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Transportation law is rapidly evolving with the advent of automation in the trucking sector. With 20 states allowing some form of automation, each with its unique set of rules and [...]

After months of reading, discussion, and speculation on what book could/should/would win the 2023 Newbery Medal, the Youth Media Awards announcement finally came on January 30--and the selections gave us [...]

Humor keeps tweens and teens reading. Why isn't there more? WHAT DO FANS OF 'DIARY OF A WIMPY KID' READ IN HIGH SCHOOL? The shelves of any teen section in [...]

Since there is no current international consensus on the optimal approach for pain management in acute pancreatitis (AP), analgesic practices may vary across different healthcare settings. This study explored global disparities in analgesic use, in particular opioids, during admission and at discharge in hospitalised AP patients. This was a post hoc analysis of the prospective PAINAP database, which included all admissions for AP between April and June 2022 with a 1‐month follow‐up. Demographic details, analgesic use, and clinical outcomes were recorded during admission and at discharge. Odds ratios (ORs) for opioid use during admission and at discharge were identified using multivariable regression analyses. Amongst the 1864 patients (52% males, median age 56 (interquartile range, 41–71)) across three different continents, simple analgesics were predominantly used as the primary analgesic (70%). Opioid use during admission was lowest in European centres (67%). Admission in Asian (OR, 2.53 (95% confidence interval (CI), 1.59–4.04), p< 0.001), and Australian (OR, 5.81 (95% CI, 3.19–10.56), p< 0.001) centres was associated with opioid administration during admission compared with European centres. Increased pain severity, longer pre‐admission pain duration, organ failure, and longer length of admission increased opioid use during admission. At discharge, Asian (OR, 2.01 (95% CI, 1.40–2.88), p< 0.001) and Australian (OR, 1.91 (95% CI, 1.28–2.85), p= 0.002) centres were associated with opioid prescription compared with European centres. Increased pain severity, longer pre‐admission pain duration, acute necrotic collections, and walled‐off necrosis also increased the likelihood of opioid prescription at discharge. There are substantial intercontinental differences in opioid use for AP pain. Accordingly, there is a need for international guidelines on pain management in AP.

After 100 years, the Newbery Medal is as popular--and controversial--as ever. People have impassioned opinions. Lots of them. And they don't hold back. On 'Heavy Medal,' the Mock Newbery blog [...]

IMPORTANCE: Biosimilar drugs provide cost-effective yet clinically indistinguishable replications of target drugs. During initial development, this class of biologic medicines was expected to revolutionize pharmaceutical markets; however, following US Food and Drug Administration approval of the first biosimilar drug in 2015, the commercialization of biosimilars has been limited. The lack of biosimilar use may be especially salient in oncology, given that biosimilar distribution in this particularly high-cost area of medicine would bring savings on the order of many billions of dollars. OBSERVATIONS: While researchers have focused on salient economic barriers to biosimilar uptake in the US, the present review provides insight regarding noneconomic barriers. This review discusses psychological, attitudinal, and educational factors among both health care professionals and payers in the US that may play a role in slowing biosimilar uptake. More specifically, these factors include a lack of health care professional education, concerns of safety and efficacy, and overly complex product naming systems. CONCLUSIONS AND RELEVANCE: The pathway to biosimilar use has been obstructed by economic elements as well as attitudinal and psychological factors. For biosimilar drugs to achieve their potential in decreasing treatment costs and thus increasing patient access, it will be essential for both economic and noneconomic factors to be identified and systematically addressed.

Using data from Midlife in the United States (N= 3,767), this study investigates how believing having money or occupational prestige is important for a good life is associated with different aspects of well-being. Actual income was positively associated with sense of purpose, personal growth, self-acceptance, environmental mastery, and life satisfaction; negatively associated with negative affect; and was not associated with autonomy, positive relations with others, or positive affect. Meanwhile, perceiving having enough money or extra money as important for a good life predicted poorerwell-being across all nine well-being indicators. Occupational prestige was positively associated with sense of purpose, autonomy, personal growth, self-acceptance, environmental mastery, and life satisfaction, whereas perceiving having occupational prestige as important was negatively associated with autonomy, personal growth, self-acceptance, positive relations with others, and positively with negative affect. The discussion focuses on how desiring money or prestige can influence well-being beyond having—or not having—those desires.

