Mortality of dialysis patients according to influenza and pneumococcal vaccination status.
Data from an immunocompromised subpopulation in which both vaccine recipients and nonrecipients have frequent opportunities for vaccination can help determine the associations between vaccination against seasonal influenza and pneumococcal disease and all-cause mortality. We surveyed dialysis centers and performed a retrospective analysis of health status at dialysis therapy initiation, vaccination for influenza and pneumococcal disease, laboratory results, and mortality associated with the 2005-2006 influenza season for patients in 3 End-Stage Renal Disease Networks across the United States. Of 1,033 dialysis facilities considered, 903 centers with a total patient population of 54,734 reported vaccination data. Analysis was limited to 36,966 patients on dialysis treatment for at least 1 year as of December 31, 2005. Vaccination status. OR for all-cause mortality (vaccinated vs unvaccinated patients). The estimated adjusted OR for mortality was significantly less than 1.0 for patient who received either vaccination and was lower for patients who had received both vaccinations than for those who had received either. Survival analysis confirmed these findings. Possible misclassification due to self-report of vaccination for some patients. Lack of vaccination date. Vaccination against influenza and pneumococcal disease is associated with improved survival in dialysis patients. The 2 vaccinations have independent effects on mortality.


House-to-house and school lameness surveys in Cameroon: a comparison of two methods for estimating the prevalence and annual incidence of paralytic poliomyelitis.
House-to-house and school lameness surveys were conducted in one urban and two rural regions of the United Republic of Cameroon. As in many other African nations, estimates of annual incidence by survey were significantly higher than those established by routine surveillance, and greater than 80% of all cases of paralysis were found to have occurred in children younger than 36 months of age. House-to-house surveys were more than six times more costly than school surveys and undoubtedly gave annual incidence rates closer to true rates. The value of the less costly school survey should not be overlooked, however, if base-line data are required at frequent intervals for use in the evaluation of control measures.


Mapping the protein domain structures of the respiratory mucins: a mucin proteome coverage study.
Mucin genes encode a family of the largest expressed proteins in the human genome. The proteins are highly substituted with O-linked oligosaccharides that greatly restrict access to the peptide backbones. The genomic organization of the N-terminal, O-glycosylated, and C-terminal regions of most of the mucins has been established and is available in the sequence databases. However, much less is known about the fate of their exposed protein regions after translation and secretion, and to date, detailed proteomic studies complementary to the genomic studies are rather limited. Using mucins isolated from cultured human airway epithelial cell secretions, trypsin digestion, and mass spectrometry, we investigated the proteome coverage of the mucins responsible for the maintenance and protection of the airway epithelia. Excluding the heavily glycosylated mucin domains, up to 85% coverage of the N-terminal region of the gel-forming mucins MUC5B and MUC5AC was achieved, and up to 60% of the C-terminal regions were covered, suggesting that more N- and sparsely O-glycosylated regions as well as possible other modifications are available at the C-terminus. All possible peptides from the cysteine-rich regions that interrupt the heavily glycosylated mucin domains were identified. Interestingly, 43 cleavage sites from 10 different domains of MUC5B and MUC5AC were identified, which possessed a non-tryptic cleavage site on the N-terminal end of the peptide, indicating potential exposure to proteolytic and/or "spontaneous cleavages". Some of these non-tryptic cleavages may be important for proper maturation of the molecule, before and/or after secretion. Most of the peptides identified from MUC16 were from the SEA region. Surprisingly, three peptides were clearly identified from its heavily glycosylated regions. Up to 25% coverage of MUC4 was achieved covering seven different domains of the molecule. All peptides from the MUC1 cytoplasmic domain were detected along with the three non-tryptic cleavages in the region. Only one peptide was identified from MUC20, which led us to successful antisera raised against the molecule. Taken together, this report represents our current efforts to dissect the complexities of mucin macromolecules. Identification of regions accessible to proteolysis can help in the design of effective antibodies and points to regions that might be available for mucin-protein interactions and identification of cleavage sites will enable understanding of their pre- and post-secretory processing in normal and disease environments.


Circulatory clearance of transfused antibody-sensitized red cells in an entirely allogenic rabbit model.
Antibodies against histocompatibility antigens on phagocytes abrogate their Fc gamma-receptor-mediated functions in vitro. Studies were carried out to determine whether this phenomenon also exists in vivo. An allogenic blood group antibody was generated in rabbits. Red cells sensitized with this antibody were internalized in vitro by rabbit phagocytes. Another allogenic antibody specific for major histocompatibility complex (MHC) antigens of rabbits was produced. Plasma containing this antibody was infused into rabbits with phagocytes expressing the corresponding MHC antigens. Thereafter, the sensitized rabbit red blood cells were transfused into the rabbits. The following 3 phases of the circulatory clearance of transfused sensitized red cells could be observed when MHC antibodies were not given prior to the transfusion: 1. initial rapid clearance of the cells (t/2 = 1.7-3.3 min), 2. release of the cells back into the circulation after 0.5-24 h and 3. terminal slow clearance which was, however, faster than that with unsensitized cells. Two independent experiments carried out on the same recipient out of the 3 recipients analysed showed that the prior treatment of the recipient with MHC-alloantibodies extended the circulatory half-life of the sensitized red cells during the terminal phase from t/2 = 1 day to t/2 = 3 and 4 days, respectively. Antibodies against MHC antigens on phagocytes can reduce the Fc gamma-receptor-mediated immune elimination of sensitized red cells. This corresponds to the observation that many cases of morbus haemolyticus neonatorum show unexpectedly reduced levels of foetal red cell destruction and a good clinical outcome if mothers not only produce antibodies to Rh (D) but also to foetal MHC antigens.


Vaginal bleeding with multicystic ovaries and a pituitary mass in a child with severe hypothyroidism.
A seven year and ten months old girl presented with cyclic vaginal bleeding and a huge abdominopelvic mass. She had clinical features of hypothyroidism. The investigation results were consistent with the diagnosis of primary hypothyroidism with precocious puberty. She also had bilaterally enlarged cystic ovaries on CT scan of abdomen and CT scan of brain showed pituitary macroadenoma. After starting treatment with thyroxine, patient became euthyroid and her general condition improved. Treatment with thyroxine alone halted the cyclic vaginal bleeding, led to rapid resolution of the ovarian cysts and regression of the pituitary mass.


The impact of negative family-work spillover on diurnal cortisol.
Both dimensions of the work-family interface, work-to-family and family-to-work spillover, have important implications for health and well-being. Despite the importance of these associations, very little is known about the physiological mechanisms through which the interplay between family and work experiences are translated into long-lasting consequences for health. This study investigated both positive and negative aspects of each spillover dimension on diurnal cortisol secretion patterns in a large panel study of working adults between the ages of 33 and 80. Greater negative family-to-work (NFW) spillover predicted lower wake-up cortisol values and a flatter (less "healthy") diurnal cortisol slope. This effect was evident even after controlling for the effects of the other spillover dimensions. These findings indicate that not all aspects of the work-family interface might impact stress physiology to the same extent and suggest that diurnal cortisol may be an important pathway through which negative aspects of the work-family interface leave their mark on health. (PsycINFO Database Record


Induction and disappearance of G2 chromatid breaks in lymphocytes after low doses of low-LET gamma-rays and high-LET fast neutrons.
To determine by means of the G2 assay the number of chromatid breaks induced by low-LET gamma-rays and high-LET neutrons, and to compare the kinetics of chromatid break rejoining for radiations of different quality. The G2 assay was performed on blood samples of four healthy donors who were irradiated with low-LET gamma-rays and high-LET neutrons. In a first set of experiments a dose-response curve for the formation of chromatid breaks was carried out for gamma-rays and neutrons with doses ranging between 0.1 and 0.5 Gy. In a second set of experiments, the kinetics of chromatid break formation and disappearance were investigated after a dose of 0.5 Gy using post-irradiation times ranging between 0.5 and 3.5 h. For the highest dose of 0.5 Gy, the number of isochromatid breaks was also scored. No significant differences in the number of chromatid breaks were observed between low-LET gamma-rays and high-LET neutrons for the four donors at any of the doses given. The dose-response curves for the formation of chromatid breaks are linear for both radiation qualities and RBEs = 1 were obtained. Scoring of isochromatid breaks at the highest dose of 0.5 Gy revealed that high-LET neutrons were, however, more effective at inducing isochromatid breaks (RBE = 6.2). The rejoining experiments further showed that the kinetics of disappearance of chromatid breaks following irradiation with low-LET gamma-rays or high-LET neutrons were not significantly different. Half-times of 0.92 h for gamma-rays and 0.84 h for neutrons were obtained. Applying the G2 assay, the results demonstrate that at low doses of irradiation, the induction as well as the disappearance of chromatid breaks is independent of the LET of the radiation qualities used (0.24 keV x microm(-1) 60Co gamma-rays and 20 keV x microm(-1) fast neutrons). As these radiation qualities produce the same initial number of double-strand breaks, the results support the signal model that proposes that chromatid breaks are the result of an exchange process which is triggered by a single double-strand break.


Representation of the spectral dominance region of pitch in the steady-state temporal discharge patterns of cochlear nucleus units.
Single-unit responses to infinitely iterated rippled noise and wideband noise were recorded from the cochlear nucleus of anesthetized chinchillas. Rippled noises had a fixed delay of 4 ms, and spectral depth was varied by attenuating the delayed version of the noise. Temporal discharge patterns were analyzed using neural autocorrelograms, and responses to rippled noises were compared to wideband noise responses. Chopper units with best frequencies in the range of the first to second harmonics of the rippled noise showed large differences in discharge patterns between rippled noise and wideband noise responses, but chopper units with best frequencies centered at higher harmonics did not show large differences. Consequently, the Chopper group of units showed no evidence of a neural representation of the dominance region. Primarylike units did show a neural representation of dominance that is related to behavioral performance. For Primarylike units with best frequencies around the third to fifth harmonics of the rippled noise, large differences in discharge patterns between rippled noise and wideband noise responses were observed. The results suggest that bushy cells play an important role in processing pitch-related information and should be included as important elements in neural models of periodicity processing.


