In vivo targeting of human DC‐SIGN drastically enhances CD8+ T‐cell‐mediated protective immunity

Vaccination is one of the oldest yet still most effective methods to prevent infectious diseases. However, eradication of intracellular pathogens and treatment of certain diseases like cancer requiring efficient cytotoxic immune responses remain a medical challenge. In mice, a successful approach to induce strong cytotoxic CD8⁺ T‐cell (CTL) reactions is to target antigens to DCs using specific antibodies against surface receptors in combination with adjuvants. A major drawback for translating this strategy into one for the clinic is the lack of analogous targets in human DCs. DC‐SIGN (DC‐specific‐ICAM3‐grabbing‐nonintegrin/CD209) is a C‐type lectin receptor with potent endocytic capacity and a highly restricted expression on human immature DCs. Therefore, DC‐SIGN represents an ideal candidate for DC targeting. Using transgenic mice that express human DC‐SIGN under the control of the murine CD11c promoter (hSIGN mice), we explored the efficacy of anti‐DC‐SIGN antibodies to target antigens to DCs and induce protective immune responses in vivo. We show that anti‐DC‐SIGN antibodies conjugated to OVA induced strong and persistent antigen‐specific CD4⁺ and CD8⁺ T‐cell responses, which efficiently protected from infection with OVA‐expressing Listeria monocytogenes. Thus, we propose DC targeting via DC‐SIGN as a promising strategy for novel vaccination protocols against intracellular pathogens.     

Evaluation of a novel automated non-invasive pulse pressure variation algorithm

In mechanically ventilated patients, Pulse Pressure Variation (PPV) has been shown to be a useful parameter to guide fluid management. We evaluated a real-time automated PPV-algorithm by comparing it to manually calculated PPV-values. In 10 critically ill patients, blood pressure was measured invasively (IBP) and non-invasively (CNAP^® Monitor, CNSystems Medizintechnik, Austria). PPV was determined manually and compared to automated PPV values: PPV_manIBP vs. PPV_autoIBP was ?0.19±1.65% (mean bias±standard deviation), PPV_manCNAP vs. PPV_autoCNAP was ?1.02±2.03% and PPV_autoCNAP vs. PPV_manIBP was ?2.10±3.14%, suggesting that the automated CNAP^® PPV-algorithm works well on both blood pressure waveforms but needs further clinical evaluation.     

Peak individual alpha frequency qualifies as a stable neurophysiological trait marker in healthy younger and older adults

The individual alpha frequency (IAF) of the human EEG reflects systemic properties of the brain, is highly heritable, and relates to cognitive functioning. Not much is known about the modifiability of IAF by cognitive interventions. We report analyses of resting EEG from a large‐scale training study in which healthy younger (20–31 years, N = 30) and older (65–80 years, N = 28) adults practiced 12 cognitive tasks for ～100 1‐h sessions. EEG was recorded before and after the cognitive training intervention. In both age groups, IAF (and, in a control analysis, alpha amplitude) did not change, despite large gains in cognitive performance. As within‐session reliability and test‐retest stability were high for both age groups, imprecise measurements cannot account for the findings. In sum, IAF is highly stable in healthy adults up to 80 years, not easily modifiable by cognitive interventions alone, and thus qualifies as a stable neurophysiological trait marker.     

PCR Followed by Electrospray Ionization Mass Spectrometry for Broad-Range Identification of Fungal Pathogens

Invasive fungal infections are a significant cause of morbidity and mortality among immunocompromised patients. Early and accurate identification of these pathogens is central to direct therapy and to improve overall outcome. PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was evaluated as a novel means for identification of fungal pathogens. Using a database grounded by 60 ATCC reference strains, a total of 394 clinical fungal isolates (264 molds and 130 yeasts) were analyzed by PCR/ESI-MS; results were compared to phenotypic identification, and discrepant results were sequence confirmed. PCR/ESI-MS identified 81.4% of molds to either the genus or species level, with concordance rates of 89.7% and 87.4%, respectively, to phenotypic identification. Likewise, PCR/ESI-MS was able to identify 98.4% of yeasts to either the genus or species level, agreeing with 100% of phenotypic results at both the genus and species level. PCR/ESI-MS performed best with Aspergillus and Candida isolates, generating species-level identification in 94.4% and 99.2% of isolates, respectively. PCR/ESI-MS is a promising new technology for broad-range detection and identification of medically important fungal pathogens that cause invasive mycoses.     

