The cGMP synthesis and PKG1 expression in murine lymphoid organs

Numerous reports indicate that cyclic 3',5' guanosine monophosphate (cGMP) is involved in the regulation of immune processes. However, the mechanisms responsible for the synthesis of this nucleotide and its signaling pathways in immune cells are still not well recognized. The aim of our studies was to establish: 1) which form of guanylyl cyclase (GC) synthesizes cGMP in murine lymphoid organs and 2) whether the same organs express the isoforms PKG1alpha and/or PKG1beta of protein kinase G, known as possible target for synthesized cGMP. Cells isolated from thymus, lymph nodes, and spleen were treated with activators (SNP, ANP, CNP, STa) of soluble or particulate cyclases. Sodium nitroprusside (SNP) elevated intracellular cGMP 2-fold in thymic and lymph node cells and about 10-fold in spleen cells. Atrial natriuretic peptide (ANP) caused modest but statistically significant increases of cGMP in cells of all three organs. Additionally, spleen cells elevated their cGMP content about 2-fold in response to C-type natriuretic protein (CNP). In cellular homogenates of the all analyzed organs, the antibody anti-PKG1beta stained the 78 kDa band corresponding to the molecular mass of PKG1. Only homogenates of spleen cells were stained by the antibody recognizing PKG1alpha. Our results indicate that in the investigated organs cGMP may be synthesized mainly by soluble GC in response to nitric oxide. The modest increase of cGMP upon stimulation by ANP suggests that in all these organs either exists only a small subpopulation of cells that express particulate cyclase GC-A or GC-A is expressed at very low level. In spleen cells, however, cyclase GC-B appears to be the more active enzyme. Elevated cGMP concentration may in turn activate PKG1beta in thymus, lymph node, and spleen cells and also PKG1alpha in spleen cells.     

Silent cerebral infarction,income, and grade retention among students with sickle cell anemia

Children with sickle cell anemia have a higher‐than‐expected prevalence of poor educational attainment. We test two key hypotheses about educational attainment among students with sickle cell anemia, as measured by grade retention and use of special education services: (1) lower household per capita income is associated with lower educational attainment; (2) the presence of a silent cerebral infarct is associated with lower educational attainment. We conducted a multicenter, cross‐sectional study of cases from 22 U.S. sites included in the Silent Infarct Transfusion Trial. During screening, parents completed a questionnaire that included sociodemographic information and details of their child's academic status. Of 835 students, 670 were evaluable; 536 had data on all covariates and were used for analysis. The students' mean age was 9.4 years (range: 5–15) with 52.2% male; 17.5% of students were retained one grade level and 18.3% received special education services. A multiple variable logistic regression model identified that lower household per capita income (odds ratio [OR] of quartile 1 = 6.36, OR of quartile 2 = 4.7, OR of quartile 3 = 3.87; P = 0.001 for linear trend), age (OR = 1.3; P < 0.001), and male gender (OR, 2.2; P = 0.001) were associated with grade retention; silent cerebral infarct (P = 0.31) and painful episodes (P = 0.60) were not. Among students with sickle cell anemia, household per capita income is associated with grade retention, whereas the presence of a silent cerebral infarct is not. Future educational interventions will need to address both the medical and socioeconomic issues that affect students with sickle cell anemia. Am. J. Hematol. 89:E188–E192, 2014. © 2014 Wiley Periodicals, Inc.     

Solvent effects on free-radical polymerization, 5. Analysis of homopolymerization rate on the basis of the reactant-solvent complex model

The rate of polymerization was described as a function of the monomer concentration of 36 monomer/solvent systems in terms of the reactant-solvent complex (RSC) model. One-, two-and three-parameter optimization procedures were used to fit the rate function to experimental data. Fitting increments were the complex equilibrium constant K and the relative monomer reactivity parameter r₁₁. Irrespective of the optimization procedure, K and r₁₁, were found to correlate with the monomer exponent n and to be K = 0 and r₁₁, = 1 at n = 1. In these cases the RSC model reduces to the classical rate model. Despite the weak character of the monomer (radical)/solvent complexation, this interaction should not be neglected in rate modelling. The RSC model is a convenient tool to describe the chain propagation separately.     

An ultrasonographic monitoring of skin condition in patients receiving radiotherapy for head and neck cancers

Radiodermatitis is one of the commonest side effects of radiotherapy. They are usually assessed by semi‐quantitative clinical scores, which are not validated and may be subject to inter‐observer variability. A few previous studies suggested that high‐frequency ultrasonography (HF‐USG) is useful in the assessment of the acute phase of radiation dermatitis in breast cancer patients. (a) To monitor skin changes by HF‐USG during the course of radiotherapy due to head and neck cancers, and (b) to determine whether there is any connection between skin sonograms and the skin scoring criteria. This prospective, observational study includes patients diagnosed with head and neck cancers, treated with radiotherapy or concomitant chemoradiation. The final analysis includes six patients. In every patient, the HF‐USG as well as dermatological assessment (target lesion score—TLS and CACE v. 4.0) were performed 4×: before, in the middle, day after, and 3 months after radiotherapy. There were significant differences between non‐irradiated skin thickness and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P < .0001), as well as between irradiated, unchanged skin thickness (TLS grade 0) and thickness of skin with clinically obvious radiodermatitis (TLS grade 1‐4; P = .0002). There was no significant difference between non‐irradiated and irradiated, unchanged skin thickness (TLS grade 0; P = .9318). In four patients, we demonstrated subepidermal low echogenic band (SLEB). HF‐USG can be useful tool to noninvasive and objective assessment of skin changes during radiotherapy.     

