Zusammenhang zwischen klinischen Befunden bei stationärer Aufnahme von Patienten, die an SARS-CoV-2 erkrankt sind, und dem Behandlungsverlauf

Die Arbeit wurde zu Beginn der COVID-19-Pandemie durchgeführt. Die drohende Kapazitätserschöpfung in der stationären Versorgung von COVID-19-Patienten erforderte eine optimale Ressourcenverteilung, um eine bestmögliche Versorgung der Patienten zu gewährleisten. Hierfür war eine gute Einschätzung des klinischen Zustandes der Patienten von großer Bedeutung. Ziel dieser retrospektiven Studie war es, herauszufinden, ob es Möglichkeiten gibt, anhand des klinischen Befundes zum Zeitpunkt der stationären Aufnahme eines COVID-19-Patienten eine Vorhersage über den Verlauf und das Outcome des Patienten zu treffen. Zur Objektivierung des klinischen Bildes bei Aufnahme wurden der NEWS, der SOFA-Score und der 4C-Mortality-Score berechnet und verglichen. Als Endpunkte wurden Parameter bestimmt, die zur Unterscheidung von kritisch kranken und weniger kritisch kranken Patienten dienten, wie zum Beispiel Aufnahme auf die Intensivstation, Verlegung zur ECMO, Krankenhausmortalität. Das Kollektiv ist im Median 78 Jahre alt und besteht zu 47% aus Frauen. Die Mortalitätsrate beträgt 30,3%. Die Auswertung ergab, dass das klinische Bild bei der stationären Aufnahme einen Vorhersagewert für den weiteren Verlauf und das Outcome des Patienten darstellt. Insgesamt ist der NEWS am besten zur schnellen Ersteinschätzung in der Akutsituation sowie zur Verlaufsbeobachtung geeignet. Für die explizite Vorhersage der Mortalität zeigen jedoch der SOFA- sowie der 4C-Mortality-Score eine bessere Performance

The diabetes-linked transcription factor Pax4 is expressed in human pancreatic islets and is activated by mitogens and GLP-1

We previously demonstrated that the transcription factor Pax4 is important for β-cell replication and survival in rat islets. Herein, we investigate Pax4 expression in islets of non-diabetic and diabetic donors, its regulation by mitogens, glucose and the incretin GLP-1 and evaluate its effect on human islet proliferation. Pax4 expression was increased in islets derived from Type 2 diabetic donors correlating with hyperglycaemia. In vitro studies on non diabetic islets demonstrated that glucose, betacellulin, activin A, GLP-1 and insulin increased Pax4 mRNA levels. Glucose-induced Pax4 expression was abolished by the inhibitors LY294002, PD98050 or H89. Surprisingly, increases in Pax4 expression did not prompt a surge in human islet cell replication. Furthermore, expression of the proliferation marker gene Id2 remained unaltered. Adenoviral-mediated expression of human Pax4 resulted in a small increase in Bcl-xL expression while Id2 transcript levels and cell replication were unchanged in human islets. In contrast, overexpression of mouse Pax4 induced human islet cell proliferation. Treatment of islets with 5-Aza-2′-deoxycytidine induced Pax4 without stimulating Bcl-xL and Id2 expression. Human Pax4 DNA binding activity was found to be lower than that of the mouse homologue. Thus, human pax4 gene expression is epigenetically regulated and induced by physiological stimuli through the concerted action of multiple signalling pathways. However, it is unable to initiate the transcriptional replication program likely due to post-translational modifications of the protein. The latter highlights fundamental differences between human and rodent islet physiology and emphasizes the importance of validating results obtained with animal models in human tissue

Modest Attenuation of HIV-1 Vpu Alleles Derived from Elite Controller Plasma

In the absence of antiretroviral therapy, infection with human immunodeficiency virus type 1 (HIV-1) can typically not be controlled by the infected host and results in the development of acquired immunodeficiency. In rare cases, however, patients spontaneously control HIV-1 replication. Mechanisms by which such elite controllers (ECs) achieve control of HIV-1 replication include particularly efficient immune responses as well as reduced fitness of the specific virus strains. To address whether polymorphisms in the accessory HIV-1 protein Vpu are associated with EC status we functionally analyzed a panel of plasma-derived vpu alleles from 15 EC and 16 chronic progressor (CP) patients. Antagonism of the HIV particle release restriction by the intrinsic immunity factor CD317/tetherin was well conserved among EC and CP Vpu alleles, underscoring the selective advantage of this Vpu function in HIV-1 infected individuals. In contrast, interference with CD317/tetherin induced NF-κB activation was little conserved in both groups. EC Vpus more frequently displayed reduced ability to downregulate cell surface levels of CD4 and MHC class I (MHC-I) molecules as well as of the NK cell ligand NTB-A. Polymorphisms potentially associated with high affinity interactions of the inhibitory killer immunoglobulin-like receptor (KIR) KIR2DL2 were significantly enriched among EC Vpus but did not account for these functional differences. Together these results suggest that in a subgroup of EC patients, some Vpu functions are modestly reduced, possibly as a result of host selection

Neural correlates of the affective properties of spontaneous and volitional laughter types

