Cologne questionnaire on speechlessness: Development and validation.

Speechlessness forms a psychological concept that describes non-speaking or silence in different situations. Speechlessness occurs in particular during emotional stress. The Cologne Questionnaire on Speechlessness (ger.: Kölner Fragebogen zur Sprachlosigkeit) is an instrument for measuring speechlessness as a function of emotional perception and processing in situations of emotional stress or existing emotional dysregulation. The questionnaire was developed in theoretical proximity to the constructs of alexithymia and expressive suppression. Item selection was performed on a first line sample of N = 307 individuals of a normal population. Acquisition of an exploratory model to classify the phenomenon was conducted within four samples in clinical and non-clinical settings. Validation of the factorial structure was performed using an overarching dataset (N = 1293) consisting of all samples. The results of a confirmatory factor analysis (CFA) indicated the best model fit (χ2 (df, 146) = 953.856; p < .001; Tucker-Lewis-Index = .891; Comparative Fit Index = .916; Root Mean Square Error of Approximation = .065; p < .001; N = 1293) with a four-factorial structure of the questionnaire. Both the overall acceptable validity and reliability recommend the application of KFS on individuals of the normal population as well as clinical subgroups. In addition, the questionnaire can also be used in the context of research on the regulation of emotions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04102-x.

[Common foundation of alexithymia and expressive suppression]. / Gemeinsame Grundlage von Alexithymie und expressiver Suppression: Ergebnisse einer empirischen Studie.

BACKGROUND: International studies could already prove a correlation between alexithymia and expressive suppression. This relationship has only been marginally considered in the German literature so far. The prioritized aim of the present study was to investigate a correlative and factorial relationship between alexithymia and expressive suppression. MATERIAL AND METHODS: A total of 317 persons participated in an online survey. Data on alexithymia and expressive suppression were collected using the German versions of the Toronto alexithymia scale (TAS-26) and the emotion regulation questionnaire (ERQ). RESULTS: The results showed highly significant correlations between the TAS-26 subscale "difficulty in identifying feelings" and the ERQ scale "suppression" (r = 0.5; p < 0.001) and between the TAS-26 subscale "difficulty in describing feelings" and the ERQ scale "suppression" (r = 0.64; p < 0.001). The results of an exploratory factor analysis revealed a two-factor solution with common factor for the TAS-26 subscales "difficulty in identifying feelings" and "difficulty in describing feelings" and the ERQ scale "suppression" with a common variance of 38.2% (χ2 = 363.843, p < 0.001, Kaiser-Meyer-Olkin, KMO, value = 0.699). CONCLUSION: The results indicate that the TAS-26 scales in the components "difficulty in identifying feelings" and "difficulty in describing feelings" and the ERQ scale "suppression" in the component of "expressive suppression" have a common construct, which is referred to with the term speechlessness.

The role of receptor MAS in microglia-driven retinal vascular development.

OBJECTIVE: The receptor MAS, encoded by Mas1, is expressed in microglia and its activation has been linked to anti-inflammatory actions. However, microglia are involved in several different processes in the central nervous system, including the promotion of angiogenesis. We therefore hypothesized that the receptor MAS also plays a role in angiogenesis via microglia. APPROACH AND RESULTS: To assess the role of MAS on vascular network development, flat-mounted retinas from 3-day-old wild-type (WT) and Mas1-/- mice were subjected to Isolectin B4 staining. The progression of the vascular front was reduced (- 24%, p < 0.0001) and vascular density decreased (- 38%, p < 0.001) in Mas1-/- compared to WT mice with no change in the junction density. The number of filopodia and filopodia bursts were decreased in Mas1-/- mice at the vascular front (- 21%, p < 0.05; - 29%, p < 0.0001, respectively). This was associated with a decreased number of vascular loops and decreased microglial density at the vascular front in Mas1-/- mice (-32%, p < 0.001; - 26%, p < 0.05, respectively). As the front of the developing vasculature is characterized by reduced oxygen levels, we determined the expression of Mas1 following hypoxia in primary microglia from 3-day-old WT mice. Hypoxia induced a 14-fold increase of Mas1 mRNA expression (p < 0.01). Moreover, stimulation of primary microglia with a MAS agonist induced expression of Notch1 (+ 57%, p < 0.05), Dll4 (+ 220%, p < 0.001) and Jag1 (+ 137%, p < 0.001), genes previously described to mediate microglia/endothelial cell interaction during angiogenesis. CONCLUSIONS: Our study demonstrates that the activation of MAS is important for microglia recruitment and vascular growth in the developing retina.

