[Functional expression of DNA binding domain of Zif268 in Escherichia coli].
As the ubiquitous nucleic acids recognizing motif, Zinc finger protein play important role in regulation of gene expression. The study of recognization specific will greatly facilitate understanding the delicate interaction of Zinc finger protein and DNA. By the choice of expression vector, the induction and culture conditions, the DNA binding domain of Zif268 was expressed in Escherichia coli partly solubly. The gel mobility shift assay shows that purified DNA binding domain can bind its natural target sequence specifically, which indicates the DNA binding domain remains its DNA binding activity in Escherichia coli. The functional expression of DNA binding domain of Zif268 will greatly facilitate the development of in vivo genetic selection assay for the study of Zinc fingers-DNA interaction.


Effect of osteopathic manipulative therapy in the attentive performance of children with attention-deficit/hyperactivity disorder.
Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder most commonly affecting children and teenagers. It is characterized by the coexistence of attention problems and impulsivity and hyperactivity. Although several studies have been conducted on the efficacy of conventional and alternative therapies in children with ADHD, few studies have specifically investigated the efficacy of osteopathic manipulative therapy (OMTh). To evaluate the efficacy of OMTh in the treatment of children with ADHD. Children aged 5 to 15 years with a primary diagnosis of ADHD who were admitted to a single neuropsychiatry unit from November 2008 to September 2009 were randomly assigned to an intervention group (OMTh + conventional care) or a control group (conventional care only). Biancardi-Stroppa Modified Bell Cancellation Test accuracy and rapidity scores were recorded for both groups at baseline and after 10 weeks. Statistical analyses included univariate tests and multivariate linear regressions. A total of 28 participants were included in the study: 14 in the OMTh group and 14 in the control group. Univariate statistical analysis showed no statistically significant differences between the intervention and control groups in terms of characteristics measured at baseline, except for psychosocial intervention (P=.05). Multivariate linear regression showed that OMTh was positively associated with changes in the Biancardi-Stroppa Test accuracy (β=7.948 points; P=.04) and rapidity (β=9.089 points; P=.03) scores. Participants who received OMTh had greater improvement in Biancardi-Stroppa Test scores than participants who received conventional care only, suggesting that OMTh can potentially increase performances of selective and sustained attention in children with ADHD. To confirm these findings, studies of larger and more diverse populations are warranted.


Refractory gastrointestinal symptoms: a combined medical psychiatric approach.
Gastroenterology has always been a collaborative specialty. Through the years, gastroenterologists have created important partnerships with pathologists, radiologists, surgeons, gynecologists, and pediatricians. These collaborative relationships have greatly enhanced patient care and research. This article reviews the literature on psychiatric comorbidity in the medical setting and gastroenterology practice in particular. The ability to recognize psychiatric comorbidity and relate it to the patient's presenting gastrointestinal (GI) complaint can pay great dividends for patients. The ability to apply these observations to help facilitate psychiatric collaboration and specifically, to initiate behavioral treatment, represents a new dimension in the care of chronic GI disorders. Finally, the relationship between physical and sexual abuse and GI illness and the usefulness of psychiatric interventions in the treatment of chronic GI disorders is reviewed in detail.


The 'entourage effect' or 'hodge-podge hashish': the questionable rebranding, marketing, and expectations of cannabis polypharmacy.
The concept of a cannabis 'entourage effect' was first coined as a hypothetical afterthought in 1998. Since then, multiple scientific reviews, lay articles, and marketing campaigns have promoted the effect as a wholly beneficial manifestation of polypharmacy expected to modulate the therapeutic effects of cannabis and its derivatives. There is reason to wonder at the authenticity of such claims. A broad definition of the entourage effect is presented, followed by brief summaries of the nature of cannabis polypharmacy and the commonly cited contributing phytochemicals, with special attention to their attendant adverse effects. A critical analysis is then offered of the primary literature that is often portrayed as suggestive of the effect in existing reviews, with further studies being drawn from PubMed and Google Scholar searches. A final discussion questions the therapeutic value of the entourage effect and offers alternate perspectives on how it might be better interpreted. Claims of a cannabis entourage effect invoke ill-defined and unsubstantiated pharmacological activities which are commonly leveraged toward the popularization and sale of ostensible therapeutic products. Overestimation of such claims in the scientific and lay literature has fostered their misrepresentation and abuse by a poorly regulated industry.


The survival motor neuron protein of Schizosacharomyces pombe. Conservation of survival motor neuron interaction domains in divergent organisms.
Spinal muscular atrophy is a common often lethal neurodegenerative disease resulting from deletions or mutations in the survival motor neuron gene (SMN). SMN is ubiquitously expressed in metazoan cells and plays a role in small nuclear ribonucleoprotein assembly and pre-mRNA splicing. Here we characterize the Schizosacharomyces pombe orthologue of SMN (yeast SMN (ySMN)). We report that the ySMN protein is essential for viability and localizes in both the cytoplasm and the nucleus. Like human SMN, we show that ySMN can oligomerize. Remarkably, ySMN interacts directly with human SMN and Sm proteins. The highly conserved carboxyl-terminal domain of ySMN is necessary for the evolutionarily conserved interactions of SMN and required for cell viability. We also demonstrate that the conserved amino-terminal region of ySMN is not required for SMN and Sm binding but is critical for the housekeeping function of SMN.


Socioeconomic status and metabolic syndrome in Southwest Iran: results from Hoveyzeh Cohort Study (HCS).
Socioeconomic status (SES) strongly predicts morbidity and premature mortality, especially for non-communicable diseases (NCDs). However, the effect of these factors on Metabolic Syndrome (MetS) is not clear yet. This study was conducted to assess the relationship between socioeconomic indicators and MetS. In this prospective cohort study, 10,009 people aged 35-70 enrolled from May 2016 to August 2018. The MetS was defined according to The Standard National Cholesterol Education Program (NCEP)-adult treatment panel III (ATP III) or NCEP-ATP III criteria. Demographics and socioeconomic data were gathered face-to-face through trained interviews. Also, lab, anthropometrics, and blood pressure measurements were assayed for participants. Logistic regression was used to estimate the association between SES and MetS, adjusted for the potential confounding factors. The overall prevalence of MetS in the participants was 39.1%. The crude odds ratios were statistically significant for all the assessed variables (p < 0.05). After adjustment for age, sex, physical activity, smoking, and alcohol use as potential confounders, the results indicated significant direct independent associations between skill level (p = 0.006) and Townsend index (p = 0.002) with MetS. In contrast, no significant associations between educational level and wealth status with MetS. The results of our study showed that SES is related to MetS. Among the four assessed SES indicators, skilled levels and Townsend score are strongly associated with MetS. We recommend considering people's SES when interventional programs are planned and conducted on MetS in similar communities.


Achieving integrated self-directed Cancer aftercare (ASICA) for melanoma: how a digital intervention to support total skin self-examination was used by people treated for cutaneous melanoma.
Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial. This paper reports on process evaluation. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved. Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up. Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool. Clinical Trials.gov , NCT03328247 . Registered on 1 November 2017.


Identification of filovirus entry inhibitors targeting the endosomal receptor NPC1 binding site.
Filoviruses, mainly consisting of Ebola viruses (EBOV) and Marburg viruses (MARV), are enveloped negative-strand RNA viruses which can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. The filovirus infection is mediated by the interaction of viral envelope glycoprotein (GP) and the human endosomal receptor Niemann-Pick C1 (NPC1). Blocking this interaction will prevent the infection. Therefore, we utilized an In silico screening approach to conduct virtual compound screening against the NPC1 receptor-binding site (RBS). Twenty-six top-hit compounds were purchased and evaluated by in vitro cell based inhibition assays against pseudotyped or replication-competent filoviruses. Two classes (A and U) of compounds were identified to have potent inhibitory activity against both Ebola and Marburg viruses. The IC50 values are in the lower level of micromolar concentrations. One compound (compd-A) was found to have a sub-micromolar IC50 value (0.86 μM) against pseudotyped Marburg virus. The cytotoxicity assay (MTT) indicates that compd-A has a moderate cytotoxicity level but the compd-U has much less toxicity and the CC50 value was about 100 μM. Structure-activity relationship (SAR) study has found some analogs of compd-A and -U have reduced the toxicity and enhanced the inhibitory activity. In conclusion, this work has identified several qualified lead-compounds for further drug development against filovirus infection.


The Effect of Berberine, a Drug From Chinese Folk Medicine, on Serum and Urinary Uric Acid Levels in Rats With Hyperuricemia.
Background The principal manifestation of hyperuricemia is gout. Many drugs are in use nowadays to treat gout, but they are linked with multiple side effects. The present study observed berberine (from Chinese folk medicine) on serum and urinary uric acid levels in rats with potassium oxonate-induced hyperuricemia. Materials and methods Thirty-six adult healthy female Sprague Dawley rats were randomly divided into six groups of six rats each. To induce hyperuricemia, all the groups except Group A were given potassium oxonate (250 mg/kg) intraperitoneally on days 1, 3, and 7. Group A, the normal control group, was given normal saline for seven consecutive days intraperitoneally. Group C was administered allopurinol (5 mg/kg body weight) intraperitoneally, and Group D, E, and F were given berberine in doses of 0.75 mg/kg, 1.25 mg/kg, and 2.5 mg/kg body weight respectively intraperitoneally for seven consecutive days, one hour after the potassium oxonate injection. On zero, first, third, and seventh day of the experiment, blood and urine samples were taken to estimate the serum and urinary uric acid levels. On days zero and 7, serum uric acid was measured by cardiac puncture, while on days 1 and 3, it was measured by the tail prick method. The uric acid was measured by an enzymatic colorimetric method and creatinine by the Jaffe method. Fractional excretion of urate was also calculated. Results Berberine lowered serum uric acid levels in rats with potassium oxonate-induced hyperuricemia with highly significant results (p-value <0.001) in all three dosages. Berberine increased the urinary uric acid level and the fractional excretion of urate in a time-dependent manner in all three dosages. This effect was maximally shown by low dose berberine with a highly significant result (p-value <0.001). Conclusion Berberine successfully decreased the serum uric acid level of hyperuricemic rats by increasing the urinary uric acid level and fractional excretion of urate.


