Altered balance of glutamatergic/GABAergic synaptic input and associated changes in dendrite morphology after BDNF expression in BDNF-deficient hippocampal neurons

Cultured neurons from bdnf-/- mice display reduced densities of synaptic terminals, although in vivo these deficits are small or absent. Here we aimed at clarifying the local responses to postsynaptic brain-derived neurotrophic factor (BDNF). To this end, solitary enhanced green fluorescent protein (EGFP)-labeled hippocampal neurons from bdnf-/- mice were compared with bdnf-/- neurons after transfection with BDNF, bdnf-/- neurons after transient exposure to exogenous BDNF, and bdnf+/+ neurons in wild-type cultures. Synapse development was evaluated on the basis of presynaptic immunofluorescence and whole-cell patch-clamp recording of miniature postsynaptic currents. It was found that neurons expressing BDNF::EGFP for at least 16 h attracted a larger number of synaptic terminals than BDNF-deficient control neurons. Transfected BDNF formed clusters in the vicinity of glutamatergic terminals and produced a stronger upregulation of synaptic terminal numbers than high levels of ambient BDNF. Glutamatergic and GABAergic synapses reacted differently to postsynaptic BDNF: glutamatergic input increased, whereas GABAergic input decreased. BDNF::EGFP-expressing neurons also differed from BDNF-deficient neurons in their dendrite morphology: they exhibited weaker dendrite elongation and stronger dendrite initiation. The upregulation of glutamatergic synaptic input and the BDNF-induced downregulation of GABAergic synaptic terminal numbers by postsynaptic BDNF depended on tyrosine receptor kinase B activity, as deduced from the blocking effects of K252a. The suppression of dendrite elongation was also prevented by block of tyrosine receptor kinase B but required, in addition, glutamate receptor activity. Dendritic length decreased with the number of glutamatergic contacts. These results illuminate the role of BDNF as a retrograde synaptic regulator of synapse development and the dependence of dendrite elongation on glutamatergic input

Citizen advisory groups for the creation and improvement of decision aids: experience from two Swiss centers for primary care.

Guidelines for patient decision aids (DA) recommend target population involvement throughout the development process, but developers may struggle because of limited resources. We sought to develop a feasible means of getting repeated feedback from users. Between 2017 and 2020, two Swiss centers for primary care (Lausanne and Bern) created citizen advisory groups to contribute to multiple improvement cycles for colorectal, prostate and lung cancer screening DAs. Following Community Based Participatory Research principles, we collaborated with local organizations to recruit citizens aged 50 to 75 without previous cancer diagnoses. We remunerated incidental costs and participant time. One center supplemented in-person meetings by mailed paper questionnaires, while the other supplemented meetings using small-group workshops and analyses of meeting transcripts. In Lausanne, we received input from 49 participants for three DAs between 2017 and 2020. For each topic, participants gave feedback on the initial draft and 2 subsequent versions during in-person meetings with ~ 8 participants and one round of mailed questionnaires. In Bern, 10 participants were recruited among standardized patients from the university, all of whom attended in-person meetings every three months between 2017 and 2020. At both sites, numerous changes were made to the content, appearance, language, and tone of DAs and outreach materials. Participants reported high levels of satisfaction with the participative process. Citizen advisory groups are a feasible means of repeatedly incorporating end-user feedback during the creation of multiple DAs. Methodological differences between the two centers underline the need for a flexible model adapted to local needs

L-isoleucine-supplemented Oral Rehydration Solution in the Treatment of Acute Diarrhoea in Children: A Randomized Controlled Trial

