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The aim of the study was to compare the effect of adding different sources of hydrolysable tannins to the sheep diet on protozoa population and carbohydrate digestion in the rumen. The study was performed in 3 Polish Lowland ewes fistulated to the rumen in a 3 × 3 Latin square design. Control sheep (CON) received (g/d): meadow hay (600), barley meal (300), soybean meal (100) and vitamin-mineral premix (20). Sheep from the experimental groups were additionally administered 12.6 g/kg DM oak bark extract (OAK) and 3.91 g/kg DM tannic acid (TAN ). The net consumption of tannins was approx. 0.4% DM for both additives. Regarding the count of protozoa, a significant interaction between diet and sampling time was documented for all ciliates (PEntodinium spp. (before feeding, 2 and 4 h after feeding; PIsotricha spp. population (4 h after feeding; POphryoscolex spp. after feeding the TAN diet increased before feeding and 2 h after feeding in comparison to the CON and OAK groups, respectively, and subsequently decreased compared to the CON diet (4 and 8 h after feeding, PEntodinium spp., which consequently reduced amylolytic activity in the rumen, without any significant effect on pH and carbohydrate fermentation in the rumen.

Unit packaging of dietary supplements - an inherent element of their manufacturing, without which they would be impossible to market — has numerous interlocking functions to fulfil, including the protective, transport, information, functional, ecological and marketing functions. The information function, however, is one of the priority functions of dietary supplement packaging. In the era of the continual development of online and self-service stores (including pharmacies), such packaging has become one of the key sources of information about dietary supplements’ features and properties, while also serving as a brand image creator and a carrier of promotional information. This raises the questions of whether and to what extent the unit packaging of dietary supplements influences the purchasing decisions of consumers, what features and elements of such packaging are crucial for consumers in the purchasing process, and what significance supplement packaging has in the purchasing process against the background of other purchasing determinants. Seeking to address these questions, herein we present selected results of an original study conducted in 2019 with a purposely selected sample of 468 dietary supplement consumers in Poland, whose main purpose was to identify the role and significance of packaging as a determinant of purchase in relation to three selected categories of dietary supplements..

Objective The aim of this study was to investigate the detection rate of unruptured intracranial aneurysms (UIAs) and incidence of aneurysmal subarachnoid haemorrhage (SAH) in relation to the rapidly changing smoking rates in Norway between 2008 and 2015. Methods The registry-based study included all patients (≥ 16 years old) admitted to a hospital in Norway between 2008 and 2015 with a primary diagnosis of aneurysmal SAH or an outpatient diagnosis of UIAs. Age group–specific and total detection rate of UIAs and incidence rate of SAH over the years were calculated. Age group–specific data on smoking habits was retrieved from a national annual survey representative of the whole Norwegian population. Results The rate of daily smokers decreased by 48% between 2008 and 2015. The detection rate of UIAs decreased by 47% from 17.3 in 2008 to 9.3 per 100,000 persons in 2015, and the incidence of SAH decreased by 30% from 11.3 in 2008 to 7.9 per 100,000 persons in 2015. The average annual decline in prevalence of daily smoking, UIA detection rate, and SAH incidence was 6.9%, 6.7%, and 4.3% per year, respectively. Multinomial logistic regression analyses revealed that the correlation between the decline in estimated daily smoking rates and decline in detection rate of UIAs (hazard ratio 52.5 CI = (14.9,∞), p < 0.00001) and incidence of SAH (hazard ratio 11.8 CI=(5.6,32.5), p < 0.00001) are statistically significant. The association is particularly strong in young and middle-aged cohorts (< 66 years old). Conclusion It is likely that reducing cigarette smoking on a population-based level strongly reduces the rates of UIAs and SAH.

