Naturalistic comparison of clomethiazole and Diazepam treatment in alcohol withdrawal: effects on oxidative stress, inflammatory cytokines and hepatic biomarkers.

Ethanol is metabolized by alcohol dehydrogenase to acetaldehyde and induces cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species that cause inflammatory liver damage. Clomethiazole, a drug approved for alcohol withdrawal treatment (AWT) in some European countries, inhibits CYP2E1. We hypothesized that clomethiazole would lead to a faster reduction in oxidative stress, inflammatory cytokines, and liver enzymes compared to diazepam treatment. We analysed respective biomarkers in 50 patients undergoing AWT and 25 healthy individuals but found no statistical difference between the two medication groups over 3-5 days. Hence, our hypothesis was not confirmed during this observation period.

Explicating the role of amygdala substructure alterations in the link between hypoleptinemia and rumination in anorexia nervosa.

OBJECTIVE: The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN-related rumination and potentially mediate the leptin-rumination relationship in AN. METHODS: Rumination (food-/weight-related) was assessed using ecological momentary assessment for a 14-day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12-29 years, majority admitted to inpatient treatment) and age-matched healthy females (n = 51) to investigate associations between rostral-medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi-level structural equation models. RESULTS: Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight-related rumination in AN; both nuclei fully mediated the effect of leptin on weight-related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females. CONCLUSION: This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.

Patterns of allergic sensitization in adults with severe asthma: the ATLAS non-interventional study.

OBJECTIVES: Severe asthma is heterogeneous, with childhood-onset asthma believed more likely to be allergic, whereas adult-onset asthma is considered typically non-allergic. However, the allergic diagnosis is typically by exclusion: if patients do not react to an allergen panel, which is not standardized and often limited to few allergens, they are considered non-allergic. The overall aim of the ATLAS study was to characterize the sensitization to allergens in severe asthma (independent of phenotype). METHODS: Single-visit, cross-sectional, non-interventional study in adults with severe asthma. Analyses were conducted for total and specific immunoglobulin E against 53 allergens, overall and in subgroups, including age at asthma onset (<20 [childhood-onset] and >40 years of age). RESULTS: Among 1010 recruited patients, 28.4% reported childhood-onset asthma and 33.6% onset >40 years of age. After excluding patients receiving omalizumab/anti-IL5 therapy, 27.6% were not sensitized to any tested allergens, whereas 19.1% were sensitized to >10 allergens. All allergens triggered sensitization in some patients. Baseline characteristics in the two onset subgroups were similar; 23.2% with childhood-onset asthma were not sensitized to any allergen, compared to 32.0% with onset >40 years of age. CONCLUSION: When a broad panel of allergens is used for sensitization testing, as many as three quarters of patients with severe asthma display sensitivity to at least one allergen, with substantial overlaps in all characteristics between the two age-at-onset subgroups. All of the tested allergens triggered a response in at least some patients, emphasizing the importance of including a broad range of allergens in any testing panel.

Immunophenotyping of Monocyte Migration Markers and Therapeutic Effects of Selenium on IL-6 and IL-1ß Cytokine Axes of Blood Mononuclear Cells in Preoperative and Postoperative Coronary Artery Disease Patients.