Antimicrobial peptides represent an important component of the innate immune defenses of living organisms, including humans. They are broad-spectrum surface-acting agents secreted by the epithelial cells of the body in response to infection. Recently, L-isoleucine and its analogues have been found to induce antimicrobial peptides. The objectives of the study were to examine if addition of L-isoleucine to oral rehydration salts (ORS) solution would reduce stool output and/or duration of acute diarrhoea in children and induce antimicrobial peptides in intestine. This double-blind randomized controlled trial was conducted at the Dhaka Hospital of ICDDR,B. Fifty male children, aged 6-36 months, with acute diarrhoea and some dehydration, attending the hospital, were included in the study. Twenty-five children received L-isoleucine (2 g/L)-added ORS (study), and 25 received ORS without L-isoleucine (control). Stool weight, ORS intake, and duration of diarrhoea were the primary outcomes. There was a trend in reduction in mean±standard deviation (SD) daily stool output (g) of children in the L-isoleucine group from day 2 but it was significant on day 3 (388±261 vs 653±446; the difference between mean [95% confidence interval (CI) (-)265 (−509, −20); p=0.035]. Although the cumulative stool output from day 1 to day 3 reduced by 26% in the isoleucine group, it was not significant. Also, there was a trend in reduction in the mean±SD intake of ORS solution (mL) in the L-isoleucine group but it was significant only on day 1 (410±169 vs 564±301), the difference between mean (95% CI) (-)154 (-288, −18); p=0.04. The duration (hours) of diarrhoea was similar in both the groups. A gradual increase in stool concentrations of ß-defensin 2 and 3 was noted but they were not significantly different between the groups. L-isoleucine-supplemented ORS might be beneficial in reducing stool output and ORS intake in children with acute watery diarrhoea. A further study is warranted to substantiate the therapeutic effect of L-isoleucine

Consumer acceptance of minced meat patties from boars in four European countries

A consumer study was performed in four EU countries to further clarify the acceptability of meat with boar taint. In Denmark, France, Italy and Poland, a total of 476 female consumers evaluated 8 meat patties from boars with varying levels of skatole (0.10-0.40μg/g fat tissue) and androstenone (0.47-2.00 μg/g fat tissue), in a pair-wise comparison with patties from castrates. Boar meat patties were always less preferred than the castrate meat patties, regardless of the level of androstenone and skatole. Acceptability of the boar meat patties decreased with increasing skatole level. In samples with low skatole levels, higher levels of androstenone also reduced acceptability among androstenone sensitive consumers. No clear threshold levels for androstenone and skatole could be identified. Maps presenting the reduction in preference due to increasing levels of skatole and androstenone, and corrected for the general acceptance of the meat product were developed, taking into account androstenone sensitivity. Further work is needed, covering the whole range of androstenone and skatole levels found in entire male pigs and for a wider set of meat products.info:eu-repo/semantics/acceptedVersio

Rashba spin–orbit coupling effect on the quantum Hall magnetoresistivity

In this paper we analyze the influence of the Rashba spin–orbit coupling on the quantum Hall magnetoresistivity in a two-dimensional electron system (2DES). The study is based on an analytical model for the integer quantum Hall effect (IQHE) and the Shubnikov-de Haas (SdH) phenomena. This model shows the behaviour of the Hall magnetoresistivity when the Rashba parameter is varied, and reproduces Hall plateaux of a 2DES confined in a III–V heterostructure. We also discuss the Rashba and Zeeman competition and its effect on the width of the Hall magnetoresistivity plateaux

Low-Luminosity Accretion in Black Hole X-ray Binaries and Active Galactic Nuclei

At luminosities below a few percent of Eddington, accreting black holes switch to a hard spectral state which is very different from the soft blackbody-like spectral state that is found at higher luminosities. The hard state is well-described by a two-temperature, optically thin, geometrically thick, advection-dominated accretion flow (ADAF) in which the ions are extremely hot (up to $10^{12}$ K near the black hole), the electrons are also hot ($\sim10^{9-10.5}$ K), and thermal Comptonization dominates the X-ray emission. The radiative efficiency of an ADAF decreases rapidly with decreasing mass accretion rate, becoming extremely low when a source reaches quiescence. ADAFs are expected to have strong outflows, which may explain why relativistic jets are often inferred from the radio emission of these sources. It has been suggested that most of the X-ray emission also comes from a jet, but this is less well established.Comment: To appear in "From X-ray Binaries to Quasars: Black Hole Accretion on All Mass Scales" edited by T. Maccarone, R. Fender, L. Ho, to be published as a special edition of "Astrophysics and Space Science" by Kluwe