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After the European Union (EU) was left by the United Kingdom (UK), a free trade area was established between these economies. Although bilateral trade in all goods is tariff-free, regulatory requirements make exports more costly and burdensome. We used a partial equilibrium model to analyze the implications of Brexit for agricultural exports from Visegrad countries (Czechia, Hungary, Poland and Slovakia). We assess trade creation and trade diversion effects resulting from an increase in non-tariff measures and border costs for 4-digit agricultural products identified as sensitive in each of the Visegrad countries. The simulations reveal that exports of sensitive products from Visegrad countries to the UK could decrease by up to 20%. While the macroeconomic importance of this change is not significant, for the producers of the sensitive goods such export losses are substantial., Competing Interests: The authors have declared that no competing interests exist.

Background: Delirium is a major cause of preventable mortality and morbidity in hospitalized adults, but accurately determining rates of delirium remains a challenge. Objective: To characterize and compare medical inpatients identified as having delirium using two common methods, administrative data and retrospective chart review. Methods: We conducted a retrospective study of 3881 randomly selected internal medicine hospital admissions from six acute care hospitals in Toronto and Mississauga, Ontario, Canada. Delirium status was determined using ICD-10-CA codes from hospital administrative data and through a previously validated chart review method. Baseline sociodemographic and clinical characteristics, processes of care and outcomes were compared across those without delirium in hospital and those with delirium as determined by administrative data and chart review. Results: Delirium was identified in 6.3% of admissions by ICD-10-CA codes compared to 25.7% by chart review. Using chart review as the reference standard, ICD-10-CA codes for delirium had sensitivity 24.1% (95%CI: 21.5–26.8%), specificity 99.8% (95%CI: 99.5–99.9%), positive predictive value 97.6% (95%CI: 94.6–98.9%), and negative predictive value 79.2% (95%CI: 78.6–79.7%). Age over 80, male gender, and Charlson comorbidity index greater than 2 were associated with misclassification of delirium. Inpatient mortality and median costs of care were greater in patients determined to have delirium by ICD-10-CA codes (5.8% greater mortality, 95% CI: 2.0–9.5 and $6824 greater cost, 95%CI: 4713–9264) and by chart review (11.9% greater mortality, 95%CI: 9.5–14.2% and $4967 greater cost, 95%CI: 4415–5701), compared to patients without delirium. Conclusions: Administrative data are specific but highly insensitive, missing most cases of delirium in hospital. Mortality and costs of care were greater for both the delirium cases that were detected and missed by administrative data. Better methods of routinely measuring delirium in hospital are needed. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has increased the number of patients in ICUs leading to a worldwide shortage of the intravenous sedative agents obligating physicians to find alternatives including inhaled sedation. Inhaled sedation in French ICU has been previously explored in 2019 (VOL'ICU study). This survey was designed to explore the use of inhaled sedation two years after our first survey and to evaluate how the COVID-19 pandemic has impacted the use of inhaled sedation. Methods: We designed a national survey, contacting medical directors of French ICUs between June and October 2021. Over a 50-item questionnaire, the survey covered the characteristics of the ICU, data on inhaled sedation, and practical aspects of inhaled ICU sedation for both COVID-19 and non-COVID-19 patients. Answers were compared with the previous survey, VOL'ICU. Results: Among the 405 ICUs contacted, 25% of the questionnaires were recorded. Most ICU directors (87%) knew about the use of inhaled ICU sedation and 63% of them have an inhaled sedation's device in their unit. The COVID-19 pandemic increased the use of inhaled sedation in French ICUs. The main reasons said by the respondent were "need for additional sedative" (62%), "shortage of intravenous sedatives" (38%) and "involved in a clinical trial" (30%). The main reasons for not using inhaled ICU sedation were "device not available" (76%), "lack of familiarity" (60%) and "no training for the teams" (58%). More than 70% of respondents were overall satisfied with the use of inhaled sedation. Almost 80% of respondents stated that inhaled sedation was a seducing alternative to intravenous sedation for management of COVID-19 patients. Conclusion: The use of inhaled sedation in ICU has increased fastly in the last 2 years, and is frequently associated with a good satisfaction among the users. Even if the COVID-19 pandemic could have impacted the widespread use of inhaled sedation, it represents an alternative to intravenous sedation for more and more physicians. [ABSTRACT FROM AUTHOR]