Multivessel coronary artery disease (CAD) is characterized by underlying chronic vascular inflammation and occlusion in the coronary arteries, where these patients undergo coronary artery bypass grafting (CABG). Since post-cardiotomy inflammation is a well known phenomenon after CABG, attenuation of this inflammation is required to reduce perioperative morbidity and mortality. In this study, we aimed to phenotype circulating frequencies and intensities of monocyte subsets and monocyte migration markers, respectively, and to investigate the plasma level of inflammatory cytokines and chemokines between preoperative and postoperative CAD patients and later, to intervene the inflammation with sodium selenite. We found a higher amplitude of inflammation, postoperatively, in terms of CCR1high monocytes and significantly increased pro-inflammatory cytokines, IL-6, IL-8, and IL-1RA. Further, in vitro intervention with selenium displayed mitigating effects on the IL-6/STAT-3 axis of mononuclear cells derived from postoperative CAD patients. In addition, in vitro selenium intervention significantly reduced IL-1ß production as well as decreased cleaved caspase-1 (p20) activity by preoperative (when stimulated) as well as postoperative CAD mononuclear cells. Though TNF-α exhibited a positive correlation with blood troponin levels in postoperative CAD patients, there was no obvious effect of selenium on the TNF-α/NF-κB axis. In conclusion, anti-inflammatory selenium might be utilized to impede systemic inflammatory cytokine axes to circumvent aggravating atherosclerosis and further damage to the autologous bypass grafts during the post-surgical period.

Sex-dependent clinical presentation, body image, and endocrine status in long-term remitted anorexia nervosa.

OBJECTIVE: Although anorexia nervosa (AN) in males has recently gained attention, knowledge of its psychological and physiological outcomes is still scarce. We explore sex-specific characteristics of long-term remitted AN with respect to residual eating disorder (ED) psychopathology, body image, and endocrinology. METHOD: We recruited 33 patients with AN in remission for at least 18 months (24 women, 9 men) and 36 matched healthy controls (HCs). Eating disorder psychopathology and body image ideals were assessed via clinical interviews, questionnaires, and an interactive 3D body morphing tool. Plasma levels of leptin, free triiodothyronine, cortisol, and sex hormones were quantified. Univariate models controlled for age and weight were used to test for the effects of diagnosis and sex. RESULTS: Both patient groups showed residual ED psychopathology but normal weight and hormone levels relative to HCs. Male remitted patients demonstrated significantly stronger muscularity-focused body image ideals, evident in interviews, self-reports, and behavioural data, than both female patients and HCs. CONCLUSIONS: Sex-specific body image characteristics in patients with remitted AN point towards the need to adjust test instruments and diagnostic criteria to male-specific psychopathology. In the future, sufficiently powered studies should evaluate the risk of men with AN developing muscle dysmorphia in the long term.

Changes in leukocytes and CRP in different stages of major depression.

BACKGROUND: We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). METHODS: We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). RESULTS: Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0-T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. CONCLUSIONS: These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.

High salt diet-induced proximal tubular phenotypic changes and sodium-glucose cotransporter-2 expression are coordinated by cold shock Y-box binding protein-1.

High salt diet (HSD) is a hallmark of blood pressure elevations, weight gain and diabetes onset in the metabolic syndrome. In kidney, compensatory mechanisms are activated to balance salt turnover and maintain homeostasis. Data on the long-term effects of HSD with respect to tubular cell functions and kidney architecture that exclude confounding indirect blood pressure effects are scarce. Additionally we focus on cold shock Y-box binding protein-1 as a tubular cell protective factor. A HSD model (4% NaCl in chow; 1% NaCl in water) was compared to normal salt diet (NSD, standard chow) over 16 months using wild type mice and an inducible conditional whole body knockout for cold shock Y-box binding protein-1 (BL6J/N, Ybx1). HSD induced no difference in blood pressure over 16 months, comparing NSD/HSD and Ybx1 wild type/knockout. Nevertheless, marked phenotypic changes were detected. Glucosuria and subnephrotic albuminuria ensued in wild type animals under HSD, which subsided in Ybx1-deficient animals. At the same time megalin receptors were upregulated. The sodium-glucose cotransporter-2 (SGLT2) was completely downregulated in wild type HSD animals that developed glucosuria. In Ybx1 knockouts, expression of AQP1 and SGLT2 was maintained under HSD; proximal tubular widening and glomerular tubularization developed. Concurrently, amino aciduria of neutral and hydrophobic amino acids was seen. In vitro translation confirmed that YB-1 translationally represses Sglt2 transcripts. Our data reveal profound effects of HSD primarily within glomeruli and proximal tubular segments. YB-1 is regulated by HSD and orchestrates HSD-dependent changes; notably, sets reabsorption thresholds for amino acids, proteins and glucose.

