The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study.

Introduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.

Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019.

BACKGROUND: Laboratory biomarkers to estimate the severity of coronavirus disease 2019 (COVID-19) are crucial during the pandemic since resource allocation must be carefully planned. AIMS: To evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalised with COVID-19. METHODS: Patients hospitalised with confirmed COVID-19 were included in the study. Laboratory data and total IgE levels were measured on admission. Lymphocyte, eosinophil, ferritin, d-dimer and C-reactive protein parameters were recorded at baseline and on the 3rd and 14th days of hospitalisation. RESULTS: The study enrolled 202 patients, of which 102 (50.5%) were males. The average age was 50.17 ± 19.68 years. Of the COVID-19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 (0-2124) vs 38.70 (0-912); P < 0.001) and serum eosinophil levels were significantly lower (0.015 (0-1.200) vs 0.040 (0-1.360); P = 0.002) in clinically worsened COVID-19 patients when compared with stable patients. The optimal cut-off for predicting clinical worsening was 105.2 ng/L, with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve = 0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and C-reactive protein levels as independent predictors. CONCLUSIONS: Our single-centre pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalised due to COVID-19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID-19 infections.

Physicians' Biological Drug Preference in Patients With Rheumatoid Arthritis and Spondyloarthritis With a History of Malignancy: Perspectives From the Treasure Database.

OBJECTIVE: Because of concerns about malignancy risks, using biological disease-modifying antirheumatic drugs (bDMARDs) in patients with a history of malignancy remains a challenging issue in rheumatology practice. This study aimed to investigate bDMARD preferences of physicians when treating of rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients with a history of malignancy. METHODS: The data for this cross-sectional study were gathered from the TReasure database using a date range of December 2017 and January 2020. Biological disease-modifying antirheumatic drug preferences were analyzed for 40 RA patients and 25 SpA patients with a history of malignancy. RESULTS: The most frequently prescribed bDMARD was rituximab, which was given to 28 RA patients (70%). For 25 patients (62.5%), the time between the diagnosis of malignancy and starting on a bDMARD regimen was less than 60 months, with a median interval of 43.5 months. Among SpA patients, the preferred bDMARDs were secukinumab and etanercept, which were each administered to 7 patients (28%). For 13 SpA patients (52%), the time between the diagnosis of malignancy and starting on bDMARDs was less than 60 months, with a median interval of 97 months. CONCLUSIONS: The observed bDMARD preferences may be related to the therapeutic effects of rituximab on lymphoproliferative malignancies, the protective effects of secukinumab on tumor progression, and the short half-life of etanercept. Biological disease-modifying antirheumatic drugs should be used in RA and SpA patients with malignancy in case of high inflammatory activity.

Is Acculturation Associated with the Cognitive Performance of Older Hispanics?

BACKGROUND: Hispanics in the United States are disproportionately affected by Alzheimer's disease and related dementias. Little is known about the impact of acculturation on cognitive performance. OBJECTIVE: This study examined the association between acculturation and cognitive performance among older Hispanics. METHODS: We analyzed cross-sectional data of 616 Hispanic participants in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 [average age = 67.15 years, %Female = 51.46, %less than high-school graduate = 52.60]. Cognitive performance was measured by two neuropsychological tests: Animal Fluency Test (AFT) and Digit Symbol Substitution Test (DSST). We used two single-item proxy measures to quantify acculturation: nativity status (non-US-born residing < 15 years in the US (low acculturation), non-US-born residing ≥15 years in the US, and US-born (high acculturation)); and language acculturation (only/mostly Spanish (low acculturation), Spanish and English, only/mostly English (high acculturation)). We used adjusted linear regression to evaluate associations between acculturation and cognitive performance. RESULTS: Results indicated poorer cognitive performance among the low-acculturated groups for both nativity and linguistic measures. Participants who were non-US-born living ≥15 years (p = 0.02) and speaking only/mostly Spanish or Spanish and English (p = 0.01 and 0.006 respectively) had significantly lower AFT scores compared to US-born and only/mostly English-speaking groups. Participants who were non-US-born living < 15 years (p < 0.0001) or non-US-born living ≥15 years (p < 0.0001) and speaking only/mostly Spanish (p = 0.0008) scored lower on the DSST than the US-born and only/mostly English-speaking participants. CONCLUSION: In summary, low acculturation is associated with poorer cognitive performance among older Hispanics. Acculturation might be an important attribute to help understand cognitive decline and dementias among Hispanics.

