Structural stability of GlcV, the nucleotide binding domain of the glucose ABC transporter of Sulfolobus solfataricus.
GlcV is the nucleotide binding domain of the ABC-type glucose transporter of the hyperthermoacidophile Sulfolobus solfataricus. GlcV consists of two domains, an N-terminal domain containing the typical nucleotide binding-fold and a C-terminal beta-barrel domain with unknown function. The unfolding and structural stability of the wild-type (wt) protein and three mutants that are blocked at different steps in the ATP hydrolytic cycle were studied. The G144A mutant is unable to dimerize, while the E166A and E166Q mutants are defective in ATP hydrolysis and dimer dissociation. Unfolding of the wt GlcV and G144A GlcV occurred with a single transition, whereas the E166A and E166Q mutants showed a second transition at a higher melting temperature indicating an increased stability of the ABCalpha/beta subdomain. The structural stability of GlcV was increased in the presence of nucleotides suggesting that the transition corresponds to the unfolding of the NBD domain. Unfolding of the C-terminal domain appears to occur at temperatures above the unfolding of the NBD which coincides with the aggregation of the protein. Analysis of the domain organization of GlcV by trypsin digestion demonstrates cleavage of the NBD domain into three fragments, while nucleotides protect against proteolysis. The cleaved GlcV protein retained the ability to bind nucleotides and to dimerize. These data indicate that the wt GlcV NBD domain unfolds as a single domain protein, and that its stability is modified by mutations in the glutamate after the Walker B motif and by nucleotide binding.


Long-term Observation of Thyroid Volume Changes in Hashimoto's Thyroiditis in a Series of Women on or off Levo-Thyroxine Treatment in an Area of Moderate Iodine Sufficiency.
Large variations in thyroid volume (TV) have been reported in Hashimoto's thyroiditis (HT). The need for long-term levo-thyroxine (L-T4) administration in order to control TV, as well as to normalise thyroid function, has not been well defined. Retrospective data on TV in 94 adult women with HT were analysed in an ambulatory setting in Liguria, an area of moderate iodine sufficiency. TV was evaluated by means of ultrasonography (US). Thyroid function, anthropometric data, smoking habits and pharmaceutical drugs were registered at each examination. At the baseline, an atrophic gland was noted in 16% of the women, and goitre in 13%. The women were evaluated 56 and 102 months after the baseline examination. At the time of each examination, 50%, 78% and 83% of women, respectively, were on L-T4 treatment. Baseline TV was not significantly different in women on/off L-T4 treatment. However, in those on L-T4, TV decreased significantly over the period of follow-up, while in those without L-T4 treatment, it did not change. By the end of the study, the percentage of L-T4-treated women with an atrophic gland had increased to 27%, and that of women with goitre had dropped to 6%; in untreated women, only minor changes were noted. There was a significant negative correlation between TV% change and baseline TSH levels in HT women on L-T4 treatment. The majority of HT women living in an area of moderate iodine sufficiency have normal TV. Moreover, long-term L-T4 treatment can be used to control TV, as well as to maintain normal thyroid parameters.


Visual sensations induced by relativistic nitrogen nuclei.
The ability of the human eye to detect nitrogen nuclei that enter the retina at speeds just above the Cerenkov threshold has been confirmed in an experiment at the Princeton Particle Accelerator. A system for beam transport and subject alignment delivered individual nitrogen nuclei onto a spot 3 millimeters in diameter on the retina at a visual angle of 7 degrees on the temporal side of the fovea. The beam particles entered the retina within 25 degrees of normal and induced visual sensations that had the appearance of streaks for three out of four subjects.


Characterization of prepared corn starch-based hydrogel membranes.
The design and development of novel hydrogel membranes prepared by crosslinking polyvinyl alcohol with heat-treated cornstarch (CS) and CS suspensions was attempted. Degradation studies of the hydrogel membranes were conducted using á -amylase. The mechanical property of the hydrogel membranes was characterized by tensile tests. The swelling behavior of the membranes was also evaluated. Methyl tetrazolium assay of the membranes was performed using mice splenocytes and the L929 cell line to establish cytocompatibility. The membranes had sufficient strength and water holding capacity. The membrane was found to be biocompatible with L929 fibroblast cells and mice splenocytes.


Effects of intrauterine infection or inflammation on fetal lung development.
1. Intrauterine infection or inflammation is common in cases of preterm birth. Preterm infants are at risk of acute respiratory distress as a result of lung immaturity; evidence of exposure to infection and/or inflammation before birth is associated with a reduced risk of neonatal respiratory distress syndrome (RDS). Experimentally induced intrauterine inflammation or infection in sheep causes a precocious increase in pulmonary surfactant in the preterm lungs that improves preterm lung function, consistent with the reduced risk of RDS in human infants exposed to infection and/or inflammation before birth. 2. The effects of intrauterine inflammation on fetal lung development appear to result from direct action of proinflammatory stimuli within the lungs rather than by systemic signals, such as the classical glucocorticoid-mediated lung maturation pathway. However, paracrine and/or autocrine production and/or metabolism of glucocorticoids in fetal lung tissue may occur as a result of inflammation-induced changes in the expression of 11β-hydroxysteroid dehydrogenase (types 1 and 2). 3. Likely candidates that mediate inflammation-induced surfactant production by the preterm lung include prostaglandin E₂ and/or other arachidonic acid metabolites. Intrauterine inflammation induces the expression of enzymes responsible for prostaglandin production in fetal lung tissue. Inhibition of prostaglandin production prevents, at least in part, the effects of inflammation on fetal lungs. 4. Our experiments are identifying mechanisms of surfactant production by the preterm lungs that may be exploited as novel therapies for preventing respiratory distress in preterm infants. Elucidation of the effects of inflammation on the fetal lungs and other organs will allow more refined approaches to the care of preterm infants exposed to inflammation in utero.


Aberrant expression of NF-κB in liver fluke associated cholangiocarcinoma: implications for targeted therapy.
Up-regulation and association of nuclear factor kappa B (NF-κB) with carcinogenesis and tumor progression has been reported in several malignancies. In the current study, expression of NF-κB in cholangiocarcinoma (CCA) patient tissues and its clinical significance were determined. The possibility of using NF-κB as the therapeutic target of CCA was demonstrated. Expression of NF-κB in CCA patient tissues was determined using immunohistochemistry. Dehydroxymethylepoxyquinomicin (DHMEQ), a specific NF-κB inhibitor, was used to inhibit NF-κB action. Cell growth was determined using an MTT assay, and cell apoptosis was shown by DNA fragmentation, flow cytometry and immunocytofluorescent staining. Effects of DHMEQ on growth and apoptosis were demonstrated in CCA cell lines and CCA-inoculated mice. DHMEQ-induced apoptosis in patient tissues using a histoculture drug response assay was quantified by TUNEL assay. Normal bile duct epithelia rarely expressed NF-κB (subunits p50, p52 and p65), whereas all CCA patient tissues (n = 48) over-expressed all NF-κB subunits. Inhibiting NF-κB action by DHMEQ significantly inhibited growth of human CCA cell lines in a dose- and time-dependent manner. DHMEQ increased cell apoptosis by decreasing the anti-apoptotic protein expressions-Bcl-2, XIAP-and activating caspase pathway. DHMEQ effectively reduced tumor size in CCA-inoculated mice and induced cell apoptosis in primary histocultures of CCA patient tissues. NF-κB was over-expressed in CCA tissues. Inhibition of NF-κB action significantly reduced cell growth and enhanced cell apoptosis. This study highlights NF-κB as a molecular target for CCA therapy.


Characterization of a Novel Rice Dynamic Narrow-Rolled Leaf Mutant with Deficiencies in Aromatic Amino Acids.
The leaf blade is the main photosynthetic organ and its morphology is related to light energy capture and conversion efficiency. We isolated a novel rice Dynamic Narrow-Rolled Leaf 1 (dnrl1) mutant showing reduced width of leaf blades, rolled leaves and lower chlorophyll content. The narrow-rolled leaf phenotype resulted from the reduced number of small longitudinal veins per leaf, smaller size and irregular arrangement of bulliform cells compared with the wild-type. DNRL1 was mapped to chromosome 7 and encoded a putative 3-deoxy-7-phosphoheptulonate synthase (DAHPS) which catalyzes the conversion of phosphoenolpyruvate and D-erythrose 4-phosphate to DAHP and phosphate. Sequence analysis revealed that a single base substitution (T-A) was detected in dnrl1, leading to a single amino acid change (L376H) in the coding protein. The mutation led to a lower expression level of DNRL1 as well as the lower activity of DAHPS in the mutant compared with the wild type. Genetic complementation and over-expression of DNRL1 could rescue the narrow-rolled phenotype. DNRL1 was constitutively expressed in all tested organs and exhibited different expression patterns from other narrow-rolled leaf genes. DNRL1-GFP located to chloroplasts. The lower level of chlorophyll in dnrl1 was associated with the downregulation of the genes responsible for chlorophyll biosynthesis and photosynthesis. Furthermore, dnrl1 showed significantly reduced levels of aromatic amino acids including Trp, Phe and Tyr. We conclude that OsDAHPS, encoded by DNRL1, plays a critical role in leaf morphogenesis by mediating the biosynthesis of amino acids in rice.


Reducing ammonia volatilization from paddy field with rice straw derived biochar.
Ammonia (NH3) volatilization is a major loss of nitrogen fertilizer in paddy fields. The incorporation of straw or biochar has been considered to be the alternative options for soil improvement and agriculture sustainability. A field experiment was conducted to evaluate the potential role of rice straw and rice straw derived biochar in controlling NH3 volatilization according to the conventional nitrogen fertilizer level (urea, 270 kg N ha-1) during one rice (Oryza sativa L., cv. Xiushui134) growing season. Four treatments comprised rice straw at the rate of 8 t ha-1 (RS); rice straw derived biochar at the rate of 2.8 t ha-1 (RSBL); rice straw derived biochar at the rate of 22.5 t ha-1 (RSBH) and a control (CK). Compared to straw application, biochar incorporation reduced the cumulative NH3 volatilization (about 20%) from paddy fields significantly (p < 0.05), promoted rice yields and plant N aboveground as well as increased the abundance of ammonia oxidation amoA genes. In contrast with the control, the ratios of NH3-N to total N input for RS, RSBL and RSBH declined significantly 4.15%, 4.40% and 11.12%, respectively (p < 0.05). Reduced NH3 volatilization in RSB treatments were mainly attributed to the decrease of NH4+-N concentration in the surface water, which could resulted from the enhancement of rice growth and the promotion of ammonia oxidation in soil. The increase of soil pH and soil CEC with biochar amendment played important roles in nitrogen retention and nitrogen cycle in soil. These results indicated that the incorporation of rice straw derived biochar instead of rice straw could be a promising approach to controlling NH3 volatilization and improving rice yield.


