Lung function decline from adolescence to young adulthood in cystic fibrosis.
Despite improving survival in cystic fibrosis (CF) patients, there is a mortality peak in early adulthood. Defining risk factors that predict significant worsening of lung disease in young adulthood may identify opportunities to improve outcomes in adults. We identified 4,680 patients in the Epidemiologic Study of Cystic Fibrosis 1994-2005 with data in both adolescence (age 14.0-17.4 years) and young adulthood (age 18.5-22.0 years) and analyzed 2,267 who had ≥5 encounters and ≥5 measurements of forced expiratory volume in 1 second (FEV(1) ) spanning ≥1 year during both adolescence and young adulthood, and ≥1 encounter with weight and height and ≥1 FEV(1) measurement age 17.5-18.5 years. We compared the annualized rates of decline in FEV(1) during adolescence and young adulthood stratified by best FEV(1) around age 18. Logistic regression was used to identify risk factors associated with substantial decline (>20 points) in FEV(1) % predicted in young adulthood. Annual rate of decline was greater in young adulthood than in adolescence. Risk factors for substantial decline included slower rate of FEV(1) decline, greater FEV(1) variability, faster body mass index (BMI) decline, male sex, chronic inhaled antibiotics, Haemophilus influenzae detection, and absence of multidrug-resistant Pseudomonas aeruginosa in adolescence, and lower than expected FEV(1) and BMI around age 18. Decline in lung function accelerates in young adults with CF, especially in those with early stage lung disease. Adolescents at risk for substantial decline in lung function in young adulthood have higher FEV(1) and worse nutritional status, among other identifiable risk factors.


Effect of reperfusion on the uptake of [3H] uridine in the gerbil brain after prolonged ischaemia.
The uptake of labelled uridine is reduced in the whole ischaemic hemispheres of gerbils subjected to unilateral carotid artery occlusion. Following circulatory restoration, brain structures that had an ischaemic insult of moderate intensity exhibit a progressively increased uptake. However, during reperfusion there is a tendency towards a clear cut definition of dead zones. This progression of the lesions seems to be related to a maturation phenomenon occurring in areas with an irreversible damage at the end of the ischaemic period.


A computer algorithm for triple radionuclide subtraction studies applied for preoperative localization of enlarged parathyroid glands.
This paper presents a computer algorithm for triple radionuclide subtraction studies and its application to preoperative localization of enlarged parathyroid glands. In the clinical examination procedure, 131I-toluidine blue was used as the principal radionuclide, 99mTcO4 and 113mIn were used to obtain additional images of the thyroid and the blood distribution respectively. A scintillation camera with a pinhole collimator and connected to a digital data aquisition system was used to record the images. Subtraction of uniform background, thyroid and blood contributions to the principal image is done automatically in the computer program. The results from a clinical study is used to illustrate the method.


The impact of cutting balloon angioplasty for the treatment of diffuse in-stent restenosis.
To determine the comparable safety and efficacy of cutting balloon angioplasty (CBA) and balloon angioplasty (BA) for diffuse in-stent restenosis (ISR). Previous studies have found that diffuse-type ISR predicts recurrence of ISR. The efficacy of CBA in this clinical setting is incompletely documented. One-hundred and seven consecutive diffuse ISR lesions (length > 10 mm) in 104 patients treated by CBA or BA were retrospectively analyzed. CBA was used in 61 lesions and BA in 46 lesions. Initial success (residual restenosis 30% with no major complications) was achieved in 99% of cases in each group. Follow-up angiography was performed in all patients at 131 93 days. Although the percent diameter stenosis after CBA was lower than after BA (19 12% versus 27 12%; p = 0.001), intravascular ultrasound (IVUS) or other QCA data were similar in the 2 groups. In follow-up angiography, recurrent restenosis rate was not statistically different between CBA (34%) and BA (52%); however, recurrent diffuse ISR was lower in the CBA group (20%) than the BA group (48%; p = 0.01). Lesion length at follow-up in the CBA group was smaller compared to the BA group (15.9 7.3 mm versus 24.2 14.4 mm; p < 0.05), while lesion length before procedure was similar. CBA for ISR is safe and effective with favorable long-term outcomes. This effect is mainly due to shortening lesion length.


Effect of protein malnutrition on CA3 hippocampal pyramidal cells in rats of three ages.
Prenatal and postnatal protein deprivation effects on CA3-hippocampal pyramidal cells were investigated in 30-, 90- and 220-day-old rats. Female rats were fed either a 6% or a 25% casein diet 5 wk before conception and the litters were maintained on their respective diet until sacrificed. In 216 rapid Golgi-impregnated cells, we measured somal size, length and diameter of apical dendrite, number of apical dendrites intersecting 10 concentric rings 38 microns apart, thorny excrescence area and length, head diameter and density of synaptic spines on 50-microns segments of apical dendrite. The present experiments showed that malnutrition produced significant reductions of somal size in animals at 220 days of age. There were significant reductions of apical dendrite diameters in animals of 30 and 90 days, and of density and head diameter of synaptic spines at the three ages studied, and significant decrease of the thorny excrescence area at 220 days of age. At this latter age, dendritic branching was significantly decreased in the last four rings representing the area into which the perforant pathway projects. In 30-day malnourished rats, dendritic branching showed a significant increase in rings 4-6 representing the area in which the Schaffer collaterals synapse. The location of the deficit in dendritic spines corresponds to the sites where mossy fibers synapse on the apical dendrites of CA3 neurons. Age-related changes normally observed in control rats (e.g., the 30-day-old control group showed the smallest somal size and 220-day-old controls the largest size) failed to occur in the malnourished rats. The deficits in spine density and dendritic branching (in animals of 220 days old) were similar to those found in our previous studies on fascia dentata.


Body size, mortality, and longevity.
The body-size dependent relationships of mortality and longevity are examined for birds and eutherian mammals. Differences between mass exponents for maximum recorded longevity and survival times for fractions of original adult populations confirm the age-dependence of mortality in both classes and a size-dependency of population-age distribution. The potential number of offspring produced by a surviving fraction of a mammalian population appears to be a size-independent ecological constant. Social structure would be more likely in larger animals since greater continuity would be provided when a higher proportion of the population consisted of senior, experienced animals, as described by the ratio of time for survival of 1 in 1000 to maximum potential lifespan: t0.001/tmax = 0.91 m0.32/2.94 m0.20 = 0.31 m0.12, that is, the expected lifespan approaches the maximum as size increases.


Identification and bioinformatic analysis of CircRNAs in the plasma of patients with very severe chronic obstructive pulmonary disease.
The differential expression of circular RNAs (circRNAs) in individuals with very severe chronic obstructive pulmonary disease (COPD) and healthy individuals was screened using microarray technology. The related functions and mechanisms were analyzed using bioinformatic methods to explore the potential of target circRNAs as biomarkers of COPD and provide insights for future pathogenesis. Thirty patients with very severe COPD and thirty healthy controls were diagnosed at The Second People's Hospital of Hefei from September 2021 to September 2022. The differential expression of circRNAs was compared and analyzed using a gene microarray and verified using quantitative real-time polymerase chain reaction (qRT-PCR) technology. A total of 90 upregulated and 29 downregulated circRNAs were screened in patients with very severe COPD and compared with those in healthy controls. qRT-PCR analysis showed that hsa_circ_0062683 of patients with very severe COPD was significantly upregulated, and hsa_circ_0089763 and hsa_circ_0008882 were significantly downregulated. By constructing the circRNA-miRNA interaction network, it was found that hsa-miR-612, hsa-miR-593-5p, hsa-miR-765, and hsa-miR-103a-2-5p are the miRNAs regulated by more differentially expressed circRNAs (DEcircRNAs). DEcircRNAs may participate in the development of COPD through hypoxia or regulation of various immune cells. Plasma circRNAs may play a helpful role in the diagnosis and assessment of COPD and be valuable disease biomarkers.


Bacterial endospore inactivation caused by outgassing of vapourous hydrogen peroxide from polymethyl methacrylate (Plexiglas).
To investigate the cause and to eliminate the inactivation of Bacillus anthracis strain Sterne spores settled onto agar and stainless steel surfaces in plastic holders. In an experimental chamber in which spores settled onto sampling surfaces, vapourous hydrogen peroxide (VHP) was used for decontamination between experiments. It was demonstrated that hydrogen peroxide (H(2)O(2)) absorbed into plastic (Plexiglas) surfaces and could outgas in the sample holders. Further experiments demonstrated that H(2)O(2) was released from Plexiglas sample holders in sufficient quantity to inactivate spores. High temperature degassing (30-35 degrees C) for several days or aluminum coating of the surfaces were two remedies found to be effective in preventing inadvertent spore inactivation. H(2)O(2) can be absorbed into plastic and released after an extended period of time (weeks), allowing a sufficient concentration to accumulate in small volumes to inactivate spores. Outgassing the plastic or coating the surface with an impermeable layer are potential solutions to reduce spore inactivation. Many studies with bacilli and other organisms are carried out using small plastic containers that may have been sterilized using H(2)O(2) or other agents. This study presents a cautionary note to ensure elimination of H(2)O(2) or other sterilizing agents to prevent spurious results.


Aging affects the responsiveness of rat peritoneal macrophages to GM-CSF and IL-4.
Macrophages undergo significant functional alterations during aging. The aim of the present study was to investigate changes of rat macrophage functions and response to M1/M2 polarization signals with age. Therefore, resident and thioglycollate-elicited peritoneal macrophages from young (3-month-old) and aged (18-19-month-old) rats were tested for phagocytic capacity and ability to secrete inflammatory mediators following in vitro stimulation with LPS and GM-CSF, and IL-4, prototypic stimulators for classically (M1) and alternatively activated (M2) macrophages, respectively. Aging increased the frequency of monocyte-derived (CCR7+ CD68+) and the most mature (CD163+ CD68+) macrophages within resident and thioglycollate-elicited peritoneal macrophages, respectively. The ability to phagocyte zymosan of none of these two cell subsets was affected by either LPS and GM-CSF or IL-4. The upregulated production of IL-1β, IL-6 and IL-10 and downregulated that of TGF-β was observed in response to LPS in resident and thioglycollate-elicited macrophages from rats of both ages. GM-CSF elevated production of IL-1β and IL-6 in resident macrophages from aged rats and in thioglycollate-elicited macrophages from young rats. Unexpectedly, IL-4 augmented production of proinflammatory mediators, IL-1β and IL-6, in resident macrophages from aged rats. In both resident and thioglycollate-elicited macrophages aging decreased NO/urea ratio, whereas LPS but not GM-SCF, shifted this ratio toward NO in the macrophages from animals of both ages. Conversely, IL-4 reduced NO/urea ratio in resident and thioglycollate-elicited macrophages from young rats only. In conclusion, our study showed that aging diminished GM-CSF-triggered polarization of elicited macrophages and caused paradoxical IL-4-driven polarization of resident macrophages toward proinflammatory M1 phenotype. This age-related deregulation of macrophage inflammatory mediator secretion and phagocytosis in response to M1/M2 activators may lead to the deficient control of infectious and/or inflammatory diseases in advanced age.