Quantum chemical calculations on elucidation of molecular structure and spectroscopic insights on 2-amino-4-methoxy-6-methylpyrimidine and 2-amino-5-bromo-6-methyl-4-pyrimidinol--a comparative study.

The FTIR and FT-Raman spectra of 2-amino-4-methoxy-6-methylpyrimidine (AMMP) and 2-amino-5-bromo-6-methyl-4-pyrimidinol (ABMP) have been recorded in the region 4000-450 and 4000-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of AMMP and ABMP were obtained by the density functional theory (DFT) using 6-311++G(∗∗) basis set. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The (1)H and (13)C NMR spectra have been recorded. The (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method. The theoretical UV-visible spectrum of the compound using TD-DFT method and the electronic properties, such as HOMO and LUMO energies, are performed by time-dependent DFT (TD-DFT) approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (ß0) and its related components of AMMP and ABMP are calculated using DFT/6-311++G(∗∗) method on the finite-field approach. The natural atomic charges of the molecules were also discussed. The change in electron density (ED) in the σ(∗) antibonding orbitals and stabilization energies E(2) have been calculated by natural bond orbital (NBO) analysis to give clear evidence of stabilization originating in the hyper conjugation of hydrogen-bonded interactions.

FT-IR, FT-Raman and DFT quantum chemical study on the molecular conformation, vibrational and electronic transitions of 1-(m-(trifluoromethyl)phenyl)piperazine.

The FTIR and FT-Raman spectra of 1-(m-(trifluoromethyl)phenyl)piperazine [TFMPP] have been recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of the compound was obtained by the density functional theory using 6-311++G(d,p) basis set. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. A detailed interpretation of the infrared and Raman spectra were also reported based on potential energy distribution (PED). UV-Vis spectrum of the compound was recorded and the electronic properties HOMO and LUMO energies were measured by TD-DFT approach. Furthermore, molecular electrostatic potential is performed and also the calculated HOMO and LUMO energies show that charge transfer occurs within the molecule.

Efficient integral equation-based analysis of finite periodic structures in the optical frequency range.

The optical response of dense finite arrays of nanoparticles can be efficiently analyzed with the help of macro basis functions obtained by employing the array scanning method. This is demonstrated by analyzing optical collimation in arrays of silver nanorods. The accuracy of the solution obtained with the proposed method has been validated by comparison with solutions obtained employing the Krylov subspace iterative method. The relative error in the electric field distribution on an observation plane above the finite array is of the order of -25 dB, while the number of unknowns is reduced by a factor of 32.

Spectroscopic (FT-IR, FT-Raman, UV and NMR) investigation, conformational stability, NLO properties, HOMO-LUMO and NBO analysis of hydroxyquinoline derivatives by density functional theory calculations.

The FTIR and FT-Raman spectra of 2-hydroxyquinoline and its derivatives have been recorded in the region 4000-400 cm(-1) and 3500-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of these compounds were obtained by the density functional theory using 6-311++G(d,p) basis sets. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. A detailed interpretation of the infrared and Raman spectra were also reported based on total energy distribution (TED). The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically simulated spectra. (1)H and (13)C NMR spectra were recorded and its corresponding nuclear magnetic resonance chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method. UV-visible spectrum of the compound was recorded and the electronic properties HOMO and LUMO energies were measured by time-dependent (TD-DFT) approach. Molecular stability and bond strength were investigated by applying the natural bond orbital analysis (NBO). The calculated HOMO and LUMO energies show that charge transfer occurs in the molecules. In addition, the non-linear optical properties were discussed from the dipole moment values and excitation wavelength in the UV-visible region.

