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Copyright of Veterinarska Stanica is the property of Croatian Veterinary Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The targeted compounds in this research, resveratrol analogs 1–14, were synthesized as mixtures of isomers by the Wittig reaction using heterocyclic triphenylphosphonium salts and various benzaldehydes. The planned compounds were those possessing the trans-configuration as the biologically active trans-resveratrol. The pure isomers were obtained by repeated column chromatography in various isolated yields depending on the heteroaromatic ring. It was found that butyrylcholinesterase (BChE) was more sensitive to the heteroaromatic resveratrol analogs than acetylcholinesterase (AChE), except for 6, the methylated thiophene derivative with chlorine, which showed equal inhibition toward both enzymes. Compounds 5 and 8 achieved the highest BChE inhibition with IC50 values of 22.9 and 24.8 μM, respectively. The same as with AChE and BChE, methylated thiophene subunits of resveratrol analogs showed better enzyme inhibition than unmethylated ones. Two antioxidant spectrophotometric methods, DPPH and CUPRAC, were applied to determine the antioxidant potential of new heteroaromatic resveratrol analogs. The molecular docking of these compounds was conducted to visualize the ligand-active site complexes' structure and identify the non-covalent interactions responsible for the complex's stability, which influence the inhibitory potential. As ADME properties are crucial in developing drug product formulations, they have also been addressed in this work. The potential genotoxicity is evaluated by in silico studies for all compounds synthesized. [ABSTRACT FROM AUTHOR]

Participants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to a reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a booster dose of NVX-CoV2373 (n = 303) or an mRNA vaccine (n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported ≥3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6–2.0) and 3.2 (3.0–3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33–1.61) and 2.4 (2.31–2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with lower reactogenicity than mRNAs. [ABSTRACT FROM AUTHOR]

Triazoles and triazolium salts are very common subunits in the structures of various drugs. Medicaments with a characteristic 1,2,3-triazole core are also being developed to treat neurodegenerative disorders associated with cholinesterase enzyme activity. Several naphtho- and thienobenzo-triazoles from our previous research emerged as being particularly promising in that sense. For this reason, in this research, new naphtho- and thienobenzo-triazoles 23–34, as well as 1,2,3-triazolium salts 44–51, were synthesized and tested. Triazolium salts 44–46 showed excellent activity while salts 47 and 49 showed very good inhibition toward both butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) enzymes. In contrast, neutral photoproducts were shown to be selective towards BChE but with very good inhibition potential as molecules 24–27. The representative of newly prepared compounds, 45 and 50, were stable in aqueous solution and revealed intriguing fluorimetric properties, characterized by a strong Stokes shift of >160 nm. Despite their condensed polycyclic structure shaped similarly to well-known DNA-intercalator ethidium bromide, the studied compounds did not show any interaction with ds-DNA, likely due to the unfavorable steric hindrance of substituents. However, the studied dyes bind proteins, particularly showing very diverse inhibition properties toward AChE and BChE. In contrast, neutral photoproducts were shown to be selective towards a certain enzyme but with moderate inhibition potential. The molecular docking of the best-performing candidates to cholinesterases' active sites identified cation–π interactions as the most responsible for the stability of the enzyme–ligand complexes. As genotoxicity studies are crucial when developing new active substances and finished drug forms, in silico studies for all the compounds synthesized have been performed. [ABSTRACT FROM AUTHOR]

The poor grade subarachnoid haemorrhage patients represent a unique cohort with lack of clear treatment protocol. Most neurosurgical units in the UK will manage them at local hospital until they make a significant recovery, this period can put them at higher risk of rebleed while with aggressive treatment a significant subset can achieve a favourable outcome. Identification of this subset is difficult and decision to treat them is associated with significant commitment of neurosurgical and ITU resources. Recent paper by Szklener has come up with a scale for prognostication in this subgroup of patients. We wanted to check the validity of this scale in our patient population and see if this scale can be used to guide early patient transfer and aggressive management at the Neurosurgical unit. We retrospectively reviewed our referral database for all poor grade subarachnoid patients referred over 2 years. Demographic information, Fisher and WFNS scores, admitting leucocyte count and outcome information as per MRS were obtained. These were scored as per the scale suggested by Szklener. A total of 115 poor grade subarachnoid patients were referred over the study time frame. 47 of them were accepted for admission. 18/47 patients achieved a favourable outcome (GOS4-5). Only 1 patient managed in peripheral hospital had a good outcome. There was a significant association between Szklener's score and achieving a favourable outcome p = 0.002. A selective admission policy could work specially with current economic climate, achieving outcomes comparable to admit-all. However, to optimise outcomes for all patients an aggressive standardised management at peripheral hospitals and a uniform admission policy assisted by Szklener score may be adopted. Szklener's model predicts the outcome better than WFNS and age but more validation is needed. [ABSTRACT FROM AUTHOR]

Copyright of Veterinarska Stanica is the property of Croatian Veterinary Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy. [ABSTRACT FROM AUTHOR]

This article examines how religious leaders navigate between tensions involving theological ideals of peace and pragmatic realities during violent conflicts. The findings are based on 75 in-depth interviews with Orthodox, Catholic, and Islamic religious leaders in Bosnia-Herzegovina, conducted between the years 2015 and 2017. The paper introduces the concepts of "theological dissonance" to describe mismatches between principles and actions, and "pastoral optimization" for the strategy of maximizing influence under constraints. Factors influencing engagement in peacebuilding include doctrinal traditions, individual differences, organizational capacity of a religious community, effective control over messaging, and audience receptivity. In terms of practical suggestions, the article proposes several measures that could enhance synergy between religious and nonreligious actors working together in this field, most notably, understanding each other's scopes and limitations and clarifying what "peace" and "peacebuilding" represent to each partner. [ABSTRACT FROM AUTHOR]

