Associations between olfactory reference disorder and social phobia - results of an internet-based study.

Despite the similar clinical features of Olfactory Reference Disorder (ORD) and Social Phobia (SP), or studies showing elevated comorbidity of the two disorders, and the conceptualization of ORD as a form of SP in the East Asian culture, to our knowledge, the relationship between ORD and SP has not been investigated. This study examined the association of ORD according to the 11th revision of the International Classification of Diseases (ICD-11) and SP in 225 German university / college students who completed self-ratings with regard to socio-demographic data and symptoms of SP and ORD within an anonymous internet-based survey. Symptoms of SP were assessed with the Social Phobia Inventory (SPIN). Symptoms of ORD according to the ICD-11 were assessed with the Olfactory Reference Disorder Questionnaire (ORDQ), developed for this study. In our sample, 86.6% of the participants who met the self-rated features for ORD also met the self-rated criteria for current SP. ORD severity scores were significantly related to SP. Participants with and without self-reported ORD differed significantly in their SP total scores. SP severity was also significantly correlated with poorer insight of ORD-related beliefs, greater ORD-related avoidance of intimate relationships and higher levels of shame and fear of rejection due to body odor. These preliminary findings indicate that ORD could be closely related to SP and highlight the need for future research on the relationship of ORD and SP in order to gain a better understanding of the development, maintenance, treatment and classification of ORD.

Associations between sleep problems and posttraumatic stress symptoms, social functioning, and quality of life in refugees with posttraumatic stress disorder.

Many patients with posttraumatic stress disorder (PTSD) suffer from sleep problems, leading to impairments in social functioning and quality of life. Refugees are at high risk for sleep problems due to stressful life circumstances and a high PTSD prevalence. However, limited data on the frequency of sleep problems in refugees with diagnosed PTSD exist. This study examined the frequency of sleep problems in refugees with PTSD and their associations with symptoms of PTSD. Additionally, we investigated the contribution of sleep problems to social functioning and quality of life. Participants (N = 70) were refugees from different countries of origin currently living in Germany. All participants met the criteria for PTSD and completed measures of PTSD symptom severity, subjective sleep problems, social impairment, and quality of life. There was a very high frequency of sleep problems in the sample (100%), and sleep problems were significantly associated with both clinician-rated, r = .47, and self-rated, r = .30, PTSD symptom severity after controlling for overlapping items. Contrary to expectations, sleep problems did not predict social impairment, d = 0.16, nor quality of life, d = 0.13, beyond the effect of other PTSD symptoms. The findings highlight the widespread frequency of sleep problems among refugees. Future studies should assess the causal nature of the association between sleep problems and measures of psychosocial functioning in more detail and examine its dynamic change over time.

AI-Supported Comprehensive Detection and Quantification of Biomarkers of Subclinical Widespread Diseases at Chest CT for Preventive Medicine.

Automated image analysis plays an increasing role in radiology in detecting and quantifying image features outside of the perception of human eyes. Common AI-based approaches address a single medical problem, although patients often present with multiple interacting, frequently subclinical medical conditions. A holistic imaging diagnostics tool based on artificial intelligence (AI) has the potential of providing an overview of multi-system comorbidities within a single workflow. An interdisciplinary, multicentric team of medical experts and computer scientists designed a pipeline, comprising AI-based tools for the automated detection, quantification and characterization of the most common pulmonary, metabolic, cardiovascular and musculoskeletal comorbidities in chest computed tomography (CT). To provide a comprehensive evaluation of each patient, a multidimensional workflow was established with algorithms operating synchronously on a decentralized Joined Imaging Platform (JIP). The results of each patient are transferred to a dedicated database and summarized as a structured report with reference to available reference values and annotated sample images of detected pathologies. Hence, this tool allows for the comprehensive, large-scale analysis of imaging-biomarkers of comorbidities in chest CT, first in science and then in clinical routine. Moreover, this tool accommodates the quantitative analysis and classification of each pathology, providing integral diagnostic and prognostic value, and subsequently leading to improved preventive patient care and further possibilities for future studies.

Modulating chitin synthesis in marine algae with iminosugars obtained by SmI2 and FeCl3-mediated diastereoselective carbonyl ene reaction.

