Exploring the conformational dynamics of alanine dipeptide in solution subjected to an external electric field: A nonequilibrium molecular dynamics simulation

In this paper, we investigate the conformational dynamics of alanine dipeptide under an external electric field by nonequilibrium molecular dynamics simulation. We consider the case of a constant and of an oscillatory field. In this context we propose a procedure to implement the temperature control, which removes the irrelevant thermal effects of the field. For the constant field different time-scales are identified in the conformational, dipole moment, and orientational dynamics. Moreover, we prove that the solvent structure only marginally changes when the external field is switched on. In the case of oscillatory field, the conformational changes are shown to be as strong as in the previous case, and non-trivial nonequilibrium circular paths in the conformation space are revealed by calculating the integrated net probability fluxes.Comment: 23 pages, 12 figure

Pharmacotherapy of heart failure A.D. 2023. Expert opinion of Working Group on Cardiovascular Pharmacotherapy, Polish Cardiac Society

Heart failure (HF) remains one of the most common causes of hospitalization and mortality among Polish patients. The position of the Section of Cardiovascular Pharmacotherapy presents the currently applicable options for pharmacological treatment of HF based on the latest European and American guidelines from 2021–2022 in relation to Polish healthcare conditions. Treatment of HF varies depending on its clinical presentation (acute/chronic) or left ventricular ejection fraction. Initial treatment of symptomatic patients with features of volume overload is based on diuretics, especially loop drugs. Treatment aimed at reducing mortality and hospitalization should include drugs blocking the renin-angiotensin-aldosterone system, preferably angiotensin receptor antagonist/neprilysin inhibitor, i.e. sacubitril/valsartan, selected beta-blockers (no class effect — options include bisoprolol, metoprolol succinate, or vasodilatory beta-blockers — carvedilol and nebivolol), mineralocorticoid receptor antagonist, and sodium-glucose cotransporter type 2 inhibitor (flozin), constituting the 4 pillars of pharmacotherapy. Their effectiveness has been confirmed in numerous prospective randomized trials. The current HF treatment strategy is based on the fastest possible implementation of all four mentioned classes of drugs due to their independent additive action. It is also important to individualize therapy according to comorbidities, blood pressure, resting heart rate, or the presence of arrhythmias. This article emphasizes the cardio- and nephroprotective role of flozins in HF therapy, regardless of ejection fraction value. We propose practical guidelines for the use of medicines, profile of adverse reactions, drug interactions, as well as pharmacoeconomic aspects. The principles of treatment with ivabradine, digoxin, vericiguat, iron supplementation, or antiplatelet and anticoagulant therapy are also discussed, along with recent novel drugs including omecamtiv mecarbil, tolvaptan, or coenzyme Q10 as well as progress in the prevention and treatment of hyperkalemia. Based on the latest recommendations, treatment regimens for different types of HF are discussed

Improved management of lysosomal glucosylceramide levels in a mouse model of type 1 Gaucher disease using enzyme and substrate reduction therapy

Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (acid βâ glucosidase), with consequent cellular accumulation of glucosylceramide (GLâ 1). The disease is managed by intravenous administrations of recombinant glucocerebrosidase (imiglucerase), although symptomatic patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy (ERT) is not an option may also be treated by substrate reduction therapy (SRT) with miglustat. To determine whether the sequential use of both ERT and SRT may provide additional benefits, we compared the relative pharmacodynamic efficacies of separate and sequential therapies in a murine model of Gaucher disease (D409V/null). As expected, ERT with recombinant glucocerebrosidase was effective in reducing the burden of GLâ 1 storage in the liver, spleen, and lung of 3â monthâ old Gaucher mice. SRT using a novel inhibitor of glucosylceramide synthase (Genzâ 112638) was also effective, albeit to a lesser degree than ERT. Animals administered recombinant glucocerebrosidase and then Genzâ 112638 showed the lowest levels of GLâ 1 in all the visceral organs and a reduced number of Gaucher cells in the liver. This was likely because the additional deployment of SRT following enzyme therapy slowed the rate of reaccumulation of GLâ 1 in the affected organs. Hence, in patients whose disease has been stabilized by intravenously administered recombinant glucocerebrosidase, orally administered SRT with Genzâ 112638 could potentially be used as a convenient maintenance therapy. In patients naïve to treatment, ERT followed by SRT could potentially accelerate clearance of the offending substrate.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147062/1/jimd0281.pd