Back to the future: implications of genetic complexity for the structure of hybrid breeding programs.
Commercial hybrid breeding operations can be described as decentralized networks of smaller, more or less isolated breeding programs. There is further a tendency for the disproportionate use of successful inbred lines for generating the next generation of recombinants, which has led to a series of significant bottlenecks, particularly in the history of the North American and European maize germplasm. Both the decentralization and the disproportionate contribution of inbred lines reduce effective population size and constrain the accessible genetic space. Under these conditions, long-term response to selection is not expected to be optimal under the classical infinitesimal model of quantitative genetics. In this study, we therefore aim to propose a rationale for the success of large breeding operations in the context of genetic complexity arising from the structure and properties of interactive genetic networks. For this, we use simulations based on the NK model of genetic architecture. We indeed found that constraining genetic space through program decentralization and disproportionate contribution of parental inbred lines, is required to expose additive genetic variation and thus facilitate heritable genetic gains under high levels of genetic complexity. These results introduce new insights into why the historically grown structure of hybrid breeding programs was successful in improving the yield potential of hybrid crops over the last century. We also hope that a renewed appreciation for "why things worked" in the past can guide the adoption of novel technologies and the design of future breeding strategies for navigating biological complexity.


Effects of self-transcendence on neural responses to persuasive messages and health behavior change.
Self-transcendence refers to a shift in mindset from focusing on self-interests to the well-being of others. We offer an integrative neural model of self-transcendence in the context of persuasive messaging by examining the mechanisms of self-transcendence in promoting receptivity to health messages and behavior change. Specifically, we posited that focusing on values and activities that transcend the self can allow people to see that their self-worth is not tied to a specific behavior in question, and in turn become more receptive to subsequent, otherwise threatening health information. To test whether inducing self-transcendent mindsets before message delivery would help overcome defensiveness and increase receptivity, we used two priming tasks, affirmation and compassion, to elicit a transcendent mindset among 220 sedentary adults. As preregistered, those who completed a self-transcendence task before health message exposure, compared with controls, showed greater increases in objectively logged levels of physical activity throughout the following month. In the brain, self-transcendence tasks up-regulated activity in a region of the ventromedial prefrontal cortex, chosen for its role in positive valuation and reward processing. During subsequent health message exposure, self-transcendence priming was associated with increased activity in subregions of the ventromedial prefrontal cortex, implicated in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The present findings suggest that having a positive self-transcendent mindset can increase behavior change, in part by increasing neural receptivity to health messaging.


Ascending urethrography using the Leech-Wilkinson intra-uterine cannula in adult male patients.
The Leech-Wilkinson Intra-Uterine Cannula used in hysterosalpingography has proved useful in ascending urethrography in the adult male patients. Lesions of the urethra, e.g., strictures, calculi, sinuses, diverticula and urethral tear are best demonstrated by ascending urethrography. This method does not replace voiding cysto-urethrography under physiological conditions.


[Basal cell carcinoma of the penis].
To report an uncommon case of basal cell carcinoma of the penis. A case of basal cell carcinoma of the penis is presented. This has been the only case of this tumor type detected in our setting. The literature is briefly reviewed. Basal cell carcinoma of the penis is rare. To date only 20 cases have been reported in the literature. To our knowledge, no case of distant metastasis has been documented. Diagnosis by gross examination may be difficult due to the broad polymorphism of this lesion and must be confirmed by histological analysis.


Two autolytic processing reactions of a satellite RNA proceed with inversion of configuration.
Both polarities of the satellite RNA of tobacco ringspot virus occur in infected cells in multimeric forms which are capable of autolytic processing, using different sequences and structures [Feldstein, P.A., et al., Proc. Nat. Acad. Sci. USA (1990) 87 (in press)]. These transesterification reactions generate a 2',3'-cyclophosphate and a 5'-hydroxyl as the two new end groups. Cleavage is at a CpA for the (+) polarity RNA and at an ApG for the (-) polarity RNA. We enzymically synthesized oligoribonucleotides with processing capability and with specific 35S-labeled phosphorothioate diesters in the Rp configuration. After processing had occurred, the terminal nucleoside-2',3'-cyclophosphorothioate diester residues were recovered from the appropriate product by digestion with nuclease and phosphatase. Comparisons with specially prepared endo- and exoisomer reference compounds by thin layer chromatography and autoradiography revealed that the [35S]cytidine- and [35S]adenosine-2',3'-cyclophosphorothioate both were endo-isomers. The results are consistent with transesterification occurring by an inline SN2(P) attack of the 2'-hydroxyl group in the autolytic processing reactions of both polarities of the satellite RNA.


Innovations in natural ingredients and their use in skin care.
Natural ingredients have been used traditionally for millennia and their application in topical creams, lotions and preparations within the traditional medicines and healing traditions of many cultures has been observed. Over the last 20 years, clinical and laboratory studies have identified the benefits of an array of natural ingredients for skin care. Consequently, a number of these ingredients and compounds are today being developed, used or considered not only for anti-aging effects, but also for use in dermatologic disorders. Certain ingredients, such as colloidal oatmeal and aloe vera, have been identified as beneficial in the treatment of psoriasis and atopic dermatitis, respectively, due to their anti-inflammatory properties. For combating acne and rosacea, green tea, niacinamide and feverfew are considered efficacious. As to hyperpigmentation and antioxidative capabilities, licorice, green tea, arbutin, soy, acai berry, turmeric and pomegranate are among those plants and compounds found to be most beneficial. Additional research is needed to determine to confirm and elucidate the benefits of these ingredients in the prevention and management of skin disease.


Early life factors and being overweight at 4 years of age among children in Malmö, Sweden.
Rising rates of obesity and overweight is an increasing public health problem all over the world. Recent research has shown the importance of early life factors in the development of child overweight. However, to the best of our knowledge there are no studies investigating the potential synergistic effect of early life factors and presence of parental overweight on the development of child overweight. The study was population-based and cross-sectional. The study population consisted of children who visited the Child Health Care (CHC) centers in Malmö for their 4-year health check during 2003-2008 and whose parents answered a self-administered questionnaire (n = 9009 children). The results showed that having overweight/obese parents was strongly associated with the child being overweight or obese. Furthermore, there was an association between unfavorable early life factors (i.e., mother smoking during pregnancy, presence of secondhand tobacco smoke early in life, high birth weight) and the development of child overweight/obesity at four years of age, while breastfeeding seemed to have a protective role. For example, maternal smoking during pregnancy was associated with an odds ratio (OR) of 1.47 (95% CI: 1.22, 1.76) for overweight and 2.31 (95% CI: 1.68, 3.17) for obesity. The results further showed synergistic effects between parental overweight and exposure to unfavourable early life factors in the development of child overweight. The present study shows the importance of early life factors in the development of child overweight and obesity, and thus puts focus on the importance of early targeted interventions.


Renal Angiomyolipoma: Radiologic Classification and Imaging Features According to the Amount of Fat.
The purposes of this article are to introduce the radiologic classifications of renal angiomyolipoma (AML) and the clinical implications, to show the imaging features of each type of AML, and to describe which types of AML should be biopsied. Renal AML can be classified according to amount of fat as fat rich, fat poor, or fat invisible. To detect fat, one needs to thoroughly evaluate the entire AML by controlling the size and shape of the ROI. Fat-invisible AML should be biopsied, and fat-poor AML requires further investigation to determine whether biopsy is necessary to differentiate it from renal cell carcinoma. If differentiation between AML and renal cell carcinoma is not clear with CT and MRI, percutaneous biopsy may be performed.


Functional assessment of restrictive eating: A three-study clinically heterogeneous and transdiagnostic investigation.
Restrictive eating is common and associated with negative psychological outcomes across the life span and eating disorder (ED) severity levels. Little is known about functional processes that maintain restriction, especially outside of narrow diagnostic categories (e.g., anorexia nervosa). Here, we extend research on operant four-function models (identifying automatic negative, automatic positive, social negative, and social positive reinforcement functions) that have previously been applied to nonsuicidal self-injury (NSSI), binge eating, and purging to restricting. We assessed restrictive eating functions in three samples: clinically heterogeneous adolescents (Study 1: N = 457), transdiagnostic adults (Study 2: N = 145), and adults with acute or recently weight-restored anorexia nervosa (Study 3: N = 45). Study 1 indicated the four-function model was a good fit for restricting (root mean square error of approximation [RMSEA] = .06, Tucker-Lewis index [TLI] = .88). This factor structure replicated in Study 2 (comparative fit index [CFI] = .97, RMSEA = .07, TLI = .97, standardized root mean square residual [SRMR] = .09). Unlike NSSI, binge eating, and purging, which have been found to primarily serve automatic negative reinforcement functions, all three present studies found automatic positive reinforcement was most highly endorsed (by up to 85% of participants). In Studies 1 and 3, automatic functions were associated with poorer emotion regulation (ps < .05). In Study 1, social functions were associated with less social support (ps < .001). Across studies, automatic functions were associated with greater restriction ps < .05). Functions varied slightly by ED diagnosis. Across ED presentation, severity, and developmental stage, restrictive eating may be largely maintained by automatic positive reinforcement, with some variability across presentations. Continued examination of restrictive eating functions will establish processes that maintain restriction, allowing more precise treatment targeting for these problematic behaviors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Liquid chromatographic determination of thiamine in infant formula products by using ultraviolet detection.
A liquid chromatographic (LC) method has been developed for determination of thiamine in infant formula products. The method involves the following steps: (a) dissolution of the formula with water, (b) pH adjustment to induce protein precipitation, (c) filtration, (d) concentration of thiamine by using a cation exchange column and extraction system, (e) cleanup of adsorbed thiamine and other contaminants on the ion exchange column by washing with water and then methanol, (f) elution of thiamine with a mixture of methanol-2M potassium chloride buffer, (g) analysis for thiamine by liquid chromatography. Thiamine is separated from its phosphate esters, the mono-, di-, and triphosphates, as well as its antagonists oxythiamine and pyrithiamine on a 6 micron particle size column and a mobile phase of 40mM triethyl-ammonium phosphate buffer-methanol (pH 7.7) (90 + 10). The method is reproducible, with relative standard deviations ranging from +/- 0.76 to +/- 1.2%, depending on the infant formula product tested. Recovery of thiamine from various infant formula products is greater than 99%. Analysis for thiamine of several commercially available infant formulas at different levels of fortification gave results that ranged from 122 to 216% of the declared levels. These results agree well with those obtained using the AOAC fluorometric method.


