Existence of multiple organ aging in animal model of emphysema induced by cigarette smoke extract.
It is commonly considered that COPD or at least emphysema represents accelerated lung aging induced in part by oxidative damage from cigarette smoke components. However, the issue if there are any aging signs in other organs in patients with COPD or emphysema remains unclear. The aim of this study is to explore whether there is multiple organ aging in the animal model of emphysema induced by cigarette smoke extract (CSE), and to ascertain the possible mechanisms, if any. The animal model of emphysema was induced by CSE. Histomorphological changes in lung, heart, liver, kidney and spleen tissues were measured after staining with hematoxylin and eosin (H&E). The concentrations of stem cell factor (SCF), CyclinD1 and superoxide dismutase (SOD) in serum were determined by ELISA kit. The expressions of p16 (INK4a), Sca-1, eNOS proteins and mRNA in lung, heart, liver, kidney and spleen tissues were detected by Western blotting and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), respectively. Decitabine (Dec) was applied to examine whether it could alter the changes caused by CSE. The histomorphology of lung tissue was significantly changed, while other organs exhibited normal structure and histomorphology. The concentrations of SCF, CyclinD1 and SOD in serum were lower in the CSE group than in the control group. The expression levels of p16(INK4a) protein and mRNA in lung, heart, liver, kidney and spleen tissues were higher in the CSE group than in the control group, while the expression levels of Sca-1 and eNOS proteins and mRNA were lower in the CSE group than in the control group, in the tissues described above. Dec could partly alleviate the damages caused by CSE and the degree of alleviation resulted by Dec varied from organ to organ. In addition to the aging of the lung tissue in the emphysema animal model induced by CSE, the tissues of the heart, liver, kidney and spleen were also in the progress of aging, but the sensibility and affinity of lung to CSE were higher than those of the other organs. Multiple organ aging may also exist in the animal model of emphysema induced by CSE. DEC can partly alleviate the multiple organ aging caused by CSE.


N-acetyl-L-cysteine and cysteine increase intracellular calcium concentration in human neutrophils.
N-acetyl-L-cysteine (NAC) and cysteine have been implicated in a number of human neutrophils' functional responses. However, though Ca(2+) signaling is one of the key signalings contributing to the functional responses of human neutrophils, effects of NAC and cysteine on intracellular calcium concentration ([Ca(2+)]i) in human neutrophils have not been investigated yet. Thus, this study was carried out with an objective to investigate the effects of NAC and cysteine on [Ca(2+)]i in human neutrophils. We observed that NAC (1 µM ~ 1 mM) and cysteine (10 µM ~ 1 mM) increased [Ca(2+)]i in human neutrophils in a concentration-dependent manner. In NAC pre-supplmented buffer, an additive effect on N-formyl-methionine-leucine-phenylalanine (fMLP)-induced increase in [Ca(2+)]i in human neutrophils was observed. In Ca(2+)-free buffer, NAC- and cysteine-induced [Ca(2+)]i increase in human neutrophils completely disappeared, suggesting that NAC- and cysteine-mediated increase in [Ca(2+)]i in human neutrophils occur through Ca(2+) influx. NAC- and cysteine-induced [Ca(2+)]i increase was effectively inhibited by calcium channel inhibitors SKF96365 (10 µM) and ruthenium red (20 µM). In Na(+)-free HEPES, both NAC and cysteine induced a marked increase in [Ca(2+)]i in human neutrophils, arguing against the possibility that Na(+)-dependent intracellular uptake of NAC and cysteine is necessary for their [Ca(2+)]i increasing activity. Our results show that NAC and cysteine induce [Ca(2+)]i increase through Ca(2+) influx in human neutrophils via SKF96365- and ruthenium red-dependent way.


Pre-AIDS mortality in the Edinburgh City Hospital HIV cohort.
In this paper, we look at the incidence and predictive factors of pre-AIDS mortality among HIV-infected individuals, and injecting drug users (IDUs) in particular, and compare IDUs with non-IDUs. 627 patients (73 per cent IDUs) of the Edinburgh City Hospital HIV Cohort were enrolled pre-AIDS and followed up until September 1994. Analyses were performed using cumulative hazard and cumulative incidence estimators for a competing risks model, the Cox proportional hazards model and the non-parametric hazard estimator of Fusaro et al. (1993). The effects of age and CD4 T-lymphocyte cell count, progressively depleted during HIV progression, were investigated. 60 deaths occurred in AIDS-free patients during follow-up; 25 were drug-related deaths in IDUs. Pre-AIDS mortality was higher among IDUs than non-IDUs (p = 0.07). The cumulative incidences of pre-AIDS death after five years from enrollment were 11 per cent in IDUs and 6 per cent in non-IDUs; the cumulative AIDS incidences were, respectively, 19 per cent and 32 per cent. After eight years, cumulative pre-AIDS death incidence was 15 per cent among IDUs; cumulative AIDS incidence among IDUs was 35 per cent. Both groups had similar risks of medically-related (non-AIDS)-MRNA-death. Age and CD4 count were both individually predictive of MRNA death (relative risks (RRs); 2.1 per decade of life, p < 0.01; and 1.9 for each 100 cells per 100 microliters lost, p < 0.0001), although when used together age was less significant (RR 1.6, p = 0.07). Neither was statistically significant for drug-related mortality, although hazard may be lower in older individuals and may increase with falling CD4 count. The drug-related mortality was 1.1 per cent: 2.3 per cent in the first two years after enrollment, and 0.4 per cent thereafter. We conclude that older HIV-infected individuals are at greater risk of medically-related death before AIDS. This risk increases as CD4 count declines. Drug-related hazard may be greater in younger individuals and may increase as CD4 counts fall, but neither effect was formally significant.


En bloc temporal bone resection using a diamond threadwire saw for malignant tumors.
The purpose of this study is to describe a new technique for en bloc temporal bone resection using a diamond threadwire saw (T-saw) as an alternative to cutting the temporal bone with an osteotome. This technique has been performed in 10 patients with external auditory canal and middle ear cancers without any injury to the internal carotid artery or jugular vein. The authors conclude that the use of a diamond threadwire saw after transposing the internal carotid artery anteriorly is a safe, simple, and reliable technique for en bloc temporal bone resection.


ABO blood group distribution in serum hepatitis.
A disproportionate excess of blood group O was found in a circumscribed outbreak of serum hepatitis among patients and staff of a haemodialysis unit. The more severe cases were also mostly of group O. This suggests that host factors may be important in the genesis of this disease.


Anti-alpha-fodrin antibodies in Sjögren syndrome and lupus erythematosus.
To investigate the prevalence of anti-alphafodrin antibody in patients with Sjogren syndrome (SS), lupus erythematosus (LE), or both and the association of this antibody with other clinical manifestations. A study of screening and diagnostic tests. Mean follow-up was 152 months (range, 4-572 months). A university hospital associated with a research laboratory in Tokyo, Japan. Nine patients with primary SS, 15 patients with SS secondary to LE, and 44 patients with LE alone. Frequencies of clinical and laboratory findings, including anti-alpha-fodrin antibody. Anti-alpha-fodrin antibody was more commonly detected in patients with primary (7/9; P<.001) and secondary (9/15; P<.001) SS than in those with LE alone (3/44). When patients with primary and secondary SS were combined and compared with those with LE alone, the sensitivity of anti-alpha-fodrin antibody was 67%, specificity was 93%, and both positive and negative predictive values were 84%. The presence of anti-alpha-fodrin antibody was associated with pernio, hyperglobulinemia, rheumatoid factor positivity, and the presence of anti-SS-B (La) antibody (P<.01) but not with annular erythema, photosensitivity, vasculitis, or renal disorder. Although anti-alpha-fodrin antibody was detected in patients with SS and in those with LE, it seemed to be more valuable for the diagnosis of SS than was anti-SS-A (Ro) because anti-alpha-fodrin was much less prevalent in patients with LE alone. It may be possible to consider this novel autoantibody as pathophysiologically associated with some extraglandular manifestations characteristically seen in patients with SS.


Calciphylaxis: how specific are the pathological features: avoiding false-positives and false-negatives.
Calciphylaxis is considered a critical inflammatory dermatosis with potentially devastating clinical consequences. Skin biopsies are expedited for evaluation and are often considered as a gold standard for diagnostic confirmation and exclusion of other conditions. The key histopathological features include a combination of vascular and extra-vascular calcifications, intravascular microthrombi, and changes related to resulting ischemia. The pathological diagnosis of calciphylaxis is not always a straightforward process as it can be influenced by a number of factors. The specificity of pathological diagnosis of calciphylaxis has been questioned and a systematic approach with multidisciplinary collaboration is required to avoid potential errors.


Plant exudates promote PCB degradation by a rhodococcal rhizobacteria.
Rhodococcus erythropolis U23A is a polychlorinated biphenyl (PCB)-degrading bacterium isolated from the rhizosphere of plants grown on a PCB-contaminated soil. Strain U23A bphA exhibited 99% identity with bphA1 of Rhodococcus globerulus P6. We grew Arabidopsis thaliana in a hydroponic axenic system, collected, and concentrated the plant secondary metabolite-containing root exudates. Strain U23A exhibited a chemotactic response toward these root exudates. In a root colonizing assay, the number of cells of strain U23A associated to the plant roots (5.7 × 10⁵ CFU g⁻¹) was greater than the number remaining in the surrounding sand (4.5 × 10⁴ CFU g⁻¹). Furthermore, the exudates could support the growth of strain U23A. In a resting cell suspension assay, cells grown in a minimal medium containing Arabidopsis root exudates as sole growth substrate were able to metabolize 2,3,4'- and 2,3',4-trichlorobiphenyl. However, no significant degradation of any of congeners was observed for control cells grown on Luria-Bertani medium. Although strain U23A was unable to grow on any of the flavonoids identified in root exudates, biphenyl-induced cells metabolized flavanone, one of the major root exudate components. In addition, when used as co-substrate with sodium acetate, flavanone was as efficient as biphenyl to induce the biphenyl catabolic pathway of strain U23A. Together, these data provide supporting evidence that some rhodococci can live in soil in close association with plant roots and that root exudates can support their growth and trigger their PCB-degrading ability. This suggests that, like the flagellated Gram-negative bacteria, non-flagellated rhodococci may also play a key role in the degradation of persistent pollutants.


