Regulation of neurotransmission in the arcuate nucleus of the rat by different neuropeptide Y receptors.
We examined the effects of peptides of the neuropeptide Y (NPY)/pancreatic polypeptide (PP) family on synaptic transmission in the arcuate nucleus in rat hypothalamic slices. Application of NPY produced two effects. In some cells NPY produced an outward current that had the properties of a K+ current. NPY also inhibited the evoked glutamatergic EPSC recorded in these arcuate neurons by a presynaptic mechanism. Although the effects of NPY on the K+ current reversed within a few minutes of washout of the peptide, its effects on the EPSC frequently were longer lasting (>30 min). Similar effects were observed using peptide YY or the NPY analog [Leu31, Pro34]NPY. Although K+ current activation by [Leu31,Pro34]NPY was blocked by the selective Y1 antagonist BIBP 3226, inhibition of the EPSC was blocked only partially. Other NPY-related peptides such as NPY(13-36), PP, and [D-Trp32]NPY also inhibited the EPSC. However, none of these peptides produced activation of the K+ current. Thus, activation of more than one NPY receptor produces synaptic inhibition in the arcuate nucleus. A Y1 receptor activates a K+ current postsynaptically, and several receptor types appear to inhibit the EPSC by a presynaptic mechanism.


Ontogenesis of learning: II. Variation in the rat's reflexive and learned responses to acoustic stimulation.
The ontogenesis of the rat's reflexive and simple learned reactions to acoustic stimulation was investigated in five experiments. The pattern of results suggests that (a) reflexive reactions to tonal stimulation emerge earlier in ontogenesis than the capacity to learn about these stimuli, and (b) the age at which simple Pavlovian conditioning is first observed depends on the nature of the acoustic conditioned stimulus (CS). Specifically, these data suggest that pups are not capable of simple Pavlovian conditioning to a 2000-Hz tone (CS) paired with an oral infusion of sucrose (US) until they are 14-15 days old. The same acoustic stimulus will, however, evoke reflexive reactions (startle inspiration) in pups as young as 10-12 days old. Additionally, when a different auditory stimulus (an intermittent train of clicks) serves as the CS, there is evidence of conditioning in pups only 12-13 days old. It is suggested that these age-related dissociations in the emergence of reflexive and simple learned responses to sound reflect a caudal-to-rostral maturational sequence of the components of the ascending auditory system.


Moderate irrigation intervals facilitate establishment of two desert shrubs in the Taklimakan Desert Highway Shelterbelt in China.
Water influences various physiological and ecological processes of plants in different ecosystems, especially in desert ecosystems. The purpose of this study is to investigate the response of physiological and morphological acclimation of two shrubs Haloxylon ammodendron and Calligonum mongolicunl to variations in irrigation intervals. The irrigation frequency was set as 1-, 2-, 4-, 8- and 12-week intervals respectively from March to October during 2012-2014 to investigate the response of physiological and morphological acclimation of two desert shrubs Haloxylon ammodendron and Calligonum mongolicunl to variations in the irrigation system. The irrigation interval significantly affected the individual-scale carbon acquisition and biomass allocation pattern of both species. Under good water conditions (1- and 2-week intervals), carbon assimilation was significantly higher than other treatments; while, under water shortage conditions (8- and 12-week intervals), there was much defoliation; and under moderate irrigation intervals (4 weeks), the assimilative organs grew gently with almost no defoliation occurring. Both studied species maintained similar ecophysiologically adaptive strategies, while C. mongolicunl was more sensitive to drought stress because of its shallow root system and preferential belowground allocation of resources. A moderate irrigation interval of 4 weeks was a suitable pattern for both plants since it not only saved water but also met the water demands of the plants.


Isolation and partial characterization of culturable endophytic Arthrobacter spp. from leaves of maize (Zea mays L.).
The presence and diversity of the endophytic Arthrobacter species are relatively uninvestigated. We determined the genotypic and physiological diversity of the endophytic Arthrobacter spp. isolated from the interior leaf tissues of four out of six maize cultivars tested, all of which were collected under field conditions. Strains A7 and A9 isolated from Król cultivar and strain A23 isolated from KB1902 cultivar were identified as A. nicotinovorans. Strains A18, A22 and A34 identified as A. nitroguajacolicus were isolated from KB1903, KB1902 and Cyrkon cultivars respectively. Isolated strains tolerate the presence of o-coumaric, p-coumaric, chlorogenic, and ferulic acids in a concentration of at least two times higher than naturally occurring in maize tissue. The presence of the nitrogenase reductase gene nifH, a marker of biological nitrogen fixation, was determined in only two strains of A. nitroguajacolicus A18 and A34. None of the tested strains released compounds inhibiting in vitro the growth of the fungi Fusarium moniliforme and F. graminearum, pathogenic to maize. Seed inoculations with the A. nicotinovorans strain A7 suppressed the development of seedlings of four maize cultivars, which were not colonized by this species of bacteria, but stimulated the development of seedlings of the host-cultivar Król. Also, the A. nitroguajacolicus strain A18, which was applied as seed treatment, suppressed the development of seedlings of three maize cultivars, which were not colonized by this species of bacteria. The occurrence of endophytic A. nicotinovorans and A. nitroguajacolicus inhabiting interior tissues of maize leaves of specific maize cultivars is a first report in literature.


Targeted Temperature Management: Effects of Initial Protocol Implementation on Patient Outcomes.
Targeted temperature management (TTM) is a strategy used by critical care nurses to mitigate negative effects of out-of-hospital cardiac arrest (OHCA); however, integration and compliance of TTM protocols into routine clinical practice can be challenging. The aims of this study are to (1) investigate the effects of initial TTM protocol implementation on patient mortality, length of stay, and discharge disposition among patients who experience OHCA and (2) evaluate initial compliance and potential barriers to newly implemented TTM protocol. A retrospective cohort design was used. Data were gathered on adult patients experiencing OHCA before and after immediate implementation of a TTM protocol within a large academic public hospital. Demographic and clinical data were abstracted from medical records of both TTM and non-TTM groups. Additional compliance data were gathered on the TTM group. Outcome variables included hospital mortality, length of stay, and discharge disposition. Total accrual was 259. Mortality decreased after protocol implementation (89.4%, 75%, P < .05), which was supported in the regression analyses (P = .05; odds ratio, 2.8). A higher proportion of subjects were discharged home after the TTM protocol (21.5% discharged home after protocol implementation vs 5.1% discharged home before protocol implementation; P < .05). Full protocol compliance was 30%. Protocol documentation was inconsistent across units and personnel. Findings suggest that even initial implementation of TTM protocols can result in positive patient outcomes. Full compliance with protocols remains difficult. Critical care nurses are integral to initiation of and adherence to therapeutic hypothermia protocols and are in a key position to develop strategies for improved compliance across departments.


Exploration of the Clinical Value and Significance of Body Mass Index, Mean Platelet Volume, and Left Atrial Structural Changes in Recurrence after Radiofrequency Ablation of Atrial Fibrillation.
This study aimed to analyze the clinical significance of body mass index (BMI), mean platelet volume (MPV), and left atrial structure in the recurrence of atrial fibrillation (AF) after treatment with catheter radiofrequency ablation. A total of 69 patients with AF who underwent catheter radiofrequency ablation at Beijing Anzhen Hospital from January 2020 to July 2021 (research group) were compared to 75 patients who underwent physical examination during the same period (control group). MPV levels were measured before and after treatment in both groups. Additionally, height and weight measurements were used to calculate BMI, while left atrial anteroposterior diameter, left atrial volume, and left atrial volume index were recorded using cardiac ultrasonography. The research group exhibited higher BMI, MPV, left atrial anteroposterior diameter, left atrial volume, and left atrial volume index compared to the control group, and these parameters decreased after treatment (P < .05). Prognostic follow-up revealed that patients with AF recurrence had higher values for these parameters than those without recurrence (P < .05). Receiver Operating Characteristic analysis indicated that all these parameters had good predictive value for prognostic recurrence of AF (P < .05). Logistic regression analysis demonstrated that all the parameters were independent risk factors for prognostic atrial fibrillation recurrence (P < .05). BMI, MPV, and left atrial structure are associated with the occurrence and development of atrial fibrillation. These parameters provide an excellent assessment of the prognosis for AF recurrence after catheter radiofrequency ablation treatment. Monitoring changes in BMI, MPV, and left atrial structure in atrial fibrillation patients can contribute to more reliable prognostic information in clinical settings.


[Application of Cocktail Probe Drugs for Detecting Influences of Raw and Processed Phellodendri Cortex on Cytochrome P450 Isoforms].
To research and compare the influences of raw and processed Phellodendri Cortex on the cytochrome P450 four isoforms by Cocktail probe drugs, and to explore the processing principle of Phellodendri Cortex. SD rats were randomly divided into raw group,processed with rice-wine group, processed with salt-water group and blank control group, which were given raw decoction, processed with rice-wine decoction, processed with salt-water decoction (3.24 g/kg) and normal saline respectively for one week, then given the mixture of four probe drugs on the 8th day, and soon after the blood samples were obtained through the orbits at a series of time-points. HPLC method was used to determine the concentrations of probe drugs in rat plasma, and pharmacokinetic parameters were estimated by DAS3.0. The effect of raw and processed Phellodendri Cortex on cytochrome P450 were judged indirectly by the pharmacokinetic parameters. Compared with the blank control group, the t½ significantly increased of theophylline in raw and processed with salt-water group. The CL/F significantly decreased and AUC(0-t) AUC(0-∞). significantly increased of theophylline in raw and processed with rice-wine groups. The t(½) AUC(0-∞) and AUC(0-∞) significantly decreased and CL/F significantly increased of dapsone in raw, processed with rice-wine and processed with salt-water group. The AUC(0-t) significantly increased of chlorzoxazone in raw and processed with salt-water group. The t(½), AUC(0-∞). and AUC(0-t) significantly decreased and CL/F significantly increased of chlorzoxazone in processed with rice-wine group. The AUC(0-t), significantly decreased of tolbutamide in raw, processed with rice-wine and processed with salt-water groups. The raw Phellodendri Cortex can inhibit CYP1A2, induce CYP3 A4 and also is need to make a further research work on CYP2C9 and CYP2E1. Meanwhile, it also can change the activities of cytochrome P450 after processed with rice-wine and salt-water. The Phellodendri Cortex processed with rice-wine can reduce the inhibitory effect of CYP1A2 and enhance induction of CYP3A4, it provides reference and basis to make an interpretation about Phellodendri Cortex processed with rice-wine.


