Search

Parkinson’s disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral neuropathy is also increasingly recognized, as the vast majority of patients show reduced intraepidermal nerve fibers, and sensory nerve conduction and sensory function is also impaired. Many case studies in the literature show that high-dose levodopa may induce or exacerbate neuropathy in PD, which is thought to involve levodopa’s metabolism to homocysteine. Here, we treated primary cultures of dorsal root ganglia and a sensory neuronal cell line with levodopa to examine effects on cell morphology, mitochondrial content and physiology, and lysosomal function. High-dose levodopa reduced mitochondrial membrane potential. At concentrations observed in the patient, levodopa enhanced immunoreactivity to beta III tubulin. Critically, levodopa reduced lysosomal content and also reduced the proportion of lysosomes that were acidic, thereby impairing their function, whereas homocysteine tended to increase lysosome content. Levodopa is a critically important drug for the treatment of PD. However, our data suggest that at concentrations observed in the patient, it has deleterious effects on sensory neurons that are not related to homocysteine.

Simple Summary: Parkinson's disease (PD) is one of the most common chronic, degenerative brain diseases worldwide. Patients are diagnosed on the basis of slowness of movement and/or tremor and/or stiffness. However, many symptoms that are not movement related are now well recognized. Patients show changes in skin sensation, and the vast majority of patients show loss of sensory neurites, which enable sensation in skin. These changes in skin sensation occur prior to diagnosis; however, sensory issues may also be exacerbated by levodopa, an important drug used in the treatment of PD. Undoubtedly, levodopa is critical for the treatment of PD, but at high doses, it has repeatedly been shown to impair sensation in PD patients. Here, we show for the first time that high-dose levodopa impairs function of sensory neurons. Importantly, we also show for the first time that lysosomes, a critical organelle involved in recycling, are impaired by levodopa concentrations observed in patients. These data are important given the well-known lysosomal dysfunction observed in PD. Our data shed light on how levodopa, the most important drug in the treatment of PD, may contribute to sensory deficits in PD. Parkinson's disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral neuropathy is also increasingly recognized, as the vast majority of patients show reduced intraepidermal nerve fibers, and sensory nerve conduction and sensory function is also impaired. Many case studies in the literature show that high-dose levodopa may induce or exacerbate neuropathy in PD, which is thought to involve levodopa's metabolism to homocysteine. Here, we treated primary cultures of dorsal root ganglia and a sensory neuronal cell line with levodopa to examine effects on cell morphology, mitochondrial content and physiology, and lysosomal function. High-dose levodopa reduced mitochondrial membrane potential. At concentrations observed in the patient, levodopa enhanced immunoreactivity to beta III tubulin. Critically, levodopa reduced lysosomal content and also reduced the proportion of lysosomes that were acidic, thereby impairing their function, whereas homocysteine tended to increase lysosome content. Levodopa is a critically important drug for the treatment of PD. However, our data suggest that at concentrations observed in the patient, it has deleterious effects on sensory neurons that are not related to homocysteine. [ABSTRACT FROM AUTHOR]

We report on a 67-year old male with advanced stage lung adenocarcinoma (initially PD-L1 negative, EGFR and ALK negative) diagnosed in 2014. The patient received 4 lines of palliative chemotherapy from 2014 to 2017, however the disease progressed. In 2015, he also received palliative hypofractionated radiotherapy to a mediastinal mass, which was causing discomfort and pain. Since there was some data, that radiotherapy could induce PD-L1 expression, a new biopsy was taken in 2017 from the irradiated mediastinal mass. Subsequent pathologic report revealed that PD-L1 status was turned to be highly positive, with tumor proportion score of 100%. Similar high expression of PD-L1 was detected in a new metastasis in the duodenum, which was excised due to a duodenal perforation in 2017. From October 2017 to October 2019, the patient had 2-years of treatment (32 courses) with pembrolizumab and has had a positive effect (partial response) on all the lesions and following stabilization of the disease. Currently, this patient is under follow up and he is in a good condition without any complaints. Last CT-scan in March 2020 showed persisting partial response. Keywords: Nsclc, Metastases, Radiotherapy, PD-L1, Pembrolizumab