An accident at work? Traumatic lesions in the skeleton of a 4th millennium BCE "wagon driver" from Sharakhalsun, Russia.

The study of ante-mortem trauma is a popular and important aspect of palaeopathological analysis. The majority of publications focus on a particular assemblage, skeletal element or type of fracture, with case studies of single individuals with multiple/unusual traumata being much rarer in the literature. This paper presents the case of an adult male from the Bronze Age site of Sharakhalsun, Russia, buried, uniquely, in a sitting position on a fully assembled wagon, who displayed evidence for multiple healed ante-mortem fractures of the cranium, axial and appendicular skeleton. The mechanisms and likely etiologies of the fractures are presented, with reference to modern and 19th century clinical literature, and possible interpretations suggested: that the individual was involved in a severe accident involving a wagon or draft animals, or both, a number of years before his death. The suggestion is also made that the unique burial position of the individual was a form of commemoration by the community of the survival and recovery of the individual from such a serious incident.

Urine of patients with acute kidney transplant rejection show high normetanephrine and decreased 2-hydroxyestrogens concentrations.

BACKGROUND: A shift from anti- to proinflammatory steroid hormones has been observed in chronic inflammation. We tested the hypothesis that this shift occurs also in kidney transplant rejection together with a rise of urinary catecholamine degradation product concentrations as a consequence of locally produced cytokines, thus further promoting rejection. METHODS: We examined 8 patients with an early rejection episode in the protocol biopsy ∼2 weeks, 9 with biopsy-proven rejection at 2-3 months, and 18 without rejection, both at 2 weeks and 3 months after transplantation. Metanephrine, normetanephrine, and 2- and 16-hydroxyestrogens concentrations were measured by EIA. RESULTS: The median urinary concentrations of normetanephrine, but not metanephrine, were significantly higher in acute kidney transplant rejection in the first 2 weeks after transplantation (P < .05). During acute kidney transplant rejection at 2-3 months, but not in the first 2 weeks, after transplantation, 2-, but not 16-hydroxyestrogens, concentrations were significantly decreased (P < .05). CONCLUSIONS: We demonstrated that the downstream product of noradrenaline conversion normetanephrine was elevated in kidney transplant rejection in the first weeks after transplantation. This change may promote rejection together with an important proinflammatory and mitogenic steroid hormone shift, which becomes increasingly relevant over time.

FOXP3+ regulatory T-cells in renal allografts: correlation with long-term graft function and acute rejection.

BACKGROUND: The interpretation of a cellular infiltrate as cytotoxic or tolerogen represents an unsolved challenge in current transplantation. The so-called regulatory CD4+ CD25+ T-cells which express the FOXP3 gene have received increasing interest with respect to this question. The existing studies concerning the role of FOXP3+ Tregs for transplant tolerance yielded contradictory results. METHODS: We examined the numbers of the FOXP3+ Tregs in two groups of renal allograft biopsies both showing cellular infiltration, but either without (n=29) or with signs of acute cellular rejection (n=26), by means of immunofluorescence and correlated the amount of FOXP3+ Tregs to renal function at the time of biopsy and after 1 and 2 years of follow up. RESULTS: The number of FOXP3+ Tregs within infiltrates in non-rejecting biopsies did not correlate with renal function after 1 and 2 years. There were no significant differences in the numbers of FOXP3+ Tregs between biopsies with or without borderline infiltrates. Increased numbers of FOXP3+ Tregs were not associated with an ameliorated severity of graft rejection and did not correlate with outcome after the rejection episode and renal function after 1 and 2 years. CONCLUSIONS: The identification of the FOXP3+ regulatory cells within the allograft cannot be considered as an appropriate marker for the interpretation of infiltrates as cytotoxic or tolerogenic or as a prognostic marker for later transplant function.

Renin, endothelial NO synthase and endothelin gene expression in the 2kidney-1clip Goldblatt model of long-term renovascular hypertension.