Experience with a large-frame, disposable external fixator.
External fixation is a temporizing measure that has a long history in the treatment of fractures. Thirty-eight newly designed large-frame external fixators were applied for acute lower-limb fractures and pelvis injuries in a level I trauma center. In 75% of cases, the frames were used for first-stage skeletal stabilization, followed by revision to plates or nails 1 to 2 weeks later. The external fixators remained in place from 4 to 28 days (median, 8 days). The fixator is composed of a low-cost plastic resin and uses modular, disposable components. The montage requires only 2 varieties of clamp, monotube rods, and fixation pins already in-house. The device is lighter than conventional fixators yet equal in rigidity. Cost analysis performed by our institution demonstrated cost savings of 20% to 25% compared to conventional external fixation. The new device is packaged sterilely and does not require autoclaving before application. Patient acceptance of the device was good. There were no complications or disadvantages associated with the use of this lower-cost device. Specifically, there were no pin tract infections, no loss of fixation, and no loosening or disassembly of the devices.


Proteome-wide Identification of Glycosylation-dependent Interactors of Galectin-1 and Galectin-3 on Mesenchymal Retinal Pigment Epithelial (RPE) Cells.
Identification of interactors is a major goal in cell biology. Not only protein-protein but also protein-carbohydrate interactions are of high relevance for signal transduction in biological systems. Here, we aim to identify novel interacting binding partners for the β-galactoside-binding proteins galectin-1 (Gal-1) and galectin-3 (Gal-3) relevant in the context of the eye disease proliferative vitreoretinopathy (PVR). PVR is one of the most common failures after retinal detachment surgeries and is characterized by the migration, adhesion, and epithelial-to-mesenchymal transition of retinal pigment epithelial cells (RPE) and the subsequent formation of sub- and epiretinal fibrocellular membranes. Gal-1 and Gal-3 bind in a dose- and carbohydrate-dependent manner to mesenchymal RPE cells and inhibit cellular processes like attachment and spreading. Yet knowledge about glycan-dependent interactors of Gal-1 and Gal-3 on RPE cells is very limited, although this is a prerequisite for unraveling the influence of galectins on distinct cellular processes in RPE cells. We identify here 131 Gal-3 and 15 Gal-1 interactors by galectin pulldown experiments combined with quantitative proteomics. They mainly play a role in multiple binding processes and are mostly membrane proteins. We focused on two novel identified interactors of Gal-1 and Gal-3 in the context of PVR: the low-density lipoprotein receptor LRP1 and the platelet-derived growth factor receptor β PDGFRB. Addition of exogenous Gal-1 and Gal-3 induced cross-linking with LRP1/PDGFRB and integrin-β1 (ITGB1) on the cell surface of human RPE cells and induced ERK/MAPK and Akt signaling. Treatment with kifunensine, an inhibitor of complex-type N-glycosylation, weakened the binding of Gal-1 and Gal-3 to these interactors and prevented lattice formation. In conclusion, the identified specific glycoprotein ligands shed light into the highly specific binding of galectins to dedifferentiated RPE cells and the resulting prevention of PVR-associated cellular events.


Incidence of cystoid macular edema after Descemet's stripping automated endothelial keratoplasty.
To determine the incidence of cystoid macular edema (CME) after Descemet's stripping automated endothelial keratoplasty (DSAEK). This study included all consecutive patients operated in a Spanish tertiary reference hospital over a period of four years. A total of 55 eyes from 47 patients matched the selection criteria. CME was diagnosed clinically at the slit-lamp and confirmed by optical coherence tomography. Six cases of CME were diagnosed postoperatively, which represented an incidence of 11%. Three patients had previously undergone DSAEK alone (7%; 3/41) and the other three, DSAEK combined with phacoemulsification (21%; 3/14). Five out of six patients with CME responded to standard therapy. CME is a possible complication after DSAEK and can be treated with standard therapy. CME appears more frequently when DSAEK is combined with phacoemulsification and posterior chamber (PC) intraocular lens (IOL) implantation. Intraoperative damage to the corneal endothelial cells might play a role in the pathogenesis of CME. As long as the causes remain unclear, we recommend administering prophylaxis when risk factors are present or when combined surgery is planned.


Vessel-Sealing Capability of Novel Microwave Sealer: Experimental Study in Animal Models.
Background. Ultrasonically activated dissectors (UADs) and radiofrequency-based devices have been considered excellent surgical devices because of their reliability and flexibility. Meanwhile, microwave-based devices have demonstrated potential with their unique heating mechanism. This study aims to compare the sealing function of a newly invented forceps-like microwave sealer (MS) with that of currently available UADs. Materials and Methods. MS and 2 examples of UADs (Harmonic Focus+ [HF+] and Sonicision [SNC]) were employed to perform mesenterectomies (in vivo) and sealing sizable vessels (ex vivo). Vessel diameter, seal time, burst pressure (BP), sealing completion, and instrument sticking were recorded. The samples underwent histological investigation for thermal damage evaluation. Results. During mesenterectomies, MS required 3 seconds and 30 W to secure a complete seal. The BP achieved by the MS seal was higher than that of HF+ and SNC on arteries (851 ± 203.7 vs 682.4 ± 287.3, P < .05; vs 833.1 ± 251.2 mmHg, P = .4523, respectively) but was not statistically different on veins (324.9 ± 203.5 vs 460.1 ± 320.3 vs 508.3 ± 350.7 mmHg, P = .215). In all trials, MS caused less sticking but exhibited similar heat-induced alterations to UADs. MS's thermal spread was not statistically more extended than that of UADs on either arteries or veins. Conclusions. MS was capable of not only sealing tiny vessels but also achieving high-pressure endurance on sizable vessels. Its forceful grasping and synchronous heating process helped create solid stumps with an acceptable thermal spread.


Effects of interleukin-2 on pulmonary and systemic transvascular fluid filtration.
Interleukin-2 (IL-2) therapy for patients with advanced cancer may be compromised by dose-limiting and life-threatening pulmonary and systemic edema. We studied the effects of bolus IL-2 infusion on lung and soft-tissue transvascular fluid and protein filtration in six sheep with chronic lung and soft-tissue lymphatic cannulation. Changes in lung (QL) and soft-tissue (QS) lymph flow were used as indicators of transvascular fluid filtration. A dose of 100,000 U/kg IL-2 was administered every 8 hours for 3 days. A significant increase (p less than or equal to 0.05) in both QL and QS was observed after each IL-2 infusion, with maximal flow occurring 2 to 3 hours after infusion. After 72 hours of IL-2 infusion, a fourfold maximal increase in QL occurred, which recovered to near-baseline values within 24 hours. Elevations in QL and QS were not associated with increases in pulmonary arterial or pulmonary arterial wedge pressures, but these elevations were associated with significant (p less than or equal to 0.05) increases in cardiac output (7.7 +/- 0.5 to 11.4 +/- 0.4 L/min) and a consistent decrease in systemic vascular resistance. A significant increase in lung lymph/plasma protein ratio (0.49 +/- 0.06 to 0.93 +/- 0.04 for albumin) revealed a marked increase in pulmonary microvascular porosity. This change, however, was not observed in the systemic microcirculation. Serum concentrations of tumor necrosis factor did not increase with the observed changes in pulmonary microvascular porosity. We conclude that IL-2 increases both pulmonary and systemic microvascular fluid flux. In addition, there is a marked increase in pulmonary, but not systemic, protein permeability that is not a consequence of changes mediated by tumor necrosis factor.


Non-stimulated, agonist-stimulated and store-operated Ca2+ influx in MDA-MB-468 breast cancer cells and the effect of EGF-induced EMT on calcium entry.
In addition to their well-defined roles in replenishing depleted endoplasmic reticulum (ER) Ca(2+) reserves, molecular components of the store-operated Ca(2+) entry pathway regulate breast cancer metastasis. A process implicated in cancer metastasis that describes the conversion to a more invasive phenotype is epithelial-mesenchymal transition (EMT). In this study we show that EGF-induced EMT in MDA-MB-468 breast cancer cells is associated with a reduction in agonist-stimulated and store-operated Ca(2+) influx, and that MDA-MB-468 cells prior to EMT induction have a high level of non-stimulated Ca(2+) influx. The potential roles for specific Ca(2+) channels in these pathways were assessed by siRNA-mediated silencing of ORAI1 and transient receptor potential canonical type 1 (TRPC1) channels in MDA-MB-468 breast cancer cells. Non-stimulated, agonist-stimulated and store-operated Ca(2+) influx were significantly inhibited with ORAI1 silencing. TRPC1 knockdown attenuated non-stimulated Ca(2+) influx in a manner dependent on Ca(2+) influx via ORAI1. TRPC1 silencing was also associated with reduced ERK1/2 phosphorylation and changes in the rate of Ca(2+) release from the ER associated with the inhibition of the sarco/endoplasmic reticulum Ca(2+)-ATPase (time to peak [Ca(2+)](CYT) = 188.7 ± 34.6 s (TRPC1 siRNA) versus 124.0 ± 9.5 s (non-targeting siRNA); P<0.05). These studies indicate that EMT in MDA-MB-468 breast cancer cells is associated with a pronounced remodeling of Ca(2+) influx, which may be due to altered ORAI1 and/or TRPC1 channel function. Our findings also suggest that TRPC1 channels in MDA-MB-468 cells contribute to ORAI1-mediated Ca(2+) influx in non-stimulated cells.


The effect of hearing loss on identification of asynchronous double vowels.
This study determined whether listeners with hearing loss received reduced benefits due to an onset asynchrony between sounds. Seven normal-hearing listeners and 7 listeners with hearing impairment (HI) were presented with 2 synthetic, steady-state vowels. One vowel (the late-arriving vowel) was 250 ms in duration, and the other (the early-arriving vowel) varied in duration between 350 and 550 ms. The vowels had simultaneous offsets, and therefore an onset asynchrony between the 2 vowels ranged between 100 and 300 ms. The early-arriving and late-arriving vowels also had either the same or different fundamental frequencies. Increases in onset asynchrony and differences in fundamental frequency led to better vowel-identification performance for both groups, with listeners with HI benefiting less from onset asynchrony than normal-hearing listeners. The presence of fundamental frequency differences did not influence the benefit received from onset asynchrony for either group. Excitation pattern modeling indicated that the reduced benefit received from onset asynchrony was not easily predicted by the reduced audibility of the vowel sounds for listeners with HI. Therefore, suprathreshold factors such as loss of the cochlear nonlinearity, reduced temporal integration, and the perception of vowel dominance probably play a greater role in the reduced benefit received from onset asynchrony in listeners with HI.