Lipoprotein and Metabolic Profiles Indicate Similar Cardiovascular Risk of Liver Steatosis and NASH.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) affects about 25% of the global population, with no reliable noninvasive tests to diagnose nonalcoholic steatohepatitis (NASH) and to differentiate between NASH and nonalcoholic fatty liver (NAFL) (steatosis alone). It is unclear if NAFL and NASH differ in cardiovascular risk for patients. Here, we compared obese NAFLD patients with a healthy cohort to test whether cholesterol compounds could represent potential noninvasive markers and to estimate associated risks. METHOD: Serum samples of 46 patients with histologically confirmed NAFLD (17 NAFL, 29 NASH) who underwent bariatric surgery were compared to 32 (9 males, 21 females) healthy controls (HCs). We analyzed epidemiological data, liver enzymes, cholesterol and lipid profile, and amino acids. The latter were analyzed by nuclear magnetic resonance spectroscopy. RESULTS: Total serum and high-density lipoprotein (HDL) cholesterol were significantly lower in the NAFLD group than in HCs, with a stronger reduction in NASH. Similar observations were made for sub-specification of HDL-p, HDL-s, SHDL-p, and LHDL-p cholesterols. Low-density lipoprotein (LDL)-s and LLDL-p cholesterol were significantly reduced in NAFLD groups. Interestingly, SLDL-p cholesterol was significantly higher in the NAFL group with a stronger elevation in NASH than in HCs. The amino acids alanine, leucin, and isoleucine were significantly higher in the NAFL and NASH groups than in HCs. CONCLUSION: We show in this study that cholesterol profiles, apolipoproteins, and amino acids could function as a potential noninvasive test to screen for NAFLD or even NASH in larger populations. However, few differences in cholesterol profiles were identified between the NAFL and NASH groups, indicating similar cardiovascular risk profiles.

Association of thyroid peroxidase antibodies with anti-neuronal surface antibodies in health, depression and schizophrenia - Complementary linkage with somatic symptoms of major depression.

Hashimoto's thyroiditis has been associated with major depression (MD) and schizophrenia (Sz) in epidemiological studies. However, diagnostically relevant antibodies (Abs) against thyroid peroxidase (TPO) and thyroglobulin (Tg) do not act directly on neurons. We hypothesized that an increased prevalence of anti-brain-Abs in thyroid-Ab-carriers could be linked with MD and Sz even without clinically manifest Hashimoto's thyroiditis. Serum samples from 638 acutely-ill patients with MD, Sz or matched controls were systematically screened for TPO- and Tg-Abs, other endocrine-Abs and a spectrum of specific anti-brain-Abs (directed against neuronal cell surface, synaptic, other neuronal or glial proteins). Analyses were based on indirect immunofluorescence in biochip mosaics of frozen tissue sections and transfected HEK293 cells expressing respective recombinant target antigens. Psychopathology was assessed on admission and after 6 weeks treatment by HAMD-21 (in MD) or PANSS (in Sz). Seroprevalence of TPO- and/or Tg-Abs was comparable in ill and healthy individuals (MD ~10%, Sz ~7%, controls ~9%) but thyroid-Abs were associated with neuronal cell surface/synaptic-Abs (p = 0.005), particularly in schizophrenia. Thyroid Ab-positive MD patients showed higher HAMD-21 scores (particularly somatic symptoms) at baseline (p = 0.026) and better reduction of symptoms after 6 weeks (p = 0.049) than thyroid-Ab-negative patients. This was unrelated to antidepressant drug dosage, thyroid hormonal-, inflammation- and anti-brain-Ab-status. No link with PANSS scores was observed in Sz. In conclusion, the co-occurrence of thyroid-Abs and neuronal surface/synaptic-Abs may be associated with Sz. Future cerebrospinal fluid research may be promising to clarify if thyroid-Ab-associated neuronal-Abs reach the brain in Sz patients. Thyroid-Ab-related differences regarding disease-severity and -course in MD are currently unexplained, but may be caused by un-identified anti-brain-Abs or a direct action of TPO-Abs on astrocytes.