Atypical Intraparenchymal Meningioma with YAP1-MAML2 Fusion in a Young Adult Male: A Case Report and Mini Literature Review.
Oncogenic Yes-associated protein (YAP) 1 fusions have been recently identified in several cases of meningioma mostly involving pediatric patients. The meningiomas harboring YAP1-MAML2, which is the most frequent fusion subtype, exhibit activated YAP1 signaling and share similarities with NF2 (neurofibromatosis type 2 gene) mutant meningiomas. We reported a rare case of atypical intraparenchymal meningioma with YAP1-MAML2 fusion in a 20-year-old male. The patient presented with an episode of seizure without a medical history. MRI revealed a lesion in the right temporal lobe without extra-axial involvement. The radiological and morphological findings, however, were indistinctive from other intracranial diseases, e.g., vascular malformation and glioma. Immunohistochemical results confirmed the presence of abundant meningothelial cells in the tumor and indicated brain invasion, supporting the diagnosis of atypical intraparenchymal meningioma. Targeted RNA fusion analysis further identified a YAP1-MAML2 rearrangement in the tumor. Non-dural-based intraparenchymal meningiomas are uncommon, and the careful selection of specific tumor markers is crucial for an accurate diagnosis. Additionally, the detection of the fusion gene provides valuable insights into the oncogenic mechanism of meningioma.


Environmental variables associated with an increased risk of invasive aspergillosis.
Information on the environmental variables that may affect the incidence of invasive aspergillosis (IA) is scarce. We sought to determine the relationship between airborne spore counts, climatic conditions and IA. We also examined whether circulating respiratory viruses predispose patients to IA in a multicentre cohort study of hospitalized adults with IA. Data on environmental mould spores, climatic conditions and circulating respiratory viruses were obtained from the Environmental Department of the Autonomous University of Barcelona, the Meteorological Service of Catalonia and the Acute Respiratory Infection Surveillance Project in Catalonia, respectively. Between 2008 and 2011, 165 patients with IA were identified. Diagnosis was based on one or more of the following: culture (125 cases), galactomannan antigen (98) and histology (34). One hundred and twenty-seven cases (77%) had criteria for probable IA and the remainder for proven IA. Environmental mould spore counts from the period 28-42 days preceding infection presented significant associations with admissions due to IA. None of the climatic conditions were associated with an increased risk of IA, but the presence of circulating respiratory viruses was associated with a higher risk of infection: the most strongly associated viruses were respiratory syncytial virus, influenza A(H1N1)pdm09 and adenovirus. In conclusion, the presence of high numbers of spores in the air increases the risk of admission due to IA. Circulating respiratory viruses appear to be associated with a higher risk of developing IA. Physicians should be aware of this association in order to optimize prevention and diagnosis strategies for IA during viral epidemic periods.


The milk thistle (Silybum marianum) compound Silibinin stimulates leukopoiesis from mouse embryonic stem cells.
The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and leukopoiesis are interrelated, the effect of Silibinin on leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO). Western blot experiments showed that upon coincubation with either the PI3K inhibitor LY294002, the STAT3 inhibitor Stattic, the AKT antagonist AKT inhibitor VIII, or the NO inhibitor L-NAME, the Silibinin-induced expression of CD18, CD45, and CD68 was abolished. Moreover, the stimulation of HIF-1α and VEGFR2 expression was blunted upon STAT3 and PI3K/AKT inhibition. Treatment of differentiating ES cells with L-NAME abolished the stimulation of VEGFR2 and VE-cadherin expression achieved with Silibinin, indicating that NO is involved in vasculogenesis and leukocyte differentiation pathways. In summary, the data of the present study demonstrate that Silibinin stimulates leukocyte differentiation of ES cells, which is associated to vasculogenesis and regulated by PI3K/AKT-, STAT3-, and NO-mediated signaling.


Biological role of fructose in the male reproductive system: Potential implications for prostate cancer.
Over the last 20 years, fructose has gradually emerged as a potential metabolic substrate capable of promoting the growth and progression of various cancers, including prostate cancer (PCa). The biological and molecular mechanisms that underlie the effects of fructose on cancer are beginning to be elucidated. This review summarizes the biological function of fructose as a potential carbon source for PCa cells and its role in the functionality of the male reproductive tract under normal conditions. The most recent biological advances related to fructose transport and metabolism as well as their implications in PCa growth and progression suggest that fructose represent a potential carbon source for PCa cells. Consequently, fructose derivatives may represent efficient radiotracers for obtaining PCa images via positron emission tomography and fructose transporters/fructose-metabolizing enzymes could be utilized as potential diagnostic and/or predictive biomarkers for PCa. The existing data suggest that restriction of fructose from the diet could be a useful therapeutic strategy for patients with PCa.


Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration.
Retina and retinal pigment epithelium (RPE) belong to the metabolically most active tissues in the human body. Efficient removal of acid load from retina and RPE is a critical function mediated by the choriocapillaris. However, the mechanism by which pH homeostasis is maintained is largely unknown. Here, we show that a functional complex of carbonic anhydrase 4 (CA4) and Na+/bicarbonate co-transporter 1 (NBC1) is specifically expressed in the choriocapillaris and that missense mutations in CA4 linked to autosomal dominant rod-cone dystrophy disrupt NBC1-mediated HCO3- transport. Our results identify a novel pathogenic pathway in which a defect in a functional complex involved in maintaining pH balances, but not expressed in retina or RPE, leads to photoreceptor degeneration. The importance of a functional CA4 for survival of photoreceptors implies that CA inhibitors, which are widely used as medications, particularly in the treatment of glaucoma, may have long-term adverse effects on vision.


[Polymorphism of the GSMT1 gene in lung cancer resistance and susceptibility].
The published studies of onco-associated genetic polymorphisms are characterized by insufficient interlaboratory reproducibility. The inconsistency of the results can be partially attributed to some characteristics of patients and control groups, which are used for the comparison of allele frequencies. For instance, many investigations involve so-called "healthy donors" as a standard. However, the efficiency of such a comparison can be questioned; indeed, as an individual life-time risk of malignancy reaches as high as 40-50%, a significant part of "healthy donors" would soon or later become the oncological patients. Here we tested the advantage of using "true" oncologically tolerant individuals as an additional control, e.g. tumor-free people, who succeeded to achieve an elderly age without signs of any neoplastic disease. GSTM1 gene polymorphism was used as a "positive control" for this novel design of molecular epidemiological study, as the GSTM1-null genotype displays slight but reproducible association with lung cancer risk. In the present investigation, GSTM1-deficiency was detected in 45% elderly tumor-free individuals, 55% healthy middle-aged donors, and 59% lung cancer patients. The minimal frequency (43%) of GSTM1(-) genotype was detected in elderly tumor-free smokers, and the maximal one (100%) was found in never-smoking lung cancer patients. Thus, the comparison of lung cancer patients to the "true" oncologically tolerant cohort (elderly tumor-free individuals, especially smokers) revealed more demonstrative deviations for the unfavorable genotype, than the traditional comparative analysis between oncological patients and healthy donors.


The influence of the rapamycin-derivate SDZ RAD on the healing of airway anastomoses.
Among the many immunosuppressive effects of SDZ RAD (40-0(2-hydroxyethyl)-rapamycin), a rapamycin derivative, is the inhibition of fibroblast proliferation. Since the long-term success of lung transplantation is limited by the development of bronchiolitis obliterans, a fibroblast-associated progressive luminal obstruction of the terminal bronchioli, the use of SDZ RAD as immunosuppressive in pulmonary graft recipients may counteract this process. However, reduction of fibroblast activity, posttransplant, may impair the healing of the bronchial anastomoses. The cervical trachea in pigs was denuded, divided and re-anastomosed with Prolene 4-0 single stitches. Control animals (group 1, n=4) were without, and study animals (group 2, n=6) were with SDZ RAD therapy (1.25 mg/kg/day, p.o., 14 days). After 14 days, the pigs were sacrificed. The anastomoses were examined histologically, and breaking strength of tracheal strips of 5-mm width was measured. All animals survived without complications. Serum levels of SDZ RAD were 30.9+/-8.7 ng/ml (recommended level 20-40 ng/ml). All anastomoses healed macroscopically without difference between the two groups. Breaking strength was significantly lower in the treated animals (group 1 vs. group 2: 11.75+/-0.35 vs. 7.69+/-1.39 N, P=0.01). Histology did not show a significant change in histoarchitecture between the groups. Although SDZ RAD significantly reduced the breaking strength of the tracheal anastomosis, no obvious histological differences between treated and untreated animals could be detected. Since this model does not reflect the clinical situation, further investigations are necessary to reveal the effect of SDZ RAD on airway wound healing in concert with a contemporary clinically used multidrug immunosuppressive regimen in allograft recipients.


Educational Paths and Substance Use from Adolescence into Early Adulthood.
This study examined how substance use trajectories from ages 15 to 23 in a community sample (N=921) were related to educational pathways. Rates of heavy drinking converged across different paths, but starting college at a 2-year college before transferring to a 4-year college was related to later increase in drinking after high school. Higher future educational attainment was negatively associated with high school marijuana use, but marijuana use increased after high school for individuals who went to 4-year colleges compared to those who did not. Noncollege youth had the highest rates of daily cigarette smoking throughout adolescence and early adulthood, while college dropouts had higher rates of smoking than college students who did not drop out. The findings support the need for universal prevention for early adult heavy drinking, addressing increases in drinking and marijuana use in 4-year colleges, and targeting marijuana use and cigarette smoking interventions at noncollege youth and college dropouts.