[Study of dual ("joker") function of glucose in cancer patients].
A relationship was studied between generation of glucose-induced reactive oxygen species capable of causing damage to DNA (genotoxic or G-effect) and insulin secretion (endocrine or hormonal effect - H-effect) in primary menopausal patients with endomrnetrial carcinoma (EC) (32) or colonic cancer (CC) (16). The study group was compared with healthy menopausal women (25) and patients with an impaired glucose tolerance (IGT) (21). Besides, we examined 32 menopausal patients (CC--6 and EC--26) more than 12 months after surgery. The following basic patterns were established: (1) H-effect was reported in EC-1 and 1GT groups nmore often than in healthy peers and those with EC-2: (2) G-effect tended to prevail in CC patients and those with EC-2 and in patients with EC-1 twelve months after operation; (3) G-effect occurred more often in primary EC patients, particularly, those with EC-2 (71%) and IGT (58%) (as compared with CC patients (33%) and healthy females (p < or = 0.001). It is suggested that a comparison of the two effects might provide a criterion for use of relevant means of prevention of certain malignancies or correction of disorders in cancer patients following radical treatment.


CDX2 upregulates SLC26A3 gene expression in intestinal epithelial cells.
SLC26A3 [downregulated in adenoma (DRA)] plays a key role in mammalian intestinal NaCl absorption, in that it mediates apical membrane Cl-/[Formula: see text] exchange. DRA function and expression are significantly decreased in diarrhea associated with inflammatory bowel disease. DRA is also considered to be a marker of cellular differentiation and is predominantly expressed in differentiated epithelial cells. Caudal-type homeobox protein-2 (CDX2) is known to regulate genes involved in intestinal epithelial differentiation and proliferation. Reduced expression of both DRA and CDX2 in intestinal inflammation prompted us to study whether the DRA gene is directly regulated by CDX2. Our initial studies utilizing CDX2 knockout (CDX2fV/fV;Cre+) mice showed a marked reduction in DRA mRNA and protein levels in proximal and distal colon. In silico analysis of the DRA promoter showed two consensus sites for CDX2 binding. Therefore, we utilized Caco-2 cells as an in vitro model to examine if DRA is a direct target of CDX2 regulation. siRNA-mediated silencing of CDX2 in Caco-2 cells resulted in a marked (~50%) decrease in DRA mRNA and protein levels, whereas ectopic overexpression of CDX2 upregulated DRA expression and also stimulated DRA promoter activity, suggesting transcriptional regulation. Electrophoretic mobility shift and chromatin immunoprecipitation assays demonstrated direct binding of CDX2 to one of the two putative CDX2 binding sites in the DRA promoter (+645/+663). In summary, our studies, for the first time, demonstrate transcriptional regulation of DRA expression by CDX2, implying that reduced expression of DRA in inflammatory bowel disease-associated diarrhea may, in part, be due to downregulation of CDX2 in the inflamed mucosa.NEW & NOTEWORTHY SLC26A3 [downregulated in adenoma (DRA)] mediates intestinal luminal NaCl absorption and is downregulated in inflammatory bowel disease-associated diarrhea. Since both DRA and caudal-type homeobox protein-2 (CDX2) are reduced in intestinal inflammation and the DRA promoter harbors CDX2 binding sites, we examined whether the DRA gene is regulated by CDX2. Our studies, for the first time, demonstrate transcriptional regulation of DRA expression by CDX2 via direct binding to the DRA promoter, suggesting that reduced expression of DRA in inflammatory bowel disease-associated diarrhea could, in part, be attributed to downregulation of CDX2.


[Phenotype Pi and alpha 1 antitrypsin deficiency in types A and B chronic obstructive bronchopneumopathies].
The authors studied 79 patients with chronic obstructive lung disease. (COLD) (FEV1/VC less than 70%). Patients with chronic asthma were excluded from the series. These patients with COLD were divided up into 2 groups, depending on radiological and clinical criteria: (1) Type A, primary emphysema, 24 patients; (2) Type B, chronic bronchitis, 49 patients. 6 patients of type X (intermediate type) were excluded. Their respiratory function tests were studied together with clinical and radiological findings and blood gases. Furthermore, were studied in each patient, the antitrypsic activity and the serum concentrations of alpha-1-antitrypsin and phenotype Pi. Group A were, on average, more obstructive than group B. The ratio FEV1/VC was 31% +/- 7% in group A, against 46% +/- 13% in group B. The serum antitrypsin activity and the serum concentration in alpha-1-AT were on average close to normal in both groups. However, group A was divided up into two populations: a small population with a low concentration of alpha-1-AT, and a large population with normal alpha-1-AT. A study of the incidence of various phenotypes in groups A and B showed a significantly higher frequency of phenotype ZZ in group A (12.5%) than in group B (10%). All ZZ subjects were of clinical type A. There was no significant difference in the incidence of other phenotypes encountered. Serum alpha-1-antitrypsin concentration was very low in 3 ZZ patients. One case with phenotype SZ and one MM showed intermediate levels. The authors emphasize the low percentage of cases of pulmonary emphysema which may be explained by an alpha-1-antitrypsin deficiency. Nevertheless, this preliminary report should be completed by a study of a larger sample of patients with COLD with control of the phenotype.


Increased Expression of QPRT in Breast Cancer Infers a Poor Prognosis and Is Correlated to Immunocytes Infiltration.
Breast cancer (BRCA) is a class of highly heterogeneous tumors. There is a positive correlation between the overall survival of BRCA and immune infiltration of the tumor microenvironment. QPRT is a rarely reported cancer gene, and the underlying mechanism is poorly understood. Based on TCGA data, the role that QPRT plays in BRCA is evaluated in this study. This study used GEPIA to analyze the expression of QPRT in BRCA and, based on the survival module, assessed the impact of QPRT on the survival of patients with BRCA. Furthermore, this study collected the BRCA data set from TCGA and, through utilizing logistic regression, discussed the relationship between QPRT expression and clinical information. Cox regression analysis was used to obtain clinicopathological features relating to the total survival rate of patients with TCGA. Besides, based on the "correlation" and CIBERSORT module, the relationship between cancer immune infiltration and QPRT was analyzed in GEPIA. Tumor status, pathological staging, and lymph nodes have an obvious correlation with the rise of QPRT expression according to the logistic regression univariate analysis. In this analysis, QPRT is expressed as a categorical-dependent variable (median expression value is 2.5). Furthermore, based on multivariate analysis, independent factors for favorable prognosis include negative pathological stage, increased QPRT expression, and remote metastasis. Among them, CIBERSORT analysis found that the increase in QPRT expression will increase with the growth of the level of immune infiltration of neutrophils, B cells, T cells, and mast cells. In addition, the "correlation" module using GEPIA was used to confirm. Taking all factors into consideration, the rise in QPRT expression is related to a good prognosis and a grown proportion of immune cells in BRCA, such as neutrophils, B cells, mast cells, and T cells. These results suggest that QPRT can be used to be a possible biological indicator to evaluate the immune infiltration level of BRCA and its prognosis.


Facilitated dissociation of transcription factors from single DNA binding sites.
The binding of transcription factors (TFs) to DNA controls most aspects of cellular function, making the understanding of their binding kinetics imperative. The standard description of bimolecular interactions posits that TF off rates are independent of TF concentration in solution. However, recent observations have revealed that proteins in solution can accelerate the dissociation of DNA-bound proteins. To study the molecular basis of facilitated dissociation (FD), we have used single-molecule imaging to measure dissociation kinetics of Fis, a key Escherichia coli TF and major bacterial nucleoid protein, from single dsDNA binding sites. We observe a strong FD effect characterized by an exchange rate [Formula: see text], establishing that FD of Fis occurs at the single-binding site level, and we find that the off rate saturates at large Fis concentrations in solution. Although spontaneous (i.e., competitor-free) dissociation shows a strong salt dependence, we find that FD depends only weakly on salt. These results are quantitatively explained by a model in which partially dissociated bound proteins are susceptible to invasion by competitor proteins in solution. We also report FD of NHP6A, a yeast TF with structure that differs significantly from Fis. We further perform molecular dynamics simulations, which indicate that FD can occur for molecules that interact far more weakly than those that we have studied. Taken together, our results indicate that FD is a general mechanism assisting in the local removal of TFs from their binding sites and does not necessarily require cooperativity, clustering, or binding site overlap.


Adenocarcinoma of the gallbladder associated with congenital choledochal cyst and anomalous pancreaticobiliary ductal junction. Case report.
In a 61-year-old woman, villous adenocarcinoma of the gallbladder was associated with a congenital choledochal cyst and anomalous pancreaticobiliary ductal junction. The patient had a history of congenital choledochal cyst treated by cystoduodenostomy 27 years previously. The condition was demonstrated by intraoperative cholangiography and histologically confirmed. Extended cholecystectomy, regional lymph node dissection, excision of the cyst and hepaticojejunostomy were performed successfully.


Hydration and ion pair formation in aqueous Y(3+)-salt solutions.
Raman spectra of aqueous yttrium perchlorate, triflate (trifluoromethanesulfonate), chloride and nitrate solutions were measured over a broad concentration range (0.198-3.252 mol L(-1)). The spectra range from low wavenumbers to 4200 cm(-1). A very weak mode at 384 cm(-1) with a full width at half height at 50 cm(-1) in the isotropic spectrum suggests that the Y(3+)- octa-aqua ion is thermodynamically stable in dilute perchlorate solutions (∼0.5 mol L(-1)) while in concentrated perchlorate solutions outer-sphere ion pairs and contact ion pairs are formed. The octa-hydrate, [Y(OH2)8](3+) was also detected in a 1.10 mol L(-1) aqueous Y(CF3SO3)3 solution. Furthermore, very weak and broad depolarized modes could be detected which are assigned to [Y(OH2)8](3+)(aq) at 100, 166, 234 and 320 cm(-1) confirming that a hexa-hydrate is not compatible with the hydrated species in solution. In yttrium chloride solutions contact ion pair formation was detected over the measured concentration range from 0.479-3.212 mol L(-1). The contact ion pairs in YCl3(aq) are fairly weak and disappear with dilution. At a concentration <0.2 mol L(-1) almost all complexes have disappeared. In YCl3 solutions, with additional HCl, chloro-complexes of the type [Y(OH2)8-nCln](+3-n) (n = 1,2) are formed. The Y(NO3)3(aq) spectra were compared with a spectrum of a dilute NaNO3 solution and it was concluded that in Y(NO3)3(aq) over the concentration range from 2.035-0.198 mol L(-1) nitrato-complexes [Y(OH2)8-n(NO3)ln](+3-n) (n = 1,2) are formed. The nitrato-complexes are weak and disappear with dilution <0.1 mol L(-1). DFT geometry optimizations and frequency calculations are reported for both the yttrium-water cluster in the gas phase and the cluster within a polarizable continuum model in order to implicitly describe the presence of the bulk solvent. The bond distance and angle for the square antiprismatic cluster geometry of [Y(OH2)8](3+) with the polarizable dielectric continuum is in good agreement with data from recent structural experimental measurements. The DFT frequency of the Y-O stretching mode of the [Y(OH2)8](3+) cluster, in a polarizable continuum, is at 372 cm(-1) in satisfactory agreement with the experimental value.