Accession of Poland to the European Single Market generated trade creation and diversion effects, which in turn resulted in a high degree of concentration of the Polish foreign trade in agri-food products with other EU countries. On the one hand, a high share of export to the markets of countries with a stable market economy is a confirmation of the Polish agri-food sector's capacity to compete on the foreign markets. On the other hand, when considering limited capability to increase food demand in the EU it provides grounds for the assumption that further export expansion to a considerable extent will depend on the potential expansion of sale to non-EU markets. In this context significant issues include diversification of target markets and search for prospective markets outside the EU, while they also determine directions of an advantageous export specialization. In the period up to 2021 the USA was the fourth non-EU export partner of Poland in the agri-food sector after the United Kingdom, Ukraine and Russia. The aim of this paper is to evaluate the level of comparative advantages of the Polish agri-food sector on the EU and US markets in 2004–2021 using Widodo's products mapping technique. The study used statistical data from the ComExt database of the European Statistical Office (Eurostat). The conducted studies showed Polish export specializations in the transatlantic trade, as confirmed by high comparative advantages, as well as a positive and steadily improving trade balances for food preparations, including meat, cereal, fruit and vegetable, as well as confectionery preparations, and less processed animal origin products (meat and offal as well as dairy produce). Poland had a disadvantageous competitive position in trade of products complementary in relation to domestic production, which import was necessary. In view of the comparative cost theory the directions of the realized export specialization were rational and should be maintained. While in trade with the other EU countries the competitive position of the Polish agri-food sector was weakened, it was strengthened on the US market. In view of the considerable EU market saturation the improved competitive capacity in the non-EU markets is a positive development, which is a promising finding particularly in the long-term perspective. [ABSTRACT FROM AUTHOR]

Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated. [ABSTRACT FROM AUTHOR]

Background: Current intensive care unit (ICU) sedation guidelines recommend strategies using non-benzodiazepine sedatives. This survey was undertaken to explore inhaled ICU sedation practice in France. Methods: In this national survey, medical directors of French adult ICUs were contacted by phone or email between July and August 2019. ICU medical directors were questioned about the characteristics of their department, their knowledge on inhaled sedation, and practical aspects of inhaled sedation use in their department. Results: Among the 374 ICUs contacted, 187 provided responses (50%). Most ICU directors (73%) knew about the use of inhaled ICU sedation and 21% used inhaled sedation in their unit, mostly with the Anaesthetic Conserving Device (AnaConDa, Sedana Medical). Most respondents had used volatile agents for sedation for <5 years (63%) and in <20 patients per year (75%), with their main indications being: failure of intravenous sedation, severe asthma or bronchial obstruction, and acute respiratory distress syndrome. Sevoflurane and isoflurane were mainly used (88% and 20%, respectively). The main reasons for not using inhaled ICU sedation were: "device not available" (40%), "lack of medical interest" (37%), "lack of familiarity or knowledge about the technique" (35%) and "elevated cost" (21%). Most respondents (80%) were overall satisfied with the use of inhaled sedation. Almost 75% stated that inhaled sedation was a seducing alternative to intravenous sedation. Conclusion: This survey highlights the widespread knowledge about inhaled ICU sedation in France but shows its limited use to date. Differences in education and knowledge, as well as the recent and relatively scarce literature on the use of volatile agents in the ICU, might explain the diverse practices that were observed. The low rate of mild adverse effects, as perceived by respondents, and the users' satisfaction, are promising for this potentially important tool for ICU sedation. [ABSTRACT FROM AUTHOR]