Improving surgical services performance through changing work culture.
Children's memorial hospital administrators knew that they needed to improve their surgical services infrastructure to accommodate growing patient volume, implement new technology, and address a major shift from inpatient to outpatient surgery. The hospital partnered with an outside consultant to better understand the impact of the work environment and culture on performance and to identify opportunities for improvement. During a seven-month period, new work processes, tools, and staff training helped significantly boost surgical services volume and revenue. Today, the hospital continues to sustain the performance gains achieved through the surgical care coordination initiative.


Clinical importance and cost of bacteremia caused by nosocomial multi drug resistant acinetobacter baumannii.
A. baumannii is an important nosocomial pathogen associated with high mortality, morbidity and medical cost. The aim of this study was to investigate risk factors for MDR A. baumannii bacteremia and also evaluate cost of hospitalization of these patients. Study was conducted in Ankara Atatürk Training and Research Hospital. Patients who were hospitalized in ICU and diagnosed for nosocomial blood stream infection (BSI) between January 2007 and December 2010 were checked retrospectively. Patients with nosocomial BSI caused by multidrug resistant A. baumannii were compared with the patients who had BSI caused by other Gram-negative microorganisms in terms of risk factors, mortality and medical costs. In multivariate analysis previous use of carbapenem, quinolone and metronidazole, and SAPS II score were found as independent risk factors. In case group; immunosupression, SAPS II score, and hospital stay until infection were independently associated with mortality in multivariate analysis. Our results suggest that the occurrence of MDR A.baumannii bacteremia was related with the usage of the wide spectrum antibiotics, and mortality rates were increased in patients that high SAPS II scores, long term hospitalization. Infection control procedures and limited antibiotic usage are very important for prevent nosocomial infections.


Csaba Horváth and preparative liquid chromatography.
Few chromatographers have been interested in furthering preparative liquid chromatography. The pioneers, Tswett, Kuhn and Lederer, A.J.P. Martin, Tiselius, isolated fractions but as an intermediate step in the analysis of their samples. The progress in electronics and sensors, and in their miniaturization has lead to the paradoxical situation that the analysts never see the transient pure fractions that their detector quantitates. Yet, over the last 25 years, preparative liquid chromatography has become an important industrial process for the separation, the extraction, and/or the purification of many pharmaceuticals or pharmaceutical intermediates, including pure enantiomers, purified peptides and proteins, compounds that are manufactured at the relatively large industrial scale of a few kilograms to several hundred tons per year. This development that has strongly affected the modem pharmaceutical industry is mainly due to the pioneering work of Csaba Horváth. His work in preparative HPLC was critical at both the practical and the theoretical levels. He was the first scientist in modem times to pay serious attention to the relationships between the curvature of the equilibrium isotherms, the competitive nature of nonlinear isotherms, and the chromatographic band profiles of complex mixtures. The thermodynamics of multi-component phase equilibria and mass transfer kinetics in chromatography attracted his interest and were the focus of ground-breaking contributions. He investigated displacement chromatography, an old method invented by Tiselius that Csaba was first to implement in HPLC. This choice was explained by the essential characteristic of displacement chromatography, in that it delivers fractions that can be far more concentrated than the feed. Remarkably, once the basics of nonlinear chromatography had been mastered in his group, most of the applications that were studied by his coworkers dealt with peptides of various sizes and with proteins. Thus, all the applications of preparative HPLC in the biotechnologies derive directly from Csaba's work. Although displacement did not pan out as a general method, the reasons are related more to practical constraints of the production of pharmaceuticals and to the long period of cheap energy that might be ending now. This report reviews Csaba's work in nonlinear chromatography.


A multi-locus continuous-time selection model.
A continuous time selection model is formulated for a diploid monoecious population with multiple alleles at each of an arbitrary number of loci, incorporating differential fertility and mortality as well as arbitrary mating and age structure. The model is simplified in the case of age-independence and for the case of a stable age distribution. The age-independent model is examined in detail for the special case of multiple alleles at each of two loci. This model is analyzed under the assumptions of random mating and additive fertilities, with close attention given to the behavior of the system with respect to Hardy-Weinberg proportions and linkage equilibrium.


[Value of silver staining technics for the analysis of nucleolar organizer regions and their morphological and functional variations].
Different aspects of nucleolus organizing materiel are found in acrocentric "variants", after specific Ag-staining. These various aspects being linked to the transcriptional activity of rRNA genes, the variant D and G chromosomes do not constitute a homogeneous group. Ag-staining shows also different types of satellite associations, some of them seems more dissociable than others.


Hyperthermia enhances the in vitro activity of 1-hexylcarbamoyl-5-fluorouracil compared to that of 5-fluorouracil.
The synergic effects on HeLa cells between 1-hexylcarbamoyl-5-fluorouracil (HCFU), a lipophilic masked compound of 5-fluorouracil (5-FU), and hyperthermia were investigated, with the following results: (1) After the cells had been exposed to the drug at 77 microM for 1, 2 or 3 days, with or without heat (43 degrees C) for 2 h, treatment with HCFU and heat inhibited cell growth by 9.2% on day 3, compared to control cells, HCFU alone, heat alone or the combined treatment with 5-FU plus heat. (2) The cells were exposed to the drugs at 77 microM or heat (43 degrees C) for 15-45 min and the colonies counted on day 14. Combined treatment with HCFU plus heat inhibited the clonogenicity of HeLa cells to 22.4% of findings in the control cells and as compared to findings with other treatments. The combination of 5-FU, n-hexylamine and heat had much the same effect as the combined effect of the treatment of HCFU plus heat. (3) Intracellular levels of the drugs did not increase with hyperthermic treatment. Our findings suggest that it is the hexylcarbamoyl structure of HCFU that relates to the synergic effect between HCFU and hyperthermia. This combination is expected to have positive effects for treating patients with malignancy.


Determining the frequency of resistance of Streptococcus pneumoniae to ciprofloxacin, levofloxacin, trovafloxacin, grepafloxacin, and gemifloxacin.
Newer fluoroquinolones have good activity against Streptococcus pneunoniae and may be useful clinically for the treatment of pneumonia. Although resistance among Streptococcus pneumoniae has been reported, it is rare. The frequency of single-step resistance and the emergence of resistance were compared in serial transfer of 49 clinical isolates of penicillin-sensitive and -resistant Streptococcus pneumoniae to ciprofloxacin, levofloxacin, trovafloxacin, grepafloxacin, and gemifloxacin. Single-step resistance frequencies to four times the minimum inhibitory concentration were 2.73 x 10(-6) (+/- 8.46 x 10(-6)) for ciprofloxacin, 1.78 x 10(-7) (+/- 4.62 x 10(-7)) for trovafloxacin, 5.45 x 10(-7) (+/- 1.24 x 10(-6)) for grepafloxacin, 6.78 x 10(-7) (+/- 1.38 x 10(-6)) for gemifloxacin, and 9.23 x 10(-8) (+/- 4.47 x 10(-7)) for levofloxacin. In serial transfer experiments, all isolates became resistant to clinically relevant levels of all fluoroquinolones after eight passages. The resistance occurred most rapidly with ciprofloxacin followed by grepafloxacin, gemifloxacin, trovafloxacin, and levofloxacin. These results show that strains with decreased susceptibility to fluoroquinolones occur frequently in cultures of Streptococcus pneumoniae, and this organism can readily become resistant to clinically relevant concentrations of fluoroquinolones in vitro.


Discrimination between fibroelastic deficiency and Barlow disease using parameters of mitral annulus derived from real-time three-dimensional echocardiography.
Discrimination between fibroelastic deficiency (FED) and Barlow disease (BD) is crucial for decision making in mitral valve surgery as BD is a more complex lesion demanding high surgical skill and experience. In our study we focused on the differentiation of FED from BD using three-dimensional (3D) echocardiographic parameters of the mitral annulus assessed by the mitral valve quantification (MVQ) program. We examined 90 patients (30 women) with FED and BD aged 37-76 years. The following parameters of the mitral annulus were assessed using the MVQ program: bicommissural and anteroposterior diameter of the mitral annulus, 3D annulus circumference, minimal surface spanning the annulus, and mitral annulus height. The study group was subdivided into 2 subgroups according to the intraoperative findings: the first subgroup comprised 60 individuals (19 women) with FED and the second subgroup comprised 30 patients (11 women) with BD. The discrimination between patients with BD and FED was carried out by univariate as well as multivariate statistical methods. BD and FED patients differed highly significantly in all parameters of the mitral annulus (t test), values of all parameters in BD being higher. In the classification tree modeling, the diagnoses were completely separated by a single parameter-mitral annulus height-with a cutoff value of 6.55 mm. This value and higher stands for BD. Multivariate analysis treating all the variables showed similar results, so the use of a single indicator variable is preferable. The only parameter-mitral annulus height-can be used for discrimination between Barlow disease and fibroelastic deficiency.