Does income inequality get under the skin? A multilevel analysis of depression, anxiety and mental disorders in Sao Paulo, Brazil.
Test the original income inequality theory, by analysing its association with depression, anxiety and any mental disorders. We analysed a sample of 3542 individuals aged 18 years and older selected through a stratified, multistage area probability sample of households from the São Paulo Metropolitan Area. Mental disorder symptoms were assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Bayesian multilevel logistic models were performed. Living in areas with medium and high-income inequality was statistically associated with increased risk of depression, relative to low-inequality areas (OR 1.76; 95% CI 1.21 to 2.55, and 1.53; 95% CI 1.07 to 2.19, respectively). The same was not true for anxiety (OR 1.25; 95% CI 0.90 to 1.73, and OR 1.07; 95% CI 0.79 to 1.46). In the case of any mental disorder, results were mixed. In general, our findings were consistent with the income inequality theory, that is, people living in places with higher income inequality had an overall higher odd of mental disorders, albeit not always statistically significant. The fact that depression, but not anxiety, was statistically significant could indicate a pathway by which inequality influences health.


TT virus infection of periodontal tissues: a controlled clinical and laboratory pilot study.
A novel single-strand, circular DNA virus has been recently isolated and named TT virus (TTV). It has been demonstrated that peripheral blood cells harbor TTV DNA, suggesting that the virus might replicate in lymphoid cells and contribute to lymphocyte imbalances with consequent immunosuppressive effects. The purpose of this study was to investigate the prevalence of TTV DNA in healthy and periodontally compromised subjects, evaluating the presence of the virus in the gingiva and saliva, and comparing virological results with clinical data. Twenty-one patients (seven males and 14 females, aged 25 to 76 years) were enrolled in the study. Eleven subjects were diagnosed with moderate periodontitis, while 10 were periodontally healthy. A sample of saliva was taken from each patient before recording the periodontal data; subsequently, a gingival biopsy was performed. A real-time polymerase chain reaction was used to quantify the presence of TTV DNA in saliva and gingival specimens. A statistically significant association was found between TTV in gingival tissue and the presence of periodontitis (P = 0.0351), while no association was observed between TTV in saliva and the presence of periodontitis (P = 0.4762). A new DNA virus (TTV) was first identified in the gingival tissue and was found to be significantly associated with the presence of periodontitis. These findings need to be investigated in further studies.


The human herpesvirus 8 homolog of Epstein-Barr virus SM protein (KS-SM) is a posttranscriptional activator of gene expression.
Homologs of the Epstein-Barr virus (EBV) SM protein exist in several human and nonhuman herpesviruses. Structure and function differ significantly among these proteins. We have cloned and characterized the human herpesvirus 8 (HHV8) gene, KS-SM, which is homologous to the EBV SM and herpes simplex virus ICP27 genes, from an HHV8-infected primary effusion lymphoma. KS-SM is shown to be a posttranscriptional activator of gene expression in cotransfection studies. KS-SM activated gene expression in a gene-specific, promoter-independent manner. In particular, KS-SM enhanced the expression of KDR/flk-1, a receptor for vascular endothelial growth factor (VEGF), in cotransfection studies. Since expression of KDR/flk-1 is increased in Kaposi's sarcoma and HHV8-infected cell cultures and VEGF enhances the proliferation of HHV8-infected cells, KS-SM may play a pathogenic role in Kaposi's sarcoma.


Understanding the financial and psychological impact of employment disruption among caregivers of pediatric HSCT recipients: a mixed methods analysis.
Pediatric hematopoietic stem cell transplantation (HSCT) confers a substantial financial burden onto patients' families. In addition to high direct medical costs, HSCTs typically require at least one caregiver to take time away from work or other responsibilities, often leading to reduced household income. Using mixed methods, we sought to understand the impact of pediatric HSCT on caregiver employment and financial need. We surveyed caregivers of living pediatric patients who underwent HSCT at one of two southeastern transplant centers between 2012 and 2018 (N = 95). We then interviewed a subset of caregivers (N = 18) to understand whether and how employment disruption contributed to financial distress. Among caregivers surveyed, the majority of household wage earners changed their work schedules to attend medical appointments and missed workdays. This resulted in income loss for 87% of families, with 31% experiencing an income reduction of over 50%. Qualitative interviews pointed to four emergent themes: (1) employment disruption exacerbated existing financial challenges; (2) parental division of labor between caregiving and providing financially led to heightened psychological distress; (3) existing employment leave and protection resources were essential but not sufficient; and (4) the ability to work remotely and having a supportive employer facilitated employment maintenance throughout the HSCT process. Expanded employment protections and access to accommodations are needed to limit the impact of HSCT on household income, health insurance, and financial hardship. Additionally, interventions are needed to ensure caregivers are equipped with the information necessary to navigate conversations with employers and prepare for the financial and psychological reality of employment disruption.


The antibody response to an HLA mismatch: a model for nonself-self discrimination in relation to HLA epitope immunogenicity.
Antibodies to HLA mismatches are specific for epitopes rather than antigens. HLAMatchmaker considers each HLA antigen as a string of eplets that represent key elements of epitopes. Certain antibodies are specific for single eplets, but recent studies have demonstrated that epitopes defined by eplet pairs always involve one nonself-eplet and a self-eplet shared between the immunizing antigen and the antibody producer. This suggests an autoreactive component of the alloantibody response to an HLA mismatch and this report expands this concept. During B-cell development, V(H) and V(L) gene rearrangements produce a diversity of Ig receptors that can recognize epitopes on autologous proteins. It is hypothesized that B cells carry low-affinity receptors for self-HLA antigens. Their interactions with self-HLA proteins will not lead to B-cell activation or antibody production. In contrast, exposure to HLA mismatches induces often strong alloantibody responses. The activation of self-HLA-specific B cell by a nonself-eplet may require that the remainder of the structural epitope of the immunizing antigen has considerable structural similarity with one of the antibody producer's alleles. This hypothesis has been tested in molecular modelling studies with six epitopes defined by human monoclonal antibodies. In each case, one allele of the antibody producer had no or few differences with the immunizing allele in antibody-accessible positions defined by a 15 Ångstrom radius of the mismatched eplet. The other alleles of the antibody producer showed significantly greater numbers of residue differences with the immunizer (5.8 ± 2.0 versus 1.0 ± 0.6, P < 0.0001). These data support the concept that HLA antibodies originate from B cells with self-HLA immunoglobulin receptors that recognize mismatched eplets as nonself entities on immunizing antigens. The nonself-self paradigm provides a new insight of HLA epitope immunogenicity and may explain why sensitized patients have antibodies to a restricted number of mismatched epitopes.


A design method for product safety.
The Product Safety Method is a method to detect and solve product safety problems. It consists of two parts, analysis and synthesis. The analysis can be used to evaluate products on their safety, by gaining insight into possible accidents with the product and into critical factors connected with either the product, the actions of the user or environmental conditions. The synthesis offers a structured list of solution strategies for the generation of effective solutions to the detected safety problems. The method may be used by both ergonomists and product designers. In conclusion problems in determining the usability and effectiveness of the method are discussed as well as how to adapt the method to fit the world of professional design practice.


Normalized glandular dose coefficients for digital breast tomosynthesis systems with a homogeneous breast model.
This work aims at calculating and releasing tabulated values of dose conversion coefficients, DgNDBT, for mean glandular dose (MGD) estimates in digital breast tomosynthesis (DBT). The DgNDBT coefficients are proposed as unique conversion coefficients for MGD estimates, in place of dose conversion coefficients in mammography (DgNDM or c, g, s triad as proposed in worldwide quality assurance protocols) used together with the T correction factor. DgNDBT is the MGD per unit incident air kerma measured at the breast surface for a 0° projection and the entire tube load used for the scan. The dataset of polyenergetic DgNDBT coefficients was derived via a Monte Carlo software based on the Geant4 toolkit. Dose coefficients were calculated for a grid of values of breast characteristics (breast thickness in the range 20-90 mm and glandular fraction by mass of 1%, 25%, 50%, 75%, 100%) and the simulated geometries, scan protocols, irradiation geometries and typical spectral qualities replicated those of six commercial DBT systems (GE SenoClaire, Hologic Selenia Dimensions, GE Senographe Pristina, Fujifilm Amulet Innovality, Siemens Mammomat Inspiration and IMS Giotto Class). For given breast characteristics, target/filter combination, tube voltage and half value layer (HVL), two spectra with two HVL values have been simulated in order to permit MGD estimates from experimental HVL values via mathematical interpolation from tabulated values. The adopted breast model assumes homogenous composition of glandular and adipose tissues; it includes a 1.45 mm thick skin envelope in place of the 4-5 mm envelope commonly adopted in dosimetry protocols. The simulation code was validated versus AAPM Task group 195 Monte Carlo reference data sets (absolute differences not higher than 1.1%) and by comparison to relative dosimetry measurements with radiochromic film in a PMMA test object (differences within the maximum experimental uncertainty of 11%). The calculated coefficients show maximum relative deviations of -17.6% and +6.1% from those provided by the DBT dose coefficients adopted in the EUREF protocol and of 1.5%, on average, from data in the AAPM TG223 report. A spreadsheet is provided for interpolating the tabulated DgNDBT coefficients for arbitrary values of HVL, compressed breast thickness and glandular fraction, in the corresponding investigated ranges, for each DBT unit modeled in this work.


Peroxidases and glycosidases in intercellular fluids from noninoculated and rust-affected wheat leaves : isozyme assay on nitrocellulose blots from two-dimensional gels.
Proteins in intercellular washing fluid (IWF) from noninoculated and stem rust-affected wheat leaves were separated by isoelectric focusing and polyacrylamide gel electrophoresis under nondenaturing conditions, transferred to nitrocellulose membranes, and assayed in situ for peroxidase and glycosidase activity.Two infection-related peroxidase isozymes were detected in addition to more than ten that were present only in noninoculated plants. One other peroxidase isozyme was present in much higher concentration in IWF from infected leaves than in IWF from noninoculated leaves.IWF contained many polymorphic glycosidases. A new method is described to localize the glycosidase isozymes accurately on nitrocellulose blots for evaluation of their substrate specificities: each blot was developed with the appropriate p-nitrophenyl glycoside to reveal glycosidase activity, then reprobed for concanavalin A-binding glycoproteins to serve as an internal reference frame for blot-to-blot comparisons. This procedure also provided information on glycosylation of the isozymes.The locations of at least 15 (out of 37) isozymes were coincident with concanavalin A binding, including those of all 10 alpha-d-mannosidases, and of 6 beta-d-xylosidases. On five areas of the blots there was coincidence of beta-d-xylosidase and alpha-l-arabinosidase activity. Three of these areas corresponded to three of the most prominent Coomassie brilliant blue-stainable IWF proteins in gels. Isozymes that could convert p-nitrophenyl-beta-d-glucoside, -beta-d-galactoside, and/or -beta-d-fucoside revealed a complex pattern of partially overlapping substrate specificities: two isozymes utilized both glucose and fucose derivatives, one utilized all three derivatives, and several others converted only one of the three substrates. No enzymes were detected with activity on p-nitrophenyl-beta-d-galactosaminide, -beta-l-fucoside, or -alpha-d-galactoside. No additional glycosidases were detected in IWF from stem rust-affected leaves.