European Consensus on Primary Prevention of Coronary Heart Disease.
The European Consensus on Primary Prevention of Coronary Heart Disease has recommended that providing care for individuals at particular risk for coronary artery disease (CAD) requires case finding through medical examinations in primary care, hospital and employment health examination settings. Decisions concerning management of elevated lipid levels should be based on overall cardiovascular risk. The goal of reducing cholesterol levels through risk reduction can ultimately be accomplished only with the implementation of health education efforts directed toward all age groups and actions by government and supranational agencies, including adequate food labelling to identify fat content, selective taxation to encourage healthful habits and wider availability of exercise facilities. Only measures directed at the overall population can eventually reach the large proportion of individuals at mildly to moderately increased risk for CAD. The European Policy Statement on the Prevention of Coronary Heart Disease recognizes that the question of lipid elevation as a risk factor for CAD involves assessment, not only of cholesterol level alone, but also of triglycerides and the HDL cholesterol lipid fraction. Five specific categories of dyslipidemia have been identified, with individualized screening and treatment strategies advised for each. It is the consensus of the study group panel members that these procedures are both practical and feasible. They begin the necessary long term process to reduce the unacceptably high levels of morbidity and mortality due to CAD throughout the European community.


Syneretic response to incremental pressures in calf lenses.
Syneretic response to pressure variation of 1 atm or more has been demonstrated previously in bovine and human lenses with nuclear magnetic resonance (NMR) relaxation measurements. This study is designed to prove that a similar response is observable in smaller pressure increments closer to the normal physiological range. Excised calf eyes were enucleated, the lenses dissected out, and immersed in medium. The lenses were exposed to incremental pressures ranging from 1 to 3 atm. At each pressure increment, a series of T1-weighted and spin echo images were acquired. Each image was segmented into seven regions of interest and tabulated. Longitudinal (T1) and transverse (T2) relaxation times were calculated from numerical fits of the experimental values to a one-term exponential expression. The relaxation parameters were obtained from fitting the image intensities to exponential equations, which yielded a relaxation time T and a pre-exponential factor M. The relaxation times and the pre-exponential terms of both parameters displayed linear dependence on pressure. There was no evidence of a threshold for syneretic response. Both T1 and T2 relaxation times decreased with increasing pressure. The pre-exponential term M2 increased with pressure, whereas M1 decreased with pressure; however, the slope of the latter was statistically not significantly different from zero. Syneretic response to pressure in calf lenses as determined by NMR relaxation measurements proved to be linearly dependent on pressure over a wide range of hydrostatic pressures. There was no range where the syneretic response was absent. These two findings allow the conclusion that the phenomenon observed hitherto at large pressure changes in vitro could be operative in vivo under physiological pressure changes during accommodation.


Situs revisited: imaging of the heterotaxy syndrome.
Situs anomalies present a diagnostic challenge to radiologists because of the overlapping spectrum of findings commonly seen in asplenia and polysplenia. In a series of 21 patients with a diagnosis of heterotaxy syndrome, all 11 asplenic patients and seven of 10 polysplenic patients had congenital heart disease. Although there was a variety of complex congenital heart disease, the most common type in both patient groups was a common atrioventricular canal. In both groups, the laterality of the aorta and stomach was quite variable, but intestinal malrotation was a constant feature. In 11 asplenic patients, the most frequent findings were a bridging liver (10 cases), absent spleen (10 cases), and left-sided inferior vena cava (nine cases). Only seven of these patients had an aorta ipsilateral to the inferior vena cava, contrary to previous thought that this finding was specific for asplenia. In the 10 polysplenic patients, bridging livers were less frequent (five cases), single (six cases) or multiple (four cases) spleens were seen, and azygous continuation with interruption of the inferior vena cava was usually present (eight cases). Although not pathognomonic of polysplenia, inferior vena cava interruption with azygous or hemiazygous continuation is the most common anatomic finding of this condition. Although the terms asplenia and polysplenia are helpful in suggesting the typical anatomy, both syndromes encompass an overlapping spectrum that needs to be described individually and may best be called heterotaxy syndrome.


[Saccoradiculography: contribution and indications in lumbar pathology in Abidjan (Ivory Coast)].
Radiculography is used a great deal in our region and is often the only method available for examination of the lumbar spine. However, there has been little evaluation of the effectiveness of radiculography for lumbar diseases. To determine its value and indications in lumbar diseases we studied 322 patients who underwent radiculography. We studied 223 patients retrospectively and 99 patients prospectively. Radiculography had a sensitivity of 100%, a specificity of 86%, a positive predictive value of 92.7% and a negative predictive value of 100%. We found that the diagnostic accuracy of radiculography was higher if the examination was requested by a neuropathologist, if the patient had been ill for more than 2 months or had cauda equina syndrome, acute root pain, paralysis or debilitation. Such precise indications make it possible to avoid excessive examination and to make the best use of radiculography, particularly in areas without CT and MRI facilities. However, the examination should always be performed by a neuroradiologist or a physician with several years' radiculography experience.


Estimating the Size and Impact of the Ecological Restoration Economy.
Domestic public debate continues over the economic impacts of environmental regulations that require environmental restoration. This debate has occurred in the absence of broad-scale empirical research on economic output and employment resulting from environmental restoration, restoration-related conservation, and mitigation actions - the activities that are part of what we term the "restoration economy." In this article, we provide a high-level accounting of the size and scope of the restoration economy in terms of employment, value added, and overall economic output on a national scale. We conducted a national survey of businesses that participate in restoration work in order to estimate the total sales and number of jobs directly associated with the restoration economy, and to provide a profile of this nascent sector in terms of type of restoration work, industrial classification, workforce needs, and growth potential. We use survey results as inputs into a national input-output model (IMPLAN 3.1) in order to estimate the indirect and induced economic impacts of restoration activities. Based on this analysis we conclude that the domestic ecological restoration sector directly employs ~ 126,000 workers and generates ~ $9.5 billion in economic output (sales) annually. This activity supports an additional 95,000 jobs and $15 billion in economic output through indirect (business-to-business) linkages and increased household spending.


Thermal transitions in hydrated layer-by-layer assemblies observed using electrochemical impedance spectroscopy.
Layer-by-layer (LbL) assemblies have been of great interest due to their versatile functionality and ease of fabrication, but their response to temperature is not completely understood. It has been recently shown that hydrated LbL assemblies of poly(diallyldimethylammonium chloride) (PDAC) and poly(styrene sulfonate) (PSS) under go a thermal transition much like a "glass-melt" transition. This thermal transition is of great interest because many LbL applications are found in water. Here, we report upon the nature of this thermal transition as probed using electrochemical impedance spectroscopy (EIS) as a function of assembly salt concentration, film thickness, and outermost layer. EIS reveals that the transition is signified by a structural rearrangement of virtual pores, resulting in increased conductivity and decreased surface coverage of the electrode. Two separate thermal transitions are obtained from changes in the film resistance (Ttr,Rf) and the charge transfer resistance (Ttr,Rct). Only Ttr,Rct is strongly dependent on film thickness, salt concentration, and outermost layer, for which values ranging from 50 to 64 °C were observed. As the assembly salt concentration increases from 0.5 M to 1.0 M NaCl, Ttr,Rct increases by about 10 °C. Below 20 layers, deviations of Ttr,Rct with respect to outermost layer appear, in which PSS-capped LbL films tend to show elevated Ttr,Rct values. These results suggest that extrinsic charge compensation plays a large role in the value of Ttr,Rct in which a large degree of extrinsic charge compensation drives Ttr,Rct towards higher values. On the other hand, Ttr,Rf is largely unaffected by assembly parameters, and closer in value to prior reports via calorimetry and quartz crystal microbalance with dissipation.


Siderophore-producing bacteria mitigate cobalt stress in black gram (Vigna mungo L.), and the mitigation strategies are associated with iron concentration.
Cobalt (Co) is considered an essential element in agriculture as it is an important constituent of vitamin B12. Due to natural and anthropogenic factors, heavy metals, especially Co, accumulate in agricultural fields, but their high exposure produces ramifications in crop plants, thereby reducing crop yield and biomass. Excessive Co in plants causes oxidative stress, and as the stress progresses, Co competes with iron (Fe) thereby decreasing chlorophyll content and resulting in Fe deficiency in plants. A major concern is to counter the Co toxicity. Therefore, the current study aimed to mitigate Co-stress or Co-toxicity by using siderophore producing microbes and simultaneously mobilize Co and iron (Fe) in required amounts. In this study, 250 bacteria were isolated from agricultural and non-agricultural soils and screened for siderophore production. Initial siderophore screening revealed that 28.8% of the isolates produced siderophore. Subsequent screening for Co-tolerance showed that 16 isolates were tolerant to up to 20,000 ppm of Co and produced ACC deaminase, siderophore (96.82-99.67%), indole-3-acetic acid (15.15-70.55 µg/mL) and phosphate solubilisation (39.33-142.67 µg/mL). A plate assay (200 mM Co stress) revealed that four isolates (KSBTS 12, SBTS 12, CWTS 5 and CWTS 10) enhanced the growth of black gram (Vigna mungo L.). Furthermore, evaluation in pot studies (2000 ppm Co stress) revealed enhanced root (60.69-174.24%) and shoot length (3.27-143.96%) compared to the control. Inoculated plants also enhanced the uptake of nitrogen (37.33-42.36 mg/g) and phosphorous (3.12-3.92 mg/g), chlorophyll content (7.60-22.97 mg/g), siderophore quantity in the soils (282.41-331.53%) and the soil respiration activity such as hydrolysis of fluorescein diacetate (11.33-24.88 µg/g), dehydrogenase enzyme (109.76-197.26 µg/g) and alkaline phosphatase (631.53-918.20 µg/g). In conclusion, CWTS 5 (Bacillus subtilis) and CWTS 10 (Bacillus albus) can be used to mitigate Co-stress and mobilize Co and Fe in plants.