RECall for Automated Genotypic Tropism Testing

Standardization of sequence chromatogram analysis is required for consistent genotypic tropism determination across laboratories. A freely available, fast, and automated chromatogram analysis tool (RECall) provided tropism interpretations equivalent to those of manual sequence editing of 521 V3 loop HIV-1 population sequences, suggesting that RECall can be useful in standardizing genotypic tropism testing across laboratories.     

A mechanical microconnector system for restoration of tissue continuity and long-term drug application into the injured spinal cord

Complete transection of the spinal cord leaves a gap of several mm which fills with fibrous scar tissue. Several approaches in rodent models have used tubes, foams, matrices or tissue implants to bridge this gap. Here, we describe a mechanical microconnector system (mMS) to re-adjust the retracted spinal cord stumps. The mMS is a multi-channel system of polymethylmethacrylate (PMMA), designed to fit into the spinal cord tissue gap after transection, with an outlet tubing system to apply negative pressure to the mMS thus sucking the spinal cord stumps into the honeycomb-structured holes. The stumps adhere to the microstructure of the mMS walls and remain in the mMS after removal of the vacuum. We show that the mMS preserves tissue integrity and allows axonal regrowth at 2, 5 and 19 weeks post lesion with no adverse tissue effects like in-bleeding or cyst formation. Preliminary assessment of locomotor function in the open field suggested beneficial effects of the mMS. Additional inner micro-channels enable local substance delivery into the lesion center via an attached osmotic minipump. We suggest that the mMS is a suitable device to adapt and stabilize the injured spinal cord after surgical resection of scar tissue (e.g., for chronic patients) or traumatic injuries with large tissue and bone damages.     

Verbal episodic memory deficits in remitted bipolar patients: A combined behavioural and fMRI study

Background

Episodic memory deficits affect the majority of patients with bipolar disorder (BD).

Aims

The study investigates episodic memory performance through different approaches, including behavioural measures, physiological parameters, and the underlying functional activation patterns with functional neuroimaging (fMRI).

Methods

26 Remitted BD patients and a matched group of healthy controls underwent a verbal episodic memory test together with monitored autonomic response, psychopathological ratings and functional magnetic resonance imaging (fMRI) during the verbal episodic memory test.

Results

Compared to healthy controls, BD patients performed significantly worse during the episodic memory task. The results further indicate that verbal episodic memory deficits in BD are associated with abnormal functional activity patterns in frontal, occipital and limbic regions, and an increase in stress parameters.

Limitations

We aimed to minimise sample heterogeneity by setting clear criteria for remission, based on the scores of a depression (BDI II) and mania scale (BRMAS) and on the DSM IV criteria. However, our patients were not symptom-free and scored higher on BDI II scores than the control group.

Conclusions

The results are of interest for the treatment of cognitive symptoms in BD patients, as persistent cognitive impairment may hamper full rehabilitation.     

Ultradian and circadian modulation of dream recall: EEG correlates and age effects

Dreaming occurs during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, which both are regulated by homeostatic, ultradian, and circadian processes. However, the magnitude of how ultradian REM and NREM sleep and its EEG correlates impact onto dream recall remains fairly unknown. In this review, we address three questions: 1. Is there an ultradian NREM–REM sleep modulation in successful dream recall, which is gated by the circadian clock? 2. What are the key electrophysiological correlates that account for dream recall during NREM and REM sleep and 3. Are there age-related changes in the ultradian and circadian regulation in dream recall and its electrophysiological correlates? Knowledge on the specific frequency and topography NREM and REM sleep differences prior to dream recall may pinpoint to the cerebral correlates that account for this cognitive process, and hint to their possible physiological meaning.