Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease

Background - Therapeutic neovascularization may constitute an important strategy to salvage tissue from critical ischemia. Circulating bone marrow–derived endothelial progenitor cells (EPCs) were shown to augment the neovascularization of ischemic tissue. In addition to lipid-lowering activity, hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) reportedly promote the neovascularization of ischemic tissue in normocholesterolemic animals. Methods and Results - Fifteen patients with angiographically documented stable coronary artery disease (CAD) were prospectively treated with 40 mg of atorvastatin per day for 4 weeks. Before and weekly after the initiation of statin therapy, EPCs were isolated from peripheral blood and counted. In addition, the number of hematopoietic precursor cells positive for CD34, CD133, and CD34/kinase insert domain receptor was analyzed. Statin treatment of patients with stable CAD was associated with an '1.5-fold increase in the number of circulating EPCs by 1 week after initiation of treatment; this was followed by sustained increased levels to '3-fold throughout the 4-week study period. Moreover, the number of CD34/kinase insert domain receptor–positive hematopoietic progenitor cells was significantly augmented after 4 weeks of therapy. Atorvastatin treatment increased the further functional activity of EPCs, as assessed by their migratory capacity

Access to side-chain carbon information in deuterated solids under fast MAS through non-rotor-synchronized mixing.

We demonstrate the accessibility of aliphatic 13C side chain chemical shift sets for solid-state NMR despite perdeuteration and fast MAS using isotropic, non-rotor-synchronized 13C-13C mixing. Combined with amide proton detection, we unambiguously and sensitively detect whole side chain to backbone correlations for two proteins using around 1 mg of sample

Protective role of natural and semi-synthetic tocopherols on TNFα-induced ros production and ICAM-1 and Cl-2 expression in ht29 intestinal epithelial cells

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, on TNFα-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNFα-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNFα represents an important proinflammatory mediator

Patient Care in High-Level Containment Care Units: In a Resourced Setting

Vasa, A., Boulter, K., Horihan, Cates, D., Piquette, C., Sullivan, J., Johnson, D, & Hewlett, A. (2019). Patient Care in High-Level Containment Care Units. In T. Cieslak, M. Kortepeter, C. Kratochvil, & J. Lawler (Eds.), Nebraska Isolation and Quarantine Manual (pp. 87-101). Lincoln, NE: University of Nebraska Press.https://digitalcommons.unmc.edu/nm_books/1000/thumbnail.jp

A mutate-and-map protocol for inferring base pairs in structured RNA

Chemical mapping is a widespread technique for structural analysis of nucleic acids in which a molecule's reactivity to different probes is quantified at single-nucleotide resolution and used to constrain structural modeling. This experimental framework has been extensively revisited in the past decade with new strategies for high-throughput read-outs, chemical modification, and rapid data analysis. Recently, we have coupled the technique to high-throughput mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure of not only that nucleotide but also its interaction partner. Carrying out the mutation and mapping for the entire system gives an experimental approximation of the molecules contact map. Here, we give our in-house protocol for this mutate-and-map strategy, based on 96-well capillary electrophoresis, and we provide practical tips on interpreting the data to infer nucleic acid structure.Comment: 22 pages, 5 figure

Understanding the errors of SHAPE-directed RNA structure modeling

Single-nucleotide-resolution chemical mapping for structured RNA is being rapidly advanced by new chemistries, faster readouts, and coupling to computational algorithms. Recent tests have shown that selective 2'-hydroxyl acylation by primer extension (SHAPE) can give near-zero error rates (0-2%) in modeling the helices of RNA secondary structure. Here, we benchmark the method using six molecules for which crystallographic data are available: tRNA(phe) and 5S rRNA from Escherichia coli, the P4-P6 domain of the Tetrahymena group I ribozyme, and ligand-bound domains from riboswitches for adenine, cyclic di-GMP, and glycine. SHAPE-directed modeling of these highly structured RNAs gave an overall false negative rate (FNR) of 17% and a false discovery rate (FDR) of 21%, with at least one helix prediction error in five of the six cases. Extensive variations of data processing, normalization, and modeling parameters did not significantly mitigate modeling errors. Only one varation, filtering out data collected with deoxyinosine triphosphate during primer extension, gave a modest improvement (FNR = 12%, and FDR = 14%). The residual structure modeling errors are explained by the insufficient information content of these RNAs' SHAPE data, as evaluated by a nonparametric bootstrapping analysis. Beyond these benchmark cases, bootstrapping suggests a low level of confidence (<50%) in the majority of helices in a previously proposed SHAPE-directed model for the HIV-1 RNA genome. Thus, SHAPE-directed RNA modeling is not always unambiguous, and helix-by-helix confidence estimates, as described herein, may be critical for interpreting results from this powerful methodology.Comment: Biochemistry, Article ASAP (Aug. 15, 2011

