Pre- versus Post-synaptic Forms of LTP in Two Branches of the Same Hippocampal Afferent.

There has been considerable controversy about pre- versus postsynaptic expression of memory-related long-term potentiation (LTP), with corresponding disputes about underlying mechanisms. We report here an instance in male mice, in which both types of potentiation are expressed but in separate branches of the same hippocampal afferent. Induction of LTP in the dentate gyrus (DG) branch of the lateral perforant path (LPP) reduces paired-pulse facilitation, is blocked by antagonism of cannabinoid receptor type 1, and is not affected by suppression of postsynaptic actin polymerization. These observations are consistent with presynaptic expression. The opposite pattern of results was obtained in the LPP branch that innervates the distal dendrites of CA3: LTP did not reduce paired-pulse facilitation, was unaffected by the cannabinoid receptor blocker, and required postsynaptic actin filament assembly. Differences in the two LPP termination sites were also noted for frequency facilitation of synaptic responses, an effect that was reproduced in a two-step simulation by small adjustments to vesicle release dynamics. These results indicate that different types of glutamatergic neurons impose different forms of filtering and synaptic plasticity on their afferents. They also suggest that inputs are routed to, and encoded by, different sites within the hippocampus depending upon the pattern of activity arriving over the parent axon.

Treating a novel plasticity defect rescues episodic memory in Fragile X model mice.

Episodic memory, a fundamental component of human cognition, is significantly impaired in autism. We believe we report the first evidence for this problem in the Fmr1-knockout (KO) mouse model of Fragile X syndrome and describe potentially treatable underlying causes. The hippocampus is critical for the formation and use of episodes, with semantic (cue identity) information relayed to the structure via the lateral perforant path (LPP). The unusual form of synaptic plasticity expressed by the LPP (lppLTP) was profoundly impaired in Fmr1-KOs relative to wild-type mice. Two factors contributed to this defect: (i) reduced GluN1 subunit levels in synaptic NMDA receptors and related currents, and (ii) impaired retrograde synaptic signaling by the endocannabinoid 2-arachidonoylglycerol (2-AG). Studies using a novel serial cue paradigm showed that episodic encoding is dependent on both the LPP and the endocannabinoid receptor CB1, and is strikingly impaired in Fmr1-KOs. Enhancing 2-AG signaling rescued both lppLTP and learning in the mutants. Thus, two consequences of the Fragile-X mutation converge on plasticity at one site in hippocampus to prevent encoding of a basic element of cognitive memory. Collectively, the results suggest a clinically plausible approach to treatment.

The Endogenous Stress Hormone CRH Modulates Excitatory Transmission and Network Physiology in Hippocampus.

Memory is strongly influenced by stress but underlying mechanisms are unknown. Here, we used electrophysiology, neuroanatomy, and network simulations to probe the role of the endogenous, stress-related neuropeptide corticotropin-releasing hormone (CRH) in modulating hippocampal function. We focused on neuronal excitability and the incidence of sharp waves (SPWs), a form of intrinsic network activity associated with memory consolidation. Specifically, we blocked endogenous CRH using 2 chemically distinct antagonists of the principal hippocampal CRH receptor, CRHR1. The antagonists caused a modest reduction of spontaneous excitatory transmission onto CA3 pyramidal cells, mediated, in part by effects on IAHP. This was accompanied by a decrease in the incidence but not amplitude of SPWs, indicating that the synaptic actions of CRH are sufficient to alter the output of a complex hippocampal network. A biophysical model of CA3 described how local actions of CRH produce macroscopic consequences including the observed changes in SPWs. Collectively, the results provide a first demonstration of the manner in which subtle synaptic effects of an endogenously released neuropeptide influence hippocampal network level operations and, in the case of CRH, may contribute to the effects of acute stress on memory.

Improving a Solid-State Qubit through an Engineered Mesoscopic Environment.