[Measurement of intestinal permeability in Crohn's disease, ulcerative colitis, sprue and idiopathic hyperamylasemia using polyethyleneglycol-400].
We investigated intestinal permeability in healthy adult volunteers, and in patients with Crohn's disease, ulcerative colitis, idiopathic sprue and idiopathic hyperamylasemia by oral administration of 10 g low molecular weight polyethylene glycol (PEG-400) and quantitation of its renal excretion over the subsequent 6 hours by high performance liquid chromatography (gel permeation HPLC). The mean amount of PEG-400 excreted during the first 6 hours by the 12 patients with Crohn's disease (3.1 +/- 0.3 g, mean +/- SE) and the 8 patients with ulcerative colitis (2.6 +/- 0.3 g) was not significantly different from the amount excreted by the 24 healthy volunteers (2.9 +/- 0.1 g). The 3 patients with idiopathic sprue excreted significantly less (1.4 +/- 0.3 g, p less than 0.05) and the 3 patients with idiopathic hyperamylasemia significantly more (4.0 +/- 0.4 g, p less than 0.05) than the healthy controls. In conclusion, no alteration of intestinal permeability could be demonstrated in patients with Crohn's disease or ulcerative colitis. However, intestinal permeability was decreased in patients with idiopathic sprue and increased in those with idiopathic hyperamylasemia.


Stereoselective verapamil disposition and dynamics in aging during racemic verapamil administration.
Stereoselective verapamil disposition and dynamics were evaluated after racemic verapamil administration of single i.v. doses, simulated steady-state intravenous infusions, chronic (1 week) administration of oral immediate-release tablets (120 mg three times daily) and chronic (1 week) administration of oral sustained-release tablets (240 mg once daily) to 15 young (mean +/- S.E.M. age 22 +/- 1 year) and 15 older (69 +/- 1 year) healthy male volunteers. After single i.v. doses S-verapamil clearance (young, 102 +/- 6 vs. older, 77 +/- 6 l/hr; P < .01) and R-verapamil clearance (young, 61 +/- 3 vs. older, 45 +/- 3 l/hr; P < .01) were similarly decreased. Electrocardiographic P-R prolongation using S-verapamil concentrations and an Emax model (young Emax, 69 +/- 8 vs. older, 42 +/- 6 msec; P < .05: young EC50, 15 +/- 1 vs. older, 23 +/- 3 ng/ml; P < .05) was greater in the young. Simulated steady-state i.v. S-verapamil clearance (young, 76 +/- 3 vs. older, 49 +/- 2 l/hr; P < .01) and R-verapamil clearance (young, 47 +/- 2 vs. older, 28 +/- 1 l/hr; P < .01) were similarly less in older subjects and this was unrelated to infusion rate. Qualitatively similar findings were observed during chronic oral (immediate release) treatment and chronic oral (sustained release) treatment. Plasma protein binding of S-verapamil was less in both groups (young, 8.5 +/- 0.4 and older, 8.0 +/- 0.5% unbound) than that of R-verapamil (young, 5.4 +/- 0.2 and older, 5.1 +/- 0.3% unbound) and not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Hydrophobic pocket targeting probes for enteroviruses.
Visualization and tracking of viruses without compromising their functionality is crucial in order to understand virus targeting to cells and tissues, and to understand the subsequent subcellular steps leading to virus uncoating and replication. Enteroviruses are important human pathogens causing a vast number of acute infections, and are also suggested to contribute to the development of chronic diseases like type I diabetes. Here, we demonstrate a novel method to target site-specifically the hydrophobic pocket of enteroviruses. A probe, a derivative of Pleconaril, was developed and conjugated to various labels that enabled the visualization of enteroviruses under light and electron microscopes. The probe mildly stabilized the virus particle by increasing the melting temperature by 1-3 degrees, and caused a delay in the uncoating of the virus in the cellular endosomes, but could not however inhibit the receptor binding, cellular entry or infectivity of the virus. The hydrophobic pocket binding moiety of the probe was shown to bind to echovirus 1 particle by STD and tr-NOESY NMR methods. Furthermore, binding to echovirus 1 and Coxsackievirus A9, and to a lesser extent to Coxsackie virus B3 was verified by using a gold nanocluster labeled probe by TEM analysis. Molecular modelling suggested that the probe fits the hydrophobic pockets of EV1 and CVA9, but not of CVB3 as expected, correlating well with the variations in the infectivity and stability of the virus particles. EV1 conjugated to the fluorescent dye labeled probe was efficiently internalized into the cells. The virus-fluorescent probe conjugate accumulated in the cytoplasmic endosomes and caused infection starting from 6 hours onwards. Remarkably, before and during the time of replication, the fluorescent probe was seen to leak from the virus-positive endosomes and thus separate from the capsid proteins that were left in the endosomes. These results suggest that, like the physiological hydrophobic content, the probe may be released upon virus uncoating. Our results collectively thus show that the gold and fluorescently labeled probes may be used to track and visualize the studied enteroviruses during the early phases of infection opening new avenues to follow virus uncoating in cells.


Updates to the spectrum model to estimate key HIV indicators for adults and children.
The Spectrum program is used to estimate key HIV indicators for national programmes. The purpose of the study is to describe the key updates made to Spectrum in the last 2 years to produce the version used in the 2013 global estimates of HIV/AIDS. The United Nations Programme on HIV/AIDS (UNAIDS) Reference Group on Estimates, Models and Projections regularly reviews new data and information needs and recommends updates to the methodology and assumptions used in Spectrum. The latest data from surveys, census and special studies are used to estimate key parameter values for countries and regions. Country-specific life tables prepared by the United National Population Division (UNPD) have been incorporated into Spectrum's demographic projections replacing the model life tables used previously. This update includes revised estimates of non-AIDS life expectancy. Incidence among all adults 15-49 years generated from curve fitting to surveillance and survey data is now split by age using incidence rate ratios derived from Analysing Longitudinal Population-based HIV/AIDS data on Africa Network data for generalized epidemics. Methods for estimating the number of AIDS orphans have been updated to include the changing effects of PMTCT and antiretroviral therapy programmes. Procedures for estimating the number of adults eligible for treatment have been updated to reflect the 2013 WHO guidelines. Program data on AIDS mortality has been used to estimate prevalence trends in Argentina, Brazil and Mexico for the 2013 estimates. Spectrum was updated for the 2013 round of HIV estimates in order to support national programmes with improved methods and data to estimating national indicators.


Internal state distributions of fragment HCO via S0 and T1 pathways of glyoxal after photolysis in the ultraviolet region.
The dynamics of photodissociation of glyoxal (HOC-COH) near the dissociation threshold on the triplet manifold are studied through measurement of distributions of nascent fragment HCO in various internal states. Three rotational levels 1(01) (*), 4(13) (*), and 3(21) (*)+3(22) (*) of vibrational state U (excitation wavelength approximately 394.4 nm, origin at 25,331.865 cm(-1)) of glyoxal in state A (1)A(u) and two other vibrational states at excitation wavelengths 390.33 and 382.65 nm are selected to produce fragment HCO. By means of fluorescence in the transition B (2)A(')-X (2)A(') of HCO, we determined the relative populations of internal states of that fragment. Rotational states of product HCO up to N=26 and K=2 are populated, and bimodal distributions of these rotational states are observed for the photolysis wavelengths used in this work. The high rotational part of the distribution with average energy near values calculated on the basis of the statistical model-phase-space theory is assigned to arise from glyoxal on its S(0) surface, and the low rotational part from the T(1) surface with an exit barrier. After photolysis near the threshold region on the triplet surface, HCO arising from the T(1) state appears to be a major component of products because these rotational levels 1(01) (*), 4(13) (*), and 3(2) (*) of U state selected are gateway states with an enhanced rate of intersystem crossing.


Predominance of CD4+ T Cells in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma and Identification of a Subset of Patients With Peripheral B-Cell Lymphopenia.
T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a morphologic variant of large B-cell lymphoma whose flow cytometry findings are not well characterized. Nineteen cases with flow cytometric immunophenotyping were identified from the case records of four institutions between 2001 and 2016. In most cases, neoplastic B cells were not detected by flow cytometry. Overall, cases showed a predominance of CD4+ T cells, which in some cases was marked. Significant coexpression of CD57 was seen on CD4+ T cells where this marker was analyzed, which correlated with PD-1 expression. Two cases also showed a profound systemic B-cell lymphopenia, which was associated in one case with hypogammaglobulinemia. Overall, our work challenges previous findings that cases of THRLBCL are rich in CD8+ T cells and highlights parallels between THRLBCL and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). Also, an association of THRLBCL with systemic B-cell lymphopenia has not been previously reported but may represent an underrecognized manifestation.


Reversibility of single-incentive selective associations.
Rats were trained to press a lever in the presence of a tone-light compound stimulus and not to press in its absence. In each of two experiments, schedules were designed to make the compound a conditioned punisher for one group and a conditioned reinforcer for the other. In Experiment 1, one group's responding produced food in the presence of the compound but not in its absence. The other group's responding terminated the compound stimulus, and food was presented only in its absence. When tone and light were later presented separately, light controlled more responding than did tone in the former group, but tone gained substantial control in the latter. The same effects were also observed within subjects when the training schedules were switched over groups. In Experiment 2, two groups avoided shock in the presence of the compound stimulus. In the absence of the compound, one group was not shocked, and the other received both response-independent and response-produced shock. When tone and light were presented separately, the former group's responding was mainly controlled by tone, but the latter group's responding was almost exclusively controlled by light. These effects were also observed within subjects when the training schedules were switched over groups. Thus, these single-incentive selective association effects (appetitive in Experiment 1 and aversive in Experiment 2) were completely reversible. The schedules in which the compound should have been a conditioned reinforcer consistently produced visual control, and auditory control increased when the compound should have become a conditioned punisher. Currently accepted accounts of selective associations based on affinities between shock and auditory stimuli and between food and visual stimuli (i.e., stimulus-reinforcer interactions) do not adequately address these results. The contingencies of reinforcement most recently associated with the compound and with its absence, rather than the nature of the reinforcer, determined whether auditory or visual stimulus control developed.