[Fractionation of stable isotopes of sulfur during its oxidation by Thiobacillus ferrooxidans].
The fractionation of sulfur isotopes was studied in the process of sulfur oxidation by Thiobacillus ferrooxidans. The isotope effect was observed at all stages of the bacterial growth during sulfur oxidation; as a result, residual sulfur became heavier whereas the fraction of colloidal sulfur and the fraction of sulfates became lighter. The isotope differences between the residual sulfur and the sulfates were greatest at the end of the lag phase (delta 34S = 0.38%) and the beginning of the stationary phase of the cultural growth (delta 34S = 0.34%). As was shown in model experiments, the phospholipids lecithin and cephalin can dissolve sulfur and form products enriched in 32S(delta 34S = -0.51 -1.60%). The mechanism of oxidation of elementary sulfur by Thiobacillus ferrooxidans is discussed.


Study of Target Edge Response Viewed Through Atmospheric Turbulence over Water.
Photographed edge response of a quadrant target made through atmospheric turbulence at a range of 1.6 km 10.7 m above water was found to fit an error function form quite accurately. A theoretical estimate of the intensity point spread function based upon a parabolic approximation to the wave structure function for a point source is consistent with the data. Assuming the validity of the approximation, thermal values of C(n) give turbulence inner scales in the millimeter range.


Molecular mechanisms of fragile X syndrome.
Fragile X syndrome is the most common form of inherited mental retardation Mutations which abolish expression of an X-linked gene, FMR1, result in pathogenesis of the disease. FMR1 encodes a cytoplasmic RNA-binding protein which interacts with two autosomal homologs, FXR1 and FXR2. These proteins are highly expressed in neurons. In addition, the FMR1/FXR proteins are associated with ribosomes. Given their RNA-binding activity and association with ribosomes, these proteins are hypothesized to bind to specific RNAs and regulate their expression at translational levels in a manner critical for correct development of neurons. Much progress has been made in FMR1 research over the past several years, but little light has yet to be shed on the physiological function of these proteins. It will be critical to define the biochemical properties of these proteins, and identify potential downstream targets to clarify the molecular mechanisms underlying the potential roles of these proteins in translation. A basic understanding of the function of this new family of RNA-binding proteins should then allow us to begin to address the question of how the lack of FMR1 expression leads to symptoms in fragile X syndrome.


Cancer stem cell traits in squamospheres derived from primary head and neck squamous cell carcinomas.
A subpopulation of cancer stem cells (CSCs), but not the majority of non-tumorigenic cancer cells, in a variety of human malignancies plays a critical role in cancer cell proliferation, invasion, metastasis, and tumor recurrence post-therapies. We report the isolation of sphere-forming cells (squamospheres) from primary head and neck squamous cell carcinomas (HNSCCs), and characterization of their CSC properties. Squamospheres appeared within 2 weeks after seeding as single-dissociated cells obtained from primary HNSCC specimens in serum-free culture conditions. Real-time RT-PCR and immunocytochemistry assays revealed that a number of stem cell markers, including CK5, OCT4, SOX2, and nestin, were up-regulated in HNSCC-driven squamospheres. Fluorescence-activated cell sorting (FACS) analysis showed that squamospheres contain enriched side population cells compared to serum-induced differentiated squamosphere cells. Furthermore, HNSCC-driven squamospheres appeared to be chemoresistant to cisplatin, 5-fluorouracil (FU), paclitaxel and doxetaxel, and showed increased levels of ABCG2, one of the ATP-binding cassette (ABC) transporters. Of particular interest, in sharp contrast to subcutaneous injection of 1×10(6) differentiated squamosphere cells, as few as 100 squamosphere cells were able to give rise to tumors in nude mice. Altogether, we assert that primary HNSCC-driven squamospheres possess CSC properties, and its functional analysis may provide a novel tool for investigating the tumorigenic process of HNSCC.


Effect of Baliospermum montanum Root Extract on Phagocytosis by Human Neutrophils.
Aqueous extract of roots of Baliospermum montanum was evaluated on preliminary basis for immunomodulatory activity by studying neutrophil phagocytic function. The different concentration of (25, 50, 100 mug/ml) of aqueous extract of roots of Baliospermum montanum was subjected to study its effect on different in vitro methods of phagocytosis such as neutrophil locomotion, chemotaxis, immunostimulant activity of phagocytosis of killed Candida albicans and qualitative nitroblue tetrazolium test by using human neutrophils. This preliminary study revealed that Baliospermum montanum extract has stimulated chemotactic, phagocytic and intracellular killing potency of human neutrophils at the different concentration. From the results obtained it can be observed that the aqueous extract of Baliospermum montanum stimulate cell-mediated immune system by increasing neutrophil function.


Supererogation in clinical research.
'Supererogation' is the notion of going beyond the call of duty. The concept of supererogation has received scrutiny in ethical theory, as well as clinical bioethics. Yet, there has been little attention paid to supererogation in research ethics. Supererogation is examined in this paper from three perspectives: (1) a summary of two analyses of 'supererogation' in moral theory, as well as an examination as to whether acts of supererogation exist; (2) a discussion of supererogation in clinical practice, including arguments that both physicians and patients can practice acts of supererogation; (3) a discussion as to why researchers, qua researchers, are not routinely recognized to perform acts of supererogation, while at the same time the very nature of research subject participation involves supererogation. The article concludes by considering three examples of supererogation on the part of researchers, with a plea that researchers' supererogatory actions be recognized as such.


Attachment disorders: assessment strategies and treatment approaches.
The aim of this special issue is to examine methods for assessing and treating attachment disorders. This target article outlines existing strategies for assessment and considers which aspects of severe attachment disturbances and disorders may be core features of the disturbance(s). The usefulness of alternative methodologies for assessment are discussed, with particular emphasis on the need for the development of clinical protocol. The applications and implications for treatment are then discussed, with particular emphasis on the nature of the underlying disturbances that should be a focus for intervention. An absence of established treatment guidelines or consensus regarding the mechanisms of change are highlighted as barriers to further progress.


The reversal of cisplatin-induced nephrotoxicity by selenium nanoparticles functionalized with 11-mercapto-1-undecanol by inhibition of ROS-mediated apoptosis.
Although cisplatin is still one of the most effective chemotherapy agents for human cancers, its clinical use is limited by serious side effects, especially nephrotoxicity. Oxidative stress is an important mediator of cisplatin-induced nephrotoxicity. In the present study, a simple method for functionalization of selenium nanoparticles by self-assembly of 11-mercapto-1-undecanol (Se@MUN) to achieve enhanced antioxidant activity and antagonis against cisplatin-induced nephrotoxicity has been demonstrated. The chemical structure of the nanoparticles was characterized by various microscopic and spectroscopic methods. The results revealed that the spherical nanoparticles were capped with MUN on the surface through formation of Se-S bond. The in vitro protective effects of Se@MUN on HK-2 proximal tubular cells against cisplatin-induced nephrotoxicity and the underlying mechanisms were also investigated. Se@MUN exhibited free radical scavenging activity and higher cellular uptake in human normal cells by comparing with SeNPs. Se@MUN significantly attenuated cisplatin-induced reduction in cell viability, appearance of Sub-G1 peak, nuclear condensation and DNA fragmentation in HK-2 cells. Activation of caspase-3 in cells exposed to cisplatin was also effectively blocked by Se@MUN. Moreover, Se@MUN significantly prevented the cisplatin-induced overproduction of intracellular ROS. Our findings suggest that Se@MUN is a promising selenium species with potential application in prevention of cisplatin-induced renal injury.


Detection of ochratoxin A in tropical wine and grape juice from Brazil.
Ochratoxin A (OTA) is the main mycotoxin found in grapes, wines and grape juices and is considered one of the most harmful contaminants to human health. In this study, samples of tropical wines and grape juices from different grape varieties grown in Brazil were analysed for their OTA content by high-performance liquid chromatography. The detection and quantification limits for OTA were 0.01 and 0.03 µg L(-1) respectively. OTA was detected in 13 (38.24%) of the samples analysed, with concentrations ranging from < 0.03 to 0.62 µg L(-1). OTA was not detected in any of the grape juice samples. Most of the red wine samples proved to be contaminated with OTA (75%), while only one white wine sample was contaminated. However, the OTA levels detected in all samples were well below the maximum tolerable limit (2 µg L(-1)) in wine and grape juice established by the European Community and Brazilian legislature. The results of this study indicate a low risk of exposure to OTA by consumption of tropical wines and grape juices from Brazil.


Getting involved: the extent and impact of patient and public involvement in the Swedish health system.
Patient and public involvement (PPI) is framed as beneficial for individuals and for the health system. However, little is known about the extent of involvement, or of its impact. Based on data from Sweden, we show that apart from voting in regional elections (76%), more people reported involvement as individual patients (23%) than part of collective activities (5%) or activities relating to a citizen perspective (4%). There was no correlation between how many people participated and the estimated impact - which was generally low. More extensive involvement is thus not linked to the potential to influence decisions. We argue that to achieve the benefits associated with PPI it is crucial to understand more about people's motivation for being involved and what underlies low estimates of impact. This requires a more systematic approach to involvement, how it is evaluated and its results communicated to participants and the society. We also argue that a future challenge for the Swedish health system, and for other similar health systems, is to support long-term collective involvement in the midst of growing individualization of health services and involvement opportunities primarily intended for patients.