A controlled quantum system can alter its environment by feedback, leading to reduced-entropy states of the environment and to improved system coherence. Here, using a quantum-dot electron spin as a control and probe, we prepare the quantum-dot nuclei under the feedback of coherent population trapping and observe their evolution from a thermal to a reduced-entropy state, with the immediate consequence of extended qubit coherence. Via Ramsey interferometry on the electron spin, we directly access the nuclear distribution following its preparation and measure the emergence and decay of correlations within the nuclear ensemble. Under optimal feedback, the inhomogeneous dephasing time of the electron, T_{2}^{*}, is extended by an order of magnitude to 39 ns. Our results can be readily exploited in quantum information protocols utilizing spin-photon entanglement and represent a step towards creating quantum many-body states in a mesoscopic nuclear-spin ensemble.

Phase-Tuned Entangled State Generation between Distant Spin Qubits.

Quantum entanglement between distant qubits is an important feature of quantum networks. Distribution of entanglement over long distances can be enabled through coherently interfacing qubit pairs via photonic channels. Here, we report the realization of optically generated quantum entanglement between electron spin qubits confined in two distant semiconductor quantum dots. The protocol relies on spin-photon entanglement in the trionic Λ system and quantum erasure of the Raman-photon path information. The measurement of a single Raman photon is used to project the spin qubits into a joint quantum state with an interferometrically stabilized and tunable relative phase. We report an average Bell-state fidelity for |ψ^{(+)}⟩ and |ψ^{(-)}⟩ states of 61.6±2.3% and a record-high entanglement generation rate of 7.3 kHz between distant qubits.

[Does annual simulation training influence the safety climate of a university hospital? : Prospective 5­year investigation using dimensions of the safety attitude questionnaire]. / Beeinflusst jährliches Simulationstraining das Sicherheitsklima einer universitären Klinik? : Prospektive Fünfjahresuntersuchung anhand Dimensionen des "Safety Attitudes Questionnaire".

BACKGROUND: Simulation-based training with a focus on non-technical skills can have a positive influence on safety relevant attitudes of participants. If an organization succeeds in training sufficient staff, it may experience a positive change in the safety climate. As the effects of a single training are of a transient nature, annual training sessions may lead to an incremental improvement of safety relevant attitudes of employees over time. In spring 2012 the Department of Anesthesia at the University Hospital of Erlangen established an annual simulation-based training for staff members (e.g. consultants, trainee anesthetists and nurse anesthetists). OBJECTIVE: The study aimed to test whether an annual simulation-based training would result in an incremental longitudinal improvement in attitudes towards teamwork, safety and stress recognition. METHODS: A survey comprising three domains (teamwork climate, safety climate and stress recognition) of the safety attitudes questionnaire (SAQ) and items addressing briefing and speaking up was distributed to all participants in an annual in-house simulation training. Participants filled out the questionnaire in the morning of each training day. The attitudes were measured before the first training series in 2012, 6 months after the first training and then every year (2013-2016). Participants generated a personalized identification code which allowed individuals to be anonymously tracked over time. Results of the 5­point Likert scale were transformed to a 100-point scale. Results were calculated at the group level and at the individual level. Univariable linear regression was used to calculate mean changes per year. RESULTS: Over a period of 5 years (2012-2016) a total of 255 individuals completed the questionnaire. Each year, 14-20% of all nurse anesthetists and 81-90% of all anesthetists participated in the simulation-based training. As a result of annual staff turnover 16-24% of participants were new staff members. A personalized code allowed the before and after comparison of 99 staff members who had participated twice or more. Physicians had a higher mean score for teamwork climate before the first training (+8.7 p < 0.001). Mean teamwork climate and safety climate scores before the first training increased over a period of 5 years (3.11 for teamwork climate, p < 0.001 and 2.73 for safety climate, p < 0.001). Repeat participation led to a bigger mean change of individual attitudes in nurse anesthetists: teamwork climate 5.2 (nurses) vs. 1.4 (physicians) and safety climate 5.3 (nurses) vs. 2.8 (physicians) without reaching significance. Participants acknowledged the importance of briefings but confirmed their existence in less than half of the cases. The frequency of briefings increased over the 5­year period. There were no changes in attitude towards speaking up. CONCLUSION: Over a 5-year period, small positive changes in attitudes towards teamwork and safety occurred. Low participation of nurse anesthetists as well as personnel turnover may have weakened the impact of simulation-based training on the safety climate.