Near Miss Reporting.
Imaging is no stranger to patient safety events. There was a tremendous opportunity at WakeMed in North Carolina to change the safety culture of the imag- ing services department and provide staff with a system that rewarded them for identifying safety risks. Most staff could articulate the difference between a near miss and an actual event, but very few staff knew how to report a near miss. Staff who did know how to report a near miss believed the online process was too lengthy. Staff also reported a fear of punitive action associated with reporting events. Imaging services leadership successfully developed and implemented a "Good Catch" program. One of the most important objectives of the program was to remove the negative stigma associated with near miss reporting.


[Therapy of chronic hepatitis].
Treatment with glucocorticosteroids alone or in combination with azathioprine can be considered the most successful therapy in "chronic active hepatitis" of the "autoimmune" type. Immunosuppressive treatment of HBs+ chronic active hepatitis remains controversial and should be confined exclusively to severe cases. Caution is even more indicated in chronic active hepatitis of the non-A-non-B type. Antiviral therapy in chronic active hepatitis is still controverted. Relatively little experience has been gained of the enormously expensive interferon treatment.


Lateral duodenal wall perforation due to plastic biliary stent migration: a case series of endoscopic closure.
Background and study aims Lateral duodenal wall perforation by a migrated stent is a potential complication of biliary stenting. By systematic database revision, we identified a series of six patients with lateral duodenal wall perforation caused by a displaced plastic biliary stent that were treated with over-the-scope clip (OTSC) between January 1, 2014 and March 31, 2019. In this series, most cases were related to stenting of benign strictures with single or double stenting and with the use of stents longer than 12 cm. OTSC permitted perforation closure in all cases. Most patients had an excellent outcome and did not need any subsequent intervention. However, one patient, who presented with a more severe pneumoretroperitoneum on computed tomography scan, required laparotomy with peritoneal lavage and eventually died due to this complication. We conclude that endoscopic treatment of these perforations with OTSC could be an effective alternative to surgery in selected patients.


Borabicyclo[3.2.0]heptadiene: A Fused Bicyclic Isomer of Borepin.
A new isomer of borepin, identified as 2-borabicyclo[3.2.0]hepta-3,6-diene by single-crystal X-ray diffraction and heteronuclear NMR spectroscopy, was obtained by reaction of 1-mesityl-2,3,4,5-tetraphenylborole with the diaminoalkyne bis(piperidyl)acetylene. Analogous reactions of the alkyne with other borole derivatives generated seven-membered borepins, in which a second equivalent of the alkyne was found to insert into the exocyclic B-C bond. Results of mechanistic DFT studies as well as differences in the reactivity of the boroles toward the diaminoalkyne are discussed.


Induction of protective immunity against microbial challenge by targeting antigens expressed by probiotic bacteria to mucosal dendritic cells.
Efficient vaccines combined with adjuvants potentiate and enhance antibody avidity and increase T cell longevity, particularly in individuals with compromised immunity. The efficacy of a novel vaccine can be improved by specifically targeting its immunogenic subunits and expressing it in live probiotic vector (i.e. Lactobacillus acidophilus) that protects vaccine bioavailability and to induces not only mucosal but also systemic immunity against microbes. Accordingly, our data clearly show that specific Lactobacillus species (L. gasseri) not only optimally activate DCs but also deliver targeted antigens to mucosal DCs via 12-mer peptides derived from a phage display library resulting in robust humoral and T cell immunity against microbial challenge. This effort is accomplished via novel tools that provide "targeting" of the vaccine, evaluation of innovative vaccine effectiveness against a wide array of microbes, and controlling gene expression/presentation technologies in probiotic lactobacilli that can be orally consumed at high levels resulting in natural delivery of a "targeted" antigen to mucosal DCs. In this review I will discuss the potential benefits and efficacy of the employed vaccine strategy that may be feasible for various studies in the field.


Asymmetrical gene flow in five co-distributed syngnathids explained by ocean currents and rafting propensity.
Ocean circulation driving macro-algal rafting is believed to serve as an important mode of dispersal for many marine organisms, leading to predictions on population-level genetic connectivity and the directionality of effective dispersal. Here, we use genome-wide single nucleotide polymorphism data to investigate whether gene flow directionality in two seahorses (Hippocampus) and three pipefishes (Syngnathus) follows the predominant ocean circulation patterns in the Gulf of Mexico and northwestern Atlantic. In addition, we explore whether gene flow magnitudes are predicted by traits related to active dispersal ability and habitat preference. We inferred demographic histories of these co-distributed syngnathid species, and coalescent model-based estimates indicate that gene flow directionality is in agreement with ocean circulation data that predicts eastward and northward macro-algal transport. However, the magnitude to which ocean currents influence this pattern appears strongly dependent on the species-specific traits related to rafting propensity and habitat preferences. Higher levels of gene flow and stronger directionality are observed in Hippocampus erectus, Syngnathus floridae and Syngnathus louisianae, which closely associated with the pelagic macro-algae Sargassum spp., compared to Hippocampus zosterae and the Syngnathus scovelli/Syngnathus fuscus sister-species pair, which prefer near shore habitats and are weakly associated with pelagic Sargassum. This study highlights how the combination of population genomic inference together with ocean circulation data can help explain patterns of population structure and diversity in marine ecosystems.


Infant hair cortisol: associations with salivary cortisol and environmental context.
Early chronic stress has enduring implications for physical and mental health outcomes. Hair cortisol concentration (HCC) has emerged as a marker of cumulative cortisol exposure, yet HCC in infants is not well understood. We examined how infant HCC relates to widely used basal salivary cortisol measures, maternal HCC, and environmental context in 111 infants assessed at 6 and 12 months of age. Maternal HCC at 6 and 12 months was correlated with infant HCC at 12 months. At 12 months, infant HCC was positively associated with waking salivary cortisol concentration (SCC), evening SCC, and area under the curve (AUC), but was independent of diurnal slope. Breastfeeding was associated with lower HCC, whereas increased sleep disruption was related to flatter slope. Reduced nighttime sleep duration was related both to higher HCC and to flatter slope. A person-focused analysis indicated that the combination of high HCC and flattened slope was associated with more environmental risks, highlighting the importance of investigating the interplay between HCC and diurnal cortisol slope. Results support the validity of HCC as a marker of cumulative cortisol exposure in infancy, while emphasizing the value of including multiple cortisol measures assessing distinct aspects of hypothalamic-pituitary-adrenal (HPA) function.


Does extraction of DNA and RNA by magnetic fishing work for diverse plant species?
An automated nucleic acid extraction procedure with magnetic particles originally designed for isolation of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) from animal tissues was tested for plant material. We isolated genomic DNA and total RNA from taxonomically diverse plant species representing conifers (Scots pine), broad-leaved trees (silver birch and hybrid aspen), dwarf shrubs (bilberry), and both monocotyledonous (regal lily) and dicotyledonous (Saint John's wort, round-leaved sundew, and tobacco) herbaceous plants. Buffers developed for DNA extraction were successfully used in addition to manufacturer's extraction kits. The quality of RNA was appropriate for many applications, but the quality of DNA was not always sufficient for polymerase chain reaction (PCR) amplification. However, we could strikingly improve the quality by eliminating the adherent compounds during the extraction or later in the PCR phase. Our results show that the use of the procedure could be extended to diverse plant species. This procedure is especially suitable for small sample sizes and for simultaneous processing of many samples enabling large-scale plant applications in population genetics, or in the screening of putative transgenic plants.


Two-frequency mutual coherence function and pulse propagation in random media.
In this work an analysis of transient wave propagation in forward scattering random media is presented. The analysis is based on evaluation of the two-frequency mutual coherence function, which is an important quantity in itself since it provides a measure of the coherence bandwidth. The coherence function is calculated by using the path integral technique; specifically, by resorting to a cumulant expansion of the path integral. In contrast to the formulas available in the literature, the solution obtained is not limited by the strength of disorder and applies equally well to both dispersive and nondispersive media, with arbitrary spectra of inhomogeneities. For the regime of weak scattering (or relatively short propagation distances) the first cumulant gives an excellent approximation coinciding with the results obtained earlier in a particular case of the Kolmogorov turbulence by solving the corresponding differential equation numerically. In the regime of strong scattering (long distances), which to our knowledge has not been covered previously, our solution demonstrates a different type of scaling dependence. It is shown that, even for power spectra with fractal behavior in a wide range of spatial frequencies, the coherence function is very sensitive to fine details of the spectrum at both small and large spatial scales. Using the cumulant expansion, the temporal moments of the pulsed wave propagating in a random medium are also considered. It is found that the temporal moments of the pulse are determined exactly by accounting for a corresponding number of the cumulants. In particular, the average time delay of the pulse is determined by the first cumulant, and the pulse width is obtained by accounting for the first two cumulants. Although the consideration of the problem is based on the model of a continuous medium, the results are also applicable to wave propagation in media containing discrete particles scattering predominantly in the forward direction.


Obstructive fibrinous tracheal pseudomembrane.
Obstructive fibrinous tracheal pseudomembrane (OFTP) is a relatively rare cause of failed extubation. OFTP may be more common than described in the literature. OFTP results from ischemic injury to tracheal mucosa and may be the initial stage of the development of tracheal stenosis. Early diagnosis and treatment can prevent re intubation and mortality. We present a rare case of OFTP. The patient was intubated for 3 days for asthma exacerbation and was appropriately discharged. The patient was seen the second time in the emergency room and was treated for asthma exacerbation on the same day. Because of persistent symptoms after 3 days, CT scan of the chest was performed, which indicated necrotizing tracheitis with gas formation within the tracheal wall. Bronchoscopy showed no evidence of necrosis, but there was a thick white plaque toughly adherent to the tracheal wall.


