Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility.

A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta-meta, meta-para, para-meta, and para-para configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV ß-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor.

The association between quality of connections and diagnostic accuracy in student-generated concept maps for clinical reasoning education with virtual patients.

Objectives: Concept maps are a learning tool that fosters clinical reasoning skills in healthcare education. They can be developed by students in combination with virtual patients to create a visual representation of the clinical reasoning process while solving a case. However, in order to optimize feedback, there is a need to better understand the role of connections between concepts in student-generated maps. Therefore, in this study we investigated whether the quality of these connections is indicative of diagnostic accuracy. Methods: We analyzed 40 concept maps created by fifth-year medical students in the context of four virtual patients with commonly encountered diagnoses. Half of the maps were created by students who made a correct diagnosis on the first attempt; the other half were created by students who made an error in their first diagnosis. The connections in the maps were rated by two reviewers using a relational scoring system. Analysis of covariance was employed to examine the difference in mean connection scores among groups while controlling for the number of connections. Results: There were no differences between the groups in the number of concepts or connections in the maps; however, maps made by students who made a correct first diagnosis had higher scores for the quality of connections than those created by students who made an incorrect first diagnosis (12.13 vs 9.09; p=0.03). We also observed students' general reluctance to use connections in their concept maps. Conclusion: Our results suggest that the quality, not the quantity, of connections in concept maps is indicative of their diagnostic accuracy.

High-Resolution X-ray Absorption and Emission Spectroscopy for Detailed Analysis of New CO2 Methanation Catalysts.

A new approach for the characterization of CO2 methanation catalysts prepared by thermal decomposition of a nickel MOF by hard X-ray photon-in/photon-out spectroscopy in form of high energy resolution fluorescence detected X-ray absorption near edge structure spectroscopy (HERFD-XANES) and valence-to-core X-ray emission (VtC-XES) is presented. In contrast to conventional X-ray absorption spectroscopy, the increased resolution of both methods allows a more precise phase determination of the final catalyst, which is influenced by the conditions during MOF decomposition.

Cr(vi) permanently binds to the lipid bilayer in an inverted hexagonal phase throughout the reduction process.

Cr(vi) is a harmful, carcinogenic agent with a high permeability rate throughout the lipid membranes. In an intracellular environment and during interactions with cellular membranes, it undergoes an instant reduction to lower oxidation states throughout radical states, recognized as the most dangerous factor for cells. The cellular membrane is the most visible cellular organelle in the interior and exterior of a cell. In this study, liposomes and non-lamellar inverted hexagonal phase lipid structures based on phosphoethanolamine (PE) were used as model cellular bilayers because of their simple composition, preparation procedure, and the many other properties of natural systems. The lipid membranes were subjected to 0.075 mM Cr(vi) for 15 min, after which the Cr content was removed via dialysis. This way, the remaining Cr content could be studied qualitatively and quantitatively. Using the combined XRF/XAS/EPR approach, we revealed that some Cr content (Cr(iii) and Cr(vi)) was still present in the samples even after long-term dialysis at a temperature significantly above the phase transition for the chosen liposome. The amount of bound Cr increased with increasing PE and -C[double bond, length as m-dash]C- bond content in lipid mixtures. Internal membrane order decreased in less fluid membranes, while in more liquified ones, internal order was only slightly changed after subjecting them to the Cr(vi) agent. The results suggest that the inverted hexagonal phase of lipid structures is much more sensitive to oxidation than the lamellar lipid phase, which can play an important role in the strong cytotoxicity of Cr(vi).

Non-uniform sampling of similar NMR spectra and its application to studies of the interaction between alpha-synuclein and liposomes.