Detecting the Cognitive Prodrome of Dementia with Lewy Bodies: A Prospective Study of REM Sleep Behavior Disorder.
Long-term studies in REM sleep behavior disorder (RBD) have shown a high rate of conversion into synucleinopathies. We aimed to prospectively follow-up a large cohort of RBD patients to identify cognitive markers for early detection of prodromal dementia. Seventy-six idiopathic RBD patients underwent polysomnography and a complete neuropsychological and neurological assessment and were then followed for a mean of 3.6 years. Cognitive characteristics at baseline were compared between patients who remained disease-free and those who developed a synucleinopathy, and between those who developed dementia first and those who developed parkinsonism first. Receiver operating characteristic curves were calculated to assess the diagnostic value of cognitive tests for detecting prodromal dementia. At follow-up, 34 patients developed a neurodegenerative disease: 19 parkinsonism-first and 15 dementia-first. RBD patients who first developed dementia were impaired at baseline in all cognitive domains (attention/executive functions, learning/memory, and visuospatial) compared to patients who developed parkinsonism. Moreover, 93% of patients who first developed dementia had mild cognitive impairment at baseline compared to 42% of patients who developed parkinsonism. RBD patients who developed parkinsonism first were similar at baseline to disease-free RBD patients on cognition. In dementia-first patients, two cognitive tests assessing attention and executive functions (Stroop Color Word Test and Trail Making Test) reliably predicted dementia (area under the curve ≥0.85) compared to parkinsonism-first patients or controls. This study shows that cognitive tests assessing attention and executive functions strongly predict conversion to dementia in RBD patients, and may be useful endpoints to determine the effectiveness of interventions to prevent cognitive deterioration in RBD patients.


[Endocrine function of the heart. Structure and biological properties of peptides secreted by the heart atrium].
Apart from the generally known functions, the heart has also an endocrine function. Atrial cardiocytes, being typical secretory cells, release peptide hormones into the blood stream: atrial natriuretic peptide containing 28 amino acids and cardiodilatin. The structure of atrial peptides was determined. It was shown that both peptides were derived from their common precursor, a protein containing 151 amino acids. The presence of specific receptors is demonstrated on plasmatic membranes of cells of kidney epithelium, arterial smooth muscle, arterial endothelium, kidney cortex and hypophysis. The interaction of atrial peptides with these receptors activates the guanylate cyclase system. The biological action of atrial peptides manifests itself in the quick, massive and instantaneous increase of diuresis and electrolyte excretion, elevated clearance of creatinine, decrease of kidney vascular resistance, intensification of glomerular filtration, inhibition of stimulated secretion of aldosterone, relaxation of blood vessels, elimination of arterial and intestinal spasm induced by various endogenous and exogenous vasoconstrictors and in correction of kidney hypertension. Various radioimmunoassays for the presence of atrial peptides in human plasma were developed; it was shown that in patients with congestive heart failure the content of atrial peptides is increased.


Persisting consequences of stroke measured by the Stroke Impact Scale.
The purpose of this study was to compare disability and quality of life as measured by the Stroke Impact Scale (SIS) of stroke patients deemed recovered (Barthel Index > or =95) with 2 stroke-free populations of community-dwelling elderly. Eighty-one stroke patients who participated in the Kansas City Stroke Registry and achieved a Barthel Index of > or =95 at 3 months after stroke and 246 stroke-free subjects enrolled in the Community Elders Study were enrolled in this study. The Community Elders Study group was further divided into 2 groups, those recruited from the Department of Veterans Affairs Health System (VA) and a those from a local health maintenance organization (HMO). Stroke patients were administered the SIS approximately 90 days after stroke, and the stroke-free community dwellers were administered a version of the SIS adapted for nonstroke subjects, the Health Impact Scale (HIS). A general linear model was used to examine differences in health outcomes measured by the SIS or HIS between the KCSR stroke patients and VA and HMO community-dwelling elders after controlling for medical comorbidities and demographics. Kansas City Stroke Registry participants were significantly older than the community study groups (P=0.0052). Selected medical conditions were similar among the 3 study groups. Old age and a history of diabetes mellitus were more likely to be associated with more deficits and poor quality of life. In stroke patients deemed recovered, stroke still affected hand function, activities and independent activities of daily living, participation, and overall physical function compared with the stroke-free community dwellers in the HMO health system even after adjustment for age and diabetes status. Stroke-free community dwellers in the VA health system also had worse social participation than the stroke-free community dwellers in the HMO health system. Research and clinicians have consistently underestimated the impact of stroke with the Barthel Index. This has major implications for the design of therapeutic trial designs and adequate assessments of social and economic sequelae of stroke.


A framework for assessing continuing professional development activities for satisfying pharmacy revalidation requirements.
The United Kingdom's pharmacy regulator contemplated using continuing professional development (CPD) in pharmacy revalidation in 2009, simultaneously asking pharmacy professionals to demonstrate the value of their CPD by showing its relevance and impact. The idea of linking new CPD requirements with revalidation was yet to be explored. Our aim was to develop and validate a framework to guide pharmacy professionals to select CPD activities that are relevant to their work and to produce a score sheet that would make it possible to quantify the impact and relevance of CPD. We adapted an existing risk matrix, producing a CPD framework consisting of relevance and impact matrices. Concepts underpinning the framework were refined through feedback from 5 pharmacist teacher-practitioners. We then asked 7 pharmacists to rate the relevance of the framework's individual elements on a 4-point scale to determine content validity. We explored views about the framework through focus groups with 6 participants and interviews with 17 participants who had used it formally in a study. The framework's content validity index was 0.91. Feedback about the framework related to 3 themes of penetrability of the framework, usefulness to completion of CPD, and advancement of CPD records for the purpose of revalidation. The framework can help professionals better select CPD activities prospectively, and makes assessment of CPD more objective by allowing quantification, which could be helpful for revalidation. We believe the framework could potentially help other health professionals with better management of their CPD irrespective of their field of practice.


Dosimetry of N⁶-formyllysine adducts following [¹³C²H₂]-formaldehyde exposures in rats.
With formaldehyde as the major source of endogenous N⁶-formyllysine protein adducts, we quantified endogenous and exogenous N⁶-formyllysine in the nasal epithelium of rats exposed by inhalation to 0.7, 2, 5.8, and 9.1 ppm [¹³C²H₂]-formaldehyde using liquid chromatography-coupled tandem mass spectrometry. Exogenous N⁶-formyllysine was detected in the nasal epithelium, with concentration-dependent formation in total as well as fractionated (cytoplasmic, membrane, nuclear) proteins, but was not detected in the lung, liver, or bone marrow. Endogenous adducts dominated at all exposure conditions, with a 6 h 9.1 ppm formaldehyde exposure resulting in one-third of the total load of N⁶-formyllysine being derived from exogenous sources. The results parallel previous studies of formaldehyde-induced DNA adducts.


Palliative care in a tertiary neonatal intensive care unit: a 10-year review.
When active treatment is no longer in the best interests of the patient, redirection of care to palliation is an important transition. We review, within a tertiary neonatal intensive care unit (NICU), the journey leading to the decision to redirect care, the means of symptom control and the provision of psychosocial supports. A retrospective review of all 166 deaths of NICU-affiliated patients during a 10- year epoch. Medical notes were reviewed, and the provision and type of, or barriers to, effective palliative care was defined. Extreme prematurity accounted for 71/145 (49%) of deaths with relatively high proportions of Māori 17/71 (25%) and Pacific Islanders 9/71 (13%). Almost all eligible infants received some form of palliation. Transition from curative to palliative care was refused by the family in a single case. Median time from decision to redirect care until first recorded action was 80 min, and median time from action until death was 60 min. The majority of infants received some form of comfort cares, (128/166) most commonly morphine (94/128, 73%). Three infants had documented seizure activity or respiratory distress but did not receive any pharmacological intervention. Psychosocial supports were offered in 98/145 (67%) of cases, but only 71/145 (49%) of families were formally offered an opportunity to discuss the infant's clinical course after their death. Clinical documentation of care plans was often incomplete, potentially leading to inconsistent delivery of care, increased risk of symptom breakthrough and/or inadequate psychosocial supports for family. Formal individualised palliative care plans are under development to standardise documentation and improve therapeutic and psychosocial interventions available to the infant and their family.


Height to first pod: A review of genetic and breeding approaches to improve combine harvesting in legume crops.
Height from soil at the base of plant to the first pod (HFP) is an important trait for mechanical harvesting of legume crops. To minimise the loss of pods, the HFP must be higher than that of the blades of most combine harvesters. Here, we review the genetic control, morphology, and variability of HFP in legumes and attempt to unravel the diverse terminology for this trait in the literature. HFP is directly related to node number and internode length but through different mechanisms. The phenotypic diversity and heritability of HFP and their correlations with plant height are very high among studied legumes. Only a few publications describe a QTL analysis where candidate genes for HFP with confirmed gene expression have been mapped. They include major QTLs with eight candidate genes for HFP, which are involved in auxin transport and signal transduction in soybean [Glycine max (L.) Merr.] as well as MADS box gene SOC1 in Medicago trancatula, and BEBT or WD40 genes located nearby in the mapped QTL in common bean (Phaseolus vulgaris L.). There is no information available about simple and efficient markers associated with HFP, which can be used for marker-assisted selection for this trait in practical breeding, which is still required in the nearest future. To our best knowledge, this is the first review to focus on this significant challenge in legume-based cropping systems.


beta-Amyloid disrupts activity-dependent gene transcription required for memory through the CREB coactivator CRTC1.
Activity-dependent gene expression mediating changes of synaptic efficacy is important for memory storage, but the mechanisms underlying gene transcriptional changes in age-related memory disorders are poorly understood. In this study, we report that gene transcription mediated by the cAMP-response element binding protein (CREB)-regulated transcription coactivator CRTC1 is impaired in neurons and brain from an Alzheimer's disease (AD) transgenic mouse expressing the human beta-amyloid precursor protein (APP(Sw,Ind)). Suppression of CRTC1-dependent gene transcription by beta-amyloid (Abeta) in response to cAMP and Ca(2+) signals is mediated by reduced calcium influx and disruption of PP2B/calcineurin-dependent CRTC1 dephosphorylation at Ser151. Consistently, expression of CRTC1 or active CRTC1 S151A and calcineurin mutants reverse the deficits on CRTC1 transcriptional activity in APP(Sw,Ind) neurons. Inhibition of calcium influx by pharmacological blockade of L-type voltage-gated calcium channels (VGCCs), but not by blocking NMDA or AMPA receptors, mimics the decrease on CRTC1 transcriptional activity observed in APP(Sw,Ind) neurons, whereas agonists of L-type VGCCs reverse efficiently these deficits. Consistent with a role of CRTC1 on Abeta-induced synaptic and memory dysfunction, we demonstrate a selective reduction of CRTC1-dependent genes related to memory (Bdnf, c-fos, and Nr4a2) coinciding with hippocampal-dependent spatial memory deficits in APP(Sw,Ind) mice. These findings suggest that CRTC1 plays a key role in coupling synaptic activity to gene transcription required for hippocampal-dependent memory, and that Abeta could disrupt cognition by affecting CRTC1 function.