Glucose homeostasis in major depression and schizophrenia: a comparison among drug-naïve first-episode patients.

There is evidence for insulin resistance in drug-naïve first-episode schizophrenia (Sz) patients. We have tested whether impaired insulin homeostasis is also present in first-episode patients with major depression (MD) and if this can be discerned from stress-related and medication effects. Homeostatic model assessment of insulin resistance (HOMA-IR) was determined in a cross-sectional cohort study of acute first-episode drug-naïve patients with MD (n = 18) or Sz (n = 24), and healthy controls (C, n = 43). Morning cortisol and catecholamine metabolites were assessed to control for hormonal stress axis activation. Subjects were matched for sex, age, body mass index and waist-hip ratio to exclude the possibility that overweight and visceral adiposity were potential confounding factors. HOMA-IR did not differ between MD and controls, but was increased in Sz compared to MD (p = 0.002) and controls (p = 0.012). Catecholamine metabolites were elevated in both patient groups, indicating presence of hormonal stress axis activation. However, diagnosis-related changes of HOMA-IR were independent from this. Impaired insulin sensitivity was absent in MD, but specifically related to the early disease course of Sz. Thus, considering previous studies in this field, MD may be related to impaired glucose/insulin homeostasis in the long-term but not in early disease stages.

Multiplex Immuno-MALDI-TOF MS for Targeted Quantification of Protein Biomarkers and Their Proteoforms Related to Inflammation and Renal Dysfunction.

Circulating proteins are widely used as biomarkers in clinical applications for the diagnosis, prediction, and treatment of numerous diseases. Immunoassays are the most common technologies for quantification of protein biomarkers and exist in various formats. Traditional immunoassays offer sensitive and fast analyses but cannot differentiate between proteoforms. Protein microheterogeneity, mainly due to post-translational modification, has been recognized as a fingerprint for different pathologies, and knowledge about proteoforms is an important step toward personalized medicine. Mass spectrometry (MS) has emerged to be a powerful technique for the characterization and quantification of proteoforms. We have established a novel four-plex immunoassay based on Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight (MALDI-TOF) MS for the targeted quantification of the inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and calprotectin (S100A8/9) and the kidney function marker cystatin C (CysC). Antibodies were covalently bound to superparamagnetic beads, which delivered robust and fast sample processing. Polyhistidine-tagged recombinant target proteins were used as internal standards for quantification. Our method identified a number of proteoforms for SAA ( n = 11), S100A8/9 ( n = 4) and CysC ( n = 4). The assay was characterized by low limits of detection (0.01-0.06 µg/mL) and low coefficients of variation (3.8-9.4%). Method validation demonstrated good between-assay agreement with immuno-turbidimetry ( R2 = 0.963 for CRP), ELISA ( R2 = 0.958 for SAA; R2 = 0.913 for S100A8/9), and nephelometry ( R2 = 0.963 for CysC). The low sample consumption of 20 µL and the high sample throughput of 384 samples per day make this targeted immuno-MALDI approach suited for assessment of inflammatory and renal status in large cohort studies based on precious biobanks samples.

A20 expression in dendritic cells protects mice from LPS-induced mortality.