The accelerated acquisition of multidimensional NMR spectra using sparse non-uniform sampling (NUS) has been widely adopted in recent years. The key concept in NUS is that a major part of the data is omitted during measurement, and then reconstructed using, for example, compressed sensing (CS) methods. CS requires spectra to be compressible, that is, they should contain relatively few "significant" points. The more compressible the spectrum, the fewer experimental NUS points needed in order for it to be accurately reconstructed. In this paper we show that the CS processing of similar spectra can be enhanced by reconstructing only the differences between them. Accurate reconstruction can be obtained at lower sampling levels as the difference is sparser than the spectrum itself. In many situations this method is superior to "conventional" compressed sensing. We exemplify the concept of "difference CS" with one such case-the study of alpha-synuclein binding to liposomes and its dependence on temperature. To obtain information on temperature-dependent transitions between different states, we need to acquire several dozen spectra at various temperatures, with and without the presence of liposomes. Our detailed investigation reveals that changes in the binding modes of the alpha-synuclein ensemble are not only temperature-dependent but also show non-linear behavior in their transitions. Our proposed CS processing approach dramatically reduces the number of NUS points required and thus significantly shortens the experimental time.

Medical students' perception of e-learning approach (MeSPeLA) - a mixed method research.

There is a discrepancy between the research exploring e-learning at medical universities in Central/Eastern and Western European countries. The aim of the MeSPeLA study was to explore the understanding, experience and expectations of Polish medical students in terms of e-learning. Questionnaire containing open-ended and closed questions supplemented by focus group discussion was validated and performed among 204 medical students in Poland before COVID-19 pandemia. Several domains: understanding of e-learning definitions; students' experience, preferences, expectations and perceptions of e-learning usefulness, advantages and disadvantages were addressed. The qualitative data were analyzed using an inductive approach. 46.0% of students chose a communication-oriented definition as the most appropriate. 7.4% claimed not to have any experience with e-learning. 76.8% of respondents indicated they had contact with e-learning. The main reported e-learning advantages were time saving and easier time management. The most common drawback was limited social interactions. The acceptance of the usage of e-learning was high. Medical undergraduates in Poland regardless of the year of studies, gender or choice of future specialization showed positive attitudes towards e-learning. Students with advanced IT skills showed a better understanding of the e-learning definition and perceived e-learning to be a more useful approach. The expectations and perceptions about e-learning in Polish medical schools seems similar to some extent to that in Western European and the United States so we can be more confident about applying some lessons from these research to Poland or other post-communist countries. Such application has been accelerated due to COVID-19 pandemia.

NMR studies of inclusion complexes: naphthalene and natural cyclodextrins.

Inclusion complexes of naphthalene (NP) with cyclodextrins (CD) have been investigated so far using non-NMR techniques resulting in inconsistent data. Here, the first application of high-field NMR spectroscopy in combination with a precise analysis of the results has allowed us to determine accurately the stoichiometry of complexes and their association constants. Titration measurements have been performed by 1H NMR spectroscopy in D2O at a magnetic field B0 of 18.8 T. NP and αCD form a 1 : 2 complex in which a single NP molecule is closed in a capsule made up of two αCD macrocycles. NP and ßCD build coexisting 2 : 1 and 2 : 2 complexes with large binding constants. Larger γCD host molecules form essentially similar complexes with NP as the ßCD but corresponding binding constants are smaller.

The influence of OSPE and PBL on competency-based pharmacy student self-assessment.

BACKGROUND: In addition to vocational education and experience, the pharmaceutical profession's proper pursuit requires acquiring and continuously improving professional competencies. In recent years, the need has been increasingly highlighted for developing a medical education system based on helping students develop their competencies. It is necessary to adapt the tools and methods for assessing competencies during formal education. It will enable students to know the directions of further personal or professional development. OBJECTIVE: The study aimed to compare pharmacy students' self-assessment outcomes before and after the Objective Structured Practical Examination (OSPE), which finished the Pharmaceutical Care course (PCc). The study's purpose was also to compare the outcomes of the self-assessment of competencies between the students of two academic years for whom classes on the PCc were provided by different methods. METHODS: The study was conducted over two academic years (2018/2019 and 2019/2020) among 5th-year students enrolled at the Faculty of Pharmacy of the Jagiellonian University Medical College (JUMC) at the end of the Pharmaceutical Care course. Different teaching methods were used in the delivery of the course in these academic years. The students self-assessed their competencies using a questionnaire consisting of a list of personal and patient care competencies. The students completed the questionnaire before and after the OSPE, which followed the completion of the PCc. RESULTS: Students' professional competencies as self-assessed after the exam were higher than those assessed before the exam. Differences were observed in both personal and patient care competencies. Students taking the course in the 2019/2020 academic year set their pre-OSPE competencies higher than students taking the PCc in 2018/2019. CONCLUSION: The self-assessment scores increased for most competencies included in the study following the OSPE. This may suggest that taking part in the exam, involvement in patient's case simulations, and self-assessment of performance at individual stages of the exam contributed to increased subjective assessment of professional competencies.