Mitochondrial complex II Is essential for gametophyte development in Arabidopsis.
Mitochondrial complex II (succinate dehydrogenase [SDH]) is part of the tricarboxylic acid cycle and the respiratory electron transport chain. Its flavoprotein subunit is encoded by two nuclear genes, SDH1-1 and SDH1-2, in Arabidopsis (Arabidopsis thaliana). The SDH1-2 gene is significantly expressed only in roots, albeit at very low level, and its disruption has no effect on growth and development of homozygous mutant plants. In contrast, SDH1-1 transcripts are ubiquitously expressed, with highest expression in flowers. Disruption of the SDH1-1 gene results in alterations in gametophyte development. Indeed, heterozygous SDH1-1/sdh1-1 mutant plants showed normal vegetative growth, yet a reduced seed set. In the progeny of selfed SDH1-1/sdh1-1 plants, distorted segregation ratios were observed, and no homozygous mutant plants were obtained. Reciprocal test crosses with the wild type demonstrated that the mutated sdh1-1 allele is not transmitted through the male gametophyte and is only partially transmitted through the female gametophyte. Consistently, microscopic analysis showed that mutant microspores develop normally until the vacuolated microspore stage, but fail to undergo mitosis I, and then cell structures are degraded and cell content disappears. On the other hand, half the mutant embryo sacs showed arrested development, either at the two-nucleate stage or before polar nuclei fusion. Down-regulation of SDH1-1 by RNA interference results in pollen abortion and a reduced seed set, as in the insertional mutant. Altogether, our results show that SDH1-1, and therefore complex II, are essential for gametophyte development.


Encapsulation of chia seed oil with curcumin and investigation of release behaivour & antioxidant properties of microcapsules during in vitro digestion studies.
In this study, it was aimed to investigate the effects of both using curcumin and microencapsulation method on in vitro release behaivour of chia seed oil and its antioxidant potential during simulated gastrointestinal (GI) tract. Maltodextrin (MD) and gum Arabic (GA) was used as wall materials for freeze dried capsules. Sample 6, having 1:3 MD to GA ratio, 1:5 chia seed oil to wall material ratio and 40% total dry matter content, was found to have the optimum results in terms of emulsion stability (CI% = 0), zeta potential (-32.2 ± 0.8 mV) and size distribution (600 ± 8 nm). Moreover, release profiles of encapsulated chia seed oil samples were evaluated to determine if curcumin addition has any significant effect. The results revealed that curcumin addition decreased the release of chia seed oil from 44.6% to 37.2%. On contrary, it increased total phenolic content of in fraction of intestine to 22 mg gallic acid equivalents (GAE)/L.


Substrate recognition and ATPase activity of the E. coli cysteine/cystine ABC transporter YecSC-FliY.
Sulfur is essential for biological processes such as amino acid biogenesis, iron-sulfur cluster formation, and redox homeostasis. To acquire sulfur-containing compounds from the environment, bacteria have evolved high-affinity uptake systems, predominant among which is the ABC transporter family. Theses membrane-embedded enzymes use the energy of ATP hydrolysis for transmembrane transport of a wide range of biomolecules against concentration gradients. Three distinct bacterial ABC import systems of sulfur-containing compounds have been identified, but the molecular details of their transport mechanism remain poorly characterized. Here we provide results from a biochemical analysis of the purified Escherichia coli YecSC-FliY cysteine/cystine import system. We found that the substrate-binding protein FliY binds l-cystine, l-cysteine, and d-cysteine with micromolar affinities. However, binding of the l- and d-enantiomers induced different conformational changes of FliY, where the l- enantiomer-substrate-binding protein complex interacted more efficiently with the YecSC transporter. YecSC had low basal ATPase activity that was moderately stimulated by apo FliY, more strongly by d-cysteine-bound FliY, and maximally by l-cysteine- or l-cystine-bound FliY. However, at high FliY concentrations, YecSC reached maximal ATPase rates independent of the presence or nature of the substrate. These results suggest that FliY exists in a conformational equilibrium between an open, unliganded form that does not bind to the YecSC transporter and closed, unliganded and closed, liganded forms that bind this transporter with variable affinities but equally stimulate its ATPase activity. These findings differ from previous observations for similar ABC transporters, highlighting the extent of mechanistic diversity in this large protein family.


Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl transferase inhibitor r115777 in human epithelial cancer cells.
Docetaxel (Taxotere, DTX) is a promoter of apoptosis in cancer cells. Since cytotoxic mechanisms of DTX are not yet fully understood, we have investigated the effects of DTX on apoptosis and ras-->Erk-mediated signal transduction in human epidermoid KB, colon HT-29 and breast HCC1937 cancer cells. We have found that the exposure to 0.78 or 1.56 or 2.5 ng/ml DTX for 48 h induced apoptosis and growth inhibition in about 50 % of KB, HCC1937 and HT-29 cell population, respectively. In these experimental conditions, PARP and caspase 3 cleavage was also showed in all cell lines. KB and HCC1937 cells express a wild type p53 while HT-29 display a mutated form. Interestingly, we have found that DTX reduces the expression of mutated p53 in HT-29 and increases the expression of wild type in KB and HCC1937 cells. Moreover, DTX reduces ubiquitination of the wild type p53 in KB and HCC1937 cells and increases the ubiquitin-conjugated form of mutated p53 in HT-29 cells. Furthermore, exposure of cancer cells to DTX for 48 h increases the expression and activity of Ras and up-regulates Raf-1 and the phosphorylated isoforms of Erk-1/2. On the bases of these data, we have hypothesized that the increased activity of the ras-->erk-dependent pathway induced by DTX could be a protective signalling from the apoptosis caused by the drug. Therefore, we have used R115777, a farnesyl transferase inhibitor that inactivates ras, in combination with DTX. The combined treatment with DTX and R115777 resulted in a strong synergism in growth inhibition in the three cell lines. These data suggest the use of the combination in these therapeutic settings even if further experiments are required for the clinical translation.


Engagement of lymphoma T cell receptors causes accelerated growth and the secretion of an NK cell-inhibitory factor.
The development of T cell lymphomas in mice that constitutively express a single T cell receptor is surveilled by the action of NK cells. We investigated the effects of engaging the lymphoma TCR in this mouse model. We stimulated lymphoma cells expressing an ovalbumin-specific TCR in vivo using listeria monocytogenes as a vehicle. Infections with listeria expressing ovalbumin but not with control bacteria caused a stable change in lymphoma cells that allowed its growth in mice with normal NK cells. TCR engagement furthermore enhanced lymphoma growth in NK-cell-depleted mice suggesting a lymphoma-intrinsic change that lead to accelerated growth. The ability to grow in mice without prior NK cell depletion did not appear to be accompanied by changes in the recognition of lymphoma by NK cells. Rather, lymphoma immunization was associated with a decrease in NK cell numbers: Leukemic phases were observed for all mice starting three to eight weeks after immunizations, and leukemias were succeeded by the disappearance of NK cells from blood. We also observed strong decreases of NK cell numbers in spleens at the time of death. Co-culture experiments showed decreases in the ability of NK cells to proliferate in response to IL-15 when post-immunization lymphoma cells were present in a mechanism that did not require direct cell contact. Together these data suggest that TCR engagement caused intrinsic changes in T cell lymphoma cells resulting in both accelerated in vivo growth and in the secretion of a factor that caused NK cell disappearance.


[19-year-old patient with adrenal cortex insufficiency--only the tip of the iceberg. Polyendocrine autoimmune syndrome type II (Schmidt syndrome)].
We report on a 19-year-old woman with polyglandular autoimmune syndrome type II (APS II). She was diagnosed with addison's disease and hypothyroidism due to chronic autoimmune thyroiditis. Her mother had celiac disease and her brohter had diabetes mellitus typ 1. Chronic autoimmune thyroiditis was diagnosed in her mother, subsequently. In patients and their relatives, who have autoimmune disorders, a search for autoimmune polyglandular syndrome is crucial. Consequently, it would be appropriate that the patient and all family members are asked for clinical signs and symptoms of autoimmune disorders. Annual measurement of morning cortisol, TSH and fasting plasma glucose may useful. Screening of affected individuals as well as their first-degree relatives for celiac disease is recommended. Therapy of APS II consists of hormone replacement therapy, but thyroxin replacement may induce life-threatening adrenal failure in a patient with untreated Addison's disease. Thus, in case of doubt hydrocortisone should be given before the thyroxine administration is started.


Lung involvement in childhood onset granulomatosis with polyangiitis.
Granulomatosis with polyangiitis is an ANCA-associated systemic vasculitis with a low incidence in the pediatric population. Lung involvement is a common manifestation in children affected by granulomatosis with polyangiitis, both at disease's onset and during flares. Its severity is variable, ranging from asymptomatic pulmonary lesions to dramatic life-threatening clinical presentations such as diffuse alveolar haemorrhage. Several radiologic findings have been described, but the most frequent abnormalities detected are nodular lesions and fixed infiltrates. Interstitial involvement, pleural disease and pulmonary embolism are less common. Histology may show necrotizing or granulomatous vasculitis of small arteries and veins of the lung, but since typical features may be patchy, the site for lung biopsy should be carefully chosen with the help of imaging techniques such as computed tomography. Bronchoalveolar lavage is helpful to confirm the diagnosis of alveolar haemorrhage. Pulmonary function tests are frequently altered, showing a reduction in the diffusion capacity for carbon monoxide, which can be associated with obstructive abnormalities related to airway stenosis. Nodular lung lesions tend to regress with immunosuppressive therapy, but lung disease may also require second line treatments such as plasmapheresis. In cases of massive diffuse alveolar haemorrhage, ventilator support is crucial in the management of the patient.


Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress.
Oxidative stress is an important inducer of cell apoptosis and plays a key role in the development of renal inflammation. The prostate apoptosis response factor-4 (Par-4) gene was originally identified in prostate cells undergoing apoptosis. Subsequently, Par-4 was found to possess potent pro-apoptotic activity in various cellular systems. However, it remains unclear whether Par-4 is involved in oxidant injury of renal tubular epithelial cells. To determine the role of Par-4 in renal proximal tubular cell apoptosis induced by oxidative stress. Par-4 gene expression was silenced by small interfering RNA. Renal proximal tubular cells were then exposed to hydrogen peroxide and the effect of Par-4 silencing on apoptosis and expression of phosphorylated Akt and vascular endothelial growth factor was determined. Hydrogen peroxide induced apoptosis and increased Par-4 expression in human renal proximal tubular epithelial cells. Par-4 silencing significantly protected renal proximal tubular cells from apoptosis via activating the PI3K/Akt signaling pathway as Akt phosphorylation was enhanced. Par-4 silencing also ameliorated the downregulation of vascular endothelial growth factor expression induced by oxidative stress. Par-4 gene silencing resulted in PI3K/Akt signaling-dependent inhibition of renal proximal tubular cell apoptosis following oxidative stress.


Mechanosensitive Piezo Channels in the Gastrointestinal Tract.
Sensation of mechanical forces is critical for normal function of the gastrointestinal (GI) tract and abnormalities in mechanosensation are linked to GI pathologies. In the GI tract there are several mechanosensitive cell types-epithelial enterochromaffin cells, intrinsic and extrinsic enteric neurons, smooth muscle cells and interstitial cells of Cajal. These cells use mechanosensitive ion channels that respond to mechanical forces by altering transmembrane ionic currents in a process called mechanoelectrical coupling. Several mechanosensitive ionic conductances have been identified in the mechanosensory GI cells, ranging from mechanosensitive voltage-gated sodium and calcium channels to the mechanogated ion channels, such as the two-pore domain potassium channels K2P (TREK-1) and nonselective cation channels from the transient receptor potential family. The recently discovered Piezo channels are increasingly recognized as significant contributors to cellular mechanosensitivity. Piezo1 and Piezo2 are nonselective cationic ion channels that are directly activated by mechanical forces and have well-defined biophysical and pharmacologic properties. The role of Piezo channels in the GI epithelium is currently under investigation and their role in the smooth muscle syncytium and enteric neurons is still not known. In this review, we outline the current state of knowledge on mechanosensitive ion channels in the GI tract, with a focus on the known and potential functions of the Piezo channels.


Expression of minichromosome maintenance 5 protein in proliferative and malignant skin diseases.
The entire minichromosome maintenance (MCM) family (MCM2-7) play roles in the initiation and elongation of DNA replication. Many studies have demonstrated that MCM proteins may be better indicators of a wide variety of proliferative or cancer cells in malignant tissues. To characterize the pattern and frequency of MCM5 expression in proliferative and malignant skin diseases in comparison with those of proliferating cell nuclear antigen (PCNA). Twelve normal skin specimens, 12 specimens of psoriasis, 21 specimens of bowenoid papulosis (BP), 16 specimens of Bowen's disease (BD), 38 specimens of skin squamous cell carcinoma (SCC), and 11 specimens of basal cell carcinoma (BCC) were subjected to immunohistochemical staining for MCM5 and PCNA. Results MCM5 protein was expressed in the lower layers of epidermis in psoriasis, while MCM5 protein were present throughout the tumor cells in BP, BD, and moderately/poorly differentiated SCC. MCM5 protein was preferentially expressed in the periphery of well-differentiated SCC or bigger nests of BCC, although some small nests of BCC seemingly showed diffuse staining patterns. The percentages of MCM5-positive cells were 15.7% in normal skin, 21.8% in psoriasis, 75.9% in BP, 83.8% in BD, 63.5% in well-differentiated SCC, 77.5% in moderately differentiated SCC, 79.8% in poorly differentiated SCC, and 21.2% in BCC in average. Well-differentiated SCC showed a significantly lower percentage of positive cells than did moderately differentiated SCC or poorly differentiated SCC. MCM5 staining basically show a similar staining pattern to that of PCNA, but more cells tended to be stained with MCM5 than with PCNA. Our results demonstrate pattern and frequency of MCM5 expression in various skin diseases and suggest that MCM5 may be a useful marker to detect cell proliferation in skin tissue sections.


Long-term evaluation of amantadine and levodopa combination in parkinsonism by double-blind corssover analyses.
Twenty-three patients with Parkinson's disease participated in long-term, double-blind evaluations of the effectiveness and side effects of amantadine in combination with levodopa therapy. Sixteen patients completed the year-long study, which consisted of randomized crossover of amantadine and placebo before levodopa was begun and again after 5 and 11 months of continuous levodopa therapy. Initially, 16 of 23 patients (70 percent) had a favorable response to amantadine during the first crossover period. After 1 year of levodopa, at least eight of 16 patients (50 percent) responded favorably to amantadine compared with placebo. Some of the amantadine responders previously had been nonresponders, and vice versa. The response to amantadine was quantitatively similar in the responders even after the patients had been receiving levodopa therapy. Amantadine should be tried as a therapeutic agent in addition to levodopa for parkinsonism if more beneficial effect is desired, even if amantadine was previously ineffective in the same patient.


[Epidemiologic behavior of malignant digestive tract tumors over a five year period in Veracruz, Mexico].
Tumors of the digestive system are considered to be a public health problem because of their elevated mortality rate. In Mexico, gastric cancer and colon cancer rank fourth and fifth, respectively, following tracheal, bronchial, and lung cancer, and there has been an increase in their frequency in the last few years. However, there are no specific studies that have evaluated their epidemiologic behavior in Veracruz. To determine the frequency of digestive system cancer in five health institutions in the city of Veracruz and to describe its epidemiologic behavior over a five-year period. Annual statistics from the following hospitals were reviewed: the Instituto Mexicano del Seguro Social, the Secretaría de Salud, the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Petróleos Mexicanos, and the Secretaría de la Defensa Nacional within the time frame of January 2005 to December 2009. Diagnoses based on histopathology were recorded, along with patient age and sex. A total of 1803 cases of digestive tract cancers were detected: 52% were men and 48% were women. A yearly increase in the number of cases was observed with colon cancer being in first place, followed by stomach cancer and rectal cancer. The increase in digestive system cancer cases over the last five years in Veracruz underlines the need to evaluate the implementation of screening programs for the at-risk population and to study the different etiologic factors involved in its manifestation.


Prevalence and associated factors of psychological distress among Korean cancer patients.
This study primarily aimed to investigate the prevalence and associated factors of psychological distress among Korean cancer patients. Its secondary objective was to classify mental illnesses among cancer patients with significant psychological distress. We administered the Modified Distress Thermometer (MDT), Hospital Anxiety and Depression Scale (HADS), and Center for Epidemiologic Studies-Depression Scale (CES-D) to consecutive, newly diagnosed cancer patients and conducted subsequent psychiatric interviews. A multiple logistic regression produced a discriminate profile of individuals with psychological distress. Among 295 participants, 85 (28.8%) were identified as patients with psychological distress. Female gender [odds ratio (OR)=1.97], low educational level (OR=2.25) and low performance status (OR=4.10) were significantly associated with this condition. Among the 38 patients with psychological distress who received psychiatric assessment, the most common mental illness was adjustment disorder (n=23, 69.7%). The results of this study showed that approximately one-third of the cancer patients suffered from psychological distress. We recommend that physicians focus on the psychological status of female cancer patients with low levels of education and poor performance status.


Possible effects of antibiotic treatment on the senstivity and growth requirements of Neisseria gonorrhoea.
The decreased sensitivity to penicillin of Neisseria gonorrhoeae has been a cause of concern during recent years. About 25% of strains sent in for routine diagnosis to the Statens Seruminstitut in 1957 were found to require roughly 20 times as much penicillin to inhibit development completely as was required for strains isolated in 1944. The stability of this reduced sensitivity to penicillin was studied in 20 strains which were subcultured daily on medium without penicillin. A comparison was also made between the sensitivity levels to penicillin and streptomycin for 1957 and 1958. A phenomenon possibly resulting from penicillin therapy of gonorrhoea was noted by the authors in June 1957, when they recorded the appearance of atypical strains having special growth requirements, low viability and weak or absent glucose-fermentation. The incidence, serology and sensitivity to antibiotics of these atypical strains were examined; further research on their different behaviour in response to changes in medium, as compared with that of typical strains, may give rise to some interesting findings.


Prevalence of leptospira in acute hepatitis syndrome and assessment of IL-8 and TNF-alpha level in leptospiral hepatitis.
To study the prevalence of leptospira in acute hepatitis syndrome and to assess interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha levels in the pathogenesis of hepatitis due to leptospiral infection. Two hundred and forty-seven consecutive cases with symptoms of acute hepatitis and 30 healthy controls were enrolled in the study and detailed clinical history was elicited from them. Enzyme-linked immunosorbent assays (ELISAs) for HAV, HBV, HCV and HEV were performed to rule out common viral aetiology of hepatitis. IgM antibodies to leptospira were detected by ELISA. IL-8 and TNF-alpha levels were estimated in leptospira-positive cases and healthy controls by ELISA. Out of 247 cases of acute hepatitis, 46 (18.62%) were observed to be positive for IgM antibodies for leptospira. The mean age of these patients was 31.99 ± 0.28 years (25 males and 21 females; M/F ratio: 1.19:1). The mean ALT, AST and ASP were raised in the majority of patients. IL-8 was found to be elevated (130.81 pg/ml) in a large majority of cases 41/46, 89.1% (P < 0.001). Patients with more severe symptoms were associated with higher levels of IL-8. One mortality was observed due to leptospira. Unpredictably, TNF-alpha level was largely suppressed (45.63 pg/ml) in most of the leptospira-positive patients in comparison with healthy controls. Leptospira-induced hepatitis should be actively looked for in patients negative for A-E viral hepatitis. IL-8 appears to play an important role in the pathogenesis of leptospiral hepatitis. High TNF-alpha should alert clinicians for aggressive in hospital management of patients.