Strategies for synthesizing polyhydroxylated piperidines such as iminosugars have received broad attention. These substances are known to interact with carbohydrate related enzymes, glycosidases and glycosyltransferases, to which also the large enzyme families of chitin synthases and cellulose synthases belong. Many chemical and biological aspects of chitin synthases remain unexplored due to the fact that modulating substances are hardly available or expensive. Starting from enantiopure D- and L-amino acids, a series of iminosugars was prepared by a Lewis acid-catalyzed cyclization of amino acid-derived unsaturated aldehydes as key step. Therefore, different Lewis acids were tested. For samarium diiodide we observed a superior stereoselectivity in comparison to iron(III) chloride and methylaluminium dichloride. To increase water solubility for testing and measurement of enzyme activity, the cyclization products were further functionalized. We established a novel biological chitin synthesis test system which allows quantitative investigation of chitin synthesis in the chitin fiber producing diatom algae Thalassiosira in vivo under the light microscope. None of the compounds displayed cytotoxicity, but two of the four iminosugars increased the length of the chitin fibers produced. This is a strong indicator that these compounds mimic carbohydrates responsible for restarting chitin polymerization.

Physiological activation and co-activation in an imagery-based treatment for test anxiety.

Objective: The effectiveness of Imagery Rescripting (IR) has been demonstrated in the treatment of various psychological disorders, but the mechanisms underlying it remain unclear. While current investigations predominantly refer to memory processes, physiological processes have received less attention. The main aim of this study is to test whether client physiological activation (i.e., arousal) and client-therapist physiological activation (i.e., synchrony) during IR segments predicted improvement on next-session outcomes and overall treatment response, and to compare these to the role of physiological (co)-activation during traditional cognitive-behavioral (CB) segments. Methods: The results are based on 177 therapy sessions from an imagery-based treatment for test anxiety with 60 clients. Client and therapist electrodermal activity was continuously monitored, next-session outcome was assessed with the Outcome Rating Scale and treatment outcome was assessed using the Test Anxiety Inventory. Results: Hierarchical linear models demonstrated that average physiological synchrony during IR segments (but not during CB ones) was significantly associated with higher well-being at both the session and the overall treatment levels. Clients' physiological arousal in either IR or CB segments was not predictive of either outcome. Conclusion: These results provide initial evidence for the idea that physiological synchrony might be an important underlying mechanism in IR.

No Changes in T1 Relaxometry After a Mean of 11 Administrations of Gadobutrol.

OBJECTIVES: Quantitative T1 relaxometry is the benchmark in imaging potential gadolinium deposition and known to be superior to semiquantitative signal intensity ratio analyses. However, T1 relaxometry studies are rare, commonly limited to a few target structures, and reported results are inconsistent.We systematically investigated quantitative T1 relaxation times (qT1) of a variety of brain nuclei after serial application of gadobutrol. MATERIALS AND METHODS: Retrospectively, qT1 measurements were performed in a patient cohort with a mean number of 11 gadobutrol applications (n = 46) and compared with a control group with no prior gadolinium-based contrast agent administration (n = 48). The following target structures were evaluated: dentate nucleus, globus pallidus, thalamus, hippocampus, putamen, caudate, amygdala, and different white matter areas. Subsequently, multivariate regression analysis with adjustment for age, presence of brain metastases and previous cerebral radiotherapy was performed. RESULTS: No assessed site revealed a significant correlation between qT1 and number of gadobutrol administrations in multivariate regression analysis. However, a significant negative correlation between qT1 and age was found for the globus pallidus as well as anterior and lateral thalamus (P < 0.05 each). CONCLUSIONS: No T1 relaxation time shortening due to gadobutrol injection was found in any of the assessed brain structures after serial administration of 11 doses of gadobutrol.

Macroangiopathy is a positive predictive factor for response to immunotherapy.

Immunotherapies demand for predictive biomarkers to avoid unnecessary adverse effects and costs. Analytic morphomics is the technique to use body composition measures as imaging biomarkers for underlying pathophysiology to predict prognosis or outcome to therapy. We investigated different body composition measures to predict response to immunotherapy. This IRB approved retrospective analysis encompassed 147 patients with ipilimumab therapy. Degree of macroangiopathy was quantified with the newly defined total plaque index (TPI), i.e. the body height corrected sum of the soft and hard plaque volume of the infrarenal aorta on portalvenous CT scans. Furthermore, mean psoas density (MPD), different adipose tissue parameters as well as degree of cerebral microangiopathy were extracted from the imaging data. Subsequent multivariate Cox regression analysis encompassed TPI, MPD, serum LDH, S100B, age, gender, number of immunotherapy cycles as well as extent of distant metastases. TPI and MPD correlated positively with PFS in multivariate analysis (p = 0.03 and p = 0.001, respectively). Furthermore, single visceral organ and/or soft tissue involvement significantly decreased progression risk (p = 0.01), whereas increased S100B level showed a trend towards PFS shortening (p = 0.05). In conclusion, degree of macroangiopathy and sarcopenia were independent predictors for outcome to immunotherapy and of equivalent significance compared to other clinical biomarkers.