Rh(I)/(III)-N-Heterocyclic Carbene Complexes: Effect of Steric Confinement Upon Immobilization on Regio- and Stereoselectivity in the Hydrosilylation of Alkynes.

Rh(I) NHC and Rh(III) Cp* NHC complexes (Cp*=pentamethylcyclopentadienyl, NHC=N-heterocyclic carbene=pyrid-2-ylimidazol-2-ylidene (Py-Im), thiophen-2-ylimidazol-2-ylidene) are presented. Selected catalysts were selectively immobilized inside the mesopores of SBA-15 with average pore diameters of 5.0 and 6.2 nm. Together with their homogenous progenitors, the immobilized catalysts were used in the hydrosilylation of terminal alkynes. For aromatic alkynes, both the neutral and cationic Rh(I) complexes showed excellent reactivity with exclusive formation of the ß(E)-isomer. For aliphatic alkynes, however, selectivity of the Rh(I) complexes was low. By contrast, the neutral and cationic Rh(III) Cp* NHC complexes proved to be highly regio- and stereoselective catalysts, allowing for the formation of the thermodynamically less stable ß-(Z)-vinylsilane isomers at room temperature. Notably, the SBA-15 immobilized Rh(I) catalysts, in which the pore walls provide an additional confinement, showed excellent ß-(Z)-selectivity in the hydrosilylation of aliphatic alkynes, too. Also, in the case of 4-aminophenylacetylene, selective formation of the ß(Z)-isomer was observed with a neutral SBA-15 supported Rh(III) Cp* NHC complex but not with its homogenous counterpart. These are the first examples of high ß(Z)-selectivity in the hydrosilylation of alkynes by confinement generated upon immobilization inside mesoporous silica.

Structure, Biosynthesis, and Biological Activity of Succinylated Forms of Bacteriocin BacSp222.

BacSp222 is a multifunctional peptide produced by Staphylococcus pseudintermedius 222. This 50-amino acid long peptide belongs to subclass IId of bacteriocins and forms a four-helix bundle molecule. In addition to bactericidal functions, BacSp222 possesses also features of a virulence factor, manifested in immunomodulatory and cytotoxic activities toward eukaryotic cells. In the present study, we demonstrate that BacSp222 is produced in several post-translationally modified forms, succinylated at the ε-amino group of lysine residues. Such modifications have not been previously described for any bacteriocins. NMR and circular dichroism spectroscopy studies have shown that the modifications do not alter the spatial structure of the peptide. At the same time, succinylation significantly diminishes its bactericidal and cytotoxic potential. We demonstrate that the modification of the bacteriocin is an effect of non-enzymatic reaction with a highly reactive intracellular metabolite, i.e., succinyl-coenzyme A. The production of succinylated forms of the bacteriocin depends on environmental factors and on the access of bacteria to nutrients. Our study indicates that the production of succinylated forms of bacteriocin occurs in response to the changing environment, protects producer cells against the autotoxicity of the excreted peptide, and limits the pathogenicity of the strain.

Development of Toughened Flax Fiber Reinforced Composites. Modification of Poly(lactic acid)/Poly(butylene adipate-co-terephthalate) Blends by Reactive Extrusion Process.