Soy isoflavone analysis: quality control and a new internal standard.
Development of a database of the soy isoflavone content of foods requires accurate and precise evaluation of different food matrixes. To evaluate accuracy, we estimated recoveries of both internal and external standards in 5 different soyfoods weekly. Standards were evaluated daily for system quality assurance. To evaluate sample precision, we analyzed soybeans and soymilk bimonthly for within-day precision and over 4 d for day-to-day precision. CVs should be < or = 8%. We validated our methods for single and multiple recovery concentrations by using our new internal standard, 2,4,4'-trihydroxydeoxybenzoin, and the external standards daidzein, genistein, and genistin. Concentrations of 12 isoflavone isomers, 3 aglycones (daidzein, genistein, and glycitein), and 9 glucosides (daidzin, genistin, glycitin, acetyldaidzin, acetylgenistin, acetylglycitin, malonyldaidzin, malonylgenistin, and malonylglycitin) were measured in a variety of soybeans and soyfoods. The extraction methods used depended on soyfood type. The HPLC conditions for soy isoflavone analysis were improved, leading to good separation with a short analysis time (60 min/sample). A data bank of concentration and distribution of isoflavones in different soybean products was assembled. A wide range of isoflavone concentrations, from < 50 microg/g to > 20,000 microg/g, was found in different soy products. The glucoside forms are almost twice the molecular weight of the aglycones; reported isoflavone concentrations should be normalized to the aglycone mass (or an isoflavonoid equivalent) rather than a simple sum of all isomers.


Postnatal neurogenesis in the vasopressin and oxytocin-containing nucleus of the pig hypothalamus.
The vasopressin and oxytocin-containing nucleus (VON) of the pig hypothalamus demonstrates dramatic postnatal growth in nucleus size, both volume and neuron number, during puberty, and continues to increase in size in the adult sexually mature female pig throughout its reproductive prime. This study was designed to show that postnatal neurogenesis is responsible for the VON growth that occurs between adolescence and maturity. Recently divided neurosecretory cells of the hypothalamus were identified in adolescent and mature non-lactating female pigs using a sequential immunohistochemistry double-labeling technique with monoclonal mouse antibodies to detect vasopressin and proliferating cell nuclear antigen (PCNA), a protein associated with the S phase of the cell cycle. A computer-assisted image-analysis system was used to assess nucleus volume and neuron counts. The VON of the mature dry sows was significantly larger in volume and number of vasopressin neurons than the VON of the adolescent pigs. Double-labeled cells were noted in the VON of both adolescent and mature dry sows, but the number and proportion of double-labeled cells was significantly higher in adolescent pigs. Our results indicate the presence of neurons containing PCNA in the VON of the pig hypothalamus. This suggests that mitosis of neurogenic precursors plays a role in the growth of the nucleus.


Is Depression an Inflammatory Disease? Findings from a Cross-Sectional Study at a Tertiary Care Center.
Evidence linking inflammation and depression is marred by several methodological inconsistencies. Further, varying information is present on the role of gender as a potential confounder in this association. To assess systemic inflammation in drug naοve depression by measuring selected pro-inflammatory (tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6]) and anti-inflammatory cytokines (transforming growth factor-beta [TGF-β]) and comparing them with a matched control group. We also aimed at exploring the differences in these markers between genders. The study was a cross-sectional one carried out a teaching cum Tertiary Care Hospital. We recruited 55 drug naοve cases diagnosed with major depression and compared them for inflammatory markers with a matched apparently healthy control group (n = 42) at baseline. The inflammatory markers were also compared between the genders. Baseline depression and stress levels were assessed using standard measures. Mann-Whitney U-test. In comparison with healthy controls, drug naοve depressed individuals demonstrated significantly raised baseline levels of TNF-α and IL-6 (P < 0.001 for both) but no difference in levels of TGF-β (P = 0.433). Neither the baseline depression nor the stress scores correlated with any of the inflammatory markers (P = 0.955 and 0.816 for TNF-α respectively). Males and females were comparable on the levels of markers studied (P = 0.986, 0.415, and 0.430 for TNF-α, IL-6 and TGF-β respectively). There is evidence for higher baseline inflammation in depression prior to starting anti-depressant therapy. Gender does not mediate this observed link between inflammation and depression.


Analysis of mesiodistal angulations of preadjusted brackets.
Manufacturers offer various prescriptions of preadjusted brackets for use in the "straight-wire" orthodontic technique. However, the need to incorporate bends in the rectangular wires during orthodontic finishing has led to concerns regarding the type of prescription chosen and the credibility of information provided by the manufacturer. The aim of this study was to compare the slot angulations of Roth prescription preadjusted metallic brackets for the maxillary left central incisor and maxillary left canine. For each tooth type, 10 brackets of three commercial brands (GAC, Forestadent and Morelli) were selected. Two individual metal matrices for brackets and tooth positioning were made for each group of teeth. Captured images were obtained by standardized ortho-radial photography with a digital camera. Images were exported and analyzed with the Image J software package. One-way ANOVA and Tukey statistical analyses were performed at the 5% significance level. For brackets of the maxillary left central incisor, differences in mean angulation were observed between the Morelli and GAC groups (p < 0.01) and between the Forestadent and GAC groups (p < 0.01). For brackets of the maxillary left canine, differences in mean angulation were found between the Morelli and GAC groups (p < 0.01) and between the Morelli and Forestadent groups (p < 0.05). In conclusion, despite their same prescription name, the different brands exhibited significantly different angulation measurements.


Evaluation of performance of predictive models for deoxynivalenol in wheat.
The aim of this study was to evaluate the performance of two predictive models for deoxynivalenol contamination of wheat at harvest in the Netherlands, including the use of weather forecast data and external model validation. Data were collected in a different year and from different wheat fields than data used for model development. The two models were run for six preset scenarios, varying in the period for which weather forecast data were used, from zero-day (historical data only) to a 13-day period around wheat flowering. Model predictions using forecast weather data were compared to those using historical data. Furthermore, model predictions using historical weather data were evaluated against observed deoxynivalenol contamination of the wheat fields. Results showed that the use of weather forecast data rather than observed data only slightly influenced model predictions. The percent of correct model predictions, given a threshold of 1,250 μg/kg (legal limit in European Union), was about 95% for the two models. However, only three samples had a deoxynivalenol concentration above this threshold, and the models were not able to predict these samples correctly. It was concluded that two- week weather forecast data can reliable be used in descriptive models for deoxynivalenol contamination of wheat, resulting in more timely model predictions. The two models are able to predict lower deoxynivalenol contamination correctly, but model performance in situations with high deoxynivalenol contamination needs to be further validated. This will need years with conducive environmental conditions for deoxynivalenol contamination of wheat.


Short-term change of handgrip strength after trigger point injection in women with muscular pain in the upper extremities.
To determine overall handgrip strength (HGS), we assessed the short-term change of HGS after trigger point injection (TPI) in women with muscular pain in the upper extremities by comparison with established pain scales. The study enrolled 50 female patients (FMS with MPS group: 29 patients with combined fibromyalgia [FMS] and myofascial pain syndrome [MPS]; MPS group: 21 patients with MPS) who presented with muscular pain in the upper extremities at Konyang University Hospital. In addition, a total of 9 healthy women (control group) were prospectively enrolled in the study. We surveyed the three groups using the following established pain scales: the Fibromyalgia Impact Questionnaire (FIQ), the 36-Item Short Form Health Survey (SF-36), and the Short Form McGill Pain Questionnaire (MPQ). HGS was measured in both hands of study participants using a handgrip dynamometer. We performed TPI (0.5% lidocaine, total 10 mL, injected at the pain site of upper extremities). After 20 minutes, we remeasured the patient's HGS and MPQ score. ANOVA analysis was conducted among groups. Based on Tukey multiple comparison test, the majority of FIQ and SF-36 subscales, total FIQ and SF-36 scores, MPQ and HGS were significantly different between FMS with MPS and the other groups. There was no statistically significant difference between MPS and control groups. Higher HGS was positively associated with enhanced physical function, negatively associated with total FIQ and MPQ scores, and positively associated with the total SF-36 score calculated using Spearman correlation. Post-TPI MPQ decreased and HGS increased. In patient groups, a negative correlation was found between MPQ and HGS. The HGS test might potentially be a complementary tool in assessing the short-term treatment effects of women with muscular pain in the upper extremities.


Sodium-dependent glucose transporter-1 as a novel immunological player in the intestinal mucosa.
In this study, we demonstrate the protective effect of the activation of sodium-dependent glucose transporter-1 (SGLT-1) on damages induced by TLR ligands, in intestinal epithelial cells and in a murine model of septic shock. In intestinal epithelial cell lines, glucose inhibited the IL-8/keratinocyte-derived chemokine production and the activation of the TLR-related transcription factor NF-kappaB stimulated by LPS or CpG-oligodeoxynucleotide. Oral ingestion of glucose was found to protect 100% of mice from lethal endotoxic shock induced by i.p. LPS administration; protection was only observed when glucose was administered orally, not by i.p. route, suggesting the important role of intestinal epithelial cells in this protection. In addition, we observed that the in vivo protection depends on an increase of anti-inflammatory cytokine IL-10. The cornerstone of the observed immunomodulatory and life-saving effects resides in activation of SGLT-1; in fact, the glucose analog 3-O-methyl-d-gluco-pyranose, which induces the transporter activity, but is not metabolized, exerted the same inhibitory effects as glucose both in vitro and in vivo. Thus, we propose that activated SGLT-1, apart from its classical metabolic function, may be a promising target for inhibition of bacteria-induced inflammatory processes and life-saving treatments, assuming a novel role as an immunological player.