A comparison of the EQ-5D-3L and ICECAP-O in an older post-acute patient population relative to the general population.
The measurement and valuation of quality of life forms a major component of economic evaluation in health care and is a major issue in health services research. However, differing approaches exist in the measurement and valuation of quality of life from a health economics perspective. While some instruments such as the EQ-5D-3L focus on health-related quality of life alone, others assess quality of life in broader terms, for example, the newly developed ICECAP-O. The aim of this study was to utilize two generic preference-based instruments, the EQ-5D-3L and the ICECAP-O, to measure and value the quality of life of older adult patients receiving post-acute care. An additional objective was to compare the values obtained by each instrument with those generated from two community-based general population samples. Data were collected from a clinical patient population of older adults receiving post-acute outpatient rehabilitation or residential transition care and two Australian general population samples of individuals residing in the general community. The individual responses to the ICECAP-O and EQ-5D-3L instruments were scored using recently developed Australian general population algorithms. Empirical comparisons were made of the resulting patient and general population sample values for the total population and dis-aggregated according to age (65-79 and 80+ years) and gender. A total of 1,260 participants aged 65-99 years (n = 86 clinical patient sample, n = 385 EQ-5D-3L general population sample, n = 789 ICECAP-O general population sample) completed one or both of the EQ-5D-3L and ICECAP-O instruments. As expected, the patient group demonstrated lower quality of life than the general population sample as measured by both quality-of-life instruments. The difference in values between the patient and general population groups was found to be far more pronounced for the EQ-5D-3L than for the ICECAP-O. The ICECAP-O was associated with a mean difference in values of 0.04 (patient group mean 0.753, SD 0.18; general population group mean 0.795, SD 0.17, respectively, p = 0.033). In contrast, the EQ-5D-3L was associated with a mean difference in values of 0.19 (patient group mean 0.595, SD 0.20; general population group mean 0.789, SD 0.02, respectively, p ≤ 0.001). The study findings illustrate the magnitude of the difference in patient and general population values according to the instrument utilized, and highlight the differences in both the theoretical underpinnings and valuation algorithms for the EQ-5D-3L and ICECAP-O instruments. Further empirical work is required in larger samples and alternative patient groups to investigate the generalizability of the findings presented here.


DNA interstrand crosslinking and sequence selectivity of dimethanesulphonates.
Members of the homologous series of alkanediol dimethanesulphonates of general formula H3C.SO2O.(CH2)n.O.SO2.CH3 have been tested for their ability to produce DNA interstrand crosslinking and DNA sequence selectivity of guanine-N7 alkylation. In a sensitive crosslinking gel assay the efficiency of DNA interstrand crosslink formation, dependent on the ability of the alkylating moiety to span critical nucleophilic distances within the DNA, was found at 6 h to be 1,6-hexanediol dimethanesulphonate (Hexa-DMS) (n = 6) greater than methylene dimethanesulphonate (MDMS) (n = 1) greater than 1,8-octanediol dimethanesulphonate (Octa-DMS) (n = 8) greater than Busulphan (n = 4). The DNA interstrand crosslinking produced by MDMS was not due to either of its hydrolysis products, formaldehyde or methanesulphonic acid (MSA). In contrast the extent of monoalkylation at guanine-N7 as determined by a modified DNA sequencing technique was found to be Busulphan much greater than Hexa-DMS = Octa-DMS, with a sequence selectivity somewhat less than that of other chemotherapeutic alkylating agents such as nitrogen mustards. MDMS at high levels induced a non-specific depurination as a result of the reduction in pH resulting from MSA release. More strikingly MDMS (and MSA) produced a single strong site of guanine reaction (depurination) in a guanine-rich 276 base pair fragment of pBR322 DNA in the sequence of 5'-ATGGTGG-3'. This was observed when non-specific depurination was negligible and was not seen with formic acid. Thus structurally similar alkylating agents can differ in their type and extent of DNA monoalkylation and interstrand crosslinking, and in some cases (e.g. MDMS/MSA) produce reactions with a high degree of selectivity.


Activation of the liver X receptor inhibits Th17 and Th1 responses in Behcet's disease and Vogt-Koyanagi-Harada disease.
Behcet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome are two intraocular inflammatory diseases that are caused by an aberrant T lymphocyte response. Th17 cells, mainly producing the cytokine IL-17, and Th1 cells, characterized by the production of the index cytokine IFN-γ, are the CD4(+) T lymphocyte subsets implicated in the pathogenesis of both BD and VKH. Suppressing the excessive response of these Th17 and Th1 cells has been reported to be an effective therapeutic approach to treat these patients and continuous efforts are being undertaken to find new methods to modulate the function of these cells. Evidence is emerging that the Liver X receptor (LXR) is an important regulator of inflammatory and immune responses and the study reported here was designed to investigate the role of LXR activation in BD and VKH. Here we demonstrate that the frequency of Th17 and Th1 cells along with the relevant cytokines IL-17, IFN-γ and corresponding transcriptional factors RORC, T-bet were all decreased following LXR activation by the agonist GW3965. LXR controlled the expression of inflammatory cytokines through an effect on NF-kappa B (NFκb) phosphorylation. Data from our study provide evidence for an association between a decreased LXR expression and disease activity in both BD and VKH, due to the fact that a lower LXR activation may result in an enhanced Th1 and Th17 immune response. Our study suggests that enhancing LXR activation may offer a potential therapeutic approach targeting aberrant immune responses by inhibiting Th1 and Th17 cell responses.


Ror2 receptor mediates Wnt11 ligand signaling and affects convergence and extension movements in zebrafish.
The receptor-tyrosine kinase Ror2 acts as an alternative receptor or co-receptor for Wnt5a and mediates Wnt5a-induced convergent extension movements during embryogenesis in mice and Xenopus as well as the polarity and migration of several cell types during development. However, little is known about whether Ror2 function is conserved in other vertebrates or is involved in other non-canonical Wnt ligands in vivo. In this study we demonstrated that overexpression of dominant-negative ror2 (ror2-TM) mRNA in zebrafish embryos resulted in convergence and extension defects and incompletely separated eyes, which is consistent with observations from slb/wnt11 mutants or wnt11 knockdown morphants. Moreover, the co-injection of ror2-TM mRNA and a wnt11 morpholino or the coexpression of ror2 and wnt11 in zebrafish embryos synergetically induced more severe convergence and extension defects. Transplantation studies further demonstrated that the Ror2 receptor responded to the Wnt11 ligand and regulated cell migration and cell morphology during gastrulation. DnRor2 inhibited the action of Wnt11, which was revealed by a decreased percentage of Wnt11-induced convergence and extension defects. Ror2 physically interacts with Wnt11. Theintracellular Tyr-647andSer-863 sites ofRor2are essential for mediating the action of Wnt11. Dishevelled and RhoA act downstream of Wnt11-Ror2 to regulate convergence and extension movements. Overall, our data suggest an important role of Ror2 in mediating Wnt11 signaling and in regulating convergence and extension movements in zebrafish.


Toxicity and efficacy of intrathecal liposomal cytarabine in children with leukemia/lymphoma relapsing in the central nervous system: a retrospective multicenter study.
The toxicity and efficacy of intrathecal liposomal cytarabine (LC) were evaluated in children with central nervous system (CNS) relapsed/refractory acute leukemia/lymphoma. Thirty patients (male:female ratio 21:9; median age 9.4 years) with CNS relapsed/resistant disease were treated with intrathecal LC at dosages adjusted for age. Twenty-seven (90%) patients simultaneously received systemic chemotherapy, including concurrent high-dose cytarabine or methotrexate in 21 (70%) cases. Of 28 patients evaluable for response, 25 patients (89%) achieved CNS complete remission and three (11%) partial remission. The median number of intrathecal LC administrations per patient was 4. The cerebrospinal fluid was cleared after a median of 3 intrathecal LC administrations. Neurological toxicity ≥ grade 3 occurred in four (13%) patients. No permanent sequelae were observed. The median overall survival was 20.9 months and the 5-year probability of survival was 46%. These encouraging data suggest that intrathecal LC is well tolerated and effective in children with relapsed/refractory CNS leukemia/lymphoma.


Modeling Infection and Tropism of Human Parainfluenza Virus Type 3 in Ferrets.
Human parainfluenza virus type 3 (HPIV-3) is a significant cause of lower respiratory tract infections, with the most severe disease in young infants, immunocompromised individuals, and the elderly. HPIV-3 infections are currently untreatable with licensed therapeutics, and prophylactic and therapeutic options are needed for patients at risk. To complement existing human airway models of HPIV-3 infection and develop an animal model to assess novel intervention strategies, we evaluated infection and transmission of HPIV-3 in ferrets. A well-characterized human clinical isolate (CI) of HPIV-3 engineered to express enhanced green fluorescent protein (rHPIV-3 CI-1-EGFP) was passaged on primary human airway epithelial cells (HAE) or airway organoids (AO) to avoid tissue culture adaptations. rHPIV3 CI-1-EGFP infection was assessed in vitro in ferret AO and in ferrets in vivo. Undifferentiated and differentiated ferret AO cultures supported rHPIV-3 CI-1-EGFP replication, but the ferret primary airway cells from AO were less susceptible and permissive than HAE. In vivo rHPIV-3 CI-1-EGFP replicated in the upper and lower airways of ferrets and targeted respiratory epithelial cells, olfactory epithelial cells, type I pneumocytes, and type II pneumocytes. The infection efficiently induced specific antibody responses. Taken together, ferrets are naturally susceptible to HPIV-3 infection; however, limited replication was observed that led to neither overt clinical signs nor ferret-to-ferret transmission. However, in combination with ferret AO, the ferret model of HPIV-3 infection, tissue tropism, and neutralizing antibodies complements human ex vivo lung models and can be used as a platform for prevention and treatment studies for this important respiratory pathogen. IMPORTANCE HPIV-3 is an important cause of pediatric disease and significantly impacts the elderly. Increasing numbers of immunocompromised patients suffer from HPIV-3 infections, often related to problems with viral clearance. There is a need to model HPIV-3 infections in vitro and in vivo to evaluate novel prophylaxis and treatment options. Currently existing animal models lack the potential for studying animal-to-animal transmission or the effect of immunosuppressive therapy. Here, we describe the use of the ferret model in combination with authentic clinical viruses to further complement human ex vivo models, providing a platform to study approaches to prevent and treat HPIV-3 infection. Although we did not detect ferret-to-ferret transmission in our studies, these studies lay the groundwork for further refinement of the ferret model to immunocompromised ferrets, allowing for studies of severe HPIV-3-associated disease. Such models for preclinical evaluation of prophylaxis and antivirals can contribute to reducing the global health burden of HPIV-3.