Background To provide age- and sex-specific incidence and case fatality rates for non-traumatic aneurysmal subarachnoid hemorrhage (aSAH) in Norway. We also studied time trends in incidence and case fatality, as well as predictors of death following aSAH. Methods A nationwide study using discharge data for patients admitted with aSAH between 2008 and 2014. Results A total of 1732 patients with aSAH were included. The mean age was 60 years (SD 14) and 63% were females. Crude annual incidence was 5.7 per 100,000 person-years (95% CI 5.4–6.0) and was higher in females (6.3 per 100,000, 95% CI 5.9–6.7) compared with males (4.9 per 100,000, 95% CI 4.5–5.3). The annual decline in aSAH incidence was 3.2% per year (p = 0.007). The cumulative proportions of fatalities at days 30, 90, and 1 year were 22%, 25%, and 37%, respectively. The 30-day mortality rate did not change during the study period. Age (HR 0.7–2.2) and aneurysms in the posterior circulation (HR 1.7, 95% CI 1.3–2.3, p = 0.001) were associated with higher 30-day case fatality following aSAH, while aneurysm repair (HR 0.2, 95% CI 0.2–0.3, p Conclusions The incidence of aSAH declined in Norway between 2008 and 2014. Case fatality following aSAH continues to be high, and the 30-day mortality during the study period was unchanged. Increasing age and aneurysms in the posterior circulation were associated with increased risk of death within 30 days following aSAH.

Objective To determine the diagnostic accuracy of routine clinico-radiological workup for a population-based selection of intracranial tumours. Methods In this prospective cohort study, we included consecutive adult patients who underwent a primary surgical intervention for a suspected intracranial tumour between 2015 and 2019 at a single-neurosurgical centre. The treating team estimated the expected diagnosis prior to surgery using predefined groups. The expected diagnosis was compared to final histopathology and the accuracy of preoperative clinico-radiological diagnosis (sensitivity, specificity, positive and negative predictive values) was calculated. Results 392 patients were included in the data analysis, of whom 319 underwent a primary surgical resection and 73 were operated with a diagnostic biopsy only. The diagnostic accuracy varied between different tumour types. The overall sensitivity, specificity and diagnostic mismatch rate of clinico-radiological diagnosis was 85.8%, 97.7% and 4.0%, respectively. For gliomas (including differentiation between low-grade and high-grade gliomas), the same diagnostic accuracy measures were found to be 82.2%, 97.2% and 5.6%, respectively. The most common diagnostic mismatch was between low-grade gliomas, high-grade gliomas and metastases. Accuracy of 90.2% was achieved for differentiation between diffuse low-grade gliomas and high-grade gliomas. Conclusions The current accuracy of a preoperative clinico-radiological diagnosis of brain tumours is high. Future non-invasive diagnostic methods need to outperform our results in order to add much value in a routine clinical setting in unselected patients.

Objectives: The growing incidence of multidrug-resistant (MDR) bacteria is an inexorable and fatal challenge in modern medicine. Colistin is a cationic polypeptide considered a “last-resort” antimicrobial for treating infections caused by MDR Gram-negative bacterial pathogens. Plasmid-borne mcr colistin resistance emerged recently, and could potentially lead to essentially untreatable infections, particularly in hospital and veterinary (livestock farming) settings. In this study, we sought to establish the molecular basis of colistin-resistance in six extraintestinal Escherichia coli strains. Methods: Molecular investigation of colistin-resistance was performed in six extraintestinal E. coli strains isolated from patients hospitalized in Medical University Hospital, Bialystok, Poland. Complete structures of bacterial chromosomes and plasmids were recovered with use of both short- and long-read sequencing technologies and Unicycler hybrid assembly. Moreover, an electrotransformation assay was performed in order to confirm IncX4 plasmid influence on colistin-resistance phenotype in clinical E. coli strains. Results: Here we report on the emergence of six mcr-1.1-producing extraintestinal E. coli isolates with a number of virulence factors. Mobile pEtN transferase-encoding gene, mcr-1.1, has been proved to be encoded within a type IV secretion system (T4SS)-containing 33.3 kbp IncX4 plasmid pMUB-MCR, next to the PAP2-like membrane-associated lipid phosphatase gene. Conclusion: IncX4 mcr-containing plasmids are reported as increasingly disseminated among E. coli isolates, making it an “epidemic” plasmid, responsible for (i) dissemination of colistin-resistance determinants between different E. coli clones, and (ii) circulation between environmental, industrial, and clinical settings. Great effort needs to be taken to avoid further dissemination of plasmid-mediated colistin resistance among clinically relevant Gram-negative bacterial pathogens.