Previous investigations of vocal expressions of emotion have identified acoustic and perceptual distinctions between expressions of different emotion categories, and between spontaneous and volitional (or acted) variants of a given category. Recent work on laughter has identified relationships between acoustic properties of laughs and their perceived affective properties (arousal and valence) that are similar across spontaneous and volitional types (Bryant & Aktipis, 2014; Lavan et al., 2016). In the current study, we explored the neural correlates of such relationships by measuring modulations of the BOLD response in the presence of itemwise variability in the subjective affective properties of spontaneous and volitional laughter. Across all laughs, and within spontaneous and volitional sets, we consistently observed linear increases in the response of bilateral auditory cortices (including Heschl's gyrus and superior temporal gyrus [STG]) associated with higher ratings of perceived arousal, valence and authenticity. Areas in the anterior medial prefrontal cortex (amPFC) showed negative linear correlations with valence and authenticity ratings across the full set of spontaneous and volitional laughs; in line with previous research (McGettigan et al., 2015; Szameitat et al., 2010), we suggest that this reflects increased engagement of these regions in response to laughter of greater social ambiguity. Strikingly, an investigation of higher-order relationships between the entire laughter set and the neural response revealed a positive quadratic profile of the BOLD response in right-dominant STG (extending onto the dorsal bank of the STS), where this region responded most strongly to laughs rated at the extremes of the authenticity scale. While previous studies claimed a role for right STG in bipolar representation of emotional valence, we instead argue that this may in fact exhibit a relatively categorical response to emotional signals, whether positive or negative

Marginal zone lymphoma complicated by protein losing enteropathy

Protein losing enteropathy (PLE) refers to excessive intestinal protein loss, resulting in hypoalbuminemia. Underlying pathologies include conditions leading to either reduced intestinal barrier or lymphatic congestion. We describe the case of a patient with long-lasting diffuse abdominal problems and PLE. Repetitive endoscopies were normal with only minimal lymphangiectasia in biopsies. Further evaluations revealed an indolent marginal zone lymphoma with minor bone marrow infiltration. Monotherapy with rituximab decreased bone marrow infiltration of the lymphoma but did not relieve PLE. Additional treatments with steroids, octreotide, a diet devoid of long-chain fatty-acids, and parenteral nutrition did not prevent further clinical deterioration with marked weight loss (23 kg), further reduction in albumin concentrations (nadir 8 g/L), and a pronounced drop in performance status. Finally, immunochemotherapy with rituximab and bendamustine resulted in hematological remission and remarkable clinical improvement. 18 months after therapy the patient remains free of gastrointestinal complaints and has regained his body weight with normal albumin levels. We demonstrate a case of PLE secondary to indolent marginal zone lymphoma. No intestinal pathologies were detected, contrasting a severe and almost lethal clinical course. Immunochemotherapy relieved lymphoma and PLE, suggesting that a high suspicion of lymphoma is warranted in otherwise unexplained cases of PLE

Speaker Sex Perception from Spontaneous and Volitional Nonverbal Vocalizations.

In two experiments, we explore how speaker sex recognition is affected by vocal flexibility, introduced by volitional and spontaneous vocalizations. In Experiment 1, participants judged speaker sex from two spontaneous vocalizations, laughter and crying, and volitionally produced vowels. Striking effects of speaker sex emerged: For male vocalizations, listeners' performance was significantly impaired for spontaneous vocalizations (laughter and crying) compared to a volitional baseline (repeated vowels), a pattern that was also reflected in longer reaction times for spontaneous vocalizations. Further, performance was less accurate for laughter than crying. For female vocalizations, a different pattern emerged. In Experiment 2, we largely replicated the findings of Experiment 1 using spontaneous laughter, volitional laughter and (volitional) vowels: here, performance for male vocalizations was impaired for spontaneous laughter compared to both volitional laughter and vowels, providing further evidence that differences in volitional control over vocal production may modulate our ability to accurately perceive speaker sex from vocal signals. For both experiments, acoustic analyses showed relationships between stimulus fundamental frequency (F0) and the participants' responses. The higher the F0 of a vocal signal, the more likely listeners were to perceive a vocalization as being produced by a female speaker, an effect that was more pronounced for vocalizations produced by males. We discuss the results in terms of the availability of salient acoustic cues across different vocalizations

In Vitro Proliferation of Adult Human Beta-Cells

A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide

Laugh Like You Mean It:Authenticity Modulates Acoustic, Physiological and Perceptual Properties of Laughter

Several authors have recently presented evidence for perceptual and neural distinctions between genuine and acted expressions of emotion. Here, we describe how differences in authenticity affect the acoustic and perceptual properties of laughter. In an acoustic analysis, we contrasted spontaneous, authentic laughter with volitional, fake laughter, finding that spontaneous laughter was higher in pitch, longer in duration, and had different spectral characteristics from volitional laughter that was produced under full voluntary control. In a behavioral experiment, listeners perceived spontaneous and volitional laughter as distinct in arousal, valence, and authenticity. Multiple regression analyses further revealed that acoustic measures could significantly predict these affective and authenticity judgements, with the notable exception of authenticity ratings for spontaneous laughter. The combination of acoustic predictors differed according to the laughter type, where volitional laughter ratings were uniquely predicted by harmonics-to-noise ratio (HNR). To better understand the role of HNR in terms of the physiological effects on vocal tract configuration as a function of authenticity during laughter production, we ran an additional experiment in which phonetically trained listeners rated each laugh for breathiness, nasality, and mouth opening. Volitional laughter was found to be significantly more nasal than spontaneous laughter, and the item-wise physiological ratings also significantly predicted affective judgements obtained in the first experiment. Our findings suggest that as an alternative to traditional acoustic measures, ratings of phonatory and articulatory features can be useful descriptors of the acoustic qualities of nonverbal emotional vocalizations, and of their perceptual implications

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data