Cryopreservation of canine sperm using egg yolk and soy bean based extenders.
Animal protein-based extenders are widely used despite being a potential source of bacterial or mycoplasma contamination. Its replacement with vegetal protein-based extenders could represent an interesting alternative for dog sperm cryopreservation. This technique could be further improved by the addition of Tris-Glucose-Citric acid (TGC) that could physically protect the spermatozoa and improve its homeostasis. The aim of this study was to evaluate a cryopreservation protocol for dog spermatozoa using a soybean-based extender (LP1℗) as well as the effects of the addition of (TGC) immediately after the semen collection. Eleven ejaculates from purebred adult dogs were collected, centrifuged in the absence or presence of TGC and processed as fresh or cryopreserved spermatozoa with: egg yolk-based extender (CaniPRO) or LP1℗. Freezing the spermatozoa in LP1℗ reduced the amplitude of the lateral head displacement, the percentage of spermatozoa that showed the intact acrosome and the mitochondrial function (P<0.05). These samples also showed a trend towards increased percentage of apoptotic spermatozoa (P<0.05). The addition of TGC before centrifugation did not improve the seminal parameters and adversely affected motility (P<0.05) in the spermatozoa cryopreserved in CaniPRO. However, TGC did not affect motility and increased (P<0.05) the percentage of intact acrosomes in the spermatozoa cryopreserved in LP1℗, reaching similar values than those cryopreserved in CaniPRO. In conclusion, LP1® plus TGC provide the same level of protection to dog spermatozoa cryopreservation than the egg yolk based extender CaniPRO when comparing standard post-thaw sperm quality parameters.


Outcome of training of maternal and child health workers in Ifo Local Government Area, Ogun State, Nigeria, on common childhood blinding diseases: a pre-test, post-test, one-group quasi-experimental study.
Maternal and child health workers (MCHWs) are often the first point of contact with pregnant women, children, and caregivers. Therefore, they can play a significant role in early detection of causes of childhood blindness, facilitate prompt referral to specialized centers and provide health education to caregivers for preventive eye care. This is a pre-test, post-test, single group, quasi-experimental study to evaluate the outcome of training MCHWs on common blinding childhood diseases. All MCHWs in Ifo Local Government Area were selected to participate in the study. Pre-training, qualitative data was obtained from two focus group discussions while quantitative data was obtained using a self-administered questionnaire. Three months post-training, quantitative data was obtained using the same self-administered questionnaire as was used pre-training. Total and percentage scores on the pre- and post-tests were calculated for each participant. A score of ≥70% was regarded as sufficient while < 70% score was regarded as insufficient. McNemar's test was used to determine differences in proportions between pre- and post-training quantitative measurements. Of the 65 MCHWs in the Local Government Area, 61 participated in the study giving a response rate of 93.8%. The age range of study participants was from 28 to 57 years with a mean age of 41 ± 8.3 years. The male: female ratio was 1:7.7. During the focus group discussions, measles was the most commonly mentioned cause of childhood blindness however, participants showed more knowledge of the signs and symptoms of new-born conjunctivitis. Based on a sufficient knowledge score of ≥70%, only one participant (1.6%) demonstrated sufficient knowledge on quantitative survey pre-training. Post-training, there was a statistically significant increase (20, 32.8%) in the proportion of participants with sufficient knowledge (McNemar's test p = .000). This study demonstrated that the training of MCHWs on common childhood blinding diseases (such as congenital cataract and congenital glaucoma) had the potential to improve knowledge regarding prevention, prompt recognition and early referral of common treatable potentially blinding diseases.


Strategies for the Long-Term Preservation of Site for Future Implantation of Cardiac Implantable Electronic Devices (CIEDs): Two Decades of Experience.
Introduction Implantation of cardiac implantable electronic devices (CIEDs) is an art of science. As the volume of implantation has increased worldwide, so has the rate of complications. Infection, fibrosis, lead and device erosion, lead displacement, right ventricle perforation, lead fracture, and insulation break are the common complications in the implantation process. This exposes the patient for reopening and threatens the implantation for further complication due to infection, fibrosis of veins, failure to retrieve the implanted wire, and failure to re-implant the device on the same site. We slightly changed our implantation technique to preserve the implantation site for future implantation and reduce the rate of complication in the index implantation. Methods This randomized control trial was conducted from January 2016 to September 2019 at Hayatabad Medical Complex Peshawar, Pakistan. A consecutive sampling technique was used to obtain a sample size of 602 patients keeping a 95% confidence interval and a 5% margin error. We adopted a strategy to take prick, for implantation of devices, inside the pocket, which reduces the number of sutures, hastens the procedure, prevents erosion, and minimizes the chance of subclavian crush syndrome and insulation break. We also selected the minimum possible length of leads. This will possibly decrease the chances of cumbersome fibrosis around the lead and device and will make future implantation convenient. Results There was a total of 602 procedures in the study period. About 253 (42%) procedures were done in the newly adopted strategy and 349 (58%) were performed in the conventional way. Our complication rate grossly reduces in the novel way of implantation in which we took our prick inside the pocket. Conclusion A slight modification in the implantation of CIEDs not only prevents the rate of complication in the index implantation but will also possibly preserve the site for future implantation.


Toward greater involvement of youth with complex communication needs in the selection of augmentative and alternative communication devices.
Purpose: The study aim was to examine the measurement properties of the Youth Evaluation of Products Scale for Augmentative and Alternative Communication (YEP-AAC) as a means to understand the product attitudes of youth toward their AAC devices.Methods: In study 1, four males and two females between the ages of 8 and 17 years (median age = 14 years) participated in face-to-face interviews. A researcher administered the YEP-AAC and then asked youths to explain the rationale for their item ratings. Two researchers analyzed masked transcripts of the interviews to predict the valence of item ratings assigned by youths. In study 2, 18 families participated in a mailed survey to examine the reliability and validity of the scale domains. Seventeen mothers/one father and their children (9 male/9 female) between the ages of 10 and 20 years participated (median age = 16 years).Results: The level of chance-corrected agreement between valences converted from youth ratings on the YEP-AAC and those assigned by researchers was fair (weighted kappa = 0.38). Internal consistencies of the scale domains were acceptable. Youths who rated their AAC devices more favourably had higher functional communication as hypothesized.Conclusion: The two studies provide support for the face validity, internal consistency and convergent validity of the YEP-AAC as a measure of the product attitudes of youth with complex communication needs.Implications for rehabilitationDeveloping reliable ways to understand the product needs, preferences and values of youth with complex communication needs will help to support the selection, acquisition and use of augmentative and alternative communication (AAC) devices.Consumer socialization helps to explain how youth may acquire the skills, knowledge and experience relevant to their role as AAC consumers.Reliable youth-report questionnaires that are grounded in consumer socialization provide an expedient way to understand the product attitudes of young consumers with complex communication needs.


Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts.
To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). Cultured FLS from patients with RA were treated with two PARP inhibitors, 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinona (DPQ) or 4-amino-1,8-naphthalimida (ANI) before TNF stimulation. PARP-1 expression was also suppressed in RA FLS by small interfering RNA (siRNA) transfection. Expression and secretion of inflammatory mediators were analysed by quantitative polymerase chain reaction and by enzyme-linked immunosorbent assay, respectively. Proliferation of RA FLS was also determined. Mitogen-activated protein kinase (MAPK) activity was analysed by western blot assay and activator protein (AP)-1 and nuclear factor (NF)kappaB binding by electrophoretic mobility shift assay. We show, for the first time, that PARP inhibition either with specific inhibitors or by siRNA transfection significantly reduced TNF-induced cytokine and chemokine expression in FLS from patients with RA. PARP inhibitors also decreased TNF-induced RA FLS proliferation. PARP inhibition reduced TNF-induced JNK phosphorylation and AP-1 and NF kappaB binding activities were partially impaired by treatment with PARP inhibitors or by PARP-1 knockdown. PARP inhibition reduces the production of inflammatory mediators and the proliferation of RA FLS (in response to TNF), suggesting that PARP inhibitors could have therapeutic benefits in RA.


Microarray characterization of gene expression changes in blood during acute ethanol exposure.
As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we performed a DNA microarray analysis of human whole blood samples from a five-time point study of subjects administered ethanol orally, followed by breathalyzer analysis, to monitor blood alcohol concentration (BAC) to discover significant gene expression changes in response to the ethanol exposure. Subjects were administered either orange juice or orange juice with ethanol. Blood samples were taken based on BAC and total RNA was isolated from PaxGene™ blood tubes. The amplified cDNA was used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR) analyses to evaluate differential gene expression. Microarray data was analyzed in a pipeline fashion to summarize and normalize and the results evaluated for relative expression across time points with multiple methods. Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. RT-qPCR was used with representative genes to confirm relative transcript levels across time to those detected in microarrays. Microarray analysis of samples representing 0%, 0.04%, 0.08%, return to 0.04%, and 0.02% wt/vol BAC showed that changes in gene expression could be detected across the time course. The expression changes were verified by qRT-PCR.The candidate genes of interest (GOI) identified from the microarray analysis and clustered by expression pattern across the five BAC points showed seven coordinately expressed groups. Analysis showed function-based networks, shared transcription factor binding sites and signaling pathways for members of the clusters. These include hematological functions, innate immunity and inflammation functions, metabolic functions expected of ethanol metabolism, and pancreatic and hepatic function. Five of the seven clusters showed links to the p38 MAPK pathway. The results of this study provide a first look at changing gene expression patterns in human blood during an acute rise in blood ethanol concentration and its depletion because of metabolism and excretion, and demonstrate that it is possible to detect changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study serves as a workflow to investigate the biology linked to expression changes across a time course and from these changes, to identify target genes that could serve as biomarkers linked to pilot performance.


Tandem organic solar cells with 20.6% efficiency enabled by reduced voltage losses.
Large voltage losses are the main obstacle for achieving high efficiency in organic solar cells (OSCs). Here we construct ternary OSCs by introducing an asymmetric small molecule acceptor AITC into PBDB-TCl : BTP-eC9 system and demonstrate the effectiveness in simultaneously decreasing energy disorder and non-radiative voltage losses. It is found that the introduction of AITC can modify domain size and increase the degree of crystallinity, which enhances open-circuit voltage and power conversion efficiency (19.1%, certified as 18.9%). Inspiringly, an output efficiency of 20.6% of the constructed tandem OSCs based on PBDB-TCl : AITC : BTP-eC9 ternary active layer output a recorded efficiency of 20.6% (certified as 20.3%), which is the highest value in OSCs field to date. This work demonstrates that decreasing the voltage losses by ternary strategy and constructing of tandem architecture are effective approaches towards improving photovoltaic performance.