OBJECTIVE: Numerous reports have shown the influence of renin, nitric oxide (NO) and the endothelin (ET) systems for regulation of blood pressure and renal function. Furthermore, interactions between these peptides have been reported. Aim of our study was to investigate the relative contribution of these compounds in long-term renovascular hypertension / renal ischemia. METHODS: Hypertension / left-sided renal ischemia was induced using the 2K1C-Goldblatt rat model. Renal renin, ET-1, ET-3 and endothelial NO synthase (eNOS) gene expression was measured by means of RNAse protection assay at different timepoints up to 10 weeks after induction of renal artery stenosis. RESULTS: Plasma renin activity and renal renin gene expression in the left kidney were increased in the clipped animals while eNOS expression was unchanged. Furthermore, an increase in ET-1 expression and a decrease of ET-3 expression was detected in early stenosis. CONCLUSIONS: While renin is obviously involved in regulation of blood pressure and renal function in unilateral renal artery stenosis, ET-1, ET-3 and endothelium derived NO do not appear to play an important role in renal adaptation processes in long-term renal artery stenosis, although ET-1 and ET-3 might be involved in short-term adaptation processes.

[Brugada syndrome]. / Das Brugada-Syndrom.

BACKGROUND: A high take-off descending ST segment associated with right bundle branch block is the typical ECG criterion of the Brugada-Brugada syndrome. It leads to ventricular fibrillation or syncopes in case of a familiar disposition. CASE REPORT: We describe a 56-year-old man in whom oral prajmalium bitartrate therapy previously prescribed for symptomatic ventricular extrasystoles unmasked an electrographic pattern characteristic of a Brugada syndrome. After the ongoing invasive diagnostic a right ventricular dysplasia in the same case is possible. The patient was treated with an ICD pacemaker.

FTY 720A mediates reduction of lymphocyte counts in human renal allograft recipients by an apoptosis-independent mechanism.

The novel immunosuppressive compound FTY 720A posseses a mode of action which is different from all other immunosuppressive drugs. The most prominent feature is a reversible decrease in peripheral lymphocyte counts observed in animal experiments. We investigated in the first human trial (phase 1) whether FTY 720A induces apoptosis of peripheral blood mononuclear cells (PBMC) in stable renal allograft recipients. Monitoring of lymphocyte counts revealed a significant and dose-dependent decrease within 6 h post-FTY 720A dose: placebo 5.1%; 0.25 mg 36.4%; 0.5 mg 40.8%; 0.75 mg 39.4%; 1 mg 45.8%; 2 mg 67.2%; 3.5 mg 64.9%. PBMC apoptosis rates did not change, as determined before intake of FTY 720A and 2 h, 6 h, 24 h and 96 h post-FTY 720A dose. We detected no significant difference in apoptosis rates between patients who received placebo or FTY 720A. However, in vitro experiments showed that high concentrations of FTY 720 A induced apoptosis in human PBMC.

Effectiveness in learning complex problem solving and salivary ion indices of psychological stress and activation.

Following Hinton et al. (1992, Biol. Psychol. 33, 63-71) and Richter et al. (1995, Biol. Psychol. 39, 131-142) ionic concentration of [K+] in unstimulated saliva was predicted to rise with perceived challenge, while lowered [Na+] was expected when experiencing psychological stress (PS). Subjects had to learn an engaging complex problem-solving 'game', via positive and negative feed-back on three 'games' lasting 2.5-3.0 h overall. Comparisons were made between three groups: (1) high success; (2) partial success ('strugglers'); and (3) total failure to learn. Saliva was sampled after resting and after each of three 'games'. Successful learners had a significant rise in [K+] on the first 'game' followed by a significant fall, consistent with task-challenge reaction followed by fast autonomic adaptation with successful learning. The 'strugglers' [Na+] fell significantly over the 'games', indicating mineralocorticoid-induced PS response of Na+ reabsorption. The 'total failure' subjects had generally significantly higher [K+] than the successful ones, showing raised tonic sympathetic relative to parasympathetic activity--this outcome being interpreted from interference theories. The 'failures' also had significantly higher tonic [Na+] on 'games'--indicating low PS as predicted from McGrath's (1976) theory.

[Clinical diagnosis and neuropathologic examination findings in 20 AIDS patients]. / Klinische Diagnose und neuropathologischer Untersuchungsbefund bei 20 AIDS-Patienten.

