Sulfonylureas exert antidiabetic action on adipocytes by inhibition of PPARγ serine 273 phosphorylation.

OBJECTIVE: Sulfonylureas (SUs) are still among the mostly prescribed antidiabetic drugs with an established mode of action: release of insulin from pancreatic ß-cells. In addition, effects of SUs on adipocytes by activation of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) have been described, which might explain their insulin-sensitizing potential observed in patients. However, there is a discrepancy between the impact of SUs on antidiabetic action and their rather moderate in vitro effect on PPARγ transcriptional activity. Recent studies have shown that some PPARγ ligands can improve insulin sensitivity by blocking PPARγ Ser-273 phosphorylation without having full agonist activity. It is unknown if SUs elicit their antidiabetic effects on adipocytes by inhibition of PPARγ phosphorylation. Here, we investigated if binding of SUs to PPARγ can interfere with PPARγ Ser-273 phosphorylation and determined their antidiabetic actions in vitro in primary human white adipocytes and in vivo in high-fat diet (HFD) obese mice. METHODS: Primary human white preadipocytes were differentiated in the presence of glibenclamide, glimepiride and PPARγ ligands rosiglitazone and SR1664 to compare PPARγ Ser-273 phosphorylation, glucose uptake and adipokine expression. Transcriptional activity at PPARγ was determined by luciferase assays, quantification of PPARγ Ser-273 phosphorylation was determined by Western blotting and CDK5 kinase assays. In silico modelling was performed to gain insight into the binding characteristics of SUs to PPARγ. HFD mice were administered SUs and rosiglitazone for 6 days. PPARγ Ser-273 phosphorylation in white adipose tissue (WAT), body composition, glucose tolerance, adipocyte morphology and expression levels of genes involved in PPARγ activity in WAT and brown adipose tissue (BAT) were evaluated. RESULTS: SUs inhibit phosphorylation of PPARγ at Ser-273 in primary human white adipocytes and exhibit a positive antidiabetic expression profile, which is characterized by up regulation of insulin-sensitizing and down regulation of insulin resistance-inducing adipokines. We demonstrate that SUs directly bind to PPARγ by in silico modelling and inhibit phosphorylation in kinase assays to a similar extend as rosiglitazone and SR1664. In HFD mice SUs reduce PPARγ phosphorylation in WAT and have comparable effects on gene expression to rosiglitazone. In BAT SUs increase UCP1 expression and reduce lipid droplets sizes. CONCLUSIONS: Our findings indicate that a part of SUs extra-pancreatic effects on adipocytes in vitro and in vivo is probably mediated via their interference with PPARγ phosphorylation rather than via classical agonistic activity at clinical concentrations.

The wooden artifacts from Schöningen's Spear Horizon and their place in human evolution.

Ethnographic records show that wooden tools played a pivotal role in the daily lives of hunter-gatherers including food procurement tools used in hunting (e.g., spears, throwing sticks) and gathering (e.g. digging sticks, bark peelers), as well as, domestic tools (e.g., handles, vessels). However, wood rarely survives in the archeological record, especially in Pleistocene contexts and knowledge of prehistoric hunter-gatherer lifeways is strongly biased by the survivorship of more resilient materials such as lithics and bones. Consequently, very few Paleolithic sites have produced wooden artifacts and among them, the site of Schöningen stands out due to its number and variety of wooden tools. The recovery of complete wooden spears and throwing sticks at this 300,000-y-old site (MIS 9) led to a paradigm shift in the hunter vs. scavenger debate. For the first time and almost 30 y after their discovery, this study introduces the complete wooden assemblage from Schöningen 13 II-4 known as the Spear Horizon. In total, 187 wooden artifacts could be identified from the Spear Horizon demonstrating a broad spectrum of wood-working techniques, including the splitting technique. A minimum of 20 hunting weapons is now recognized and two newly identified artifact types comprise 35 tools made on split woods, which were likely used in domestic activities. Schöningen 13 II-4 represents the largest Pleistocene wooden artifact assemblage worldwide and demonstrates the key role woodworking had in human evolution. Finally, our results considerably change the interpretation of the Pleistocene lakeshore site of Schöningen.

