Quality measurement of out-patient neuropsychological therapy after stroke in Germany: definition of indicators and retrospective pilot study

Background: In contrast to the hospital setting, today little work has been directed to the definition, measurement, and improvement of the quality of out-patient medical and therapeutic care. We developed a set of indicators to measure the quality of out-patient neuropsychological therapy after stroke. Methods: The indicators cover core and interdisciplinary aspects of out-patient neuropsychological work such as mediation of patients into social care in case of need. Selection of the quality-indicators was done together with a consensus group of out-patient therapists and supported by evidence, validity, reliability as well as estimated relevance and variability with the quality of care. The set of indicators was further tested in a retrospective cohort study. Anonymous data of 104 patients were collected from out-patient clinical records of five clinics between November 2017 and April 2018. Associations between process and outcome quality were estimated exploitatively. Results: Results allowed for the identification of areas with greater variability in the quality of process care and indicated that attention training as recommended by current guidelines had the lowest overall rate for meeting the quality-aim (met in 44% of the cases). This was followed by time<1month until the start of therapy (63% met) and mediation into social care in case of need (65% met). We further observed that overall quality and involving relatives in the therapy was associated with higher rates of professional reintegration (p-value=0.03). However, the need for mediation into social care was associated with a reduced chance for successful professional reintegration (p-value=0.009). Conclusion: In conclusion, we describe a first set of quality indicators which cover different aspects of out-patient neuropsychological therapy and sufficient variability with care. First data further suggests that meeting the specified quality aims may indeed have relevant effects on outcomes

The efficacy and sustainability of the CIMBAA transgenic Cry1B/Cry1C Bt cabbage and cauliflower plants for control of lepidopteran pests

In 2003 the Collaboration on Insect Management for Brassicas in Asia and Africa (CIMBAA) public/private partnership selected the Cry1B/Cry1C Bt protein combination as having the potential to provide effective and sustainable control of diamondback moth (DBM), Plutella xylostella. Following transformations and extensive plant selection, insect efficacy trials were undertaken in 2008 to 2010 in north India (Murthal near New Delhi) and south India (near Bengaluru) in large scale screen-house experiments using artificial infestations on the best performing (Elite Event) plant lines and on hybrids produced from them. Plant damage was scored on a scale of 0 (no visible damage) to 4 (plant effectively destroyed). For DBM, cabbage cluster caterpillar (Crocidolomia binotalis), cabbage webworm (Hellula undalis) and semi-looper (Trichoplusia ni) there was zero insect survival and a zero damage score on the Elite Event lines and on their hybrids, while control plants had 50 to 100% insect survival (depending on species, life stage and trials) and damage scores of 3.3 to 4. Cabbage white (Pieris brassicae) and common army worm (Spodoptera litura) showed some larval survival and damage scores up to 1.4 (especially in early trials) but no survival to pupation. Screening of DBM populations worldwide (inc. 18 populations for Cry1B and 13 for Cry1C from India) showed mean LC50s close to that of international susceptible strains. To date F2 screening has not identified the presence of resistance genes in DBM in the field. Cry1B resistance was slowly developed artificially in the laboratory but 1C resistance and resistance to the Cry1B/1C combination was harder to develop and had higher fitness costs. The ‘resistant’ lines showed some extended survival of stunted DBM larvae on dual gene Bt plants but no survival to pupation. There was no cross-resistance between Cry1B and Cry1C. Resistance to both genes was autosomal and recessive. Beneficial insects were demonstrated to have the potential to provide additional mortality on rare surviving insects in Bt fields. Aphids were well controlled for the first 40 days post-transplanting using imidacloprid pelleted onto seed and, if necessary, by 1-2 Verticillium lecanii sprays thereafter. Surviving S. litura and Helicoverpa armigera in Bt sprayed fields were well controlled by one or two application

Photo‐biocatalytic Cascades:Combining Chemical and Enzymatic Transformations Fueled by Light

In the field of green chemistry, light – an attractive natural agent – has received particular attention for driving biocatalytic reactions. Moreover, the implementation of light to drive (chemo)enzymatic cascade reactions opens up a golden window of opportunities. However, there are limitations to many current examples, mostly associated with incompatibility between the enzyme and the photocatalyst. Additionally, the formation of reactive radicals upon illumination and the loss of catalytic activities in the presence of required additives are common observations. As outlined in this review, the main question is how to overcome current challenges to the exploitation of light to drive (chemo)enzymatic transformations. First, we highlight general concepts in photo-biocatalysis, then give various examples of photo-chemoenzymatic (PCE) cascades, further summarize current synthetic examples of PCE cascades and discuss strategies to address the limitations