Background: Perioperative infections, particularly surgical site infections pose significant morbidity and mortality. Phagocytosis is a critical step for microbial eradication. We examined the effect of commonly used anesthetics on macrophage phagocytosis and its mechanism. Methods: The effect of anesthetics (isoflurane, sevoflurane, propofol) on macrophage phagocytosis was tested using RAW264.7 mouse cells, mouse peritoneal macrophages, and THP-1 human cells. Either opsonized sheep erythrocytes or fluorescent labeled Escherichia coli were used as phagocytic objects. The activation of Rap1, a critical protein in phagocytosis was assessed using the active Rap1 pull-down and detection kit. To examine anesthetic binding site(s) on Rap1, photolabeling experiments were performed using azi-isoflurane and azi-sevoflurane. The alanine scanning mutagenesis of Rap1 was performed to assess the role of anesthetic binding site in Rap1 activation and phagocytosis. Results: Macrophage phagocytosis was significantly attenuated by the exposure of isoflurane (50% reduction by 1% isoflurane) and sevoflurane (50% reduction by 1.5% sevoflurane), but not by propofol. Photolabeling experiments showed that sevoflurane directly bound to Rap1. Mutagenesis analysis demonstrated that the sevoflurane binding site affected Rap1 activation and macrophage phagocytosis. Conclusions: We showed that isoflurane and sevoflurane attenuated macrophage phagocytosis, but propofol did not. Our study showed for the first time that sevoflurane served as a novel small GTPase Rap1 inhibitor. The finding will further enrich our understanding of yet-to-be determined mechanism of volatile anesthetics and their off-target effects. The sevoflurane binding site was located outside the known Rap1 functional sites, indicating the discovery of a new functional site on Rap1 and this site would serve as a pocket for the development of novel Rap1 inhibitors. [ABSTRACT FROM AUTHOR]

Delirium is a common complication of vascular surgery. The protective effect of preoperative statins on delirium after vascular surgery is controversial. The authors hypothesized that preoperative statin administration would decrease the incidence of delirium after vascular surgery. From May 2010 to May 2015, 1,132 patients underwent vascular surgery. Postoperative delirium was diagnosed from patients’ medical records. The incidence of delirium was 11.5%. The preoperative statin exposure was not associated with reduced delirium in the univariate analysis. After adjusting for covariates, preoperative statin exposure was associated with reduced delirium (OR, 0.54; 95% CI, 0.33–0.87; p = 0.011). This favor effect of statin for delirium was observed after propensity matching (OR, 0.59; 95% CI, 0.34–1.02; p = 0.060). However, the median hospital lengths of stay and in-hospital mortality were not statistically different between the two groups. CRP(C-reactive protein) levels in the unmatched population were lower in the preoperative statin group compared with the other group (p<0.001), however, there was only numerically different without statistical difference after matching (p = 0.083). Preoperative statin use was associated with a decreased incidence of postoperative delirium in patients who underwent vascular surgery. However, preoperative statin did not reduce mortality rate and hospital stay. [ABSTRACT FROM AUTHOR]

Light causes damage to the retina (phototoxicity) and decreases photoreceptor responses to light. The most harmful component of visible light is the blue wavelength (400–500 nm). Different filters have been tested, but so far all of them allow passing a lot of this wavelength (70%). The aim of this work has been to prove that a filter that removes 94% of the blue component may protect the function and morphology of the retina significantly. Three experimental groups were designed. The first group was unexposed to light, the second one was exposed and the third one was exposed and protected by a blue-blocking filter. Light damage was induced in young albino mice (p30) by exposing them to white light of high intensity (5,000 lux) continuously for 7 days. Short wavelength light filters were used for light protection. The blue component was removed (94%) from the light source by our filter. Electroretinographical recordings were performed before and after light damage. Changes in retinal structure were studied using immunohistochemistry, and TUNEL labeling. Also, cells in the outer nuclear layer were counted and compared among the three different groups. Functional visual responses were significantly more conserved in protected animals (with the blue-blocking filter) than in unprotected animals. Also, retinal structure was better kept and photoreceptor survival was greater in protected animals, these differences were significant in central areas of the retina. Still, functional and morphological responses were significantly lower in protected than in unexposed groups. In conclusion, this blue-blocking filter decreases significantly photoreceptor damage after exposure to high intensity light. Actually, our eyes are exposed for a very long time to high levels of blue light (screens, artificial light LED, neons…). The potential damage caused by blue light can be palliated. [ABSTRACT FROM AUTHOR]