The outburst of the coronavirus pandemic in Poland has led to specific measures related to covid, which affected unequally different age groups. Children were presented as “spreaders” of the disease, and a threat to the societies’ safety. Such fears led to new disciplining practices, such as prohibiting children from leaving the house without adult’s supervision during the first wave of pandemic in Poland. In the consequence of those special measures, the pandemic crisis challenged and blurred some previously existing boundaries, such as those between home and school, private and public, health and illness, online and offline, etc. In this paper, we examine how Polish children experienced their childhood through playful activities during the COVID-19 pandemic. Using data from three different research projects conducted during the COVID-19 pandemic in Poland, we reflect on the children’s understandings of what is safe. Our focus is on various spaces which either enabled or restrained such activities, and on active work of children in finding and creating a safe space. We argue that, in the circumstances in which known-to-date divisions blurred, children’s seeking of safe spaces, in literal and metaphoric sense, were the means to deal with the new realities. These were primarily negotiable spaces, created through various social practices such as play.

AbstractAphids (Hemiptera: Aphididae) are herbivorous insects which deprive plants of nutrients by feeding on the phloem sap and transmission of plant viruses. In the present study, the susceptibility of selected white-berried grapevine (Vitisspp.) cultivars “Aurora”, “Bianca”, “Muskat Letni” and “Solaris” to the black bean aphid (Aphis fabaeScop.) and the green peach aphid (Myzus persicae(Sulz.) was evaluated using the Electrical Penetration Graph (EPG) technique. The content of major flavonoids and stilbenoids in grapevine leaves and leaf anatomy parameters that might have affected aphid probing were also analyzed. Based on the success rate in reaching the phloem vessels and feeding on phloem sap, the studied grapevine cultivars can be assigned to various groups of susceptibility. Cultivars “Bianca” and “Muskalt Letni” are susceptible to A. fabaeand M. persicae, respectively (aphids reach phloem phase and show short bouts of sap ingestion); “Muskat Letni” shows low susceptibility to A. fabae, while “Aurora” and “Bianca” to M. persicae(only 50% aphids reach phloem phase and no sap ingestion occurs); “Solaris” is resistant to A. fabaeand M. persicae(no phloem phase present). Anatomical structure of leaves was similar in all cultivars and no mechanical barriers for aphid probing were observed. However, the content of individual flavonoids and silbenoids differed among cultivars. We hypothesize that the high content of piceid in the leaves of “Solaris” may be responsible for the rejection of this cultivar by both aphid species. The study demonstrated that the risk of the direct damage due to A. fabaeand M. persicaefeeding on grapevines is low. However, considering the intense aphid probing activity within leaf epidermis and mesophyll, A. fabaeand M. persicaemay pose a serious threat as vectors of non-persistent and semi-persistent viruses to white-berried grapevines.

Aims/BackgroundFeedback from foundation trainees in Blackpool highlighted low levels of confidence with the prospect of surgical on-call shifts. Key areas of concern were assessing and managing the acute surgical patient, identifying which patients need an operation and having the technical skills to proficiently assist in theatre. This lack of confidence prevents trainees engaging in what should be an educational and rewarding rotation.MethodsThe authors designed and facilitated a day of workshops, addressing these key educational needs. Bespoke to the trust's services, lectures were delivered by core surgical trainees on the assessment and management of acute surgical patients in general surgery, urology and trauma and orthopaedics. For the development of technical skills, an afternoon of surgical skills workshops covered suturing, knot tying, laparoscopic principles and theatre etiquette. Small groups of foundation trainees rotated through each workshop, delivered by surgical registrars (ST3+), to ensure high fidelity training.ResultsPre- and post-course questionnaires assessed the efficacy of teaching. Out of a total of 72 foundation trainees, 55 attended the teaching day, of which 45 (81.8%) completed pre- and post-course surveys using a six-point modified Likert scale. Rates for satisfactory confidence levels while on-call improved from 66 to 100% of participants after the course. Suturing skills satisfaction rose from 37.5 to 100%, among other impact markers.DiscussionAll trainees that attended the course displayed a marked improvement. This course is now being incorporated into foundation teaching programmes at a regional level and has scope to be expanded nationally.