Previous biological tests have shown that some resveratrol analogs exhibited significant antioxidative and cholinesterase inhibitory potential, as evidenced by lower IC50 values compared to the established standards, resveratrol and galantamine, respectively. Photochemical transformations were made in parallel on these compounds in the presence of porphyrin photocatalysts in batch and microreactor, showing the significant advantage of flow photochemistry concerning productivity, selectivity, and yields. In this research, the products of photocatalysis and direct irradiation (photolysis) of resveratrol analogs were compared to elucidate how the types and ratios of the products depend on the excitation energy, to reveal the effects of the substituent on the photoinduced reactions and to rationalize experimentally and computationally the nature and ratio of the obtained products. Thus, two main paths were computed in agreement with the experimental results: isomerization with the participation of triplet state intermediates to yield the experimentally detected cis-isomers and subsequent cyclization following a pathway not available for the trans-isomers. The investigation of five model compounds confirmed the advantages of the flow photoreactor in the photochemical reactions of heterocyclic resveratrol analogs. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 variants continue to emerge, vaccination remains a critical tool to reduce the COVID-19 burden. Vaccine reactogenicity and the impact on work productivity/daily activities are recognized as contributing factors to vaccine hesitancy. To encourage continued COVID-19 vaccination, a more complete understanding of the differences in reactogenicity and impairment due to vaccine-related side effects across currently available vaccines is necessary. The 2019nCoV-406 study (n = 1367) was a prospective observational study of reactogenicity and associated impairments in adults in the United States and Canada who received an approved/authorized COVID-19 vaccine. Compared with recipients of mRNA COVID-19 booster vaccines, a smaller percentage of NVX-CoV2373 booster recipients reported local and systemic reactogenicity. This study's primary endpoint (percentage of participants with ≥50% overall work impairment on ≥1 of the 6 days post-vaccination period) did not show significant differences. However, the data suggest that NVX-CoV2373 booster recipients trended toward being less impaired overall than recipients of an mRNA booster; further research is needed to confirm this observed trend. The results of this real-world study suggest that NVX-CoV2373 may be a beneficial vaccine option with limited impact on non-work activities, in part due to the few reactogenicity events after vaccination. [ABSTRACT FROM AUTHOR]

We perform a detailed study of the covariance properties of the symplectic potential of general relativity on a null hypersurface, and of the different polarizations that can be used to study conservative as well as leaky boundary conditions. This allows us to identify a one-parameter family of covariant symplectic potentials. We compute the charges and fluxes for the most general phase space with arbitrary variations. We study five symmetry groups that arise when different restrictions on the variations are included. Requiring stationarity as in the original Wald-Zoupas prescription selects a unique member of the family of symplectic potentials, the one of Chandrasekaran, Flanagan and Prabhu. The associated charges are all conserved on non-expanding horizons, but not on flat spacetime. We show that it is possible to require a weaker notion of stationarity which selects another symplectic potential, again in a unique way, and whose charges are conserved on both non-expanding horizons and flat light-cones. Furthermore, the flux of future-pointing diffeomorphisms at leading-order around an outgoing flat light-cone is positive and reproduces a tidal heating plus a memory term. We also study the conformal conservative boundary conditions suggested by the alternative polarization and identify under which conditions they define a non-ambiguous variational principle. Our results have applications for dynamical notions of entropy, and are useful to clarify the interplay between different boundary conditions, charge prescriptions, and symmetry groups that can be associated with a null boundary. [ABSTRACT FROM AUTHOR]

The article results from the creation and implementation of a 1-year online Memory Studies Certificate Program at UCLouvain (Belgium). It describes the program designed by a team of researchers with different disciplinary backgrounds (i.e. sociology, political science, psychology, philosophy) and with different pedagogical styles. After this description, the article highlights key lessons informed by data from lecturers' internal discussions and a survey involving the pioneer student cohort enrolled during the 2021–2022 academic year. This experience shows the importance of teaching as a way of contributing to field of Memory studies. As a counterpoint to the relentless publish-or-perish ethos, which often favors expedited dissemination of fragmented knowledge, creating a study program necessitates deep understanding and cohesive dialogue. [ABSTRACT FROM AUTHOR]

New 1,2,3-triazolo(thieno)stilbenes were synthesized as mixtures of isomers and efficiently photochemically transformed to their corresponding substituted thienobenzo/naphtho-triazoles in high isolated yields. The resulting photoproducts were studied as acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitors without or with interconnected inhibition potential of TNF-α cytokine production. The most promising anti-inflammatory activity was shown again by naphtho-triazoles, with a derivative featuring 4-pentenyl substituents exhibiting notable potential as a cholinesterase inhibitor. To identify interactions between ligands and the active site of cholinesterases, molecular docking was performed for the best potential inhibitors. Additionally, molecular dynamics simulations were employed to assess and validate the stability and flexibility of the protein–ligand complexes generated through docking. [ABSTRACT FROM AUTHOR]