Human mesangial cells and peripheral blood mononuclear cells produce vascular permeability factor.
Vascular permeability factor, or vascular endothelial growth factor (VPF/VEGF) is a disulfide-linked dimeric glycoprotein of about 40 kD that promotes fluid and protein leakage from blood vessels. Various human tumor cell lines and cells including fetal vascular smooth muscle cells produce VPF/VEGF. Since glomerular mesangial cells (MC) are closely related to vascular smooth muscle cells, we examined whether cultured human MC produce VPF/VEGF. Northern blotting analysis revealed that cultured human MC expressed a 3.7 kilobases (kb) VPF/VEGF mRNA. Human peripheral blood mononuclear cells (PBMC) also expressed VPF/VEGF transcripts of 8.6 and 3.8 kb. Although the sizes of the transcripts suggested the existence of unique molecular species of VPF/VEGF mRNA in PBMC, RT-PCR analysis revealed that PBMC as well as human MC expressed 121, 165, and 189 amino acid-containing isoforms of VPF/VEGF, implying that there are no unique alternative splicing products of VPF/VEGF mRNA in PBMC. Fetal calf serum and 12-o-tetradecanoyl- phorbol-13-acetate (TPA) transiently enhanced VPF/VEGF mRNA expression in cultured human MC. Transforming growth factor-beta 1 enhanced VPF/VEGF mRNA expression in cultured human MC at least within 24 hours. Dexamethasone (DEX) inhibited the TPA-induced increase in VPF/VEGF mRNA expression, whereas DEX did not change the basal level. The DEX depressed the TPA-induced increase in VPF/VEGF mRNA expression is therefore probably a result of transcriptional control. VPF/VEGF protein was detected in cultured human MC with immunoperoxidase staining using anti-VPF/VEGF antibody. TPA increased VPF/VEGF protein levels as well as those of VPF/VEGF mRNA in cultured human MC.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of Candida dubliniensis in Venezuela.
Over the past decades there has been a significant increase in fungal infections caused by Candida species, and continues to be common in immunocompromised individuals infected with the human immunodeficiency virus (HIV). Although Candida albicans remains the fungal species most frequently isolated as an opportunistic oral pathogen, other non-albicans are often identified in this cohort of patients, including C. dubliniensis. This yeast is closely related to and shares many phenotypic characteristics with C. albicans. Colonies of these two species appear morphologically identical when not grown on special media. The shared phenotypic characteristics of C. dubliniensis and C. albicans suggest that many C. dubliniensis isolates may have been misidentified as C. albicans in the past. The present studies aim is to recover and identify C. dubliniensis, and presumptive clinical C. albicans, from the oral cavities of HIV-seropositive individuals, comparing conventional media to obtain a simple, low-cost and reliable identification system for C. dubliniensis. A total of 16 isolates (3,98%) had been obtained from 402 HIV infected individuals with recurrent oropharyngitis and were identified as C. dubliniensis. Out of these C. dubliniensis isolates 19% were resistant, with MICs above 64 microg/ml to fluconazole. This constitutes, to the authors knowledge the first recovery of this organism in Venezuela.


Thymic crosstalk restrains the pool of cortical thymic epithelial cells with progenitor properties.
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs). These ClonoTECs are EpCAM+MHCII-Foxn1lo cells that lack traits of mature cTECs or mTECs but co-express stem-cell markers, including CD24 and Sca-1. Supportive of their progenitor identity, ClonoTECs reintegrate within native thymic microenvironments and generate cTECs or mTECs in vivo. Strikingly, the frequency of cTECs with the potential to generate ClonoTECs wanes between the postnatal and young adult immunocompetent thymus, but it is sustained in alymphoid Rag2-/-Il2rg-/- counterparts. Conversely, transplantation of wild-type bone marrow hematopoietic progenitors into Rag2-/-Il2rg-/- mice and consequent restoration of thymocyte-mediated TEC differentiation diminishes the frequency of colony-forming units within cTECs. Our findings provide evidence that the cortical epithelium contains a reservoir of epithelial progenitors whose abundance is dynamically controlled by continual interactions with developing thymocytes across lifespan.


The potential-method--an economic evaluation tool.
Measuring the effect of safety and health on production is a difficult value to gauge. This article introduces the Potential, which is an instrument for economic analysis that incorporates different changes in conditions. While there are a number of problems associated with methods to determine these calculations, this method is a good indicator of the effects of safety and health and produces more than 300 variables with much less input. Organizations can use this method effectively to determine how safety and health measure can improve their bottom line. A positive business case is highlighted.


A Novel endo-1,4-β-mannanase from Bispora antennata with good adaptation and stability over a broad pH range.
An endo-β-1,4-mannanase encoding gene, man5, was cloned from Bispora antennata CBS 126.38, which was isolated from a beech stump. The cDNA of man5 consists of 1,299 base pairs and encodes a 432-amino-acid protein with a theoretical molecular mass of 46.6 kDa. Deduced MAN5 exhibited the highest amino acid sequence identity of 58% to a β-mannanase of glycoside hydrolase family 5 from Aspergillus aculeatus. Recombinant MAN5 was expressed in Pichia pastoris and purified to electrophoretic homogeneity. The specific activity of the final preparation towards locust bean gum was 289 U mg(-1). MAN5 showed optimal activity at pH 6.0 and 70 °C and had good adaptation and stability over a broad range of pH values. The enzyme showed more than 60% of peak activity at pH 3.0-8.0 and retained more than 80% of activity after incubation at 37 °C for 1 h in both acid and alkaline conditions (pH 4.0-11.0). The K (m) and V (max) values were 1.33 mg ml(-1) and 444 μmol min(-1) mg(-1) and 1.17 mg ml(-1) and 196 μmol min(-1) mg(-1) for locust bean gum and konjac flour, respectively. Of all tested metal ions and chemical reagents, Co(2+), Ni(2+), and β-mercaptoethanol enhanced the enzyme activity at 1 mM, whereas other chemicals had no effect on or partially inhibited the enzyme activity. MAN5 was highly resistant to acidic and neutral proteases (trypsin, α-chymotrypsin, collagenase, subtilisin A, and proteinase K). By virtue of the favorable properties of MAN5, it is possible to apply this enzyme in the paper and food industries.


Single-Cell Analysis Reveals Unexpected Cellular Changes and Transposon Expression Signatures in the Colonic Epithelium of Treatment-Naïve Adult Crohn's Disease Patients.
The intestinal barrier comprises a monolayer of specialized intestinal epithelial cells (IECs) that are critical in maintaining mucosal homeostasis. Dysfunction within various IEC fractions can alter intestinal permeability in a genetically susceptible host, resulting in a chronic and debilitating condition known as Crohn's disease (CD). Defining the molecular changes in each IEC type in CD will contribute to an improved understanding of the pathogenic processes and the identification of cell type-specific therapeutic targets. We performed, at single-cell resolution, a direct comparison of the colonic epithelial cellular and molecular landscape between treatment-naïve adult CD and non-inflammatory bowel disease control patients. Colonic epithelial-enriched, single-cell sequencing from treatment-naïve adult CD and non-inflammatory bowel disease patients was investigated to identify disease-induced differences in IEC types. Our analysis showed that in CD patients there is a significant skew in the colonic epithelial cellular distribution away from canonical LGR5+ stem cells, located at the crypt bottom, and toward one specific subtype of mature colonocytes, located at the crypt top. Further analysis showed unique changes to gene expression programs in every major cell type, including a previously undescribed suppression in CD of most enteroendocrine driver genes as well as L-cell markers including GCG. We also dissect an incompletely understood SPIB+ cell cluster, revealing at least 4 subclusters that likely represent different stages of a maturational trajectory. One of these SPIB+ subclusters expresses crypt-top colonocyte markers and is up-regulated significantly in CD, whereas another subcluster strongly expresses and stains positive for lysozyme (albeit no other canonical Paneth cell marker), which surprisingly is greatly reduced in expression in CD. In addition, we also discovered transposable element markers of colonic epithelial cell types as well as transposable element families that are altered significantly in CD in a cell type-specific manner. Finally, through integration with data from genome-wide association studies, we show that genes implicated in CD risk show heretofore unknown cell type-specific patterns of aberrant expression in CD, providing unprecedented insight into the potential biological functions of these genes. Single-cell analysis shows a number of unexpected cellular and molecular features, including transposable element expression signatures, in the colonic epithelium of treatment-naïve adult CD.


Effect of Different Z-Inducers on the Stabilization of Z Portion in BZ-DNA Sequence: Correlation Between Experimental and Simulation Data.
In this study we show the outstanding agreement between simulation and experimental data concerning the efficient stabilization effect by NaCl of Z conformation. We demonstrate by circular dichroism (CD) experiments that Na(+) not only is able to induce a B to Z form transition in a short (GC)3 alternated portion of a sequence having 17 basis, but also is the best stabilizer in comparison with other Z inducers used (spermine and NiCl2). This result was confirmed by free energy calculations.


Primary central nervous system extranodal NK/T-cell lymphoma, nasal type: case report and review of the literature.
Primary central nervous system (CNS) extranodal NK/T-cell lymphoma, nasal type (NKTCL), is an extremely rare tumor. To the best of our knowledge, only four cases have been described previously. Here, we report a case of primary CNS NKTCL in a 25-year-old immunocompetent Chinese male. The patient presented with worsening dizziness, headaches, and vomiting for approximately 2 weeks. Magnetic resonance imaging demonstrated three masses with solid components entirely in the parenchyma of the right hemisphere, and no sinonasal/nasopharyngeal lesions were found. The patient underwent a partial resection of the right temporal mass. Histological examination revealed that intermediate-sized, pleomorphic lymphocytes were arranged in an angiocentric distribution with large geographic necroses. The tumor cells expressed CD3ε, CD56, TIA-1, granzyme B, and Epstein-Barr virus-encoded RNAs. A rearrangement study showed T-cell receptor γ-chain gene rearrangement with monoclonal appearance. Postoperative chemotherapy and radiotherapy were also given, but the lymphoma failed to respond to therapy and the patient died 18 months later. Our observation and the four others found in the literature indicate that primary CNS NKTCL occurs predominantly in adult males. This is the youngest patient with primary CNS NKTCL reported.


Effect of topical betaxolol on the acute rise of aqueous flare induced by highly selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits.
To evaluate the role of topical betaxolol on experimental ocular inflammation in rabbits. Transcorneal diffusion of highly selective agonists for prostaglandin E2 receptor subtypes (EP), 25 microg/ml, with the use of a glass cylinder, was performed to produce aqueous flare elevation in pigmented rabbits. Betaxolol was topically administered before EP agonist application. Aqueous flare was measured with a laser flare cell meter. Performing topical instillation of 0.5% betaxolol 4 times inhibited 52 +/- 9% of EP2-agonist (ONO-AE1-259-01)-induced aqueous flare elevation. The inhibition of flare elevation was dependent on the number of betaxolol instillations. Betaxolol did not suppress the elevation induced by an EP4 agonist (ONO-AE1-392). Betaxolol inhibited EP2-agonist-induced aqueous flare elevation in pigmented rabbits.