[Regulatory effect of CCN3 on proliferation of mouse embryonic fibroblasts and its mechanism].
To investigate the role of NOV/CCN3 in regulating the proliferation of mesenchymal stem cells (MSCs) and its regulatory mechanism and assess the value of CCN3 as a proliferative factor in bone tissue engineering. Mouse embryonic fibroblasts (MEFs) were used as the MSC model, in which CCN3 expression was up-regulated and downregulated by transfection with the recombinant adenovirus vectors Ad-CCN3 and Ad-siCCN3, respectively. Flow cytometry was used to analyze the changes in cell cycle and apoptosis of the transfected cells. Western blotting was used to detect the expression levels of the proliferation indicators (PCNA, cyclin E, and cyclin B1) and the apoptosis indicators (Bax and Bcl-2) to assess the effect of modulation of CCN3 expression on MEF proliferation and apoptosis. CCN3 protein secretion by the cells was detected using ELISA. RT-qPCR and Western blotting were employed to analyze the changes in the expressions of Notch1, ligand DLL1, the downstream key proteins or genes (Hey1, P300, H3K9) and MAPK pathway-related proteins ERK1+2 and p-ERK1+2. Flow cytometry showed that compared with the control cells, MEFs transfected with Ad-CCN3 exhibited significantly increased cell proliferation index (P < 0.01) and lowered cell apoptosis rate (P < 0.05) with obviously enhanced expressions of PCNA, cyclin E and Bcl-2 proteins (P < 0.05). The results of RT-qPCR and Western blotting demonstrated that CCN3 overexpression significantly promoted the expression of Notch1 in the Notch signaling pathway (P < 0.001), inhibited the expressions of DLL1, Hey1, P300, and H3K9 (P < 0.05), and increased the protein expressions of ERK1+2 and P-ERk1+2 in the MAPK pathway (P < 0.01). CCN3 over-expression promotes the proliferation and inhibits apoptosis of MEFs possibly by inhibiting the classical Notch signaling pathway and activating the MAPK pathway via binding to Notch1, suggesting the potential value of CCN3 as a proliferative factor of MSCs in bone tissue engineering.


Asthma and allergic rhinitis co-morbidity: a cross-sectional questionnaire study on adolescents aged 13-14 years.
There is scarce epidemiological population-based data on the prevalence of asthma and allergic rhinitis (AR) co-morbidity in adolescents. The aim was to verify asthma and AR prevalence rates in order to emphasise asthma/AR co-morbidity. Cross-sectional study using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire in adolescents aged 13-14 years, chosen randomly from public schools in Belo Horizonte, Brazil. A total of 3262 students were identified, 3083 (47.3% males) of whom completed the questionnaire (response rate 94.7%). The prevalence of symptoms related to asthma and AR co-morbidity was 8.4% (95% CI, 8.09-10.25). Among asthmatic adolescents, symptoms of AR were reported in 46.5% (95% CI, 42.60-52.08%). There is a high prevalence of adolescent asthma and AR co-morbidity in this area of Brazil. This co-morbidity is an important health issue that requires strategic application of primary health care facilities to achieve adequate control of both asthma and allergic rhinitis.


[Sildenafil citrate (viagra) treatment in patients with diabetes mellitus].
To evaluate different dosages of vasoactive drug viagra in patients with erectile dysfunction suffering from diabetes mellitus (DM) type I and II. Viagra in doses 25, 50 and 100 mg was given to 30 DM patients with different forms of erectile dysfunction. The response was obtained in 70.3% of cases. The highest effect was achieved with the dose 100 mg (the response rate 68.5% of patients). The dose 50 mg was effective in 31.5%, 25 mg in 0% of patients. Most nonresponders had low testosterone levels in the blood.


Treatment of the thylakoid membrane with surfactants : assessment of effectiveness using the chlorophyll a absorption spectrum.
Treatment of higher plant (Nicotiana tabacum L. var. Samsun) chloroplast thylakoid membranes with surfactants results in a shift of the chlorophyll a absorption maximum in the red spectral region from its in vivo value of 678.5 nanometers to shorter wavelengths. The magnitude of this shift is correlated with membrane disruption, and is not necessarily due to the release of pigment from pigment-protein complexes present in the membrane. Membrane disruption has been measured by the amount of pigment in the supernatant fraction after centrifugation of surfactant treated membranes. For an equivalent amount of disruption, the extent of the blue-shift is influenced by the ionic nature of the surfactant: anionic surfactants cause small shifts, cationic surfactants cause the largest ( approximately 10 nanometers) shifts, and nonionic surfactants produce intermediate shifts. The wavelength of maximum absorbance of chlorophyll a in the red region is a convenient criterion for assessing the potential utility of different surfactants for studies on the structure, composition and function of higher plant thylakoid membranes.


URETEROCALICOSTOMY FOR RECONSTRUCTION OF THE UPPER URINARY TRACT.
The paper provides a retrospective study of long-term results of ureterocalicostomy (UC) performed in one specialized center. The study included 37 patients who underwent UC as a primary (43.2%) or secondary (56.8%) operation for intrarenal hydronephrosis or urolithiasis. All surgical interventions were classified into two groups according to the type of kidney resection: Type I - if the kidney parenchyma was more than 10 mm, the entire lower pole of the kidney was removed (72.9%); Type II - if the parenchyma was less than 10 mm, a part of the lower pole (1.5-2.0 cm) was removed in the zone of maximal parenchymal thinning (24.3%). All resections, depending on the angle of their plane, were also divided into transverse (48.6%) and oblique (51.4%). Early postoperative complications were observed in 14 (37.8%) patients. All complications were not severe and were classified as Grade I-II according to the Clavien-Dindo system. The univariate analysis showed that the predictors of UC complications are the long duration of the operation, warm renal ischemia for more than 20 minutes, the secondary nature of the operation, as well as the presence of acute pyelonephritis and urinary extravasation before the operation. The rate of good long-term results was 81.1% (n=30), satisfactory - 13.5% (n=5), poor - 5.4% (n=2). The reliable prognostic value in terms of negative surgery results had: the thickness of the renal parenchyma below 10 mm, as well as the use of Type II resection of the renal parenchyma. Conclusion. A high level of good UC results was demonstrated. The most important predictor was the renal parenchyma thickness less than 10 mm.


[Neurocutaneous melanosis and malignant melanoma].
A 36-year-old man presented with a giant congenital melanocytic nevus and multiple disseminated melanocytic nevi. After he had developed neurological symptoms (grand mal seizures), a cerebral metastasis of a malignant melanoma without a primary melanoma was found. The patient was diagnosed as having a neurocutaneous melanosis with a cerebral metastasis. In spite of a variety of therapeutic attempts (surgery, radiation therapy and chemotherapy) he followed a rapidly progressive, lethal course with increased intracranial pressure, hydrocephalus and spinal metastases.


Traumatic event re-exposure in injecting drug users.
Drug users have very high rates of lifetime exposure to traumatic events, leading to significant psychiatric complications. In spite of the high rate of lifetime exposure, very little is known about the rate of ongoing re-exposure to new traumatic events in drug users. We investigated the rate of traumatic event re-exposure in male and female injecting drug users using syringe exchange services in Baltimore (N = 197). Participants were assessed monthly for traumatic event re-exposure for 16 months. Averaged over the entire follow-up period, 27% of participants were re-exposed to a traumatic event each month and 72% were re-exposed over the 16-month study period. Women were over twice as likely to report any traumatic event re-exposure as men (adjusted odds ratio [AOR] = 2.48; 95% CI = 1.54-3.99), with the specific events of life-threatening illness, death of a loved one, and injury or illness of a loved one being more common in women than men. Traumatic event re-exposure occurs far more often than previously reported, with women injecting drug users at the highest risk. Reassessment of traumatic events may help to identify people most in need and encourage entry into treatment.


Effect of extracellular volume expansion on erythrocyte sodium transport in rats.
The effects of extracellular volume expansion (EVE) on the major sodium transport systems and sodium and potassium contents in rat erythrocytes have been examined in the present study. Study has been performed in anesthetized Wistar rat weighing about 300 g. Acute extracellular volume expansion (EVE) was induced by a constant intravenous saline infusion (3% body wt, 3 hours). Rats anaesthetized and catheterized but not expanded were used as controls. Arterial blood samples from control and expanded rats were obtained at the same time, and assayed immediately. Intracellular sodium and potassium concentration and ouabain sensitive (Na(+)-K(+)-pump) and bumetanide sensitive (Na(+)-K(+)-cotransport system) outward Na+ fluxes in erythrocytes were measured. The effect of plasma on erythrocyte transport was also analyzed by measuring 86Rb uptake. Neither of two plasma cations (Na+ and K+) were modified by the EVE. Also intracellular Na+ and K+ levels remained unvariable. Total Na+ efflux was not modified by EVE, but pump-mediated Na+ efflux was smaller after than before EVE. The ouabain-inhibible Na+ efflux rate constant decreased after EVE (from 687 +/- 81 to 525 +/- 29 h-1 x 10(-3); P less than 0.05). Both Na(+)-K(+)cotransport-mediated Na+ efflux and passive permeability increased significantly after EVE. The incubation with plasma from saline-infused animals induced a significant decrease in Rb uptake rate constant, that was not observed after incubation with plasma from non-expanded rats.(ABSTRACT TRUNCATED AT 250 WORDS)


PET-CT image fusion using random forest and à-trous wavelet transform.
New image fusion rules for multimodal medical images are proposed in this work. Image fusion rules are defined by random forest learning algorithm and a translation-invariant à-trous wavelet transform (AWT). The proposed method is threefold. First, source images are decomposed into approximation and detail coefficients using AWT. Second, random forest is used to choose pixels from the approximation and detail coefficients for forming the approximation and detail coefficients of the fused image. Lastly, inverse AWT is applied to reconstruct fused image. All experiments have been performed on 198 slices of both computed tomography and positron emission tomography images of a patient. A traditional fusion method based on Mallat wavelet transform has also been implemented on these slices. A new image fusion performance measure along with 4 existing measures has been presented, which helps to compare the performance of 2 pixel level fusion methods. The experimental results clearly indicate that the proposed method outperforms the traditional method in terms of visual and quantitative qualities and the new measure is meaningful.