Disorders of the central nervous system (CNS) associated with HIV infections are becoming increasingly important in the area of clinical diagnosis and treatment of patients with AIDS. The aim of this retrospective analysis of 20 patients with AIDS who died in 1989 was to compare clinical diagnosis, neuroradiological findings and treatment with the results of neuropathological studies. The neuropathological examinations revealed primary CNS lymphoma (high-grade non-Hodgkin's lymphoma) in seven cases, cerebral toxoplasmosis in four cases, haemorrhagic infarction in three cases, cerebral cryptococcosis in three cases, and one case each of infiltration of the dura by a peripheral Burkitt's lymphoma, cytomegalovirus encephalitis and bacterial meningitis. A remarkably high percentage of CNS lymphomas with no distinct clinical or neuroradiological differentiation criteria were found in this study. On the basis of these data, we conclude that stereotactic biopsy and histological diagnosis should be recommended for patients with focal intracerebral lesions who fail to respond to suitable anti-parasitic treatment.

[Prenatal diagnosis of malignant intracranial teratoma in the fetus]. / Pränatale Diagnostik eines fetalen malignen intrakraniellen Teratoms.

At 24 weeks of gestation, an intracranial cystic lesion of 3 cm diameter, without further associated foetal malformations, was detected by ultrasound in a 25-year old nullipara prima gravida, during routine prenatal care. Within 5 weeks, the cystic mass developed into a predominantly solid tumour located at the 3rd ventricle, showing patterns of a rapidly growing malignant intracerebral process. At 29 weeks of gestation, pregnancy was terminated by sectio parva because of a progressive hydrocephalus with a biparietal diameter of 10.2 cm. Autopsy confirmed a malignant teratoma. Foetal intracranial teratomas are rare. Diagnosis and therapy should be carried out in perinatal centres.

[Basic diagnostic program in dizziness and syncope symptoms: value of electrophysiologic studies of the heart]. / Diagnostisches Basisprogramm bei der Symptomatik Schwindel und Synkope: Stellenwert elektrophysiologischer Untersuchungen des Herzens.

Syncopes and preceding signs and symptoms, particularly also in form of appearances of giddiness, are, including specialists of various branches, among others ENT, neurology, orthopaedics and ophthalmology, always to be classified according to the fact whether or not a cardiovascular disease is to be regarded as cause. If there is the suspicion, both special non-invasive investigations and such ones which possibly are to be performed invasively are indicated. The latter come after the non-invasive investigations partly on account of the expenditure (technique of heart catheterization) and the possibilities of complication. The testing of the sinus node with the highly frequent atrial stimulation and single stimulus technique, the lead of the His-potential and the performance of a ventricular programmed stimulation are the fundamental programmes of an electrophysiologic investigation. In an analysis carried out more than 3 years could be found that in two thirds of the 45 invasively examined patients the diagnosis could be precised and enhanced, respectively, and that the main disturbances related to the signs and symptoms were a sick sinus syndrome, AV-asequences and ventricular arrhythmias.

Activation of human neutrophil phospholipase D by three separable mechanisms.

Activation of human neutrophils by receptor-mediated agonists, the Ca2+ ionophore A23187, or the protein kinase C activator phorbol myristate acetate all stimulated phospholipase D activity. This was demonstrated by the increased formation of phosphatidic acid, and in the presence of ethanol, phosphatidylethanol (PEt) accumulation. EGTA completely inhibited A23187-induced PEt formation, but only one-half of the fMLP-induced PEt accumulation. Staurosporin, an inhibitor of protein kinase C, strongly inhibited PMA-induced PEt formation, but actually stimulated the formation of PEt in response to fMLP by several-fold. Thus, increased cytosolic Ca2+ and activated protein kinase C can each lead to activation of phospholipase D, but neither is required for receptor-mediated activation of phospholipase D activity. Wortmannin is an irreversible inhibitor of the oxidative burst, but does not inhibit NADPH oxidase or known components of signal transduction. Wortmannin inhibited activation of phospholipase D in response to fMPL. It did not directly inhibit phospholipase D, as the response to A23187 was unaffected. Wortmannin did not inhibit other fMPL-stimulated events, such as aggregation or adherence. We conclude that inhibition by wortmannin defines a third pathway to activation of phospholipase D. Further, its effect on phospholipase D correlates with its effect on the respiratory burst.