Membrane-associated nucleotide sugar reactions: influence of mutations affecting lipopolysaccharide on the first enzyme of O-antigen synthesis.
Both the synthesis of lipopolysaccharide O-antigen and the synthesis of peptidoglycan in Salmonella typhimurium proceed via membrane-bound glycosylated lipid intermediates. The first enzyme of each pathway transfers a sugar phosphate from a nucleotide sugar to the glycosyl carrier lipid (P-GCL). Each enzyme catalyzes an exchange reaction between the reaction product urine monophosphate, and the nucleotide sugar substrate. Several strains of S. typhimurium defective in lipopolysaccharide synthesis accumulate glycosylated lipid intermediates under appropriate conditions. In addition, strains lysogenic for phage P22 synthesize a glucose derivative of the carrier lipid. These strains were used to demonstrate the P/GCL requirement of the exchange reaction catalyzed by galactose-diphosphoglycosyl carrier lipid (GCL-PP-Gal) synthetase, the first enzyme of O-antigen synthesis. Enzyme activity is greatly reduced when glycosylated P-GCL accumulates on the cytoplasmic membrane. The exchange reaction catalyzed by the first enzyme of peptidoglycan synthesis is unaffected by the accumulation of O-antigen fragments on the carrier lipid and may interact with a different pool of P-GCL within the membrane. GCL-PP-Gal synthetase activity cannot be detected in the membranes of two rfa mutants that synthesize incomplete lipopolysaccharide core. Either the synthesis of GCL-PP-Gal synthetase or the stable integration of the enzyme into the membrane structure may be disrupted in the rfa mutants. Peptidoglycan synthesis is unaffected by the mutations affecting the core glycosyltransferases.


Functional insights from structures of coactivator-associated arginine methyltransferase 1 domains.
Coactivator-associated arginine methyltransferase 1 (CARM1), a protein arginine methyltransferase recruited by several transcription factors, methylates a large variety of proteins and plays a critical role in gene expression. We report, in this paper, four crystal structures of isolated modules of CARM1. The 1.7 A crystal structure of the N-terminal domain of CARM1 reveals an unexpected PH domain, a scaffold frequently found to regulate protein-protein interactions in a large variety of biological processes. Three crystal structures of the CARM1 catalytic module, two free and one cofactor-bound forms (refined at 2.55 A, 2.4 A and 2.2 A, respectively) reveal large structural modifications including disorder to order transition, helix to strand transition and active site modifications. The N-terminal and the C-terminal end of CARM1 catalytic module contain molecular switches that may inspire how CARM1 regulates its biological activities by protein-protein interactions.


Roles of hormonal and nutritional factors in the regulation of rat liver alcohol dehydrogenase activity and ethanol elimination rate in vivo.
Fasting reduced the liver alcohol dehydrogenase (ADH) activity by 51% (p less than 0.001). Insulin, within 2 hr, increased the ADH activity found in fasted animals by 28% (p less than 0.02). Insulin administration failed to stimulate the reduced ADH activity in diabetic rats. However, ADH activity in the diabetic-fed rats decreased by 52-54% (p less than 0.001) compared to normal-fed rats regardless of whether they were meal-fed or refed the normal chow. Glucagon blocked by 15% (p less than 0.02) the increase in ADH activity associated with refeeding. Furthermore, insulin caused a marginal stimulation of ethanol elimination rate (EER) when administered to fasted rats. All these results imply that insulin and glucagon may not be the only determining factors in the control of liver ADH activity associated with fasting and refeeding. Meal-feeding or refeeding a high carbohydrate fat-free diet compared to the normal chow-diet caused 29% (p less than 0.001) and 36% (p less than 0.05) decreases in ADH activity, respectively. Concomitant decreases in EER caused by high carbohydrate fat-free diet feeding were also observed under identical conditions. These results raise the possibility that the amount and the type of carbohydrate may be crucial in the regulation of ADH and EER. Alternatively, the presence of fat may be important in maintaining the normal level of ADH and EER.


Human cytidine triphosphate synthetase 1 interacting proteins.
We investigated the interacting proteins and intracellular localization of CTP synthetase 1 (CTPS1) in mammalian cells. CTPS1 interacted with a GST- peptidyl prolyl isomerase, Pin1 fusion (GST-Pin1) in a Ser 575 (S575) phosphorylation-dependent manner. Immunoprecipitation experiments demonstrated that CTPS1 also bound tubulin, and thirteen additional coimmunoprecipitating proteins were identified by mass spectrometry. Immunolocalization experiments showed that tubulin and CTPS1 colocalized subcellularly. Taxol treatment enhanced this but cotreatment of cells with the CTPS inhibitor, cyclopentenyl cytosine (CPEC), and taxol failed to disrupt the colocalization. Thus, these studies provide novel information on the potential interacting proteins that may regulate CTPS1 function or intracellular localization.


Depletion of Chk1 leads to premature activation of Cdc2-cyclin B and mitotic catastrophe.
Mitotic catastrophe occurs as a result of the uncoupling of the onset of mitosis from the completion of DNA replication, but precisely how the ensuing lethality is regulated or what signals are involved is largely unknown. We demonstrate here the essential role of the ATM/ATR-p53 pathway in mitotic catastrophe from premature mitosis. Chk1 deficiency resulted in a premature onset of mitosis because of abnormal activation of cyclin B-Cdc2 and led to the activation of caspases 3 and 9 triggered by cytoplasmic release of cytochrome c. This deficiency was associated with foci formation by the phosphorylated histone, H2AX (gammaH2AX), specifically at S phase. Ectopic expression of Cdc2AF, a mutant that cannot be phosphorylated at inhibitory sites, also induced premature mitosis and foci formation by gammaH2AX at S phase in both embryonic stem cells and HCT116 cells. Depletion of ATM and ATR protected against cell death from premature mitosis. p53-deficient cells were highly resistant to lethality from premature mitosis as well. Our results therefore suggest that ATM/ATR-p53 is required for mitotic catastrophe that eliminates cells escaping Chk1-dependent mitotic regulation. Loss of this function might be important in mammalian tumorigenesis.


Visualization and quantification of transparent exopolymer particles (TEP) in freshwater using an auto-imaging approach.
Most water sources are full of microscopic transparent exopolymer particles (TEP), which are currently regarded as a major initiator of biofilm formation. This study developed and applied an auto-imaging FlowCAM-based method for online observation and quantification of TEP in freshwater. Samples from reservoirs in Taiwan with a wide range of water quality were directly used to develop this methodology. Factors that potentially affect the measurement were tested. The results showed that characteristics of the particles measured instantaneously after staining samples with Alcian blue differed significantly from those measured at steady states, as a result of particle aggregation. Compared to traditional microscopic methods, this proposed method provides a simple, rapid, and less labor-intensive analysis with particle morphological conservation and a large number of particle attributes. By overcoming the limitations from the former, this technique would offer routine monitoring of these transparent particles from various freshwater sources and feed water in membrane filtration, hence facilitating the use of TEP as a critical parameter for biofouling investigation in water treatment. Application of the method for Taiwan reservoirs showed a wide variety of morphological forms of TEP and its abundance, up to 25,000 ppm.


Slug-Flow Microextraction Mass Spectrometry for Enhanced Detection of Analytes in Human Tear Fluids using Noninvasive Microsampling and Nanoelectrospray Ionization via a Capillary.
In vivo noninvasive sampling and sensitive analysis of human tear fluids at the microliter level is an important but challenging task in investigating eye health. In this work, capillary microsampling coupled with slug-flow microextraction mass spectrometry (SFME-MS) was developed for enhanced detection of analytes in human tear fluids. As low as 1.0 μL of human tear fluid could be directly sampled using a capillary, and extraction/spray solvent was then loaded into the capillary to perform slug-flow microextraction and direct nanoelectrospray ionization (nESI) of analytes. All analytical procedures, including tear microsampling, microextraction, and ionization of analytes, were performed using a capillary. Enhanced detection of therapeutic drugs and disease biomarkers in human tear fluids was successfully demonstrated. Acceptable analytical performances including sensitivity, reproducibility, and quantitation were obtained. It is found that the use of SFME could improve the nESI-MS detection of trace analytes over 100-fold that depends on the chemical properties of analytes. Overall, this study showed that SFME-nESI-MS is a highly effective method for enhanced detection of trace analytes in tear fluids and is expected to be a potentially powerful tool in significant biological and clinical applications.


Are cyclic lipopeptides produced by Bacillus amyloliquefaciens S13-3 responsible for the plant defence response in strawberry against Colletotrichum gloeosporioides?
The antagonistic strain Bacillus amyloliquefaciens strain S13-3 decreased the severity of strawberry anthracnose caused by Colletotrichum gloeosporioides. The foliar application of S13-3 triggered the expression of pathogenesis-related proteins, chitinase and β-1,3-glucanase, in strawberry leaves. We identified lipopeptide antibiotics, including iturin A, fengycin, mixirin, pumilacidin and surfactin, produced and secreted by S13-3. Iturin A and surfactin elicited the gene expression of the pathogenesis-related proteins in strawberry leaves, suggesting that antagonistic strain S13-3 confers resistance to strawberry leaves through the production of lipopeptide antibiotics. In fact, iturin A and surfactin triggered induced systemic resistance on strawberry plants, resulting in the reduction of the severity of anthracnose disease caused by Colletotrichum gloeosporioides. The bifunctional activity of S13-3, which consists of the antagonistic effect and the induction of plant defence response by the antibiotics produced by it, may make S13-3 an innovative biological control agent against phytopathogens in strawberry. This study tries to determine whether biocontrol of phytopathogens by Bacillus amyloliquefaciens in strawberry can be connected to induced plant resistance. The results suggested that the antagonistic strain B. amyloliquefaciens S13-3 confers resistance to strawberry through the production of lipopeptide antibiotics.