DCs contribute to immune homeostasis under physiological conditions and regulate the immune activation during infection. The deubiquitinase A20 inhibits the activation of NF-κB-dependent immune reactions, and prevents the hyperactivation of DCs under steady-state conditions. However, the role of DC-specific A20 under pathological conditions is unknown. Here, we demonstrate that upon injection of low-dose LPS, mice with DC-specific A20 deletion (CD11c-Cre A20(fl/fl) ) died within 6 h, whereas A20(fl/fl) controls survived. LPS-induced mortality in CD11c-Cre A20(fl/fl) mice was characterized by increased serum levels of IL-2, IL-10, IL-12, IFN-γ, and TNF. Upon LPS stimulation, the activation of NF-κB and ERK-NFATc3 pathways were enhanced in A20-deficient DCs, resulting in an increased production of IL-2, IL-12, and TNF both in vitro and in vivo. Targeted inhibition of ERK in A20-deficient DCs abolished the increased production of IL-2. A20-deficient DCs failed to induce LPS tolerance, which was independent of T cells and the intestinal flora, since T-cell depletion and decolonization of CD11c-Cre A20(fl/fl) mice could not prevent death of LPS-challenged CD11c-Cre A20(fl/fl) mice. In conclusion, these findings show that DC-specific A20 preserves immune homeostasis in steady-state conditions and is also required for LPS tolerance.

Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up.

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1ß and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1ß expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1ß and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.

TIGIT signaling and its influence on T cell metabolism and immune cell function in the tumor microenvironment.

One of the key challenges for successful cancer therapy is the capacity of tumors to evade immune surveillance. Tumor immune evasion can be accomplished through the induction of T cell exhaustion via the activation of various immune checkpoint molecules. The most prominent examples of immune checkpoints are PD-1 and CTLA-4. Meanwhile, several other immune checkpoint molecules have since been identified. One of these is the T cell immunoglobulin and ITIM domain (TIGIT), which was first described in 2009. Interestingly, many studies have established a synergistic reciprocity between TIGIT and PD-1. TIGIT has also been described to interfere with the energy metabolism of T cells and thereby affect adaptive anti-tumor immunity. In this context, recent studies have reported a link between TIGIT and the hypoxia-inducible factor 1-α (HIF1-α), a master transcription factor sensing hypoxia in several tissues including tumors that among others regulates the expression of metabolically relevant genes. Furthermore, distinct cancer types were shown to inhibit glucose uptake and effector function by inducing TIGIT expression in CD8+ T cells, resulting in an impaired anti-tumor immunity. In addition, TIGIT was associated with adenosine receptor signaling in T cells and the kynurenine pathway in tumor cells, both altering the tumor microenvironment and T cell-mediated immunity against tumors. Here, we review the most recent literature on the reciprocal interaction of TIGIT and T cell metabolism and specifically how TIGIT affects anti-tumor immunity. We believe understanding this interaction may pave the way for improved immunotherapy to treat cancer.

Dynamic Amygdala Nuclei Alterations in Relation to Weight Status in Anorexia Nervosa Are Mediated by Leptin.

OBJECTIVE: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels. METHOD: T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n = 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n = 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n = 271) using linear mixed effects models. RESULTS: Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d = 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei. CONCLUSION: Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN. PLAIN LANGUAGE SUMMARY: The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weight-restoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Homologous and Heterologous Anti-COVID-19 Vaccination Does Not Induce New-Onset Formation of Autoantibodies Typically Accompanying Lupus Erythematodes, Rheumatoid Arthritis, Celiac Disease and Antiphospholipid Syndrome.

The COVID-19 pandemics has caused the death of almost six million people worldwide. In order to establish collective immunity, the first vaccines that were approved in Germany were the vector virus-based vaccine Vaxzevria and the mRNA vaccines Comirnaty and Spikevax, respectively. As it was reported that SARS-CoV-2 can trigger autoimmunity, it is of significant interest to investigate whether COVID-19 vaccines evoke the formation of autoantibodies and subsequent autoimmunity. Here, we analyzed immune responses after different vaccination regimens (mRNA/mRNA, Vector/Vector or Vector/mRNA) with respect to anti-SARS-CoV-2-specific immunity and the development of autoantibodies well known for their appearance in distinct autoimmune diseases. We found that anti-SARS-CoV-2 antibody levels were 90% lower after Vector/Vector vaccination compared to the other vaccinations and that Vector/mRNA vaccination was more effective than mRNA/mRNA vaccination in terms of IgM and IgA responses. However, until 4 months after booster vaccination we only detected increases in autoantibodies in participants with already pre-existing autoantibodies whereas vaccinees showing no autoantibody formation before vaccination did not respond with sustained autoantibody production. Taken together, our study suggests that all used COVID-19 vaccines do not significantly foster the appearance of autoantibodies commonly associated with lupus erythematodes, rheumatoid arthritis, Celiac disease and antiphospholipid-syndrome but provide immunity to SARS-CoV-2.