Quantitative assessment of hepatic function: modified look-locker inversion recovery (MOLLI) sequence for T1 mapping on Gd-EOB-DTPA-enhanced liver MR imaging.
To determine whether multislice T1 mapping of the liver using a modified look-locker inversion recovery (MOLLI) sequence on gadoxetic acid-enhanced magnetic resonance imaging (MRI) can be used as a quantitative tool to estimate liver function and predict the presence of oesophageal or gastric varices. Phantoms filled with gadoxetic acid were scanned three times using MOLLI sequence to test repeatability. Patients with chronic liver disease or liver cirrhosis who underwent gadoxetic acid-enhanced liver MRI including MOLLI sequence at 3 T were included (n = 343). Pre- and postcontrast T1 relaxation times of the liver (T1liver), changes between pre- and postcontrast T1liver (ΔT1liver), and adjusted postcontrast T1liver (postcontrast T1liver-T1spleen/T1spleen) were compared among Child-Pugh classes. In 62 patients who underwent endoscopy, all T1 parameters and spleen sizes were correlated with varices. Phantom study showed excellent repeatability of MOLLI sequence. As Child-Pugh scores increased, pre- and postcontrast T1liver were significantly prolonged (P < 0.001), and ΔT1liver and adjusted postcontrast T1liver decreased (P < 0.001). Adjusted postcontrast T1liver and spleen size were independently associated with varices (R (2) = 0.29, P < 0.001). T1 mapping of the liver using MOLLI sequence on gadoxetic acid-enhanced MRI demonstrated potential in quantitatively estimating liver function, and adjusted postcontrast T1liver was significantly associated with varices. • T1 mapping using MOLLI sequence can be achieved within a breath-hold. • T1liver measured by MOLLI sequence provided excellent short-term repeatability. • Precontrast and postcontrast T1liver were significantly prolonged as Child-Pugh scores increased. • Adjusted postcontrast T1liver and spleen size were independently associated with varices.


Size versus shape differences: contrasting voxel-based and volumetric analyses of the anterior cingulate cortex in individuals with acute posttraumatic stress disorder.
Two studies found morphological differences in the anterior cingulate cortex (ACC) of individuals with chronic posttraumatic stress disorder (PTSD). We sought to replicate and extend these findings in a sample of individuals with acute PTSD. The ACCs of individuals with acute PTSD (n = 14) and matched healthy control subjects (n = 14) were compared using voxel-based morphometry (VBM), semi-automated volumetric analyses, and probabilistic maps. Posttraumatic stress disorder diagnosis was ascertained by a psychologist using a structured interview. Voxel-based morphometry analyses revealed significantly less gray-matter density in the right pregenual ACC and in the left insula of the PTSD group. However, volumetric analyses of the ACC revealed no significant differences between groups. Probabilistic maps of the labels of the pregenual ACC indicated that the difference between groups in gray matter density was due to shape differences. Although there are no volumetric differences in the ACC of acute PTSD individuals compared with normal control subjects, significant shape differences exist, which might indicate volumetric differences in the surrounding structures.


Retroperitoneal lymph node dissection for Wilms' tumor.
Nephrectomy for Wilms' tumor was performed on 58 patients over a 20-yr period, and retroperitoneal lymphadenectomy was performed on 35 who presented with no demonstrable metastases. The survival rate was 100% for 19 clinical group I patients with negative nodes. Positive nodes in 9 instances led to 5 long-term survivors and significantly influenced staging as a guide for further therapy.


Porcine alanine transaminase after liver allo-and xenotransplantation.
Aspartate transaminase (AST) and alanine transaminase (ALT) are measured following liver transplantation as indicators of hepatocellular injury. During a series of orthotopic liver allo-and xenotransplants, we observed that there was an increase in AST in all cases. The anticipated concomitant rise in ALT did not occur when a wild-type (WT) pig was the source of the liver graft, but did occur when a baboon or a genetically engineered (α1,3-galactosyltransferase gene-knockout [GTKO]) pig was the source of the graft. We hypothesized that the cience of Galα1,3Gal in GTKO pig livers may render pig hepatocytes similar to human and baboon hepatocytes in their response to hepatocellular injury. Reviewing the literature, after WT pig liver allotransplantation or xenotransplantation, in the majority of reports, although changes in AST were reported, no mention was made of changes in ALT, suggesting that there was no change in ALT. However, Ramirez et al. reported two cases of liver xenotransplants from hCD55 pigs, following which there were increases in both AST and ALT, suggesting that it is not simply the cience of expression of Galα1,3Gal that is the cause. We acknowledge that our observation is based on a small number of experiments, but we believe it is worth recording.


Pyrrole alkaloids from the fruiting bodies of edible mushroom Lentinula edodes.
Nine pyrrole alkaloid derivatives, including four new ones (1-4), were isolated from the wild mushroom Lentinula edodes for the first time. Their chemical structures were determined using UV-Vis spectroscopy, IR spectroscopy, MS, NMR spectroscopy, and single-crystal X-ray diffraction techniques. Compound 1, a previously unreported bicylo-pyrrole aldehyde homologue, was found to be a major component, approximately 8.2 μg g -1 in the dry powder of L. edodes. Compound 1 showed cytotoxicity against SMMC-772 (IC50 15.8 μM) without any cytotoxic effect on LO2, a normal hepatic cell line; compounds 1 and 2 displayed weak immunosuppressive activities by inhibiting the proliferation of induced T cells; compound 3 showed inhibition activity on the proliferation of HaCaT cell line (IC50 25.4 μM) and weak antioxidant activity at a concentration of 50 μM.


Real-time 3-dimensional fetal echocardiography with an instantaneous volume-rendered display: early description and pictorial essay.
Random fetal motion, rapid fetal heart rates, and cumbersome processing algorithms have limited reconstructive approaches to 3-dimensional fetal cardiac imaging. Given the recent development of real-time, instantaneous volume-rendered sonographic displays of volume data, we sought to apply this technology to fetal cardiac imaging. We obtained 1 to 6 volume data sets on each of 30 fetal hearts referred for formal fetal echocardiography. Each volume data set was acquired over 2 to 8 seconds and stored on the system's hard drive. Rendered images were subsequently processed to optimize translucency, smoothing, and orientation and cropped to reveal "surgeon's eye views" of clinically relevant anatomic structures. Qualitative comparison was made with conventional fetal echocardiography for each subject. Volume-rendered displays identified all major abnormalities but failed to identify small ventricular septal defects in 2 patients. Important planes and views not visualized during the actual scans were generated with minimal processing of rendered image displays. Volume-rendered displays tended to have slightly inferior image quality compared with conventional 2-dimensional images. Real-time 3-dimensional echocardiography with instantaneous volume-rendered displays of the fetal heart represents a new approach to fetal cardiac imaging with tremendous clinical potential.


Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease.
Satellite cells are adult myogenic stem cells that repair damaged muscle. The enduring capacity for muscle regeneration requires efficient satellite cell expansion after injury, their differentiation to produce myoblasts that can reconstitute damaged fibres and their self-renewal to replenish the muscle stem cell pool for subsequent rounds of injury and repair. Emerging studies indicate that misregulation of satellite cell fate and function can contribute to age-associated muscle dysfunction and influence the severity of muscle diseases, including Duchenne muscular dystrophy (DMD). It has also become apparent that satellite cell fate during muscle regeneration and ageing, and in the context of DMD, is governed by an intricate network of intrinsic and extrinsic regulators. Targeted manipulation of this network may offer unique opportunities for muscle regenerative medicine.


Effectiveness of exercise at workplace in physical fitness: uncontrolled randomized study.
To investigate the effectiveness of workplace exercise for employee health by means of health-related physical activity components. A randomized uncontrolled study with 20 workers was carried out during three months to evaluate a workplace exercise program. The selected outcomes were flexibility, body mass, fat percentage, lean mass, blood pressure, and heart rate. For statistical analysis, the paired t test and the intent-to-treat analysis were used. There was a significant increase in weight, fat percentage, blood pressure, and heart rate. However the clinical significance was 10% in the size of the effect. The changes verified in the outcomes analyzed were not significant; the variables are within normality ranges proposed by academic organizations.


Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer.
With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0-1 considered to have excellent response and grades of 2-3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.


Epidural-evoked potentials: a more specific indicator of spinal cord ischemia.
The purpose of this experimental study was to examine the differences between peripheral nerve stimulation and direct spinal stimulation in generating cortical somatosensory-evoked potential (SEP) responses for monitoring spinal cord ischemia during thoracic aorta cross-clamping. Adult mongrel dogs (n = 6) were placed under general anesthesia and a left thoracotomy was performed. A conventional stimulating electrode was placed over the posterior tibial nerve (PN-SEP), and a special bipolar electrode was placed epidurally over the spinal cord at L1-2 (SC-SEP). The aorta was cross-clamped proximal to the left subclavian artery. Stimulations were alternately performed through both electrodes, and SEP responses were continuously monitored. The cross-clamp was released after one hour and the animal was observed for another hour prior to sacrifice. Excellent SEPs were obtained with six stimuli over 3 sec via the SC-SEP stimulus in contrast to the 200 stimulations over 90 sec required for the PN-SEP stimulus. Aortic cross-clamping resulted in a significantly longer mean time to loss of SEPs for SC-SEP (mean +/- SEM, 13.7 +/- 1.0 min for SC-SEP vs 11.3 +/- 0.7 min for PN-SEP, P less than 0.05). Likewise, unclamping of the aorta consistently resulted in a shorter mean time to return of SEPs for SC-SEP compared with PN-SEP. These data indicate that direct epidural stimulation for evoked cortical responses is a more sensitive means of determining the adequacy of posterior spinal cord blood flow as reflected by posterior spinal cord function.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of inorganic constituents in marine mammal tissues.
Analyses of selected tissues from the Alaska Marine Mammal Tissue Archival Project (AMMTAP) have provided comprehensive information related to levels of 36 trace elements and methyl-mercury in marine mammal tissues. Liver, kidney and muscle tissues from two northern fur seals, four ringed seals and six belukha whales were analyzed. The bulk of the investigated tissues and additional tissues from a total of 65 marine mammals are banked in the AMMTAP. The results are compared to literature values for trace element concentrations in marine mammal tissues and their relevance to environmental studies is discussed.


Adaptation and Innovation in Spiritual-Psycho-Social Support of Displaced Muslim Refugees.
There are over 26 million refugees worldwide, and the majority are Muslims who hail from diverse cultural and geographical backgrounds. It is widely recognized that refugees are at high risk for mental health concerns and are in need of cultural and psychological adaptations to improve their well-being. Given the paucity of data in religio-spiritual adaptation using psychological interventions, the authors propose developing a religio-spiritual training resource that could help humanitarian aid workers and other professionals understand the needs of displaced Muslim refugees (Al-Nuaimi & Qoronfleh, 2020). Here, the authors present a religio-spiritual model that uses evidence-based psychological interventions to provide transcultural religiously and spiritually driven psychological care for displaced Muslim refugees.


