Evidence for spatially-responsive neurons in the rostral thalamus

Damage involving the anterior thalamic and adjacent rostral thalamic nuclei may result in a severe anterograde amnesia, similar to the amnesia resulting from damage to the hippocampal formation. Little is known, however, about the information represented in these nuclei. To redress this deficit, we recorded units in three rostral thalamic nuclei in freely-moving rats (the parataenial nucleus, the anteromedial nucleus and nucleus reuniens). We found units in these nuclei possessing previously unsuspected spatial properties. The various cell types show clear similarities to place cells, head direction cells, and perimeter/border cells described in hippocampal and parahippocampal regions. Based on their connectivity, it had been predicted that the anterior thalamic nuclei process information with high spatial and temporal resolution while the midline nuclei have more diffuse roles in attention and arousal. Our current findings strongly support the first prediction but directly challenge or substantially moderate the second prediction. The rostral thalamic spatial cells described here may reflect direct hippocampal/parahippocampal inputs, a striking finding of itself, given the relative lack of place cells in other sites receiving direct hippocampal formation inputs. Alternatively, they may provide elemental thalamic spatial inputs to assist hippocampal spatial computations. Finally, they could represent a parallel spatial system in the brain

Regional differences in physicians’ behavior and factors influencing the intensity of PCSK9 inhibitor therapy with alirocumab: a subanalysis of the ODYSSEY APPRISE study

BackgroundDespite better accessibility of the effective lipid-lowering therapies, only about 20% of patients at very high cardiovascular risk achieve the low-density lipoprotein cholesterol (LDL-C) goals. There is a large disparity between European countries with worse results observed for the Central and Eastern Europe (CEE) patients. One of the main reasons for this ineffectiveness is therapeutic inertia related to the limited access to appropriate therapy and suitable dosage intensity. Thus, we aimed to compare the differences in physicians’ therapeutic decisions on alirocumab dose selection, and factors affecting these in CEE countries vs. other countries included in the ODYSSEY APPRISE study.MethodsODYSSEY APPRISE was a prospective, single-arm, phase 3b open-label (≥12 weeks to ≤30 months) study with alirocumab. Patients received 75 or 150 mg of alirocumab every 2 weeks, with dose adjustment during the study based on physician's judgment. The CEE group in the study included Czechia, Greece, Hungary, Poland, Romania, Slovakia, and Slovenia, which we compared with the other nine European countries (Austria, Belgium, Denmark, Finland, France, Germany, Italy, Spain, and Switzerland) plus Canada.ResultsA total of 921 patients on alirocumab were involved [modified intention-to-treat (mITT) analysis], including 114 (12.4%) subjects from CEE countries. Therapy in CEE vs. other countries was numerically more frequently started with lower alirocumab dose (75 mg) at the first visit (74.6 vs. 68%, p = 0.16). Since week 36, the higher dose was predominantly used in CEE patients (150 mg dose in 51.6% patients), which was maintained by the end of the study. Altogether, alirocumab dose was significantly more often increased by CEE physicians (54.1 vs. 39.9%, p = 0.013). Therefore, more patients achieved LDL-C goal at the end of the study (<55 mg/dl/1.4 mmol/L and 50% reduction of LDL-C: 32.5% vs. 28.8%). The only factor significantly influencing the decision on dose of alirocumab was LDL-C level for both countries’ groups (CEE: 199.2 vs. 175.3 mg/dl; p = 0.019; other: 205.9 vs. 171.6 mg/dl; p < 0.001, for 150 and 75 mg of alirocumab, respectively) which was also confirmed in multivariable analysis (OR = 1.10; 95% CI: 1.07–1.13).ConclusionsDespite larger unmet needs and regional disparities in LDL-C targets achievement in CEE countries, more physicians in this region tend to use the higher dose of alirocumab, they are more prone to increase the dose, which is associated with a higher proportion of patients reaching LDL-C goals. The only factor that significantly influences decision whether to increase or decrease the dose of alirocumab is LDL-C level

Kinetics of Graphene Growth on Liquid Copper by Chemical Vapor Deposition

We report a combined experimental and computational study of the kinetics of graphene growth during chemical vapor deposition on a liquid copper catalyst. The use of liquid metal catalysts offers bright perspectives for controllable large-scale, high-quality synthesis technologies of two-dimensional materials. We carried out a series of growth experiments varying CH4-to-H2 pressure ratios and deposition temperature. By monitoring the graphene flake morphology in real time during growth using in situ optical microscopy in radiation mode, we explored the morphology and kinetics of the growth within a wide range of experimental conditions. Following an analysis of the flakes' growth rates, we conclude that the growth mode was attachment-limited. The attachment and detachment activation energies of carbon species are derived as 1.9 +- 0.3 eV and 2.0 +- 0.1 eV, respectively. We also conducted free-energy calculations by a moment tensor potential trained to density functional theory data. Our simulations propose that carbon dimers are most likely the active carbon species during growth, with attachment and detachment barriers of 1.71 +- 0.15 eV and 2.09 +- 0.02 eV, respectively, being in good agreement with the experimental results