Recycling of incinerated sewage sludge ash as an adsorbent for heavy metals removal from aqueous solutions.
The management of large quantities of incinerated sewage sludge ash (ISSA) is problematic. Environmental and economic benefits can be achieved by using ISSA as an adsorbent for heavy metals removal due to its exceptionally porous structure and active components. In this study, the feasibility of using ISSA to treat heavy metals (Cd(II), Cu(II) and Zn(II)) contaminated waters from both single- and binary-metal systems were investigated. The results showed that the pH of the solution played a pivotal role in the adsorption of heavy metals by ISSA and the optimal pH for the adsorption of these metals was around 6.00. The adsorption process of Cu(II), Cd(II), and Zn(II) in a single-metal system was similar and fast. The equilibrium data followed the Freundlich isotherm model and the corresponding adsorption capacity was 0.13, 0.11 and 0.06 mmol/g, respectively. However, the presence of other competitive metal ions had adverse effects on both the adsorption rate and the adsorption capacity for the target metal ions. The affinity of ISSA towards the metals followed the order of Cu(II) > Cd(II) > Zn(II). The difference in pH value and Ca or Na concentration of the solution after adsorption revealed that cation exchange played a fundamental role in the adsorption of the target metals, while electrostatic attraction and precipitation were insignificant. Over all, the application of ISSA as an adsorbent would be a promising option to both relieve the waste disposal pressure and mitigate the complex heavy metals pollution.


Acute abdomen due to ovarian congestion: a fallopian tube accompanied by a paratubal cyst, coiling tightly round the ovary.
We experienced an unreported rare case with an adnexal mass causing severe acute abdomen during pregnancy. A 30-year-old Japanese pregnant woman was transported to our hospital for her right lower abdominal pain at 30 weeks of gestation. Magnetic resonance imaging and ultrasound demonstrated a cyst measuring 3-4 cm in diameter adjacent to the right ovary, and a parovarian cyst was considered to be the most probable diagnosis. We strongly suspected torsion of the ovarian pedicle or fallopian tube in conjunction with her clinical symptoms. Laparotomy revealed that the elongated right fallopian tube accompanied by a paratubal cyst was coiling tightly 2.5 times round the right ovary, causing apparent congestion and enlargement of the right ovary. Soon after we released the congested right ovary from the coiling of the fallopian tube, the congestion subsided. The postoperative course was favorable, and pregnancy and delivery were uneventful.


Hearing loss following intratympanic instillation of gentamicin for the treatment of unilateral Meniere's disease.
To determine the incidence, extent, and time course of hearing loss following instillation of intratympanic gentamicin using a predetermined fixed protocol for incapacitating unilateral Meniere's disease and to determine whether such loss is associated with any identifiable risk factors. A retrospective analysis of all patients treated with intratympanic gentamicin between 1988 and 1998 using American Academy of Otolaryngology-Head and Neck Surgery reporting guidelines (1985 and 1995). A predetermined regimen using a fixed dose (gentamicin 26.7 mg/mL administered three times daily for 4 consecutive days) was used. The records of patients treated with this particular protocol were reviewed. The relationship between pretreatment hearing acuity, pretreatment bithermal caloric response, duration of symptoms, and previous treatment to post-treatment hearing were analyzed with respect to hearing. Complete vestibular and audiologic data over a minimum 2-year follow-up were available for 85 individuals. Sixty-three patients (74.1%) had unchanged or improved hearing, and 22 patients (25.9%) realized hearing loss. In 80% of the latter, it occurred during the first month post-treatment. When hearing acuity at the 1-month post-treatment interval remained unchanged (91.1%), it was likely to remain so over the next 23 months. A significantly higher incidence of profound hearing loss was noted in patients who developed hearing loss in the first month, as compared with those who developed hearing loss at a later period (p = .0207, relative risk = 1.5). Re-treatment was not associated with hearing loss. The only identifiable risk factor for developing hearing loss was pretreatment hearing acuity stages 3 and 4 (pure-tone average > 40 dB) (p = .022, relative risk = 1.5). Hearing loss is a recognized complication of treatment with intratympanic gentamicin, occurring in approximately 26% of individuals. In those individuals in whom hearing acuity has remained unchanged after the first month interval, significant worsening of hearing is unlikely, and patients can be reassured accordingly.


Dissociation of histamine release and clinical improvement following treatment of acquired cold urticaria by prednisone.
1 Corticosteroids are known to suppress evoked histamine release from human skin in vitro. Therefore the effect of prednisone, on cold evoked histamine release and clinical response was studied in six patients with acquired cold urticaria. 2 Following cold challenge all six patients developed an immediate urticarial response of the forearm and elevation of histamine levels, measured by superfusion cascade bioassay of the venous blood draining the forearm. 3 After treatment with prednisone, in an oral dose of 20-25 mg for 1 to 5 days, a suppression of evoked histamine release occurred in all but one patient. However, there was no corresponding decrease of erythema or oedema, though pruritus was improved in most patients. 4 The lack of clinical improvement in erythema and oedema, despite reduction in histamine levels, suggests that histamine may not be the principal mediator of the vascular response to cold challenge in acquired cold urticaria.


A differential scanning calorimetric study of Newcastle disease virus: identification of proteins involved in thermal transitions.
The irreversible thermal denaturation of Newcastle disease virus was investigated using different techniques including high-sensitivity differential scanning calorimetry, thermal gel analysis intrinsic fluorescence, and neuraminidase activity assays. Application of a successive annealing procedure to the scanning calorimetric endotherm of Newcastle disease virus furnished four elementary thermal transitions below the overall endotherm; these were further identified as coming from the denaturation of each viral protein. The shape of these transitions, as well as their scanrate dependence, was explained by assuming that thermal denaturation takes place according to the kinetic scheme N-->(k)D, where k is a first-order kinetic constant that changes with temperature, as given by the Arrhenius equation; N is the native state; and D is the denatured state. On the basis of this model, activation energy values were calculated. The data obtained with the other methods used in this work support the proposed two-state kinetic model.


Study on the mechanism of PM2.5 affecting Th1/Th2 immune imbalance through the notch signaling pathway in asthmatic mice.
Some research has shown that PM2.5 causes Th1/Th2 immune imbalance and aggravates asthma. However, the exact mechanism of PM2.5 causing aggravation of asthma remains unclear. The purpose of this study was to investigate whether exposure to PM2.5 exacerbates Th1/Th2 immune imbalance through the Notch signaling pathway. Eight-week-old SPF female BALF/c mice were sensitized by ovalbumin to establish an asthma mouse model. PM2.5 exposure was carried out by aerosol inhalation of PM2.5 (510 μg/m3) after each provocation. The lung function of mice was measured and Splenic T lymphocyte subsets were detected. Notch signaling pathway was tested. The levels of interferon (IFN)-γ and interleukin (IL)-4 in serum and bronchoalveolar lavage fluid were determined. The results showed that the expression of the mRNA and protein of Notch1 and Hes1 in the asthma group were significantly higher than those in healthy controls. The levels of IL-4 were also remarkably high; while the levels of IFN-γ were remarkably low in serum and BALF, the Th1% and Th1/Th2 ratios were significantly lower, and Th2% was significantly higher in the asthma group than in the healthy controls. PM2.5 promoted further activation of the Notch signaling pathway and aggravated Th1/Th2 immune imbalance in asthmatic mice. γ-secretase inhibitor can partially inhibit the activation of the Notch signaling pathway and alleviate aggravation of immune imbalance. In conclusion, the asthmatic mice had a Th1/Th2 immune imbalance and an overactivated Notch signaling pathway. PM2.5 further aggravated Th1/Th2 immune imbalance by activating the Notch signaling pathway.


An NMR study of translational diffusion and structural anisotropy in magnetically alignable nonionic surfactant mesophases.
The diffusion of both water and surfactant components in aqueous solutions of the nonionic surfactant "C12E6"--which includes hexagonal, cubic, lamellar, and micellar mesophases--has been studied by pulsed-field-gradient NMR. Diffusion coefficients were measured in unaligned samples in all of these phases. They were also obtained in the hexagonal and lamellar phases in oriented monodomain samples that were aligned by slow cooling from the micellar phase in an 11.7 T magnet. Measured water and soap diffusion coefficients in the NMR-isotropic cubic and (high-water-content) micellar phases as well as diffusion anisotropy measurements in the magnetically aligned hexagonal phase were quantitatively consistent with the constituent structures of these phases being identical surfactant cylinders, with only the fraction of surface-associated water varying with the water-soap molar ratio. The values of the water and soap diffusion coefficients in the oriented lamellar phase suggest an increase in defects and obstructions to soap diffusion as a function of increasing water content, while those in the low-water-content micellar phase rule out the presence of inverse micelles.