Linking routinely collected healthcare administrative data is a valuable method for conducting research on morbidity outcomes, but linkage quality and accuracy needs to be assessed for bias as the data were not collected for research. The aim of this study was to describe the rates of linking data on children with and without congenital anomalies to regional or national hospital discharge databases and to evaluate the quality of the matched data. Eleven population-based EUROCAT registries participated in a EUROlinkCAT study linking data on children with a congenital anomaly and children without congenital anomalies (reference children) born between 1995 and 2014 to administrative databases including hospital discharge records. Odds ratios (OR), adjusted by region, were estimated to assess the association of maternal and child characteristics on the likelihood of being matched. Data on 102,654 children with congenital anomalies were extracted from 11 EUROCAT registries and 2,199,379 reference children from birth registers in seven regions. Overall, 97% of children with congenital anomalies and 95% of reference children were successfully matched to administrative databases. Information on maternal age, multiple birth status, sex, gestational age and birthweight were >95% complete in the linked datasets for most regions. Compared with children born at term, those born at ≤27 weeks and 28–31 weeks were less likely to be matched (adjusted OR 0.23, 95% CI 0.21–0.25 and adjusted OR 0.75, 95% CI 0.70–0.81 respectively). For children born 32–36 weeks, those with congenital anomalies were less likely to be matched (adjusted OR 0.78, 95% CI 0.71–0.85) while reference children were more likely to be matched (adjusted OR 1.28, 95% CI 1.24–1.32). Children born to teenage mothers and mothers ≥35 years were less likely to be matched compared with mothers aged 20–34 years (adjusted ORs 0.92, 95% CI 0.88–0.96; and 0.87, 95% CI 0.86–0.89 respectively). The accuracy of linkage and the quality of the matched data suggest that these data are suitable for researching morbidity outcomes in most regions/countries. However, children born preterm and those born to mothers aged <20 and ≥35 years are less likely to be matched. While linkage to administrative databases enables identification of a reference group and long-term outcomes to be investigated, efforts are needed to improve linkages to population groups that are less likely to be linked. [ABSTRACT FROM AUTHOR]

Since early 2022, various Omicron variants have dominated the SARS-CoV-2 pandemic in most countries. All Omicron variants are B-cell immune escape variants, and antibodies induced by first-generation COVID-19 vaccines or by infection with earlier SARS-CoV-2 variants largely fail to protect individuals from Omicron infection. In the present study, we investigated the effect of Omicron infections in triple-vaccinated and in antigen-naive individuals. We show that Omicron breakthrough infections occurring 2-3.5 months after the third vaccination restore B-cell and T-cell immune responses to levels similar to or higher than those measured 14 days after the third vaccination, including the induction of Omicron-neutralizing antibodies. Antibody responses in breakthrough infection derived mostly from cross-reacting B cells, initially induced by vaccination, whereas Omicron infections in antigen-naive individuals primarily generated B cells binding to the Omicron but not the Wuhan spike protein. Although antigen-naive individuals mounted considerable T-cell responses after infection, B-cell responses were low, and neutralizing antibodies were frequently below the limit of detection. In summary, the detection of Omicron-associated B-cell responses in primed and in antigennaive individuals supports the application of Omicron-adapted COVID-19 vaccines, but calls into question their suitability if they also contain/encode antigens of the original Wuhan virus. [ABSTRACT FROM AUTHOR]

Naphtho-triazoles and thienobenzo-triazoles have so far proven to be very potent inhibitors of the enzyme butyrylcholinesterase (BChE). Based on these results, in this work, new thienobenzo-thiazoles were designed and synthesized, and their potential inhibitory activity was tested and compared with their analogs, naphtho-oxazoles. The synthesis was carried out by photochemical cyclization of thieno-thiazolostilbenes obtained in the first reaction step. Several thienobenzo-thiazoles and naphtho-oxazoles have shown significant potential as BChE inhibitors, together with the phenolic thiazolostilbene being the most active of all tested compounds. These results are significant as BChE has been attracting growing attention due to its positive role in the treatment of Alzheimer's disease. Computational examination based on the DFT approach enabled the characterization of the geometry and electronic structure of the studied molecules. Furthermore, the molecular docking study, accompanied by additional optimization of complexes ligand-active site, offered insight into the structure and stabilizing interactions in the complexes of studied molecules and BChE. [ABSTRACT FROM AUTHOR]

This study aims to test the inhibition potency of new thienobenzo/naphtho-triazoles toward cholinesterases, evaluate their inhibition selectivity, and interpret the obtained results by molecular modeling. The synthesis of 19 new thienobenzo/naphtho-triazoles by two different approaches resulted in a large group of molecules with different functionalities in the structure. As predicted, most prepared molecules show better inhibition of the enzyme butyrylcholinesterase (BChE), considering that the new molecules were designed according to the previous results. Interestingly, the binding affinity of BChE for even seven new compounds (1, 3, 4, 5, 6, 9, and 13) was similar to that reported for common cholinesterase inhibitors. According to computational study, the active thienobenzo- and naphtho-triazoles are accommodated by cholinesterases through H-bonds involving one of the triazole's nitrogens, π-π stacking between the aromatic moieties of the ligand and aromatic residues of the active sites of cholinesterases, as well as π-alkyl interactions. For the future design of cholinesterase inhibitors and search for therapeutics for neurological disorders, compounds with a thienobenzo/naphtho-triazole skeleton should be considered. [ABSTRACT FROM AUTHOR]

The goal of this study is to perform a detailed sensitivity test to find the optimal value of the variance ratio r for four different post-processing forecasts that use the Kalman filter (KF) for the point-based wind gust predictions. The four forecasts analyzed in this paper are KF (KF applied to the raw NWP time series), KFAN (KF applied to the simple analog method time series), KFAS (KF applied to NWP forecasts in analog space), and KF-KFAS (KF applied to the KFAS time series). The wind gust impacts the severity of wind-related events. It is usually not a prognostic but a diagnostic variable in NWP models, which makes it an excellent candidate for post-processing. The results suggest that for the KF and KFAS forecasts the r value of 0.01 should be used, whereas for the KFAN and KF-KFAS forecasts the r value should be set to 0.001. The proposed values are considered optimal since they lead to excellent results for the overall data, and the results remain satisfactory even for strong wind. It, however, needs to be mentioned that the usage of different r values always comes with certain trade-offs. The r values smaller than proposed can sometimes slightly improve the overall result, but often lead to considerably worse results for the strong wind. On the other hand, the r values greater than proposed often show good quality of strong wind forecasts but lead to worse results overall. Even so, if the focus is set on extreme events, higher r values than proposed could be considered, but with caution. [ABSTRACT FROM AUTHOR]