Colorectal liver metastases: state-of-the-art management and surgical approaches.
The liver is the most common site of metastasis for patients with colorectal cancer, and resection is associated with significantly improved survival for selected patients. Advancements in perioperative care, operative technique, and multidisciplinary management have led to improved outcomes for patients with colorectal liver metastases (CLM). This review discusses recent advances in perioperative management, patient selection and prognostication, and surgical technique that make up the state-of-the-art management for patients with CLM. Novel approaches to prognostication and measurement of treatment response, such as tumor somatic mutational profiling and circulating tumor DNA (ctDNA), are revolutionary instruments for patient selection and treatment sequence. Further, refinements to surgical approaches for patients with bilateral CLM, including two-stage hepatectomy (TSH), are available for these patients and may lead to improved surgical outcomes. The advances discussed in this review will result in more patients being considered for resection and refined selection for perioperative care strategies that will lead to improved survival for patients with CLM.


Impaired vascular smooth muscle cell force-generating capacity and phenotypic deregulation in Marfan Syndrome mice.
Mechanisms whereby fibrillin-1 mutations determine thoracic aorta aneurysms/dissections (TAAD) in Marfan Syndrome (MFS) are unclear. Most aortic aneurysms evolve from mechanosignaling deregulation, converging to impaired vascular smooth muscle cell (VSMC) force-generating capacity accompanied by synthetic phenotype switch. However, little is known on VSMC mechanoresponses in MFS pathophysiology. Here, we investigated traction force-generating capacity in aortic VSMC cultured from 3-month old mg∆lpn MFS mice, together with morpho-functional and proteomic data. Cultured MFS-VSMC depicted marked phenotype changes vs. wild-type (WT) VSMC, with overexpressed cell proliferation markers but either lower (calponin-1) or higher (SM alpha-actin and SM22) differentiation marker expression. In parallel, the increased cell area and its complex non-fusiform shape suggested possible transition towards a mesenchymal-like phenotype, confirmed through several markers (e.g. N-cadherin, Slug). MFS-VSMC proteomic profile diverged from that of WT-VSMC particularly regarding lower expression of actin cytoskeleton-regulatory proteins. Accordingly, MFS-VSMC displayed lower traction force-generating capacity and impaired contractile moment at physiological substrate stiffness, and markedly attenuated traction force responses to enhanced substrate rigidity. Such impaired mechanoresponses correlated with decreased number, altered morphology and delocalization of focal adhesions, as well as disorganized actin stress fiber network vs. WT-VSMC. In VSMC cultured from 6-month-old mice, phenotype changes were attenuated and both WT-VSMC and MFS-VSMC generated less traction force, presumably involving VSMC aging, but without evident senescence. In summary, MFS-VSMC display impaired force-generating capacity accompanying a mesenchymal-like phenotype switch connected to impaired cytoskeleton/focal adhesion organization. Thus, MFS-associated TAAD involves mechanoresponse impairment common to other TAAD types, but through distinct mechanisms.


Seroepidemiological study of Rift Valley fever (RVF) in animals in Saudi Arabia.
Serological prevalence of IgG antibodies against Rift Valley fever (RVFV) virus was investigated in 22 major localities in five different regions of Saudi Arabia where vaccination against RVF virus (RVFV) is not practiced. The study excludes the southwestern region where a major outbreak of RVF occurred in 2000 and where annual vaccination of ruminants is practiced. Sheep and goat IgG-sandwich ELISA were used to test serum samples from sheep and goats, and bovine IgG-sandwich ELISA was used to test cattle sera. A nonspecies-specific, nonantibody isotype-specific ELISA was used to test camel sera. A total of 3,480 sheep, goats, cattle and camels with no previous history of vaccination against RVFV were randomly tested. All tested animals were negative for IgG class antibodies against the virus except four out of 1,508 sheep and three out of 913 goats, which tested positive. All animals were clinically normal and no evidence was found of virus activity in the studied areas. It is, therefore, most likely that those rare positive cases, which constituted 0.002% of the total animals tested, were either false positives or vaccinates smuggled from the outbreak zone. The need for regular monitoring of animals both within the outbreak zone of 2000 and other parts of the kingdom is strongly emphasized.


Relearning how to learn: enrolled nurse transition to degree at a New Zealand rural satellite campus.
The demise of enrolled nurse (EN) training in New Zealand hastened the development of transition to registration/degree programmes for enrolled nurses. A North Island tertiary institution developed a flexible course to enabled ten enrolled nurses working in rural settings, the majority of whom were Māori, to continue working while studying at a small satellite campus. An exploratory, descriptive, qualitative research study utilizing focus group interviews was undertaken to examine the factors that assisted or hindered their transition. Two major categories emerged from comparative analysis of the data. One category entitled 'relearning how to learn', demonstrated the cognitive and behavioural adaptations made and is the focus of this paper. The other category 'barriers and catapults', demonstrated the physical and environmental factors that influenced the students' transition but is outside the scope of this paper. Recent changes in New Zealand nursing education have witnessed the clarification of scopes of nursing practice and the controversial development of a new Certificate in Health Science (Nurse Assistant). Currently enrolled nurses are again facing threats to employment and it is envisaged that many will be seeking to undertake transition to registered nurse in the near future.


Plasmodium falciparum SSB tetramer binds single-stranded DNA only in a fully wrapped mode.
The tetrameric Escherichia coli single-stranded DNA (ssDNA) binding protein (Ec-SSB) functions in DNA metabolism by binding to ssDNA and interacting directly with numerous DNA repair and replication proteins. Ec-SSB tetramers can bind ssDNA in multiple DNA binding modes that differ in the extent of ssDNA wrapping. Here, we show that the structurally similar SSB protein from the malarial parasite Plasmodium falciparum (Pf-SSB) also binds tightly to ssDNA but does not display the same number of ssDNA binding modes as Ec-SSB, binding ssDNA exclusively in fully wrapped complexes with site sizes of 52-65 nt/tetramer. Pf-SSB does not transition to the more cooperative (SSB)(35) DNA binding mode observed for Ec-SSB. Consistent with this, Pf-SSB tetramers also do not display the dramatic intra-tetramer negative cooperativity for binding of a second (dT)(35) molecule that is evident in Ec-SSB. These findings highlight variations in the DNA binding properties of these two highly conserved homotetrameric SSB proteins, and these differences might be tailored to suit their specific functions in the cell.


Pegaptanib: in exudative age-related macular degeneration.
Pegaptanib, an aptamer, is an antagonist of vascular endothelial growth factor that has shown efficacy in the treatment of patients with exudative age-related macular degeneration (AMD). In two randomised, double-masked trials in patients with exudative AMD (n=1208), the proportion of responders (those losing <15 letters of visual acuity) at 54 weeks was significantly higher in intravitreous pegaptanib 0.3 mg recipients than in those receiving sham injections (70% vs 55%; p<0.001). These trials were conducted concurrently and analysed as a single study; the treatments were given every 6 weeks for 48 weeks. The improvement in visual acuity with pegaptanib was maintained in a 1-year extension of these trials. Similar favourable results with pegaptanib 0.3 mg were seen in terms of the secondary efficacy endpoints (e.g. proportion of patients experiencing severe loss of visual acuity or legal blindness in the study eye). These vision-improving effects of pegaptanib were associated with beneficial angiographic effects. Intravitreous pegaptanib 0.3-3 mg was well tolerated with most ocular adverse events being mild-to-moderate and transient. Serious injection-related adverse events occurred in <or=1.3% of patients treated with pegaptanib. There were no systemic adverse events that could be definitely attributed to pegaptanib.


Radiotherapy-related axillary artery occlusive disease: percutaneous transluminal angioplasty and stenting. Two case reports and review of the literature.
Radiotherapy-related axillary artery occlusive disease is a relatively rare condition. This complication is usually encountered in patients with breast carcinoma treated by radiotherapy and might be frequently concealed by the presence of lymphoedema. We discuss this rare complication of radiotherapy treatment for breast cancer and present two cases and their successful treatment by a modified percutaneous transluminal angioplasty and stenting technique. A review of literature on the subject is also presented.


The fish diversity in the upper reaches of the Salween River, Nujiang River, revealed by DNA barcoding.
Nujiang River (NR), an essential component of the biodiversity hotspot of the Mountains of Southwest China, possesses a characteristic fish fauna and contains endemic species. Although previous studies on fish diversity in the NR have primarily consisted of listings of the fish species observed during field collections, in our study, we DNA-barcoded 1139 specimens belonging to 46 morphologically distinct fish species distributed throughout the NR basin by employing multiple analytical approaches. According to our analyses, DNA barcoding is an efficient method for the identification of fish by the presence of barcode gaps. However, three invasive species are characterized by deep conspecific divergences, generating multiple lineages and Operational Taxonomic Units (OTUs), implying the possibility of cryptic species. At the other end of the spectrum, ten species (from three genera) that are characterized by an overlap between their intra- and interspecific genetic distances form a single genetic cluster and share haplotypes. The neighbor-joining phenogram, Barcode Index Numbers (BINs) and Automatic Barcode Gap Discovery (ABGD) identified 43 putative species, while the General Mixed Yule-coalescence (GMYC) identified five more OTUs. Thus, our study established a reliable DNA barcode reference library for the fish in the NR and sheds new light on the local fish diversity.


Transcatheter aortic valve replacement for stenotic bicuspid aortic valves: Systematic review and meta analyses of observational studies.
The aim of this study was to perform a systematic review and meta-analyses of observational studies of transcatheter aortic valve replacement (TAVR) for bicuspid aortic valve stenosis (BcAV). TAVR for BcAV stenosis has been associated with an increased incidence of paravalvular leaks, valve malposition, pacemaker placement and all-cause mortality. The conclusions drawn have been limited by small sample sizes. The use of TAVR for BcAV stenosis remains controversial. We searched multiple databases from the inception of the databases through September 30, 2016 for studies of TAVR for BcAV stenosis. We included all observational studies with more than one patient and at least 1 month of outcomes. We analyzed 13 observational studies with 758 patients. Meta analyses showed device success rate of 95% [95% confidence interval (CI) 90.2% to 98.5%] and an early safety event in 16.9% [95% CI 12.2% to 22%]. At 30 days, moderate to severe paravalvular leak was seen in 12.2% [95% CI 3.1% to 24.8%] and new pacemaker implantation in 17.9% [95% CI 14.2% to 22%]. All-cause mortality was 3.7% [95% CI 2.1% to 5.6%], which should be viewed in the context of an STS PROM of 5.0%. This analysis suggests that TAVR for BcAV is not associated with excess mortality. The incidence of paravalvular leaks and pacemaker implant is increased compared to tricuspid aortic valve cohorts undergoing TAVR, and operators should weigh these potential complications against the clinical benefit provided by TAVR for BcAV patients at high risk for surgical valve replacement.


Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke.
Some patients with mild or improving ischemic stroke symptoms do not receive intravenous tissue plasminogen activator (tPA) because they look "too good to treat" (TGT); however, some have poor outcomes. We retrospectively analyzed data from a prospective single-center study between 2002 and 2004. TGT patients were those arriving within 3 hours of symptom onset and not treated with intravenous tPA solely because of mild or improving symptoms. Of 128 patients presenting within 3 hours, 41 (34%) were not given tPA because of mild or improving stroke. Of the TGT patients, 11 of 41 (27%) died or were not discharged home because of neurological worsening (n=6) or persistent "mild" neurological deficit (n=5). No single variable at presentation was associated with death or lack of home discharge. There were 10 of 41 TGT patients (24%) who had > or =4-point improvement in National Institutes of Health Stroke Scale score before tPA decision; these patients were more likely to have subsequent neurological worsening (relative risk, 4.1, 95% CI, 1.1 to 15.4; P=0.05). A substantial minority of patients deemed too good for intravenous tPA were unable to be discharged home. A re-evaluation of the stroke severity criteria for tPA eligibility may be indicated.


Effective degree household network disease model.
An ordinary differential equation (ODE) epidemiological model for the spread of a disease that confers immunity, such as influenza, is introduced incorporating both network topology and households. Since most individuals of a susceptible population are members of a household, including the household structure as an aspect of the contact network in the population is of significant interest. Epidemic curves derived from the model are compared with those from stochastic simulations, and shown to be in excellent agreement. Expressions for disease threshold parameters of the ODE model are derived analytically and interpreted in terms of the household structure. It is shown that the inclusion of households can slow down or speed up the disease dynamics, depending on the variance of the inter-household degree distribution. This model illustrates how households (clusters) can affect disease dynamics in a complicated way.


Plant-specific expression of antipredator behaviour by larval damselflies.
In this study of interactions between larval damselflies (Zygoptera: Coenagrionidae) and pumpkinseed sunfish (Lepomis gibbosus) we focus on the behaviour of the damselfly prey. First we document a prey behaviour in which damselflies use plant stems or leaves to hide from pumpkinseeds. We then test two hypotheses: (1) that damselfly 'hiding' is a specific antipredator behaviour and (2) that 'hiding' occurs more frequently in plant habitats where damselflies experience greater risk of predation. Since plant species growth forms can influence predation risk, our second hypothesis implies that hiding behaviour is conditional upon the type of vegetation providing habitat structure. Conditional expression of antipredator behaviour according to vegetation type may be important in littoral environments, since predator-prey interactions can occur in habitats with a wide range of macrophyte growth forms. The first hypothesis was supported by our findings that damselfly hiding increased in frequency in the presence of pumpkinseeds, that it was related to the frequency of predator approaches, and that its use reduced damselfly predation risk in high risk habitats. The second hypothesis was supported by our results that damselfly hiding rates were greater in the high risk Scirpus habitats than in the lower risk Potamogeton habitats. These results indicate that prey behaviour can influence predator-prey interactions, and that variation in plant growth form can influence prey behaviour, thus contributing to the impact of habitat structure on predator-prey dynamics.


Alpha lipoic acid (ALA) modulates expression of apoptosis associated proteins in hippocampus of rats exposed during postnatal period to sodium arsenite (NaAsO2).
The present study focused on the role of exogenous alpha lipoic acid (ALA) in amelioration of inorganic arsenic (iAs) induced effects on apoptosis and apoptosis associated proteins in developing rat hippocampus. NaAsO2 (1.5/2.0 mg/kg bw) alone or along with ALA (70 mg/kg bw) was administered to rat pups (experimental groups) by intraperitoneal (i.p.) route from postnatal day (PND) 4-15. Controls received no treatment/distilled water/ALA. On PND 16, the animals were perfusion fixed and the brains were processed for paraffin embedding (CV and TUNEL staining) and cryopreservation (immunohistochemistry). The fresh brain tissue was used for Western blotting. Significant increase was observed in TUNEL positive cells and Bax (pro-apoptotic protein) expression in hippocampal sub-regions of iAs alone treated groups, whereas Bcl-2 expression was intensified in animals receiving ALA with iAs. Densitometric analysis (Western blots) revealed optimal restoration of Bax and Bcl-2 ratio in animals receiving ALA with iAs, thereby suggesting the protective role of ALA in iAs induced developmental neurotoxicity.


Learning environment and emotional well-being: A qualitative study of undergraduate nursing students.
Students can experience multiple stressors during their academic life which have an impact on their emotional health and academic progress. This study sought to explore students' understanding of and factors affecting their emotional well-being in an undergraduate nursing programme at a private nursing institution in Karachi, Pakistan. In this qualitative study, data were collected through individual semi-structured interviews using a self-designed guide from 16 participants in total, drawn from various years of the selected undergraduate programme. Participants noted that the quality of the 'learning environment' was a key influence on their emotional well-being. They highlighted faculty role and teaching approaches, academic expectations and availability of learning resources as important factors that affected their emotional well-being as well as their academic performance. Institutional support was also deemed important. Factors associated with a 'hidden curriculum' were found to be a threat to students' emerging sense of professionalism. Suggestions are given as to how the learning environment in the nursing programme under study can be improved to take into account students' emotional well-being. Emphasis needs to be laid on developing supportive faculty role to provide conducive learning environment and professional development of students. Efforts to develop stress-free academic environment with supportive institutional policies need to be considered.


Occurrence of Cucumber mosaic virus on vanilla (Vanilla planifolia Andrews) in India.
Cucumber mosaic virus (CMV) causing mosaic, leaf distortion and stunting of vanilla (Vanilla planifolia Andrews) in India was characterized on the basis of biological and coat protein (CP) nucleotide sequence properties. In mechanical inoculation tests, the virus was found to infect members of Chenopodiaceae, Cucurbitaceae, Fabaceae and Solanaceae. Nicotiana benthamiana was found to be a suitable host for the propagation of CMV. The virus was purified from inoculated N. benthamiana plants and negatively stained purified preparations contained isometric particles of about 28 nm in diameter. The molecular weight of the viral coat protein subunits was found to be 25.0 kDa. Polyclonal antiserum was produced in New Zealand white rabbit, immunoglobulin G (IgG) was purified and conjugated with alkaline phosphatase enzyme. Double antibody sandwich-enzyme linked immunosorbent assay (DAS-ELISA) method was standardized for the detection of CMV infection in vanilla plants. CP gene of the virus was amplified using reverse transcriptase-polymerase chain reaction (RT-PCR), cloned and sequenced. Sequenced region contained a single open reading frame of 657 nucleotides potentially coding for 218 amino acids. Sequence analyses with other CMV isolates revealed the greatest identity with black pepper isolate of CMV (99%) and the phylogram clearly showed that CMV infecting vanilla belongs to subgroup IB. This is the first report of occurrence of CMV on V. planifolia from India.


Primary spinal epidural non-Hodgkin's diffuse large B-cell lymphoma: A case report.
Rare disease like primary spinal epidural diffuse large B-cell lymphoma should be considered as a differential diagnosis in patients presenting with back pain and rapid neurological deterioration in the lower extremities.


Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failure.
Left ventricular (LV) dilation, which is a predictor of survival in humans with chronic heart failure (CHF), is limited by a mixed endothelin ETA-ETB antagonist. Whether selective ETA receptor blockade influences LV dilation is unknown. We determined, in a rat model of CHF, the effects of the ETA receptor blocker LU 135,252 on LV remodeling. Rats were subjected to coronary artery ligation and treated for ten weeks with placebo or LU 135,252 (LU), at a dose of 10 or 30 mg kg-1 day-1. Systolic blood pressure and heart rate (plethysmography) were determined in conscious animals before and after four and ten weeks of treatment. At these time points, cardiac output and LV dimensions were measured in anesthetized rats by transthoracic echocardiography. LV hemodynamics were determined in anesthetized rats after ten weeks. Pressor responses to ET-1 (1 nmol/kg, i.v.) and sarafotoxin S6c (0.3 ng/kg, i.v.) were measured, to assess the efficacy of ET receptor antagonism and the lack of blockade of ETB receptor blockade, respectively. The pressor response to ET-1 was significantly reduced by LU (% change in systolic blood pressure: sham: 9 +/- 1; CHF: 5 +/- 1; CHF LU: 0 +/- 3 and -4 +/- 2% for the low and high dose, respectively). LU did not affect the response to sarafotoxin (CHF: -37 +/- 3; CHF LU: -29 +/- 3 and -28 +/- 2% for the low and high dose, respectively). Both doses of LU decreased systolic blood pressure, but only the high dose of LU reduced heart rate. Furthermore, LU restored cardiac output dose-dependently throughout the study. Both doses of LU limited LV dilatation and deterioration of LV fractional shortening to the same extent. After ten weeks, LU normalized LV end-diastolic- and central venous pressures, but did not affect LV dP/dtmax or dP/dtmin. LU did not prevent the development of cardiac hypertrophy, but reduced LV collagen density. In this rat model, the selective ETA receptor blocker LU, at the dose of 30 mg kg-1 day-1, reduced blood pressure and heart rate, limited progressive left ventricular remodeling and improved cardiac hemodynamics and function. These effects of LU might have important clinical relevance in the treatment of heart failure.


Fisheries subsidies reform in China.
Subsidies are widely criticized in fisheries management for promoting global fishing capacity growth and overharvesting. Scientists worldwide have thus called for a ban on "harmful" subsidies that artificially increase fishing profits, resulting in the recent agreement among members of the World Trade Organization to eliminate such subsidies. The argument for banning harmful subsidies relies on the assumption that fishing will be unprofitable after eliminating subsidies, incentivizing some fishermen to exit and others to refrain from entering. These arguments follow from open-access governance regimes where entry has driven profits to zero. Yet many modern-day fisheries are conducted under limited-access regimes that limit capacity and maintain economic profits, even without subsidies. In these settings, subsidy removal will reduce profits but perhaps without any discernable effect on capacity. Importantly, until now, there have been no empirical studies of subsidy reductions to inform us about their likely quantitative impacts. In this paper, we evaluate a policy reform that reduced fisheries subsidies in China. We find that China's subsidy reductions accelerated the rate at which fishermen retired their vessels, resulting in reduced fleet capacity, particularly among older and smaller vessels. Notably, the reduction of harmful subsidies was only partly responsible for reducing fleet capacity; an increase in vessel retirement subsidies was also a necessary driver of capacity reduction. Our study demonstrates that the efficacy of removing harmful subsidies depends on the policy environment in which removals occur.