Neurotensin(8-13) analogs as dual NTS1 and NTS2 receptor ligands with enhanced effects on a mouse model of Parkinson's disease.

The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders.

Immobility-associated thromboprotection is conserved across mammalian species from bear to human.

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.

A Predictive Model to Identify Treatment-related Risk Factors for Odontoid Fracture Nonunion Using Machine Learning.

STUDY DESIGN: Multicenter retrospective analysis of routinely collected data. OBJECTIVE: The underlying aim of this study was to identify potential treatment-related risk factors for odontoid fracture nonunion while accounting for known patient- and injury-related risk factors. SUMMARY OF BACKGROUND DATA: Type II and III odontoid fractures represent the most common cervical spine fracture in elderly patients and are associated with a relatively high nonunion rate. The management of odontoid fractures is controversial and treatment strategies range from conservative treatment to extensive surgical stabilization and fusion. METHODS: A total of 415 individuals who sustained odontoid fracture and were treated in either of four tertiary referral centers in Austria and Germany were included in the study. We included the following potential contributing factors for fracture nonunion in cross-validated extreme gradient boosted (XGBoost) and binary logistic regression models: age, gender, fracture displacement, mechanism of injury (high vs. low energy), fracture classification (Anderson II vs. III), presence of comorbidities (Charlson comorbidity index), and treatment (conservative, anterior screw fixation with one or two screws, posterior C1/C2 spondylodesis, cervico-occipital C0-C4 fusion). RESULTS: In our cohort, 187 (45%) had radiologically confirmed odontoid nonunion six months postinjury. The odds for nonunion increase significantly with age, and are lower in type III compared to type II fractures. Also, odds for nonunion are significantly lower in posterior C1/C2 spondylodesis, and C0-C4 fusion compared to conservative treatment. Importantly, odds are not statistically significantly lower in the group treated with anterior screw fixation compared to conservative treatment. The factors gender, fracture displacement, mechanism of injury, and the presence of comorbidities did not produce significant odds. CONCLUSION: Higher age, type II fractures, and conservative treatment are the main risk factors for odontoid nonunion. Anterior screw fixation did not differ significantly from conservative treatment in terms of fracture union. LEVEL OF EVIDENCE: 3.

[A naturalistic study on the effects of antidepressants (e. g. SSRI) and acetyl salicylic acid (ASA) on the self-rated perception of the psychotherapeutic process of inpatient psychosomatic treatment and its results: Could ASA be beneficial?] / Eine naturalistische Untersuchung zur Auswirkung häufiger antidepressiver Medikationen (wie SSRI) und der Acetylsalicylsäure (ASS) auf die Selbstbeurteilungen der Wahrnehmung und des Ergebnisses stationärer Psychotherapie: Könnte ASS förderlich sein?

Objectives: Psychic perceptions are at the core of psychotherapeutic processes and modifiable by certain psychopharmacologic agents including antidepressants and cyclooxygenase (COX) inhibitors like acetylsalicylic acid (ASA). Methods: We analyzed the medical records of 208 participants, and used the weekly mean dosages and the number of weeks in therapy to predict ward experience (Stationserfahrungsbogen) and symptom burden (symptom-check list 90-R) by means of linear regression analyses and four repeated measures. Results: Time predicted symptom relief. ASA signified a more favorable ward experience and a trend towards less suffering. Antidepressants did not predict symptom burden or ward experience, except for amitriptyline's inverse relationship with process perception. Discussion: Regarding process perception and therapy outcome, amitriptyline might have unfavorable effects at dose reductions, whereas COX-inhibition could be beneficial at higher dosages. Similar findings have already been described with regard to COX-inhibition in depression and schizophrenia.

The Unhappy Shoulder: A Conceptual Review of the Psychosomatics of Shoulder Pain.

