Transcranial Magnetic Stimulation for the treatment of tinnitus: Effects on cortical excitability

<p>Abstract</p> <p>Background</p> <p>Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an innovative treatment for chronic tinnitus. The aim of the present study was to elucidate the underlying mechanism and to evaluate the relationship between clinical outcome and changes in cortical excitability. We investigated ten patients with chronic tinnitus who participated in a sham-controlled crossover treatment trial. Magnetic-resonance-imaging and positron-emission-tomography guided 1 Hz rTMS were performed over the auditory cortex on 5 consecutive days. Active and sham treatments were separated by one week. Parameters of cortical excitability (motor thresholds, intracortical inhibition, intracortical facilitation, cortical silent period) were measured serially before and after rTMS treatment by using single- and paired-pulse transcranial magnetic stimulation. Clinical improvement was assessed with a standardized tinnitus-questionnaire.</p> <p>Results</p> <p>We noted a significant interaction between treatment response and changes in motor cortex excitability during active rTMS. Specifically, clinical improvement was associated with an increase in intracortical inhibition, intracortical facilitation and a prolongation of the cortical silent period. These results indicate that intraindividual changes in cortical excitability may serve as a correlate of response to rTMS treatment.</p> <p>Conclusion</p> <p>The observed alterations of cortical excitability suggest that low frequency rTMS may evoke long-term-depression like effects resulting in an improvement of subcortical inhibitory function.</p

Interaction of climate change with effects of conspecific and heterospecific density on reproduction

We studied the relationship between temperature and the coexistence of great titParus majorand blue titCyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density-dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.Peer reviewe

Mycobacteria Attenuate Nociceptive Responses by Formyl Peptide Receptor Triggered Opioid Peptide Release from Neutrophils

In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR) and/or toll like receptor (TLR) agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively). Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, β-endorphin) antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim at selective FPR agonists to boost endogenous analgesia

The genome landscape of indigenous African cattle

Background: The history of African indigenous cattle and their adaptation to environmental and human selection pressure is at the root of their remarkable diversity. Characterization of this diversity is an essential step towards understanding the genomic basis of productivity and adaptation to survival under African farming systems. Results: We analyze patterns of African cattle genetic variation by sequencing 48 genomes from five indigenous populations and comparing them to the genomes of 53 commercial taurine breeds. We find the highest genetic diversity among African zebu and sanga cattle. Our search for genomic regions under selection reveals signatures of selection for environmental adaptive traits. In particular, we identify signatures of selection including genes and/ or pathways controlling anemia and feeding behavior in the trypanotolerant N’Dama, coat color and horn development in Ankole, and heat tolerance and tick resistance across African cattle especially in zebu breeds. Conclusions: Our findings unravel at the genome-wide level, the unique adaptive diversity of African cattle while emphasizing the opportunities for sustainable improvement of livestock productivity on the continent

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

Variation in clutch size in relation to nest size in birds

Peer reviewe

Determinants of Cone and Rod Functions in Geographic Atrophy: AI-Based Structure-Function Correlation

Purpose To investigate the association between retinal microstructure and cone- and rod-function in geographic atrophy (GA) secondary to age-related macular degeneration (AMD) using artificial-intelligence-(AI) algorithms. Design Prospective, observational case series Methods Forty-one eyes of 41 patients (75.8±8.4 years; 22 female) from a tertiary referral hospital were included (Directional-Spread-in-Geographic-Atrophy (DSGA) natural history study; NCT02051998). Mesopic, dark-adapted (DA) cyan and red sensitivity were assessed using fundus-controlled perimetry (“microperimetry”); retinal microstructure using spectral-domain optical-coherence-tomography (SD-OCT), fundus autofluorescence (FAF) and near-infrared-reflectance (IR) imaging. Layer-thicknesses and -intensities and FAF- and IR-intensities were extracted for each test-point. We evaluated the cross-validated mean absolute error (MAE) for random-forest-based predictions of retinal sensitivity with and without patient-specific training-data and the increase mean-squared error (%IncMSE) as measure of feature-importance. Results Retinal sensitivity was predicted with a MAE of 4.64 dB for mesopic, 4.89 dB for DA cyan and 4.40 dB for DA red testing in absence of patient-specific data. Partial addition of patient-specific sensitivity data to the training sets decreased the MAE to 2.89 dB, 2.86 dB and 2.77 dB. For all three types of testing, the outer nuclear layer-thickness constituted the most important predictive feature (35.0, 42.22 and 53.74 %IncMSE). Spatially-resolved mapping of “inferred sensitivity” revealed regions with differential degrees of mesopic and DA cyan sensitivity loss outside of the GA lesions. Conclusions “Inferred sensitivity” accurately reflected retinal function in patients with GA. Mapping of “inferred sensitivity” could facilitate monitoring of disease progression and serve as “quasi functional” surrogate outcome in clinical trials, especially in consideration of retinal regions beyond areas of GA

Imaging Measurable (Minimal) Residual Disease in Multiple Myeloma

Purpose of Review The availability of effective anti-myeloma therapies has led to the concept of new response categories that define responses deeper than conventionally defined complete response (CR). In cases of CR, deepest response, defined as minimal residual disease (MRD)-negative status, has been independently associated with prolonged progression-free survival and overall survival. In spite of an unmeasurable MRD, most patients eventually relapse. Because current methodology using flow cytometry or gene sequencing focuses on sampling MRD primarily from bone marrow, the low-level disease that may be present at other places in the skeleton and/or at extra-skeletal sites could be ultimately responsible for clinical relapse. Relevantly, sensitive imaging has the potential to complement MRD assessment by providing a complete picture of the entire bone/bone marrow compartment and extramedullary sites. Recent Findings The International Myeloma Working Group (IMWG) has come up with new response categories of MRD negativity with or without the absence of disease on imaging. Multiple studies support the notion that FDG-PET has higher specificity over MRI as MRD assessment adjunct because the detection of FDG-PET-positive lesions has prognostic value in patients with multiple myeloma at diagnosis and at time of relapse. MR techniques, including functional variations, and new PET tracers add additional information for MRD evaluation. Summary We provide an overview discussing the shortcomings and advantages of various imaging strategies that can complement the current MRD methodology. We need more trials investigating the new PET tracers and functional MRI as MRD assessment tools. In order for sensitive imaging to be validated for MRD evaluation and response-adapted treatment algorithms, we recommend that prospective clinical trials incorporate the imaging-based definitions of newly defined IMWG response and MRD criteria