Mechanical and matrix effects of short and long-duration exposure to beta-aminopropionitrile in elastase-induced model abdominal aortic aneurysm in mice.
Evaluate the mechanical and matrix effects on abdominal aortic aneurysms (AAA) during the initial aortic dilation and after prolonged exposure to beta-aminopropionitrile (BAPN) in a topical elastase AAA model. Abdominal aortae of C57/BL6 mice were exposed to topical elastase with or without BAPN in the drinking water starting 4 days before elastase exposure. For the standard AAA model, animals were harvested at 2 weeks after active elastase (STD2) or heat-inactivated elastase (SHAM2). For the enhanced elastase model, BAPN treatment continued for either 4 days (ENH2b) or until harvest (ENH2) at 2 weeks; BAPN was continued until harvest at 8 weeks in one group (ENH8). Each group underwent assessment of aortic diameter, mechanical testing (tangent modulus and ultimate tensile strength [UTS]), and quantification of insoluble elastin and bulk collagen in both the elastase exposed aorta as well as the descending thoracic aorta. BAPN treatment did not increase aortic dilation compared with the standard model after 2 weeks (ENH2, 1.65 ± 0.23 mm; ENH2b, 1.49 ± 0.39 mm; STD2, 1.67 ± 0.29 mm; and SHAM2, 0.73 ± 0.10 mm), but did result in increased dilation after 8 weeks (4.3 ± 2.0 mm; P = .005). After 2 weeks, compared with the standard model, continuous therapy with BAPN did not have an effect on UTS (24.84 ± 7.62 N/cm2; 18.05 ± 4.95 N/cm2), tangent modulus (32.60 ± 9.83 N/cm2; 26.13 ± 9.10 N/cm2), elastin (7.41 ± 2.43%; 7.37 ± 4.00%), or collagen (4.25 ± 0.79%; 5.86 ± 1.19%) content. The brief treatment, EHN2b, resulted in increased aortic collagen content compared with STD2 (7.55 ± 2.48%; P = .006) and an increase in UTS compared with ENH2 (35.18 ± 18.60 N/cm2; P = .03). The ENH8 group had the lowest tangent modulus (3.71 ± 3.10 N/cm2; P = .005) compared with all aortas harvested at 2 weeks and a lower UTS (2.18 ± 2.18 N/cm2) compared with both the STD2 (24.84 ± 7.62 N/cm2; P = .008) and ENH2b (35.18 ± 18.60 N/cm2; P = .001) groups. No differences in the mechanical properties or matrix protein concentrations were associated with abdominal elastase exposure or BAPN treatment for the thoracic aorta. The tangent modulus was higher in the STD2 group (32.60 ± 9.83 N/cm2; P = .0456) vs the SHAM2 group (17.99 ± 5.76 N/cm2), and the UTS was lower in the ENH2 group (18.05 ± 4.95 N/cm2; P = .0292) compared with the ENH2b group (35.18 ± 18.60 N/cm2). The ENH8 group had the lowest tangent modulus (3.71 ± 3.10 N/cm2; P = .005) compared with all aortas harvested at 2 weeks and a lower UTS (2.18 ± 2.18 N/cm2) compared with both the STD2 (24.84 ± 7.62 N/cm2; P = .008) and ENH2b (35.18 ± 18.60 N/cm2; P = .001) groups. Abdominal aortic elastin in the STD2 group (7.41 ± 2.43%; P = .035) was lower compared with the SHAM2 group (15.29 ± 7.66%). Aortic collagen was lower in the STD2 group (4.25 ± 0.79%; P = .007) compared with the SHAM2 group (12.44 ± 6.02%) and higher for the ENH2b (7.55 ± 2.48%; P = .006) compared with the STD2 group. Enhancing an elastase AAA model with BAPN does not affect the initial (2-week) dilation phase substantially, either mechanically or by altering the matrix content. Late mechanical and matrix effects of prolonged BAPN treatment are limited to the elastase-exposed segment of the aorta. This paper explores the use of short- and long-term exposure to beta-aminopropionitrile to create an enhanced topical elastase abdominal aortic aneurysm model in mice. Readouts of aneurysm severity included loss of mechanical stability and vascular extracellular matrix composition reminiscent of what is seen in the course of human disease. Additionally, we show that the thoracic aorta, unlike the findings below the renal arteries, is not damaged in our animal model.


The "Breast-4Y" web app for breast cancer prevention at young age: Development, evaluation, and validation.
Improving knowledge of risk factors, signs and symptoms positively influence an individual's intention to acquire healthy lifestyle behaviors to prevent breast cancer, to identify breast cancer risk early and seek health advice early. The aim of the present study was to develop and to assess the usability and quality of a web-app (Breast-4Y) designed specifically for younger women to improve their knowledge about breast cancer risk factors and symptoms as well as protective behaviors to reduce their risk. The development of the Breast-4Y web-app, based on Health Belief Model and the Behaviour Change Wheel, comprised four steps: i) analysis of scientific literature regarding breast cancer risk factors, symptoms and preventive lifestyle behaviors; ii) design of web-app; iii) content review by experts; iv) quality and usability assessment by the end-users (n = 20). Web-app usability was evaluated using the Spanish version of the System Usability Scale for the Assessment of Electronic Tools and the quality using the Spanish version of uMARS. The contents were rated 4.25 or above, indicating high content quality. The mean usability score was 84.9 (SD 12.4), the mean rating for objective quality and subjective quality dimensions mean were 4.2 (SD 0.4) and 3.4 (0.777) respectively, indicating excellent usability and quality. Positive associations (p < .05) were observed between numbers of app used and attitudes to change (r = 0.479), and intention to change (r = 0.539). Strong positive associations (p < .001) were also observed between usability satisfaction and attitudes to change (r = 0.584), intention to change (r = 0.656), and help-seeking (r = 0.656). This study provided evidence that Breast-4Y has adequate contents, high quality, and usability. Breast-4Y can be tested in pragmatic trials to assess their effectiveness to reduce the risk of breast cancer, raise women's awareness of breast cancer risk factors, increase women's knowledge of breast cancer symptoms, and adopt protective lifestyle behaviors.


The social production of substance abuse and HIV/HCV risk: an exploratory study of opioid-using immigrants from the former Soviet Union living in New York City.
Several former Soviet countries have witnessed the rapid emergence of major epidemics of injection drug use (IDU) and associated HIV/HCV, suggesting that immigrants from the former Soviet Union (FSU) may be at heightened risk for similar problems. This exploratory study examines substance use patterns among the understudied population of opioid-using FSU immigrants in the U.S., as well as social contextual factors that may increase these immigrants' susceptibility to opioid abuse and HIV/HCV infection. In-depth interviews were conducted with 10 FSU immigrants living in New York City who initiated opioid use in adolescence or young adulthood, and with 6 drug treatment providers working with this population. Informed by a grounded theory approach, interview transcripts were inductively coded and analyzed to identify key themes. The "trauma" of the immigration/acculturation experience was emphasized by participants as playing a critical role in motivating opioid use. Interview data suggest that substance use patterns formed in the high-risk environment of the FSU may persist as behavioral norms within New York City FSU immigrant communities - including a predilection for heroin use among youth, a high prevalence of injection, and a tolerance for syringe sharing within substance-using peer networks. Multiple levels of social context may reproduce FSU immigrants' vulnerability to substance abuse and disease such as: peer-based interactional contexts in which participants typically used opioids; community workplace settings in which some participants were introduced to and obtained opioids; and cultural norms, with roots in Soviet-era social policies, stigmatizing substance abuse which may contribute to immigrants' reluctance to seek disease prevention and drug treatment services. Several behavioral and contextual factors appear to increase FSU immigrants' risk for opioid abuse, IDU and infectious disease. Further research on opioid-using FSU immigrants is warranted and may help prevent increases in HIV/HCV prevalence from occurring within these communities.


Total magnetic resonance imaging burden of cerebral small-vessel disease is associated with post-stroke depression in patients with acute lacunar stroke.
Despite extensive studies on post-stroke depression (PSD), the role of the total burden of cerebral small-vessel disease (cSVD) in its pathogenesis remains unclear. We conducted a magnetic resonance imaging (MRI)-based cohort study to investigate the relationship between total MRI burden of cSVD and PSD among patients with first-ever lacunar stroke. From June 2013 to January 2016, 374 patients were consecutively recruited. PSD was identified using the Chinese version of the Structured Clinical Interview for DSM-IV. Brain MRI presence of silent lacunar infarcts, white-matter lesions, cerebral microbleeds and enlarged perivascular spaces was summed to an ordinal score between 0 and 4. Multivariable logistic regression analysis was performed to determine the contribution of total MRI cSVD burden in the prediction of PSD. Ninety patients (24.1%) were diagnosed with PSD at 3 months after stroke. Only two MRI markers of cSVD, asymptomatic lacunar infarcts and white-matter lesions, were related to PSD [odds ratio (OR), 3.167; 95% confidence interval (CI), 1.879-5.338; P = 0.001 and OR, 2.284; 95% CI, 1.403-3.713; P = 0.001, respectively]. Moreover, higher total MRI cSVD burden was an independent predictor for PSD (high tertile OR, 4.577; 95% CI, 2.400-8.728; P = 0.001) after adjusting for individual cSVD MRI marker and other potential confounders. This study demonstrated that greater total MRI burden of cSVD may predict the presence of PSD in patients with acute lacunar stroke.


The efficacy of cystatin C assay in the prediction of glomerular filtration rate. Is it a more reliable marker for renal failure?
We determined the sensitivity, specificity, receiver operating characteristics and correlation between cystatin C (cysC) and two widely used markers of renal function, creatinine clearance and serum creatinine, in 244 patients (84 diabetics, 84 hypertensive and 76 healthy subjects). Renal failure was defined as creatinine clearance of less than either 80 or 60 mL/min. Variables were evaluated for two definitions of renal failure and compared between patient groups. Correlation coefficients with cysC were -0.87 for creatinine clearance and 0.92 for creatinine in patients with hypertension; -0.90 for creatinine clearance and 0.97 for creatinine in diabetics; and -0.61 for creatinine clearance and 0.94 for creatinine in the control group. The receiver operating characteristic curves with a cut-off value of 60 mL/min were similar for creatinine and cysC, while at 80 mL/min they were 0.626 for creatinine and 0.813 for cysC levels. We classified the patients into three groups with respect to creatinine clearance (1, >80 mL/min; 2, 60-80 mL/min; 3, <60 mL/min). Mean creatinine (p<0.0001) and cysC (p<0.0001) levels were significantly different between all the groups. Sensitivity, specificity and predictive values were higher for cysC levels, particularly in diabetics and hypertensive patients. The current study suggests that cysC is preferable for detecting temporal changes in renal function in the early stages of renal insufficiency.