Quantification of Circulating Endothelial Progenitor Cells Using the Modified ISHAGE Protocol

Circulating endothelial progenitor cells (EPC), involved in endothelial regeneration, neovascularisation, and determination of prognosis in cardiovascular disease can be characterised with functional assays or using immunofluorescence and flow cytometry. Combinations of markers, including CD34+KDR+ or CD133+KDR+, are used. This approach, however may not consider all characteristics of EPC. The lack of a standardised protocol with regards to reagents and gating strategies may account for the widespread inter-laboratory variations in quantification of EPC. We, therefore developed a novel protocol adapted from the standardised so-called ISHAGE protocol for enumeration of haematopoietic stem cells to enable comparison of clinical and laboratory data.In 25 control subjects, 65 patients with coronary artery disease (CAD; 40 stable CAD, 25 acute coronary syndrome/acute myocardial infarction (ACS)), EPC were quantified using the following approach: Whole blood was incubated with CD45, KDR, and CD34. The ISHAGE sequential strategy was used, and finally, CD45(dim)CD34(+) cells were quantified for KDR. A minimum of 100 CD34(+) events were collected. For comparison, CD45(+)CD34(+) and CD45(-)CD34(+) were analysed simultaneously. The number of CD45(dim)CD34(+)KDR(+) cells only were significantly higher in healthy controls compared to patients with CAD or ACS (p = 0.005 each, p<0.001 for trend). An inverse correlation of CD45(dim)CD34(+)KDR(+) with disease activity (r = -0.475, p<0.001) was confirmed. Only CD45(dim)CD34(+)KDR(+) correlated inversely with the number of diseased coronaries (r = -0.344; p<0.005). In a second study, a 4-week de-novo treatment of atorvastatin in stable CAD evoked an increase only of CD45(dim)CD34(+)KDR(+) EPC (p<0.05). CD45(+)CD34(+)KDR(+) and CD45(-)CD34(+)KDR(+) were indifferent between the three groups.Our newly established protocol adopted from the standardised ISHAGE protocol achieved higher accuracy in EPC enumeration confirming previous findings with respect to the correlation of EPC with disease activity and the increase of EPC during statin therapy. The data of this study show the CD45(dim) fraction to harbour EPC

Cognitive behaviour therapy versus counselling intervention for anxiety in young people with high-functioning autism spectrum disorders: a pilot randomised controlled trial

The use of cognitive-behavioural therapy (CBT) as a treatment for children and adolescents with autism spectrum disorder (ASD) has been explored in a number of trials. Whilst CBT appears superior to no treatment or treatment as usual, few studies have assessed CBT against a control group receiving an alternative therapy. Our randomised controlled trial compared use of CBT against person-centred counselling for anxiety in 36 young people with ASD, ages 12–18. Outcome measures included parent- teacher- and self-reports of anxiety and social disability. Whilst each therapy produced improvements inparticipants, neither therapy was superior to the other to a significant degree on any measure. This is consistent with findings for adults

Опыт использования расширенного транстрицепитального доступа при остеосинтезе сложных переломов дистального метаэпифиза плечевой кости