CLARK, Zion & James S. Hirsch. Zion Unmatched. 32p. Candlewick. Aug. 2021. Tr $17.99. ISBN 9781536224184. Gr 2-4--A visual and motivational picture book autobiography. Zion Clark was born without legs, [...]

Graphical Abstract

AbstractThe peach-potato aphid Myzus persicae(Sulzer) and the black bean aphid Aphis fabaeScopoli are polyphagous and cosmopolitan hemipterans, therefore they can infest grapevines in all areas of cultivation. Electrical Penetration Graph (EPG) technique was applied to monitor the probing behavior of A. fabaeand M. persicaeon Vitis amurensisRupr., Vitis ripariaMichaux, and Vitis viniferaL. The content of major flavonoids and stilbenoids in grapevine leaves and epidermal thickness, distance between abaxial leaf surface and phloem, and the simulated shortest pathway from epidermis to phloem that might have affected aphid probing were also analyzed. Aphid probing was limited mainly to non-vascular tissues on the three studied grapevine species. Phloem phase occurred in 32%, 14%, and 6% of A. fabaeand in 76%, 39%, and 74% of M. persicaeon V. amurensis, V. ripariaand V. vinifera, respectively. Phloem phase consisted of only salivation into sieve elements and lasted less than 2.5 minutes on average in all aphids. The time to reach the first phloem phase on grapevines was 5.0 hours in A. fabaeand 2.6–3.6 hours in M. persicae. Of the analyzed flavonoids, catechin, epicatechin, and quercetin occurred in all grapevine species, while rutin – in V. amurensisand V. ripariaand isorhamnetin only in V. amurensis. Of the analyzed stilbenoids, piceid occurred in all grapevines, resveratrol in V. amurensisand V. vinifera, and ε-viniferin only in V. vinifera. Aphid behavior demonstrated that V. amurensis, V. ripariaand V. viniferaare not attractive host plants to A. fabaeand M. persicae. It is likely that the content of flavonoids and stilbenoids contributes to the limited susceptibility of the three grapevine species to A. fabaeand M. persicae, while the observed slight differences in the anatomical structure of the leaves seem not significant in this context.

The European Society of Human Genetics—Young Committee (ESHG-Y) aims to support young human geneticists by developing strategies and programs for better education and creating a strong network in all European countries. In this report, we present the ESHG-Y projects conducted since its conception. We organized the educational sessions at the ESHG Annual Conference, the European Dysmorphology Meetings, and a virtual session in collaboration with the European Board of Medical Genetics (EBMG). Also, the ESHG-Y regularly promotes relevant activities and succeeded in creating an active network of young geneticists. Our representatives have a supportive role in well-known organizations such as: ESHG Board, ESHG Scientific Program Committee, ESHG Education Committee, EBMG, ERN-Ithaca, Unique - Rare Chromosome Disorder Support group, Orphanet, EuroGEMS, MOOC BIG and more. Taking into consideration all activities and ongoing projects, we can state that the ESHG-Y successfully achieves its objectives and brings young professionals together.

The article announces the selection of Amina Luqman-Dawson's book "Freewater" as the winner of the 2023 Newbery Medal, announced on January 30. 2023. It states that Luqman-Dawson became the only third person to win both thew Newbery Medal and the Coretta Scott King Author Award in the same year. An overview of some seminal books from the award's first century is offered including "The Story of Mankind" by Hendrick Willem van Loon and "Charlotte's Web" by E. B. White.