Investigation of the Adsorption Behavior of Organic Sulfur in Coal via Density Functional Theory (DFT) Calculation and Molecular Simulation.
In this paper, we have investigated the chemical adsorption behavior of O2 on five types of organic sulfur (thiol, sulfoxide, thioether, sulfone, and thiophene) in polycyclic aromatic hydrocarbon (PAH) sheets using density functional theory (DFT) calculations. Here, the adsorption energy of O2-organic sulfur exceeds that of O2-PAH. Sulfone tends to be more favorable for oxidation reactions than other organic sulfur compounds and PAH by energy gap and deformation charge density analyses. A large charge transfer occurs between O2 and organic sulfur compounds by charge analysis. A radical distribution function (RDF) analysis shows that O2/CO2/N2 is preferentially adsorbed on nitrogen/sulfur/oxygen-containing functional groups in coal. To inhibit the reaction of sulfur-containing coal with oxygen, the physical adsorption of pure gas (CO2/O2/N2) and binary mixed gases (CO2 + O2/N2 + O2/CO2 + N2) is conducted at different temperatures and geological depths using molecular dynamics (MD) and grand canonical Monte Carlo (GCMC) simulations. The adsorption capacities of five types of organic sulfur with respect to the pure gases decrease with increasing temperature and increase with increasing depth. For O2/CO2, CO2/N2, and O2/N2 binary gas systems, the order with respect to adsorption amount is CO2 > O2 > N2. The factor of adsorption capacities is also evaluated, and the results show that pore volume plays a key role in adsorption behavior.


Spectroscopic and theoretical approaches for studying radical reactions in class I ribonucleotide reductase.
Ribonucleotide reductases (RNRs) catalyze the production of deoxyribonucleotides, which are essential for DNA synthesis and repair in all organisms. The three currently known classes of RNRs are postulated to utilize a similar mechanism for ribonucleotide reduction via a transient thiyl radical, but they differ in the way this radical is generated. Class I RNR, found in all eukaryotic organisms and in some eubacteria and viruses, employs a diferric iron center and a stable tyrosyl radical in a second protein subunit, R2, to drive thiyl radical generation near the substrate binding site in subunit R1. From extensive experimental and theoretical research during the last decades, a general mechanistic model for class I RNR has emerged, showing three major mechanistic steps: generation of the tyrosyl radical by the diiron center in subunit R2, radical transfer to generate the proposed thiyl radical near the substrate bound in subunit R1, and finally catalytic reduction of the bound ribonucleotide. Amino acid- or substrate-derived radicals are involved in all three major reactions. This article summarizes the present mechanistic picture of class I RNR and highlights experimental and theoretical approaches that have contributed to our current understanding of this important class of radical enzymes.


Exploring the Potential of Broadband Complementary Metal Oxide Semiconductor Micro-Coil Nuclear Magnetic Resonance for Environmental Research.
With sensitivity being the Achilles' heel of nuclear magnetic resonance (NMR), the superior mass sensitivity offered by micro-coils can be an excellent choice for tiny, mass limited samples such as eggs and small organisms. Recently, complementary metal oxide semiconductor (CMOS)-based micro-coil transceivers have been reported and demonstrate excellent mass sensitivity. However, the ability of broadband CMOS micro-coils to study heteronuclei has yet to be investigated, and here their potential is explored within the lens of environmental research. Eleven nuclei including 7Li, 19F, 31P and, 205Tl were studied and detection limits in the low to mid picomole range were found for an extended experiment. Further, two environmentally relevant samples (a sprouting broccoli seed and a D. magna egg) were successfully studied using the CMOS micro-coil system. 13C NMR was used to help resolve broad signals in the 1H spectrum of the 13C enriched broccoli seed, and steady state free precession was used to improve the signal-to-noise ratio by a factor of six. 19F NMR was used to track fluorinated contaminants in a single D. magna egg, showing potential for studying egg-pollutant interactions. Overall, CMOS micro-coil NMR demonstrates significant promise in environmental research, especially when the future potential to scale to multiple coil arrays (greatly improving throughput) is considered.


Thiol-linked peroxidase activity of human sensitive to apoptosis gene (SAG) protein.
SAG (sensitive to apoptosis gene), a novel zinc RING finger protein, which is redox responsive and protects mammalian cells from apoptosis, is a metal chelator and a potential reactive oxygen species (ROS) scavenger, but its antioxidant properties have not been completely defined. Here, we show that SAG possesses a potent peroxidase property to decompose hydrogen peroxide in the presence of dithiothreitol (DTT). However, without DTT as a reducing equivalent, SAG was not able to destroy hydrogen peroxide. The peroxidase activity was completely abolished by the reaction of SAG with N-ethylmaleimide (NEM), a chemical modification agent for the sulfhydryl of proteins. These observations suggested that the sulfhydryl of cysteines in SAG could function as strong nucleophiles to destroy hydrogen peroxide. In addition to the peroxidase activity used to remove hydrogen peroxide, SAG also showed t-butylhydroperoxide (t-BOOH) and fatty acid hydroperoxide-selective peroxidase activity.


[An experimental study of the water balance and acid-base state of the blood during infusions of the plasma substitute oksiamal].
The influence of the plasma substitute oxyamal on shifts in the water and acid-base balance of the blood was studied in experiments on dogs with simulated severe hemorrhagic shock. Oxyamal therapy of the severe hemorrhagic shock led to a stable reduction of the volume of circulating plasma and blood, and to a rapid normalization of blood circulation. No disorders were observed in the fluid distribution in the body, acid-base balance rapidly recovered that has evidenced a full-value transcapillary water-ion exchange.


The role of hemopoietic growth factors in self-renewal and differentiation of IL-3-dependent multipotential stem cells.
A multipotent hemopoietic cell line has been employed to assess the influence of the hemopoietic growth factors, IL-3, GM-CSF, G-CSF, and CSF-1 on the processes of self-renewal, the generation of lineage restricted progenitor cells and the production of mature neutrophils and macrophages. At a high concentration of IL-3, the cells undergo self-renewal and demonstrate little or no ability to undergo differentiation in the presence of the other growth factors. In the absence of IL-3, the cells show minimal (GM-CSF) or no (G-CSF or CSF-1) ability to respond to these other growth factors. When combined with a low concentration of IL-3, the ability of the cells to respond to GM-CSF, G-CSF, and CSF-1 is enhanced and a selective preference for the neutrophil or macrophage lineage is seen depending on the combination used, i.e., the presence of CSF-1 preferentially promotes macrophage development and G-CSF preferentially promotes neutrophil development. Conditions optimal for neutrophil development were seen using a combination of low IL-3 concentrations plus GM-CSF plus G-CSF. In such conditions, the cells undergo extensive proliferation and progressively lose their clonogenic potential (i.e., differentiation much greater than self-renewal) and acquire the biochemical markers characteristic of fully mature phagocytes.


Toxicogenomic studies of human neural cells following exposure to organophosphorus chemical warfare nerve agent VX.
Organophosphorus (OP) compounds represent an important group of chemical warfare nerve agents that remains a significant and constant military and civilian threat. OP compounds are considered acting primarily via cholinergic pathways by binding irreversibly to acetylcholinesterase, an important regulator of the neurotransmitter acetylcholine. Many studies over the past years have suggested that other mechanisms of OP toxicity exist, which need to be unraveled by a comprehensive and systematic approach such as genome-wide gene expression analysis. Here we performed a microarray study in which cultured human neural cells were exposed to 0.1 or 10 μM of VX for 1 h. Global gene expression changes were analyzed 6, 24, and 72 h post exposure. Functional annotation and pathway analysis of the differentially expressed genes has revealed many genes, networks and canonical pathways that are related to nervous system development and function, or to neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In particular, the neuregulin pathway impacted by VX exposure has important implications in many nervous system diseases including schizophrenia. These results provide useful information valuable in developing suitable antidotes for more effective prevention and treatment of, as well as in developing biomarkers for, VX-induced chronic neurotoxicity.


The Arabidopsis F-box protein SKP1-INTERACTING PARTNER 31 modulates seed maturation and seed vigor by targeting JASMONATE ZIM DOMAIN proteins independently of jasmonic acid-isoleucine.
F-box proteins have diverse functions in eukaryotic organisms, including plants, mainly targeting proteins for 26S proteasomal degradation. Here, we demonstrate the role of the F-box protein SKP1-INTERACTING PARTNER 31 (SKIP31) from Arabidopsis (Arabidopsis thaliana) in regulating late seed maturation events, seed vigor, and viability through biochemical and genetic studies using skip31 mutants and different transgenic lines. We show that SKIP31 is predominantly expressed in seeds and that SKIP31 interacts with JASMONATE ZIM DOMAIN (JAZ) proteins, key repressors in jasmonate (JA) signaling, directing their ubiquitination for proteasomal degradation independently of coronatine/jasmonic acid-isoleucine (JA-Ile), in contrast to CORONATINE INSENSITIVE 1, which sends JAZs for degradation in a coronatine/JA-Ile dependent manner. Moreover, JAZ proteins interact with the transcription factor ABSCISIC ACID-INSENSITIVE 5 (ABI5) and repress its transcriptional activity, which in turn directly or indirectly represses the expression of downstream genes involved in the accumulation of LATE EMBRYOGENESIS ABUNDANT proteins, protective metabolites, storage compounds, and abscisic acid biosynthesis. However, SKIP31 targets JAZ proteins, deregulates ABI5 activity, and positively regulates seed maturation and consequently seed vigor. Furthermore, ABI5 positively influences SKIP31 expression, while JAZ proteins repress ABI5-mediated transactivation of SKIP31 and exert feedback regulation. Taken together, our findings reveal the role of the SKIP31-JAZ-ABI5 module in seed maturation and consequently, establishment of seed vigor.


Ultrasonography for nasogastric tube placement verification: an additional reference.
Nasogastric tube (NGT) insertion is a common procedure performed by community nurses, but verifying correct placement can be challenging due to the limitations of conventional methods. This study aimed to investigate the effectiveness of point-of-care ultrasonography (POCUS) for verifying NGT placement and to explore the feasibility of using this imaging modality as the first-line reference for NGT placement verification. The validity of the gastric aspirate pH test was also evaluated. This was a single-centre, retrospective, single-blind study using a convenience sample of patients who required NGT placement in home settings. POCUS was performed by a trained community nurse, and the pH test was performed after tube insertion. The results of the POCUS and pH test were compared. A total of 68 patients with a mean age of 82.13±9.43 years were included. The sensitivity and specificity were found to be 95.45% and 100%, respectively, for POCUS, and 90.91% and 100%, for the pH test. POCUS can provide accurate diagnostic imaging of nasogastric tube position and avoid X-ray controls. This imaging modality can complement pH testing in community settings where X-ray scans are not readily available.