Potential range of impact of an ecological trap network: the case of timber stacks and the Rosalia longicorn

Although the negative impact of timber stacks on populations of saproxylic beetles is a well-known phenomenon, there is relatively little data concerning the scale of this impact and its spatial aspect. Beech timber stored in the vicinity of the forest can act as an ecological trap for the Rosalia longicorn (Rosalia alpina), so in this study we have attempted to determine the spatial range of the impact of a network of timber stacks. Timber stacks in the species’ range in the study area were listed and monitored during the adult emergence period in 2014–2016. Based on published data relating to the species’ dispersal capabilities, buffers of four radii (500, 1000, 1600, 3000 m) were delineated around the stacks and the calculated ranges of potential impact. The results show that the percentage of currently known localities of the Rosalia longicorn impacted by stacks varies from 19.7 to 81.6%, depending on the assumed impact radius. The percentage of forest influenced by timber stacks was 77% for the largest-radius buffer. The overall impact of the ecological trap network is accelerated by fragmentation of the impact-free area. It was also found that forests situated close to the timber stacks where the Rosalia longicorn was recorded were older and more homogeneous in age and species composition than those around stacks where the species was absent. Such results suggest that timber stacks act as an ecological trap in the source area of the local population

Diagnosis and treatment of thyroid cancer in children in the multicenter analysis in Poland for PPGGL

Introduction: Differentiated thyroid carcinoma (DTC) in children presents different biological behavior in comparison to adults. Authors presents preliminary results of multicenter analysis concerning incidence, diagnostics and treatment of DTC in children. Material and methods: The study is a retrospective analysis of 107 pediatric patients from 14 academic centers based on the data from 2000 to 2005 obtained by questionnaire in hospitals involved in the treatment of DTC in children. Results: Papillary thyroid cancer was diagnosed in 83 children, follicular thyroid cancer in 10 children and medullary thyroid cancer in 14 children. Incidence of DTC in children was estimated between 18 and 23 cases per year. The biggest group of patients consisted of children between 11 and 15 years of age, with girls to boys ratio 3.3 : 1. Clinically DTC in children presented most often as solitary thyroid nodule. Cervical lymphadenopathy was observed in 42% of patients. Intraoperative verification indicated metastatic nodes in 50% of children. Low stage DTC predominated (T1 in 36% and T2 in 26% of children). One step surgery was performed in 65% of children with DTC, two step surgery in 25% of patients. I131 therapy was undertaken in 80% of children. Lung metastases were indicated in post therapeutic studies in 14% of children with DTC. Prophylactic thyroidectomies were performed in 79% of children in the group of patients with MTC and RET gene mutations. Conclusions: The necessity of introduction of unified therapeutic standard in children with DTC in Poland is underlined.Wstęp: Zróżnicowane raki tarczycy (DTC, differentiated thyroid carcinoma) występują u dzieci rzadko. Większość przypadków wykrywanych jest w wieku 11-17 lat. W odróżnieniu od dorosłych DTC u dzieci prezentują odmienne zachowanie biologiczne. Mała liczba przypadków DTC w poszczególnych ośrodkach oraz względnie łagodny ich przebieg utrudniają ocenę występowania i leczenia DTC u dzieci w Polsce, uzależniając ją od wysiłków włożonych w uzyskanie rzetelnych danych. Autorzy przedstawiają wstępne wyniki analizy wieloośrodkowej dotyczące występowania, diagnostyki i leczenia DTC u dzieci. Materiał i metody: Podjęte badania są retrospektywną analizą obejmującą lata 2000-2005, opartą na danych z historii chorób uzyskanych z ankiet rozesłanych do ośrodków dla dzieci i dorosłych podejmujących leczenie DTC. Do analizy zgłoszono 107 pacjentów z 14 ośrodków akademickich w Polsce. Analizie poddano wiek i płeć dzieci z DTC, wielkość i lokalizację zmian w tarczycy, sposoby rozpoznawania DTC, rodzaje i zakres wykonywanych zabiegów operacyjnych oraz leczenie uzupełniające izotopem J131. Wyniki: Raka brodawkowatego stwierdzono u 83 dzieci, pęcherzykowego u 10 dzieci, a rdzeniastego u 14 dzieci. Częstość występowania DTC u dzieci w Polsce wahała się między 18 a 23 przypadkami rocznie. W województwach: mazowieckim i połączonych wielkopolskim i lubuskim wykazano w okresie 2000-2005 wyższą (24 i 25) częstość występowania DTC, w pozostałych województwach wykazywano od 2 do 10 przypadków DTC. Największą grupę pacjentów stanowiły dzieci w wieku 11-15 lat, a stosunek dziewcząt do chłopców wynosił 3,3 : 1. Klinicznie DTC prezentowały się najczęściej jako pojedyncze guzki tarczycy. Limfadenopatię szyjną w badaniu klinicznym stwierdzono u 42% pacjentów, a śródoperacyjnie u 50% dzieci. U większości pacjentów dominowały niższe stopnie zaawansowania DTC (T1 u 36% i T2 u 26% dzieci). Operacje jednoetapowe wykonano u 65% dzieci, operacje dwuetapowe u 25% dzieci, a profilaktyczne tyreoidektomie u 79% dzieci z grupy pacjentów z rakiem rdzeniastym tarczycy (MTC, medullary thyroid cancinoma) i mutacją genu Ret. Leczenie izotopowe J131 podjęto u 80% dzieci. Przerzuty do płuc w scyntygrafii poterapeutycznej wykazano u 14% dzieci z DTC. Wnioski: We wnioskach podkreśla się konieczność wdrożenia na terenie całego kraju ujednoliconego i ocenianego na podstawie obiektywnych przesłanek sposobu postępowania z dziećmi z DTC