Copyright of HUM: Journal of the Faculty of Arts at the University of Mostar is the property of University of Mostar, Faculty of Arts and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this research, the synthesis, photochemistry, and computational study of new cis- and trans-isomers of amino-thienostilbenes is performed to test the efficiency of their production and acid resistance, and to investigate their electronic structure, photoreactivity, photophysical characteristics, and potential biological activity. The electronic structure and conformations of synthesized thienostilbene amines and their photocyclization products are examined computationally, along with molecular modeling of amines possessing two thiophene rings that showed inhibitory potential toward cholinesterases. New amino-styryl thiophenes, with favorable photophysical properties and proven acid resistance, represent model compounds for their water-soluble ammonium salts as potential styryl optical dyes. The comparison with organic dyes possessing a trans-aminostilbene subunit as the scaffold shows that the newly synthesized trans-aminostilbenes have very similar absorbance wavelengths. Furthermore, their functionalized cis-isomers and photocyclization products are good candidates for cholinesterase inhibitors because of the structural similarity of the molecular skeleton to some already proven bioactive derivatives. [ABSTRACT FROM AUTHOR]

Lavender (Lavandula angustifolia Mill.) is a perennial, aromatic, medicinal, and decorative plant widespread in the Mediterranean. Due to the high content of essential oil and numerous beneficial properties, it is an extremely valued plant species. In Bosnia and Herzegovina, lavender is cultivated mainly for the needs of the cosmetic and pharmaceutical industries. In this research, the antioxidant activity and acetylcholinesterase inhibition of essential oil (EO) and extracts isolated from lavender were evaluated. L. angustifolia EO was isolated using whole plant material in the flowering period by steam distillation and analyzed by gas chromatography (GC) with flame-ionization (FID) and mass spectrometric (MS) detection. Extracts were prepared by ultrasonic extraction in solvents of different polarities. Total phenolic content in extracts was determined using Folin-Ciocalteu reagent. The antioxidant activity of EO and extracts was examined by two methods, 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging activities and ferric reducing/antioxidant power (FRAP), while the acetylcholinesterase (AChE) inhibitory potential was determined using modified Ellman's method. The EO was high in content of linalool (27.72%) and linalyl acetate (22.82%), followed by a-pinene (9.82%), lavandulol acetate (7.32%), trans-caryophyllene (5.70%), and others. In total, 24 components were identified. Total phenol content was highest in water and ethanol extracts (45.3 and 14.40 mg gallic acid equivalent (GAE)/g dry extract). Polar extracts indicate good antioxidant power according to both methods, while EO can be considered as good inhibitor of AChE. [ABSTRACT FROM AUTHOR]

Real-world patterns of care and attrition of la/mUC patients eligible for systemic therapy following PD-1/L1 inhibitors are not well understood. In an ambispective chart review of patients with la/mUC after PD-1/L1 discontinuation, only one third received subsequent treatment. Prior to the introduction of novel therapies, real-world outcomes following treatment with PD-1/L1 inhibitor therapy were poor. Introduction: The patterns of care and attrition of locally advanced or metastatic urothelial carcinoma (la/mUC) patients eligible for systemic therapy following PD-1/L1 inhibitors are unclear. The objective of this study was to evaluate the clinical characteristics and treatment patterns among patients with la/mUC following discontinuation of first-line (1L) or second-line (2L) PD-1/L1 inhibitor therapy. Methods: An ambispective, multisite, chart review study was conducted in the United States, including patients with la/mUC. Eligible patients had initiated and subsequently discontinued PD-1/L1 therapy in the 1L or 2L setting for la/mUC between May 2016 and July 2018; with follow-up through October 2019. Patient characteristics, treatments, and overall survival (OS) were described. Patients had the option to complete a 1-time patient reported outcomes (PRO) survey. Results: Among 300 patients included in the chart review, 198 (66%) received 1L PD- 1/L1 inhibitor and 102 (34%) received 2L PD-1/L1 inhibitor. Following discontinuation of PD-1/L1 inhibitor therapy, 34% (n = 68) received subsequent therapy in 2L and 29% (n = 30) in third-line (3L). The median OS post-1L PD-1/L1 inhibitor was 9.4 (95% CI 8.6-NA) and 2.5 months (95% CI 2.24-3.50) for those who received and did not receive subsequent therapy, respectively. Following 2L PD-1/L1 inhibitor discontinuation, the median OS was 5.7 (95% CI 5.1-7.8) and 3.98 (95% CI 3.29-4.87) months for those who received and did not receive subsequent therapy, respectively. Among those with PRO data, 64% reported experiencing cancer-related pain and 29.6% received an opioid. Only 12.7% reported having a caregiver, requiring approximately 13 h/d of service. Conclusion: The symptom and caregiver burden are high among real-world patients with la/mUC who discontinued 1L or 2L PD-1/L1 inhibitors and outcomes are dismal, with a minority receiving subsequent therapy. Patterns of care in the setting of 1L maintenance avelumab and novel agents require further investigation. [ABSTRACT FROM AUTHOR]

