Repetitive spinal motor neuron discharges following single transcranial magnetic stimulation: relation to dexterity

Transcranial magnetic stimulation allows to study the properties of the human corticospinal tract non-invasively. After a single transcranial magnetic stimulus, spinal motor neurons (MNs) sometimes fire not just once, but repetitively. The biological significance of such repetitive MN discharges (repMNDs) is unknown. To study the relation of repMNDs to other measures of cortico-muscular excitability and to physiological measures of the skill for finely tuned precision movements, we used a previously described quadruple stimulation (QuadS) technique (Z'Graggen et al. 2005) to quantify the amount of repMNDs in abductor digiti minimi muscles (ADMs) on both sides of 20 right-handed healthy subjects. Skillfulness for finger precision movements of both hands was assessed using a finger tapping task. In 16 subjects, a follow-up examination was performed after training of either precision movements (n=8) or force (n=8) of the left ADM. The size of the QuadS response (amplitude and area ratios) was greater in the dominant right hand than in the left hand (QuadS amplitude ratio: 47.1±18.1 versus 37.7±22.0%, Wilcoxon test: P<0.05; QuadS area ratio: 49.7±16.2% versus 36.9±23.0%, Wilcoxon test: P<0.05), pointing to a greater amount of repMNDs. Moreover, the QuadS amplitude and area increased significantly after finger precision training, but not after force training. This increase of repMNDs correlated significantly with the increase in performance in the finger tapping task. Our results demonstrate that repMNDs are related to handedness and therefore probably reflect supraspinal excitability differences. The increase of repMNDs after skills training but not after force training supports the hypothesis of a supraspinal origin of repMND

IDENTIFICATION OF CRITICAL POINTS IN MONITORING THE ORIGIN OF BEEF

Javnost sve više traži transparentnost u proizvodnji hrane. Osim dobro opisanih i dokumentiranih metoda proizvodnje, pouzdano identificiranje podrijetla hrane od životinja na svakom stupnju proizvodnje postaje sve važnije. Stoga ja ovaj parametar središnja točka u provođenju sustava menadžmenta procesa orijentiranog na kakvoću u proizvodnji životinja. Ovo je osobito točno za proizvodnju govedine zbog moguće veze izmedu BSE i Creutzfeld – Jacob sindroma. DNA analiza životinja i hrane od njih proizvedene pruža potencijalno najvišu razinu pouzdanosti u traganju za podrijetlom. Zaključci : Pouzdano traganje za podrijetlom govedine može se provesti na osnovi DNA analiza. - ldentificirane su kritične točke za uzimanje uzoraka tkiva na različitim stupnjevima klanja i prerade. Nakon toga postupak uzimanja uzoraka se poboljšao. - Prosječno 4% polovica dobilo je pogrešne naljepnice u postupku klanja u našem istraživanju. To upućuje na potrebu poboljšanja sustava menadžmenta kakvoće u klaonicama. - Troškovi primijenjenog sustava praćenja za sada su previsoki za široku primjenu u praksi.The public increasingly demands transparency in the production of foodstuff. Beside well characterized and documented production methods the reliable identification of the origin of animal derived food at any point of the production process becomes more important. Therefore, this parameter is a central point in the implementation of process - oriented quality management systems in animal production. This is especially true for beef production due to the potential relationship between BSE and Creutzfeld -Jacob- Syndrome. The DNA analysis of the animals and foodstuff produced of them provides potentially the highest level of reliability for the tracing of origin

Introducing innovative cellular therapies into the clinic: a 2-year retrospective experience of a chimeric antigen receptor T-cell programme at a single centre in Switzerland

AIM OF THE STUDY Chimeric antigen receptor T (CAR-T) cells are a powerful form of immune-cell therapy for patients with relapsed/refractory B-cell lymphoma and acute B lymphoblastic leukaemia. CAR-T cells have been commercially available in Switzerland since 2018. Because of the complexity and costs of this treatment it is critical to review patient outcomes in real-world settings, to examine whether the promising results from pivotal trials can be reproduced and to identify clinical parameters that determine their efficacy. METHODS Here we present results of a retrospective study analysing outcomes of patients treated with CAR-T cells in a single academic centre in Switzerland during the first two years after commercial approval (BASEC-No. 2020-02271). Cytokine release syndrome (CRS), immune-cell associated neurotoxicity syndrome (ICANS), responses to treatment, ancillary laboratory studies and administrative specifics of CAR-T treatment were examined and are discussed. RESULTS From October 2018 to August 2020 CAR-T cell therapy was evaluated in 34 patients, mostly with relapsed/refractory aggressive B-cell lymphoma (87% had refractory disease). Thirty-one patients underwent leukapheresis. Three of 31 patients (9.6%) died of rapid disease progression before the CAR-T cell product was delivered, two patients were enrolled into a clinical trial, three patients were not given CAR-T cells for other reasons. Ultimately, 23 patients were infused with a commercial CAR-T cell product and included in this analysis. Fourteen (61%) patients received bridging therapy while waiting for a median of 41 days (range 31-62) for delivery of the CAR-T cell product. Toxicity and severe side effects were rare (CRS >3 in 13%, ICANS > grade 3 in 10% of patients), manageable and resolved completely thereafter. The best overall response rate was 65%, with complete responses in 38% of lymphoma patients. At 12 months postinfusion, 61% of patients were alive and 35% progression free. With a median follow-up of 14 months, 13/23 (56%) patients were alive at the time of writing. CONCLUSION CAR-T cell therapy proved to be safe and manageable under adequate hospital conditions. Outcomes resemble results from pivotal trials. The majority of patients was heavily pretreated and refractory at the time of CAR-T cell infusion. Patient selection, time point of leukapheresis, bridging strategies and timing of CAR-T cell infusion may be critical to further improve outcomes

