Summary
Background
Gut‐directed hypnotherapy can reduce IBS symptoms, but the mechanisms underlying this therapeutic effect remain unknown.
Aim
To determine the effect of hypnotherapy and educational ...intervention on brain responses to cued rectal distensions in IBS patients.
Methods
Forty‐four women with moderate‐to‐severe IBS and 20 healthy controls (HCs) were included. Blood oxygen level dependent (BOLD) signals were measured by functional Magnetic Resonance Imaging (fMRI) during expectation and delivery of high‐ (45 mmHg) and low‐intensity (15 mmHg) rectal distensions. Twenty‐five patients were assigned to hypnotherapy (HYP) and 16 to educational intervention (EDU). Thirty‐one patients completed treatments and posttreatment fMRI.
Results
Similar symptom reduction was achieved in both groups. Clinically successful treatment (all responders) was associated with significant BOLD attenuation during high‐intensity distension in the dorsal and ventral anterior insula (cluster size 142, P = 0.006, and cluster size 101, P = 0.005 respectively). Moreover HYP responders demonstrated a pre–post treatment BOLD attenuation in posterior insula (cluster sizes 59, P = 0.05) while EDU responders had a BOLD attenuation in prefrontal cortex (cluster size 60, P = 0.05). Pre–post differences for expectation conditions were almost exclusively seen in the HYP group. Following treatment, the brain response to distension was similar to that observed in HCs, suggesting that the treatment had a normalising effect on the central processing abnormality of visceral signals in IBS.
Conclusions
The abnormal processing and enhanced perception of visceral stimuli in IBS can be normalised by psychological interventions. Symptom improvement in the treatment groups may be mediated by different brain mechanisms. Clinical trial number: NCT01815164.
This review discusses antibacterial peptides from the perspective of development into clinically useful chemotherapeutic drugs using short lactoferricin based peptides as examples. The review shows ...how important features for antibacterial activity can be identified and explored using the molecular properties of a range of natural and non-natural amino acids. The results have been further refined quantitatively using a "soft-modelling" approach where important structural parameters that influence the antibacterial activity of 15-residue model peptides were identified. The review describes how this knowledge is utilised to generate pharmacophores for antibacterial efficacy. These pharmacophores turn out to be surprisingly small and relatively consistent between typical Gram-negative and Gram-positive bacteria leading to the discovery of a novel class of short synthetic cationic antimicrobial peptides. These compounds are found to have high antibacterial activity against several bacterial strains that are resistant to commercial antibiotics, and are promising as future clinical candidates for treatment of infections caused by several clinically relevant pathogens.
Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, ...doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18–60 years with two or more risk factors (stage III–IV, elevated lactate dehydrogenase levels, performance status 2–4). To our knowledge, this is the first study comparing these two regimens in this patient group.
We obtained data for the period 2004–2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety.
Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P = 0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P = 0.02).
R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.
Cationic antibacterial peptides have been proclaimed as new drugs against multiresistant bacteria. Their limited success so far is partially due to the size of the peptides, which gives rise to ...unresolved issues regarding administration, bioavailability, metabolic stability, and immunogenicity. We have systematically investigated the minimum antibacterial motif of cationic antibacterial peptides regarding charge and lipophilicity/bulk and found that the pharmacophore was surprisingly small, opening the opportunity for development of short antibacterial peptides for systemic use.
We analysed the effect of the 2018 European drought on greenhouse gas (GHG) exchange of five North European mire ecosystems. The low precipitation and high summer temperatures in Fennoscandia led to ...a lowered water table in the majority of these mires. This lowered both carbon dioxide (CO
) uptake and methane (CH
) emission during 2018, turning three out of the five mires from CO
sinks to sources. The calculated radiative forcing showed that the drought-induced changes in GHG fluxes first resulted in a cooling effect lasting 15-50 years, due to the lowered CH
emission, which was followed by warming due to the lower CO
uptake. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
Background
Irritable bowel syndrome (IBS) patients show evidence of altered central processing of visceral signals. One of the proposed alterations in sensory processing is an altered engagement of ...endogenous pain modulation mechanisms. The aim was to test the hypothesis that IBS patients with (IBS‐S) and without visceral hypersensitivity (IBS‐N) differ in their ability to engage endogenous pain modulation mechanism during habituation to repeated visceral stimuli.
Methods
Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in 33 IBS patients with and without visceral hypersensitivity and 18 healthy controls (HCs). BOLD response to early and late phase of the distension series was compared within and between groups.
Key Results
While BOLD response was similar during the early phase of the experiment, IBS‐S showed greater BOLD response than IBS‐N and HCs during the late phase of the distension series. IBS‐S showed increasing BOLD response both to the anticipation and delivery of low intensity rectal distensions in brain regions including insula, anterior and mid cingulate cortex. IBS‐N showed decreasing BOLD response to repeated rectal distensions in brain regions including insula, prefrontal cortex and amygdala.
Conclusions & Inferences
These findings are consistent with compromised ability of IBS‐S to respond to repeated delivery of rectal stimuli, both in terms of sensitization of sensory pathways and habituation of emotional arousal. The fact that both IBS subgroups met Rome criteria, and did not differ in terms of reported symptom severity demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.
Brain blood oxygen level dependent (BOLD) response was measured during repeated rectal distension and its anticipation in IBS patients with and without visceral hypersensitivity. BOLD response to early and late phase of the distension series was measured. Our findings are consistent with a compromised ability of IBS subjects with visceral hypersensitivity to respond to repeated delivery of an aversive rectal stimulus, both in terms sensitization of sensory pathways and habituation to emotional arousal. The fact that both IBS subgroups did not differ in terms of reported symptom severity or duration demonstrates that similar symptom patterns can result from different underlying neurobiological mechanisms.
ABSTRACT Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for ...neutrino events with deposited energies TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, -induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index −2.50 0.09 and a flux at 100 TeV of . Under the same assumptions, an unbroken power law with index −2 is disfavored with a significance of 3.8 (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 (p = 1.7%) if instead we compare the best fit to a spectrum with index −2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a e fraction of 0.18 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 (p = 0.014%).
Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We ...dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.
This review focuses on important structural features affecting the antimicrobial activity of 15-residue derivatives of lactoferricins. Our investigations are based on an alanine-scan of a 15-residue ...bovine lactoferricin derivative that revealed the absolute necessity of two tryptophan residues for antimicrobial activity. This "tryptophan-effect" was further explored in homologous derivatives of human, caprine, and porcine lactoferricins by the incorporation of one additional tryptophan residue, and by increasing the content of tryptophan in the bovine derivative to five residues. Most of the resulting peptides display a substantial increase in antimicrobial activity. To identify which molecular properties make tryptophan so effective, a series of bovine lactoferricin derivatives were prepared containing non-encoded unnatural aromatic amino acids, which represented various aspects of the physicochemical nature of tryptophan. The results clearly demonstrate that tryptophan is not unique since most of the modified peptides were of higher antimicrobial potency than the native peptide. The size and three-dimensional shape of the inserted "super-tryptophans" are the most important determinants for the high antimicrobial activity of the modified peptides. This review also describes the use of a "soft-modeling" approach in order to identify important structural parameters affecting the antimicrobial activity of modified 15-residue murine lactoferricin derivatives. This QSAR-study revealed that the net charge, charge asymmetry, and micelle affinity of the peptides were the most important structural parameters affecting their antimicrobial activity.Key words: antimicrobial peptides, lactoferricin, non-encoded aromatic amino acids, tryptophan.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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