Resveratrol is a natural bioactive non-flavonoid polyphenol that protects from cardiovascular disease, neurodegenerative diseases and various cancers. Unfortunately, the amounts of resveratrol in plants are low and therefore, chemical synthesis is still the main way to obtain this valuable structure. In this work, Wittig reaction was chosen as the synthetic route for the study on technology influence in batch vs. micro- or milliflow reactors during the production of new resveratrol-like compounds. A series of reactions was carried out by batch synthesis, and intensified in a milli- and a microreactor, changing the reaction conditions to increase the efficiency and productivity of the process. Results were compared based on conversion, yield, productivity and trans/cis ratio. Similar yields and conversions were obtained in all reaction systems, but in much shorter time in the milli- and microscale compared to the batch reactor. On the other hand, higher productivities were obtained in the millireactor and microreactor, making them better systems for the proposed reactions of new heterocyclic resveratrol analogues synthesis. [ABSTRACT FROM AUTHOR]

Background: Parents of children who have a congenital anomaly can experience significant worry about their child's health. Access to clear, helpful, and trustworthy information can provide a valuable source of support. In this study the aim was to explore the information needs of parents/carers of children with congenital anomalies across Europe.Method: A cross-sectional online survey was developed in nine languages to measure parents' information needs, including: (1) the 'helpfulness'/'trustworthiness' of information received from eight relevant sources, and (2) overall satisfaction with information received. Parents/carers of children (0-10 years) with cleft lip, spina bifida, congenital heart defect [CHD] requiring surgery, and/or Down syndrome were recruited online via relevant organisations in 10 European countries from March-July 2021. Quantitative analyses using multivariable logistic regressions were performed.Results: One thousand seventy parents/carers of children with a cleft lip (n = 247), spina bifida (n = 118), CHD (n = 366), Down syndrome (n = 281), and Down syndrome with CHD (n = 58) were recruited in Poland (n = 476), the UK (n = 120), Germany (n = 97), the Netherlands/Belgium (n = 74), Croatia (n = 68), Italy (n = 59), other European countries (n = 92), and not specified/non-European countries (n = 84). Most participants were mothers (92%) and aged 31-40 years (71%). Participants were most likely to rate support groups (63%), patient organisations (60%), specialist doctors/nurses (58%), and social media (57%) as 'very helpful' information sources. 'Very trustworthy' ratings remained high for specialist doctors/nurses (61%), however, they declined for support groups (47%), patient organisations (48%), and social media (35%). Germany had the highest proportion of participants who were 'very satisfied' (44%, 95% CI = 34%-54%) with information, whereas this percentage was lowest in Croatia (11%, 95% CI = 3%-19%) and Poland (15%, 95% CI = 11%-18%). Parents of children with Down syndrome had significantly lower satisfaction ratings than parents of children with CHD; 13% (95% CI = 8%-18%) reported being 'very satisfied' compared to 28% (95% CI = 23%-33%) in the CHD group.Conclusions: Findings suggest that informal sources of information (e.g. support groups) are of value to parents, however, they are not deemed as trustworthy as specialist medical sources. Satisfaction ratings differed across countries and by anomaly, and were particularly low in Croatia and Poland, as well as for parents of children with Down syndrome, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Identification of immune phenotypes linked to durable graft-versus-leukemia (GVL) response following donor lymphocyte infusions (DLI) is of high clinical relevance. In this prospective observational study of 13 AML relapse patients receiving therapeutic DLI, we longitudinally investigated changes in differentiation stages and exhaustion markers of T cell subsets using cluster analysis of 30-color spectral flow cytometry during 24 months follow-up. DLI cell products and patient samples after DLI were analyzed and correlated to the clinical outcome. Analysis of DLI cell products revealed heterogeneity in the proportions of naïve and antigen experienced T cells. Cell products containing lower levels of effector memory (eff/m) cells and higher amounts of naïve CD4+ and CD8+ T cells were associated with long-term remission. Furthermore, investigation of patient blood samples early after DLI showed that patients relapsing during the study period, had higher levels of CD4+ eff/m T cells and expressed a mosaic of surface molecules implying an exhausted functional state. Of note, this observation preceded the clinical diagnosis of relapse by five months. On the other hand, patients with continuous remission retained lower levels of exhausted CD4+ eff/m T cells more than four months post DLI. Moreover, lower frequencies of exhausted CD8+ eff/m T cells as well as higher amounts of CD4+temra CD45RO+ T cells were present in this group. These results imply the formation of functional long-term memory pool of T cells. Finally, unbiased sample analysis showed that DLI cell products with low levels of eff/m cells both in CD4+ and CD8+ T cell subpopulations associate with a lower relapse incidence. Additionally, competing risk analysis of patient samples taken early after DLI revealed that patients with high amounts of exhausted CD4+ eff/m T cells in their blood exhibited significantly higher rates of relapse. In conclusion, differentially activated T cell clusters, both in the DLI product and in patients post infusion, were associated with AML relapse after DLI. Our study suggests that differences in DLI cell product composition might influence GVL. In-depth monitoring of T cell dynamics post DLI might increase safety and efficacy of this immunotherapy, while further studies are needed to assess the functionality of T cells found in the DLI. [ABSTRACT FROM AUTHOR]