Nucleus reuniens of the thalamus contains head direction cells

Discrete populations of brain cells signal heading direction, rather like a compass. These ‘head direction’ cells are largely confined to a closely-connected network of sites. We describe, for the first time, a population of head direction cells in nucleus reuniens of the thalamus in the freely-moving rat. This novel subcortical head direction signal potentially modulates the hippocampal CA fields directly and, thus, informs spatial processing and memor

The Anatomical Boundary of the Rat Claustrum

The claustrum is a subcortical nucleus that exhibits dense connectivity across the neocortex. Considerable recent progress has been made in establishing its genetic and anatomical characteristics, however, a core, contentious issue that regularly presents in the literature pertains to the rostral extent of its anatomical boundary. The present study addresses this issue in the rat brain. Using a combination of immunohistochemistry and neuroanatomical tract tracing, we have examined the expression profiles of several genes that have previously been identified as exhibiting a differential expression profile in the claustrum relative to the surrounding cortex. The expression profiles of parvalbumin (PV), crystallin mu (Crym), and guanine nucleotide binding protein (G protein), gamma 2 (Gng2) were assessed immunohistochemically alongside, or in combination with cortical anterograde, or retrograde tracer injections. Retrograde tracer injections into various thalamic nuclei were used to further establish the rostral border of the claustrum. Expression of all three markers delineated a nuclear boundary that extended considerably (∼500 μm) beyond the anterior horn of the neostriatum. Cortical retrograde and anterograde tracer injections, respectively, revealed distributions of cortically-projecting claustral neurons and cortical efferent inputs to the claustrum that overlapped with the gene marker-derived claustrum boundary. Finally, retrograde tracer injections into the thalamus revealed insular cortico-thalamic projections encapsulating a claustral area with strongly diminished cell label, that extended rostral to the striatum

Position of the Polish Cardiac Society on therapeutic targets for LDL cholesterol concentrations in secondary prevention of myocardial infarctions

Cardiovascular diseases account for 43% of deaths in Poland. The COVID-19 pandemic increased the number of cardiovascular deaths by as much as 16.7%. Lipid metabolism disorders are observed in about 20 million Poles. Lipid disorders are usually asymptomatic, they cause a significant increase in the risk of cardiovascular diseases. Up to 20% of patients who experience an acute coronary syndrome (ACS) may experience a recurrence of a cardiovascular event within a year, and up to 40% of these patients may be re-hospitalized. Within 5 years after a myocardial infarction, 18% of patients suffer a second ACS and 13% have got a stroke. Lipid-lowering therapy is an extremely important element of comprehensive management, both in primary and secondary prevention, and its main goal is to prevent or extend the time to the onset of heart or vascular disease and reduce the risk of cardiovascular events. A patient with a history of ACS belongs to the group of a very high risk of a cardiovascular event due to atherosclerosis. In this group of patients, low-density lipoprotein cholesterol levels should be aimed below 55 mg/dl (1.4 mmol/l). Many scientific guidelines define the extreme risk group, which includes not only patients with two cardiovascular events within two years, but also patients with a history of ACS and additional clinical factors: peripheral vascular disease, multivessel disease (multilevel atherosclerosis), or multivessel coronary disease, or familial hypercholesterolemia, or diabetes with at least one additional risk factor: elevated Lp(a) >50 mg/dl or hsCRP >3 mg/l, or chronic kidney disease (eGFR <60 ml/min/1.73 m2). In this group of patients, the LDL-C level should be aimed at below 40 mg/dl (1.0 mmol/l). Achieving therapeutic goals in patients after ACS should occur as soon as possible. For this purpose, a high-dose potent statin should be added to the therapy at the time of diagnosis, and ezetimibe should be added if the goal is not achieved after 4–6 weeks. Combination therapy may be considered in selected patients from the beginning. After 4–6 weeks of combination therapy, if the goal is still not achieved, adding a proprotein convertase subtilisin/kexin type 9 protein inhibitor or inclisiran should be considered. In order to increase compliance with the recommendations, Polish Cardiac Society and Polish Lipid Society propose to attach in the patient’s discharge letter a statement clearly specifying what drugs should be used and what LDL-C values should be achieved. It is necessary to cooperate between the patient and the doctor, to follow the recommendations and take medicines regularly, to achieve and maintain therapeutic goals

The correlation between reading and mathematics ability at age twelve has a substantial genetic component

