Challenges In Conformational Analysis Of Flexible Molecules

The conformational analysis represents the first step toward a detailed characterization and understanding of the structure-function relationships of molecular systems. In this respect spectroscopic experiments on isolated bio- and organic-molecules allow detection of different binding schemes and three-dimensional (3D) conformations without perturbing effects of the environment. Detection of multiple 3D-geometries concomitantly present in an experimental mixture can be facilitated by “in situ” structural changes induced either by thermal variations, or the interaction with near-IR (NIR) to ultraviolet (UV) light. These sophisticated experiments need to be supported by accurate and reliable computational studies allowing to link the rich experimental data to the desired information on the structure and properties of complex molecular systems. Therefore a reliable computational approach should be able to provide a balanced description of all interactions allowing for extended mapping of the whole conformational space, including the accurate prediction of equilibrium structures, their relative positions on the potential energy surface (PES), free energies corresponding to the specific experimental conditions and the spectroscopic properties. Computations based on the second-order perturbation theory (VPT2) allow accounting for the anharmonicity of both wave function and properties. This results in a correct description of the intensity of non-fundamental transitions and more accurate band-shapes. Moreover, the same anharmonic force fields as employed in the determination of vibrational spectra allow considering vibrational corrections to molecular properties or thermodynamic functions. For flexible molecules, the large amplitude-motion (LAM) free approach, where all LAMs anharmonic constants are excluded, allows overcoming problems due to contaminating the overall VPT2 treatment and higher frequency vibrations. The most reliable structural, spectroscopic and energetic results can be obtained combining various computational methods ranging from density functional theory (DFT) to coupled-cluster (CC), with the latter representing also references for the benchmarking of different DFT methodologies

Anharmonic Effects on Vibrational Spectra Intensities: Infrared, Raman, Vibrational Circular Dichroism, and Raman Optical Activity

The aim of this paper is 2-fold. First, we want to report the extension of our virtual multifrequency spectrometer (VMS) to anharmonic intensities for Raman optical activity (ROA) with the full inclusion of first- and second-order resonances for both frequencies and intensities in the framework of the generalized second-order vibrational perturbation theory (GVPT2) for all kinds of vibrational spectroscopies. Then, from a more general point of view, we want to present and validate the performance of VMS for the parallel analysis of different vibrational spectra for medium-sized molecules (IR, Raman, VCD, ROA) including both mechanical and electric/magnetic anharmonicity. For the well-known methyloxirane benchmark, careful selection of density functional, basis set, and resonance thresholds permitted us to reach qualitative and quantitative agreement between experimental and computed band positions and shapes. Next, the whole series of halogenated azetidinones is analyzed, showing that it is now possible to interpret different spectra in terms of mass, electronegativity, polarizability, and hindrance variation between closely related substituents, chiral spectroscopies being particular effective in this connection

Localisation of exogenous surfactants in cell membranes in the air-blood barrier: rat model

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier

What might cause pain in the thyroid gland? Report of a patient with subacute thyroiditis of atypical presentation