Spinal muscular atrophy is a severe neuromuscular disorder with an autosomal recessive inheritance pattern. The disease-causing gene is SMN1, and its paralogue, SMN2, is a disease course modifier. Both genes SMN1and SMN2show over 99.9% sequence identity and a high rate of crossing over in the genomic region. Due to this reason, SMN1/SMN2is usually excluded from the whole-genome sequencing (WGS) analysis and investigated with traditional methods, such as MLPA and qPCR. Recently, novel bioinformatic algorithms dedicated to analyzing this particular genomic region have been developed. Here, we analyze the SMN1/SMN2genomic region with a dedicated program, SMNCopyNumberCaller. We report a similar prevalence of SMN1gene deletion carrier status (1 per 41 people) to published data from the Polish population (1 per 35 people). Additionally, SMNCopyNumberCaller can identify SMN2CNVs and SMN2Δ7-8present in 153 healthy Polish individuals.Two other programs for the CNV analysis in standard genomic regions were not able to provide reliable results. Using WGS-based tools for SMN1/2genomic region analysis is not only an efficient method in terms of time but will also enable more complex analysis such screening for markers related with a silent carrier status and identification of further genetic modifiers. Although still an experimental method, soon WGS-based SMN1/SMN2carrier identification may become a standard method for patients screened with WGS for other purposes.

This review aims at providing an extensive discussion of modern constraints relevant for dense and hot strongly interacting matter. It includes theoretical first-principle results from lattice and perturbative QCD, as well as chiral effective field theory results. From the experimental side, it includes heavy-ion collision and low-energy nuclear physics results, as well as observations from neutron stars and their mergers. The validity of different constraints, concerning specific conditions and ranges of applicability, is also provided.

WILLIAMS, Andrea. Baseball's Leading Lady: Effa Manley and the Rise and Fall of the Negro Leagues. 336p. Roaring Brook. Jan. 2021. Tr $19.99. ISBN 9781250623720. Gr 6-9--An important hole in [...]

The article provides information on categorizing books in the libraries based on genres. Topics include reaction of Jasmine Warga to how her work "A Rover's Story" has been categorized by librarians, how libraries make the browsing experience more user-friendly, and the need of each library to find what works for them and their community.

This article is an attempt at investigating new meanings and significance of computer-based entertainment during the COVID-19 pandemic. The authors explore how and to what extent students in Poland have been using electronics for entertainment during the global crisis, what emotions appeared and whether they were able and willing to engage in an auto-reflexive process. The article presents the results of the questionnaire interview designed for the purposes of this particular study. The authors chose to reveal the multi-facetedness of the theme in question, i.e. focus on the possibilities and the future that computer-based etertainment offers, leading to transformations both externally and internally.

ABSTRACTThis paper presents 66 radiocarbon (14C) dates obtained at 33 key sites from the Polish part of the European Sand Belt. These calibrated dating results were compared to 34 high-resolution 14C dates obtained from a fluvial-aeolian sediments to identify pedogenic phases from the late Pleniglacial interval to the early Holocene. These identified pedogenic phases were correlated with Greenland ice-core records, revealing high sensitivity of the fluvio-aeolian paleoenvironment to climate changes. Two pedogenic phases were identified from the late Pleniglacial interval (Greenland Stadial GS-2.1b and GS-2.1a), three from the Bølling-Allerød interstadial (Greenland Stadial GI-1), one from the late Allerød–Younger Dryas boundary, and at least one from the Younger Dryas. The ages of these pedogenic phases reveal a distinct delay of 50–100 calendar years after the onset of cool climate conditions during GI-1, reflecting gradual withdrawal of vegetation. Soil horizons from the early Holocene do not show any clear relation with climate change, where breaks in soil formation were caused by local factors such as human activity.

Hot sand can lead to deteriorated physical properties and molding problems, but it is difficult to avoid. The only methods of eliminating the issue are to stop recirculating return green [...]

Introduction:Many kidney recipients struggle with medication adherence and are at greater risk for adverse post-transplant outcomes. Historically, research has focused on single immunosuppressants alone, though all medications within a prescribed regimen are essential for positive outcomes. Research question:Explore predictors of medication regimen nonadherence among a diverse sample of adult kidney recipients by using multiple measures of adherence. Design:A cross-sectional analysis was performed using data from an ongoing clinical trial that enrolled 234 kidney recipients from a large transplant center. We used linear and logit regression models to examine associations of demographic characteristics, social determinants of health, and clinical characteristics with (a) self-reported regimen adherence, measured by the Adherence Starts with Knowledge 12 scale, and (b) immunosuppressant adherence, captured by calculated risk score based on Tacrolimus measurements. Results:Kidney recipients with limited health literacy, overall poorer health, and higher levels of depression demonstrated significantly poorer regimen adherence. Recipients who had dual public/private insurance, took a greater number of medications, and had shorter time since transplant demonstrated significantly poorer immunosuppressant adherence. Conclusion:Social determinants (health literacy and insurance status), and clinical characteristics (overall health status, depression, number of medications, and time since transplant) played significant roles in regimen and immunosuppressant adherence among kidney recipients in our sample. Self-reported adherence, particularly in relation to full medication regimens, can highlight modifiable barriers that might otherwise be overlooked by focusing on adherence to a single immunosuppressant. Depression and health literacy can be assessed and addressed to improve adherence among adult kidney recipients.