[The 2-Scale Model of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to Assess Vision-Related Quality of Life]. / Das 2-Skalen-Modell des National Eye Institute Visual Function Questionnaire (NEI-VFQ) zur Erfassung der sehbezogenen Lebensqualität.

Aim This study addresses the examination of the factorial validity of the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ 39) and the neuro-ophthalmological supplement in a German sample. Method Eighty-one patients with visual field defects affecting at least one eye answered the NEI-VFQ 39 and the supplement. Theoretical factor structures reported in the manuals were examined in confirmatory factor analysis. Because of a misfit, items retained after item analysis were subjected to exploratory factor analysis. Results The originally postulated factor structures could not be replicated. Many items revealed floor effects. The 21 remaining items could be assigned to two factors - "visual functioning" and "socio-emotional impairment". Conclusion The weakness of the theoretical factors can be avoided by using the 2-scale model.

Direct photonic coupling of a semiconductor quantum dot and a trapped ion.

Coupling individual quantum systems lies at the heart of building scalable quantum networks. Here, we report the first direct photonic coupling between a semiconductor quantum dot and a trapped ion and we demonstrate that single photons generated by a quantum dot controllably change the internal state of a Yb^{+} ion. We ameliorate the effect of the 60-fold mismatch of the radiative linewidths with coherent photon generation and a high-finesse fiber-based optical cavity enhancing the coupling between the single photon and the ion. The transfer of information presented here via the classical correlations between the σ_{z} projection of the quantum-dot spin and the internal state of the ion provides a promising step towards quantum-state transfer in a hybrid photonic network.

Impairment of synaptic plasticity by the stress mediator CRH involves selective destruction of thin dendritic spines via RhoA signaling.

Stress is ubiquitous in modern life and exerts profound effects on cognitive and emotional functions. Thus, whereas acute stress enhances memory, longer episodes exert negative effects through as yet unresolved mechanisms. We report a novel, hippocampus-intrinsic mechanism for the selective memory defects that are provoked by stress. CRH (corticotropin-releasing hormone), a peptide released from hippocampal neurons during stress, depressed synaptic transmission, blocked activity-induced polymerization of spine actin and impaired synaptic plasticity in adult hippocampal slices. Live, multiphoton imaging demonstrated a selective vulnerability of thin dendritic spines to this stress hormone, resulting in depletion of small, potentiation-ready excitatory synapses. The underlying molecular mechanisms required activation and signaling of the actin-regulating small GTPase, RhoA. These results implicate the selective loss of dendritic spine sub-populations as a novel structural and functional foundation for the clinically important effects of stress on cognitive and emotional processes.

The influence of four different anticoagulants on dynamic light scattering of platelets.

For testing of dynamic light scattering of platelets with ThromboLUX (TLX) in platelet-rich plasma (PRP) derived from venous whole blood (vWB), anticoagulation is needed. We compared TLX score in PRPs containing citrate, ethylene-diamine-tetraacetic-acid (EDTA), citrate-phosphate-dextrose-adenine (CPDA) or citrate-theophylline-adenosine-dipyridamole. Initial and late TLX scores were measured after 30-120 min or four to six hours, respectively. Compared with citrate, mean differences in initial TLX score were only significant for CPDA. Also, mean differences between initial and late TLX scores were only significant for CPDA. TLX failed to detect EDTA-induced platelet alterations. The clinical relevance of TLX needs further studies.

Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2).