Testing for Thyroid Peroxidase and Antineuronal Antibodies in Depression and Schizophrenia.

Dietary interventions and physical exercise may improve some symptoms in mental illnesses such as major depression and schizophrenia. Hashimoto's thyroiditis is a known risk factor for these conditions and is marked by the presence of circulating antibodies to thyroid peroxidase (TPO) and thyroglobulin (TG). This chapter presents a protocol to determine if patients with major depression or schizophrenia contain high circulating levels of these antibodies relative to healthy controls. We also describe a procedure testing for the presence of other circulating biomarkers related to brain function, including antibodies directly related to neuronal function. This analysis was performed by screening biochip mosaics of frozen tissue sections and transfected HEK293 cells expressing target antigens using patient and control sera. Finally, we describe a correlation analysis of these markers with symptom scores at baseline and after 6 weeks treatment of the patients using antipsychotics or antidepressants as appropriate.

Hair-Based Assessment of Sex Steroid Hormones in Patients with Anorexia Nervosa.

Anorexia nervosa (AN) is a complex psychiatric disorder accompanied by a variety of endocrine effects. Altered levels of the sex steroid hormones progesterone and dehydroepiandrosterone (DHEA) have been shown to occur in patients with AN using short-term hormonal measurement methods based on blood, saliva, and urine samples. However, since sex steroid hormone levels fluctuate during the menstrual cycle, these measurement methods require a great deal of effort due to the need to collect multiple samples in order to correctly determine the basal level of sex hormones. In contrast, hair-based assessments provide a marker of accumulated longer-term hormone exposure using a single, non-invasive sample. The aim of this study was to investigate sex steroid hormone levels via hair-based assessments in acutely underweight AN in comparison with healthy, age-matched, female control participants. Additionally, we compared progesterone and DHEA hair levels longitudinally during inpatient treatment in AN. Collected hair samples were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) to determine a monthly hormone level of progesterone and DHEA. Our results indicate that DHEA hair hormone levels were similar across groups but progesterone was suppressed in underweight AN compared with healthy controls. In the longitudinal design, no significant change in hair hormone levels during partial weight restoration in patients with AN was observed. Our findings suggest that hair analysis can be used to detect suppressed progesterone levels in severe AN, and that progesterone does not increase during short-term weight restoration.

Re-Expression of Tafazzin Isoforms in TAZ-Deficient C6 Glioma Cells Restores Cardiolipin Composition but Not Proliferation Rate and Alterations in Gene Expression.

Tafazzin-an acyltransferase-is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was to investigate if specific isoforms like Δ5 can restore the wild type phenotype with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aimed to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and (Ingenuity Pathway Analyis) IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells could fully restore CL composition and-as proven for Δ5-this is naturally associated with restoration of mitochondrial respiration. A similar restoration of CL-composition could not be observed after re-expression of an enzymatically dead full-length rat TAZ (H69L; TAZMut). Re-expression of only rat full length TAZ could restore proliferation rate. Surprisingly, the Δ5 variant failed to restore wild-type proliferation. Further, as expected, re-expression of the TAZMut variant completely failed to reverse the gene expression changes, whereas re-expression of the TAZ-FL variant largely did so and the Δ5 variant to somewhat less extent. Very likely TAZ-deficiency provokes substantial long-lasting changes in cellular lipid metabolism which contribute to changes in proliferation and gene expression, and are not or only very slowly reversible.