Influence of diagnostic classification on gender ratio in schizophrenia - a meta-analysis of youths hospitalized for psychosis.
The research literature on hospital admissions for psychoses in youths was reviewed in order to test whether there was a gender ratio discrepancy in diagnostic subgroups; the effect of the diagnostic criteria classification on this measure was also investigated. A meta-analysis was conducted on 12 primary studies by assessing the male/female odds ratio (OR) in the schizophrenia and mood disorders with psychosis subgroups as well as the amount of variability between studies. Study inclusion criteria were: patients between the ages of 8 and 19, at least 15 patients with psychosis and a standardized diagnostic criteria classification system such as DSM, ICD or RDC. The male/female OR measured in this meta-analysis implies that a male subject with psychosis is 1.7 times as likely to obtain a diagnosis of schizophrenia; conversely, a female subject with psychosis is 2.1 times as likely to be assigned in the mood disorders with psychosis subgroup. Disparity in diagnostic criteria nomenclature (ICD-9 vs. DSM) could account for a statistically significant difference in male/female OR for the schizophrenia subgroup in a subset of 11 studies. Under the narrower definition of schizophrenia in studies using DSM diagnostic criteria classification, the shift towards a greater proportion of patients diagnosed with mood disorders with psychosis could be explained by the time criteria; the simultaneous emergence of the gender ratio difference is discussed. This study shows that subtle changes in diagnostic criteria in psychiatric illnesses can greatly influence observational data pertaining to youths.


Has the incidence of empyema in Scottish children continued to increase beyond 2005?
The incidence of empyema increased dramatically in children during the 1990s and early 2000s. We investigated the relationship between changes in the incidence of childhood empyema in Scotland following the 2006 introduction of routine heptavalent conjugate pneumococcal vaccination (PCv-7) and the 2010 introduction of the 13-valent (PCV-13) vaccine. This was a whole-population study of Scottish hospital admissions between 1981 and 2013 using ICD (International Classification of Diseases)-9 and ICD-10 diagnostic codes for empyema. The number of admissions for pneumonia and croup was also captured to give insight into secular trends in admissions with other related and unrelated respiratory presentations. There were 217 admissions with empyema between 1981 and 2005 (mean incidence 9 cases/million/year) and 323 between 2006 and 2013 (mean incidence 47 cases/million/year), p<0.001. The introduction of conjugate vaccines in 2006 was associated with an overall increase in admissions for empyema of 2.0 (95% CI 1.4 to 2.8) per 100 000 children, however, the incidence rate ratio for empyema admission between 2010 and 2013 was lower relative to 2006-2009 (0.78 (95% CI 0.63 to 0.98)). Secular changes in pneumonia, but not croup, were comparable with those for empyema. The incidence of empyema in Scottish children initially rose in children aged 1 to 9 years after the introduction of routine conjugate pneumococcal vaccination, however, empyema incidence has fallen since 2010 when the PCV-13 was introduced.


Systems-wide effects of short-term feed deprivation in obese mice.
While prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.


Depression and COPD in older people: a review and discussion.
Depression affects approximately 40% of patients with chronic obstructive pulmonary disease (COPD) and is largely untreated. This review draws on the author's studies and the available literature to examine the problem. Older people with COPD experience moderate levels of depression, but this goes largely unrecognized and untreated. The prevalence, severity and risk factors for depression in this population are discussed. Treatment, in the form of pulmonary rehabilitation and antidepressant drug therapy, are discussed, but in the absence of well-controlled trials, it is difficult to draw any firm conclusions about the benefits of these therapies. However, an appropriate home care package, with the support of respiratory nurses, is of some benefit to housebound patients with COPD because it helps to relieve depression and improve their quality of life, especially among those with a high level of depressive symptoms.


Nanoscale hydrophobic recovery: A chemical force microscopy study of UV/ozone-treated cross-linked poly(dimethylsiloxane).
Chemical force microscopy (CFM) in water was used to map the surface hydrophobicity of UV/ozone-treated poly(dimethylsiloxane) (PDMS; Sylgard 184) as a function of the storage/recovery time. In addition to CFM pull-off force mapping, we applied indentation mapping to probe the changes in the normalized modulus. These experiments were complemented by results on surface properties assessed on the micrometer scale by X-ray photoelectron spectroscopy and water contact-angle measurements. Exposure times of < or = 30 min resulted in laterally homogeneously oxidized surfaces, which are characterized by an increased modulus and a high segmental mobility of PDMS. As detected on a sub-50-nm level, the subsequent "hydrophobic recovery" was characterized by a gradual increase in the pull-off forces and a decrease in the normalized modulus, approaching the values of unexposed PDMS after 8-50 days. Lateral imaging on briefly exposed PDMS showed the appearance of liquid PDMS in the form of droplets with an increasing recovery time. Longer exposure times (60 min) led to the formation of a hydrophilic silica-like surface layer. Under these conditions, a gradual surface reconstruction within the silica-like layer occurred with time after exposure, where a hydrophilic SiOx-enriched phase formed < 100-nm-sized domains, surrounded by a more hydrophobic matrix with lower normalized modulus. These results provide new insights into the lateral homogeneity of oxidized PDMS with a resolution in the sub-50-nm range.


Evaluation of the quality of the management of cancer of the corpus uteri--selection of relevant quality indicators and implementation in Belgium.
Describe the methodology and selection of quality indicators (QI) to be implemented in the EFFECT (EFFectiveness of Endometrial Cancer Treatment) project. EFFECT aims to monitor the variability in Quality of Care (QoC) of uterine cancer in Belgium, to compare the effectiveness of different treatment strategies to improve the QoC and to check the internal validity of the QI to validate the impact of process indicators on outcome. A QI list was retrieved from literature, recent guidelines and QI databases. The Belgian Healthcare Knowledge Center methodology was used for the selection process and involved an expert's panel rating the QI on 4 criteria. The resulting scores and further discussion resulted in a final QI list. An online EFFECT module was developed by the Belgian Cancer Registry including the list of variables required for measuring the QI. Three test phases were performed to evaluate the relevance, feasibility and understanding of the variables and to test the compatibility of the dataset. 138 QI were considered for further discussion and 82 QI were eligible for rating. Based on the rating scores and consensus among the expert's panel, 41 QI were considered measurable and relevant. Testing of the data collection enabled optimization of the content and the user-friendliness of the dataset and online module. This first Belgian initiative for monitoring the QoC of uterine cancer indicates that the previously used QI selection methodology is reproducible for uterine cancer. The QI list could be applied by other research groups for comparison.


Early and Late Surgical Outcomes after Geometrical Infarct Exclusion for Post-Infarct Ventricular Septal Perforation.
Ventricular septal perforation (VSP) is a critical complication of acute myocardial infarction. Various surgical procedures for it have been developed; however, surgical outcomes remain unsatisfactory. In 2010, we introduced geometrical infarct exclusion (GIE) as a modification of the Komeda-David technique. This retrospective study compared the surgical outcomes of our geometric infarct exclusion technique to those of other surgical procedures. This study included 38 patients who underwent surgery for VSP. They were divided into patients who underwent GIE (GIE group; n = 17) and those who underwent other procedures (non-GIE group; n = 21). The clinical outcomes of the two groups were compared. Operation, cardiopulmonary bypass, and cardiac arrest times in the GIE group were significantly longer than those in the non-GIE group (p <0.001). A residual shunt was observed in one patient (5.8%) in the GIE group and eight (38.0%) in the non-GIE group (p = 0.026). No patients in the GIE group required a reoperation for the residual shut, while two patients required it in the non-GIE group (p = 0.492). Operative mortality was insignificantly different between the two groups. Geometric infarct exclusion has a longer procedural time than does other surgical procedures but can reduce the rates of residual shunts and reoperations.


Ferumoxytol-Enhanced MR Lymphography for Detection of Metastatic Lymph Nodes in Genitourinary Malignancies: A Prospective Study.
OBJECTIVE. The objective of our study was to evaluate the utility of ferumoxytol-enhanced MR lymphography (MRL) in detection of metastatic lymph nodes (LNs) in patients with prostate, bladder, and kidney cancer. SUBJECTS AND METHODS. This phase 2 single-institution study enrolled patients with confirmed prostate (arm 1), bladder (arm 2), and kidney (arm 3) cancer and evidence of suspected LN involvement. Participants underwent ferumoxytol-enhanced MRL 24 and 48 hours after IV injection of 7.5 mg Fe/kg of ferumoxytol. A retrospective quantitative analysis was performed to determine the optimal timing for ferumoxytol-enhanced MRL using percentage change in normalized signal intensity (SI) from baseline to 24 and 48 hours after injection, which were estimated using the linear mixed-effects model in which time (24 vs 48 hours), diseases status, and time and disease status interaction were the fixed-effects independent variables. Differences in normalized SI values between subgroups of lesions were estimated by forming fixed-effects contrasts and tested by the Wald test. RESULTS. Thirty-nine patients (n = 30, arm 1; n = 6, arm 2; n = 3, arm 3) (median age, 65 years) with 145 LNs (metastatic, n = 100; benign, n = 45) were included. LN-based sensitivity, specificity, positive predictive value, and negative predictive value of ferumoxytol-enhanced MRL was 98.0%, 64.4%, 86.0%, and 93.5%, respectively. Sensitivity and specificity of ferumoxytol-enhanced MRL did not vary by LN size. Metastatic LNs showed a significantly higher percentage decrease of normalized SI on MRL at 24 hours after ferumoxytol injection than at 48 hours after ferumoxytol injection (p = 0.023), whereas the normalized SI values for nonmetastatic LNs were similar at both imaging time points (p = 0.260). CONCLUSION. Ferumoxytol-enhanced MRL shows high sensitivity in the detection of metastatic LNs in genitourinary cancers independent of LN size. The SI difference between benign and malignant LNs on ferumoxytol-enhanced MRL appears similar 24 and 48 hours after ferumoxytol injection, suggesting that imaging can be performed safely within 1 or 2 days of injection. Although ferumoxytol-enhanced MRL can be useful in settings without an available targeted PET agent, issues of iron overload and repeatability of ferumoxytol-enhanced MRL remain concerns for this method.