Interfacial compliance, energy dissipation, frequency effects, and long-term fretting corrosion performance of Ti-6Al-4V/CoCrMo interfaces.
Fretting corrosion in modular orthopedic implants is a well-documented process that may be associated with adverse local tissue reactions, pain, and revisions. Engineering modular junction interfaces to withstand applied fretting motion without surface abrasion could prevent implant degradation and surface damage. Previous work on geometrically modified Ti-6Al-4V/CoCrMo interfaces with increased compliance showed reduced fretting currents and surface damage during short term, variable-load in vitro testing. This study assesses the same interfaces under long-term conditions using an in vitro pin-on-disk fretting corrosion test apparatus. Preliminary variable-load frequency testing of typical control pin geometries showed a frequency-dependent current response, with underlying contact conditions of metal-metal interfaces that remained unchanged. One-million-cycle testing showed diminished fretting currents in all groups by 5 × 105 cycles, but consistently lower currents in the high-compliance group. Corresponding fretting currents and work of fretting measurements of high-compliance pins confirmed that minimal fretting was experienced at the interface, with elastic bending of the pin accounting for almost all applied displacement. Debris generated during testing were composed of titanium and chromium oxides, small amounts of cobalt and molybdenum oxides, and sodium and phosphate originating from the surrounding test solution. Post-test analyses of sample surfaces revealed substantially more surface damage on CoCrMo disks than Ti-6Al-4V pins, thought to be a result of adhesive wear of mixed oxide debris on the pin and abrasion of the disk by the oxide debris layer. Surface damage to high-compliance pins suggests some abrasion is unavoidable with geometric modifications.


Percutaneous absorption of indomethacin from transparent oil/water gels in rabbits.
The percutaneous absorption of indomethacin from transparent oil in water gels (TOW gels) has been studied in rabbits and compared with absorption from a hydrophilic gel and from a spray formulation. The area under the curve and the Cmax values in plasma were significantly higher for the TOW gels in comparison with the other formulations after single application. The pH of the aqueous phase of the TOW gels did not significantly influence the bioavailability. After multiple application the TOW gels induced a larger increase in AUC (vs first application) in comparison with the other formulations. None of the formulations without drug damaged the skin after multiple application. For indomethacin formulations skin damage was more pronounced with the hydrophilic gel than for the TOW gels and spray formulation.


[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].
Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.


A study on the effects of pica and iron-deficiency anemia on oxidative stress, antioxidant capacity and trace elements.
Pica is defined as developmentally inappropriate consumption of nonnutritive substances for at least 1 month. There are a few studies on serum trace element levels of patients with pica. The literature contains contracting data on the levels of oxidative stress and antioxidant levels in patients with iron-deficiency anemia (IDA). The effect of pica on oxidative stress and antioxidant capacity has not been investigated yet. The present study evaluated the effects of pica and IDA on oxidative stress and antioxidant capacity as well as on the levels of trace elements including serum zinc and selenium in 47 children with IDA plus pica, 22 children with IDA only and 21 nonanemic children as controls. The results demonstrated significantly lower levels of serum selenium and zinc in pica and IDA groups compared to the control group. Total oxidant levels were highest in the pica group and consistently, the lowest total antioxidant capacity was observed again in the pica group. Comparison of pica and IDA groups yielded significantly lower levels of total antioxidant levels and significantly higher oxidative stress index in the pica group. Consequently, it is thought that the detrimental effects of pica within the organism were mediated by adverse impacts on antioxidant capacity and oxidative stress. These effects should be kept in mind while managing patients with pica.


On time: developmental timing within and across species.
Organisms across species differ in the relative size and complexity of their tissues to serve the specific purposes of the host. Correct timing is a crucial ingredient in the development of tissues, as reaching the right size and complexity requires a careful balance between cellular proliferation and differentiation. Premature or delayed differentiation, for instance, can result in tissue imbalance, malformation or malfunction. Despite seemingly rigid constraints on development, however, there is flexibility in both the timing and differentiation trajectories within and between species. In this Spotlight, we discuss how time is measured and regulated in development, and question whether developmental timing is in fact different between species.


Choosing the best endoscopic approach for post-bariatric surgical leaks and fistulas: Basic principles and recommendations.
Post-surgical leaks and fistulas are the most feared complication of bariatric surgery. They have become more common in clinical practice given the increasing number of these procedures and can be very difficult to treat. These two related conditions must be distinguished and characterized to guide the appropriate treatment. Leak is defined as a transmural defect with communication between the intra and extraluminal compartments, while fistula is defined as an abnormal communication between two epithelialized surfaces. Traditionally, surgical treatment was the preferred approach for leaks and fistulas and was associated with high morbidity with significant mortality rates. However, with the development of novel devices and techniques, endoscopic therapy plays an increasingly essential role in managing these conditions. Early diagnosis and endoscopic therapy initiation after clinical stabilization are crucial to success since clinical success rates are higher for acute leaks and fistulas when compared to late and chronic leaks and fistulas. Several endoscopic techniques are available with different mechanisms of action, including direct closure, covering/diverting or draining. The treatment should be individualized by considering the characteristics of both the patient and the defect. Although there is a lack of high-quality studies to provide standardized treatment algorithms, this narrative review aims to provide a summary of the current scientific evidence and, based on this data and our extensive experience, make recommendations to help choose the best endoscopic approach for the management of post-bariatric surgical leaks and fistulas.


Clinical studies with the NOVA ISE for IMg2+.
The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.


[Effects of perioperative transcutaneous electrical acupoint stimulation on postoperative analgesia in patients undergoing shoulder arthroscopic surgery].
To observe and evaluate the effects of transcutaneous electrical acupoint stimulation (TEAS) at different time points on postoperative analgesia in perioperative period in patients undergoing shoulder arthroscopic surgery, and to explore the optimal time to use TEAS for shoulder arthroscopic surgery. A total of 120 patients undergoing unilateral shoulder arthroscopy under general anesthesia, graded withⅠtoⅡaccording to ASA criteria were randomly divided into 3 groups, 40 patients in each one. The patients in the group A were treated with preoperative TEAS at sham acupoints combined with postoperative TEAS at Hegu (LI 4) and Neiguan (PC 6); the patients in the group B were treated with preoperative TEAS at Hegu (LI 4) and Neiguan (PC 6) combined with postoperative TEAS at sham acupoints; the patients in the group C were treated with TEAS at sham acupoints before and after operation. The parameters of TEAS were dilatational wave, 2 Hz/100 Hz in frequency, 30 min. When the resting-state visual analogue scale (VAS) of incision was more than 3 points, the patient-controlled intravenous analgesia (PCIA) pump of sufentanil was administered to maintain the VAS no more than 3 points. The time point when PCIA pump was firstly used, the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery were recorded. Intraoperative anesthetic doses were recorded in the three groups. The resting-state and task-state VAS were evaluated at 0, 6, 12, 24 hours after surgery; the patient's satisfaction rate and adverse effects were recorded. The time when PCIA pump was firstly used in the group A and the group B was significantly longer than that in the group C, and the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery in the group A and group B were significantly less than those in the group C (all P<0.05); the incidence of postoperative nausea-vomiting and sore throat was reduced (all P<0.05). The time when PCIA pump was firstly used in the group A was significantly longer than that in the group B, and the used dose of sufentanil and effective pressing number of PCIA pump within 24 hours after surgery in the group A were significantly less than those in the group B (all P<0.05); no significant difference of the incidence of postoperative nausea-vomiting and sore throat was observed between the group A and group B (both P>0.05). There were no statistically significant difference in VAS score at different postoperative time points and postoperative analgesia satisfaction rate between the two groups (all P>0.05). Perioperative TEAS could improve the postoperative analgesia in patients undergoing arthroscopic shoulder surgery, delay the time when PCIA pump is firstly used, reduce the dosage of postoperative analgesics and adverse events. Compared before surgery, postoperative TEAS has better analgesia.


Medium resolution computergraphics: another approach.
This paper discusses the rationale leading to the purchase of a medium resolution computergraphics system and modification of existing computer software for the production of scientific publication graphs and presentation color slides. Capabilities of the system and components are reported.


Simplified obturation of tapered canal preparations.
Canals shaped to wider tapers, specifically .06 mm and .08 mm, have traditionally been associated with thermoplastic fills. However, the canals shaped to .06 mm and .08 mm tapers correlate very closely to the shape of fine-medium and medium gutta-percha points, respectively. Combining the placement of these single-point fills with the patented EZ-Fill bi-directional spiral for well-controlled placement of the EZ-Fill epoxy resin sealer gives the dentist the ability to simplify the obturation procedure with results that are at least equal to those achieved with lateral condensation and thermoplastic techniques.


Modified Antimesenteric Tapering Enteroplasty: An Alternative Technique for the Treatment of Dysfunctional Anastomosis in Patients With Short Bowel.
Several techniques have been described to taper the dilated small bowel to improve intestinal motility and decrease complications related to overdilated small bowel, including longitudinal intestinal lengthening and tapering, serial transverse enteroplasty, and spiral intestinal lengthening and tailoring. We propose an alternative technique designed to optimize bowel function and minimize the effects of recurrent small-bowel bacterial overgrowth in patients with short or ultra-short gut syndrome and dysfunctional anastomosis with maintenance of the actual absorptive surface. The dilated side-to-side anastomosis is identified, and the mesentery leaves from both the proximal and distal small-bowel loops are separated by using blunt dissection. The previous anastomosis is divided longitudinally with a GI stapler. Once the small-bowel transection is completed, 2 separate blind loops of intestine are created, each one with half the circumference of the dilated side-to-side anastomosis. The antimesenteric stapled line is then reinforced with an outer layer of running suture. The blind loops of the tapered small bowel are then trimmed and anastomosed in an end-to-end isoperistaltic fashion in 2 layers. There were no postoperative complications. The length of the tapering ranged from 10 to 23 cm, corresponding to approximately 16% (range, 13%-20%) of the remaining small-bowel length. Three of 4 patients presented significant improvement of their symptoms and were able to have their parenteral support discontinued. Modified antimesenteric tapering enteroplasty is an alternative technique to improve intestinal motility and treat patients with short-bowel syndrome and dysfunctional side-to-side anastomosis without the need for further small-bowel resection. This bowel-sparing technique represents a valuable option in the armamentarium of the surgeon who manages patients with intestinal failure.