Background. The preferred treatment for intra-articular displaced fractures is open reduction and internal fixation. The need to obtain a better visualization of the fracture geometry made it necessary to develop a large number of new approaches and their modifications.Material and methods. The study included 186 patients with an intra-articular fracture of the distal humerus, who underwent plate osteosynthesis using the standard technique. The main group included 112 patients who were operated on using ETTA. The comparison group included 74 patients with a similar type of fracture, who were operated on using chevron olecranon osteotomy. The groups were comparable in terms of age, gender, mechanism of injury, and nature of the fracture. Long-term results were evaluated in 186 patients (minimum follow-up period – 12 months).Results. Comparative analysis revealed that the time of surgery was reduced by an average of 20 minutes (p=0.03) in the main group. The immediate and medium-term results were assessed according to the data of physical examinations, control radiography, dynamics of the increase in the amplitude of motion in the elbow joint. The results were comparable. When assessing complications, the migration of fixators was detected in 5.5% in the main group and 16% in the comparison group. In the comparison group, failure of union of the olecranon after osteotomy, migration of wires with skin perforation, and reactive bursitis were observed.Conclusion. 1. The extended transtriceps approach provides good visualization for fixing fractures of the distal humerus. 2. Evaluation of treatment results confirms that osteosynthesis using this access allows to reduce the time and trauma of the operation, to avoid complications associated with osteotomy of the olecranon, and to carry out successful postoperative rehabilitation, achieving good functional results. Актуальность. Предпочтительным методом лечения для внутрисуставных переломов со смещением является открытая репозиция и внутренняя фиксация. Необходимость получения лучшей визуализации геометрии перелома заставила предложить большое количество новых доступов и их модификаций.Цель. Разработка показаний для расширенного транстрицепитального доступа (РТТД) и определение функциональных результатов при фиксации переломов дистального отдела с использованием данного доступа.Материал и методы. В исследование включены 186 пациентов с внутрисуставным переломом дистального отдела плечевой кости, которым был выполнен остеосинтез пластинами по стандартной методике. В основную группу вошли 112 пациентов, которые были оперированы с использованием РТТД. В группу сравнения вошли 74 пациента с аналогичным типом перелома, которые были оперированы с применением шевронной остеотомии локтевого отростка. Группы были сопоставимы по возрасту, полу, механизму травмы и характеру перелома. Отдаленные результаты были оценены у 186 пациентов (минимальный срок наблюдения — 12 месяцев).Результаты. При сравнительном анализе было выявлено, что длительность оперативного вмешательства сократилось в среднем на 20 минут (р=0,03) в основной группе. Ближайшие и среднесрочные результаты оценивали по данным физикальных осмотров, контрольной рентгенографии, динамике прироста амплитуды движения в локтевом суставе. Результаты были сопоставимы. При оценке осложнений миграция фиксаторов выявлена в 5,5% у основной группы и 16% в группе сравнения. В группе сравнения к осложнениям добавились несращение локтевого отростка после остеотомии, миграция спиц с перфорацией кожи, реактивный бурсит.Выводы. 1. Расширенный транстриципитальный доступ обеспечивает хорошую визуализацию для фиксации переломов дистального отдела плечевой кости. 2. Оценка результатов лечения подтверждает, что остеосинтез с применением этого доступа позволяет сократить время и травматичность операции, избежать осложнений, связанных с остеотомией локтевого отростка, позволяет проводить успешную послеоперационную реабилитацию, достигая хороших функциональных результатов.

Value of minimum intensity projections for chest CT in COVID-19 patients

Purpose: To investigate whether minimum intensity projection (MinIP) reconstructions enable more accurate depiction of pulmonary ground-glass opacity (GGO) compared to standard transverse sections and multiplanar reformat (MPR) series in patients with suspected coronavirus disease 2019 (COVID-19). Method: In this multinational study, chest CT scans of 185 patients were retrospectively analyzed. Diagnostic accuracy, diagnostic confidence, image quality regarding the assessment of GGO, as well as subjective time-efficiency of MinIP and standard MPR series were analyzed based on the assessment of six radiologists. In addition, the suitability for COVID-19 evaluation, image quality regarding GGO and subjective time-efficiency in clinical routine was assessed by five clinicians. Results: The reference standard revealed a total of 149 CT scans with pulmonary GGO. MinIP reconstructions yielded significantly higher sensitivity (99.9 % vs 95.6 %), specificity (95.8 % vs 86.1 %) and accuracy (99.1 % vs 93.8 %) for assessing of GGO compared with standard MPR series. MinIP reconstructions achieved significantly higher ratings by radiologists concerning diagnostic confidence (medians, 5.00 vs 4.00), image quality (medians, 4.00 vs 4.00), contrast between GGO and unaffected lung parenchyma (medians, 5.00 vs 4.00) as well as subjective time-efficiency (medians, 5.00 vs 4.00) compared with MPR-series (all P &lt;.001). Clinicians preferred MinIP reconstructions for COVID-19 assessment (medians, 5.00 vs 3.00), image quality regarding GGO (medians, 5.00 vs 3.00) and subjective time-efficiency in clinical routine (medians, 5.00 vs 3.00). Conclusions: MinIP reconstructions improve the assessment of COVID-19 in chest CT compared to standard images and may be suitable for routine application