Small airways dysfunction in influenza A virus infection: therapeutic role and potential mode of action of amantadine.
Previous studies have demonstrated alterations in gas exchange and pulmonary mechanics in presumed and documented viral upper respiratory infections. In our laboratory, using sensitive and noninvasive testing, we have demonstrated significant and prolonged alterations of pulmonary mechanics in uncomplicated natural influenza A infection, which implicate increased resistance in small airways as the cause of dysfunction. Amantadine administration in established influenza A infection has been associated with an accelerated improvement of clinical illness and pulmonary physiologic dysfunction. Preliminary study suggests that this is due to neither cholinergic blockade nor bronchodilation.


Intermediate-term mortality and incidence of ICD therapy in octogenarians after cardiac resynchronization therapy.
Clinical outcomes of cardiac resynchronization therapy (CRT) in patients over the age of 80 have not been well described. We retrospectively identified 96 consecutive patients ≥ 80 years old who underwent an initial implant or an upgrade to CRT, with or without defibrillator (CRT-D vs. CRT-P), at our institution between January 2003 and July 2008. The control cohort consisted of 177 randomly selected patients < 80 years old undergoing CRT implant during the same time period. The primary efficacy endpoint was all-cause mortality at 36 months, assessed by Kaplan-Meier time to first event curves. In the octogenarian cohort, mean age at CRT implant was 83.1 ± 2.9 years vs. 60.1 ± 8.8 years among controls (P < 0.001). Across both groups, 70% were male, mean left ventricular ejection fraction (LVEF) was 24.8% ± 14.1% and QRS duration was 154 ± 24.8 ms, without significant differences between groups. Octogenarians were more likely to have ischemic cardiomyopathy (74% vs. 37%, P < 0.001) and more likely to undergo upgrade to CRT instead of an initial implant (42% vs. 19%, P < 0.001). The rate of appropriate defibrillator shocks was lower among octogenarians (14% vs. 27%, P = 0.02) whereas the rate of inappropriate shocks was similar (3% vs. 6%, P = 0.55). At 36 months, there was no significant difference in the rate of all-cause mortality between octogenarians (11%) and controls (8%, P = 0.381). Appropriately selected octogenarians who are candidates for CRT have similar intermediate-term mortality compared to younger patients receiving CRT.


Preparing for the inevitable: the death of a living liver donor.
Living donor liver transplantation (LDLT) is associated with a low but finite and well-documented risk of donor morbidity and mortality, so organizations and individuals involved in this activity must accept the fact that a donor death is a question of when and not if. Studies in the field of crisis management show that preparing for the inevitable not only is critical in preparing institutions to better respond to catastrophic events but more importantly plays a crucial role in preventing them. This article describes the background of crisis management with specific reference to the death of a living liver donor and proposes a general framework that can be adopted by LDLT programs around the world.


Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis?
Regional anesthesia is known to prevent or attenuate the surgical stress response; therefore, inhibiting surgical stress by paravertebral anesthesia might attenuate perioperative factors that enhance tumor growth and spread. The authors hypothesized that breast cancer patients undergoing surgery with paravertebral anesthesia and analgesia combined with general anesthesia have a lower incidence of cancer recurrence or metastases than patients undergoing surgery with general anesthesia and patient-controlled morphine analgesia. In this retrospective study, the authors examined the medical records of 129 consecutive patients undergoing mastectomy and axillary clearance for breast cancer between September 2001 and December 2002. Fifty patients had surgery with paravertebral anesthesia and analgesia combined with general anesthesia, and 79 patients had general anesthesia combined with postoperative morphine analgesia. The follow-up time was 32 +/- 5 months (mean +/- SD). There were no significant differences in patients or surgical details, tumor presentation, or prognostic factors. Recurrence- and metastasis-free survival was 94% (95% confidence interval, 87-100%) and 82% (74-91%) at 24 months and 94% (87-100%) and 77% (68-87%) at 36 months in the paravertebral and general anesthesia patients, respectively (P = 0.012). This retrospective analysis suggests that paravertebral anesthesia and analgesia for breast cancer surgery reduces the risk of recurrence or metastasis during the initial years of follow-up. Prospective trials evaluating the effects of regional analgesia and morphine sparing on cancer recurrence seem warranted.


Deprescribing in a family health team: a study of chronic proton pump inhibitor use.
BACKGROUND Proton pump inhibitors (PPIs) are often used inappropriately, without an indication, or for longer durations than recommended. Few tools exist to guide reassessment of their continued use and deprescribing if required. We aimed to reduce inappropriate drug use by developing and implementing a PPI deprescribing tool and process in a family medicine unit. ASSESSMENT OF PROBLEM Primary care providers of adults taking a PPI for 8 weeks with an upcoming periodic health examination were reminded to reassess therapy via electronic medical record (EMR) messaging. A PPI Deprescribing Tool was uploaded into the EMR as a second reminder and to guide reassessment and deprescribing where indicated. Ten weeks after the examination a chart review assessed changes to PPI use. A follow up survey of providers assessed the utility and barriers to implementing the Deprescribing Tool. RESULTS Forty-three of 46 patients on PPIs (93%) had their PPI reassessed, resulting in 11 patients (26%) having their PPI deprescribed. Strategies for Improvement Routine reassessment of long-term medications is often overlooked because of extensive demands on primary care providers' time. Deprescribing likely improved because potentially eligible patients were identified to the provider and a tool was provided at the time of the encounter to guide the deprescribing process. LESSONS Reassessment and deprescribing of PPIs can be supported by implementing a standardised process and use of guidance tools for clinicians. Providers found the timely and selective reminder message to deprescribe the most useful component of the intervention. KEYWORDS proton pump inhibitor; deprescribing; reassessment; primary care; medication therapy management; gastroesophageal reflux disease.


Hypothesis for mammary tumorigenesis in Sprague-Dawley rats exposed to certain triazine herbicides.
The symmetrical triazine herbicides have been used for the preemergence control of broadleaf weeds for nearly three decades. Recently, certain members of this class, primarily the chlorotriazines (substituted in the 2 position), have been shown to evoke an increased incidence of mammary tumors in female Sprague-Dawley rats. This response was noted when these chemicals were administered in the diet for 2 yr, and most often at dietary feeding levels at or above the maximum tolerated dose (MTD). At levels exceeding the MTD the health of these animals was compromised, as manifested by toxicity-related reduced survival that was not associated with the occurrence of mammary tumors. Mammary tumors in rats frequently occur as a result of the influence of endogenous estradiol and prolactin. Those hormones, as well as progesterone, growth-stimulating, luteinizing, and follicle-stimulating hormones, were measured after 24 mo of dietary administration of the chlorotriazine, simazine. The plasma hormone pattern seen in aged female Sprague-Dawley rats administered 1000 ppm simazine in the diet for 24 mo resembled that noted for aged female controls, except that the difference was more pronounced in the simazine-treated group. These results suggest that prolonged exposure of Sprague-Dawley females to excessive levels of triazines affects the neuroendocrine system, which in turn alters the pathology of the mammary gland. These changes are comparable to those that occur naturally as the rat ages. Changes in neuroendocrine control could result in the expression of an earlier onset and/or an increased incidence of mammary tumors, which already occur at a high spontaneous rate in aging Sprague-Dawley female rats.


[Echocardiographic study of the coronary vessels].
The coronary arteries were studied in normal subjects and in patients with coronary heart disease, using two-dimensional echocardiography. The authors succeeded in obtaining the image of the major trunk of the left and of the opening of the right coronary artery and in ascertaining various forms of coronary artery lesions. In twenty cases the findings of echocardiography and coronary angiography were compared.


Naringin and Hesperidin Counteract Diclofenac-Induced Hepatotoxicity in Male Wistar Rats via Their Antioxidant, Anti-Inflammatory, and Antiapoptotic Activities.
This study is aimed at evaluating the preventive effect and at suggesting the mode of actions of naringin and hesperidin and their combination in diclofenac-induced hepatotoxicity. Male Wistar rats, intraperitoneally injected with diclofenac sodium (3 mg/kg b.wt/day), were orally treated with naringin (20 mg/kg b.wt/day) and hesperidin (20 mg/kg b.wt/day) and their combination for 4 weeks. The administrations of naringin and hesperidin to diclofenac-injected rats led to a significant decrease in the elevated serum ALT, AST, LDH, ALP, GGT, total bilirubin, TNF-α, and IL-17 levels as well as liver lipid peroxidation and liver p53 and caspase-3 mRNA expressions. In contrast, serum IL-4 level, liver GSH content, and liver GPx and SOD activities increased. In association, diclofenac-induced deleterious histological alterations including hydropic degeneration, cytoplasmic vacuolization, apoptosis, and focal hepatic necrosis of hepatocytes associated with inflammatory cells' infiltration were remarkably improved by treatments with naringin and hesperidin. In conclusion, naringin, hesperidin, and their combination, which was the most potent, counteract diclofenac-induced liver injury via antioxidant, anti-inflammatory, and antiapoptotic actions. Thus, this study recommends the use of naringin and hesperidin or their combination to resolve the side effects of drugs like diclofenac on the liver.


Ultrasonographic evaluation at 6-month follow-up of plantar fasciitis after extracorporeal shock wave therapy.
The aim of this study was to investigate the effect of extracorporeal shock wave therapy (ESWT) on the ultrasonographic appearance of chronically painful, proximal plantar fasciitis. Twenty-two patients with a unilateral proximal plantar fasciitis were prospectively enrolled after unsuccessful conservative treatment lasting 6 months. The contralateral plantar fascia was used as the control. ESWT (3x3000 shock waves/session of 0.2 mJ/mm2) was performed at weekly intervals. The thickness of the plantar fascia was measured ultrasonographically about 2 cm distal of the medial calcaneal tuberosity. Pain estimation on a visual analogue scale (VAS) and the comfortable walking time were recorded. No local anaesthesia was applied. Follow-up was done at 6, 12 and 24 weeks. Before ESWT, the plantar fasciitis side was ultrasonographically significantly thicker than the control side (p<0.05), whereas 6 months after ESWT, the thickness of the fascia was no longer significantly different. The decrease in thickness of the plantar fasciitis side was significant (p<0.05). Pain during activities of daily living decreased by 79% according to the VAS, and the comfortable walking time increased, both significantly (p<0.01). In patients with little pain (VAS<30), the thickness of the plantar fasciitis side was significantly less (p<0.01) compared with patients who still suffered more pain (VAS>30). After ESWT, the thickness of the plantar fascia in patients with plantar fasciitis decreased, pain and walking time improved (all significantly).