Quantification of the aromaticity of 2-alkylidenethiazolines subjected to push-pull activity.
Through-space NMR shieldings (TSNMRSs) of a series of 2-alkylidenethiazolines subjected to push-pull activity have been calculated by the GIAO method employing the nucleus-independent chemical shift (NICS) concept and visualized as iso-chemical-shielding surfaces (ICSSs). The ICSSs were applied to quantify and visualize the degree of aromaticity of the studied compounds, which has been shown to be in excellent correlation with the push-pull behavior, quantified by the quotient (π*/π) method. Dissection of the absolute magnetic shielding values into individual contributions of bonds and lone pairs by the natural chemical shielding-natural bond orbital (NCS-NBO) analysis has revealed unexpected details.


Information-oriented patients and physician career satisfaction: is there a link?
Patients' increasing use of alternative sources of information besides their physician and more active involvement in medical decision making may be changing relationships between physicians and their patients. We term patients who provide medical information to their physicians from sources other than their physician as information-oriented patients and investigate the relationship between having such patients and physician career satisfaction. We find that having more information-oriented patients is significantly associated with lower physician career satisfaction. Though healthcare information from alternative sources other than their physicians is thought to promote better-informed patient choices, the adverse relationship with physician career satisfaction found in this study may have important implications for patient access and quality of care.


[Changes in the lipid composition of embryonic cells of the mussel Mytilus trossulus during cryopreservation].
A comparative analysis of the lipid composition of embryonic cells of the mussel Mytilus trossulus prior to, and after, cryopreservation in liquid nitrogen was carried out in the presence of two types of cryoprotectors: 1) dimethylsulfoxide and trehalose; and 2) dimethylsulfoxide, trehalose, total lipid extract from the mussel Crenomytilus grayanus, alpha-tocopherol and ascorbic acid. It was found that not only the cell viability but also the fatty acid composition of cell lipids after cryopreservation depend on the composition of cryoprotectors used. The content of saturated fatty acids, monoenic and polyenic fatty acids, the omega 3/omega 6 ratio, and the index of nonsaturation in the fatty acid composition of lipids was shown to change remarkably after cryopreservation. Possible reasons of these changes are discussed.


Behavioral and technological interventions targeting glycemic control in a racially/ethnically diverse population: a randomized controlled trial.
Diabetes self-care by patients has been shown to assist in the reduction of disease severity and associated medical costs. We compared the effectiveness of two different diabetes self-care interventions on glycemic control in a racially/ethnically diverse population. We also explored whether reductions in glycated hemoglobin (HbA1c) will be more marked in minority persons. We conducted an open-label randomized controlled trial of 376 patients with type 2 diabetes aged ≥18 years and whose last measured HbA1c was ≥7.5% (≥58 mmol/mol). Participants were randomized to: 1) a Chronic Disease Self-Management Program (CDSMP; n = 101); 2) a diabetes self-care software on a personal digital assistant (PDA; n = 81); 3) a combination of interventions (CDSMP + PDA; n = 99); or 4) usual care (control; n = 95). Enrollment occurred January 2009-June 2011 at seven regional clinics of a university-affiliated multi-specialty group practice. The primary outcome was change in HbA1c from randomization to 12 months. Data were analyzed using a multilevel statistical model. Average baseline HbA1c in the CDSMP, PDA, CDSMP + PDA, and control arms were 9.4%, 9.3%, 9.2%, and 9.2%, respectively. HbA1c reductions at 12 months for the groups averaged 1.1%, 0.7%, 1.1%, and 0.7%, respectively and did not differ significantly from baseline based on the model (P = .771). Besides the participants in the PDA group reporting eating more high-fat foods compared to their counterparts (P < .004), no other significant differences were observed in participants' diabetes self-care activities. Exploratory sub-analysis did not reveal any marked reductions in HbA1c for minority persons but rather modest reductions for all racial/ethnic groups. Although behavioral and technological interventions can result in some modest improvements in glycemic control, these interventions did not fare significantly better than usual care in achieving glycemic control. More research is needed to understand how these interventions can be most effective in clinical practice. The reduction in HbA1c levels found in our control group that received usual care also suggests that good routine care in an integrated healthcare system can lead to better glycemic control. Clinicaltrials.gov Identifier: NCT01221090.


Relationship between mRNA expression levels of CYP3A4, CYP3A5 and SXR in peripheral mononuclear blood cells and aging in young kidney transplant recipients under tacrolimus treatment.
The activity of several key enzymes involved in the metabolism of many drugs is subject to change closely related to the age of patients. This possibility must also be considered in the case of tacrolimus, the most important calcineurins inhibitor, which is widely used in pediatric kidney transplantation. As well as in the liver and intestine, some of the enzymes involved in the metabolism of tacrolimus were also isolated in the peripheral blood mononuclear cells (PBMCs), where also appear to play an important regulatory action. Therefore, the influence of some external factors on the expression of specific mRNA can be determined noninvasively. The correlation between the levels of mRNA specific for key enzymes SXR, CYP3A and ABCB1 involved in the metabolism of tacrolimus was evaluated in PBMCs obtained from a selected population of 29 young kidney transplant recipients. A possible correlation between the expression of these specific mRNAs and tacrolimus pharmacokinetics was also investigated. The patients' age and their blood concentrations of SXR mRNA were directly correlated with the expression of CYP3A4, CYP3A5 mRNAs, but not of ABCB1 mRNA in the PBMCs. tacrolimus-normalized daily dose was strongly correlated with patient's age and multivariable regression indicates the CYP3A4-specific mRNA as the sole independent variable influencing tacrolimus concentration-to-dose ratio. Aging and SXR mRNA significantly affect the expression of CYP3A4- and CYP3A5-specific mRNA as measured by their concentration in PBMC.


Scorpion toxins from Centruroides noxius and Tityus serrulatus. Primary structures and sequence comparison by metric analysis.
The complete primary structures of toxin II-14 from the Mexican scorpion Centruroides noxius Hoffmann and toxin gamma from the Brazilian scorpion Tityus serrulatus Lutz and Mello have been determined. Cleavage of toxin gamma after Met-6 with CNBr produced the 55-residue peptide 7-61, which maintained the four disulphide bonds but was not toxic to mice at a dose 3 times the lethal dose of native toxin gamma. Pairwise comparison by metric analysis of segment 1-50 of toxin gamma and the corresponding segments from two other South American scorpion toxins, five North American scorpion toxins, nine North African scorpion toxins and one Central Asian scorpion toxin showed that the three Brazilian toxins are intermediate between the North American and North African toxins. This result is consistent with the hypothesis that the South American and African continents were joined by a land connection in the distant past.


Real-time detection of caspase-3-like protease activation in vivo using fluorescence resonance energy transfer during plant programmed cell death induced by ultraviolet C overexposure.
Caspase-like proteases have been demonstrated to be involved in plant programmed cell death (PCD). Here, the time scale of caspase-3-like protease activation was investigated in single living plant cells undergoing PCD induced by ultraviolet C (UV-C) overexposure. The real-time detection of caspase-3-like protease activation was achieved by measuring the degree of fluorescence resonance energy transfer (FRET) within a recombinant substrate containing enhanced cyan fluorescent protein (ECFP) linked by a peptide possessing the caspase-3 cleavage sequence, DEVD, to enhanced yellow fluorescent protein (EYFP; i.e. ECFP-DEVD-EYFP). Microscopic observations demonstrated that the ECFP-DEVD-EYFP fusion protein could be expressed correctly and the FRET from ECFP to EYFP could be found in transfected Arabidopsis (Arabidopsis thaliana) protoplasts. At 30 min after exposure to UV-C, caspase-3-like protease activation indicated by the decrease in FRET ratio occurred, taking about 1 h to reach completion in single living protoplasts. Mutation in the DEVD tag or a caspase-3 inhibitor could prevent the changes in FRET ratio induced by UV-C treatment, confirming that the decrease in FRET ratio was due to the cleavage of fusion protein as a result of caspase-3-like protease activation. This activation was further confirmed by in vitro caspase-3 substrate assay and western-blot analysis, showing the occurrence of cleavage in ECFP-DEVD-EYFP protein but not in the protein with a mutant DEVD tag. In summary, these results represent direct evidence for the activation of caspase-3-like protease in UV-C-induced PCD, and the FRET technique is a powerful tool for monitoring key events of PCD in living cells in real time.


Convergence analysis of the Newton algorithm and a pseudo-time marching scheme for diffuse correlation tomography.
We propose a self-regularized pseudo-time marching scheme to solve the ill-posed, nonlinear inverse problem associated with diffuse propagation of coherent light in a tissuelike object. In particular, in the context of diffuse correlation tomography (DCT), we consider the recovery of mechanical property distributions from partial and noisy boundary measurements of light intensity autocorrelation. We prove the existence of a minimizer for the Newton algorithm after establishing the existence of weak solutions for the forward equation of light amplitude autocorrelation and its Fréchet derivative and adjoint. The asymptotic stability of the solution of the ordinary differential equation obtained through the introduction of the pseudo-time is also analyzed. We show that the asymptotic solution obtained through the pseudo-time marching converges to that optimal solution provided the Hessian of the forward equation is positive definite in the neighborhood of optimal solution. The superior noise tolerance and regularization-insensitive nature of pseudo-dynamic strategy are proved through numerical simulations in the context of both DCT and diffuse optical tomography.