Towards a representative reference for MRI-based human axon radius assessment using light microscopy

Non-invasive assessment of axon radii via MRI bears great potential for clinical and neuroscience research as it is a main determinant of the neuronal conduction velocity. However, there is a lack of representative histological reference data at the scale of the cross-section of MRI voxels for validating the MRI-visible, effective radius (reff). Because the current gold standard stems from neuroanatomical studies designed to estimate the bulk-determined arithmetic mean radius (rarith) on small ensembles of axons, it is unsuited to estimate the tail-weighted reff. We propose CNN-based segmentation on high-resolution, large-scale light microscopy (lsLM) data to generate a representative reference for reff. In a human corpus callosum, we assessed estimation accuracy and bias of rarith and reff. Furthermore, we investigated whether mapping anatomy-related variation of rarith and reff is confounded by low-frequency variation of the image intensity, e.g., due to staining heterogeneity. Finally, we analyzed the error due to outstandingly large axons in reff. Compared to rarith, reff was estimated with higher accuracy (maximum normalized-root-mean-square-error of reff: 8.5 %; rarith: 19.5 %) and lower bias (maximum absolute normalized-mean-bias-error of reff: 4.8 %; rarith: 13.4 %). While rarith was confounded by variation of the image intensity, variation of reff seemed anatomy-related. The largest axons contributed between 0.8 % and 2.9 % to reff. In conclusion, the proposed method is a step towards representatively estimating reff at MRI voxel resolution. Further investigations are required to assess generalization to other brains and brain areas with different axon radii distributions

Phenylalanine hydroxylase contributes to serotonin synthesis in mice

This is the final version. Available from the Federation of American Society of Experimental Biology via the DOI in this record.Serotonin is an important signaling molecule in the periphery and in the brain. The hydroxylation of tryptophan is the first and rate-limiting step of its synthesis. In most vertebrates, two enzymes have been described to catalyze this step, tryptophan hydroxylase (TPH) 1 and 2, with expression localized to peripheral and neuronal cells, respectively. However, animals lacking both TPH isoforms still exhibit about 10% of normal serotonin levels in the blood demanding an additional source of the monoamine. In this study, we provide evidence by the gain and loss of function approaches in in vitro and in vivo systems, including stable-isotope tracing in mice, that phenylalanine hydroxylase (PAH) is a third TPH in mammals. PAH contributes to serotonin levels in the blood, and may be important as a local source of serotonin in organs in which no other TPHs are expressed, such as liver and kidney.Saint Petersburg State University (SPbU)Bundesministerium für Bildung und Forschung (BMBF)Deutsches Zentrum für Herz-Kreislaufforschung (DZHK)Volkswagen Foundation (VolkswagenStiftung

Fiber-orientation independent component of R(2)* obtained from single-orientation MRI measurements in simulations and a post-mortem human optic chiasm

The effective transverse relaxation rate (R(2)*) is sensitive to the microstructure of the human brain like the g-ratio which characterises the relative myelination of axons. However, the fibre-orientation dependence of R(2)* degrades its reproducibility and any microstructural derivative measure. To estimate its orientation-independent part (R(2,iso)*) from single multi-echo gradient-recalled-echo (meGRE) measurements at arbitrary orientations, a second-order polynomial in time model (hereafter M2) can be used. Its linear time-dependent parameter, β(1), can be biophysically related to R(2,iso)* when neglecting the myelin water (MW) signal in the hollow cylinder fibre model (HCFM). Here, we examined the performance of M2 using experimental and simulated data with variable g-ratio and fibre dispersion. We found that the fitted β(1) can estimate R(2,iso)* using meGRE with long maximum-echo time (TE(max) ≈ 54 ms), but not accurately captures its microscopic dependence on the g-ratio (error 84%). We proposed a new heuristic expression for β(1) that reduced the error to 12% for ex vivo compartmental R(2) values. Using the new expression, we could estimate an MW fraction of 0.14 for fibres with negligible dispersion in a fixed human optic chiasm for the ex vivo compartmental R(2) values but not for the in vivo values. M2 and the HCFM-based simulations failed to explain the measured R(2)*-orientation-dependence around the magic angle for a typical in vivo meGRE protocol (with TE(max) ≈ 18 ms). In conclusion, further validation and the development of movement-robust in vivo meGRE protocols with TE(max) ≈ 54 ms are required before M2 can be used to estimate R(2,iso)* in subjects

Improvement of in vitro and early in utero porcine clone development after somatic donor cells are cultured under hypoxia