Vibrational spectroscopic (FT-IR and FT-Raman) studies, natural bond orbital analysis and molecular electrostatic potential surface of Isoxanthopterin.

The FTIR and FT-Raman spectra of Isoxanthopterin have been recorded in the region 4000-450 and 4000-100 cm(-1), respectively. The optimized geometry, frequency and intensity of the vibrational bands of Isoxanthopterin were obtained by the density functional theory (DFT) using 6-311++G(d,p) basis set. The harmonic vibrational frequencies were scaled and compared with experimental values. The observed and the calculated frequencies are found to be in good agreement. The (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method. The UV-visible spectrum was also recorded and compared with the theoretical values. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (ß0), related properties (ß, α0 and Δα) and the Mulliken charges of the molecule were also computed using DFT calculations. Stability of the molecule arising from hyperconjugative interactions, charge delocalization have been analyzed using natural bond orbital (NBO) analysis. The results show that charge in electron density (ED) in the σ* and π* antibonding orbitals and second order delocalization energies (E2) confirms the occurrence of intramolecular charge transfer (ICT) within the molecule. Information about the charge density distribution of the molecule and its chemical reactivity has been obtained by mapping molecular electrostatic potential surface. In addition, the non-linear optical properties were discussed from the dipole moment values and excitation wavelength in the UV-visible region.

Molecular structure, vibrational, UV, NMR, hyperpolarizability, NBO and HOMO-LUMO analysis of Pteridine2,4-dione.

The FTIR and FT-Raman spectra of Pteridine2,4-dione has been recorded in the region 4000-450 and 4000-100 cm(-1), respectively. The tautomeric stability, optimized geometry, frequency and intensity of the vibrational bands of Pteridine2,4-dione were obtained by the density functional theory (DFT) using 6-311++G(d,p) basis set. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The (1)H and(13)C NMR spectra chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method. The theoretical UV-Vis spectrum of the compound using CIS method and the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (ß(0)) of these novel molecular system and related properties (ß, α(0) and Δα) of Pteridine2,4-dione are calculated using DFT/6-311++G (d,p) method on the finite-field approach. The Mulliken charges, the values of electric dipole moment (µ) of the molecule were computed using DFT calculations. The change in electron density (ED) in the σ(*) antibonding orbitals and stabilization energies E(2) have been calculated by natural bond (NBO) analysis to give clear evidence of stabilization originating in the hyper conjugation of hydrogen-bonded interactions.

Spectroscopic, electronic structure and natural bond analysis of 2-aminopyrimidine and 4-aminopyrazolo[3,4-d]pyrimidine: a comparative study.

The FTIR and FT-Raman spectra of 2-aminopyrimidine (2-AP) and 4-aminopyrazolo[3,4-d]pyrimidine (4-APP) has been recorded in the region 4000-400 and 3500-100 cm(-1), respectively. The tautomeric stability, optimized geometry, frequency and intensity of the vibrational bands of 2-AP and 4-APP were obtained by the DFT level using 6-31G(d) and 6-31G(d,p) basis sets. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. A detailed interpretation of the infrared and Raman spectra of 2-AP and 4-APP are also reported based on total energy distribution (TED). The observed and the calculated frequencies are found to be in good agreement. The experimental spectra also coincide satisfactorily with those of theoretically simulated spectra. The (1)H and (13)C NMR spectra have been simulated using the gauge independent atomic orbital (GIAO) method. The theoretical UV-Vis spectrum of the compound using CIS method and the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The first order hyperpolarizability (ß(0)) of these novel molecular system and related properties (ß, α(0) and Δα) of 2-AP and 4-APP are calculated using DFT/6-31G(d) method on the finite-field approach. The Mulliken charges, the values of electric dipole moment (µ) of the molecule were computed using DFT calculations. The change in electron density (ED) in the σ(∗) antibonding orbitals and stabilization energies E(2) have been calculated by natural bond (NBO) analysis to give clear evidence of stabilization originating in the hyper conjugation of hydrogen-bonded interactions.