Impact of Dietary Fiber Consumption on Insulin Resistance and the Prevention of Type 2 Diabetes.
Large prospective cohort studies consistently show associations of a high dietary fiber intake (>25 g/d in women and >38 g/d in men) with a 20-30% reduced risk of developing type 2 diabetes (T2D), after correction for confounders. It is less well recognized that these effects appear to be mainly driven by high intakes of whole grains and insoluble cereal fibers, which typically are nonviscous and do not relevantly influence postprandial glucose responses [i.e., glycemic index (GI)] or are strongly fermented by the gut microbiota in the colon. In contrast, a dietary focus on soluble, viscous, gel-forming, more readily fermentable fiber intakes derived from fruit and certain vegetables yields mixed results and generally does not appear to reduce T2D risk. Although disentangling types of fiber-rich foods and separating these from possible effects related to the GI is an obvious challenge, the common conclusion that key metabolic effects of high-fiber intake are explained by mechanisms that should mainly apply to the soluble, viscous type can be challenged. More recently, studies in humans and animal models focused on gaining mechanistic insights into why especially high-cereal-fiber (HCF) diets appear to improve insulin resistance (IR) and diabetes risk. Although effects of HCF diets on weight loss are only moderate and comparable to other types of dietary fibers, possible novel mechanisms have emerged, which include the prevention of the absorption of dietary protein and modulation of the amino acid metabolic signature. Here we provide an update of our previous review from 2008, with a focus on mechanistic insights of how HCF diets may improve IR and the risk of developing T2D.


Cryptic Phosphorylation-Mediated Divergent Biosynthesis of High-Carbon Sugar Nucleoside Antifungals.
Establishing a general biosynthetic scheme for natural products is critical for a broader understanding of natural product biosynthesis and the structural prediction of metabolites based on genome sequence information. High-carbon sugar nucleoside antimicrobials are an underexplored class of natural products with unique structures and important biological activities. Recent studies on C6 sugar nucleoside antifungal natural products, such as nikkomycins and polyoxins, revealed a novel biosynthetic mechanism involving cryptic phosphorylation. However, the generality of this biosynthetic mechanism remained unexplored. We here report in vitro characterization of the biosynthesis of a C7 sugar nucleoside antifungal, malayamycin A. Our results demonstrate that the malayamycin biosynthetic enzymes specifically accept 2'-phosphorylated biosynthetic intermediates, suggesting that cryptic phosphorylation-mediated biosynthesis is conserved beyond C6 sugar nucleosides. Furthermore, the results suggest a generalizable divergent biosynthetic mechanism for high-carbon sugar nucleoside antifungals. In this model, C6 and C7 sugar nucleoside biosyntheses proceed via a common C8 sugar nucleoside precursor, and the sugar size is determined using the functions of α-ketoglutarate (α-KG)-dependent dioxygenases (NikI/PolD for C6 sugar nucleosides and MalI for C7 sugar nucleosides). These results provide an important guidance for the future genome-mining discovery of high-carbon sugar nucleoside antimicrobials.


[Characteristics of responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency].
Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.


[A CASE OF ANAPHYLAXIS INDUCED BY VITAMIN B1 DERIVATIVE IN VITAMIN B INFUSION FORMULATION FOR INTRAVENOUS INJECTION].
A woman in her 20s presented to our clinic with a lower gastrointestinal infection. When we administered intravenous antibacterial and vitamin infusions, she developed anaphylaxis. We performed skin tests to investigate the cause, and an intradermal test was positive for a 1% intravenous vitamin complex. We then performed a component-specific test, which was positive for thiamine disulfide phosphate, a vitamin B1 derivative. We therefore diagnosed anaphylaxis due to thiamine disulfide phosphate. No previous reports have described cross-reactivity between vitamin B1 derivatives. In our case, however, the patient tested positive for fluthiamine hydrochloride, suggesting cross-reactivity. Intravenous vitamin complexes are used in daily clinical practice and should be administered with caution because of the possibility of anaphylaxis, although it occurs infrequently.


Increased mediator complex subunit 15 expression is associated with poor prognosis in hepatocellular carcinoma.
Mediator complex subunit 15 (MED15) is a coactivator involved in the regulated transcription of RNA polymerase II-dependent genes and serves an oncogenic role in numerous types of cancer. However, the expression and function of MED15 in hepatocellular carcinoma (HCC) remain unknown. In the present study, the aim was to investigate the expression and clinical significance of MED15 in HCC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analysis revealed that MED15 mRNA and protein levels were significantly upregulated in HCC tissues compared with those in the corresponding adjacent non-tumor liver tissues. Furthermore, analyzing data from The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and GSE14520 datasets revealed a significant correlation between MED15 expression and the tumor size (P=0.033), Barcelona Clinic Liver Cancer stage (P=0.031), α-fetoprotein levels (P=0.002) and metastasis risk (P=0.001). Furthermore, patients with high MED15 expression levels had a shorter survival time compared with those with low MED15 expression levels (P<0.05). Univariate and multivariate analyses further revealed that MED15 may be an independent prognostic factor for the overall survival of HCC patients (hazard ratio, 1.762; 95% confidence interval, 1.077-2.882; P<0.05). In addition, MED15 expression was positively associated with hypoxia-inducible factor 1α expression in the TCGA-LIHC and GSE14520 datasets (P<0.01). In conclusion, the data reported in the present study indicated that MED15 is overexpressed in HCC and may represent a novel prognostic biomarker for patients with HCC.


The Effect of the Mediterranean Diet on Hypertension: A Systematic Review and Meta-Analysis.
The adoption of a Mediterranean diet (MD) pattern of eating is often described as a strategy to help prevent or manage hypertension. However, this dietary regimen has not been reviewed systematically for its efficacy against hypertension. Therefore, the purpose of this study was to analyze the effect of interventions of at least 1 year duration on blood pressure (BP) values through a systematic review and meta-analysis. The focus was on interventions comparing an MD with a low-fat diet. The authors accessed and searched PubMed and Scopus databases up to March, 2015. Randomized control trials comparing MD vs low-fat diet were included. The researchers assessed the methodological quality, extracted the valid data, and conducted the meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Six trials (more than 7,000 individuals) were identified. Meta-analysis showed that interventions aiming at adopting an MD pattern for at least 1 year reduced both the systolic BP and diastolic BP levels in individuals with normal BP or mild hypertension. The effect was higher for the systolic BP (-1.44 mm Hg) but also consistent for the diastolic BP (-0.70 mm Hg). However, the results have to be interpreted with caution owing to the reduced number of studies eligible for inclusion in this meta-analysis. This situation limited the statistical power of the analyses. Furthermore, in all analyses, the pooled effect estimation showed a high evidence of heterogeneity, which compromises the validity of the pooled estimates. A positive and significant association was found between the MD and BP in adults. However, in all cases the magnitude of the effect was small. Based on this limited group of studies and their heterogeneity, the authors found insufficient convincing evidence to suggest that the MD decreased BP. Further standardized research is urgently needed to reach evidence-based conclusions to clarify the role of MD in BP management, particularly in Europe and other societies where prevalence of cardiovascular diseases is increasing.


Comparative biocontrol ability of chitinases from bacteria and recombinant chitinases from the thermophilic fungus Thermomyces lanuginosus.
Microbial chitinases (EC 18.104.22.168) are known to hydrolyse the chitinous gut epithelium of insects and cell walls of many fungi. In this study, seven chitinases from different bacteria and fungi were produced, characterized and their biocontrol abilities against graminaceous stem borers Eldana saccharina, Chilo partellus and Sesamia calamistis were assessed. All chitinases were stable over broad ranges of pH and temperature, however, recombinant fungal chitinases were more acid-stable than the bacterial counterparts. Chitinases from the thermophilic filamentous fungi Thermomyces lanuginosus SSBP (Chit1) and from Bacillus licheniformis (Chit lic) caused 70% and 80% mortality, respectively, in second instar larvae of E. saccharina. Six of the seven partially-purified microbial chitinases inhibited Aspergillus niger, A. flavus, A. alliaceus, A. ochraceus, Fusarium verticillioides and Mucor sp. Overall, microbial chitinases show promise as biocontrol agents of fungi and stalk-boring lepidopterans.


Two-species competition with high dispersal: the winning strategy.
This paper is motivated by the following simple question: how does diffusion affect the competition outcomes of two competing species that are identical in all respects other than their strategies on how they spatially distribute their birth rates. This may provide us with insights into how species learn to compete in a relatively stable setting, which in turn may point out species evolution directions. To this end, we formulate some extremely simple two-species competition models that have either continuous or discrete diffusion mechanisms. Our analytical work on these models collectively and strongly suggests the following in a fast diffusion environment: where different species have the same birth rates on average, those that do well are those that have greater spatial variation in their birth rates. We hypothesize that this may be a possible explanation for the evolution of grouping behavior in many species. Our findings are confirmed by extensive numerical simulation work on the models.