The presented study focuses on the development of flax fiber (FF) reinforced composites prepared with the use of poly(lactic acid)/poly(butylene adipate-co-terephthalate)-PLA/PBAT blend system. This type of modification was aimed to increase impact properties of PLA-based composites, which are usually characterized by high brittleness. The PLA/PBAT blends preparation was carried out using melt blending technique, while part of the samples was prepared by reactive extrusion process with the addition of chain extender (CE) in the form of epoxy-functionalized oligomer. The properties of unreinforced blends was evaluated using injection molded samples. The composite samples were prepared by compression molding technique, while flax fibers reinforcement was in the form of plain fabric. The properties of the laminated sheets were investigated during mechanical test measurements (tensile, flexural, impact). Differential scanning calorimetry (DSC) analysis was used to determine the thermal properties, while dynamic mechanical thermal analysis (DMTA) and heat deflection temperature (HDT) measurements were conducted in order to measure the thermomechanical properties. Research procedure was supplemented with structure evaluation using scanning electron microscopy (SEM) analysis. The comparative study reveals that the properties of PLA/PBAT-based composites were more favorable, especially in the context of impact resistance improvement. However, for CE modified samples also the modulus and strength was improved. Structural observations after the impact tests confirmed the presence of the plastic deformation of PLA/PBAT matrix, which confirmed the favorable properties of the developed materials. The use of PBAT phase as the impact modifier strongly reduced the PLA brittleness, while the reactive extrusion process improves the fiber-matrix interactions leading to higher stiffness and strength.

Fundamental Characterization, Photophysics and Photocatalysis of a Base Metal Iron(II)-Cobalt(III) Dyad.

A new base metal iron-cobalt dyad has been obtained by connection between a heteroleptic tetra-NHC iron(II) photosensitizer combining a 2,6-bis[3-(2,6-diisopropylphenyl)imidazol-2-ylidene]pyridine with 2,6-bis(3-methyl-imidazol-2-ylidene)-4,4'-bipyridine ligand, and a cobaloxime catalyst. This novel iron(II)-cobalt(III) assembly has been extensively characterized by ground- and excited-state methods like X-ray crystallography, X-ray absorption spectroscopy, (spectro-)electrochemistry, and steady-state and time-resolved optical absorption spectroscopy, with a particular focus on the stability of the molecular assembly in solution and determination of the excited-state landscape. NMR and UV/Vis spectroscopy reveal dissociation of the dyad in acetonitrile at concentrations below 1 mM and high photostability. Transient absorption spectroscopy after excitation into the metal-to-ligand charge transfer absorption band suggests a relaxation cascade originating from hot singlet and triplet MLCT states, leading to the population of the 3 MLCT state that exhibits the longest lifetime. Finally, decay into the ground state involves a 3 MC state. Attachment of cobaloxime to the iron photosensitizer increases the 3 MLCT lifetime at the iron centre. Together with the directing effect of the linker, this potentially makes the dyad more active in photocatalytic proton reduction experiments than the analogous two-component system, consisting of the iron photosensitizer and Co(dmgH)2 (py)Cl. This work thus sheds new light on the functionality of base metal dyads, which are important for more efficient and sustainable future proton reduction systems.

How we prepared our operating theatre for patients with SARS-CoV-2 virus.

The COVID-19 disease continues to cause a global pandemic. The University Hospital in Krakow has been designated as one of the COVID-19 hospitals. To prepare for the pandemic we needed to implement strategies that would protect the health care workers, reduce in-hospital transmission, and provide optimal care for the patients. In the operating department, these preparations involve the cooperation of multiple teams and can pose significant difficulties. Here, we describe measures taken in response to the COVID-19 outbreak. These include, adjustments made in OR set-ups, modification of workflow and processes, and the introduction of adequate personal protective equipment. We believe that these containment measures are required in order to provide an adequate quality of care to COVID-19 patient and to minimise the risk of cross-infection to staff members and other patients.

Surgical Interventions in Patients Hospitalised with COVID-19. A Review of Seven Months of Experience Working in a COVID-19 Dedicated Centre.