New resveratrol–thiophene and resveratrol–maltol hybrids were synthesized as cholinesterase inhibitors and antioxidants. As with photostability experiments, biological tests also found remarkable differences in the properties and behavior of thiophene and maltol hybrids. While resveratrol–thiophene hybrids have excellent inhibitory and antioxidant properties (similar to the activity of reference drug galantamine), maltols have been proven to be weaker inhibitors and antioxidants. The molecular docking of selected active ligands gave insight into the structures of docked enzymes. It enabled the identification of interactions between the ligand and the active site of both cholinesterases. The maltols that proved to be active cholinesterase inhibitors were able to coordinate Fe3+ ion, forming complexes of 1:1 composition. Their formation constants, determined by spectrophotometry, are very similar, lgK = 11.6–12.6, suggesting that Fe3+ binds to the common hydroxy-pyranone moiety and is hardly affected by the other aromatic part of the ligand. Accordingly, the characteristic bands in their individual absorption spectra are uniformly red-shifted relative to those of the free ligands. The crystal structures of two new resveratrol–maltol hybrids were recorded, giving additional information on the molecules' intermolecular hydrogen bonds and packing. In this way, several functionalities of these new resveratrol hybrids were examined as a necessary approach to finding more effective drugs for complicated neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Heterologous prime/boost vaccination with a vector-based approach (ChAdOx-1nCov-19, ChAd) followed by an mRNA vaccine (e.g. BNT162b2, BNT) has been reported to be superior in inducing protective immunity compared to repeated application of the same vaccine. However, data comparing immunity decline after homologous and heterologous vaccination as well as effects of a third vaccine application after heterologous ChAd/BNT vaccination are lacking. Here we show longitudinal monitoring of ChAd/ChAd (n = 41) and ChAd/BNT (n = 88) vaccinated individuals and the impact of a third vaccination with BNT. The third vaccination greatly augments waning anti-spike IgG but results in only moderate increase in spike-specific CD4 + and CD8 + T cell numbers in both groups, compared to cell frequencies already present after the second vaccination in the ChAd/BNT group. More importantly, the third vaccination efficiently restores neutralizing antibody responses against the Alpha, Beta, Gamma, and Delta variants of the virus, but neutralizing activity against the B.1.1.529 (Omicron) variant remains severely impaired. In summary, inferior SARS-CoV-2 specific immune responses following homologous ChAd/ChAd vaccination can be compensated by heterologous BNT vaccination, which might influence the choice of vaccine type for subsequent vaccination boosts. Vaccines against SARS-CoV-2 have changed the course of the COVID-19 pandemics, but waning immunity necessitates repeated immunization. Authors here show that immunity declines faster following two doses of vector-based vaccine compared to a first dose of vector-based vaccine followed by boosting with an mRNA vaccine, but application of an mRNA vaccine as a third dose minimises the difference between the two groups. [ABSTRACT FROM AUTHOR]

Background: Congenital anomalies are a leading cause of childhood morbidity, but little is known about the long-term outcomes. Objective: To quantify the burden of disease in childhood for children with congenital anomalies by assessing the risk of hospitalisation, the number of days spent in hospital and proportion of children with extended stays (≥10 days). Methods: European population-based record-linkage study in 11 regions in eight countries including children with congenital anomalies (EUROCAT children) and without congenital anomalies (reference children) living in the same regions. The children were born between 1995 and 2014 and were followed to their tenth birthday or 31/12/2015. European meta-analyses of the outcome measures were performed by two age groups, <1 year and 1–4 years. Results: 99,416 EUROCAT children and 2,021,772 reference children were linked to hospital databases. Among EUROCAT children, 85% (95%-CI: 79–90%) were hospitalised in the first year and 56% (95%-CI: 51–61%) at ages 1–4 years, compared to 31% (95%-CI: 26–37%) and 25% (95%-CI: 19–31%) of the reference children. Median length of stay was 2–3 times longer for EUROCAT children in both age groups. The percentages of children with extended stays (≥10 days) in the first year were 24% (95%-CI: 20–29%) for EUROCAT children and 1% (95%-CI: 1–2%) for reference children. The median length of stay varied greatly between congenital anomaly subgroups, with children with gastrointestinal anomalies and congenital heart defects having the longest stays. Conclusions: Children with congenital anomalies were more frequently hospitalised and median length of stay was longer. The outlook improves after the first year. Parents of children with congenital anomalies should be informed about the increased hospitalisations required for their child's care and the impact on family life and siblings, and they should be adequately supported. [ABSTRACT FROM AUTHOR]

Tricuspid atresia is a congenital malformation of the tricuspid valve resulting in a lack of blood flow between the right atrium and the right ventricle. Management generally involves staged surgical intervention enabling affected individuals to survive into adulthood. Although surgical intervention greatly improves morbidity and mortality in this patient population, there are many long-term complications associated with the creation of a surgical shunt. We report a case of a 33-year-old male with tricuspid atresia who underwent Fontan surgery as a child and presented to our hospital with acute liver failure. [ABSTRACT FROM AUTHOR]

In the paper by Sergije Dimitrijević, A New Series of New Types of Serbian Medieval Coins [Нова серија нових врста српског средњовековног новца], published in the journal Starinar [Старинар] in 1964–1965, we have come across a peculiar piece of information – that there used to be a sub-type of the follaro coin from the town of Ulcinj, which usually had a depiction of the Virgin Mary with Christ on the obverse, and a depiction of the city walls with a tree in the gate on the reverse. More precisely, in his work Dimitrijević mentions an Ulcinj-type follaro with a human figure with its arms and legs apart, standing in the city gate instead of the tree. We have made an attempt to find this never before published specimen of the Ulcinj follaro, and have come to the conclusion that the currency in question is not that of Ulcinj, but a follaro from the town of Drivast (modern-day Drisht), with a depiction of the Virgin Mary with Christ on the obverse and the city walls with a lily inside the gate on the reverse. The striking similarity in the manufacturing process of these two coins, in terms of both the depiction on the obverse and that on the reverse, points to a single pair of artisan hands behind the coin moulds for minting of both towns. [ABSTRACT FROM AUTHOR]