INTRODUCTION: Chronic pain is a multifaceted disorder genuinely entangled with psychic and psychosomatic symptoms, which are typically involved in the processes of chronification. The impingement syndrome of the shoulder is no exception to this rule, but several studies have shown respective peculiarities among those with pain and impingement of the shoulder. Notably, chronic pain is a lateralized experience, and, similarly, its psychosomatic correlates may be attached to the hemispheres functionally. AIM: The present review therefore gives an overview of the respective findings, with regard not only to psychopathology, but also to personality factors and psychologic trauma, since the latter are reportedly associated with chronic pain. Moreover, we acknowledge symmetry as a possible pathogenic factor. METHODS: This narrative review followed the current standards for conducting narrative studies. Based on prior findings, our research strategy included the relevance of psychotraumatologic and symmetrical aspects, as well as comorbidity. We retrieved the relevant literature reporting on the impact of psychopathology as well as personality features on shoulder pain, as published up to January 2022 from the Medline database (1966-2022). Study selecton: We included numerous studies, and considered the contextual relevance of studies referring to the neuropsychosomatics of chronic pain. RESULTS: Pain-specific fears, depression, and anxiety are important predictors of shoulder pain, and the latter is generally overrepresented in those with trauma and PTSD. Moreover, associations of shoulder pain with psychological variables are stronger as regards surgical therapies as compared to conservative ones. This may point to a specific and possibly trauma-related vulnerability for perioperative maladaptation. Additionally, functional hemispheric lateralization may explain some of those results given that limb pain is a naturally lateralized experience. Not least, psychosocial risk factors are shared between shoulder pain and its physical comorbidities (e.g., hypertension), and the incapacitated state of the shoulder is a massive threat to the function of the human body as a whole. CONCLUSIONS: This review suggests the involvement of psychosomatic and psychotraumatologic factors in shoulder impingement-related chronic pain, but the inconclusiveness and heterogeneity of the literature in the field is possibly suggestive of other determinants such as laterality.

Analysis of genotoxic N-nitrosamines in active pharmaceutical ingredients and market authorized products in low abundance by means of liquid chromatography - tandem mass spectrometry.

In 2018, high levels of the IARC class IIA carcinogen N-nitrosodimethylamine (NDMA) were analytically verified in the active pharmaceutical ingredient (API) valsartan, resulting in extensive regulatory action on angiotensin-II-receptor antagonists and recall of finished drug products by the pharmaceutical industry to ensure patient safety. The root cause of contamination was the unintended reaction of common reagents utilized during drug synthesis. This lead to serious effects on drug quality and immediate regulatory action. Thus, routine analysis of drug product contents are inevitable and necessitate thoroughly performed work up procedures of the product as well as adequate validated analytical methods. The nature of N-nitrosamines (NA), ranging from small, semi-volatile compounds up to highly polar molecules, effort sophisticated requirements in terms of instrumental analysis. Up today, gas as well as liquid chromatographic devices coupled to mass spectrometers are the most widespread systems for analysis. Gas chromatographic - mass spectrometric (GC-MS) systems, obviously superior towards liquid chromatography - mass spectrometry (LC-MS) for detecting small volatile compounds like NDMA, reach their limits for broadly designed studies including polar or acidic NA. In this study, a complementary and highly sensitive approach by means of liquid chromatography - tandem mass spectrometry (LC-MS/MS) is presented, including detection of 13 NA deduced from major classes of secondary amines. Thereby, the fully validated approach was performed in accordance to ICH and European Medicines Agency (EMA) guidelines. Quantitative proof-of-concept measurements with various APIs and market authorized tablets as representative drug formulations conclude applicability for further presumably contaminated substances. The approach employs organic or inorganic extraction steps with solid phase extraction (SPE). The limit of detection for the most prominent NA, NDMA and N-diethylnitrosamine (NDEA), were both 0.025 parts-per-billion (ppb) per matrix, respectively.

Omicron's binding to sotrovimab, casirivimab, imdevimab, CR3022, and sera from previously infected or vaccinated individuals.