The Coronavirus Disease 2019 (COVID-19) pandemic has made changes to the traditional way of performing surgical consultations. The aim of the present study was to assess the need for surgical care performed by various surgical specialties among patients infected with COVID-19 hospitalized in a COVID-19 dedicated hospital. All surgical consultations performed for patients infected with COVID-19 in a COVID dedicated hospital in a seven month period were evaluated. Data on demographics, surgical specialty, consult reason, procedure performed, and whether it was a standard face to face or teleconsultation were gathered. Out of 2359 COVID-19 patients admitted to the hospital in the seven month period, 229 (9.7%) required surgical care. Out of those 108 consultations that did not lead to surgery, 71% were managed by telemedicine. A total of 36 patients were operated on while suffering from COVID-19. Out of them, only three patients admitted primarily for COVID-19 pneumonia underwent emergency surgery. The overall mortality among those operated on was 16.7%. Conclusions: Patients hospitalised with COVID-19 may require surgical care from various surgical specialties, especially during peaks of the pandemic. However, they rarely require a surgical procedure and only occasionally require major surgery. A significant portion of potentially surgical problems could be managed by teleconsultations.

Determination of Crystal-Field Splitting Induced by Thermal Oxidation of Titanium.

The electronic structure of transition-metal oxides is a key component responsible for material's optical and chemical properties. Specifically for metal-oxide structures, the crystal-field interaction determines the shape, strength, and occupancy of electronic orbitals. Consequently, the crystal-field splitting and resulting unoccupied state populations can be foreseen as modeling factors of the photochemical activity. Herein, we study the formation of crystal-field effects during thermal oxidation of titanium in an ambient atmosphere and range of temperatures. The X-ray absorption spectroscopy is employed for quantitative analysis of average t2g-eg crystal-field splitting (Δoct) and relative t2g/eg bands occupancy. The obtained result shows that Δoct changes as a function of temperature from 1.97 eV for a passive oxide layer created on a Ti metal surface at room temperature to 2.41 eV at 600 °C when the material changes into the TiO2 rutile phase. On the basis of XAS data analysis, we show that the Δoct values determined from L2 and L3 absorption edges are equal, indicating that the 2p1/2 and 2p3/2 core holes screen the t2g and eg electronic states in a similar manner.

Temperature as an Extra Dimension in Multidimensional Protein NMR Spectroscopy.

NMR spectroscopy is a particularly informative method for studying protein structures and dynamics in solution; however, it is also one of the most time-consuming. Modern approaches to biomolecular NMR spectroscopy are based on lengthy multidimensional experiments, the duration of which grows exponentially with the number of dimensions. The experimental time may even be several days in the case of 3D and 4D spectra. Moreover, the experiment often has to be repeated under several different conditions, for example, to measure the temperature-dependent effects in a spectrum (temperature coefficients (TCs)). Herein, a new approach that involves joint sampling of indirect evolution times and temperature is proposed. This allows TCs to be measured through 3D spectra in even less time than that needed to acquire a single spectrum by using the conventional approach. Two signal processing methods that are complementary, in terms of sensitivity and resolution, 1) dividing data into overlapping subsets followed by compressed sensing reconstruction, and 2) treating the complete data set with a variant of the Radon transform, are proposed. The temperature-swept 3D HNCO spectra of two intrinsically disordered proteins, osteopontin and CD44 cytoplasmic tail, show that this new approach makes it possible to determine TCs and their non-linearities effectively. Non-linearities, which indicate the presence of a compact state, are particularly interesting. The complete package of data acquisition and processing software for this new approach are provided.

General surgeons' attitudes towards COVID-19: A national survey during the SARS-CoV-2 virus outbreak.

BACKGROUND: The COVID-19 global pandemic left the unprepared health care systems struggling to mount a measured response. This gave rise to important questions about surgeons' attitude towards surgical practice and the level of preparation at work. METHODS: Cross-sectional web-based national survey distributed to general surgeons by e­mail over a period of 7 days. RESULTS: Among 304 responders, 42.6% were working in the hospital with COVID-19 patients. Three quarters of all surgeons (74.5%) were afraid of contracting the disease. While 42% expressed a fear for their own life while caring for COVID-19 patients, 90.1% were afraid of transmitting the disease to family members. The average reported level of PPE provided at the workplace was significantly higher among the group which was not afraid of contracting COVID-19 than among the group afraid of contracting COVID-19 (4.0 vs. 3.12, p = 0.02). Nearly all surgeons (93.8%) agreed that cancer surgeries should be continued during the pandemic and 49% perceived laparoscopy as a safe approach when operating on COVID-19 positive patients. CONCLUSION: A high proportion of surgeons admitted being afraid of working during the COVID-19 pandemic, which had various implications for their attitude towards surgical practice. Protecting health care workers is an important component of public health measures for addressing the epidemic.