The Norwood operation as first-stage palliation for hypoplastic left heart syndrome has been standardized in most centers. However, in the presence of anomalies of aortic arch anatomy or position, or other anatomical variants, important modifications of the procedure may become necessary. This report summarizes surgical techniques to address these challenges.

To analyze near‐term cerebroplacental Doppler, heart morphology, and neonatal biometry in isolated hypoplastic left heart syndrome (HLHS) relative to healthy controls. This retrospective study included 55 fetuses with HLHS (29 with mitral valve stenosis [MS]/aortic valve atresia [AA], 14 with MS/aortic valve stenosis, and 12 with mitral valve atresia [MA]/[AA]) diagnosed prenatally between 2010 and 2019 at 2 referral centers and 101 healthy controls. Ultrasound assessment included umbilical artery (UA), middle cerebral artery (MCA) pulsatility index (PI), and cerebroplacental ratio (CPR), with neonatal weight, length, head circumference (HC), Apgar score, and UA pH measured at birth. In total, 32.7% of HLHS fetuses had abnormal MCA‐PI and UA‐PI, and 38.2% had CPRs below the fifth percentile before birth. All tested Doppler parameters differed from those of the healthy controls (P≤ .01). Birth weight and length were comparable between HLHS and control fetuses, whereas birth HCs were smaller in the HLHS group than in the control group (P= .018). In both groups, increased UA‐PI correlated with lower birth weight, but only HLHS fetuses with UA‐PI > the 95th percentile had a lower median HC at birth than those with normal UA‐PI (P= .045). The median UA‐PI percentile was higher in fetuses with MA than in fetuses with MS (P= .015). The ascending aortic diameter correlated with birth weight (P= .036) and birth length (P= .039). Abnormal cerebroplacental hemodynamics are evident in a high percentage of near‐term fetuses with HLHS, and increased placental resistance may contribute to birth weight and HC. Moreover, heart morphology may impact placental circulation and neonatal biometry.

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•Targetable NRASmutation were identified in pediatric neuroendocrine-like tumors.•Primary and metastatic PDX cells harbor phenotypic and genetic differences.•MEK inhibition decreases primary and metastatic PDX cell viability and motility.

BackgroundBiallelic pathogenic variants in FXR1have recently been associated with two congenital myopathy phenotypes: a severe form associated with hypotonia, long bone fractures, respiratory insufficiency and infantile death, and a milder form characterised by proximal muscle weakness with survival into adulthood.ObjectiveWe report eight patients from four unrelated families with biallelic pathogenic variants in exon 15 of FXR1.MethodsWhole exome sequencing was used to detect variants in FXR1.ResultsCommon clinical features were noted for all patients, which included proximal myopathy, normal serum creatine kinase levels and diffuse muscle atrophy with relative preservation of the quadriceps femoris muscle on muscle imaging. Additionally, some patients with FXR1-related myopathy had respiratory involvement and required bilevel positive airway pressure support. Muscle biopsy showed multi-minicores and type I fibre predominance with internalised nuclei.ConclusionFXR1-related congenital myopathy is an emerging entity that is clinically recognisable. Phenotypic variability associated with variants in FXR1can result from differences in variant location and type and is also observed between patients homozygous for the same variant, rendering specific genotype–phenotype correlations difficult. Our work broadens the phenotypic spectrum of FXR1-related congenital myopathy.