Demography and Dispersal Ability of a Threatened Saproxylic Beetle: A Mark-Recapture Study of the Rosalia Longicorn (Rosalia alpina)

The Rosalia longicorn or Alpine longhorn (Coleoptera: Cerambycidae) is an endangered and strictly protected icon of European saproxylic biodiversity. Despite its popularity, lack of information on its demography and mobility may compromise adoption of suitable conservation strategies. The beetle experienced marked retreat from NW part of its range; its single population survives N of the Alps and W of the Carpathians. The population inhabits several small patches of old beech forest on hill-tops of the Ralska Upland, Czech Republic. We performed mark-recapture study of the population and assessed its distribution pattern. Our results demonstrate the high mobility of the beetle, including dispersal between hills (up to 1.6 km). The system is thus interconnected; it contained ∼2000 adult beetles in 2008. Estimated population densities were high, ranging between 42 and 84 adult beetles/hectare a year. The population survives at a former military-training ground despite long-term isolation and low cover of mature beech forest (∼1%). Its survival could be attributed to lack of forestry activities between the 1950s and 1990s, slow succession preventing canopy closure and undergrowth expansion, and probably also to the distribution of habitat patches on conspicuous hill-tops. In order to increase chances of the population for long term survival, we propose to stop clear-cuts of old beech forests, increase semi-open beech woodlands in areas currently covered by conifer plantations and active habitat management at inhabited sites and their wider environs

Nitrogenase activity of bacterial endophytes in the sandy-loam soil under grass cultivation

A dinitrogen fixation by bacteria living in symbiosis with leguminous plants is a widespread and well-known phenomenon. However, also some free-living bacteria, frequently entering into associations with various plants, reveal capabilities of fixing molecular nitrogen. Such endophytes include bacteria like Acetobacter diazotrophicus and Herbaspirillum seropediceae, discovered in countries of the tropical climate, where they lived in associatins with plants characteristic for this climate as: sugar cane, sorgo and grasses. Until now, however, very little is known about the occurrence of these bacteria in the climate of the temperate zone. Therefore, the objective of this experiment was to find out the influence of the inoculation of Italian ryegrass, Bromus willdenowii and Festulolium braunii with Acetobacter diazotrophicus and Herbaspillirum seropedieae on N2 fixation