Functional diversity among p24 subfamily members.
The p24 protein family plays an important but unclear role at the ER (endoplasmic reticulum)-Golgi interface. A p24 member from each subfamily (p24alpha(3), beta(1), gamma(3) and delta(2)) is upregulated with the prohormone POMC (pro-opiomelanocortin) when Xenopus laevis intermediate pituitary melanotrope cells are physiologically activated. Here we explored the role of p24 by generating and analysing Xenopus with melanotrope cell-specific transgene expression of p24beta(1) or p24gamma(3), two of the p24 proteins coexpressed with POMC, and compared the results with those previously reported for the two other coexpressed p24s (p24alpha(3) and p24delta(2)). The transgene expression of p24beta(1) or p24gamma(3) did not affect the endogenous p24 proteins or affected only endogenous p24gamma(3) respectively, whereas in transgenics expressing p24alpha(3) and p24delta(2), the levels of all endogenous p24 proteins were strongly decreased. Nevertheless, as for p24alpha(3) but albeit to a lesser extent, in the p24beta(1)-transgenic melanotrope cells the rate of cargo cleavage was reduced, probably reflecting reduced cargo transport from the ER, and POMC glycosylation and sulfation in the Golgi were not affected. The p24gamma(3)-transgenic cells displayed features of both the p24alpha(3)-transgenics (reduced cargo cleavage, normal POMC sulfation) and the p24delta(2)-transgenics (affected POMC glycosylation). Our results show that the four upregulated proteins p24alpha(3), beta(1), gamma(3) and delta(2) have non-redundant roles in the early secretory pathway, and suggest that each p24 subfamily member provides a proper ER/Golgi subcompartmental microenvironment, together allowing correct secretory protein transport and processing.


Antioxidant activity and bioaccessibility of phenols-enriched edible casein/caseinate coatings during in vitro digestion.
Active films were developed for food coating applications. Entrapped phenol susceptibility to digestion was studied. Sodium caseinate (Na-CN) coatings were formulated with 0, 10, 20% Casein (CN) incorporating selected phenols as model antioxidants. This study investigated phenol/CN/Na-CN interactions, in vitro bioaccessibility of phenols and CN role in phenols retention during in vitro gastric and pancreatic digestion. The antioxidant activity of catechin (CAT), rutin (RUT), chlorogenic acid (CHL), gallic acid (GAL), and tannic acid (TA) in coatings varied with the phenolic compound type and CN concentration and was related to phenol hydrophobic binding to CN. ABTS method gave activities ranged from 412 down to 213, and DPPH method gave values from 291·7 to 190·9. An inverse relationship was found with CN content due to CN/phenol interaction. During digestion, a part of phenols was degraded by alkaline pH of pancreatic fluid. Simultaneously, CN proteolysis led to release of phenols and the bioaccessibility index remained above 80% for all phenols. The results suggested the possibility of protecting phenols against oxidation and digestive alteration by entrapment in CN and Na-CN coating films. These positive results showed the ability to produce antioxidant-enriched edible coatings to increase food protection and phenol nutritional intake.


A Survey of the Microbiological Quality of Processed Cheese Products.
A study done in 1980 to 1981 assessed the overall bacteriological quality of three varieties of domestic and imported processed cheese products. All of the 78 lots tested had counts of <1.8 Escherichia coli and coliforms/g, and had no staphylococcal thermonuclease activity. Domestic products had significantly higher levels of aerobic sporeformers than imported products (α = 0.05), whereas the differences in levels of anaerobic sporeformers in these products were not significant. Results of this study indicated that good manufacturing practices were used during the processing of these products.


Imbalance of CD45R and CDw29 helper cell subsets after seven days of culture from penicillin hypersensitive patients.
Specific PBMC proliferation to penicillin represents one of the in vitro diagnostic procedures to show antigenic sensitization. Nine patients with suggestive clinical history of penicillin hypersensitivity, significant stimulation index in the lymphocyte transformation test (LTT), and increased CD25 expression were selected. Their phenotypic expression of T-cell subset markers was compared with that of six normal subjects after 7 days of culture. Higher percentages of CD45R and CDw29 positive cells were found in penicillin-hypersensitive patients. This group of patients showed a significantly (P less than 0.01) higher percentage of CD45R positive cells compared with normal subjects, after 7 days of culture. The percentage of CD45R cells did not differ between patients and normal subjects at day 0, and the progressive decrease of CD45R positive cells in culture of normal subjects was not observable in our patients. These results suggest that the patients with penicillin hypersensitivity have an imbalance of CD45R/CDw29 ratio after 7 days of culture, with a higher expression of CD45R positive cells.


Microperimetry as Part of Multimodal Assessment to Evaluate and Monitor Myopic Traction Maculopathy.
To characterize a population of high myopes with myopic traction maculopathy (MTM), to assess their retinal function, and to correlate it with anatomic status. This was an observational cross-sectional study including 50 eyes from 27 patients. Demographic and clinical data were analyzed. Macular structure was assessed with spectral domain optical coherence tomography (SD-OCT, Heidelberg®) and macular function was studied with Microperimeter MP-3, NIDEK®. The average for central foveal thickness (CFT) and choroid thickness (CT) was 213±151 μm and 36±23 μm, respectively, in a total of 50 eyes from 27 patients. In the microperimetry analysis, the average sensitivity on the foveal-centered 12º polygon (CPS) was 14.37±9.1 dB. CT was negatively associated with the bivariate contour ellipse areas (BCEA) 1 (r=-0.314; p=0.034), 2 (r=-0.314; p=0.034), and 3 (r=-0.316; p=0.033). CPS had a strong positive correlation with best-corrected visual acuity (BCVA) (r=0.661; p=0.000). We found a trend to worse microperimetric results in eyes with schisis (n=19) (p>0.05) but eyes with atrophic areas (n=33) presented significant inferior CPS (p<0.001). The presence of staphyloma showed significant impact on macular sensitivities in eyes with areas of macular atrophy/fibrosis (p<0.05). Macular microperimetry analysis can have a role as part of a multimodal anatomo-functional assessment for a more precise characterization of the high myopic patients with MTM, optimizing medical and surgical decisions.


Anisotropy and non-homogeneity of an Allomyrina Dichotoma beetle hind wing membrane.
Biomimetics is one of the most important paradigms as researchers seek to invent better engineering designs over human history. However, the observation of insect flight is a relatively recent work. Several researchers have tried to address the aerodynamic performance of flapping creatures and other natural properties of insects, although there are still many unsolved questions. In this study, we try to answer the questions related to the mechanical properties of a beetle's hind wing, which consists of a stiff vein structure and a flexible membrane. The membrane of a beetle's hind wing is small and flexible to the point that conventional methods cannot adequately quantify the material properties. The digital image correlation method, a non-contact displacement measurement method, is used along with a specially designed mini-tensile testing system. To reduce the end effects, we developed an experimental method that can deal with specimens with as high an aspect ratio as possible. Young's modulus varies over the area in the wing and ranges from 2.97 to 4.5 GPa in the chordwise direction and from 1.63 to 2.24 GPa in the spanwise direction. Furthermore, Poisson's ratio in the chordwise direction is 0.63-0.73 and approximately twice as large as that in the spanwise direction (0.33-0.39). From these results, we can conclude that the membrane of a beetle's hind wing is an anisotropic and non-homogeneous material. Our results will provide a better understanding of the flapping mechanism through the formulation of a fluid-structure interaction analysis or aero-elasticity analysis and meritorious data for biomaterial properties database as well as a creative design concept for a micro aerial flapper that mimics an insect.


When two strands are better than one: the mediators and modulators of the cellular responses to double-stranded RNA.
Double-stranded RNA is a potent inducer of interferon, a modulator of the expression of a number of other genes involved in the response of cells to virus infection, an activator of the interferon-induced antiviral state, and may be involved in differentiation, induction of apoptosis, and control of oncogenic transformation. This review will attempt to summarize what is known about the cellular proteins that act to mediate the response of cells to double-stranded RNA and the viral and cellular macromolecules that may be able to modulate these responses.


Interfacial interactions of semiconductor with graphene and reduced graphene oxide: CeO2 as a case study.
The pursuit of superb building blocks of light harvesting systems has stimulated increasing efforts to develop graphene (GR)-based semiconductor composites for solar cells and photocatalysts. One critical issue for GR-based composites is understanding the interaction between their components, a problem that remains unresolved after intense experimental investigation. Here, we use cerium dioxide (CeO2) as a model semiconductor to systematically explore the interaction of semiconductor with GR and reduced graphene oxide (RGO) with large-scale ab initio calculations. The amount of charge transferred at the interfaces increases with the concentration of O atoms, demonstrating that the interaction between CeO2 and RGO is much stronger than that between CeO2 and GR due to the decrease of the average equilibrium distance between the interfaces. The stronger interaction between semiconductor and RGO is expected to be general, as evidenced by the results of two paradigms of TiO2 and Ag3PO4 coupled with RGO. The interfacial interaction can tune the band structure: the CeO2(111)/GR interface is a type-I heterojunction, while a type-II staggered band alignment exists between the CeO2(111) surface and RGO. The smaller band gap, type-II heterojunction, and negatively charged O atoms on the RGO as active sites are responsible for the enhanced photoactivity of CeO2/RGO composite. These findings can rationalize the available experimental reports and enrich our understanding of the interaction of GR-based composites for developing high-performance photocatalysts and solar cells.


Leeches and Caudal Analgesia After Replantation for Glans Amputation During Neonatal Circumcision.
Neonatal circumcision is one of the most commonly performed surgical procedures in the world. As with all surgeries, it carries risks, including rare, but devastating complications, such as glans, and/or penile shaft amputation. Complete glans amputation with successful replantation has been previously reported. Herein we report a case of complete amputation at the penile midshaft in a 28-day-old neonate with a unique approach to postoperative care including the use of leech therapy, topical heparin, and caudal analgesia following successful microvascular replantation.