The uncertainty of the post-Brexit relations between the UK and the remaining EU-27 countries has caused political and economic concerns (Kroll and Leuffen, 2016). The ongoing negotiations concerning future relations cover various scenarios that may have different impacts on the individual economies in both an economic and a political sense. The article analyses consequences of the British voters' decision to withdraw from the European Union through the lens of a disintegration process and its main objective is to identify the scale and the nature of individual countries vulnerability toward Brexit. It demonstrates purely economic approach to the critical assessment of Brexit, with focus on building rankings of losers. In this way, we contribute to the ongoing debate on the Brexit negotiation process by providing strong arguments in favour of certain policy decisions. In line with the 'neighbour country hypothesis' and 'small country hypothesis', we assume that small economies will experience moderate to high negative consequences of Brexit, while larger ones will not be affected as much, having regard, however, to the country's location in relation to the UK.

Brexit has caused a visible disruption in the so far fairly unobstructed segue to regional integration. Our research is based on a survey of Polish companies operating in British markets and aims to see how companies responded to the changes caused by Brexit and whether certain groups of companies exhibit similar characteristics in response to the observed uncertainty. The perception of uncertainty was measured in two separate dimensions - uncertainty towards the future arrangements between EU and UK and uncertainty over the institutional agility in the UK. The results are analysed using the cluster method. We found that the vast majority of companies remain unaffected; however, we have delimited two other groups - which even if are smaller in size - react differently. The medium and large companies that have significantly longer experience in the British market and that not only trade but also invest in the UK exhibit far greater concern.

Abstract:This article recovers a Jewish and Christian tradition about King Hezekiah as a censor and gatekeeper of scriptural texts. While modern scholarship often assumes that "traditional" interpreters had an ahistorical approach to the Bible, a thread of speculation about Hezekiah's role in canon formation reveals that ancient readers were aware that their texts had a history: theories about their transmission were themselves a kind of biblical interpretation. This cluster of traditions rests on two aspects of Hezekiah's portrayal in the Bible—the transmission of proverbs in his court (Prov 25:1) and Hezekiah as an anti-idolater (2 Kings)—which intertwine to refashion him as a curator of public knowledge who distinguishes between texts to be transmitted and texts to be suppressed. The motif has been overlooked because it exists largely in marginal references, but the data reveal a shared discourse about how the Bible emerged as a result of suppression and selection from a later body of revelation. Recovering this tradition challenges the sharp distinction between "traditional" and "historical-critical" approaches, which also speculate about Hezekiah's role in the Bible's origins. It also reveals a type of biblical interpretation that is unthreatened by the idea that Scripture developed over time—instead, speculation about the textual history of the Bible becomes another mode of animating biblical characters and episodes.

Background: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design, In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3x4 factorial trial of bisoprolol, a [[beta].sub.1]-selective adrenergic blocking agent, and hydrochlorothiazide. Methods: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. Results: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. Conclusions: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.

Certain high-risk populations, such as diabetics and blacks, have sustained elevation in blood pressure and heart rate throughout the day and night, with blunting of the usual diurnal viriability pattern. This may contribute to their higher incidence of left ventricular hypertrophy (blacks) and cardioviascular complications (diebetics). Hypertensives who maintain a diurnal pattern of blood pressure variation still exhibit higher daytime and nocturnal blood pressure levels than normotensives. Thus, to achieve maximum effectiveness in treating hypertension, 24-hour control of blood pressure is necessary. Antihypertensive agents should effectively reduce blood pressure consistently throughout a 24-hour period. The objective of this study was to assess the effects of amlodipine, 5 mg once daily, on blood pressure measured by 24-hour ambulatory monitoring in a randomized, double-blind, placebo-controlled single-site study. Patients with mild-to-moderate essential hypertension were randomized to receive amlodipine (n = 11) or placebo (n = 5) in a 2:1 ratio. A 4-week single-blind placebo run-in period was followed by a 4-week double-blind phase. Ambulatory monitoring of blood pressure was carried out for 24 hours at the end of each 4-week phase. Patients receiving amlodipine had significantly lower blood pressure compared with placebo 24 hours after the last dose (supine blood pressure - 25.1/ - 10.1 mm Hg; standing blood pressure - 212.2/ - 9/7 mm Hg) after 4 weeks of treatment. This effect was clearly demonstrated by the 24-hour postdose measurement and the mean blood pressure over the 24-hour interval as measured by ambulatory recordings. The mean hourly ambulatory recordings showed that amlodipine maintained both diastolic and systolic pressures below the baseline levels at every hour during the 24-hour observation period. Nine of 10 evaluable patients (90%) on amlodipine responded vs only 1 of 5 patients (20%) on placebo. The decrease in blood pressure for the amlodipine patients was not accompanied by a significant increase in pulse rate. Amlodipine was well tolerated; possibly drug-related side effects of intermittent headache and nocturia were experienced by 1 patient each; the latter had been present during the placebo run-in phase. Amlodipine is effective, well tolerated, and may be administered once daily for effective 24-hour blood pressure control. (Am J Cardiol 1994;73:39A-43A)