Background: Celiac disease (CeD) and inflammatory bowel disease (IBD) are accompanied by impaired immune responses. To study the immune regulation of these diseases, we evaluated the expression levels of pro-inflammatory (IL-8 and IL-17 A) and anti-inflammatory (IL-10) cytokines in intestinal biopsy specimens of CeD and IBD patients in comparison to healthy subjects. Methods and Results: Intestinal biopsies were collected from 33 patients with IBD, 47 patients with CeD, and 20 healthy individuals. Total RNA was extracted and mRNA expression levels of IL-8, IL-17 A and IL-10 were assessed by qPCR. P-value < 0.05 was considered statistically significant. The expression levels of IL-8 and IL-17 A were higher in biopsies of IBD (UC and CD) and CeD patients compared to the control group (P < 0.05). IBD patients (UC and CD) had higher IL-8 intestinal level than CeD patients (P < 0.0001 and P = 0.0007, respectively). The expression of IL-10 was significantly down-regulated in intestinal biopsies of CeD and IBD patients compared with controls (P < 0.001). In addition, the expression level of this cytokine was significantly lower in IBD patients (P < 0.001 for UC patients and P < 0.0001 for CD patients) than CeD group. Conclusions: The three selected pro- and anti-inflammatory cytokines showed a similar expression pattern in both IBD and CeD patients. As IBD and CeD are immune-mediated disorders and are accompanied by inflammatory events, the understanding of the similarities and differences among them can help researchers to find out useful candidate therapeutic protocols. We suggest that larger cohort studies be organized to achieve more insights into this regulation. [ABSTRACT FROM AUTHOR]

Evaluating long-term protection against SARS-CoV-2 variants of concern in convalescing individuals is of high clinical relevance. In this prospective study of a cohort of 46 SARS-CoV-2 patients infected with the Wuhan strain of SARS-CoV-2 we longitudinally analyzed changes in humoral and cellular immunity upon early and late convalescence. Antibody neutralization capacity was measured by surrogate virus neutralization test and cellular responses were investigated with 31-colour spectral flow cytometry. Spike-specific, isotype-switched B cells developed already during the disease phase, showed a memory phenotype and did not decrease in numbers even during late convalescence. Otherwise, no long-lasting perturbations of the immune compartment following COVID-19 clearance were observed. During convalescence anti-Spike (S1) IgG antibodies strongly decreased in all patients. We detected neutralizing antibodies against the Wuhan strain as well as the Alpha and Delta but not against the Beta, Gamma or Omicron variants for up to 7 months post COVID-19. Furthermore, correlation analysis revealed a strong association between sera anti-S1 IgG titers and their neutralization capacity against the Wuhan strain as well as Alpha and Delta. Overall, our data suggest that even 7 month after the clearance of COVID-19 many patients possess a protective layer of immunity, indicated by the persistence of Spike-specific memory B cells and by the presence of neutralizing antibodies against the Alpha and Delta variants. However, lack of neutralizing antibodies against the Beta, Gamma and Omicron variants even during the peak response is of major concern as this indicates viral evasion of the humoral immune response. [ABSTRACT FROM AUTHOR]

Tricuspid atresia is a congenital malformation of the tricuspid valve resulting in a lack of blood flow between the right atrium and the right ventricle. Management generally involves staged surgical intervention enabling affected individuals to survive into adulthood. Although surgical intervention greatly improves morbidity and mortality in this patient population, there are many long-term complications associated with the creation of a surgical shunt. We report a case of a 33-year-old male with tricuspid atresia who underwent Fontan surgery as a child and presented to our hospital with acute liver failure. [ABSTRACT FROM AUTHOR]

Copyright of Ars Adriatica is the property of Sveuciliste u Zadru (University of Zadar) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Contemporary Issues / Suvremene Teme is the property of Centar za Politoloska Istrazivanja and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This report aims at providing an overview of the objective, sample, methodology and procedure of the study of Bosnia‐Herzegovinian Dietary Survey of adolescents, adults and pregnant women. The methodology for conducting the food consumption survey was in line with the European Food Safety Authority's guidelines published in 2014. For the survey, a random sample stratified by age, gender and place of residence was drawn from the national population register. The sampled subjects were distributed over four different seasons and the survey calendar was organized to capture an adequate proportion of weekdays and weekend days at population group level. Detailed food consumption information was collected by using the 24‐hour recall method on two non‐consecutive days for each participant. The data collection was complemented with a FPQ, including foods/beverages interesting for their nutritional value or potential risk. Data were collected for 1384 people in the following age groups: 534 adolescents and 850 adults, and data for 134 pregnant women. The achieved response rate was 69.2% for general population and 67% for pregnant women. [ABSTRACT FROM AUTHOR]

Antigen-specific tissue-resident memory T cells (Trms) and neutralizing IgA antibodies provide the most effective protection of the lungs from viral infections. To induce those essential components of lung immunity against SARS-CoV-2, we tested various immunization protocols involving intranasal delivery of a novel Modified Vaccinia virus Ankara (MVA)-SARS-2-spike vaccine candidate. We show that a single intranasal MVA-SARS-CoV-2-S application in mice strongly induced pulmonary spike-specific CD8+ T cells, albeit restricted production of neutralizing antibodies. In prime-boost protocols, intranasal booster vaccine delivery proved to be crucial for a massive expansion of systemic and lung tissue-resident spike-specific CD8+ T cells and the development of Th1 - but not Th2 - CD4+ T cells. Likewise, very high titers of IgG and IgA anti-spike antibodies were present in serum and broncho-alveolar lavages that possessed high virus neutralization capacities to all current SARS-CoV-2 variants of concern. Importantly, the MVA-SARS-2-spike vaccine applied in intramuscular priming and intranasal boosting treatment regimen completely protected hamsters from developing SARS-CoV-2 lung infection and pathology. Together, these results identify intramuscular priming followed by respiratory tract boosting with MVA-SARS-2-S as a promising approach for the induction of local, respiratory as well as systemic immune responses suited to protect from SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

