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Inflammation is implicated in Alzheimer's disease (AD), and specific single nucleotide polymorphisms (SNPs) in inflammatory cytokine genes are associated with increased AD risk. Whether the same polymorphisms also predict domain-specific cognitive change in cognitively healthy older adults is unclear. Specific SNPs in three cytokine genes, IL-1β (rs16944), IL-6 (rs1800795), and TNFα (rs1800629) were assessed for association with longitudinal trajectories spanning up to 16 years of global cognitive function, episodic memory, attention and working memory, and executive function in a sample of 324 non-demented older adults. Only rs1800629 (TNFα) was associated with significant change in global cognitive function over time [γ = 5.22; 95% CI: 0.61, 9.83; p = 0.027]. Despite an association with AD risk, rs16944 and rs1800795 may not predict cognitive decline in cognitively healthy older adults. The presence of an A at rs1800629 (TNFα) may have broad, protective effects on cognitive function, over time. More validation studies are needed to determine whether specific cytokine SNPs are associated with respective serum levels to further understanding of AD biomarkers that may also serve as markers of cognitive decline.

We conducted a preregistered multilaboratory project (k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result (d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect (d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

Artykuł charakteryzuje wpływ wydanego w latach 1882–1883 Dziennika intymnego Henriego-Frédérica Amiela na twórczość i światopogląd Henryka Sienkiewicza, zwłaszcza zaś na jego powieść Bez dogmatu. Polski pisarz zapoznał się z dziełem Amiela na pewno na początku 1890 roku. Wydaje się jednak, że sława Amiela, potęgowana szkicami o nim Ernesta Renana i Paula Bourgeta, już wcześniej zaważyła na przeorientowaniu się twórczych zainteresowań Sienkiewicza odchodzącego pod koniec lat 80. XIX wieku od epiki historycznej ku problemom współczesności i formie powieści pierwszoosobowej. Przedmiotem analizy porównawczej jest więc głośna w Europie powieść Bez dogmatu (1891) przedstawiająca kryzys nowoczesnej tożsamości europejskiej. Analiza zarówno powieści, jak i epistolografii Sienkiewicza wykazuje liczne analogie światopoglądowe z myślą Amiela, zwłaszcza w kwestii rozumienia przyczyn kryzysu kultury europejskiej oraz człowieka drugiej połowy XIX wieku. Obaj pisarze wskazywali na destrukcyjny wpływ racjonalistycznej autoanalizy, metodologii pozytywizmu odniesionej do humanistyki oraz mechanistycznie pojmowanej idei postępu. Sienkiewicza do Amiela zbliżyły także polityczny profetyzm i stosunek do ruchów rewolucyjnych, charakterystyczny dla przedstawicieli nowoczesnego konserwatyzmu europejskiego reprezentowanego przez Edmunda Burke’a i Alexisa de Tocqevilla. Sienkiewicz and Amiel. About a Meeting of Mind and Two Modern Intimist Strategies The article presents the influence of Henri-Frédéric Amiel’s The Journal Intime published between 1882–1883 on the works and world-view of the 1905 Polish Nobel Prize winner Henryk Sienkiewicz, and in particular on his novel Without Dogma. The Polish writer must have read Amiel’s journal around early 1890. It seems however, that Amiel’s popularity, amplified by Ernest Renan’s and Paul Bourget’s sketches about him, had already induced a shift in Sienkiewicz’s artistic interests, who in the late 1880s moved from historical epics in favour of the issues of modernity and a first- -person-narrative novel. The comparative analysis investigates the Europe-famous novel Without Dogma (1891) touching upon the crisis of modern European identity. The analysis of the novel, as well as Sienkiewicz’s epistolography, points out to a number of world-view analogies with Amiel, especially in terms of where they saw the roots of the crisis of European culture and humanity in the second half of the 19th century. Both writers emphasized the destructive influence of rationalist self- -analysis, positivist methodology drawing on humanities, and a mechanical perception of the idea of progress. Sienkiewicz also shared Amiel’s political prophetism and approach to revolutionary movements, characteristic for representatives of modern European conservatism professed by Edmund Burke and Alexis de Tocqueville.

Background: Robot-assisted partial nephrectomy (RAPN) is a challenging procedure that is influenced by a multitude of factors. Objective: To assess the impact of prior surgical experience on perioperative outcomes in RAPN. Design, setting, and participants: In this retrospective multicenter study, results for 2548 RAPNs performed by 25 surgeons at eight robotic referral centers were analyzed. Perioperative data for all consecutive RAPNs from the start of each individual surgeon’s experience were collected, as well as the number of prior open or laparoscopic kidney surgeries, pelvic surgeries (open, laparoscopic, robotic), and other robotic interventions. Intervention: Transperitoneal or retroperitoneal RAPN. Outcome measurements and statistical analysis: The impact of prior surgical experience on operative time, warm ischemia time (WIT), major complications, and margin, ischemia, complication (MIC) score (negative surgical margins, WIT ≤20 min, no major complications) was assessed via univariate and multivariable regression analyses accounting for age, gender, body mass index (BMI), American Society of Anesthesiologists score, PADUA score, and RAPN experience. Results and limitations: BMI, PADUA score, and surgical experience in RAPN had a strong impact on perioperative outcomes. A plateau effect for the learning curve was not observed. Prior laparoscopic kidney surgery significantly reduced the operative time (p