Alkaloids obtained from plants belonging to the Amaryllidaceae and Lycopodiaceae families are of great interest due to their numerous properties. They play a very important role mainly due to their strong antioxidant, anxiolytic and anticholinesterase activities. The bioactive compounds obtained from these two families, especially galanthamine and huperzine A, have found application in the treatment of the common and incurable dementia-like Alzheimer’s disease. Thanks to this discovery, there has been a breakthrough in its treatment by significantly improving the patient’s quality of life and slowing down disease symptoms – albeit with no chance of a complete cure. Therefore, a continuous search for new compounds with potent anti-AChE activity is needed in modern medicine. In obtaining new therapeutic bioactive phytochemicals from plant material, the isolation process and its efficiency are crucial. Many techniques are known for isolating bioactive compounds and determining their amounts in complex samples. The most commonly utilized methods are extraction using different variants of organic solvents allied with chromatographic and spectrometric techniques. Optimization of these methods and modification of their procedures potentially allows researchers to obtain the expected results. The aim of this paper is to present known techniques for the isolation of alkaloids, especially from three species Narcissus, Lycopodium and Huperzia that are a rich source of AChE inhibitors. In addition, innovative combinations of chromatographic and spectrometric methods and novel TLC-bioautography will be presented to enable researchers to better study the bioactivity of alkaloids.

Background: Alzheimer’s disease is one of the leading health problems characterized by the accumulation of Aβ and hyperphosphorylated tau that account for the senile plaque formations causing extensive cognitive decline. Many of the clinical diagnoses of Alzheimer’s disease are made in the late stages, when the pathological changes have already progressed. Objective: The objective of this study is to evaluate the promising therapeutic effects of a natural compound, lycoramine, which has been shown to have therapeutic potential in several studies and to understand its mechanism of action on the molecular level via differential protein expression analyses. Methods: Lycoramine and galantamine, an FDA approved drug used in the treatment of mild to moderate AD, were administered to 12 month-old 5xFAD mice. Effects of the compounds were investigated by Morris water maze, immunohistochemistry and label- free differential protein expression analyses. Results: Here we demonstrated the reversal of cognitive decline via behavioral testing and the clearance of Aβ plaques. Proteomics analysis provided in-depth information on the statistically significant protein perturbations in the cortex, hippocampus and cerebellum sections to hypothesize the possible clearance mechanisms of the plaque formation and the molecular mechanism of the reversal of cognitive decline in a transgenic mouse model. Bioinformatics analyses showed altered molecular pathways that can be linked with the reversal of cognitive decline observed after lycoramine administration but not with galantamine. Conclusion: Lycoramine shows therapeutic potential to halt and reverse cognitive decline at the late stages of disease progression, and holds great promise for the treatment of Alzheimer’s disease.