Quantum mechanical study of the structure and spectroscopic (FT-IR, FT-Raman, 13C, 1H and UV), NBO and HOMO-LUMO analysis of 2-quinoxaline carboxylic acid.

The FTIR and FT-Raman spectra of 2-quinoxaline carboxylic acid (2-QCA) has been recorded in the region 4000-450 and 4000-100 cm(-1), respectively. The conformational analysis, optimized geometry, frequency and intensity of the vibrational bands of 2-QCA were obtained by the density functional theory (DFT) with complete relaxation in the potential energy surface using 6-31G(d) basis set. The harmonic vibrational frequencies were calculated and the scaled values have been compared with experimental FTIR and FT-Raman spectra. The observed and the calculated frequencies are found to be in good agreement. The (1)H and(13)C NMR spectra have been recorded and (1)H and (13)C nuclear magnetic resonance chemical shifts of the molecule were also calculated using the gauge independent atomic orbital (GIAO) method and their respective linear correlations were obtained. The theoretical UV-visible spectrum of the compound using CIS method and the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The calculated HOMO and LUMO energies show that charge transfer occurs within molecule. The Mulliken charges, the values of electric dipole moment (µ) of the molecule were computed using DFT calculations. The change in electron density (ED) in the σ* antibonding orbitals and stabilization energies E(2) have been calculated by natural bond (NBO) analysis to give clear evidence of stabilization originating in the hyper conjugation of hydrogen-bonded interactions.

Salt intake and hypervolemia in the development of hypertension in peritoneal dialysis patients.

Peritoneal dialysis (PD) patients are often volume-expanded and have higher-than-normal blood pressure (BP) levels. In the present study, we aimed to investigate the role of fluid balance and salt intake for BP control in our PD patients. The study included 37 patients undergoing PD and having complete data for 3 consecutive months. Patients were allocated to one of two groups based on measured BP in the preceding 3 months: hypertensive patients (BP > 140/90 mmHg) and normotensive patients (did not meet the hypertensive BP criteria). Volume status was evaluated by bioimpedance analysis. The 37 patients (18 women, 19 men) had a mean age of 46.4 years. The hypertensive and normotensive groups included 17 and 20 patients respectively. Sex, age, and time on PD were similar between the groups. Weight (77.3 +/- 20.3 kg vs. 64.5 +/- 9.8 kg, p < 0.05), total sodium load (2649.2 +/- 621.9 mmol vs. 2272.4 +/- 511.9 mmol, p < 0.05), daily total sodium removal (160.5 +/- 74.4 mmol vs. 112.1 +/- 48.0 mmol, p < 0.05), extracellular water (19.4 +/- 4.3 L vs. 16.4 +/- 3.5 L, p < 0.05), and normalized extracellular water (11.6 +/- 1.9 L vs. 10.1 +/- 1.8 L, p < 0.05) were all significantly higher in the hypertensive group. Despite higher fluid and sodium removal, hypertensive patients were more hypervolemic than normotensive patients. Increasing fluid and salt removal by peritoneal ultrafiltration results in an increased financial burden and also causes serious clinical problems. Restricting fluid and salt intake is an alternative and safer strategy to maintain good fluid balance.

Tracheobronchopathia osteochondroplastica: an unusual presentation.

A 24-year-old woman presented with chronic cough and noisy breathing. Chest x-ray revealed diffuse irregularity and narrowing of the tracheal lumen. Thorax computed tomography showed irregularity, stenosis, and areas of ossification throughout the trachea and both main bronchia. Flexible bronchoscopy revealed multiple nodules protruding into the tracheal lumen. Histopathology of the nodules confirmed the diagnosis of "tracheobronchopathia osteochondroplastica." Tracheobronchopathia osteochondroplastica is a rare, benign disease that is characterized by multiple cartilaginous and osseous submucosal nodules protruding through tracheal lumen and large bronchia. The etiology is still unexplained.