Genetically engineered pigs serve as excellent biomedical and agricultural models. To date, the most reliable way to generate genetically engineered pigs is via somatic cell nuclear transfer (SCNT), however, the efficiency of cloning in pigs is low (1–3 percent). Somatic cells such as fibroblasts frequently used in nuclear transfer utilize the tricarboxylic acid cycle and mitochondrial oxidative phosphorylation for efficient energy production. The metabolism of somatic cells contrasts with cells within the early embryo, which predominately use glycolysis. We hypothesized that fibroblast cells could become blastomere-like if mitochondrial oxidative phosphorylation was inhibited by hypoxia and that this would result in improved in vitro embryonic development after SCNT. In a previous study, we demonstrated that fibroblasts cultured under hypoxic conditions had changes in gene expression consistent with increased glycolytic/gluconeogenic metabolism. The goal of this pilot study was to determine if subsequent in vitro embryo development is impacted by cloning porcine embryonic fibroblasts cultured in hypoxia. Here we demonstrate that in vitro measures such as early cleavage, blastocyst development, and blastocyst cell number are improved (4.4 percent, 5.5 percent, and 17.6 cells, respectively) when donor cells are cultured in hypoxia before nuclear transfer. Survival probability was increased in clones from hypoxic cultured donors compared to controls (8.5 vs. 4.0 [plus or minus] 0.2). These results suggest that the clones from donor cells cultured in hypoxia are more developmentally competent and this may be due to improved nuclear reprogramming during somatic cell nuclear transfer

HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: Results from a prospective observational study in Germany.

Aims: Since 2017, HIV pre-exposure prophylaxis (PrEP) care has been provided through an intersectoral collaboration at WIR (Walk-in-Ruhr, Center for Sexual Health and Medicine, Bochum, Germany). The aim of this study was to establish possible impact of COVID-restrictions on the sexual behavior of PrEP users in North Rhine-Westphalia. Methods: The current PrEP study collected data of individuals using PrEP, their sexual behavior and sexually transmitted infections (STIs) before (each quarter of year 2018) and during the COVID-19 pandemic (each quarter of year 2020). Results: During the first lockdown in Germany from mid-March until May 2020, PrEP-care appointments at WIR were postponed or canceled. Almost a third of PrEP users had discontinued their PrEP intake in the 2nd quarter of 2020 due to alteration of their sexual behavior. The number of sexual partners decreased from a median of 14 partners in the previous 6 months in 1st quarter of 2020, to 7 partners in 4th quarter of 2020. Despite such a significant reduction in partner number during the pandemic in comparison to the pre-pandemic period, a steady rate of STIs was observed among PrEP users in 2020. Conclusion: The SARS-CoV-2-pandemic has impacted PrEP-using MSM in North Rhine-Westphalia with respect to their PrEP intake regimen and sexual behavior in 2020. Our study revealed a steady rate of STI among PrEP users even during the pandemic, thus highlighting the importance of ensuring appropriate HIV/STI prevention services in times of crisis

The association of homeobox gene expression with stem cell formation and morphogenesis in cultured Medicago truncatula

Somatic embryogenesis (SE) is induced in vitro in Medicago truncatula 2HA by auxin and cytokinin but rarely in wild type Jemalong. The putative WUSCHEL (MtWUS), CLAVATA3 (MtCLV3) and the WUSCHEL-related homeobox gene WOX5 (MtWOX5) were investigated in M. truncatula (Mt) and identified by the similarity to Arabidopsis WUS, CLV3 and WOX5 in amino acid sequence, phylogeny and in planta and in vitro expression patterns. MtWUS was induced throughout embryogenic cultures by cytokinin after 24–48 h and maximum expression occurred after 1 week, which coincides with the induction of totipotent stem cells. During this period there was no MtCLV3 expression to suppress MtWUS. MtWUS expression, as illustrated by promoter-GUS studies, subsequently localised to the embryo, and there was then the onset of MtCLV3 expression. This suggests that the expression of the putative MtCLV3 coincides with the WUS-CLAVATA feedback loop becoming operational. RNAi studies showed that MtWUS expression is essential for callus and somatic embryo production. Based on the presence of MtWUS promoter binding sites, MtWUS may be required for the induction of MtSERF1, postulated to have a key role in the signalling required for SE induced in 2HA. MtWOX5 expressed in auxin-induced root primordia and root meristems and appears to be involved in pluripotent stem cell induction. The evidence is discussed that the homeobox genes MtWUS and MtWOX5 are “hijacked” for stem cell induction, which is key to somatic embryo and de novo root induction. In relation to SE, a role for WUS in the signalling involved in induction is discussed