Glymphatic Pathway of Gadolinium-Based Contrast Agents Through the Brain: Overlooked and Misinterpreted.

BACKGROUND: The "glymphatic system" (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo. METHODS: Heavily T2-weighted fluid-attenuated inversion recovery (hT2w-FLAIR) magnetic resonance imaging was obtained before, and 3 hours and 24 hours after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces, and white matter hyperintensities were quantified by applying the Fazekas scoring system. FINDINGS: Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3 hours and 24 hours time points compared with baseline. Although no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between Fazekas scoring system and SI increase in the perivascular spaces 3 hours post injection was shown. INTERPRETATION: Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the correlation found between deep white matter hyperintensities, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.

[Therapy of a common otitis media in the infancy]. / Antibiotika bei unkomplizierter Otitis media im Kindesalter?

The therapy of an acute otitis media has been questioned due to increasing bacterial resistance during the last years. Two recent studies dealing with efficiency of the antibiotic treatment regarding diseased children younger tha 2 or 3 years are recommending antibiotic drugs compared to the use of placebo. How are the results of the studies to be interpreted?

Postnatal changes in morphology and dendritic organization of neurones located in the area of the Kölliker-Fuse nucleus of rat.

The Kölliker-Fuse nucleus (KF) is an integral part of the central pattern generator for breathing and shows postnatal development of synaptic functions and cyto-architectural structure. Here, we analyzed the postnatal changes in cell morphology of biocytin-labelled KF neurones. Developmental analyses revealed an increasing size of somas and dendritic length. These changes were accompanied by changes in the orientation of the main dendritic branches from a diffuse orientation in neonates to a predominant medio-lateral orientation in juveniles. These developmental changes may allow for synaptic contacts with multiple ascending fibre tracts required for the processing of multi-modal respiratory inputs in the KF.

Enhanced hypoxia susceptibility in hippocampal slices from a mouse model of rett syndrome.

Rett syndrome is a neurodevelopmental disorder caused by mutations in the X-chromosomal MECP2 gene encoding for the transcriptional regulator methyl CpG binding protein 2 (MeCP2). Rett patients suffer from episodic respiratory irregularities and reduced arterial oxygen levels. To elucidate whether such intermittent hypoxic episodes induce adaptation/preconditioning of the hypoxia-vulnerable hippocampal network, we analyzed its responses to severe hypoxia in adult Rett mice. The occurrence of hypoxia-induced spreading depression (HSD)--an experimental model for ischemic stroke--was hastened in Mecp2-/y males. The extracellular K+ rise during HSD was attenuated in Mecp2-/y males and the input resistance of CA1 pyramidal neurons decreased less before HSD onset. CA1 pyramidal neurons were smaller and more densely packed, but the cell swelling during HSD was unaffected. The intrinsic optical signal and the propagation of HSD were similar among the different genotypes. Basal synaptic function was intact, but Mecp2-/y males showed reduced paired-pulse facilitation and higher field potential/fiber volley ratios, but no increased seizure susceptibility. Synaptic failure during hypoxia was complete in all genotypes and the final degree of posthypoxic synaptic recovery indistinguishable. Cellular ATP content was normal in Mecp2-/y males, but their hematocrit was increased as was HIF-1alpha expression throughout the brain. This is the first study showing that in Rett syndrome, the susceptibility of telencephalic neuronal networks to hypoxia is increased; the underlying molecular mechanisms apparently involve disturbed K+ channel function. Such an increase in hypoxia susceptibility may potentially contribute to the vulnerability of male Rett patients who are either not viable or severely disabled.

Postnatal emergence of synaptic plasticity associated with dynamic adaptation of the respiratory motor pattern.