SARS-CoV-2 Omicron is the first pandemic variant of concern exhibiting an abrupt accumulation of mutations particularly in the receptor-binding domain that is a critical target of vaccination induced and therapeutic antibodies. Omicron's mutations did only marginally affect the binding of ACE2, and the two antibodies Sotrovimab and CR3022 but strongly impaired the binding of Casirivimab and Imdevimab. Moreover, as compared with Wuhan, there is reduced serum reactivity and a pronounced loss of competitive surrogate virus neutralization (sVN) against Omicron in naïve vaccinees and in COVID-19 convalescents after infection and subsequent vaccination. Finally, although the booster vaccination response conferred higher titers and better sVN, the effect was nonetheless significantly lower compared with responses against Wuhan. Overall, our data suggest that the antigenicity of Omicrons receptor binding motive has largely changed but antibodies such as Sotrovimab targeting other conserved sites maintain binding and therefore hold potential in prophylaxis and treatment of Omicron-induced COVID-19.

Are Anxiety and Depression Taking Sides with Knee-Pain in Osteoarthritis?

INTRODUCTION: Total knee arthroplasty (TKA) bears a potential of rendering patients unsatisfied with the operation as a result of negative affectivity related to osteoarthritis and TKA. Not only is pain a lateralized experience, but negative affect and other psychosomatic correlates of pain might also be processed on grounds of lateralization. Lateralization in this context is likely linked to the amygdalae, which display differential left/right patterns of association with psychopathology. What is noteworthy is that osteoarthritis itself is linked not only to negative effects but also to childhood abuse. METHOD: The present study tests lateralization of psychosomatic correlates of knee-pain using the brief symptom inventory-18 (BSI-18), the dissociative experiences scale (FDS-20), the pain catastrophizing scale (PCS), the Tampa scale of kinesiophobia (TSK), the childhood trauma screener (CTS) and WOMAC. More precisely, we were interested in predicting the side of operations by means of the above-mentioned constructs using binary logistic regression, based on 150 participants (78 left knees) awaiting TKA for knee-osteoarthritis. RESULTS: Somatization (p = 0.003), childhood abuse (p = 0.04) and pain-catastrophizing (p = 0.04) predicted operations on the right side. Anxiety (p = 0.001) and kinesiophobia (p = 0.002) predicted operations on the left side. CONCLUSIONS: Knee-pain may be differentially modulated by its psychosomatic correlates as a result of lateralization and corresponding patterns of psychosomatic reagibility.

Eating disorder related research using Amazon Mechanical Turk (MTurk): Friend or foe?: Commentary on Burnette et al. (2021).

Burnette et al. reported a study that they sought to undertake to validate common eating disorder questionnaires in sexual and gender minorities. The researchers took advantage of the online recruitment platform Amazon Mechanical Turk (MTurk). Contrary to their expectations, the study proved not feasible due to invalid answering. Thus, Burnette et al. raise concerns against the trustworthiness of crowd-sourced data that may be undermined by financial interests and other kinds of motivations. Our commentary highlights the potential of the COVID-19 pandemic to inflate especially those intentions, which are monetary. Against the background of the COVID-19 pandemic, a further problem seems to be that the anonymity of online crowd sourcing platforms might tempt participants to provide inconsistent answers, possibly reflecting tendencies of reactance. The reported pattern of paradoxical responses in Burnette et al.'s work does not reflect malingering; rather we believe that the study might have served some participants as an outlet for negative emotions. We discuss mechanisms of quality control and highlight the lack of interpersonal interaction associated with online data collections.

Quantification of Degradation Products Formed during Heat Sterilization of Glucose Solutions by LC-MS/MS: Impact of Autoclaving Temperature and Duration on Degradation.

Heat sterilization of glucose solutions can lead to the formation of various glucose degradation products (GDPs) due to oxidation, hydrolysis, and dehydration. GDPs can have toxic effects after parenteral administration due to their high reactivity. In this study, the application of the F0 concept to modify specific time/temperature models during heat sterilization and their influence on the formation of GDPs in parenteral glucose solutions was investigated using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glucose solutions (10%, w/v) were autoclaved at 111 °C, 116 °C, and 121 °C for different durations. The GDPs glyoxal, methylglyoxal, glucosone, 3-deoxyglucosone/3-deoxygalactosone, 3,4-dideoxyglucosone-3-ene, and 5-hydroxymethylfurfural were quantified after derivatization with o-phenylenediamine by an optimized LC-MS/MS method. For all GDPs, the limit of detection was <0.078 µg/mL, and the limit of quantification was <0.236 µg/mL. The autoclaving time of 121 °C and 15 min resulted in the lowest levels of 3-DG/3-DGal and 5-HMF, but in the highest levels of GO and 2-KDG. The proposed LC-MS/MS method is rapid and sensitive. So far, only 5-HMF concentrations are limited by the regulatory authorities. Our results suggest reconsidering the impurity limits of various GDPs, especially the more toxic ones such as GO and MGO, by the Pharmacopoeias.