Background The growing incidence of MDR Gram-negative bacteria is a rapidly emerging challenge in modern medicine. Objectives We sought to establish the role of intrinsic drug-resistance regulators in combination with specific genetic mutations in 11 Enterobacter cloacae isolates obtained from a single patient within a 7 week period. Methods The molecular characterization of eight carbapenem-resistant and three carbapenem-susceptible E. cloacae ST89 isolates included expression-level analysis and WGS. Quantitative PCR included: (i) chromosomal cephalosporinase gene (ampC); (ii) membrane permeability factor genes, e.g. ompF, ompC, acrA, acrB and tolC; and (iii) intrinsic regulatory genes, e.g. ramA, ampR, rob, marA and soxS, which confer reductions in antibiotic susceptibility. Results In this study we describe the influence of the alterations in membrane permeability (ompF and ompC levels), intrinsic regulatory genes (ramA, marA, soxS) and intrinsic chromosomal cephalosporinase AmpC on reductions in carbapenem susceptibility of E. cloacae clinical isolates. Interestingly, only the first isolate possessed the acquired VIM-4 carbapenemase, which has been lost in subsequent isolates. The remaining XDR E. cloacae ST89 isolates presented complex carbapenem-resistance pathways, which included perturbations in permeability of bacterial membranes mediated by overexpression of ramA, encoding an AraC/XylS global regulator. Moreover, susceptible isolates differed significantly from other isolates in terms of marA down-regulation and soxS up-regulation. Conclusions Molecular mechanisms of resistance among carbapenem-resistant E. cloacae included production of acquired VIM-4 carbapenemase, significant alterations in membrane permeability due to increased expression of ramA, encoding an AraC/XylS global regulator, and the overproduction of chromosomal AmpC cephalosporinase.

The main objective of this study is the enantioselective synthesis of carboxyhydroxyphosphonates by lipase-catalyzed reactions. For this purpose, racemic dimethyl and dibutyl 1-butyryloxy-1-carboxymethylphosphonates were synthesized and hydrolyzed, using a wide spectrum of commercially available lipases from different sources (e.g., fungi and bacteria). The best hydrolysis results of dimethyl 1-butyryloxy-1-carboxymethylphosphonate were obtained with the use of lipases from Candida rugosa, Candida antarctica, and Aspergillus niger, leading to optically active dimethyl 1-carboxy-1-hydroxymethylphosphonate (58%–98% enantiomeric excess) with high enantiomeric ratio (reaching up to 126). However, in the case of hydrolysis of dibutyl 1-butyryloxy-1-carboxymethylphosphonate, the best results were obtained by lipases from Burkholderia cepacia and Termomyces lanuginosus, leading to optically active dibutyl 1-carboxy-1-hydroxymethylphosphonate (66%–68% enantiomeric excess) with moderate enantiomeric ratio (reaching up to 8.6). The absolute configuration of the products after biotransformation was also determined. In most cases, lipases hydrolyzed (R) enantiomers of both compounds.

In 1995 a 16-year old girl was diagnosed with a large left thalamic AVM that was considered unsuitable for microsurgical resection and was treated with radiotherapy twice, which led to angiographic cure. She re-presented 19 years after initial treatment with a symptomatic acute thalamic haemorrhage. Her digital subtraction angiography was negative for arterio-venous shunting. MRI/MRA showed cystic change with adjacent contrast enhancement in the region of the previously irradiated arteriovenous malformation. The patient underwent an interhemispheric transcallosal resection of the left thalamic haemorrhagic lesion via a contralateral craniotomy. Intra-operatively there was a cystic cavity filled with blood products in association with thrombosed, calcified vessels as well as actively filling vessels. Histologically there were aggregated abnormal blood vessels with a dilated lumen and surrounded by brain parenchyma. Some of the vessel walls were thickened with fibrosis and some were arterialised with presence of elastin fibres. Potential mechanisms for the delayed haemorrhage are discussed.

For the first time, photosensitization of selected alkaline titanates with surface charge transfer complexes has been proven. Activation of BaTiO3, SrTiO3 and CaTiO3 to visible as well as ultraviolet light has been achieved by impregnation with catechol, salicylic acid and 2,3-naphthalenediol. Simple modification of titanates with organic compounds forming inner-sphere CT complexes with Ti atoms located at the surface of semiconductors resulted in coloration of the materials. Even though acceptor electronic states of titanates are characterized by a higher energy compared with titania (even up to 0.75 eV higher for CaTiO3), complexes formed at their surface absorb in similar or even broader optical range of visible light. Beside changes in the absorption properties, used modifications also strongly influenced their photoelectrochemical and photocatalytic properties. In contrast to similarly modified titanium dioxide, modified titanates show significantly improved photocatalytic activity not only under visible light but also within ultraviolet range of radiation. Remarkably increased efficiency of photocurrent generation within the UV range of radiation may suggest that apart from observed electron transfer from HOMO of the complex to conduction band (CB) of the semiconductor also an indirect photosensitization mechanism involving the electron transfer from the excited complexes to the CB of titanates may take place.