Ultrasonographic Evaluation of Zone II Partial Flexor Tendon Lacerations of the Fingers: A Cadaveric Study.
Accurate assessment of zone II partial flexor tendon lacerations in the finger is clinically important. Surgical repair is recommended for lacerations of greater than 50% to 60%. Our goal was to evaluate ultrasonographic test characteristics and accuracy in identifying partial flexor tendon lacerations in a cadaveric model. From fresh-frozen above-elbow human cadaveric specimens, 32 flexor digitorum profundus tendons were randomly selected to remain intact or receive low- or high-grade lacerations involving 10% to 40% and 60% to 90% of the radioulnar width within Verdan Zone II, respectively. Static and dynamic ultrasonography using a linear array 14-MHz transducer was performed by a blinded musculoskeletal radiologist. Sensitivities, specificities, and other standard test performance metrics were calculated. Actual and measured percentages of tendon laceration were compared by the paired t test. After randomization, 24 tendons were lacerated (12 low- and 12 high-grade), whereas 8 remained intact. The sensitivity and specificity in detecting the presence versus absence of a partial laceration were 0.54 and 0.75, respectively, with positive and negative likelihood ratio values of 2.17 and 0.61. For low-grade lacerations, the sensitivity and specificity were 0.25 and 0.85, compared to 0.83 and 0.85 for high-grade lacerations. Ultrasonography underestimated the percentage of tendon involvement by a mean of 18.1% for the study population as a whole (95% confidence interval, 9.0% to 27.2%; P < .001) but accurately determined the extent for correctly diagnosed high-grade lacerations (-6.7%; 95% confidence interval, -18.7% to 5.2%; P = .22). Ultrasonography was useful in identifying and characterizing clinically relevant high-grade zone II partial flexor digitorum profundus lacerations in a cadaveric model.


GABAergic modulation of striatal cholinergic interneurons: an in vivo microdialysis study.
Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABAA and the GABAB receptor. Using in vivo microdialysis, we have studied the effect of intrastriatal application of the GABAA-selective compounds muscimol and bicuculline and the GABAB-selective compounds baclofen and 2-hydroxysaclofen, agonists and antagonists, respectively, at GABA receptors, on the output of striatal acetylcholine (ACh). Intrastriatal infusion of 1 and 10 mumol/L concentrations of the GABAA antagonist bicuculline resulted in a significant increase in striatal ACh output, whereas infusion of 1 and 10 mumol/L concentrations of the GABAA agonist muscimol significantly decreased the output of striatal ACh. Both compounds were ineffective in changing the output of striatal ACh at lower concentrations. Infusion of concentrations up to 100 mumol/L of the GABAB-selective antagonist 2-hydroxy-saclofen failed to affect striatal ACh output, whereas infusion of 10 and 100 mumol/L baclofen, but not 0.1 and 1 mumol/L baclofen, significantly decreased the output of striatal ACh. Thus, agonist-stimulation of GABAA and GABAB receptors decreases the output of striatal ACh in a dose-dependent fashion, whereas the GABAAergic system appears to inhibit tonically the output of striatal ACh via GABAA receptors, but not via GABAB receptors. We hypothesize that although GABAA mediated regulation of striatal ACh occurs via GABA receptors on the cholinergic neuron, the GABAB mediated effects may be explained by presynaptic inhibition of the glutamatergic input of the striatal cholinergic neuron.


Bleeding diatheses and preoperative screening.
Bleeding disorders pose a significant perioperative risk. Surgeons and surgical consultants should have a working knowledge of the cell-based coagulation model. Careful screening for bleeding diatheses begins with a careful history and physical examination. It is paramount to ascertain what medications and nonprescribed supplements and herbal preparations a patient is taking, as these medications can have significant effects on perioperative bleeding tendencies. Finally, screening laboratory-based coagulation assays are available. These must be used judiciously with regard to a patient's history and the clinical circumstances surrounding the surgical stressor.


Carboxymethyl cellulose gels immobilized Ag/AgCl-ZnO nanoparticles for improving sunlight-catalyzed antibacterial performance.
Antibacterial sodium carboxymethyl cellulose (CMC) gels were prepared via immobilizing ZnO and/or Ag/AgCl in situ to inhibit the aggregation of nano-photocatalyst. Epichlorohydrin was used as a crosslinking agent to prepare CMC gel, simultaneously introducing chlorine-containing branch chains as Cl reservoir to deposit AgCl. The composite gels presented pH responsive swelling properties, with the minimum swelling ratio at pH 8 and pH 4 for CMC gels containing Ag/AgCl and ZnO, respectively. Zn2+ release from the nanocomposite gels was much greater in acidic than in neutral. Photocatalytic degradation constants of methyl orange by the composite gels under sunlight were greater than UV irradiation. Ag/AgCl loaded gel showed a degradation rate of 71.3 % under sunlight for 1 h, with a rate constant approximately 10.2 times higher than ZnO loaded gel. Extract liquids with the gel content below 0.33 mg/mL were noncytotoxicity. The nanocomposite gels presented good bactericidal rate against E. coli and S. aureus under sunlight for 6 h, comparatively to those in dark for 24 h. Bacteriostatic activity of Ag/AgCl loaded gel under sunlight for 6 h was much greater than that in dark for 24 h. The biocompatible nanocomposite gels with sunlight-catalyzed antibacterial activity would broaden the application of CMC gels.


[Rate of gluconeogenesis in the liver of rats with myocardial infarction].
It has been shown for the first time that the rate of glucose synthesis from endogenous non-carbohydrate compounds in the perfused liver of rats with occlusion of the descending branch of the left coronary artery increased. Gluconeogenesis appeared to be the most intense by the third day after occlusion. The rate of gluconeogenesis was identical both in control and experimental animals by the 10th and 20th days after occlusion.


First in vivo evaluation of the mutagenic effect of Brazilian green propolis by comet assay and micronucleus test.
Propolis is a hive product containing chiefly beeswax and plant-derived substances such as resin and volatile compounds. Propolis has been used in various parts of the world as an antiseptic and wound healer since ancient times, and interest in the product has recently increased. Considering the lack of data concerning the in vivo mutagenicity of green propolis, the capacity of this natural product to cause damage to the DNA was evaluated, using the alkaline single-cell gel electrophoresis (SCGE) and micronucleus test, in the peripheral blood cells of mice. The doses tested by gavage were 1000, 1500 and 2000 mg/kg. Micronucleus and SCGE assays showed that green propolis caused an increase in the damage to DNA in the peripheral blood cells of mice. The polychromatic:normochromatic erythrocytes ratio was not statistically different from the negative control. Considering the doses and the results obtained in this study, the acute consumption of green propolis produced some mutagenic effects on the blood cells of mice.


TRPC channel expression during calcium-induced differentiation of human gingival keratinocytes.
Extracellular calcium is an important regulator of keratinocyte differentiation. An increase in intracellular calcium ion concentration is required for activation of calcium-induced keratinocyte differentiation. The signaling elements in this differentiation response include the calcium sensing receptor, phospholipase C, release of calcium ions from intracellular stores, and store-operated calcium channels. Nothing is currently known about the calcium-entry channels activated by the increase in external calcium. However, canonical transient receptor potential (TRPC) channels have been identified as store-operated calcium channels in several tissues. To examine the expression of TRPC channels in human gingival keratinocytes (HGKs) in primary culture under both low calcium (basal) and high calcium (differentiating) conditions, and in gingival tissue. TRPC channel expression was evaluated via RT-PCR, Western blots, and immunohistology. TRPC1, TRPC5, TRPC6 and TRPC7 mRNAs were detected in undifferentiated keratinocytes. Their levels initially increased, then decreased during calcium-induced differentiation. TRPC1 and TRPC6 protein expression reflected these changes. TRPC channels are present in both proliferating and differentiating keratinocytes in primary culture and in gingival tissue. The above expression patterns suggest that these channels may be involved in calcium-induced differentiation of keratinocytes.


Binding of phytoestrogens to rat uterine estrogen receptors and human sex hormone-binding globulins.
The interaction of phytoestrogens with the most important binding sites of steroid hormones, i.e. sex hormone-binding globulin and estrogen receptors, was investigated. Relative binding affinities and association constants for 21 compounds among them isoflavones, flavones, flavonols, flavanones, chalcones and lignans were determined. The lignan nordihydroguaiaretic acid weakly displaced 17beta-[3H]-estradiol from estrogen receptor and Scatchard analysis suggests non-conformational changes. Compounds from Glycyrrhiza glabra, liquiritigenin and isoliquiritigenin, showed estrogenic affinities to both receptors. 18beta-Glycyrrhetinic acid displaced 17beta-[3H]-estradiol from sex hormone-binding globulin but not from the estrogen receptor. Phytoestrogens compete with 17beta-estradiol much stronger than with 5alpha-dihydrotestosterone for binding to sex hormone-binding globulin.


Effects of smoking on coronary blood flow velocity and coronary flow reserve assessed by transthoracic Doppler echocardiography.
Smoking is a well-known risk factor for cardiovascular disease. Coronary blood flow velocity (CFV) can be measured directly with transthoracic Doppler echocardiography (TTDE) which is conducted immediately after smoking. The purpose of this study was to evaluate the chronic and acute effects of smoking on coronary blood flow and coronary flow reserve (CFR) by the use of TTDE. Healthy volunteers (11 smokers and 9 nonsmokers) with a mean age of 27 +/- 3 years were included. Smoking was abstained for at least 4 hours before the study. CFV was measured at the distal left anterior descending coronary artery by TTDE at baseline and during intravenous adenosine infusion (140 microg/kg per minute) in all participants. For smokers, CFV was measured immediately after consecutively smoking two cigarettes and during adenosine infusion. CFR and coronary vascular resistance index (CVRI) showed no significant difference between nonsmokers and smokers (CFR: 3.5 +/- 0.8 vs 3.6 +/- 0.6, P = ns, CVRI: 0.28 vs 0.28, P = ns) at baseline. CFR significantly decreased (3.6 +/- 0.6 to 2.8 +/- 0.7, P = 0.008) and CVRI markedly increased (0.28 to 0.35, P = 0.012) after smoking. After 4 hours of abstinence from smoking, CFR and CVRI in smokers were similar to those of nonsmokers. However, consecutively smoking two cigarettes acutely reduced CFR and increased CVRI. These findings suggested that smoking could reduce coronary blood flow immediately, even in healthy people.