The shape of the three-phase respiratory motor pattern (inspiration, postinspiration, late expiration) is controlled by a central pattern generator (CPG) located in the ponto-medullary brainstem. Synaptic interactions between and within specific sub-compartments of the CPG are subject of intensive research. This review addresses the neural control of postinspiratory activity as the essential determinant of inspiratory/expiratory phase duration. The generation of the postinspiratory phase depends on synaptic interaction between neurones of the nucleus tractus solitarii (NTS), which relay afferent inputs from pulmonary stretch receptors, and the pontine Kölliker-Fuse nucleus (KF) as integral parts of the CPG. Both regions undergo significant changes during the first three postnatal weeks in rodents. Developmental changes in glutamatergic synaptic functions and its modulation by brain-derived neurotrophic factor may have implications in synaptic plasticity within the NTS/KF axis. We propose that dependent on these developmental changes, the CPG becomes permissive for short- and long-term plasticity associated with environmental, metabolic and behavioural adaptation of the breathing pattern.

Emergence of brain-derived neurotrophic factor-induced postsynaptic potentiation of NMDA currents during the postnatal maturation of the Kolliker-Fuse nucleus of rat.

The Kölliker-Fuse nucleus (KF) contributes essentially to respiratory pattern formation and adaptation of breathing to afferent information. Systems physiology suggests that these KF functions depend on NMDA receptors (NMDA-R). Recent investigations revealed postnatal changes in the modulation of glutamatergic neurotransmission by brain-derived neurotrophic factor (BDNF) in the KF. Therefore, we investigated postnatal changes in NMDA-R subunit composition and postsynaptic modulation of NMDA-R-mediated currents by BDNF in KF slice preparations derived from three age groups (neonatal: postnatal day (P) 1-5; intermediate: P6-13; juvenile: P14-21). Immunohistochemistry showed a developmental up-regulation of the NR2D subunit. This correlated with a developmental increase in decay time of NMDA currents and a decline of desensitization in response to repetitive exogenous NMDA applications. Thus, developmental up-regulation of the NR2D subunit, which reduces the Mg(2+) block of NMDA-R, causes these specific changes in NMDA current characteristics. This may determine the NMDA-R-dependent function of the mature KF in the control of respiratory phase transition. Subsequent experiments revealed that bath-application of BDNF progressively potentiated these repetitively evoked NMDA currents only in intermediate and juvenile age groups. Pharmacological inhibition of protein kinase C (PKC), as a downstream component of the BDNF-tyrosine kinase B receptor (trkB) signalling, prevented BDNF-induced potentiation of NMDA currents. BDNF-induced potentiation of NMDA currents in later developmental stages might be essential for synaptic plasticity during the adaptation of the breathing pattern in response to peripheral/central commands. The lack of plasticity in neonatal neurones strengthens the hypothesis that the respiratory network becomes permissive for activity-dependent plasticity with ongoing postnatal development.

Developmental changes in brain-derived neurotrophic factor-mediated modulations of synaptic activities in the pontine Kölliker-Fuse nucleus of the rat.

The Kölliker-Fuse nucleus (KF), part of the respiratory network, is involved in the modulation of respiratory phase durations in response to peripheral and central afferent inputs. The KF is immature at birth. Developmental changes in its physiological and anatomical properties have yet to be investigated. Since brain-derived neurotrophic factor (BDNF) is of major importance for the maturation of neuronal networks, we investigated its effects on developmental changes in the KF on different postnatal days (neonatal, P1-5; intermediate, P6-13; juvenile, P14-21) by analysing single neurones in the in vitro slice preparation and network activities in the perfused brainstem preparation in situ. The BDNF had only weak effects on the frequency of mixed excitatory and inhibitory spontaneous postsynaptic currents (sPSCs) in neonatal slice preparations. Postnatally, in the intermediate and juvenile age groups, a significant augmentation of the sPSC frequency was observed in the presence of 100 pm BDNF (+23.5+/-12.6 and +76.7+/-28.4%, respectively). Subsequent analyses of BDNF effects on evoked excitatory postsynaptic currents (eEPSCs) revealed significant enhancement of eEPSC amplitude of +20.8+/-7.0% only in juvenile stages (intermediates, -13.2+/-4.8%). On the network level, significant modulation of phrenic nerve activity following BDNF microinjection into the KF was also observed only in juveniles. The data suggest that KF neurones are subject to BDNF-mediated fast synaptic modulation after completion of postnatal maturation. After maturation, BDNF contributes to modulation of fast excitatory neurotransmission in respiratory-related KF neurones. This may be important for network plasticity associated with the processing of afferent information.