Phospholipid remodeling in human neutrophils. Parallel activation of a deacylation/reacylation cycle and platelet-activating factor synthesis.

A23187 stimulated two enzymatic activities of human neutrophils (polymorphonuclear leukocytes), phospholipase A2 and fatty acyl-CoA acyltransferase, which resulted in a stimulated deacylation/reacylation cycle. The incorporation of fatty acids, other than arachidonic or eicosapentaenoic acid, into diacyl and alkylacyl species of choline phosphoglycerides was stimulated by 10-fold by A23187. These fatty acids were exclusively incorporated into the sn-2 position, and [3H]glycerol labeling showed there was no stimulation of de novo synthesis. A23187 also stimulated fatty acid incorporation into other phospholipids, but de novo synthesis accounted for a portion of this uptake. Inhibitors of protein kinase C prevented the stimulated recycling of phosphatidylcholine, and the simultaneous induction of platelet-activating factor synthesis, by inhibiting phospholipase A2 activation. They inhibited [3H]arachidonate release from prelabeled polymorphonuclear leukocytes, but had no effect on in vitro fatty acyl-CoA acyltransferase or acetyl-CoA acetyltransferase activity. Extracts from A23187-treated cells contained a fatty acyl-CoA acyltransferase, which did not utilize arachidonoyl-CoA, that was 2.3-fold more active than that of control extracts. Phosphatase treatment decreased this stimulated activity by 66%. Thus, A23187 stimulated a phospholipase A2 activity that generated both 1-alkyl and 1-acyl lysophosphatidylcholines. A stimulated acetyltransferase used a portion of the alkyl species for platelet-activating factor synthesis, while the acyl species and residual alkyl species were rapidly reacylated to phosphatidylcholine by a stimulated acyl-transferase. Arachidonate, an eicosanoid precursor, was spared by this process.

Protein kinase C activity appears to be required for the synthesis of platelet-activating factor and leukotriene B4 by human neutrophils.

Human neutrophils synthesize platelet-activating factor (PAF) and leukotriene B4 (LTB4) when stimulated with the Ca2+ ionophore A23187. These processes are enhanced to a variable extent by phorbol 12-myristate 13-acetate (PMA), a direct activator of protein kinase C. The long chain amines sphingosine, stearylamine (Hannun, Y.A., Loomis, C.R., Merrill, A.H., Jr., and Bell, R.M. (1986) J. Biol. Chem. 261, 12604-12609), and palmitoylcarnitine competitively inhibit activation of purified protein kinase C in vitro and inhibit protein kinase C-mediated activation of the respiratory burst in human neutrophils (Wilson, E., Olcott, M.C., Bell, R.M., Merrill, A.H., Jr., and Lambeth, J.D. (1986) J. Biol. Chem. 261, 12616-12623). These amines were found to inhibit A23187-induced PAF and LTB4 synthesis. Inhibition of PAF and LTB4 synthesis occurred in parallel; half-maximal inhibition by sphingosine occurred at 7 microM, with complete inhibition at 15 microM. PMA by itself did not induce the synthesis of PAF or LTB4, although it did enhance PAF and LTB4 synthesis at suboptimal concentrations of A23187. PMA reversed long chain amine inhibition of PAF and LTB4 accumulation. Reversal of the inhibition of PAF and LTB4 accumulation occurred in parallel, was concentration-dependent, and was complete by approximately 3 x 10(-8) M PMA. The inactive 4 alpha-phorbol didecanoate ester did not reverse inhibition at these concentrations. Sphingosine completely prevented the A23187-induced release of [3H]arachidonate and its various metabolites from [3H]arachidonate-labeled cells. PMA, but not 4 alpha-phorbol didecanoate, restored arachidonate release and its metabolism. Therefore, while activation of protein kinase C is not sufficient to induce PAF and LTB4 synthesis, its action appears to be required to couple a rise in intracellular Ca2+ to their synthesis. This coupling occurs at the level of the initial reaction in the production of lipid mediators, a phospholipase A2-like activity that mobilizes the two substrates 1-O-alkyl-sn-glycero-3-phosphocholine and arachidonic acid from complex lipids.