, perinatal loss, and infertility with a focus on providing a comprehensive overview to empower clinicians in treating this population.

Recent Findings: Rates of psychiatric illness are increased in people that experience perinatal loss and infertility. The research remains largely below the clear need for focused screening, prevention, and treatment.

Genome-wide DNA Methylation Profiling in Lyme Neuroborreliosis Reveals Altered Methylation Patterns of HLA Genes.

Lyme neuroborreliosis (LNB) is a complex neuroinflammatory disorder caused by Borrelia burgdorferi, which is transmitted through tick bites. Epigenetic alterations, specifically DNA methylation (DNAm), could play a role in the host immune response during infection. In this study, we present the first genome-wide analysis of DNAm in peripheral blood mononuclear cells from patients with LNB and those without LNB.

Different Psychological Processes in Traditional and ACT-Enhanced ERP for Obsessive-Compulsive Disorder.

Acceptance and commitment therapy (ACT) has been shown to promote willingness to experience intrusive thoughts among individuals with obsessive-compulsive disorder (OCD). Exposure with response prevention (ERP) delivered from an ACT framework (i.e.

The contribution of guilt sensitivity in the prediction of obsessive-compulsive disorder symptom dimensions: Replication and extension.

Background: Obsessive-compulsive disorder (OCD) is associated with particular cognitive processes, such as beliefs about the importance of intrusive thoughts. The present study examined the explanatory power of guilt sensitivity to OCD symptom dimensions after controlling for well-established cognitive predictors.

Methods: 164 patients with OCD completed self-reported measures of OCD and depressive symptoms, obsessive beliefs, and guilt sensitivity.

Situating reproductive coercion in the sociocultural context: An ecological model to inform research, practice, and policy in the United States.

Reproductive coercion (RC) can be conceptualized as any behavior that limits one's ability to make decisions about their reproductive health. Here, we broaden this definition to consider the impact of systemic and sociocultural factors on RC using an ecological model. Specifically, we use Bronfenbrenner's model as a framework for organizing the multilevel factors that influence reproductive coercion (RC) and its impacts on individual health.

Psychological distress and treatment preferences among parents amidst the COVID-19 pandemic.

The COVID-19 pandemic has presented many stressors for parents. This study was conducted to examine treatment preferences and barriers to care amidst COVID-19. Parents ( ​= ​95) completed self-report measures.

Cognitive behavioral therapy (CBT) plus attention bias modification (ABM) reduces anxiety sensitivity and depressive symptoms in panic disorder: A pilot randomized trial.

Background: Cognitive bias theories propose that reducing threat hypervigilance in mental disorders can augment cognitive behavioral therapy (CBT) outcomes. However, no studies have tested whether adding attention bias modification (ABM) can effectively enhance CBT's effects on anxiety sensitivity (AS), electromyography (EMG), and skin conductance (SC) for panic disorder (PD). This pilot randomized controlled trial (RCT) thus aimed to evaluate the efficacy of CBT + ABM (vs.

Efficacy of Virtual Care for Depressive Disorders: Systematic Review and Meta-analysis.

Background: The COVID-19 pandemic has created an epidemic of distress-related mental disorders such as depression, while simultaneously necessitating a shift to virtual domains of mental health care; yet, the evidence to support the use of virtual interventions is unclear.

Objective: The purpose of this study was to evaluate the efficacy of virtual interventions for depressive disorders by addressing three key questions: (1) Does virtual intervention provide better outcomes than no treatment or other control conditions (ie, waitlist, treatment as usual [TAU], or attention control)? (2) Does in-person intervention provide better outcomes than virtual intervention? (3) Does one type of virtual intervention provide better outcomes than another?

Methods: We searched the PubMed, EMBASE, and PsycINFO databases for trials published from January 1, 2010, to October 30, 2021. We included randomized controlled trials of adults with depressive disorders that tested a virtual intervention and used a validated depression measure.

Prediction of Human Clinical Pharmacokinetics with ANDROMEDA by Prosilico: Predictions for an Established Benchmarking Data Set, a Modern Small Drug Data Set, and a Comparison with Laboratory Methods.

There is an ongoing aim to replace animal and laboratory models with methods. Such replacement requires the successful validation and comparably good performance of the alternative methods. We have developed an prediction system for human clinical pharmacokinetics, based on machine learning, conformal prediction and a new physiologically-based pharmacokinetic model, i.

RNA-sequencing and mass-spectrometry proteomic time-series analysis of T-cell differentiation identified multiple splice variants models that predicted validated protein biomarkers in inflammatory diseases.