Heteronuclear diatomic rare gas molecular cations feature excited electronic terms with charge transfer character located several eV above the ground term. The role of such terms in collisions involving heteronuclear ions is studied theoretically under conditions typical of the plasma-based sources of UV and IR radiation. Calculations were carried out for processes of dissociative excitation, dissociative recombination and electron impact bound–bound excitation in Ar/Xe and Kr/Xe plasmas using the recently developed semiclassical approach combined with the ab initio data for potential energy curves and oscillator strengths of electronic transitions. The approach consistently describes the contributions from the entire rovibrational manifold to the processes studied. The cross sections of the processes mentioned are calculated for wide ranges of gas temperatures and electron energies. We show that the processes considered are quite effective when they are accompanied by transitions to charge transfer terms. For the range of electron energies typical of active media of UV and IR radiation sources the cross sections exceed those reported for the processes usually considered to involve transitions between the ground and first excited electronic state. The excitation of charge transfer electronic terms can play an important role in the kinetics of rare gas mixture plasmas.

Studies of radiative transitions between ground and charge transfer excited terms of heteronuclear rare-gas (ArXe)+ and (KrXe)+ ions with small and moderate dissociation energies ( D 0 ArXe + = 179 and D 0 KrXe + = 389 meV) are reported. Potential energy curves and dipole transition matrix elements are evaluated using ab initio calculations based on the CASSCF method followed by the NEVPT2 treatment and perturbative description of relativistic effects as implemented in the ORCA suite. We develop an efficient approach for the calculations of Boltzmann-averaged cross sections, rate constants, and absorption and emission coefficients associated with the integral contributions of bound–bound and bound–free transitions from a manifold of rovibrational states of the (RgXe)+ ion. A similar approach is used for the description of the free–free and free–bound transitions between different electronic terms of a quasimolecular (RgXe)+ ion temporarily formed during a collision of Ar or Kr atoms with Xe+ ions. Our method is based on the quantal version of the theory of non-adiabatic transitions in molecular and quasimolecular systems combined with the approximation of a quasicontinuum for rovibrational energy levels. This allowed us to obtain a semianalytic expression for the integral absorption properties particularly relevant at elevated temperatures. We perform a comprehensive analysis of the identified radiative processes in local thermodynamic equilibrium plasmas of rare gas Rg/Xe mixtures containing both atomic, Xe+, and molecular, RgXe+, ions and determine their role in the formation of the absorption and emission spectra in a wide range of wavelengths and gas temperatures. The results obtained are in good agreement with the available experimental data. [ABSTRACT FROM AUTHOR]

Märksõna koostöö on kõrghariduse võlu- ja võtmesõna, mis aitab toime tulla piiratud ressursside ning kasvava konkurentsiga. Ühise õpetamise vorme on kõrgkoolides kasutusel palju, alates loengute jagamisest eri õppejõudude vahel kuni õpetamiseni võrdselt vastutavate ja panustavate partneritena dialoogi pidades. Artiklis kirjeldatakse ja analüüsitakse Eleri Lõhmuse ja Henry Naritsa koosõpetamise kogemust audiovisuaalse produktsiooni praktilisel kursusel Tartu Ülikooli ühiskonnateaduste instituudis 2018. aasta sügissemestril. Artikkel põhineb autoetnograafiliselt dokumenteeritud materjalil, mida Lõhmus ja Narits kogusid ühistöö käigus. Artikli kolmas autor tegi intervjuud üliõpilastega, et lisada autoetnograafilistele tähelepanekutele õppija vaatepunkt. Kogutud empiirilise materjali analüüs osutab, et koosõpetamine kõrgkoolis on efektiivne ja arendav kõigile osalistele, aga õppetöö õnnestumine sõltub planeerimis- ja refleksioonioskustest ning vajab praegusest rohkem formaalset tuge. Summary