Purpose: Cauda equina syndrome (CES) is a spinal emergency with clinical symptoms and signs that have low diagnostic accuracy. National guidelines in the United Kingdom (UK) state that all patients should undergo an MRI prior to referral to specialist spinal units and surgery should be performed at the earliest opportunity. We aimed to evaluate the current practice of investigating and treating suspected CES in the UK. Materials and Methods: A retrospective, multicentre observational study of the investigation and management of patients with suspected CES was conducted across the UK, including all patients referred to a spinal unit over 6 months between 1st October 2016 and 31st March 2017. Results: A total of 28 UK spinal units submitted data on 4441 referrals. Over half of referrals were made without any previous imaging (n = 2572, 57.9%). Of all referrals, 695 underwent surgical decompression (15.6%). The majority of referrals were made out-of-hours (n = 2229/3517, 63.4%). Patient location and pre-referral imaging were not associated with time intervals from symptom onset or presentation to decompression. Patients investigated outside of the spinal unit experienced longer time intervals from referral to undergoing the MRI scan. Conclusions: This is the largest known study of the investigation and management of suspected CES. We found that the majority of referrals were made without adequate investigations. Most patients were referred out-of-hours and many were transferred for an MRI without subsequently requiring surgery. Adherence to guidelines would reduce the number of referrals to spinal services by 72% and reduce the number of patient transfers by 79%.

2-Hydroxy-2-(ethoxyphenylphosphinyl)acetic acid, a new type of organophosphorus compound possessing two stereogenic centers, was investigated. Racemic 2-butyryloxy-2-(ethoxyphenylphosphinyl)acetic acid was synthesized and hydrolyzed using four bacterial species as biocatalysts. In all cases the reaction was more or less stereoselective and isomers bearing a phosphorus atom with an (SP)-configuration were hydrolyzed preferentially. The observed (1)H and (31)P NMR chemical shifts of Mosher esters of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid were correlated with the configurations of both stereogenic centers of all four stereoisomers.

Glioblastoma is the commonest malignant brain tumor in adults. Most patients develop progressive disease before they die. However, survival after developing progressive disease is infrequently reported. We identified patients with histologically proven disease who were treated with concurrent chemoradiotherapy during 2006–2013. We analyzed overall survival (OS), progression-free survival and postprogression survival (PPS) in relation to age, O6-methylguanine-DNA methyltransferase promoter methylation and extent of surgical resection. We identified 166 patients. Median survival was 13.5 months; 2-year OS was 21.7%. Median progression-free survival and PPS were 7.03 and 4.53 months, respectively. Age and extent of surgical resection were correlated with OS. Only the extent of surgical resection was associated with PPS. Our work suggests that the established prognostic factors for glioblastoma do not appear to help predict PPS.

Three strains of microorganisms: Bacillus subtilis, Serratia liquefaciens and Escherichia coli were tested as whole-cell biocatalysts for the kinetic resolution of isomers of two new phosphonoacetic acid derivatives. Used compounds possess two chiral centres – one at the carbon adjacent to both functional groups and the other at the phosphorus. Biocatalytic hydrolysis of 2-butyryloxy-2-(butoxyetoxyphosphinyl)acetic acid and 2-butyryloxy-2-(isobutoxyetoxyphosphinyl)acetic acid with whole cells of Bacillus subtilis produced corresponding hydroxyphosphonates with diastereoselectivity ranging from 50 to 60%.

Polarized infrared spectra of liquid crystalline 4-chloro-2'-hydroxy-4'-alkyloxyazobenzenes (CHAB) with C(5), C(6), and C(7) alkyl chains measured at 25 °C were compared, with particular attention being paid to the influence of chain length on formation of ordered boundary layers. The effect of chain elongation is discussed on the basis of calculations of the optimized geometry of dimeric species, which reflects the role of association in ordered phases. The impact of the varying intermolecular interactions on the spectra of C(5), C(6), and C(7) derivatives measured as a function of the polarization angle is analyzed by principal component analysis (PCA). The polarization-angle-dependent results are contrasted with the transition moment directions obtained from the density functional theory (DFT) calculations. The continuum spread down to 500 cm(-1) and a pseudoband at ca. 600 cm(-1) ascribed to the Fermi resonance between ν(OH) and γ(OH) modes is an additional phenomenon whose features also depend on alkyl chain length.