Protective Effects of 1,8-Cineole Microcapsules Against Inflammation and Gut Microbiota Imbalance Associated Weight Loss Induced by Heat Stress in Broiler Chicken.
Intestinal microbiota dysregulation is considered the primary trigger of low-grade inflammation responsible for weight loss due to heat stress. 1,8-Cineole is the major bacteriostatic agent in eucalypt and possesses remarkable anti-inflammatory properties. However, the mechanisms of its effect on intestinal microbiota remain unclear. In this study, 1,8-cineole was prepared into microcapsules prior to use as feed supplement in chickens. The microencapsulation efficiency and chemical stability of 1,8-cineole microcapsules were evaluated. The chicken treatment with 1,8-cineole microcapsules (1 or 3%) for 45 days, in the presence or absence of heat stress for fifteen days, commenced on Day 31, with or without an antibiotics mix (Abx) for three days on Day 27. Performance parameters were measured once a week from Day 30 through Day 45. Surface and entrapped concentration of 1,8-cineole was estimated as 7.89 g/100 g powder in the microcapsules. The time to maximal concentration (Tmax), terminal half-life (T1/2), and the area under plasma concentration-time curve (AUC0-t) of the encapsulated 1,8-cineole were higher than those of the nonencapsulated in treated chickens, although the maximal concentrations (Cmax) were similar. Chickens treated under higher temperatures with 1,8-cineole microcapsules exhibited lower levels of grade inflammation and higher body weight gain. Dietary 1,8-cineole microcapsules recovered the normal structure of upper ileum and altered the ratio of gut microbiota under heat stress and increased the ratio of Lactobacillus and Escherichia, whereas the proportion of Salmonella decreased based on 16S rRNA analysis of the upper ileum microbiota. In vitro, 1,8-cineole effectively inhibited the growth of Salmonella as demonstrated by inhibition zone assay. In summary, our findings elucidated the interaction between 1,8-cineole and intestinal microbiota as a new mechanism for the anti-heat stress effect of 1,8-cineole in preventing low-grade inflammation and weight loss. The results suggest that 1,8-cineole microcapsules may be a good feed supplement to protect against heat stress injury.


Kir subfamily in frog retina: specific spatial distribution of Kir 6.1 in glial (Müller) cells.
We show by immunocytochemistry in frog retina that most members of the Kir subfamily are expressed in specific neuronal compartments. However, Kir 6.1, the pore-forming subunit of K(ATP) channels, is expressed exclusively in glial Müller cells. Müller cell endfeet display strong Kir 6.1 immunolabel throughout the retina, whereas the somata are labeled only in the retinal periphery. This spatial pattern is similar to that of Kir 4.1, of the ratio of inward to outward K+ currents, and of spermine/spermidine immunoreactivity. We suggest that the co-expression of Kir 4.1 and Kir 6.1 subunits may enable the cells to maintain their high K+ conductance and hyperpolarized membrane potentials both at high ATP levels (Kir 4.1) and during ATP deficiency (Kir 6.1).


Patient reported outcome measures in rhinology.
Patient rated outcome measures (PROMs) are increasingly being used to supplement clinical measures of disease in order to assess how disease and medical intervention impacts on quality of life. As the primary aim of treatment for most rhinological conditions is to improve quality of life they have particular relevance in our sub-specialty. Some PROMs have been developed for particular conditions or treatments (disease-specific measures) while others were developed to be used in all patient groups or healthy individuals (generic measures). There are an increasing number of both disease-specific and global measures available for use in rhinological conditions, and they are reviewed. Both factors limiting wide scale adoption of PROMs into routine practice, and limitations of PROMs are also discussed.


Regulatory standards and guidance for the use of health applications for self-management in Africa: scoping review protocol.
Despite health applications becoming ubiquitous and with enormous potential to facilitate self-management, regulatory challenges such as poor application quality, breach of data privacy and limited interoperability have impeded their full adoption. While many countries now have digital health-related policies/strategies, there is also a need for regulatory standards and guidance that address key regulatory challenges associated with the use of health applications. Currently, it is unclear the status of countries in Africa regarding regulatory standards and guidance that address the use of health applications.This protocol describes the process of conducting a scoping review which aims to investigate the extent to which regulatory standards and guidance address the use of health applications for self-management within the WHO African Region countries. The review will follow the methodological framework for conducting a scoping study by Arksey and O'Malley (2005), and the updated methodological guidance for conducting a Joanna Briggs Institute (JBI) scoping review. Given that regulatory standards and guidance are unlikely to be available in scientific databases, we will search Scopus, Google, OpenGrey, WHO Regional Office for Africa Library (AFROLIB), African Index Medicus (AIM), websites of WHO, ITU and Ministries of Health, repositories for digital health policies. We will also search the reference lists of included documents, and contact key stakeholders in the region. Results will be reported using descriptive qualitative content analysis based on the review objectives. The policy analysis framework by Walt and Gilson (1994) will be used to organise findings. A summary of the key findings will be presented using tables, charts and maps. The collection of primary data is not anticipated in this study and hence ethical approval will not be required. The review will be published in a peer-reviewed journal while key findings will be shared with relevant organisations and/or presented at conferences.


The measurement of blood density to investigate protein deposition at the blood/hollow fiber membrane interface during ultrafiltration.
Concentration polarization and secondary membrane formation change the membrane hydraulic permeability of capillary filters during hemofiltration reducing initial value filtration rates up to 50%. This leads to a significant loss of filter efficiency which must be taken into consideration when designing filters for long-term application such as in implantable artificial kidneys. By measuring blood density uninterrupted over a period of time using the mechanical oscillatory technique it is possible to follow the dynamics of protein deposition at the interface between the blood and capillary walls. The resulting picture of the deposition behaviour can lead to a better understanding of time-dependent filtration where flow and pressure conditions change. Protein deposition (Pt) with polysulfone membranes in relation to the effective capillary surface was in the range of 2.2. mg/(h x cm2) according to a logarithmic function (Pt = a + b x log(t)).


Studies on the inhibitory action of mercury upon proteinase K.
In proteinase K, Cys73 is located "below" the imidazole of the active site His69. In a 2.4-A resolution x-ray crystal structure of the complex formed between the enzyme and HgAc2, two Hg(II) positions are found: a fully occupied site, covalently bound to Cys73 (S gamma), which disrupts the catalytic triad (Asp39-His69-Ser224), and a 2-fold disordered (25 and 35% occupancy), noncovalent complexation to His72, Cys73, and Thr76 of lower affinity. The enzyme is inhibited noncompetitively at low concentrations and competitively above stoichiometric concentrations of Hg(II), but it retains 7% residual activity. This can be rationalized if the molecule is flexible enough to permit transient formation of the catalytic triad. Except for the active site, only minor structural changes are observed upon binding of Hg(II), but the thermal stability is reduced by 4 degrees C.


Pectin methylesterase inhibitor cDNA from kiwi fruit.
We have newly isolated one partial pectin methylesterase inhibitor (PMEI) and two full-length cDNA clones from a kiwi fruit cDNA library. The two full-length cDNA clones, Adpmei-1 and Adpmei-2, had an open reading frame of 185 amino acids, including a predicted signal peptide sequence necessary for localization in the cell-wall space. As the deduced amino acid sequence of the cloned fragment was almost same as the sequence of the previously purified PMEI protein (Camardella et al., Eur J Biochem 267:4561-4565), the clones were considered to be cDNAs encoding PMEI protein. Southern blot analysis indicated a low-copy number of the PMEI genes. Transgenic analysis of asparagus calli expressing a kiwi fruit PMEI gene driven by the CaMV 35S promoter demonstrated in vivo inhibition effects of PMEI on the endogenous pectin methylesterase (PME) activity. The relative expression levels of the PMEI genes in kiwi fruit, analyzed by competitive PCR, increased with the progression of fruit maturation. Given that PME activity also showed its highest level at the fully ripened stage of maturation, the increase in PMEI expression may not indicate direct inhibitory effects on the PME activity and fruit maturation process.


Transvenous ventricular pacing options in Ebstein's anomaly.
Transvenous pacing in patients with Ebstein's anomaly is challenging due to anatomical abnormalities of the tricuspid valve and right heart chambers. This paper describes the various transvenous ventricular lead placement options for permanent pacing in patients with Ebstein's anomaly. In Ebstein's anomaly, stable long-term ventricular pacing can be achieved by positioning the lead either in the atrialised right ventricle, true right ventricle or the cardiac venous system. The pitfalls and advantages of pacing from these sites with the electrocardiographic and chest X-ray appearances are described.


Expanding world of ballistosporous yeasts: Distribution in the phyllosphere, systematics and phylogeny.
Ecological and systematic aspects of ballistosporous yeasts inhabiting the phyllosphere of the Asia-Pacific region were reviewed in the light of recent advances. In the past 20 years, the extensive isolation studies of ballistosporous yeasts were carried out in the Asia-Pacific region, and the following new species were found in the phyllosphere of the main island of Japan, of the Ogasawara Islands in the Pacific Ocean, and of Thailand, New Zealand, and the Yunnan Province of China: Bensingtonia ingoldii, B. intermedia, B. miscanthi, B. naganoensis, B. musae, B. sakaguchii, B. subrosea, B. thailandica, and B. yamatoana; Bullera boninensis, B. coprosmaensis, B. hannae, B. huiaensis, B. miyagiana, B. mrakii, B. oryzae, B. penniseticola, B. pseudoalba, B. schimicola, B. sinensis, B. unica, B. variabilis, and B. waltii; Kockovaella imperatae, K. machilophila, K. phaffii, K. sacchari, K. schimae, and K. thailandica; Sporobolomyces blumeae, S. coprosmae, S. coprosmicola, S. dimmenae, S. draycophyllus, S. falcatus, S. griseoflavus, S. inositophilus, S. lactophilus, S. linderae, S. novazealandicus, S. nylandii, S. oryzicola, S. poonsookiae, S. ruber, S. sasicola, S. subbrunneus, S. taupoensis, S. vermiculatus, S. xanthus, and S. yunnanensis; and Udeniomyces megalosporus. Yeast species containing Q-10(H(2)), a monohydrated ubiquinone, have long been considered to be rare yeasts; however, these yeasts were proved to be common in the tropical and subtropical phyllosphere of Asia. The chemotaxonomic and molecular phylogenetic studies based on the sequence analysis of 18S rDNA revealed the heterogeneity of ballistosporous yeasts, which comprised species with polyphyletic phylogenetic origins. A new phylogenetic cluster, Subbrunneus, was newly found in the class Urediniomycetes as the fifth phylogenetical cluster of this class, based on the analysis of 18S rDNA sequences. The Subbrunneus cluster comprises four ballistosporous yeast species found in the phyllosphere of Japan and New Zealand. The future perspectives of basidiomycetous yeast systematics are discussed.