A National Surveillance Survey on Noncommunicable Disease Risk Factors: Suriname Health Study Protocol.
Noncommunicable diseases (NCDs) are the leading cause of death in low- and middle-income countries. Therefore, the surveillance of risk factors has become an issue of major importance for planning and implementation of preventive measures. Unfortunately, in these countries data on NCDs and their risk factors are limited. This also prevails in Suriname, a middle-income country of the Caribbean, with a multiethnic/multicultural population living in diverse residential areas. For these reasons, "The Suriname Health Study" was designed. The main objective of this study is to estimate the prevalence of NCD risk factors, including metabolic syndrome, hypertension, and diabetes in Suriname. Differences between specific age groups, sexes, ethnic groups, and geographical areas will be emphasized. In addition, risk groups will be identified and targeted actions will be designed and evaluated. In this study, several methodologies were combined. A stratified multistage cluster sample was used to select the participants of 6 ethnic groups (Hindustani, Creole, Javanese, Maroon, Chinese, Amerindians, and mixed) divided into 5 age groups (between 15 and 65 years) who live in urban/rural areas or the hinterland. A standardized World Health Organization STEPwise approach to surveillance questionnaire was adapted and used to obtain information about demographic characteristics, lifestyle, and risk factors. Physical examinations were performed to measure blood pressure, height, weight, and waist circumference. Biochemical analysis of collected blood samples evaluated the levels of glucose, high-density-lipoprotein cholesterol, total cholesterol, and triglycerides. Statistical analysis will be used to identify the burden of modifiable and unmodifiable risk factors in the aforementioned subgroups. Subsequently, tailor-made interventions will be prepared and their effects will be evaluated. The data as collected allow for national inference and valid analysis of the age, sex, and ethnicity subgroups in the Surinamese population. A publication of the basic survey results is anticipated in mid-2015. Secondary results on the effect of targeted lifestyle interventions are anticipated in late 2017. Using the data collected in this study, the national prevalence of NCD risk factors will be approximated and described in a diverse population. This study is an entry point for formulating the structure of NCD prevention and surveillance.


Polytenization of the ribosomal genes on the X and Y chromosomes of Drosophila melanogaster.
It has previously been shown (Endow and Glover 1979), that polytenization of the ribosomal genes in D. melanogaster Ore-R X/Y cells and in hybrid X/X cells (Endow 1980) involves replication of genes predominantly from one of the cell's two nucleolus organizers. This analysis takes advantage of strain-specific differences in X and Y chromosome rDNA hybridization patterns detected using the Southern blotting technique. In this report, I extend the previous observations by examining polytene rDNA patterns in wild-type and hybrid X/Y cells. A dominance hierarchy for the X and Y chromosomes from three strains of D. melanogaster is presented and possible mechanisms of replicative dominance are discussed.


Assembly and activation of the phagocyte NADPH oxidase. Specific interaction of the N-terminal Src homology 3 domain of p47phox with p22phox is required for activation of the NADPH oxidase.
The phagocyte NADPH oxidase is activated during phagocytosis to produce superoxide, a precursor of microbicidal oxidants. The activation involves assembly of membrane-integrated cytochrome b558 comprising gp91(phox) and p22(phox), two specialized cytosolic proteins (p47(phox) and p67(phox)), each containing two Src homology 3 (SH3) domains, and the small G protein Rac. In the present study, we show that the N-terminal SH3 domain of p47(phox) binds to the C-terminal cytoplasmic tail of p22(phox) with high affinity (KD = 0.34 microM). The binding is specific to this domain among several SH3 domains including the C-terminal one of p47(phox) and the two of p67(phox) and requires the Pro156-containing proline-rich sequence but not other putative SH3 domain-binding sites of p22(phox). Replacement of Trp193 by Arg in the N-terminal SH3 domain completely abrogates the association with p22(phox). A mutant p47(phox) with this substitution is incapable of supporting superoxide production under cell-free activation conditions. These findings provide direct evidence that the interaction between the N-terminal SH3 domain of p47(phox) and the proline-rich region of p22(phox) is essential for activation of the NADPH oxidase.


[Dependence of the degree of antibacterial and antiphage action of ozone on cell and phage particle concentrations in nutrient media].
The work was aimed at studying the inactivating effect of ozone on Escherichia coli K-12 AB1157, Pseudomonas aeruginosa PA01, Erwinia herbicola EH103 and their phages T4, SM and I4. The degree of bacterial and phage inactivation was found to increase with a decrease in their initial concentration during the treatment. The effect depends on differences in the quantity of ozone per cell or per phage particle in the reaction medium. This conclusion is based on the fact that, irrespective of the suspension density, the amount of surviving bacteria and phages plotted versus O3 concentration and recalculated per one bacterial cell or phage particle is described graphically by one and the same curve typical of a strain under study. This technique for assessing the sensitivity of microbiological objects to ozone can be used in order to compare experimental data obtained in different laboratories.


A sensitive kinetic latex agglutination immunoassay adapted to centrifugal analysis.
Latex reagents for HCG obtained from commercially available pregnancy test kits were adapted for use on Instrumentation Laboratory's Multistat III Plus centrifugal analyzer. The clearance rate of an agglutinating reaction mixture can be measured by absorbance over a time period of 15 min. The automated system has a sensitivity of less than 5 mIU HCG/ml in buffer or urine with a range of up to 100 mIU HCG/ml. Statistical analyses on urine samples indicated CVs of between 7.6% and 10.7% for within-run precision and between 6.8% and 10.8% for between-run precision. The correlation between the centrifugal latex agglutination method and two commercially available RIAs was found to be about 87%.


Measuring functional status in chronic lung disease: conclusions from a randomized control trial.
The optimal method of assessing the effect of treatment on the day-to-day function of patients with chronic airflow limitation has not yet been established. Therefore, we examined the performance of the 6-min walk test, a rating of dyspnea following the walk test, and three different questionnaires measuring dyspnea in daily activities, in a controlled trial of inhaled salbutamol and oral theophylline in 24 patients with primary fixed chronic airflow limitation. Clinically important and statistically significant effects of salbutamol and theophylline on dyspnea during the day-to-day activities were detected by each measure, but the Chronic Respiratory Questionnaire (CRQ) was more powerful than the other questionnaires, either the Oxygen Cost Diagram or the Medical Research Council Dyspnea Questionnaire as modified by the Rand Corporation. Changes in the CRQ dyspnea score showed a higher correlation with changes in spirometry, walk test score, dyspnea following the walk test, and global ratings of dyspnea than did the other two measures. We conclude that the CRQ is a responsive, valid measure of functional status for clinical trials in chronic lung disease.


[The role of NGF and BDNF in mature brain activity regulation].
Neurotrophins are associated with the maintenance of optimal functional state of CNS neurons and modulation of synaptic plasticity for more than 20 years. However, integral and noncontradictory hypotheses of their true role in those processes were proposed only recently. This review describes the modern concepts of the involvement of nerve growth factor and brain-derived neurotrophic factor in the maintenance of brain activity and the prospects for their use in therapy.


Design of a Bioinert Interface Using an Amphiphilic Block Copolymer Containing a Bottlebrush Unit of Oligo(oxazoline).
We designed an amphiphilic block copolymer, poly(methyl methacrylate)-block-poly[oligo(2-ethyl-2-oxazoline) methacrylate] (PMMA-b-P[O(Ox)MA]), suitable for bioinert coating. Angular-dependent X-ray photoelectron spectroscopy and neutron reflectivity measurements revealed that the outermost surface of a dried film of PMMA-b-P[O(Ox)MA] was covered with the PMMA block-rich layer. Once the film came into contact with water, the P[O(Ox)MA] bottlebrush block was segregated toward the water interface. This structural rearrangement in the outermost region of the film resulted in the formation of the swollen oligo(oxazoline) layer with excellent bioinertness in terms of the suppression of serum protein adsorption and NIH3T3 fibroblast adhesion.


Chemical Potential Differences in the Macroscopic Limit from Fluctuations in Small Systems.
We present a new method for computing chemical potential differences of macroscopic systems by sampling fluctuations in small systems. The small system method, presented by Schnell et al. [Schnell et al., J. Phys. Chem. B, 2011, 115, 10911], is used to create small embedded systems from molecular dynamics simulations, in which fluctuations of the number of particles are sampled. The sampled fluctuations represent the Boltzmann distributed probability of the number of particles. The overlapping region of two such distributions, sampled from two different systems, is used to compute their chemical potential difference. Since the thermodynamics of small systems is known to deviate from the classical thermodynamic description, the particle distributions will deviate from the macroscopic behavior as well. We show how this can be utilized to calculate the size dependence of chemical potential differences and eventually extract the chemical potential difference in the thermodynamic limit. The macroscopic chemical potential difference is determined with a relative error of 3% in systems containing particles that interact through the truncated and shifted Lennard-Jones potential. In addition to computing chemical potential differences in the macroscopic limit directly from molecular dynamics simulation, the new method provides insights into the size dependency that is introduced to intensive properties in small systems.


Countering imbalanced datasets to improve adverse drug event predictive models in labor and delivery.
The IOM report, Preventing Medication Errors, emphasizes the overall lack of knowledge of the incidence of adverse drug events (ADE). Operating rooms, emergency departments and intensive care units are known to have a higher incidence of ADE. Labor and delivery (L&D) is an emergency care unit that could have an increased risk of ADE, where reported rates remain low and under-reporting is suspected. Risk factor identification with electronic pattern recognition techniques could improve ADE detection rates. The objective of the present study is to apply Synthetic Minority Over Sampling Technique (SMOTE) as an enhanced sampling method in a sparse dataset to generate prediction models to identify ADE in women admitted for labor and delivery based on patient risk factors and comorbidities. By creating synthetic cases with the SMOTE algorithm and using a 10-fold cross-validation technique, we demonstrated improved performance of the Naïve Bayes and the decision tree algorithms. The true positive rate (TPR) of 0.32 in the raw dataset increased to 0.67 in the 800% over-sampled dataset. Enhanced performance from classification algorithms can be attained with the use of synthetic minority class oversampling techniques in sparse clinical datasets. Predictive models created in this manner can be used to develop evidence based ADE monitoring systems.