We compute the Hamiltonian surface charges of gravity for a family of conservative boundary conditions, that include Dirichlet, Neumann, and York’s mixed boundary conditions defined by holding fixed the conformal induced metric and the trace of the extrinsic curvature. We show that for all boundary conditions considered, canonical methods give the same answer as covariant phase space methods improved by a boundary Lagrangian, a prescription recently developed in the literature and thus supported by our results. The procedure also suggests a new integrable charge for the Einstein-Hilbert Lagrangian, different from the Komar charge for non-Killing and non-tangential diffeomorphisms. We study how the energy depends on the choice of boundary conditions, showing that both the quasi-local and the asymptotic expressions are affected. Finally, we generalize the analysis to non-orthogonal corners, confirm the matching between covariant and canonical results without any change in the prescription, and discuss the subtleties associated with this case. [ABSTRACT FROM AUTHOR]

Copyright of Health Bulletin / Zdravstveni Glasnik is the property of Faculty of Health Studies, University of Mostar and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Conceptually, Critical Theory Between Klein and Lacan is an impressive text, offering both a comparative analysis of Kleinian and Lacanian psychoanalysis, which are generally considered to be incommensurable, and presenting a dialogue between the two authors, one strongly based in Lacanian theory, the other much closer to Kleinian psychoanalysis. Its ambition is to trace the influence these two psychoanalysts had for the broadly conceptualized critical theory, as well as to suggest some ways in which this encounter can and should be more productive. [ABSTRACT FROM AUTHOR]

Here, we described the case of a B cell-deficient patient after CD19 CAR-T cell therapy for refractory B cell Non-Hodgkin Lymphoma with protracted coronavirus disease 2019 (COVID-19). For weeks, this patient only inefficiently contained the virus while convalescent plasma transfusion correlated with virus clearance. Interestingly, following convalescent plasma therapy natural killer cells matured and virus-specific T cells expanded, presumably allowing virus clearance and recovery from the disease. Our findings, thus, suggest that convalescent plasma therapy can activate cellular immune responses to clear SARS-CoV-2 infections. If confirmed in larger clinical studies, these data could be of general importance for the treatment of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Olmesartan-induced enteropathy is an underreported phenomenon, first described in 2012. While olmesartan's antihypertensive properties were confirmed early on, its association with a sprue-like enteropathy was subsequently noted. Although this association has been reported with olmesartan, there have been few reports of this association with other angiotensin-receptor blockers. We present a case of a 79-year-old male who presented with diarrhea, weight loss, jaundice, and transaminitis. Further history revealed that he had been taking olmesartan 40 mg daily for hypertension. Workup of his diarrhea and jaundice included duodenal and liver biopsies revealed findings consistent with a sprue-like enteropathy and an autoimmune hepatitis-like pattern. On discontinuation of olmesartan, his 1-month follow-up revealed significant improvement in his clinical status as well as his liver function tests. Olmesartan is an effective antihypertensive medication; however, physicians must be mindful of its side effect of causing a sprue-like enteropathy and liver injury. Patients should be counseled on discontinuing olmesartan, and they should be started on an alternative therapy for hypertension. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) has emerged as the infectious agent causing the pandemic coronavirus disease 2019 (COVID-19) with dramatic consequences for global human health and economics. Previously, we reached clinical evaluation with our vector vaccine based on modified vaccinia virus Ankara (MVA) against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes an infection in humans similar to SARS and COVID-19. Here, we describe the construction and preclinical characterization of a recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein (MVA-SARS-2-S). Genetic stability and growth characteristics of MVA-SARS-2-S, plus its robust expression of S protein as antigen, make it a suitable candidate vaccine for industrial-scale production. Vaccinated mice produced S-specific CD8+ T cells and serum antibodies binding to S protein that neutralized SARS-CoV-2. Primeboost vaccination with MVA-SARS-2-S protected mice sensitized with a human ACE2-expressing adenovirus from SARS-CoV-2 infection. MVA-SARS-2-S is currently being investigated in a phase I clinical trial as aspirant for developing a safe and efficacious vaccine against COVID-19. [ABSTRACT FROM AUTHOR]

The article discusses Post-Conflict Memory as Performative Justice. Examples of the latter are the anamnestic prayer in Christianity and the Passover liturgy in Judaism. Memory, therefore, can have performative effects – it can make. a past event experientially real again. When it comes to traumatic memories, there is one crucial difference: They do not aim to recreate the original trauma, but rather they generate a new condition or relationship.

This document is a correction notice for an article titled "Gene expression analysis of intestinal IL-8, IL-17 A and IL-10 in patients with celiac and inflammatory bowel diseases" published in Molecular Biology Reports. The correction provides updated affiliation details for one of the authors, Maryam Eslami. The original article has been corrected, and Springer Nature remains neutral with regard to jurisdictional claims and institutional affiliations. The corrected article can be found online. The document also includes the contact information for Mohammad Rostami-Nejad, the corresponding author. [Extracted from the article]