AIMS: Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of attention, impairments of memory, as well as frontal-executive and visuospatial dysfunctions. As the possible morphological correlates of these cognitive SCA2 deficits are unclear we examined the cholinergic basal forebrain nuclei, which are believed to be crucial for several aspects of normal cognition and may contribute to impairments of cognitive functions under pathological conditions. METHODS: We studied pigment-Nissl-stained thick tissue sections through the cholinergic basal forebrain nuclei (that is, medial septal nucleus, nuclei of the diagonal band of Broca, basal nucleus of Meynert) of four clinically diagnosed and genetically confirmed SCA2 patients and of 13 control individuals according to the pathoanatomical approach. The pathoanatomical results were confirmed by additional quantitative investigations of these nuclei in the SCA2 patients and four age- and gender-matched controls. RESULTS: Our study revealed a severe and consistent neuronal loss in all of the cholinergic basal forebrain nuclei (medial septal nucleus: 72%; vertical nucleus of the diagonal band of Broca: 74%; horizontal limb of the diagonal band of Broca: 72%; basal nucleus of Meynert: 86%) of the SCA2 patients studied. Damage to the basal forebrain nuclei was associated with everyday relevant cognitive deficits only in our SCA2 patient with an additional Braak and Braak stage V Alzheimer's disease (AD)-related tau pathology. CONCLUSIONS: The findings of the present study: (1) indicate that the mutation and pathological process underlying SCA2 play a causative role for this severe degeneration of the cholinergic basal forebrain nuclei and (2) may suggest that degeneration of the cholinergic basal forebrain nuclei per se is not sufficient to cause profound and global dementia detrimental to everyday practice and activities of daily living.

[Sonographic criteria for the differentiation of benign and malignant breast lesions using real-time spatial compound imaging in combination with XRES adaptive image processing]. / Dignitätskriterien der Mammasonografie unter Anwendung des Real-Time Compound Image in Kombination mit dem XRES Adaptiv Image Processing.

PURPOSE: The purpose of the study was to analyze sonographic criteria for the differentiation of benign and malignant breast lesions using real-time spatial compound imaging (CT) in combination with adaptive image processing (XRES). MATERIALS AND METHODS: In a retrospective analysis of 460 patients, the sonographic criteria: shape, orientation, margin, echo pattern and posterior acoustic features were determined using CT and XRES. All investigations were performed using a 12 MHz linear transducer. The findings were classified according to the DEGUM criteria analogous to BIRADS and were histologically confirmed by core needle or vacuum biopsy. Statistical analysis was performed using a Chi-square test, logistic uni- and multivariate regression analysis and an ROC-curve analysis to detect the false-positive rate. RESULTS: All investigated diagnostic criteria were significant in the descriptive analysis (Chi-squared). The multivariate analysis showed that the criteria of irregular shape versus round, and not circumscribed margin versus circumscribed margin as well as the posterior acoustic features of enhanced versus reduced have a significant influence on the prediction of a malignant finding. The univariate analysis also showed a statistical significance using the indifferent and not parallel orientation versus parallel. To attain a detection rate of > 95 %, a false-positive rate of 60 % must be expected. CONCLUSION: This study shows that when using CT in combination with XRES, the analyzed sonographic criteria for the differentiation of benign and malignant breast lesions are still of diagnostic value. In particular, the shape, margin and posterior sonographic features are important.

Yeast interaction on Chardonnay wine composition: Impact of strain and inoculation time.

It is of great importance to understand the molecular characteristics and substantial chemical transformations due to yeast-yeast interaction. Non-targeted metabolomics was used to unravel must in fermentation composition, inoculated with non-Saccharomyces (NS) yeasts and Saccharomyces cerevisiae (S) for sequential fermentation. ultrahigh-resolution mass spectrometry was able to distinguish thousands of metabolites and provides deep insights into grape must composition allowing better understanding of the yeast-yeast interactome. The dominance of S, characterized by a metabolic richness not found with NS, is dependent on inoculation time and on the yeast species present. Co-inoculation leads to the formation of new compounds, reflecting a reshuffling of yeast metabolism linked to interaction mechanisms. Among the modifications observed, metabolomic unravels deep changes in nitrogen metabolism due to yeast-yeast interactions and suggests that the redistribution pattern affects two different routes, the pentose phosphate and the amino acid synthesis pathways.