Aims. Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II-receptor antagonists (ARB) and angiotensin receptor blocker/neprilysin inhibitor (ARNI) use. Methods and Results. ACEi and ARBs were generally used in 87.6% of all HF patients in 2012 (n=154 627); 84.5% in 2013 (n=170 861); 83.5% in 2014 (n=186 963); 81.6% in 2015 (n=198 844); 80.1% in 2016 (n=205 793); 78.0% in 2017 (n=212 152) and in 76.7% in 2018 (n=219 235). In a sub-analysis of patients with a medical procedure and/or examination using an I50.x ICD code accounted for in the given year, ACEi and ARBs were generally used in 99.3% in 2012 (n=63 250); 96% in 2013 (n=62 241); 95.2% in 2014 (n=64 414); 93.3% in 2015 (n=65 217); 91.8% in 2016 (n=65 236); 90.1% in 2017 (n=65 761) and in 88.6% in 2018 (n=66 332). In 2018, the majority of patients with HF were prescribed ramipril (n=49 909; 17.5%) and perindopril (n=44 332; 15.5%). The mostly prescribed ARBs in 2018 were telmisartan (n=18 669; 6.5%); losartan (n=13 935; 4.9%) and valsartan (n=4 849; 1.7%). In 24.5% of cases, ACEIs and ARBs were prescribed in a fixed combination with another drug. ARNI became gradually more prescribed from 2018 (n=9 659 in November 2020). Conclusion. In an analysis of ACEIs, ARBs and ARNIs utilization in all patients treated for heart failure in the given year in the whole country, we found a comparable rate of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Ramipril and perindopril remained the mostly prescribed ACEIs and telmisartan became the mostly prescribed ARB. Since 2018, ARNIs began to be widely prescribed.

The trapping of Poly-ADP-ribose polymerase (PARP) on DNA caused by PARP inhibitors (PARPi) triggers acute DNA replication stress and synthetic lethality (SL) in BRCA2-deficient cells. Hence, DNA damage is accepted as a prerequisite for SL in BRCA2-deficient cells. In contrast, here we show that inhibiting ROCK in BRCA2-deficient cells triggers SL independently from acute replication stress. Such SL is preceded by polyploidy and binucleation resulting from cytokinesis failure. Such initial mitosis abnormalities are followed by other M phase defects, including anaphase bridges and abnormal mitotic figures associated with multipolar spindles, supernumerary centrosomes and multinucleation. SL was also triggered by inhibiting Citron Rho-interacting kinase, another enzyme that, similarly to ROCK, regulates cytokinesis. Together, these observations demonstrate that cytokinesis failure triggers mitotic abnormalities and SL in BRCA2-deficient cells. Furthermore, the prevention of mitotic entry by depletion of Early mitotic inhibitor 1 (EMI1) augmented the survival of BRCA2-deficient cells treated with ROCK inhibitors, thus reinforcing the association between M phase and cell death in BRCA2-deficient cells. This novel SL differs from the one triggered by PARPi and uncovers mitosis as an Achilles heel of BRCA2-deficient cells.

Aims. Sub-analysis of a retrospective nation-wide observational analysis of heart failure (HF) epidemiology reported to the Czech National Registry of Reimbursed Health Services between 2012 and 2018 aimed at beta-blockers (BBs) utilization. Methods and Results. The beta-blockers were generally used in 81.8% of all patients treated for HF in 2012 (n=52 140); 81.8% in 2013 (n=53 058); 83.1% in 2014 (n=56 221); 82.1% in 2015 (n=57 421); 83.3% in 2016 (n=59 187); 82.2% in 2017 (60 058) and in 81.4% in 2018 (n=60 966). In 2018, the majority of patients treated for HF were prescribed metoprolol (22 974; 30.7%) and bisoprolol (21 001; 28%). Carvedilol was prescribed in 7 331 patients treated for HF (9.8%), nebivolol in 5 392 HF patients. Despite its primary indication, betaxolol was used in 2 341 patients treated for HF (3.1%). All other beta-blockers were used in less than 1% of HF patients. In some of the mostly used BBs, their prescription in patients treated for HF changed in the last years (metoprolol 32.4% in 2012, 30.7% in 2018; bisoprolol 20.3% in 2012, 28% in 2018; carvedilol 18.3% in 2012, 9.8% in 2018; nebivolol 2.5% in 2012, 7.2% in 2018; betaxolol 4.2% in 2012, 3.1% in 2018). Conclusion. In an analysis of beta-blockers utilization in all patients treated for heart failure in the given year in the whole country, we have found only slightly lower amount of drug prescription in comparison with specific heart failure registries. This indicates a good translation of current standard of care into common clinical practice. Metoprolol remained the mostly prescribed drug. The prescription of bisoprolol and nebivolol has increased at the expense of carvedilol.