GABAergic inhibitory neurons are a large population of neurons in the central nervous system (CNS) of mammals and crucially contribute to the function of the circuitry of the brain. To identify specific cell types and investigate their functions labelling of cell populations by transgenic expression of fluorescent proteins is a powerful approach. While a number of mouse lines expressing the green fluorescent protein (GFP) in different subpopulations of GABAergic cells are available, GFP expressing mouse lines are not suitable for either crossbreeding to other mouse lines expressing GFP in other cell types or for Ca2+-imaging using the superior green Ca2+-indicator dyes. Therefore, we have generated a novel transgenic mouse line expressing the red fluorescent protein tdTomato in GABAergic neurons using a bacterial artificial chromosome based strategy and inserting the tdTomato open reading frame at the start codon within exon 1 of the GAD2 gene encoding glutamic acid decarboxylase 65 (GAD65). TdTomato expression was observed in all expected brain regions; however, the fluorescence intensity was highest in the olfactory bulb and the striatum. Robust expression was also observed in cortical and hippocampal neurons, Purkinje cells in the cerebellum, amacrine cells in the retina as well as in cells migrating along the rostral migratory stream. In cortex, hippocampus, olfactory bulb and brainstem, 80% to 90% of neurons expressing endogenous GAD65 also expressed the fluorescent protein. Moreover, almost all tdTomato-expressing cells coexpressed GAD65, indicating that indeed only GABAergic neurons are labelled by tdTomato expression. This mouse line with its unique spectral properties for labelling GABAergic neurons will therefore be a valuable new tool for research addressing this fascinating cell type. [ABSTRACT FROM AUTHOR]

The genetic treatment of neurodegenerative diseases still remains a challenging task since many approaches fail to deliver the therapeutic material in relevant concentrations into the brain. As viral vectors comprise the risk of immune and inflammatory responses, human serum albumin (HSA) nanoparticles were found to represent a safer and more convenient alternative. Their ability to cross the blood-brain barrier (BBB) and deliver drugs into the brain in order to enhance gene-based therapy has been previously demonstrated. The present study deals with the development of pGL3-PEI-coated HSA nanoparticles and subsequent in vitro testing in cerebellar granular and HeLa cells. The luciferase control vector pGL3 was chosen as reporter plasmid encoding for the firefly luciferase protein, linear polyethylenimine (22 kDa) as endosomolytic agent for enhancing the cells’ transfection. Studies on particle characteristics, their cellular uptake into aforementioned cell lines and on subcellular localisation, and transfection efficiency in the cerebellar cells proved the feasibility of nanoparticle-based gene delivery. [ABSTRACT FROM AUTHOR]

Lampreys are one of the two surviving groups of the agnathan (jawless) stages in vertebrate evolution and are thus ideal candidates for elucidating the evolution of visual systems. This study investigated the retinal amino acid neurochemistry of the southern hemisphere lamprey Geotria australis during the downstream migration of the young, recently-metamorphosed juveniles to the sea and during the upstream migration of the fully-grown and sexually-maturing adults to their spawning areas. Glutamate and taurine were distributed throughout the retina, whilst GABA and glycine were confined to neurons of the inner retina matching patterns seen in most other vertebrates. Glutamine and aspartate immunoreactivity was closely matched to Müller cell morphology. Between the migratory phases, few differences were observed in the distribution of major neurotransmitters i.e. glutamate, GABA and glycine, but changes in amino acids associated with retinal metabolism i.e. glutamine and aspartate, were evident. Taurine immunoreactivity was mostly conserved between migrant stages, consistent with its role in primary cell functions such as osmoregulation. Further investigation of glutamate signalling using the probe agmatine (AGB) to map cation channel permeability revealed entry of AGB into photoreceptors and horizontal cells followed by accumulation in inner retinal neurons. Similarities in AGB profiles between upstream and downstream migrant of G. australis confirmed the conservation of glutamate neurotransmission. Finally, calcium binding proteins, calbindin and calretinin were localized to the inner retina whilst recoverin was localized to photoreceptors. Overall, conservation of major amino acid neurotransmitters and calcium-associated proteins in the lamprey retina confirms these elements as essential features of the vertebrate visual system. On the other hand, metabolic elements of the retina such as neurotransmitter precursor amino acids and Müller cells are more sensitive to environmental changes associated with migration. [ABSTRACT FROM AUTHOR]