Optical stark effect and dressed exciton states in a Mn-doped CdTe quantum dot.

We report on the observation of spin-dependent optically dressed states and the optical Stark effect on an individual Mn spin in a semiconductor quantum dot. The vacuum-to-exciton or the exciton-to-biexciton transitions in a Mn-doped quantum dot are optically dressed by a strong laser field, and the resulting spectral signature is measured in photoluminescence. We demonstrate that the energy of any spin state of a Mn atom can be independently tuned by using the optical Stark effect induced by a control laser. High resolution spectroscopy reveals a power-, polarization-, and detuning-dependent Autler-Townes splitting of each optical transition of the Mn-doped quantum dot. This experiment demonstrates an optical resonant control of the exciton-Mn system.

[Significations of extremely elevated C-reactive protein: about 91 cases in a French hospital center]. / Significations d'une protéine C-réactive supérieure à 500mg/l: à propos de 91 prélèvements dans un centre hospitalier brestois.

This report is devoted to 91 extremely elevated protein C-reactive levels. Patients characteristics, etiologies of inflammation, comorbidities and microbiology are subjected to wide variations. Mortality is high (37 % and 51 %, 30 and 90 days later).

Parents as transition experts? Qualitative findings from a pilot parent-led peer support group.

BACKGROUND: This paper focuses on the introduction of parents as 'transition experts' within a paediatric rehabilitation hospital. Through the personal experience of raising a young adult with special healthcare needs, Family Facilitators are knowledgeable about the processes of social and healthcare service transfer and transition to adulthood. Following a needs assessment, a pilot transition support group was established for parents of youth who were eligible for augmentative communication support. The goal was to provide informational, emotional and affirmational support during this stressful period. This study examined the impact of the Family Facilitator-led Transition Peer Support Group on parents' knowledge, skill and level of support in planning for the future. METHODS: Qualitative methods were used to explore benefits, limitations and outcomes of the parent support group. In addition to a review of 10 narrative field notes maintained for each session by the Family Facilitator and four session feedback forms, a 90-min focus group was conducted with eight core members. RESULTS: Qualitative examination of the data revealed three themes: (i) increased awareness related to personal challenges in planning and shifting viewpoints on future orientation; (ii) increased active planning with regard to knowledge building and actions taken; and (iii) the value of experiential knowledge. CONCLUSIONS: Parents reported gaining new knowledge and became more active and future-oriented in their planning. Further, they strongly valued the facilitator role and benefited from the social support provided by the group. Findings provide a unique snapshot of parental needs. Individualized support with an emphasis on citizenship, participation and inclusion were targeted topics. Future work should continue to explore optimal mechanisms for the provision of parent-focused transition support and the inclusion of parents as experts within healthcare settings.

[The neuroophthalmic supplement to the NEI-VFQ: test statistics and validation with a cohort of patients with pre- and postchiasmatic damage]. / Das neuroophthalmologische Supplement des NEI-VFQ: Teststatistische Überprüfung und Validierung an einer Stichprobe prä- und postchiasmatisch geschädigter Patienten.

BACKGROUND: The National Eye Institute Visual Function Questionnaire (NEI-VFQ) is not sufficient to assess vision-related quality of life in patients with vision impairments caused by neuroophthalmic deficits. The neuroophthalmic supplement to the NEI-VFQ is currently only available in an English version. The supplement was translated into German and three items concerning visual field loss were added. MATERIAL AND METHODS: NEI-VFQ and supplement data were collected from 62 pre- and postchiasmatic patients with visual field defects and from 245 healthy reference persons. NEI-VFQ and supplement were psychometrically tested and validated. Relations between visual field variables and vision-related quality of life were assessed. RESULTS: The patient group showed diminished quality of life in 10 NEI-VFQ subscales and in eight supplement items when compared to age-matched healthy controls. Correlations between supplement and visual field diagnostic variables demonstrate moderate relations between visual field loss and deterioration of vision-related quality of life. A Cronbach's α of 0.81 for the supplement can be increased to 0.92 in combination with the NEI-VFQ, the sole application of the NEI-VFQ generates an alpha of 0.93 in this sample. A factor analysis reveals four factors that cover the 13 items capturing the following issues: 'severity/problems due to the visual field defect", "unusual eyelid appearances", "blurry vision/double vision" and "diverse vision of both eyes"; 72 % of the variance can be explained by these four factors. CONCLUSION: The German translation of the neuroophthalmic supplement to the NEI-VFQ captures additional vision-specific problems beyond the sole NEI-VFQ that are often reported by patients with vision impairments after brain damage. Although the relevance of some items can be questioned, nevertheless the supplement qualifies for an enhanced outline of subjective vision impairments that are not included in the previous NEI-VFQ.