Podostre ziarniniakowe zapalenie tarczycy, zwane inaczej chorobą de Quervaina lub bolesnym podostrym zapaleniem tarczycy, jest najczęstszą patologią gruczołu tarczowego odpowiedzialną za występowanie bolesności okolicy szyi. Inne przyczyny bólu w tej lokalizacji muszą zostać uwzględnione w diagnostyce różnicowej, zwłaszcza jeśli objawy występujące u pacjenta są niejednoznaczne bądź mylące. Autorzy przedstawili przypadek 39-letniej kobiety, u której rozpoznano podostre ziarniakowe zapalenie tarczycy, którego obraz kliniczny, biochemiczny oraz radiologiczny różnił się znacząco od typowego przebiegu tego schorzenia. Wstępnego rozpoznania podostrego ziarniniakowego zapalenia tarczycy dokonano na podstawie występujących objawów, wyniku badania ultrasonograficznego oraz biopsji aspiracyjnej cienkoigłowej. Jednak przeprowadzone analizy biochemiczne sugerowały nieobecność procesu zapalnego oraz tyreotoksykozy. Co więcej, technetowa scyntygrafia tarczycy wykazała prawidłowy wychwyt izotopu. Nie zaobserwowano klinicznej ani ultrasonograficznej odpowiedzi na glikokortykosteroidy. Mimo zastosowanego leczenia objawy u pacjentki stopniowo narastały, a ból zaczął znacząco upośledzać jej funkcjonowanie. Ostatecznie pacjentka przebyła zabieg całkowitego wycięcia tarczycy. W rezultacie objawy ustąpiły, jednak obraz makroskopowy preparatu operacyjnego gruczołu tarczowego nasuwał podejrzenie procesu nowotworowego. Niemniej jednak badanie histopatologiczne pobranego materiału potwierdziło wstępne rozpoznanie choroby de Quervaina, zatem poprzednie wyniki badań nie pozostawały w zgodzie z tą diagnozą. Przypadek ten potwierdza możliwość atypowego przebiegu podostrego ziarniniakowego zapalenia tarczycy. Dodatkowo wskazuje na możliwość rozważenia leczenia operacyjnego u pacjentów z ciężkim, przetrwałym, upośledzającym funkcjonowanie bólem gruczołu tarczowego w przebiegu podostrego ziarniniakowego zapalenia tarczycy. (Pol J Endocrinol 2012; 63 (2): 138–142)Subacute granulomatous thyroiditis (SAT), also known as de Quervain’s thyroiditis or painful subacute thyroiditis, is the commonest thyroid condition responsible for neck tenderness. Other causes of pain in the thyroid gland should be taken into consideration during differential diagnosis, especially when a patient presents with misleading or equivocal signs and symptoms. We report the case of a 39 year-old woman diagnosed as having SAT whose clinical, biochemical and radiological presentation varied significantly from the common SAT manifestation. A tentative diagnosis of SAT was made based on the presented symptoms, ultrasonography and fine-needle biopsy results. However, biochemical analysis suggested neither inflammatory process nor the presence of thyrotoxicosis. Moreover, technetium scan of the thyroid revealed normal uptake of the isotope and there was neither clinical nor ultasonographic response for corticosteroids. The patient’s symptoms, despite being prescribed typical treatment, gradually deteriorated and the pain became increasingly debilitating. Eventually, the patient underwent total thyroidectomy. As a result, she has become free of symptoms, but the macroscopic picture of thyroid gland, noted during the operation, gave a suspicion of neoplastic process. Nevertheless, histological study of flow samples confirmed the tentative diagnosis of de Quervain’s thyroiditis, despite all previous findings that were not suggestive of it. This report confirms the likelihood that SAT can present atypically. Additionally, it indicates that surgical treatment may be considered in patients with severe, debilitating, persistent thyroid gland pain connected with SAT clinical course. (Pol J Endocrinol 2012; 63 (2): 138–142

Absorption-emission symmetry breaking and the different origins of vibrational structures of the 1Qy and 1Qx electronic transitions of pheophytin a

© 2019 Author(s). The vibrational structure of the optical absorption and fluorescence spectra of the two lowest-energy singlet electronic states (Qy and Qx) of pheophytin a were carefully studied by combining low-resolution and high-resolution spectroscopy with quantum chemical analysis and spectral modeling. Large asymmetry was revealed between the vibrational structures of the Qy absorption and fluorescence spectra, integrally characterized by the total Huang-Rhys factor and reorganization energy in absorption of SvibA = 0.43 ± 0.06, λA = 395 cm-1 and in emission of SvibE = 0.35 ± 0.06, λE = 317 cm-1. Time-dependent density-functional theory using the CAM-B3LYP, ωB97XD, and MN15 functionals could predict and interpret this asymmetry, with the exception of one vibrational mode per model, which was badly misrepresented in predicted absorption spectra; for CAM-B3LYP and ωB97XD, this mode was a Kekulé-type mode depicting aromaticity. Other computational methods were also considered but performed very poorly. The Qx absorption spectrum is broad and could not be interpreted in terms of a single set of Huang-Rhys factors depicting Franck-Condon allowed absorption, with Herzberg-Teller contributions to the intensity being critical. For it, CAM-B3LYP calculations predict that SvibA (for modes >100 cm-1) = 0.87 and λA = 780 cm-1, with effective x and y polarized Herzberg-Teller reorganization energies of 460 cm-1 and 210 cm-1, respectively, delivering 15% y-polarized intensity. However, no method was found to quantitatively determine the observed y-polarized contribution, with contributions of up to 50% being feasible