Unwillingly traumatizing: is there a psycho-traumatologic pathway from general surgery to postoperative maladaptation?

BACKGROUND: Surgery may possibly be undermined by psychologic, psychiatric and psychosomatic problems, as long as these problems interfere with a patient's capacity to cope with surgery adaptively. Recent studies have shown that interpersonal trauma, e.g. abuse or neglect, and its correlates are involved in the adaptation to surgery. This observation is heuristically coherent, given the respective traumatization is an interpersonal event occurring in a relationship. Notably, surgery inevitably leads to the violation of physical boundaries within a doctor-patient relationship. Based on the principles of psycho-traumatologic thinking, such a constellation is deemed qualified to activate posttraumatic symptoms in the traumatized. METHOD: The present topical review summarizes the respective findings which point to a subgroup of patients undergoing surgery, in whom difficulty bearing tension and confiding in others may cause adaptive problems relevant to surgery. Although this theorizing is empirically substantiated primarily with respect to total knee arthroplasty (TKA), a pubmed-research reveals psychopathologic distress to occur prior to surgery beyond TKA. Likewise, posttraumatic distress occurs in large numbers in the context of several operations, including cardiac, cancer and hernia surgery. CONCLUSION: Aspects of psychological trauma may be linked to the outcomes of general surgery, as well, e.g. biliary, hernia or appendix surgery. The mechanisms possibly involved in this process are outlined in terms of a hierarchical organization of specific anxiety and negative affect as well as in terms of psychodynamics which imply the unconscious action of psychologic defenses at their core. IMPLICATIONS: Not least, we encourage the screening for trauma and its correlates including defenses prior to general surgery in order to identify surgical candidates at risk of, e.g. chronic postoperative pain, before the operation.

Identification and quantification of glucose degradation products in heat-sterilized glucose solutions for parenteral use by thin-layer chromatography.

During heat sterilization of glucose solutions, a variety of glucose degradation products (GDPs) may be formed. GDPs can cause cytotoxic effects after parenteral administration of these solutions. The aim of the current study therefore was to develop a simple and quick high-performance thin-layer chromatography (HPTLC) method by which the major GDPs can be identified and (summarily) quantified in glucose solutions for parenteral administration. All GDPs were derivatized with o-phenylenediamine (OPD). The resulting GDP derivatives (quinoxalines) were applied to an HPTLC plate. After 20 minutes of chamber saturation with the solvent, the HPTLC plate was developed in a mixture of 1,4-dioxane-toluene-glacial acetic acid (49:49:2, v/v/v), treated with thymol-sulfuric acid spray reagent, and heated at 130°C for 10 minutes. Finally, the GDPs were quantified by using a TLC scanner. For validation, the identities of the quinoxaline derivatives were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glyoxal (GO)/methylglyoxal (MGO) and 3-deoxyglucosone (3-DG)/3-deoxygalactosone (3-DGal) could be identified and quantified in pairs, glucosone (2-KDG), 5-hydroxymethylfurfural (5-HMF), and 3,4-dideoxyglucosone-3-ene (3,4-DGE) each individually. For 2-KDG, the linearity of the method was demonstrated in the range of 1-50 µg/mL, for 5-HMF and 3,4-DGE 1-75 µg/mL, for GO/MGO 2-150 µg/mL, and for 3-DG/3-DGal 10-150 µg/mL. All GDPs achieved a limit of detection (LOD) of 2 µg/mL or less and a limit of quantification (LOQ) of 10 µg/mL or less. R2 was 0.982 for 3.4-DGE, 0.997 for 5-HMF, and 0.999 for 2-KDG, 3-DG/3-DGal, and GO/MGO. The intraday precision was between 0.4 and 14.2% and the accuracy, reported as % recovery, between 86.4 and 112.7%. The proposed HPTLC method appears to be an inexpensive, fast, and sufficiently sensitive approach for routine quantitative analysis of GDPs in heat-sterilized glucose solutions.