Immunotherapy after bone marrow transplantation.
Residual disease after bone marrow transplantation (BMT) can either cause relapse or persist in a balanced state in which immune mechanisms keep control over malignant cell proliferation. After allogeneic BMT the latter mechanism [summarized as graft-versus-leukemia (GVL)] is probably supported by cellular (e.g. T lymphocytes, natural killer cells) and humoral (e.g. cytokines) effectors and often linked to clinical manifestations of GVHD. Preclinical and clinical studies are now emerging in which cytokines, such as interleukin-2 or interferons, are given after BMT to support cellular immune function particularly in situations in which GVL does not occur. We summarize here results from both pre-clinical and clinical studies that are relevant to the design of protocols seeking to improve elimination of residual malignant disease in BMT patients by modulation of the immune system.


The prevalence and correlates of alcohol use and alcohol use disorders: a population based study in Colombo, Sri Lanka.
Alcohol use is increasing in non-Western countries. However, the effects of this increase on the prevalence of alcohol use disorders (AUD) remains unknown, particularly in South Asia. This study aimed to estimate the prevalence of alcohol use and AUD in the Colombo District, Sri Lanka. Environmental risk factors and psychiatric correlates were also examined. The Composite International Diagnostic Interview was used to assess alcohol use and psychiatric disorders in a population based sample of 6014 twins and singletons in the Colombo region of Sri Lanka. Lifetime alcohol use on 12 or more occasions was estimated at 63.1 % (95 % CI: 61.3-64.9) in men and 3.7 % (95 % CI: 3.0-4.3) in women. Prevalence of lifetime alcohol abuse and alcohol dependence in men was 6.2 % (95 % CI: 5.3-7.1) and 4.0 % (95 % CI: 3.3-4.7) respectively. Lower standard of living was independently associated with alcohol use and dependence but not abuse. Significant associations between lifetime AUD and other psychiatric disorders were observed. Lower prevalence of alcohol use and AUD was observed compared to Western countries. Prevalence of alcohol use and AUD were higher than previous reports. Socio-demographic and environmental risk factors appear to be similar across cultures as were associations between AUD and other psychiatric disorders.


Effect of deworming on nutritional status of ascaris infested slum children of Dhaka, Bangladesh.
This randomized double blind community trial was conducted on Ascaris infested children (n = 85) aged 2 to 12 years and was aimed to study the impact of deworming on nutritional status, in an urban slum of Dhaka, Bangladesh. The change of weight gain was significantly higher in children given anthelmintics than those given placebo (0.92 kg vs. 0.54 kg). A multiple linear regression model shows that after controlling sex, deworming and height were positively correlated while age and weight were negatively correlated with weight change.


Enhanced SCAP glycosylation by inflammation induces macrophage foam cell formation.
Inflammatory stress promotes foam cell formation by disrupting LDL receptor feedback regulation in macrophages. Sterol Regulatory Element Binding Proteins (SREBPs) Cleavage-Activating Protein (SCAP) glycosylation plays crucial roles in regulating LDL receptor and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) feedback regulation. The present study was to investigate if inflammatory stress disrupts LDL receptor and HMGCoAR feedback regulation by affecting SCAP glycosylation in THP-1 macrophages. Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The translocation of SCAP from the endoplasmic reticulum (ER) to the Golgi was detected by confocal microscopy. We demonstrated that exposure to inflammatory cytokines increased lipid accumulation in THP-1 macrophages, accompanying with an increased SCAP expression even in the presence of a high concentration of LDL. These inflammatory cytokines also prolonged the half-life of SCAP by enhancing glycosylation of SCAP due to the elevated expression of the Golgi mannosidase II. This may enhance translocation and recycling of SCAP between the ER and the Golgi, escorting more SREBP2 from the ER to the Golgi for activation by proteolytic cleavages as evidenced by an increased N-terminal of SREBP2 (active form). As a consequence, the LDL receptor and HMGCoAR expression were up-regulated. Interestingly, these effects could be blocked by inhibitors of Golgi mannosidases. Our results indicated that inflammation increased native LDL uptake and endogenous cholesterol de novo synthesis, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in macrophages. These data imply that inhibitors of Golgi processing enzymes might have a potential vascular-protective role in prevention of atherosclerotic foam cell formation.


Estrogen replacement therapy and incidence of self-reported physician-diagnosed arthritis.
This longitudinal study examined the association between use of estrogen replacement therapy and incidence of self-reported, physician-diagnosed arthritis. Data of 2,416 postmenopausal women who participated in the National Health and Nutrition Examination Survey Epidemiological Follow-Up Study were used in this study. Women, free of self-reported arthritis at entry into study and for 3 years thereafter, were questioned about use of estrogen and physician-diagnosed arthritis at each of the follow-up waves of study. Proportional hazard regression models were used for the analysis. Use of ERT was found to be associated with higher risk of incident arthritis, after adjusting for potential confounders (RR = 1.61, CI 1.37-1.89). Whenever use of ERT was replaced by duration of use in the regression model, ERT users for a year or less significantly increased their risk of incident arthritis (RR = 1.37, CI 1.07-1.74). The risk increased by 30 and 96% with hormone use for 1 to 4 and 4 to 10 years, respectively, and by 104% with hormone use for 10 or more years. Results suggest that users of ERT were at higher risk of developing arthritis and the longer the use of the hormone, the higher the risk.


A comparison between bromodeoxyuridine and 3H thymidine labeling in human breast tumors.
The fraction of tumor cells in the DNA synthesis (S) phase of the cell cycle is a strong prognostic indicator in human breast cancer. Most studies measuring S-phase in primary tumors have used either in vitro labeling with 3H thymidine or DNA flow cytometry. The former involves a cumbersome and time-consuming radioactive assay, while the latter is heavily dependent on the quality of the preparation and the effectiveness of the algorithms used. In this study, in vivo or in vitro labeling with bromodeoxyuridine (BrdUrd) was compared with in vitro labeling using 3H thymidine in a series of 33 human breast tumors. Thymidine labeling showed strong correlation with both in vitro (r = 0.96) and in vivo (r = 0.83) BrdUrd incorporation. The reliability between observers was higher for BrdUrd counting (r = 0.94) than for thymidine counting (r = 0.87). The mean labeling index of 15 tumors labeled in vivo with BrdUrd was 5.9% compared to 4.7% for 18 tumors labeled in vitro (p = 0.34). There was poor correlation between flow cytometric and microscopic analysis of BrdUrd incorporation (r = 0.37). We conclude that microscopic analysis of in vivo or in vitro BrdUrd incorporation is a rapid and reliable method to estimate breast tumor proliferation.


Relationship of secretion of GnRH in vitro to changes in pituitary concentrations of LH and FSH and serum concentrations of LH during lactation in sows.
The objectives of this study were (1) to determine whether release of GnRH in vitro was related to concentrations of LH and FSH in serum and pituitaries and to oestradiol in serum of sows at mid- or late lactation, and (2) to determine whether weaning at mid-lactation changes concentrations of these hormones from values expected at mid-lactation to values expected at late lactation. Multiparous crossbred sows were killed on day 14 (n = 5) or day 28 (n = 5) of lactation or on day 14 post partum after litters had been weaned on day 10 (n = 5). Blood samples were taken every 6 h for 4 days before sows were killed, and the preoptic suprachiasmatic area, medial basal hypothalamus, stalk median eminence, anterior pituitary and ovaries were collected at slaughter. Sows killed on day 14 after having their litters weaned on day 10 had more (P < 0.01) preovulatory follicles (> 6 mm in diameter) than lactating sows killed on day 14 or 28 (7.0 +/- 1.2 versus 0.2 +/- 0.1 and 1.5 +/- 0.8, respectively). Concentrations of LH, FSH and oestradiol in serum during 90 h before slaughter were greater (P < 0.05) in weaned sows and lactating sows killed on day 28 than in lactating sows killed on day 14 (LH: 0.72 +/- 0.3 and 0.68 +/- 0.3 versus 0.45 +/- 0.2 ng ml-1; FSH: 39.3 +/- 2.7 and 57.3 +/- 4.0 versus 28.8 +/- 1.6 ng ml-1; oestradiol: 10.9 +/- 1.6 and 5.6 +/- 0.7 versus 2.7 +/- 0.2 pg ml-1, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Role of surface termination in forming type-II photocatalyst heterojunctions: the case of TiO2/BiVO4.
In this work we investigate TiO2 and BiVO4 nanostructures by means of density functional theory (DFT) calculations, to provide an estimate of the band alignment in TiO2/BiVO4 interfaces, highly active in photo-electrochemistry and photocatalytic water splitting. Calculations were carried out with both DFT range separated and self-consistent dielectric dependent hybrid functionals (HSE06 and PBE0DD). The impact of systems' size has been investigated. The converged electronic levels of TiO2 and BiVO4 surfaces have been used to predict the band alignment in TiO2/BiVO4 heterostructures. Results indicated that when TiO2 (101) surface is matched with BiVO4 (110), a type-II alignment is obtained, where the band edges of BiVO4 are higher in energy that those of TiO2. This picture is favorable for charge-carriers separation upon photoexcitation, where electrons move toward TiO2 and holes toward BiVO4. On the contrary, if TiO2 (101) is interfaced to BiVO4 (010) the offset between the band edges is negligible, thus reducing the driving force toward separation of charge carriers. These results rationalize the dependence on the facet's exposure of the observed photocatalytic performances of TiO2/BiVO4 composites, where the TiO2 (101)/BiVO4 (110) interface outperforms the TiO2 (101)/BiVO4 (010) one.


InsP3R-associated cGMP kinase substrate (IRAG) is essential for nitric oxide-induced inhibition of calcium signaling in human colonic smooth muscle.
Nitric oxide (NO)-mediated relaxation of colonic smooth muscle is crucial for the maintenance of human gut function. The molecular mechanisms of NO-dependent smooth muscle relaxation involve cyclic GMP-mediated inhibition of store-dependent calcium signaling. Recently, IRAG (inositol 1,4,5-trisphophate receptor-associated cGMP kinase substrate) has been characterized as a novel target molecule of cGMP-dependent protein kinase (cGKI) mediating NO-/cGMP-dependent inhibition of inositol 1,4,5-trisphosphate (InsP(3))-dependent calcium release in transfected COS cells. The aim of the present study was to characterize IRAG expression and its functional role in NO-dependent signaling in human colonic smooth muscle. Reverse transcriptase-PCR revealed IRAG mRNA expression in human colon, rectum, and cultured colonic smooth muscle cells. In cultured human colonic smooth muscle cells, bradykinin (BK) elicited InsP(3)-dependent calcium transients that were repeatable and independent of extracellular calcium. The NO donor sodium nitroprusside and the specific cGK activator 8-(4-chlorophenylthio)guanosine-3',5'-cyclic-monophosphate (8-pCPT-cGMP) significantly inhibited BK-induced increase in intracellular calcium. Cells transfected with antisense oligonucleotides raised against IRAG (IRAG-AS) showed strongly decreased IRAG protein expression. In these cells, sodium nitroprusside and 8-pCPT-cGMP both failed to modulate BK-induced calcium transients. Thus, endogenous IRAG appears to be essentially involved in the NO/cGK-dependent inhibition of InsP(3)-dependent Ca(2+)-signaling in colonic smooth muscle.


Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.
Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.


Purification and characterization of a protein that permits early detection of lung cancer. Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4.
We have reported that a mouse monoclonal antibody 703D4, detects lung cancer 2 years earlier than routine chest x-ray or cytomorphology. We purified the 703D4 antigen to elucidate its role in early lung cancer biology, using Western blot detection after SDS-polyacrylamide gel electrophoresis. Purification steps included anion exchange chromatography, preparative isoelectric focusing, polymer-based C18-like, and analytical C4 reverse phase high performance liquid chromatography. After 25-50,000-fold purification, the principal immunostaining protein was > 95% pure by Coomassie staining. The NH2 terminus was blocked, so CNBr digestion was used to generate internal peptides. Three sequences, including one across a site of alternate exon splicing, all identified a single protein, heterogeneous nuclear ribonucleoprotein-A2 (hnRNP-A2). A minor co-purifying immunoreactive protein resolved at the final C4 high performance liquid chromatography step is the splice variant hnRNP-B1. Northern analysis of RNA from primary normal bronchial epithelial cells demonstrated a low level of hnRNP-A2/B1 expression, consistent with immunohistochemical staining of clinical samples, and increased hnRNP-A2/B1 expression was found in lung cancer cells. hnRNP-A2/B1 expression is under proliferation-dependent control in normal bronchial epithelial cell primary cultures, but not in SV40-transformed bronchial epithelial cells or tumor cell lines. With our clinical data, this information suggests that hnRNP-A2/B1 is an early marker of lung epithelial transformation and carcinogenesis.


Self-healing codes: How stable neural populations can track continually reconfiguring neural representations.
As an adaptive system, the brain must retain a faithful representation of the world while continuously integrating new information. Recent experiments have measured population activity in cortical and hippocampal circuits over many days and found that patterns of neural activity associated with fixed behavioral variables and percepts change dramatically over time. Such "representational drift" raises the question of how malleable population codes can interact coherently with stable long-term representations that are found in other circuits and with relatively rigid topographic mappings of peripheral sensory and motor signals. We explore how known plasticity mechanisms can allow single neurons to reliably read out an evolving population code without external error feedback. We find that interactions between Hebbian learning and single-cell homeostasis can exploit redundancy in a distributed population code to compensate for gradual changes in tuning. Recurrent feedback of partially stabilized readouts could allow a pool of readout cells to further correct inconsistencies introduced by representational drift. This shows how relatively simple, known mechanisms can stabilize neural tuning in the short term and provides a plausible explanation for how plastic neural codes remain integrated with consolidated, long-term representations.


Modern veterinary blood banking practices and their applications in companion animal practice.
There are two main reasons for blood component therapy: the need for an increase in oxygen-carrying capacity and improved hemostasis. Additionally, blood component therapy is used to increase plasma protein concentrations. Component therapy entails separating whole blood into its cellular and plasma components and administering the appropriate blood component based on the patient's needs. General considerations such as compatibility, defined expectations of benefits, and topics including specific disease screening, preparation of blood components, preparation of blood products for administration, and typing and crossmatching in relation to blood component therapy and its application in companion animal practice are discussed.


Digital Light Processing 3D Printing of Enhanced Polymers via Interlayer Welding.
Digital light processing (DLP) 3D printing is advantageous in high printing efficiency and printing resolution for fabricating complex structures across various applications. However, the layer-by-layer curing manner of DLP leads to weak interlayer adhesion and the anisotropic mechanical properties of printed objects. Here, linear polymers are introduced into commercial resins to weld the interlayer by the diffusion and entanglement of linear polymers after DLP printing via heat treatment. This introduction of linear polymers not only shows a strengthening and toughening effect on the printed objects, but also has no negative impact on the DLP printability. The tensile strengths of objects containing 4.7 wt% polycaprolactone can reach up to ≈500% of that of neat samples in any printing direction. This simple strategy by adding linear polymers into printing resins provides an effective access to prepare DLP printed objects with improved mechanical properties as well as ensure printing resolution and printing efficiency.


Decree concerning the Council of the Health Insurance Fund (Abortion clinics), 22 August 1985.
This Decree has been made in regard to item (e) of Subsection 1 of Section 52 of the Dutch General Law on Exceptional Health Care Costs of 14 December 1967 (Stb. 617). Under Article 1, abortion clinics licensed under Article 2 of the Law on the Termination of Pregnancy of 1 May 1981 (Stb. 275) qualify for a contribution from the General Fund for Exceptional Health Care Costs for treatment relating to termination of pregnancy (that is, other than the employment of a method intended to prevent the implantation of a fertilized egg in the uterus) and for after-care. Clinics may not receive payment for subsidized services.


Pattern of congenital heart disease among Egyptian children: a 3-year retrospective study.
Congenital heart disease (CHD) is a multifactorial birth defect which has variable demographic characteristics among children in different geographical areas. This study aimed to detect the distribution of demographic data, perinatal risk factors, types, age, and mode of presentation of CHD among Egyptian children. The medical records of 1005 patients were included. They were 545 males (54%) and 462 females (46%) with a ratio of 1.2:1. Acyanotic CHD was encountered in 79.2%. Isolated ventricular septal defect and tetralogy of Fallot were the most common acyanotic and cyanotic lesions, respectively. The majority was diagnosed within the first year of life (86.7%) and was born to young mothers (91.3%). The accidental discovery of a murmur was the most frequent presentation (35%). Heart failure was detected in 44%, audible murmurs in 74.4%, maternal illnesses in 54%, consanguinity in 44.6%, prematurity in 19.3%, assisted reproduction in 11.7%, family history of CHD in 9.2%, abortions in 7.1%, and extracardiac anomalies in 3.6% of the studied population. Down syndrome (DS) was the most commonly occurring chromosomal anomaly, and the atrioventricular septal defect was the most characteristic cardiac lesion found among them. There is no sex predilection among Egyptian children with CHD. Most of the cases are diagnosed in early infancy. Accidental discovery of a murmur is the most common mode of presentation. A variety of predisposing risk factors are abundant in the Egyptian population. DS is the most common chromosomal anomaly linked to CHD. Establishment of a national medical birth registry containing all information about all births in Egypt is needed for adequate surveillance and monitoring of perinatal health problems and congenital birth defects so that preventive measures can be early implemented. Proper and detailed data collection should be fulfilled in the medical records of every single patient.


Characterization of monocyte-derived dendritic cells in recent-onset diabetes mellitus type 1.
Dendritic cells (DC) may play an important role in the immunopathogenesis of type 1 diabetes mellitus (DM-1). In this study, we have analyzed phenotypical changes during cytokine-driven maturation from CD14+ monocytes to mature DC and DC-dependent T-cell stimulation in recent-onset pediatric DM-1 patients and healthy controls. DC maturation was monitored by flow cytometric analyses for the expression of surface markers (HLA-DR, CD1a, CD40, CD80, CD86, CD83, CD14, CD32, mannose-receptor, and CD11c). Flow cytometric analysis of isolated peripheral blood monocytes did not reveal apparent differences between patients and controls. During DC maturation no obvious differences in the expression patterns of surface markers over time or evidence for maturation impairments in DM-1 patients could be appreciated. Solely, a marginal, but significant, transient down-regulation of CD1a on Day 3 (mean MDFI 3.82 vs 7.25; P = 0.021), which was accompanied by an increase of IL-6, could be observed. The comparison of mature DCs (Day 10) between patients and controls indicated no significant differences, except for CD83 (mean MDFI 1.7 vs 1.5; P = 0.042) and CD80 (mean MDFI 15.92 vs 12.73; P = 0.042). Moreover, no difference in T-cell stimulatory capacity was seen. In conclusion, our analysis of a cohort of recent-onset DM-1 patients and controls does not support a role for disease-related alterations in cytokine-driven maturation of monocyte-derived DC.


Immunogenicity assays for antibody-drug conjugates: case study with ado-trastuzumab emtansine.
Antibody-drug conjugates (ADCs) such as Kadcyla™ (ado-trastuzumab emtansine [T-DM1]) present covalently bound cytotoxic drugs, which may influence their immunogenicity potential compared with antibody therapies. Therefore, ADCs require assay strategies that allow measurement of responses to all the molecular components. The immunogenicity strategy for T-DM1 used a risk-based, tiered approach that included screening and titration to detect antitherapeutic antibodies; confirmation of positive responses; and characterization to assess whether the immune response is primarily to the antibody or to the linker-drug and/or new epitopes in trastuzumab resulting from conjugation. The tiered immunogenicity assay strategy for T-DM1 allowed detection of antitherapeutic antibodies to all components of the ADC in multiple nonclinical and clinical studies. Characterization strategies implemented in clinical studies provided additional insights into the specificity of the immune response.


Analytic model for the complex effective index dispersion of metamaterial-cladding large-area hollow core fibers.
We present a mathematical model that allows interpreting the dispersion and attenuation of modes in hollow-core fibers (HCFs) on the basis of single interface reflection, giving rise to analytic and semi-analytic expressions for the complex effective indices in the case where the core diameter is large and the guiding is based on the reflection by a thin layer. Our model includes two core-size independent reflection parameters and shows the universal inverse-cubed core diameter dependence of the modal attenuation of HCFs. It substantially reduces simulation complexity and enables large scale parameter sweeps, which we demonstrate on the example of a HCF with a highly anisotropic metallic nanowire cladding, resembling an indefinite metamaterial at high metal filling fractions. We reveal design rules that allow engineering modal discrimination and show that metamaterial HCFs can principally have low losses at mid-IR wavelengths (< 1 dB/m at 10.6 µm). Our model can be applied to a great variety of HCFs with large core diameters and can be used for advanced HCF design and performance optimization, in particular with regard to dispersion engineering and modal discrimination.