Effectiveness of chitosan against wine-related microorganisms.
The antimicrobial action of chitosan against wine related microorganisms, including Lactobacillus plantarum, Saccharomyces cerevisiae, Oeonococcus oeni, Lactobacillus hilgardii, Brettanomyces bruxellensis, Hanseniaspora uvarum and Zygosaccharomyces bailii was examined in laboratory media. In order to assess the potential applicability of chitosan as a microbial control agent for wine, the effect of chitosan, applied individually and/or in combination with sulphur dioxide (SO2), on the growth of microorganisms involved in various stages of winemaking and on the fermentative performance of S. cerevisiae was investigated. Of the seven wine-related microorganisms studied, S. cerevisiae exhibited the strongest resistance to antimicrobial action of chitosan in laboratory media with a minimum inhibitory concentration (MIC) greater than 2 g/L. L. hilgardii, O. oeni and B. bruxellensis were the most susceptible to chitosan since they were completely inactivated by chitosan at 0.2 g/L. The MIC of chitosan for L. plantarum, H. uvarum and Z. bailii was 2, 0.4 and 0.4 g/L, respectively. In wine experiments, it was found that chitosan had a retarding effect on alcoholic fermentation without significantly altering the viability and the fermentative performance of S. cerevisiae. With regard to non-Saccharomyces yeasts (H. uvarum and Z. bailii) involved in winemaking, the early deaths of these yeasts in mixed cultures with S. cerevisiae were not probably due to the antimicrobial action of chitosan but rather due to ethanol produced by the yeasts. The complex interactions between chitosan and wine ingredients as well as microbial interactions during wine fermentation considerably affect the efficacy of chitosan. It was concluded that chitosan was worthy of further investigation as an alternative or complementary preservative to SO2 in wine industry.


Central adaptation to repeated galvanic vestibular stimulation: implications for pre-flight astronaut training.
Healthy subjects (N = 10) were exposed to 10-min cumulative pseudorandom bilateral bipolar Galvanic vestibular stimulation (GVS) on a weekly basis for 12 weeks (120 min total exposure). During each trial subjects performed computerized dynamic posturography and eye movements were measured using digital video-oculography. Follow up tests were conducted 6 weeks and 6 months after the 12-week adaptation period. Postural performance was significantly impaired during GVS at first exposure, but recovered to baseline over a period of 7-8 weeks (70-80 min GVS exposure). This postural recovery was maintained 6 months after adaptation. In contrast, the roll vestibulo-ocular reflex response to GVS was not attenuated by repeated exposure. This suggests that GVS adaptation did not occur at the vestibular end-organs or involve changes in low-level (brainstem-mediated) vestibulo-ocular or vestibulo-spinal reflexes. Faced with unreliable vestibular input, the cerebellum reweighted sensory input to emphasize veridical extra-vestibular information, such as somatosensation, vision and visceral stretch receptors, to regain postural function. After a period of recovery subjects exhibited dual adaption and the ability to rapidly switch between the perturbed (GVS) and natural vestibular state for up to 6 months.


TRIM59 facilitates the proliferation of colorectal cancer and promotes metastasis via the PI3K/AKT pathway.
Tripartite motif-containing 59 (TRIM59) belongs to the tripartite motif (TRIM) protein family and is upregulated in various malignancies. However, its expression in colorectal cancer (CRC) is still unknown. In the present study, we examined the expression and biological function of TRIM59 in CRC. We analyzed CRC tissues and cells by quantitative real-time polymerase chain reaction. Kaplan-Meier survival analysis was used to evaluate the prognostic significance of TRIM59 in CRC patients. Furthermore, we investigated the role of TRIM59 in CRC growth and metastasis. The potential mechanism underlying the regulation of cell metastasis by TRIM59 was determined by western blotting. TRIM59 expression was conspicuously overexpressed in CRC tissues and CRC cell lines compared to that noted in the corresponding normal control cells. Patients with higher TRIM59 expression had poorer prognosis. Furthermore, knockdown of TRIM59 suppressed cell proliferation through the induction of apoptosis and inhibited migration and invasion significantly in vitro. Further investigation revealed that knockdown of TRIM59 effectively reversed the expression of epithelial-mesenchymal transformation‑related proteins vimentin, Snail and E-cadherin. Our preliminary results confirm that TRIM59 can be mediated by PI3K/AKT signaling. TRIM59 functions as an oncogene in CRC progression, which could be a novel target for the detection and treatment of CRC.


Modeling simple repeat expansion diseases with iPSC technology.
A number of human genetic disorders, including Huntington's disease, myotonic dystrophy type 1, C9ORF72 form of amyotrophic lateral sclerosis and several spinocerebellar ataxias, are caused by the expansion of various microsatellite sequences in single implicated genes. The neurodegenerative and neuromuscular nature of the repeat expansion disorders considerably limits the access of researchers to appropriate cellular models of these diseases. This limitation, however, can be overcome by the application of induced pluripotent stem cell (iPSC) technology. In this paper, we review the current knowledge on the modeling of repeat expansion diseases with human iPSCs and iPSC-derived cells, focusing on the disease phenotypes recapitulated in these models. In subsequent sections, we provide basic practical knowledge regarding iPSC generation, characterization and differentiation into neurons. We also cover disease modeling in iPSCs, neuronal stem cells and specialized neuronal cultures. Furthermore, we also summarize the therapeutic potential of iPSC technology in repeat expansion diseases.


Comparison of new formulas of stannous fluoride toothpastes with other commercially available fluoridated toothpastes: A systematic review and meta-analysis of randomised controlled trials.
The aim of this study was to systematically review and analyse the difference in efficacy of stannous fluoride toothpaste formulations in comparison to other fluoridated toothpastes without stannous fluoride. A systematic search of the literature was performed according to PRISMA guidelines. A search strategy was developed to answer the study question and was performed in PubMed-Medline databases. Inclusion criteria were randomised controlled clinical trials comparing stannous fluoride toothpaste formulations with other fluoridated toothpastes not containing stannous fluoride. The search in PubMed-Medline databases resulted in 384 articles; 23 articles were downloaded for review, 16 articles were included in the report and six could be used for meta-analysis. All studies were randomised controlled clinical trials that compared clinical outcomes between toothpastes with stannous fluoride combinations and toothpastes with only fluoride. The overall results of the 16 studies favoured the stannous fluoride formulations. However, in a meta-analysis of the randomised controlled clinical trials, it was demonstrated that stannous fluoride toothpaste formulations provided significantly better outcomes based on the Gingival Index (SMD -0.14, 95% CI -0.20, -0.07, P = 0.0001), but not the Modified Gingival Index (SMD -0.30, 95% CI -0.7, 0.09, P = 0.13). The antibacterial properties of stannous seem to provide favourable results when formulated with a fluoridated toothpaste. This systematic review highlights the lack of homogenous research available to rigorously compare stannous fluoride toothpaste formulations with other fluoridated toothpastes without stannous fluoride.


Kidnapping intergroup young: an alternative strategy to maintain group size in the group-living pied babbler (Turdoides bicolor).
Both inter- and intragroup interactions can be important influences on behaviour, yet to date most research focuses on intragroup interactions. Here, we describe a hitherto relatively unknown behaviour that results from intergroup interaction in the cooperative breeding pied babbler: kidnapping. Kidnapping can result in the permanent removal of young from their natal group. Since raising young requires energetic investment and abductees are usually unrelated to their kidnappers, there appears no apparent evolutionary advantage to kidnapping. However, kidnapping may be beneficial in species where group size is a critically limiting factor (e.g. for reproductive success or territory defence). We found kidnapping was a highly predictable event in pied babblers: primarily groups that fail to raise their own young kidnap the young of others, and we show this to be the theoretical expectation in a model that predicts kidnapping to be facultative, only occurring in those cases where an additional group member has sufficient positive impact on group survival to compensate for the increase in reproductive competition. In babblers, groups that failed to raise young were also more likely to accept extragroup adults (hereafter rovers). Groups that fail to breed may either (i) kidnap intergroup young or (ii) accept rovers as an alternative strategy to maintain or increase group size. This article is part of the theme issue 'Intergroup conflict across taxa'.


Low Plasma Levels of Fibroblast Growth Factor-21 in Patients with Peripheral Artery Disease.
Fibroblast growth factor-21 (FGF-21) is a metabolic regulator with beneficial effects on glucolipid metabolism. Since FGF-21 has lipid-lowering, anti-inflammatory and anti-oxidant properties, it may play a protective role against atherosclerosis. However, blood FGF-21 levels in coronary artery disease (CAD) or peripheral artery disease (PAD) have not been elucidated. We measured plasma FGF-21 levels in 417 patients undergoing coronary angiography, who also had ankle-brachial index test for PAD screening. CAD was found in 224 patients (1-vessel [1-VD], n=92; 2-vessel [2-VD], n=65; 3-vessel disease [3-VD], n=67). No significant difference was found in the FGF-21 levels between 224 patients with CAD and 193 without CAD (median 26.0 vs. 25.9 pg/mL). FGF-21 levels in 4 groups of CAD(-), 1-VD, 2-VD, and 3-VD were 25.9, 37.2, 19.4, and 0.0 pg/mL. FGF-21 tended to be highest in 1-VD and lowest in 3-VD, but the difference did not reach statistical significance. PAD was found in 38 patients. Compared to the 379 patients without PAD, 38 with PAD had CAD more often (87% vs. 50%), especially 3-VD (P<0.001). FGF-21 levels were lower in patients with PAD than in those without PAD (0.0 vs. 30.7 pg/mL, P<0.02). In multivariate analysis, the FGF-21 level was an independent factor for PAD, but not for CAD. Odds ratio for PAD was 2.13 (95%CI=1.01-4.49) for a low FGF-21 level (<15.6 pg/mL). No significant difference was found in the FGF-21 levels between patients with and without CAD. However, FGF-21 levels were low in patients with PAD, and were a factor for PAD independent of atherosclerotic risk factors.