[Postoperative Dissociation after Knee Replacement and its Influence on the Course of Pain]. / Postoperative Dissoziation nach Totalem Kniegelenkersatz und ihr Einfluss auf den Schmerzverlauf.

OBJECTIVE: Even after successful knee replacement, one in 5 patients complains of chronic pain. Previous studies suggest that surgical interventions trigger postoperative traumatic stress in some patients. The aim of this explorative study is to investigate whether postoperative dissociation occurs as a manifestation of postoperative traumatic stress after total knee replacement. In addition, it should be investigated whether these patients have more chronic postoperative pain 1 year postoperatively and to what extent the course of pain differs from the other patients. METHODS: 201 Patients who underwent primary knee TEP were studied. They answered questionnaires on knee pain (WOMAC) and dissociation (FDS-20) at 3 measurement points: 1 day preoperatively (T1), 10 weeks postoperatively (T2) and 1 year postoperatively (T3). RESULTS: Data from 145 patients could be analyzed. The incidence for postoperative dissociation is 8.3%. Not only do patients with postoperative dissociation report more chronic postoperative pain after 1 year (p=0,016), but also their postoperative pain levels decreases less than in the patients without postoperative dissociation (p=0,025). DISCUSSION: The findings provide evidence that postoperative dissociation occurs as a manifestation of postoperative traumatic stress after total knee replacement. Even if dissociation seems to be a defense mechanism for the regulation of overstraining affects in the short term, it is associated with more chronic postoperative pain in the long term. Furthermore, the patients with postoperative dissociation benefit less in a 1-year follow-up from total knee replacement in terms of pain reduction. CONCLUSION: Strategies to reduce dissociation could lead to better results after knee TEP implementation and should be investigated in future intervention studies.

A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization.

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels. METHODS: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated. RESULTS: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum. CONCLUSIONS: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.

Emotion processing and regulation in major depressive disorder: A 7T resting-state fMRI study.

Dysfunctions in bottom-up emotion processing (EP), as well as top-down emotion regulation (ER) are prominent features in pathophysiology of major depressive disorder (MDD). Nonetheless, it is not clear whether EP- and ER-related areas are regionally and/or connectively disturbed in MDD. In addition, it is yet to be known how EP- and ER-related areas are interactively linked to regulatory behavior, and whether this interaction is disrupted in MDD. In our study, regional amplitude of low frequency fluctuations (ALFF) and whole-brain functional connectivity (FC) of meta-analytic-driven EP- and ER-related areas were compared between 32 healthy controls (HC) and 20 MDD patients. Then, we aimed to investigate whether the EP-related areas can predict the ER-related areas and regulatory behavior in both groups. Finally, the brain-behavior correlations between the EP- and ER-related areas and depression severity were assessed. We found that: (a) affective areas are regionally and/or connectively disturbed in MDD; (b) EP-ER interaction seems to be disrupted in MDD; overburden of emotional reactivity in amygdala may inversely affect cognitive control processes in prefrontal cortices, which leads to diminished regulatory actions. (c) Depression severity is correlated with FC of affective areas. Our findings shed new lights on the neural underpinning of affective dysfunctions in depression.

Local glutamate in cingulate cortex subregions differentially correlates with affective network activations during face perception.

The cingulate cortex is involved in emotion recognition/perception and regulation. Rostral and caudal subregions belong to different brain networks with distinct roles in affective perception. Despite recent accounts of the relevance of cingulate cortex glutamate (Glu) on blood-oxygen-level-dependent (BOLD) responses, the specificity of the subregional Glu levels during emotional tasks remains unclear. Seventy-two healthy participants (age = 27.33 ± 6.67, 32 women) performed an affective face-matching task and underwent magnetic resonance spectroscopy (MRS) at 7 Tesla. Correlations between the BOLD response during emotion perception and Glu concentration in the pregenual anterior cingulate cortex (pgACC) and anterior midcingulate cortex (aMCC) were compared on a whole-brain level. Post hoc specificity of the association with an affect was assessed. Lower Glu in the pgACC correlated with stronger activation differences between negative and positive faces in the left inferior and superior frontal gyrus (L IFG and L SFG). In contrast, lower Glu in the aMCC correlated with BOLD contrasts in the posterior cingulate cortex (PCC). Furthermore, negative face detection was associated with prolonged response time (RT). Our results demonstrate a subregion-specific involvement of cingulate cortex Glu in interindividual differences during viewing of affective facial expressions. Glu levels in the pgACC were correlated with frontal area brain activations, whereas Glu in the salience network component aMCC modulated responses in the PCC-precuneus. We show that region-specific metabolite mapping enables specific activation of different BOLD signals in the brain underlying emotional perception.