High thiopurine metabolite concentrations associated with lymphopenia in inflammatory bowel disease (IBD) pediatric patients receiving aminosalicylates combined with azathioprine.

OBJECTIVE: Aminosalicylates are widely used with azathioprine in the treatment of IBD. The association results in an increase in 6-TGN levels in adults with IBD with a difference in the occurrence of myelotoxic effects. Scarce data are available in pediatric population. We proposed to investigate the effect of the coadministration of aminosalicylates on thiopurine concentrations in pediatric IBD patients. MATERIALS AND METHODS: Data from 71 patients treated for at least 1 y by azathioprine and aminosalicylates were recorded. 6-TGN and 6-MeMPN concentrations, blood cell counts and liver function tests were compared between patients taking and those not taking aminosalicylates. RESULTS: Aminosalicylate therapy was associated with a significant increase in mean 6-TGN but also 6-MeMPN concentrations. In patients in remission, 6-TGN level was related to aminosalicylate dosage (r = 0.561, p = 0.010). Lymphopenia rate was higher in patients receiving combined therapy compared to monotherapy whereas a slight rise in leucopenia was found. CONCLUSIONS: This observation suggests that the higher frequency of lymphopenia may be associated with the elevated 6-TGN concentrations recovered in patients treated with aminosalicylates. This combination does not improve remission rate but could increase adverse effects especially lymphopenia.

Basement membrane antibodies in sera of haematopoietic cell recipients are associated with graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GvHD) occurs frequently after haematopoietic cell transplantation (HCT). Mucocutaneous lesions of GvHD may mimic bullous autoimmune dermatoses, and 10 cases of concurrent GvHD and a bullous autoimmune disease have been reported in the literature. OBJECTIVE: To determine the frequency of circulating antibodies to the cutaneous basement membrane zone (BMZ) in HCT patients with GvHD in comparison with HCT patients without GvHD, psoriasis patients and healthy controls. SUBJECTS AND METHODS: We examined 42 patients with chronic GvHD, 18 HCT patients without GvHD, 11 psoriasis patients and 40 healthy controls, prospectively. Sera were tested by indirect immunofluorescence (IIF) on salt-split skin, NC16a-ELISA and immunoblot using keratinocyte extracts. Univariate statistical analyses and logistic regression were performed to assess possible correlations of graft and patient characteristics with the presence of BMZ antibodies. RESULTS: Circulating basement membrane zone (BMZ) antibodies were detected in 10/42 (24%) GvHD sera by immunoblot, but not in any of the HCT sera from patients without GvHD (0/18; 0%). The antibodies targeted collagen VII, BP230, collagen XVII/BP180 or p200/laminin gamma1. Clinically manifest bullous autoimmune dermatoses (bullous pemphigoid or epidermolysis bullosa acquisita) were found in two GvHD patients. 1/11 (9%) psoriasis sera and 1/40 (2.4%) healthy control sera reacted with collagen XVII or BP230, respectively. CONCLUSIONS: Circulating BMZ antibodies are significantly associated with chronic GvHD in contrast to uncomplicated HCT. Recurrent mucocutaneous lesions in chronic inflammatory skin disorders may liberate antigens, which may lead to production of BMZ antibodies, particularly in the context of GvHD-mediated reduced self-tolerance.