HYPERSENSITIVE TO RED AND BLUE 1, a ZZ-type zinc finger protein, regulates phytochrome B-mediated red and cryptochrome-mediated blue light responses.
Plant photoreceptors that regulate photomorphogenic development include red/far-red-light-absorbing phytochromes and blue/UV-A-light-absorbing cryptochromes. We have undertaken a genetic screen to identify additional components downstream of the photoreceptors in Arabidopsis thaliana. We identified a short hypocotyl mutant under red and blue light, hypersensitive to red and blue 1 (hrb1). Mutation in HRB1 also enhances the end-of-day far-red light response, inhibits leaf expansion and petiole elongation, and attenuates the expression of CAB3 and CHS. Double mutant analysis indicates that phyB is epistatic to hrb1 under red light, and cry1 cry2 is epistatic to hrb1 under blue light for both hypocotyl growth and light-regulated gene expression responses. HRB1 localizes to the nucleus and belongs to a protein family of Drought induced 19 (Di19). HRB1 and all other family members contain a ZZ-type zinc finger domain, which in other organisms is implicated in protein-protein interactions between dystrophin and calmodulin and between transcriptional adaptors and activators. HRB1 activity is also required for red and blue light-induced expression of PHYTOCHROME INTERACTING FACTOR 4 (PIF4). pif4 shows a very similar hypersensitive response as hrb1 to both red light and blue light and is epistatic to hrb1 in control of light-regulated gene expression responses. Thus, the roles of HRB1 and PIF4 together in regulating both red and blue light responses may represent points where red light signaling and blue light signaling intersect.


Odor-baited trap trees: a new approach to monitoring plum curculio (Coleoptera: Curculionidae).
We compared a trap approach with a trap-tree approach to determine the need and timing of insecticide applications against overwintered adult plum curculios, Conotrachelus nenuphar (Herbst.), in commercial apple orchards in Massachusetts in 2002. All traps and trap trees were baited with benzaldehyde (attractive fruit odor) plus grandisoic acid (attractive pheromone). Sticky clear Plexiglas panel traps placed at orchard borders, designed to intercept adults immigrating from border areas by flight, captured significantly more adults than similarly placed black pyramid traps, which are designed to capture adults immigrating primarily by crawling, or Circle traps wrapped around trunks of perimeter-row trees, which are designed to intercept adults crawling up tree trunks. None of these trap types, however, exhibited amounts of captures that correlated significantly with either weekly or season-long amounts of fresh ovipositional injury to fruit by adults. Hence, none appears to offer high promise as a tool for effectively monitoring the seasonal course of plum curculio injury to apples in commercial orchards in Massachusetts. In contrast, baiting branches of selected perimeter-row trees with benzaldehyde plus grandisoic acid led to significant aggregation (14-15-fold) of ovipositional injury, markedly facilitating monitoring of the seasonal course of injury to apples. A concurrent experiment revealed that addition of other synthetic fruit odor attractants to apple trees baited with benzaldehyde plus grandisoic acid did not enhance aggregation of ovipositional injury above that of this dual combination. We conclude that monitoring apples on odor-baited trap trees for fresh ovipositional injury could be a useful new approach for determining need and timing of insecticide application against plum curculio in commercial orchards.


Antibiotic resistance in Staphylococcus aureus isolated at an Australian hospital between 1946 and 1981.
A total of 517 strains of Staphylococcus aureus isolated at a hospital in Melbourne, Australia between 1946 and 1981 was examined for resistance to a range of antimicrobial agents and for the presence of plasmid DNA. The use of mixed-culture transfer and restriction endonuclease analysis showed that the determinants for resistance to penicillin and to the heavy metals were carried by several related plasmids of (15-23) X 10(6) mol. wt, and that tetracycline resistance was encoded on a plasmid of 2.8 X 10(6) mol. wt in strains isolated before 1970. These phenotypes were chromosomally encoded in the majority of strains isolated thereafter. Resistance to chloramphenicol throughout the study period was plasmid-mediated. Of five aminoglycoside-resistance phenotypes, one was plasmid-mediated and three were chromosomally encoded. The remaining phenotype, specifying low-level gentamicin resistance, was found to be located on the chromosome of early isolates, but in later strains was borne by an 18 X 10(6) mol. wt plasmid which also encoded resistance to quaternary ammonium compounds.


[Medicines and oral healthcare 1. What oral healthcare providers need to know about medicines].
Many patients who visit a dentist, oral hygienist or other oral healthcare provider use medicines. As a result of the ageing of the Dutch population, the number of patients using medicines will further increase, including the number of patients who are using more than one medicine. In addition to medicines, many patients, including healthy individuals, use self-care medications. Both medicines and self-care medications can interfere with dental treatment and/or may serve as an explanation for changes that dentists, oral hygienists or other oral healthcare providers observe in and around the mouth. With a series of articles about medicines and oral healthcare, attention will be given to this issue, an issue that will be increasingly important in the future. In addition, suggestions will be made in these articles for medicines for disorders in the head and neck region, keeping in mind that these suggestions should not be seen as dogmatic.


Regenerative medicine in urology.
Regenerative medicine is an emerging field that is focused on the repair, replacement or regeneration of tissues and organs. It involves multiple disciplines dedicated to delivering different aspects of the regeneration process, including cell biology, material sciences and bioengineering. The development of tissue engineering strategies incorporating the use of autologous stem cells holds particular promise for overcoming insufficiencies from using cells from the patient's own diseased tissues and providing solutions for treatment of many disorders of the genitourinary tract. Many experimental projects have successfully utilized stem cells and several pilot studies in humans indicate the potential of stem cell therapy. However, the discipline is still young and further knowledge of both materials and stem cell biology is required before this promise can be realized through clinical application. This review examines the principles related to regenerative medicine and bioengineering focusing on the stem cell isolation expansion and clinical application. Analysis of current achievements will be reviewed alongside the challenges that remain to be addressed in considering the present and future perspectives of regenerative medicine applied to urology.


Cognitive function and the risk of death in chronic kidney disease.
Cognitive impairment is a risk factor for death in dialysis patients and the general population. We sought to determine if cognitive impairment is associated with death in people with non-dialysis-dependent chronic kidney disease (CKD), and if so, whether this relationship is greater in the CKD population compared to the general population. National Health and Nutrition Examination Survey-III participants older than 60 years were asked to subtract 3 from 20 five times and to perform immediate and delayed recall of three items. A cognitive score of 0-11 was assigned based on the number of correct responses. Participants were categorized according to cognitive score (11, 9-10, 6-9, and 0-5) and CKD status. Survival analyses were conducted using Cox models. Within the CKD subpopulation, those in the lowest cognitive score group had a twofold increased hazard of death compared to those with maximum score. Within the non-CKD subpopulation, those in the lowest cognitive score group had a 46% increased hazard of death compared to those with maximum score. However, the difference in the hazards of death in the CKD and non-CKD subpopulations with the lowest cognitive score was not significant (p = 0.99). Low cognitive score is associated with an increased risk of death in elderly individuals with and without CKD; however, there was no interaction of CKD and low cognitive score in this analysis.


The Parkes Lecture. Heat and the testis.
The evidence for the lower temperature of the testes of many mammals is summarized, and the reasons suggested for the descent of the testes into a scrotum are discussed. Descriptions are given of the various techniques used for studying the effects of heat on the testis, whole body heating, local heating of the testes (by inducing cryptorchidism, scrotal insulation or immersion of the scrotum in a water bath), and heating of tissue or cell preparations in vitro. The effects of heat are discussed, effects on the testis (weight, histology, physiology, biochemistry and endocrinology), on the numbers and motility of spermatozoa in rete testis fluid and semen, on fertilizing ability of spermatozoa and on the subsequent development of the embryos produced when spermatozoa from heated testes are used to fertilize normal ova. The possible mechanisms for the damaging effects of heat are discussed, as well as the importance of heat-induced abnormalities in male reproduction in domestic animals and humans.


Anyonic behavior of an intermediate-statistics fermion gas model.
We study the high-temperature behavior of an intermediate-statistics fermionic gas model whose quantum statistical properties enable us to effectively deduce the details about both the interaction among deformed (quasi)particles and their anyonic behavior. Starting with a deformed fermionic grand partition function, we calculate, in the thermodynamical limit, several thermostatistical functions of the model such as the internal energy and the entropy by means of a formalism of the fermionic q calculus. For high temperatures, a virial expansion of the equation of state for the system is obtained in two and three dimensions and the first five virial coefficients are derived in terms of the model deformation parameter q. From the results obtained by the effect of fermionic deformation, it is found that the model parameter q interpolates completely between bosonlike and fermionic systems via the behaviors of the third and fifth virial coefficients in both two and three spatial dimensions and in addition it characterizes effectively the interaction among quasifermions. Our results reveal that the present deformed (quasi)fermion model could be very efficient and effective in accounting for the nonlinear behaviors in interacting composite particle systems.


[Unilateral angioedema of the tongue and the floor of the mouth as a side-effect of ACE-inhibitors].
An 80-year-old woman who was medically compromised had recurrent diffuse unilateral swelling of the tongue and the floor of the mouth. The clinical working diagnosis of angioedema as a result of the use of ACE-inhibitors (lisinopril) was made. In consultation with the cardiologist in charge of her case and the general practitioner, the ACE-inhibitor was discontinued. The patient's complaints subsequently ceased.


Importance of injection site for coronary blood flow determinations by microspheres in rats.
Because coronary blood flow (CBF) determinations require that blood and microspheres be uniformly mixed in the root of the aorta, we developed a technique of left-atrial (LA) catheterization in rats and compared the variability of results obtained by LA injection and left-ventricular (LV) injection as regards systemic [cardiac output (CO)], proximal (coronary), and distal (renal, cerebral) flows in anesthetized animals. CBF values averaged 410 +/- 224 and 358 +/- 99 (SD) ml.min-1.100 g-1 from LV and LA injection, respectively, or 5.7 +/- 2.9 and 4.9 +/- 1.3 (SD) %CO. The variability with LA injection was significantly lower than with LV injection as shown by the marked differences in standard deviations obtained with the two methods (224 vs. 99 ml.min-1.100 g-1 or 2.9 vs. 1.3 %CO, P greater than 0.01). In contrast, no significant difference in variability was found for either CO or more distal regional flows. These results indicate that LV injections might be adequate for systemic flow and regional flows to relatively distal beds but that accurate measurements of CBF require LA injection of microspheres.