Profiling of mRNA expression is an important method to identify biomarkers but complicated by limited correlations between mRNA expression and protein abundance. We hypothesised that these correlations could be improved by mathematical models based on measuring splice variants and time delay in protein translation. We characterised time-series of primary human naïve CD4 T cells during early T helper type 1 differentiation with RNA-sequencing and mass-spectrometry proteomics.

Co-occurring depression and obsessive-compulsive disorder: A dimensional network approach.

Background: Depressive and obsessive-compulsive (OCD) symptoms often co-occur and a number of possible explanations for this co-occurrence have been explored, including shared biological and psychosocial risk factors. Network approaches have offered a novel hypothesis for the link between depression and OCD: functional inter-relationships across the symptoms of these conditions. The few network studies in this area have relied largely on item, rather than process-level constructs, and have not examined relationships dimensionally.

Plasma protein profiling reveals dynamic immunomodulatory changes in multiple sclerosis patients during pregnancy.

Multiple sclerosis (MS) is a chronic autoimmune neuroinflammatory and neurodegenerative disorder of the central nervous system. Pregnancy represents a natural modulation of the disease course, where the relapse rate decreases, especially in the 3 trimester, followed by a transient exacerbation after delivery. Although the exact mechanisms behind the pregnancy-induced modulation are yet to be deciphered, it is likely that the immune tolerance established during pregnancy is involved.

The Impact of Reference Data Selection for the Prediction Accuracy of Intrinsic Hepatic Metabolic Clearance.

In vitro-in vivo prediction results for hepatic metabolic clearance (CL) and intrinsic CL (CL) vary widely among studies. Reasons are not fully investigated and understood. The possibility to select favorable reference data for in vivo CL and CL and unbound fraction in plasma (f) is among possible explanations.

In Silico Predictions of the Gastrointestinal Uptake of Macrocycles in Man Using Conformal Prediction Methodology.

The gastrointestinal uptake of macrocyclic compounds is not fully understood. Here we applied our previously validated integrated system based on machine learning and conformal prediction to predict the passive fraction absorbed (f), maximum fraction dissolved (f), substrate specificities for major efflux transporters and total fraction absorbed (f) for a selected set of designed macrocyclic compounds (n = 37; MW 407-889 g/mol) and macrocyclic drugs (n = 16; MW 734-1203 g/mole) in vivo in man. Major aims were to increase the understanding of oral absorption of macrocycles and further validate our methodology.

Inhibition of IL17A Using an Affibody Molecule Attenuates Inflammation in ApoE-Deficient Mice.

The balance between pro- and anti-inflammatory cytokines released by immune and non-immune cells plays a decisive role in the progression of atherosclerosis. Interleukin (IL)-17A has been shown to accelerate atherosclerosis. In this study, we investigated the effect on pro-inflammatory mediators and atherosclerosis development of an Affibody molecule that targets IL17A.

predictions of the human pharmacokinetics/toxicokinetics of 65 chemicals from various classes using conformal prediction methodology.

Pharmacokinetic/toxicokinetic (PK/TK) information for chemicals in humans is generally lacking. Here we applied machine learning, conformal prediction and a new physiologically-based PK/TK model for prediction of the human PK/TK of 65 chemicals from different classes, including carcinogens, food constituents and preservatives, vitamins, sweeteners, dyes and colours, pesticides, alternative medicines, flame retardants, psychoactive drugs, dioxins, poisons, UV-absorbents, surfactants, solvents and cosmetics.About 80% of the main human PK/TK (fraction absorbed, oral bioavailability, half-life, unbound fraction in plasma, clearance, volume of distribution, fraction excreted) for the selected chemicals was missing in the literature.

Progesterone Inhibits the Establishment of Activation-Associated Chromatin During T1 Differentiation.

T1-mediated diseases such as multiple sclerosis (MS) and rheumatoid arthritis (RA) improve during pregnancy, coinciding with increasing levels of the pregnancy hormone progesterone (P4), highlighting P4 as a potential mediator of this immunomodulation. Here, we performed detailed characterization of how P4 affects the chromatin and transcriptomic landscape during early human T1 differentiation, utilizing both ATAC-seq and RNA-seq. Time series analysis of the earlier events (0.

prediction of volume of distribution of drugs in man using conformal prediction performs on par with animal data-based models.

Volume of distribution at steady state (V) is an important pharmacokinetic endpoint. In this study we apply machine learning and conformal prediction for human V prediction, and make a head-to-head comparison with rat-to-man scaling, allometric scaling and the Rodgers-Lukova method on combined and data, using a test set of 105 compounds with experimentally observed V.The mean prediction error and % with <2-fold prediction error for our method were 2.