Dissecting how genetic and environmental influences impact on learning is helpful for maximizing numeracy and literacy. Here we show, using twin and genome-wide analysis, that there is a substantial genetic component to children’s ability in reading and mathematics, and estimate that around one half of the observed correlation in these traits is due to shared genetic effects (so-called Generalist Genes). Thus, our results highlight the potential role of the learning environment in contributing to differences in a child’s cognitive abilities at age twelve

Surgical treatment of rectal cancer in Poland — a report from a prospective, multi-centre observational study PSSO_01 conducted under the auspices of the Polish Society of Surgical Oncology

Introduction. Since 2016, as part of the PSSO_01 multi-centre research project conducted under the auspices of the Polish Society of Surgical Oncology, clinical data on rectal cancer treatment have been collected. The objective of the study was to illustrate the state of early results of surgical treatment. Material and methods. The research project is multi-centre in nature. Data shall be collected electronically. The study protocol does not impose or suggest any course of procedure. It only systematizes the way data are collected for scientific purposes. The analysis of early results of surgical treatment was compared with the results of population studies from other European countries (Netherlands, Belgium). Results. By the end of June 2018, 736 patients were registered in the study. In 399 (54.2%) an anterior resection was performed. More than half of patients undergoing subsequent surgical treatment (54.2%) receive neoadjuvant treatment, with the percentage of patients undergoing radiotherapy or radiochemical treatment for lower rectal cancer being about 70%. Most patients (96%) are operated in elective procedure. The percentage of laparoscopic surgeries is low (8.6%). Postoperative complications are observed in 21.1% of patients. Severe complications (grades III–V according to Clavien-Dindo classification) occur in 7.6% of patients undergoing surgery. Postoperative mortality is 1.1%. Discussion. Although the project does not have the character of a registry and does not allow for drawing wider conclusions concerning the compliance with the standards of qualification for neoadjuvant treatment, the important information is that more than half of rectal cancer patients receive preoperative treatment, and the percentage of severe postoperative complications does not exceed 10%. Conclusions. The results of the PSSO_01 project are representative and reflect the actual situation concerning surgical treatment of rectal cancer patients in Poland

Leczenie chirurgiczne raka odbytnicy w Polsce — raport z prospektywnego, wieloośrodkowego badania obserwacyjnego PSSO_01 prowadzonego pod auspicjami Polskiego Towarzystwa Chirurgii Onkologicznej

Wstęp. Od 2016 roku w ramach wieloośrodkowego projektu badawczego PSSO_01 prowadzonego pod auspicjami Polskiego Towarzystwa Chirurgii Onkologicznej, gromadzone są dane kliniczne dotyczące leczenia raka odbytnicy. Celem pracy było zobrazowanie stanu dotyczącego wczesnych wyników leczenia chirurgicznego. Materiał i metody. Projekt badawczy ma charakter wieloośrodkowy. Dane gromadzone są elektronicznie. Protokół badania nie narzuca ani nie sugeruje żadnego sposobu postępowania, systematyzuje jedynie sposób zbierania danych w celach naukowych. Analiza dotycząca wczesnych wyników leczenia chirurgicznego została porównana z rezultatami populacyjnych badań z innych krajów europejskich (Holandia, Belgia). Wyniki. Do końca czerwca 2018 roku w badaniu zarejestrowano 736 chorych. U 399 (54,2%) wykonano resekcję przednią. Leczenie neoadiuwantowe otrzymała ponad połowa chorych, poddanych następnie leczeniu operacyjne­mu (54,2%), przy czym odsetek pacjentów poddanych radio- bądź radiochemioterapii z powodu raka dolnej części odbytnicy wyniósł około 70%. Większość chorych (96%) operowana była w trybie planowym. Odsetek operacji wykonanych techniką laparoskopową jest niski (8,6%). Powikłania pooperacyjne zaobserwowano u 21,1% chorych. Ciężkie powikłania (III–V st. wg klasyfikacji Claviena-Dindo) sięgały 7,6% operowanych chorych. Śmiertelność po­operacyjna wyniosła 1,1%. Dyskusja. Chociaż projekt nie ma charakteru rejestru i nie pozwala na wyciągniecie szerszych wniosków dotyczących przestrzegania standardów kwalifikacji do leczenia neoadiuwantowego, istotną informacją jest to, że ponad połowa chorych na raka odbytnicy otrzymuje leczenie przedoperacyjne, a odsetek ciężkich powikłań pooperacyjnych nie przekracza 10%. Wnioski. Wyniki projektu PSSO_01 są reprezentatywne i odzwierciedlają faktyczną sytuację dotyczącą leczenia chirurgicznego chorych na raka odbytnicy w Polsce