The energetic and spectral properties of the valence-bound CH2CN– anion are calculated. New data on the dependences of the energy of the ground and lowermost excited electronic states on the key geometric parameters of the system are presented. It is shown that the use of the accurate quantum-chemical approach yields a significant reduction of the inversion barrier in the system under study. [ABSTRACT FROM AUTHOR]

A number of optical and kinetic properties of heavy heteronuclear ions of inert gases ArXe+ and KrXe+ formed in the plasma of inert gas mixtures is investigated. Various types of nonadiabatic phototransitions between the ground and excited electronic terms of such ions, which are accompanied by charge exchange, are considered. The contributions of bound–free (photodissociation) and bound–bound phototransitions to the total photoabsorption coefficient under the conditions of thermal excitation of the entire vibration–rotation quasi-continuum are analyzed. We report on the results of calculation of the effective cross sections and rate constants of these processes of continuous absorption of electromagnetic radiation of the visible and UV ranges by ArXe+ and KrXe+ ions at different temperatures of the ionic plasma component. The resonant mechanism of dissociation of ArXe+ and KrXe+ ions by an electron impact in the processes of dissociative recombination and direct dissociative excitation is also considered. Analysis performed in this work extends the physical pattern of radiation-induced and collisional processes in the plasmas of Rg/Xe inert gas mixtures (Rg = Ar, Kr) excited by an electron beam, in gas discharges, and during optical pumping. The results of this study can be used for constructing kinetic models of active media of gas and plasma lasers, radiation sources of the UV range, excimer laser tubes, and microplasma cell arrays. [ABSTRACT FROM AUTHOR]

Using cover crops in fallow periods of crop production is an important management tool for reducing nitrate leaching and therefore improving nitrogen availability for subsequent crops. We estimated the short-term effect of five cover crop species on the yield of successive spring barley (Hordeum vulgare L.) for two years in Estonia. The cover crop species used in the study were winter rye (Secale cereale L.), winter turnip rape (Brassica rapa spp. oleifera L.), forage radish (Raphanus sativus L. var. longipinnatus), hairy vetch (Vicia villosa Roth), and berseem clover (Trifolium alexandrinum L.). The results indicated that out of the five tested cover crops, forage radish and hairy vetch increased the yield of subsequent spring barley, whereas the other cover crops had no effect on barley yield. All cover crop species had low C:N ratios (11−17), suggesting that nitrogen (N) was available for barley early in the spring.

Cover crops play an important role in preventing nutrient loss, reducing agricultural inputs, improving soil quality and environmental sustainability. The objectives of the study were to determine the biomass and nitrogen accumulation of cover crops and their effect on the following spring barley (Hordeum vulgare L.). Field trials with cover crop species winter rye (Secale cereale L), winter turnip rape (Brassica rapa spp. oleifera L.), forage radish (Raphanus sativus L. var. longipinnatus), hairy vetch (Vicia villosa Roth), and berseem clover (Trifolium alexandrinum L.) were carried out during four growing seasons (2016/17, 2017/18, 2018/19, and 2019/20) at the Estonian Crop Research Institute (present: The Centre of Estonian Rural Research and Knowledge, METK). Cover crop biomass and N accumulation in autumn and in spring depended on species and growing conditions. The biomass and nitrogen (N) accumulation were at their lowest in the first growing season (2016/17) due to lowest level of effective temperatures. Forage radish accumulated the highest amount of biomass and N in autumn. Berseem clover accumulated lowest amount of biomass and N in the year with drought conditions (2018) before sowing. Among overwintered cover crops, hairy vetch accumulated the highest amount of N in the spring although its biomass was similar to winter turnip rape. Winter rye had the lowest biomass and N accumulation in spring. As an average over the four years, only forage radish and hairy vetch significantly increased the yield of subsequent barley. None of the cover crops had a negative effect on barley, as the yield level following other species was similar to the control without cover crop. The knowledge about cover crop selection is useful to integrate suitable species into Estonian cropping systems. [ABSTRACT FROM AUTHOR]