Impact of continued mailed fecal tests in the patient-centered medical home: Year 3 of the Systems of Support to Increase Colon Cancer Screening and Follow-Up randomized trial.
The current study was conducted to determine the effect of continuing a centralized fecal occult blood test (FOBT) mailed program on screening adherence. A patient-level randomized controlled trial was conducted in 21 patient-centered medical home primary care clinics between January 2010 and November 2012. A total of 2208 patients ranging in age from 52 to 75 years in a substudy of the Systems of Support to Increase Colon Cancer Screening and Follow-Up (SOS) trial were randomized at year 3 to continued automated interventions (Continued group), which included mailed information regarding colorectal cancer (CRC) screening choices, and were mailed stool kit tests or to a group in which interventions were stopped (Stopped group). The main outcomes and measures were the completion of CRC screening in year 3 and by subgroup characteristics, respectively. Adherence to CRC screening in year 3 was found to be significantly higher in patients in the Continued group compared with those in the Stopped group (53.3% vs 37.3%; adjusted net difference, 15.6% [P<.001]). This difference was entirely due to greater completion of FOBT (adjusted net difference, 18.0% [P<.001]). Year 3 CRC screening rates were highest in patients in the Continued group completing FOBT in both years 1 and 2 (77.2%), followed by patients completing only 1 FOBT in 1 of the 2 years (44.6%), with low rates of CRC testing reported among patients not completing any FOBT within the first 2 years (18.1%). A centralized mailed FOBT CRC screening program continued to be more effective than patient-centered medical home usual-care interventions, but only for those patients who had previously completed FOBT testing. Research is needed regarding how to engage patients not completing CRC testing after being mailed at least 2 rounds of FOBT tests. Cancer 2016;122:312-321. © 2015 American Cancer Society.


[A clinico-physiological study on the generators of short latency somatosensory evoked potential].
The purpose of this paper is to locate the generators of each wave component in the short latency somatosensory evoked potential (SSEP), by means of cumulative analysis of the SSEP obtained from various localized lesions in the upper cervical cord through brain stem and cerebral subcortical structures. Since there are considerable inconsistency of naming each component in the literature, SSEP to median nerve stimulation of 10 normal subjects were examined by two different recordings, i.e. recording from an electrode at the parietal scalp with a reference electrode on Erb's point (Par.-Erb), and the other at the frontal scalp with a reference electrode on Cv 7 (Fro.-Cv 7), and the SSEP was carefully studied. In normal subjects, the SSEP by Par.-Erb lead yielded 5 negative components (N 7, N 11, N 16, N 18 & N 26) and 4 positive components (P 9, P 13, P 22 & P 42), while by Fro.-Cv 7 5 negative components (N 7, N 10, N 12, N 16 & N 28) and 5 positive components (P 9, P 11, P 13, P 20 & P 44). Thirty three patients were subjected to analyse the influence of localized lesions to each component of the SSEP and the recording was evaluated in regard to (a) identification of each component, (b) latency of each component and inter-peak latency difference exceeding 2 SD, and (c) over 50% asymmetry and laterality of the amplitude. Cervical spondylotic myelopathy, high cervical cord tumor, tonsillar herniation, pontine infarct and hemorrhage, circumscribed thalamic lesion, and vascular lesion of centrum semiovale were carefully examined with CT scan and the findings were compared with neurological findings periodically. SSEP was taken repeatedly, especially before and after operative intervention, and alteration of the component was referred to the clinical progress of the lesion. In conclusion, results obtained from our present observation indicated that P 9 was the extramedullary projection, P 11 was intramedullary origin of the lower cervical cord, P 13 was medulla oblongata origin and P 13-N 16 was projection from medulla oblongata to thalamus. N 16-N 18 and N 26 were considered projection from thalamus to hand area of the parietal lobe with some association area and N 28 had the generator widely based on frontal projection system. These findings appeared to be quite useful for topographic diagnosis and functional evaluation of the lesions in central nervous system.


Cloacimonadota metabolisms include adaptations in engineered environments that are reflected in the evolutionary history of the phylum.
Phylum Cloacimonadota (previously Cloacimonetes, WWE1) is an understudied bacterial lineage frequently associated with engineered and wastewater systems. Cloacimonadota members were abundant and diverse in metagenomic datasets from a municipal landfill, prompting an examination of phylogenetic relationships, metabolic diversity, and pangenomic dynamics across the phylum, based on the 30 publicly available genomes and 24 new metagenome-assembled genomes (MAGs) from landfill samples. We found that Cloacimonadota have distinct evolutionary histories associated with engineered versus natural environments and identified genomic features and metabolic strategies that correlate to habitat of origin. Metabolic reconstructions for MAGs predict an anaerobic, acetogenic, and mixed fermentative and flavin-bifurcation-based anaerobic respiratory lifestyle for the majority of Cloacimonadota surveyed. Genomes from engineered ecosystems encode a suite of genes not typically found in genomes from natural environments including acetate kinase, genes for cysteine degradation to pyruvate, increased diversity of carbon utilization enzymes, and different mechanisms for generating membrane potential and ATP synthesis. This phylum-level examination also clarifies the distribution of functions previously observed for members of the phylum, where propionate oxidation and reverse TCA cycles are not common components of Cloacimonadota metabolism.


Regional differentiation and post-glacial expansion of the Atlantic silverside, Menidia menidia, an annual fish with high dispersal potential.
The coastal marine environment of the Northwest Atlantic contains strong environmental gradients that create distinct marine biogeographic provinces by limiting dispersal, recruitment, and survival. This region has also been subjected to numerous Pleistocene glacial cycles, resulting in repeated extirpations and recolonizations in northern populations of marine organisms. In this study, we examined patterns of genetic structure and historical demography in the Atlantic silverside, Menidia menidia, an annual marine fish with high dispersal potential but with well-documented patterns of clinal phenotypic adaptation along the environmental gradients of the Northwest Atlantic. Contrary to previous studies indicating genetic homogeneity that should preclude regional adaptation, results demonstrate subtle but significant (FST = 0.07; P < 0.0001) genetic structure among three phylogeographic regions that partially correspond with biogeographic provinces, suggesting regional limits to gene flow. Tests for non-equilibrium population dynamics and latitudinal patterns in genetic diversity indicate northward population expansion from a single southern refugium following the last glacial maximum, suggesting that phylogeographic and phenotypic patterns have relatively recent origins. The recovery of phylogeographic structure and the partial correspondence of these regions to recognized biogeographic provinces suggest that the environmental gradients that shape biogeographic patterns in the Northwest Atlantic may also limit gene flow in M. menidia, creating phylogeographic structure and contributing to the creation of latitudinal phenotypic clines in this species.


Biochemical and genetic characterization of the pathways for trehalose metabolism in Propionibacterium freudenreichii, and their role in stress response.
Propionibacterium freudenreichii accumulates high levels of trehalose, especially in response to stress. The pathways for trehalose metabolism were characterized, and their roles in response to osmotic, oxidative and acid stress were studied. Two pathways were identified: the trehalose-6-phosphate synthase/phosphatase (OtsA-OtsB) pathway, and the trehalose synthase (TreS) pathway. The former was used for trehalose synthesis, whereas the latter is proposed to operate in trehalose degradation. The activities of OtsA, OtsB and TreS were detected in cell extracts; the corresponding genes were identified, and the recombinant proteins were characterized in detail. In crude extracts of P. freudenreichii, OtsA was specific for ADP-glucose, in contrast to the pure recombinant OtsA, which used UDP-, GDP- and TDP-glucose, in addition to ADP-glucose. Moreover, the substrate specificity of OtsA in cell extracts was lost during purification, and the recombinant OtsA became specific to ADP-glucose upon incubation with a dialysed cell extract. The level of OtsA was enhanced (approximately twofold) by osmotic, oxidative and acid stress, whereas the level of TreS remained constant, or it decreased, under identical stress conditions. Therefore, the OtsA-OtsB pathway plays an important role in the synthesis of trehalose in response to stress. It is most likely that trehalose degradation proceeds via TreS to yield maltose, which is subsequently catabolized via amylomaltase activity. Hydrolytic activities that are potentially involved in trehalose degradation (trehalase, trehalose phosphorylase, trehalose-6-phosphate phosphorylase and trehalose-6-phosphate hydrolase) were not present. The role of trehalose as a common response to three distinct stresses is discussed.


An engineered food-grade Lactococcus lactis strain for production and delivery of heat-labile enterotoxin B subunit to mucosal sites.
Recent researches have been focusing on mucosal immune adjuvants, which play the key roles in mucosal immunization and have become the limitation for non-injected vaccine development. Escherichia coli heat-labile enterotoxin B subunit (LTB) was regarded as a promising mucosal adjuvant for its nontoxicity and potent activity. LTB preparation issues have always been recurring, in part owing to that the recombinant LTB expressed by E. coli does not act as its native form. We constructed an engineered Lactococcus lactis strain using a food-grade expression system. The LTB secreted by the engineered strain was detected in the culture supernatant, constituting 10.3% of the supernatant proteins, and recognized by mouse anti-LTB antibodies. The engineered strain, co-administered orally to SPF BALB/c mice with a H. pylori vaccine candidate expressing Lpp20 antigen, could significantly enhance the Lpp20-induced mucosal SIgA antibody responses against H. pylori. This is the first report that LTB was efficiently produced and delivered via using a food-grade lactococcal expression system, which offers a novel production and utilization mode of this crucial mucosal adjuvant. The engineered L. lactis strain secreting LTB has considerable potential for oral vaccine formulation owing to its outstanding safety, adjuvant activity and high-level production.


Ontogeny and regional distribution of hormone-producing cells in the embryonic pancreas of Alligator mississippiensis.
The hormones of the endocrine pancreas are believed to play an important role in early development. The development of the pancreas and the appearance of hormone-producing cells during embryogenesis have been extensively studied in mammals and birds. Relatively little work has been done in other vertebrates, and there are no published studies regarding the order Crocodilia. Given the pivotal phylogenetic position of crocodilians, Alligator mississippiensis provides an interesting species in which to study the embryonic development of the endocrine pancreas. The aims of the present study were (1) to investigate the morphological development of the pancreas and (2) to determine the initial appearance and regional distribution of the pancreatic endocrine cells in the embryonic alligator. At each stage of development serial sections of pancreatic tissue were stained with hematoxylin and eosin to aid in morphological description. Using immunocytochemistry sections were stained to detect the presence of insulin, glucagon, somatostatin, and pancreatic polypeptide. The dorsal pancreatic bud was first observed at stage 8, coincident with the appearance of insulin-containing and glucagon-containing cells. Somatostatin-containing cells were first detected at stage 10. At stage 13 the ventral pancreatic bud was first observed. At stage 14 the dorsal and ventral pancreatic buds fused and insulin, glucagon, and somatostatin were found throughout the pancreas. Not until stage 17 was pancreatic polypeptide first detected. Unlike the other hormones, pancreatic polypeptide was rare or absent in the dorsal region of the pancreas. In later stages of development, somatostatin-containing cells were the most abundant and constituted 35-40% of all hormone-containing cells. The sequence of appearance of insulin and glucagon found in the alligator is the same as that found in mammals and birds.