Total left main coronary artery occlusion in a female patient after AVSD surgical repair in childhood as a cause of non ST elevation myocardial infarction

A case of a 51-year-old woman with symptoms of non-ST-segment elevation acute coronary syndrome and concomitant atrial flutter is presented. Patient underwent atrioventricular septal defect repair in childhood. Coronary angiography showed total occlusion of left main coronary artery and massive collateral network originating from right coronary artery supplying entire left coronary artery. Ablation of atrial flutter had been performed and patient was subsequently submitted to mitral valve replacement, tricuspid valvuloplasty and coronary artery bypass grafting. The potential causes of left main occlusion are in this case discussed.     

All near-infrared multiparametric luminescence thermometry using Er3+, Yb3+-doped YAG nanoparticles

This paper presents four new temperature readout approaches to luminescence nanothermometry in spectral regions of biological transparency demonstrated on Yb³⁺/Er³⁺-doped yttrium aluminum garnet nanoparticles. Under the 10 638 cm⁻¹ excitation, down-shifting near infrared emissions (>10 000 cm⁻¹) are identified as those originating from Yb³⁺ ions'' ²F_5/2 → ²F_7/2 (∼9709 cm⁻¹) and Er³⁺ ions'' ⁴I_13/2 → ⁴I_15/2 (∼6494 cm⁻¹) electronic transitions and used for 4 conceptually different luminescence thermometry approaches. Observed variations in luminescence parameters with temperature offered an exceptional base for studying multiparametric temperature readouts. These include the temperature-dependence of: (i) intensity ratio between emissions from Stark components of Er^{3+ 4}I_13/2 level; (ii) intensity ratio between emissions of Yb³⁺ (²F_5/2 → ²F_7/2 transition) and Er³⁺ (⁴I_13/2 → ⁴I_15/2 transition); (iii) band shift and bandwidth and (iv) lifetime of the Yb³⁺ emission (²F_5/2 → ²F_7/2 transition) with maximal sensitivities of 1% K⁻¹, 0.8% K⁻¹, 0.09 cm⁻¹ K⁻¹, 0.46% K⁻¹ and 0.86% K⁻¹, respectively. The multimodal temperature readout provided by this material enables its application in different luminescence thermometry setups as well as improved the reliability of the temperature sensing by the cross-validation between measurements.

Four completely new NIR luminescence temperature readouts in the second and third biological windows are demonstrated with YAG:Er³⁺, Yb³⁺ nanoparticles.     

Non‐invasive left ventricular myocardial work indices in healthy adolescents at rest

Global myocardial work (GMW) provides a metric of left ventricular (LV) function and energy consumption. Its non-invasive assessment by echocardiography correlates with invasive measures and normal values have been reported in healthy adults. We aimed to establish normal values in a healthy adolescent population. Fifty-two healthy adolescents (mean age?=?14.5?±?2.0 years, range 11–19 years, 62% male) with normal echocardiograms were included. Brachial cuff blood pressure was obtained immediately following apical imaging in the supine position. Post-processing of echocardiograms for speckle tracking strain measurement and derivation of global myocardial work indices from LV pressure–strain loops was performed. The mean global work index (GWI) was 1802.0?±?264.4 mmHg% with mean global work efficiency of 95.5?±?1.1%. The mean global constructive work (GCW) was 2054.5?±?297.3 mmHg%, and the mean global wasted work 83.8?±?28.1 mmHg%. On multivariable analysis, there were significant associations between both GWI and GCW with systolic blood pressure (β coefficient?=?0.57, p?<?0.001; β coefficient?=?0.67, p?<?0.001 respectively) and LV global longitudinal strain (GLS) (β coefficient = ? 0.56, p?<?0.001; β coefficient = ? 0.52, p?<?0.001 respectively). There were no associations with any of the work indices with age, sex, body surface area, heart rate or LV ejection fraction. This study provides echocardiographic reference ranges for non-invasive indices of GMW in normal adolescents.

     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.     

Dynamic changes in specific anti-L-asparaginase antibodies generation during acute lymphoblastic leukemia treatment

Background

L-asparaginase (L-asp) remains one of the key components of acute lymphoblastic leukemia therapy. Immune reactions to the drug are associated with its diminished activity. The aim of the study was to determine the level of IgM, IgG and IgE-class anti-L-asp antibodies during the induction and reinduction phases of acute lymphoblastic leukemia therapy and their influence on L-asp activity.