Trabeculectomy or Transscleral Cyclophotocoagulation as Initial Treatment of Secondary Childhood Glaucoma in Northern Tanzania.
The purpose is to describe the outcome of trabeculectomy with transscleral cyclophotocoagulation (TSCPC) as an initial intervention for secondary childhood glaucoma in Northern Tanzania. A retrospective, consecutive case series was analyzed of all children with secondary childhood glaucoma who underwent initial trabeculectomy or TSCPC between 2000 and 2013 at a referral eye unit in Northern Tanzania. Retrospective data were collected on causes of glaucoma, intraocular pressure (IOP), visual acuity, complications, and subsequent interventions. Outcomes were evaluated using Kaplan-Meier survival analysis and compared with Cox regression analysis. The main outcome measure was failure (IOP>21 mm Hg). Thirty-six eyes of 27 children (male, 21; median age, 9 y; range, 0.3 to 15 y) with secondary childhood glaucoma underwent trabeculectomy (19 eyes, 53%) or TSCPC (17 eyes, 47%). Causes included ocular trauma (13, 36%), previous cataract surgery (12, 33%), congenital aniridia (5, 14%), Sturge-Weber syndrome (2, 6%), steroid-induced glaucoma (2, 6%), uveitis (1, 3%), and unspecified leucoma (1, 3%). After 12 months, success was achieved in 48% after trabeculectomy and 18% after TSCPC, with visual acuity remaining unchanged in 11 of 14 (79%) and 4 of 5 eyes (80%), respectively. One third of the children did not return for follow-up after 1 year. Distance to the hospital (>100 km) was a significant risk factor for trabeculectomy failure (P=0.031). A high proportion of secondary childhood glaucoma in Northern Tanzania was caused by trauma and previous cataract surgery. Trabeculectomy was associated with better IOP control but also a higher complication rate. The ability to maintain visual function was comparable after both interventions. Failure was associated with a journey to the eye hospital (>100 km) possibly leading to late presentation with advanced disease and erratic follow-up.


Hydrogen gas inhalation ameliorates lung injury after hemorrhagic shock and resuscitation.
Hemorrhagic shock and resuscitation (HSR) is known to cause inflammatory reactions in the lung parenchyma and acute lung injury, increasing the risk of complications that can lead to death. Hydrogen gas has shown to inhibit the formation and eliminate reactive oxygen species (ROS), which are known to cause reperfusion injury. Hence, the purpose of this study was to investigate the protective effect of 2% inhaled hydrogen gas on post-HSR lung injury. Rats weighing 300-500 g were divided into three groups: sham, HSR, and hydrogen (H2)/HSR groups. In the latter two groups, HSR was induced via femoral vein cannulation. Gas containing 2% hydrogen gas was inhaled only by those in the H2/HSR group. Lung tissue and abdominal aorta blood were obtained for histologic examination and arterial blood gas analyses, respectively. Neutrophil infiltration and proinflammatory mediators were also measured. PO2 was lower in the HSR and H2/HSR groups than in the sham group. Blood lactate level was not significantly different between the sham and H2/HSR groups, but it was significantly higher in the HSR group. Infiltration of inflammatory cells into the lung tissues was more frequent in the HSR group. Myeloperoxidase (MPO) activity was significantly different among the three groups (highest in the HSR group). All proinflammatory mediators, except IL-6, showed a significant difference among the three groups (highest in the HSR group). Inhalation of 2% hydrogen gas after HSR minimized the extent of lung injury by decreasing MPO activity and reducing infiltration of inflammatory cells into lung tissue.


Hemocoagulase might not control but worsen gastrointestinal bleeding in an elderly patient with type II respiratory failure.
Hemocoagulase has been successfully used for the management of bleeding in patients undergoing surgery. Local spray of hemocoagulase during endoscopic therapy may be effective for the management of gastrointestinal bleeding. In China, intravenous infusion of hemocoagulase is given by some physicians for the treatment of gastrointestinal bleeding. However, the potential adverse events secondary to hemocoagulase, such as hypofibrinogenemia, are poorly recognized. In this paper, we reported an elderly patient with type II respiratory failure in whom hemocoagulase might induce hypofibrinogenemia and further worsen gastrointestinal bleeding. We highlighted that fibrinogen levels should be cautiously monitored in patients receiving hemocoagulase.


Effect of ultrasound transmission gel on ultrasound-guided fine needle aspiration cytological specimens of thyroid.
To investigate prospectively the diagnostic impact of ultrasound coupling gel on thyroid specimens obtained under ultrasound guidance. Patients presenting for ultrasound-guided fine needle aspiration (USG-FNA) of the thyroid were invited to participate in the study. Four specimens per nodule were collected: two using chlorhexdine wash and two using sterile, colourless ultrasound gel as couplant according to routine protocol. All slides were analysed in a blinded fashion by two senior cytologists for the presence or absence of ultrasound gel-induced artefacts. The presence of gel-induced artefacts between the two groups was analyzed using Pearson's chi-square test. Kappa statistics were used to measure the inter-rater agreement between the cytologists. Twenty thyroid nodules comprising 80 specimen slides were collected. On slides collected with gel, cytological artefacts were detected in 60-65% of cases compared with 10-15% of cases without gel (P<0.001). The inter-rater agreement between the two observers was very good (κ=0.84). Two of the 14 patients required repeat FNA due to non-diagnostic cytology results caused by inadequate sampling and gel-induced artefacts. Clinical cytopathologists, radiologists and sonographers should be aware of the potential for ultrasound gel to cause significant artefacts on cytological specimens. Our findings suggest that staff involved in USG-FNA cytology should remove the gel carefully before taking the aspirate.


Maxillofacial trauma: managing potentially dangerous and disfiguring complex injuries [digest].
Patients with maxillofacial trauma require a careful evaluation due to the anatomical proximity of the maxillofacial region to the head and neck. Facial injuries can range from soft-tissue lacerations and nondisplaced nasal fractures to severe, complex fractures, eye injuries, and possible brain injury. Though the Advanced Trauma Life Support (ATLS) guidelines provide a framework for the management of trauma patients, they do not provide a detailed reference for many subtle or complex facial injuries. This issue adds a more comprehensive and systematic approach to the secondary survey of the maxillofacial area and emergency department management of injuries to the face. In addition to an overall review of maxillofacial trauma pathophysiology, associated injuries, and physical examination, this review will also discuss relevant imaging, treatment, and disposition plans. [Points & Pearls is a digest of Emergency Medicine Practice].


Nutritional geometry and fitness consequences in Drosophila suzukii, the Spotted-Wing Drosophila.
Since its arrival to North America less than a decade ago, the invasive Spotted-Wing Drosophila (Drosophila suzukii) has inflicted substantial economic losses on soft fruit agriculture due to its ability to oviposit into ripening fruits. More effective management approaches for this species are needed, but little is known about the factors that influence behavioral choices made by D. suzukii when selecting hosts, or the consequences that their offspring experience when developing in different environments. Using a nutritional geometry methodology, we found that the ratio of proteins-to-carbohydrates (P:C) present in media greatly influenced adult D. suzukii behavior and subsequent offspring development. Whereas adult flies showed a strong bias in their oviposition and association behaviors toward carbohydrate-rich foods, larval survival and eclosion rate were strongly dependent on protein availability. Here, we explore the preference-performance hypothesis (PPH), in which females are predicted to oviposit on medias that provide the greatest offspring benefits, in regard to its relevance in D. suzukii behavior and consequences for management. Our results provide valuable insight into the ecology and evolution of this species that may hopefully lead to more effective management strategies.


Modulation of CD40-activated B lymphocytes by N-acetylcysteine involves decreased phosphorylation of STAT3.
B lymphocyte activation, maturation and reshaping require the interaction of its receptor CD40 with its ligand CD154, which is expressed on activated T lymphocytes. Metabolism in activated B lymphocytes is also characterized with several REDOX changes including fluctuation of Reactive Oxygen Species (ROS). Herein, we first confirm that stimulation of human peripheral blood B lymphocyte with CD154 increases intracellular ROS level. Then, by treatments with two well-known antioxidants, N-acetylcysteine (NAC) and Trolox, we further investigate the influence of REDOX fluctuation in CD40-activated B lymphocyte homeostasis in long term culture (13 days). Treatments with NAC increase viability, decrease proliferation and Ig secretion and enhance homoaggregation of B lymphocytes while Trolox only induces a marginal increase of their Ig secretion. The NAC-induced homoaggregation phenotype is paralleled with increased expressions of CD54, CD11a, CD27 and CD38. Mechanistically, a 24h exposure of B lymphocytes with NAC is sufficient to show strong inhibition of STAT3 phosphorylation. Besides, the treatment of B lymphocytes with the STAT3 inhibitor VI increases viability and decreases proliferation and secretion as in NAC-treated cells thus showing a role for STAT3 in these NAC-induced phenotypes. This study done in a human-based model provides new findings on how REDOX fluctuations may modulate CD40-activated B lymphocytes during immune response and provide additional hints on NAC its immunomodulatory functions.


Effects of optic flow on the kinematics of human gait: a comparison of young and older adults.
This experiment studied the effect of imposed optic flow on human locomotion. Six young and 6 older adults were exposed to various patterns of optic flow while walking in a moving hallway. Results showed few cases of impaired postural control (staggers, parachute reactions). No falls were recorded. Kinematic patterns of gait were altered when vision was absent or inconsistent optic flow was presented: Ninety two percent of the subjects' mean step velocity differed from their step velocities under normal vision. Compared with imposed central flow, peripheral optic flow was not dominant in inducing kinematic changes. Characteristic gait profiles were obtained, depending on flow direction. Global backward flow tended to slow down step velocity, whereas subjects' step velocity increased during conditions of forward flow. The results suggest that subjects attempted to match their own walking speed to the velocity of the moving visual scenes. It is concluded that in an uncluttered environment, imposed optic flow has a modulating rather than a destabilizing effect on human locomotion.


New vaccines against tuberculosis.
In September 2000, recognizing the effect of communicable diseases as obstacles to development in poorer countries, the European Commission assembled a special round table on 'accelerated action targeted at major communicable diseases within the context of poverty reduction'. The three major communicable diseases discussed were tuberculosis (TB), malaria and HIV. One outcome of this discussion was a workshop examining issues related to the fight against TB in Africa, which took place in Gorée, Sénégal, in May 2001. The timing was propitious, as new vaccines for TB (recombinant MVA and BCG, and adjuvanated recombinant fusion proteins or peptide constructs), are just beginning to enter human clinical trials. All but the last of these have shown promise in animal models, up to and including non-human primates, and all are strongly immunogenic and apparently safe. Humans trials for safety and efficacy are thus the logical next step. This review summarizes recent advances in tuberculosis vaccine development, with a special emphasis on issues raised at the Gorée meeting about testing and deploying new generation vaccines in TB-endemic areas such as Africa.