Different dextran esters with various degrees of substitution (1, 2 and 3) were synthesized by esterification reaction, with three acid anhydrides: acetic anhydride, propionic anhydride, and butyric anhydride, separately. These modified polysaccharides were characterized by FT-IR, 1H NMR and 13C NMR spectroscopies. Enzymatic degradation of biopolymers by dextranase was also studied. The polymers showing the best degradation profiles were chosen to design blended free films in combination with a polymethacrylate (Eudragit® RS 30D) as a sustained release system for targeting to the colon. These free films were evaluated by permeability of theophylline used as tracer in different in vitro media of the gastro intestinal tract, in presence or in absence of dextranase. From these studies, it was concluded that dextran esters having the lower degree of substitution and constituted of short carbohydrate chains showed the best and significant enzymatic degradation and could be used as a promising carrier for specific colon drug delivery system. Keywords: Colon-Specific Drug Delivery; Polysaccharides; Dextran; Dextranase; Dextran esters; Enzymatic Degradation; Eudragit® RS 30D; Sid-by-side diffusion cell

A wide spectrum of commercially available lipases and microbial whole cells catalysts were tested for biotransformations of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid 1 and its butyryl ester. The best results were achieved for biocatalytic hydrolysis of ester: 2-butyryloxy-2-(ethoxyphenylphosphinyl)acetic acid 2 performed by lipase from Candida cylindracea, what gave optically active products with 85% enantiomeric excess, 50% conversion degree and enantioselectivity 32.9 for one pair of enantiomers. Also enzymatic systems of Penicillium minioluteum and Fusarium oxysporum were able to hydrolyze tested compound with high enantiomeric excess (68–93% ee), enantioselectivity (44 for one pair of enantiomers) and conversion degree about 50–55%. Enzymatic acylation of hydroxyphosphinate was successful in case when porcine pancreas lipase was used. After 4days of biotransformation the conversion reaches 45% but the enantiomeric enrichment of the isomers mixture do not exceed 43%. Obtained chiral compounds are valuable derivatizing agents for spectroscopic (NMR) evaluation of enantiomeric excess for particular compounds (e.g. amino acids).

Biodegradable capacities of fungal strains of Fusarium oxysporum (DSMZ 2018) and Fusarium culmorum (DSMZ 1094) were tested towards racemic mixture of chiral 2-hydroxy-2-(ethoxyphenylphosphinyl) acetic acid—a compound with two stereogenic centres. The effectiveness of decomposition was dependent on external factors such as temperature and time of the process. Optimal conditions of complete mineralization were established. Both Fusarium species were able to biodegrade every isomer of tested compound at 30°C, but F. culmorum required 10 days and F. oxysporum 11 days to accomplish the process, which was continuously monitored using the 31P NMR technique.

In bioprocesses lipases are typically used in immobilized form, irrespective of type of reaction systems, to ensure an even distribution of catalysts in water restricted media and/or to facilitate separation and reuse. In these studies we report on the selection of appropriate enzyme-carrier preparation for hydrolysis reaction in aqueous and biphasic systems and transesterification in organic solvent. For this Candida rugosa lipase was bound by adsorption or covalent attachment onto various carriers to give 24 preparations. Selection of proper preparation was based on reactivity, thermal stability (4 h at 60°C), possibility of drying and operational stability in 17-23 successive batch processes of 4-nitrophenyl palmitate hydrolysis in water. Activity of preparations varied from 20 to 5100 U∙mL(-1) but the most stable preparations were those of moderate activity: bound by adsorption or covalent attachment to NH₂-Kieselgel or acrylic carrier (retained activity over 90%). Selected preparations were used for hydrolysis of ethyl (1-butyryloxyethyl)-phenylphosphinate in biphasic system, and, after drying, in ethyl (1-hydroxyethyl)-phenyl-phosphinate transesterification. In this study operational stability was the principal criterion of selection. In water system, lipase covalently bound to NH₂-Kieselgel was the best - preserved 50% of initial activity in consecutive batch processes. In biphasic system and lipase covalently bound to acrylic and NH₂-Kieselgel the values were 90 or 77%, respectively, whereas in organic solvent, when lipase was immobilized on NH₂-Kieselgel by adsorption, it was 50%. Thus, NH₂-Kieselgel appears to be an universal matrix for investigated lipase immobilization and can be used in all reaction systems.