Забезпечення розвитку інноваційності промислових підприємств при активізації інтелектуального капіталу суспільства

Проаналізовано стан і умови інноваційної діяльності підприємств в Україні. Досліджено проблеми неефективності державної політики в економічній сфері щодо розвитку інноваційності промислових підприємств. Розроблено пропозиції з удосконалення структури і напрямів діяльності державної політики щодо розвитку інноваційності промислових підприємств при активізації інтелектуального капіталу суспільства.Проанализированы состояние и условия инновационной деятельности предприятий в Украине. Исследованы проблемы неэффективности государственной политики в экономической сфере относительно развития инновационности промышленных предприятий. Разработаны предложения по усовершенствованию структуры и направлений деятельности государственной политики относительно развития инновационности промышленных предприятий при активизации интеллектуального капитала.The state and terms of innovative activity of enterprises in Ukraine are analyzed. Problems of inefficiency of public policy are investigated in an economic sphere in relation to innovativeness development of industrial enterprises. Suggestions for the improvement of structure and directions public policy activity in relation to innovativeness development of the industrial enterprises during activation of the society intellectual capital are worked out

Sedimentological evidence for pronounced glacial‐interglacial climate fluctuations in NE Tibet in the latest Pliocene to early Pleistocene

The intensification of Northern Hemisphere glaciation (iNHG) and uplift of the Tibetan Plateau have been argued to be among the main drivers of climate change in midlatitude Central Asia during the Pliocene/Pleistocene. While most proxy records that support this hypothesis are from regions outside the Tibetan Plateau (such as from the Chinese Loess Plateau), detailed paleoclimatic information for the plateau itself during that time has yet remained elusive. Here we present a temporally highly resolved (~500 years) sedimentological record from the Qaidam Basin situated on the northeastern Tibetan Plateau that shows pronounced glacial‐interglacial climate variability during the interval from 2.7 to 2.1 Ma. Glacial (interglacial) intervals are generally characterized by coarser (finer) grain size, minima (maxima) in organic matter content, and maxima (minima) in carbonate content. Comparison of our results with Earth's orbital parameters and proxy records from the Chinese Loess Plateau suggests that the observed climate fluctuations were mainly driven by changes in the Siberian High/East Asian winter monsoon system as a response to the iNHG. They are further proposed to be enhanced by the topography of the Tibetan Plateau and its impact on the position and intensity of the westerlies

On Hirschman and log-Sobolev inequalities in mu-deformed Segal-Bargmann analysis

We consider a deformation of Segal-Bargmann space and its transform. We study L^p properties of this transform and obtain entropy-entropy inequalities (Hirschman) and entropy-energy inequalities (log-Sobolev) that generalize the corresponding known results in the undeformed theory.Comment: 42 pages, 3 figure

Prevalence of adult ADHD in an all-female prison unit.

There is increasing evidence suggesting a link between ADHD and criminality, including a strong association between ADHD symptoms and the likelihood of being on probation or in prison. Most studies investigating the prevalence of ADHD in prison populations have focused on adult male offenders. In the current study, 69 female prisoners were screened for both childhood and adult ADHD symptoms using the Barkley Adult ADHD Rating Scale-IV. The results indicate that 41 % of the prisoners met the diagnostic criteria for ADHD in childhood and continued to meet criteria for ADHD as adults. More importantly, young female prisoners (aged 18-25) were significantly more likely to report symptoms of ADHD than older prisoners. Prisoners who reported symptoms of ADHD also reported high levels of impairment associated with these symptoms. A better understanding of the prevalence of ADHD in female prison units can highlight specific areas for intervention during rehabilitation, as well as the management of serious incidents within prison

Quantification of glyphosate and aminomethylphosphonic acid from microbiome reactor fluids

Rationale: Glyphosate is one of the most widely used herbicides and it is suspected to affect the intestinal microbiota through inhibition of aromatic amino acid synthesis via the shikimate pathway.In vitromicrobiome bioreactors are increasingly used as model systems to investigate effects on intestinal microbiota and consequently methods for the quantitation of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in microbiome model systems are required. Methods: An optimized protocol enables the analysis of both glyphosate and AMPA by simple extraction with methanol:acetonitrile:water (2:3:1) without further enrichment steps. Glyphosate and AMPA are separated by liquid chromatography on an amide column and identified and quantified with a targeted tandem mass spectrometry method using a QTRAP 5500 system (AB Sciex). Results: Our method has a limit of detection (LOD) in extracted water samples of <2 ng/mL for both glyphosate and AMPA. In complex intestinal medium, the LOD is 2 and 5 ng/mL for glyphosate and AMPA, respectively. These LODs allow for measurement at exposure-relevant concentrations. Glyphosate levels in a bioreactor model of porcine colon were determined and consequently it was verified whether AMPA was produced by porcine gut microbiota. Conclusions: The method presented here allows quantitation of glyphosate and AMPA in complex bioreactor fluids and thus enables studies of the impact of glyphosate and its metabolism on intestinal microbiota. In addition, the extraction protocol is compatible with an untargeted metabolomics analysis, thus allowing one to look for other perturbations caused by glyphosate in the same sample