Perceptions of clinical teachers acting as examiners regarding the value of Objective Structured Clinical Examinations.

OBJECTIVES: OSCE (Objective Structured Clinical Examination) is a common method of assessing clinical skills used at many universities. An important and at the same time difficult aspect of good examination preparation is obtaining a properly trained and well-motivated group of assessors. To effectively recruit and maintain cooperation with assessors, it is worth to know their opinion. The aim of this study was to investigate the opinions of teacher-examiners about OSCE and to identify the factors that could shape this opinion and influence on motivation. METHODS: A cross-sectional study was conducted using a questionnaire on teachers who participated as OSCE examiners. This questionnaire consisted of 21 questions about their perceptions. Answers were rated in a five-point Likert-type scale. Chi-square or Fisher's exact test was used to analyze the data. RESULTS: A total of 49 (out of 52) teachers participated in this study. Nearly 90% of examiners believed that it is fair, more than 90% that it is transparent. Despite the fact that 67% of examiners believe the examination is difficult to organize and 71% believe it is stressful for students, according to 72% of respondents the OSCE has a positive effect on learning. More than 91% of examiners believed that the OSCE is an appropriate test to assess students' skills. Opinions about examination were independent of specialty, seniority, gender or taking the OSCE as students. CONCLUSION: Teacher-examiners viewed the OSCE as a fair and transparent examination, adequate for assessment of skills and, despite it being difficult to organize, worth doing as it is appropriate to assess practical skills and positively influences students' motivation to learn tested skills.

Self-Medication-Related Behaviors and Poland's COVID-19 Lockdown.

(1) Background: The SARS-CoV-2 pandemic has changed the functioning of Polish health systems. Telemedicine has been developed and access to prescription drugs (Rx) has been facilitated. This study examined whether these changes and the imposition of a three-month lockdown caused Polish people to engage in more self-medication-related behaviors. (2) Method: After the fourth (final) stage of defrosting the Polish economy, an online survey of a quota sample of 1013 Polish respondents was conducted. (3) Results: Almost half of the respondents (45.6%) indicated that they had engaged in at least one behavior associated with inappropriate self-medication during the lockdown (e.g., 16.6% took medication as a precaution, and 16.8% took an Rx formulation without consultation). Some of these people had never engaged in such behaviors prior to the lockdown. Linear regression showed that higher values of a composite ("lockdown") index of self-medication-related behaviors occurring during lockdown were predicted by greater religiosity and the presence of children in a household. Also, independent samples t-tests showed that people who were afraid for their financial future and people who feared for their health obtained higher lockdown index scores than people not having such worries. (4) Conclusions: Self-medication-related behaviors were more common among Poles before lockdown than during the lockdown (which is unsurprising given that the lengths of the periods compared were hugely different), worryingly, many people exhibited such behaviors for the first time during the lockdown.

In pursuit of COVID-19 surgical risk stratification to manage a limited workforce and supplies in minimally invasive surgery.

The protective barriers used so far in surgery do not provide adequate protection against SARS-CoV-2 virus, and reinforced protective equipment is needed. The rapid increase in the number of patients and the worldwide panic associated with the increasingly low availability of protective equipment has resulted in a shortage of protective equipment in many hospitals. Appropriatepersonal protective equipment must be provided so that the surgical team proceeding to surgery is not excluded from the further struggle for patients' health, especially in MIS. Reckless and excessive use of maximum protective equipment may result in a severe shortage of these products when the number of infected persons requiring surgery increases. The use of a structured infection risk scheme for medical staff, depending on the results of reverse transcription polymerase chain reaction assays and COVID-19 symptoms, combined with the division of protection equipment into three groups, allows easy selection of an appropriate clothing scheme for the clinical setting.