[Immunologic laboratory testing in clinical practice for rheumatoid arthritis].
The recent clinical practices for rheumatoid arthritis have changed greatly. First, biologic agents such as tumor necrosis factor blocker have been developed as well as disease-modifying antirheumatic drugs, with great efficacy in intractable RA. On the other hand, the importance of early effective therapeutic intervention has been recognized since early treatment prevents the progression of joint damage. However, early diagnosis of RA is not so easy because of the lack of appropriate diagnostic criteria. New laboratory tests have appeared for the diagnosis and prognostic prediction of RA. Among them, anticyclic citrullinated peptide antibodies (anti-CCP), which bind epitopes containing citrulline, seem to be attracting the most attention. Although rheumatoid factor (RF) is the only serologic marker among the seven classification criteria of the American College of Rheumatology (ACR) for RA, variability of the RF assay within laboratories and/or between laboratories, and quality assurance has not been established. We must address the standardization of RF assay as soon as possible.


Electrical Tuning of Exciton Binding Energies in Monolayer WS_{2}.
We demonstrate continuous tuning of the exciton binding energy in monolayer WS_{2} by means of an externally applied voltage in a field-effect transistor device. Using optical spectroscopy, we monitor the ground and excited excitonic states as a function of gate voltage and track the evolution of the quasiparticle band gap. The observed decrease of the exciton binding energy over the range of about 100 meV, accompanied by the renormalization of the quasiparticle band gap, is associated with screening of the Coulomb interaction by the electrically injected free charge carriers at densities up to 8×10^{12} cm^{-2}. Complete ionization of the excitons due to the electrical doping is estimated to occur at a carrier density of several 10^{13} cm^{-2}.


[Health education from the perspective of contemporary challenges and threats].
The latest socio-economical changes have had a great impact on the perception of health issues. The definition of health according to the WHO is often citied here as a kind of postulate of psychical, psychological and sociological well being. Health education takes an important part in propagating ideas of promoting and protecting health and also shaping life skills. Health education especially affects schools but it also has an impact on family and local community. Contemporary definitions of health education underline that it is also a process of learning how to take care of one's own health and that of others'. This attitude to health corresponds with the changing health problems affecting society. Despite implementing many programs and actions promoting health and preventing diseases on a world and European scale, there still exist many problems in this area. They are particularly due to disproportionate access to medical help and technological development resulting from low awareness, but most of all, from the low socioeconomic status of the people involved. The school, as a place where health education takes place, has the right and obligation to influence health behaviors of pupils and the whole of society.


Importance of temporal changes in myocardial strain in Takotsubo cardiomyopathy.
Strain imaging is a sensitive marker of myocardial dysfunction and may be underused in Takotsubo cardiomyopathy (TC). We present a case of biventricular TC in which early improvement in left ventricular longitudinal strain predated subsequent improvement in ejection fraction. Early temporal patterns of strain of the left and right ventricles have not previously been described in TC. Our case illustrates how strain can be a sensitive marker for myocardial dysfunction and recovery in TC. Increased use of strain in TC may have further implications on prognosis and management.


Herpetiform pemphigus, a variable pattern of pemphigus.
A patient with the clinical features of dermatitis herpetiformis and the histological features of pemphigus, subcorneal dermatosis and dermatitis herpetiformis did not respond to treatment with pyridine or sulfones. Systemic steroids and azothioprine were effective. Immunofluorescence studies demonstrated circulating pemphigus antibodies and IgG bound in vivo in the intercellular spaces of the epidermis.


Optical authentication method based on correspondence ghost imaging.
Ghost imaging technology has a great application potential in optical security because of its non-local characteristics. In this paper, on the basis of computational ghost imaging, an optical authentication scheme is proposed that utilizes the correspondence imaging technique for the preliminary reconstruction of the object image, and then authenticates the image by a nonlinear correlation algorithm. Different from the previous optical authentication schemes that usually adopted random selection of measurements, this authentication method consciously selects the bucket detector measurement values with large fluctuation and can achieve authentication using ultra-low data volumes less than 1% of the Nyquist limit. In brief, this scheme is easy to implement and has a simpler algorithm and higher stability, which is a tremendous advantage in practical optical authentication systems. The simulation and physical experimental results demonstrate the feasibility of the scheme.


Synthesis of 6- and 7-Membered N-Heterocycles Using α-Phenylvinylsulfonium Salts.
A concise synthesis of stereodefined C-substituted morpholines, piperazines, azepines, and oxazepines in moderate to excellent yields (27% to 75%) is reported by reaction of 1,2- or 1,3-amino alcohol/1,2- or 1,3-diamine with an α-phenylvinylsulfonium salt. High levels of regio- and diastereoselectivity (from 2:1 to >20:1) are observed through judicious choice of base (Cs2CO3) and solvent (CH2Cl2). Reactions are performed at ambient temperature and open to air and do not require anhydrous solvent. The deprotection of the N-sulfonamide protecting groups (N-Ts and N-Ns) is also demonstrated. Factors affecting regio- and diastereocontrol are discussed.


Citryl Ornithine Is an Intermediate in a Three-Step Biosynthetic Pathway for Rhizoferrin in Francisella.
The Gram-negative bacterium Francisella tularensis secretes the siderophore rhizoferrin to scavenge necessary iron from the environment. Rhizoferrin, also produced by a variety of fungi and bacteria, comprises two citrate molecules linked by amide bonds to a central putrescine (diaminobutane) moiety. Genetic analysis has determined that rhizoferrin production in F. tularensis requires two enzymes: FslA, a siderophore synthetase of the nonribosomal peptide synthetase-independent siderophore synthetase (NIS) family, and FslC, a pyridoxal-phosphate-dependent decarboxylase. To discern the steps in the biosynthetic pathway, we tested F. tularensis strain LVS and its ΔfslA and ΔfslC mutants for the ability to incorporate potential precursors into rhizoferrin. Unlike putrescine supplementation, supplementation with ornithine greatly enhanced siderophore production by LVS. Radioactivity from L-[U-14C] ornithine, but not from L-[1-14C] ornithine, was efficiently incorporated into rhizoferrin by LVS. Although neither the ΔfslA nor the ΔfslC mutant produced rhizoferrin, a putative siderophore intermediate labeled by both [U-14C] ornithine and [1-14C] ornithine was secreted by the ΔfslC mutant. Rhizoferrin was identified by liquid chromatography and mass spectrometry in LVS culture supernatants, while citryl-ornithine was detected as the siderophore intermediate in the culture supernatant of the ΔfslC mutant. Our findings support a three-step pathway for rhizoferrin production in Francisella; unlike the fungus Rhizopus delemar, where putrescine functions as a primary precursor for rhizoferrin, biosynthesis in Francisella preferentially starts with ornithine as the substrate for FslA-mediated condensation with citrate. Decarboxylation of this citryl ornithine intermediate by FslC is necessary for a second condensation reaction with citrate to produce rhizoferrin.


Renal involvement as a unique manifestation of hemophagocytic syndrome.
Renal-limited hemophagocytic syndrome (HPS) is a rare clinical setting characterized by abnormal activation of the immune system. Fever associated with pancytopenia, hepatosplenomegaly with liver dysfunction, and hypofibrinogenemia are usually observed in HPS. From a histological level, the presence of non-malignant macrophages infiltrating bone marrow and organs represents the hallmark of this condition. Non-malignant macrophages are associated with phagocytizing activities involving other blood cells. While primary HPS is usually associated with inherited dysregulation of the immune system, secondary HPS usually occurs in the context of infection or is linked to a neoplastic process. Clinical presentation varies and can potentially lead to life-threatening settings. While renal involvement has frequently been reported, however, detailed descriptions of the kidney manifestations of HPS are lacking. More critically, the diagnosis of HPS is rarely supported by renal biopsy specimens. We report four rare cases of biopsy-proven renal-limited HPS in patients presenting with acute kidney injury (AKI). The available evidence on this topic is critically discussed in light of the possible emergence of an autonomous entity characterized by an isolated kidney involvement.


The politics of birth control, 1920-1940: the impact of professionals.
Before the 1920s, a birth control movement arose in the United States out of socialist, feminist, and other radical groups concerned with women's rights and sexual freedom. After 1920 the birth control movement became gradually transformed into a respectable, nonradical reform cause, the recipient of large grants from big business, with women's rights secondary to an overriding concern with medical health and population control. This transformation was achieved through the professionalization of the birth control movement-that is, its takeover by professional experts, almost all male, in place of the radical amateur women, fighting for their own interests, who initiated it. The article examines two groups of professionals who were particularly influential in this transformation: doctors and academic eugenists. The former made birth control a medical issue, held back the development of popular sex education, and stifled a previously developing feminist approach to women's birth control needs. The later contributed racism to the birth control movement, helping to transform it into a population control movement with racist and anti-feminist overtones. Both groups, while they made contributions to the technology of contraception, simultaneously held back the spread of birth control by transforming the campaign for it from a popular, participatory cause to a professional staff lobbying operation.