Hepatoblastoma remains one of the most difficult childhood tumors to treat and is alarmingly understudied. We previously demonstrated that Proviral Insertion site in Maloney murine leukemia virus (PIM) kinases, specifically PIM3, are overexpressed in human hepatoblastoma cells and function to promote tumorigenesis. We aimed to use CRISPR/Cas9 gene editing with dual gRNAs to introduce large inactivating deletions in the PIM3 gene and achieve stable PIM3 knockout in the human hepatoblastoma cell line, HuH6. PIM3 knockout of hepatoblastoma cells led to significantly decreased proliferation, viability, and motility, inhibited cell-cycle progression, decreased tumor growth in a xenograft murine model, and increased animal survival. Analysis of RNA sequencing data revealed that PIM3 knockout downregulated expression of pro-migratory and pro-invasive genes and upregulated expression of genes involved in apoptosis and differentiation. Furthermore, PIM3 knockout decreased hepatoblastoma cancer cell stemness as evidenced by decreased tumorsphere formation, decreased mRNA abundance of stemness markers, and decreased cell surface expression of CD133, a marker of hepatoblastoma stem cell-like cancer cells. Reintroduction of PIM3 into PIM3 knockout cells rescued the malignant phenotype. Successful CRISPR/Cas9 knockout of PIM3 kinase in human hepatoblastoma cells confirmed the role of PIM3 in promoting hepatoblastoma tumorigenesis and cancer cell stemness.

In this study, Turtola et al. set out to study the exact requirements for polyadenosine (pA) tail length control. Using in vivo and in vitro approaches in budding yeast, the authors report a three-layered control of nuclear poly(A) tail synthesis, where one primary mechanism is backed up by two “fail-safe” mechanisms. Nuclear poly(A) binding protein Nab2p executes the primary control. When Nab2p is limiting, the nuclear pool of Pab1p, the second major PABP in yeast, controls the process. When both PABPs are absent, the cleavage and polyadenylation factor (CPF) limits pA tail synthesis.

The article presents the views of various librarians about the Newbery Medal on its 100th anniversary in 2021. Topics discussed include the word that respondents pick to describe the Newbery, book titles that had strong support as desrving non-medalists, and cinematic depictions of Newbery titles.

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The article describes three interlaboratory experiments concerning 222Rn determination in water samples. The first two experiments were carried out with the use of artificial radon waters prepared by the Laboratory of Radiometric Expertise (LER), Institute of Nuclear Physics, Polish Academy of Sciences in Kraków in 2014 and 2018. The third experiment was performed using natural environment waters collected in the vicinity of the former uranium mine in Kowary in 2016. Most of the institutions performing radon in water measurements in Poland were gathered in the Polish Radon Centre Network, and they participated in the experiments. The goal of these exercises was to evaluate different measurement techniques used routinely in Polish laboratories and the laboratories’ proficiency of radon in water measurements. In the experiment performed in 2018, the reference values of 222Rn concentration in water were calculated based on the method developed at LER. The participants’ results appeared to be worse for low radon concentration than for high radon concentrations. The conclusions drawn on that base indicated the weaknesses of the used methods and probably the sampling. The interlaboratory experiments, in term, can help to improve the participants’ skills and reliability of their results.

Purpose: To report 12-month outcomes of a Polish National Treatment Program using aflibercept and ranibizumab in eyes with wet, age-related macular degeneration in routine clinical practice.Material and Methods: This was a non-randomized, retrospective, observational multicenter study. Anonymous data contained in the electronic Therapeutic Program Monitoring System were utilized in this study.Results: The study population consisted of 2828 eyes from 2718 patients. The median age was 76.0 [70.0, 81.0] years; 61.7% were female. Best corrected visual acuity increased from 58.86 [50.05, 69.95] letters to 65.1 [50.1, 73.9] letters (p < 0.001). The median change in best corrected visual acuity was 0.0 [−4.0, 12.2] letters: 2.9 [−2.9, 15.1] letters for treatment-naïve eyes and 0.0 [−4.0, 8.8] letters for those continuing treatment (p < 0.001). The median central retinal thickness was significantly reduced from 341.0 [281.0, 422.0] to 275.0 [221.0, 344.0] μm (p < 0.001). The median number of visits was 9.0 [8.0, 9.0]. The median number of injections was 7.0 [6.0, 8.0]: 8.0 [7.0, 8.0] for treatment-naïve eyes and 6.0 [5.0, 7.0] for those continuing treatment (p < 0.001).Conclusion: Eyes treated as part of the Polish therapeutic program gained functional stability and morphological improvement. Treatment-naïve eyes showed the greatest functional benefit.