Changes in the bronchial epithelia in patients with immotile cilia syndromes

Immotile cilia syndromes is a cause of recurrent infection of the airways and recurrent bronchopneumonias. Among the ciliary abnormalities are found changes in the structure of the microtubules, unco-ordinated ciliary movements caused by the absence of inner or outer or both dynein arms, and abnormalities of the kinetosomes and/or rete ridges. In patients with ciliary dyskinaesia bronchitis occurs early in life (during infancy) and usually has a recurrent tendency, so that bronchial biopsy is frequently undergone for diagnostic purposes. In this study we include 127 bronchial biopsies from patients (from 2 months to 49 years) unsuccessfully treated for recurrent respiratory tract infections. When performing regular diagnostic procedures on the light and electron microscopic level, we have looked for cilia abnormalities and also focused on changes within the mucosa and submucosa. The most common abnormality recorded was absence of the inner dynein arms, but in 40 cases neither of the dynein arms were present. Only a few patients had classical Kartagener’s syndrome. Special attention is drawn to biopsies from elderly patients, in whom long-standing infections were followed by extensive damage to the bronchial epithelium, including even a total absence of ciliated cells. In some cases enhanced regenerative processes and some foci of squamous metaplasia were found. In two cases even foci of low-grade dysplasia were diagnosed

Localisation of exogenous surfactants in cell membranes in the air-blood barrier : rat model

The use of exogenous surfactants has been introduced into the therapy of patients of different ages. Much better results have been obtained in the treatment of respiratory distress syndrome with surfactants enriched with surfactant proteins. In the following study we used protein-containing surfactants (survanta and curosurf). The aim of the following study was to determine the localisation of artificial surfactants in the lung tissue. Using the Immunogold Technique, biotinylated surfactant proteins were traced in the air-blood barriers. In all lungs the exogenous surfactant was present only in some alveoli. In these parts small areas of atelectasis as well as oedema and transudate accumulation were seen. These changes were less severe after biotinylated curosurf treatment. In electron microscope studies we found surfactant elements in the air-blood barrier and other structures of the alveolar septa. Immunogold studies confirm the presence of biotynylated surfactant in the elements of the air-blood barrier

Surgical treatment of morbid obesity and metabolic disorders

Nadmierna masa ciała stanowi jeden z najpoważniejszych problemów współczesnej opieki zdrowotnej. Należy do pięciu głównych czynników odpowiedzialnych za ogólną liczbę zgonów na świecie, ściśle związanych z chorobami układu sercowo-naczyniowego, nowotworami, a także wieloma innymi schorzeniami będącymi konsekwencją otyłości olbrzymiej. Metody zachowawcze leczenia patologicznej otyłości, do których należą zmiana stylu życia pod względem wprowadzenia restrykcji żywieniowych oraz zwiększenia aktywności fizycznej, a także leczenie farmakologiczne, w większości przypadków pozwalają na utratę 5–15% masy ciała. Osiągnięte wyniki są zwykle mało zadowalające i krótkotrwałe. Chirurgia bariatryczna/metaboliczna jest uważana obecnie za najskuteczniejszą metodę leczenia otyłości olbrzymiej. Wykazano poprawę lub całkowite ustąpienie patologii i chorób współistniejących z otyłością, między innymi: cukrzycy typu 2, nadciśnienia tętniczego, dyslipidemii czy nieprawidłowej tolerancji glukozy po operacjach metabolicznych. Jedną z najistotniejszych pooperacyjnych zmian jest znaczna poprawa jakości życia, przejawiająca się w wielu jego aspektach, co dla pacjenta może stanowić szczególnie ważny czynnik przemawiający za wdrożeniem leczenia operacyjnego.Excessive weight and obesity are currently among the most serious public heath problem. They are the fifth leading cause of mortality and morbidity, closely related to cardiovascular disease, cancer and other comorbidities, which increase throughout the range of moderate to severe obesity. Conservative treatment of morbidly obese, based on lifestyle modification such as dietary restriction, physical activity and pharmacotherapy, often lead to 5–15% excess body weight loss and nonexistent long-term success. Bariatric or metabolic surgery is considered as the most effective treatment of the morbidly obese patients, providing to sustained long-time weight loss and reduced obesity related morbidity and deaths. The positive effect of bariatric surgery is documented in many studies as improvement or remission of: type 2 diabetes mellitus, hypertension, dyslipidemia, impaired glucose tolerance and other obesity-related diseases. One of the most expected and very important postoperative change is a significant improvement of patients quality of life in its many aspects

„Ostałówek. Miejsce wspólne” – projekt animacyjny inspirowany doświadczeniami etnograficznymi

„Ostałówek. A common place” – an animation project inspired by ethnographic experiences The article is an overview of activities undertaken by means of cultural animation, based on previous deepened ethnographic research. It refers to the matter of using anthropology as an instrument to stimulate societies endangered with exclusion. Th e project „Ostałówek. A common place”, carried out in one of the villages in Radomszczyzna (near Szydłowiec), was introduced as an example