[Differentiation effect of hexamethylene bisacetamide (HMBA) on mucoepidermoid carcinoma in vivo].
The differentiation effect of HMBA was examined in mucoepidermoid carcinoma transplanted to athymic mice. The animals were divided into HMBA and control groups. The effects were evaluated by inhibitory rate of tumor growth, the survival period and the morphological changes of cells. The results showed that the inhibitory rate of tumor growth was 71.7%, the survival period of HMBA group was 49.6 days while control group was 38.3 days, the cells of HMBA group tended to become more mature, and the mean number of AgNORs was also significantly reduced. These results indicate that HMBA can induce the MEC-1 cells to differentiate toward nomal or benign cells in vivo.


Nocturnal Accumulation of Malic Acid Occurs in Mesophyll Tissue without Proton Transport to Epidermal Tissue in the Inducible Crassulacean Acid Metabolism Plant Mesembryanthemum crystallinum: EVIDENCE AGAINST A PREVIOUS HYPOTHESIS.
The inducible Crassulacean acid metabolism plant, Mesembryanthemum crystallinum, accumulates malic acid, i.e. equivalent amounts of malate anions and protons in the mesophyll cells at night. Levels of malate and titratable acidity are low in the epidermal tissue and do not change significantly during the day/night cycle. This result is in contrast to a recent report (Bloom 1979 Plant Physiol 64: 919-923) that the synthesis of malic acid during dark CO(2) fixation is associated with an equivalent exchange of inorganic cations from epidermal tissue with protons in the mesophyll cells.


Myocardial perfusion in Friedreich's ataxia: assessment by dipyridamole thallium-201 imaging.
In order to assess myocardial perfusion in patients with Friedreich's ataxia, we carried out dipyridamole-thallium imaging in 13 cardiologically asymptomatic patients (aged 16 to 39; mean age 24) with various degrees of left ventricular hypertrophy; all showed electrocardiographic ST and/or T wave abnormalities before scintigraphy. After dosing with dipyridamole-201 thallium, we found: a completely reversible perfusion defect in the apical and a partially reversible defect in the posterolateral wall of the left ventricle in 1 case; a partially reversible perfusion defect in the anterior and posterior walls of the left ventricle in 1 case; and a persistent anterolateral perfusion defect in 1 case. The remaining 10 patients showed no scintigraphic abnormalities. The fact that only 1 of our patients showed a completely reversible perfusion defect, possibly consistent with regional myocardial ischemia, suggests that ischemia does not play a major role in the pathogenesis of the cardiac involvement in Friedreich's ataxia.


Evaluation of the benefit of the bispyridinium compound MB327 for the antidotal treatment of nerve agent-poisoned mice.
The potency of the bispyridinium non-oxime compound MB327 [1,1'-(propane-1,3-diyl)bis(4-tert-butylpyridinium) diiodide] to increase the therapeutic efficacy of the standard antidotal treatment (atropine in combination with an oxime) of acute poisoning with organophosphorus nerve agents was studied in vivo. The therapeutic efficacy of atropine alone - or atropine in combination with an oxime, MB327, or both an oxime and MB237 - was evaluated by the determination of LD50 values of several nerve agents (tabun, sarin and soman) in mice with and without treatment. The addition of MB327 increased the therapeutic efficacy of atropine alone, and atropine in combination with an oxime, against all three nerve agents, although differences in the LD50 values only reached statistical significance for sarin. In conclusion, the addition of the compound MB327 to the standard antidotal treatment of acute poisonings with nerve agents was beneficial regardless of the chemical structure of the nerve agent, although at the dose employed, MB327 in combination with atropine, or atropine and an oxime, provided only a modest increase in protection ratio. These results from mice, and previous ones from guinea-pigs, provide consistent evidence for additional, albeit modest, efficacy resulting from the inclusion of the antinicotinic compound MB327 in standard antidotal therapy. Given the typically steep probit slope for the dose-lethality relationship for nerve agents, such modest increases in protection ratio could provide significant survival benefit.


Host-virus interaction and viral evasion.
With each infectious pandemic or outbreak, the medical community feels the need to revisit basic concepts of immunology to understand and overcome the difficult times brought about by these infections. Regarding viruses, they have historically been responsible for many deaths, and such a peculiarity occurs because they are known to be obligate intracellular parasites that depend upon the host's cell machinery for their replication. Successful infection with the production of essential viral components requires constant viral evolution as a strategy to manipulate the cellular environment, including host internal factors, the host's nonspecific and adaptive immune responses to viruses, the metabolic and energetic state of the infected cell, and changes in the intracellular redox environment during the viral infection cycle. Based on this knowledge, it is fundamental to develop new therapeutic strategies for controlling viral dissemination, by means of antiviral therapies, vaccines, or antioxidants, or by targeting the inhibition or activation of cell signaling pathways or metabolic pathways that are altered during infection. The rapid recovery of altered cellular homeostasis during viral infection is still a major challenge. Here, we review the strategies by which viruses evade the host's immune response and potential tools used to develop more specific antiviral therapies to cure, control, or prevent viral diseases.


Targeting the NOD-Like Receptor Pyrin Domain Containing 3 Inflammasome to Improve Healing of Diabetic Wounds.
Significance: Chronic skin wounds are a significant health problem around the world, often leading to amputation and even death. Although persistent inflammation is a hallmark of these poorly healing wounds, few available therapies have been designed to target inflammation. In this review, we summarize available evidence of the role of the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in impaired wound healing and describe strategies to inhibit the inflammasome to improve wound healing. Recent Advances: The NLRP3 inflammasome plays an important physiological role in skin wound healing, during which transient inflammasome activity contributes to both epidermal and dermal healing. In contrast, sustained activity of the NLRP3 inflammasome leads to impaired epidermal and dermal healing associated with diabetes. Of importance, preclinical studies have demonstrated that inhibiting the NLRP3 inflammasome-induced resolution of inflammation, increased granulation tissue formation and collagen deposition, and accelerated reepithelialization and wound closure. Critical Issues: NLRP3 inflammasome inhibitors have appealing potential for translation into therapies for chronic wounds. Although preclinical studies have shown promising results, there is a need for human/clinical studies to evaluate dosing formulations, potential therapeutic effects, dose-response relationships, and possible side effects. Future Directions: Among strategies to inhibit the NLRP3 inflammasome, glyburide, metformin, peroxisome proliferator-activated receptor agonists, and the dipeptidyl peptidase 4 inhibitor saxagliptin appear to be closest to clinical translation, as these drugs are already Food and Drug Administration approved for other indications. Future clinical studies are needed to develop topical formulations of these drugs, and to assess the safety and efficacy of these inhibitors, to improve healing of chronic wounds.


Laser remodelling of nodular nasal lupus pernio.
Disfiguring nodular nasal lupus pernio is a rare condition that responds poorly to medical management. We have treated three affected patients with carbon dioxide laser remodelling, and report their progress 6 years, 2 years and 16 months following treatment, respectively. Although the abnormal granulomatous tissue was debulked rather than completely excised, the wounds healed within 4 weeks in all patients. The cosmetic results are acceptable and have been maintained in two of the patients, perhaps a reflection of their overall systemic sarcoidosis control.


Thrombin generation by calibrated automated thrombography in goat plasma: Optimization of an assay.
The goat model of atrial fibrillation (AF) allows investigation of the effect of AF on coagulation. However, assays for goat plasma are not available from commercial sources. Calibrated automated thrombography (CAT) provides a global view of the coagulation profile by assessing in vitro thrombin generation (TG). We describe the customization of the CAT assay in goat platelet-poor plasma (PPP) and in factor Xa (FXa)-inhibitor-anticoagulated PPP. TG was initiated in the presence of phospholipids and either (a) PPP reagent, reagent low, or reagent high; (b) goat brain protein extraction (GBP); or (c) Russell's viper venom-factor X activator (RVV-X). Contact activation was assessed by adding corn trypsin inhibitor. Different concentrations of prothrombin complex concentrate (PCC) were used to determine the sensitivity of both the GBP and RVV-X method. To obtain FXa-inhibitor anticoagulated plasma, rivaroxaban was added to plasma. TG settings with human reagents were not suitable for goat plasma. TG triggered with GBP increased peak height and ETP values. Similarly, the RVV-X method produced comparable TG curves and was more sensitive to PCC titration. Finally, both methods were able to detect the decrease in clotting potential induced by FXa inhibition. This is the first study that reports the customization of the CAT assay for goats. The GBP and RVV-X methods were comparable in triggering TG in goat plasma. The RVV-X method seemed to better discriminate changes in TG curves due to increases in clotting potential as well as to FXa inhibition by rivaroxaban in goat plasma.


Photorefractive keratectomy using the meditec MEL 70 G-scan laser for hyperopia and hyperopic astigmatism.
To evaluate the results of photorefractive keratectomy (PRK) using Gaussian flying spot technology in the treatment of hyperopia and hyperopic astigmatism. Two hundred eyes were evaluated with 12-month follow-up. An Asclepion-Meditec MEL 70 G-scan flying spot ArF excimer laser with a Gaussian scanner was used (6.0-mm treatment zone and 9.0-mm transition zone). Eyes were divided into four groups: Group 1 (spherical hyperopia up to +3.50 D and astigmatism less than 1.00 D, n=62); Group 2 (hyperopia up to +3.50 D and astigmatism of 1.00 D or more, n=44); Group 3 (hyperopia greater than +3.50 D and astigmatism less than 1.00 D, n=56); and Group 4 (hyperopia greater than +3.50 D and astigmatism of 1.00 D or more, n=38). In Group 1, 82.2% (51/62 eyes) were within +/-0.50 D of target refraction; 88.7% (55/62 eyes) had 20/20 or better uncorrected visual acuity; 1.6% (1/62 eye) lost two or more lines, 3.2% (2/62 eyes) gained two or more lines of spectacle-corrected visual acuity. In Group 2, 68.1% (30/44 eyes) were within +/-0.50 D; 77.2% (34/44 eyes) had 20/20 or better uncorrected visual acuity; 9.1% (4/44 eyes) lost two or more lines of spectacle-corrected visual acuity. In Group 3, 76.8% (43/56 eyes) were within +/-0.50 D; 78.6% (44/56 eyes) had 20/20 or better uncorrected visual acuity; 5.4% (3/56 eyes) lost two or more lines of spectacle-corrected visual acuity. In Group 4, 42% (16/38 eyes) were within +/-0.50 D; 60.5% (23/38 eyes) had 20/20 or better uncorrected visual acuity; 15.8% (6/38 eyes) lost two or more Snellen lines. PRK with the flying spot Meditec MEL 70 G-scan was most safe and effective for low hyperopia.