The Pain Paradox of Borderline Personality and Total Knee Arthroplasty (TKA): Recruiting Borderline Personality Organization to Predict the One-Year Postoperative Outcome.

BACKGROUND: TKA is a common treatment for arthropathies of the knee; however, its results are compromised by psychosocial equivalents of pain: prior research suggests persistent pain and dysfunction after TKA not only to be linked to psychological symptoms such as depression or anxiety but also to psychodynamic determinants of borderline personality, namely borderline personality organization. Osteoarthritis (OA) and Rheumatoid arthritis (RA), the main indications for TKA, are themselves linked to personality factors and disorders, e.g. borderline. The present study investigates the influence of borderline personality organization (BPO) on the outcomes of TKA one year postoperatively. METHODS: We studied 144 patients scheduled for primary TKA before and after the operation using the IPO-16 and the WOMAC for the assessment of knee pain and function. RESULTS: Non-parametric correlations were found between primitive defenses and knee-pain, not function. Linear regression showed prediction of knee pain and knee function by the preoperative WOMAC scores (p<0.01), whereas there was additional prediction of knee-pain by gender (p=0.03) and primitive defenses (p=0.04). DISCUSSION: The results suggest a psychodynamic mechanism of maladaptation after TKA apparently representing the bodily manifestations of fundamental psychic defenses.

Carbon-fibre-reinforced PEEK: An alternative material for flexion bushings of rotating hinged knee joints?

BACKGROUND: For prosthetic knee joints of the hinged type, typically polyethylene (PE) flexion bushings are used between axis and femoral component to prevent metallic wear. Nevertheless, PE-wear can lead to periprosthetic osteolysis followed by aseptic loosening of the implant. Based on high creep and wear resistance carbon-fibre-reinforced polyether ether ketones (CFR-PEEKs) could provide an alternative material to ultra-high-molecular-weight polyethylene (UHMWPE) for this bearing type. METHODS: Flexion bushings of four different materials were investigated (CFR-PEEK pitch fibres, CFR-PEEK PAN fibres, virgin PEEK without carbon fibres and UHMWPE) using a bushing tester. For determination of the polymeric and metallic wear, gravimetric measurements and particle analyses were performed. RESULTS: The polymeric wear rates of CFR-PEEK PAN (6.657 ±â€¯0.714 mg/106 cycles) and CFR-PEEK pitch (32.085 ±â€¯2.748 mg/106 cycles) were significantly higher compared to the polymeric wear rates of virgin PEEK (0.764 ±â€¯0.283 mg/106 cycles) or UHMWPE (-0.015 ±â€¯0.011 mg/106 cycles) (p < .001). In addition, the metallic wear rates were significantly higher when using bushings made of CFR-PEEK PAN (3.373 ±â€¯0.214 mg/106 cycles) and CFR-PEEK pitch (3.604 ±â€¯0.355 mg/106 cycles), than when using bushings made of virgin PEEK (0.177 ±â€¯0.049 mg/106 cycles) or UHMWPE (0.031 ±â€¯0.011 mg/106 cycles) (p < .001). The mean particle size of the two CFR-PEEK groups was significantly smaller compared to the virgin PEEK and UHMWPE group (p < .001). CONCLUSION: According to these results, the clinical use of CFR-PEEK in combination with CoCr could lead to higher wear rates and this should be avoided. Virgin PEEK may still be considered as an alternative to UHMWPE to use it for flexion bushings in a hinged knee joint.