[A potential for prevention of bicycling-related head injuries].
Bicycle helmets prevent head injury in bicycle riders. Still, only a portion of bicycle riders in Norway use bicycle helmets. The aim of this study was to estimate the number of head injuries among bicycle riders that might be prevented by increased helmet use in Norway. We used data from the Norwegian National Injury Register for the years 1995 and 1996 to estimate the number of bicycle injuries in Norway. In order to estimate the number of bicycle users and helmet users in different age groups, we used data from earlier surveys of bicycle use. Data on the effectiveness of helmet promotion interventions have been obtained from a systematic review of the literature. The overall annual incidence rate was 92 injuries per 100,000 bicycle users. The incidence varied with age and was highest among children. If every rider used a helmet, about 1,600 head injuries would be avoided every year, of these, 800 among children aged 0-14. Currently available helmet promotion interventions may improve the use among children by about 40%, thus preventing about 1,500 head injuries over a period of three years. Successful helmet promotion interventions use a combination of health education and helmet distribution strategies. There is a significant health improvement potential in promoting bicycle helmets in Norway by implementation of evaluated modes of intervention.


Clonidine and a novel clonidine analog AL-12 cause sympathoinhibition in spontaneously hypertensive and diabetic spontaneously hypertensive rats.
This study examined the sympathoinhibitory effects of clonidine and a novel clonidine analog, AL-12, in rat models of genetic hypertension and a combined state of genetic hypertension and diabetes. Rats in the treatment groups were given either clonidine or AL-12 while the respective control groups received either saline or Tween 80 for 6 days. Physiological data were collected during this period, which was followed by acute studies on day 7 when bolus administrations (i.v.) of graded doses of noradrenaline, phenylephrine and methoxamine were carried out. It was observed that in AL-12-treated nondiabetic spontaneously hypertensive rats (SHR), the pressure responses to all adrenergic agonists were greater (p < 0.05) in the treated group, while in the diabetic SHR rats a larger pressure response was observed only to noradrenaline (p < 0.05). In nondiabetic SHR rats treated with clonidine, a greater (p < 0.05) pressure response was observed only in the case of phenylephrine. In the diabetic SHR rats treated with clonidine, the pressure responses to the adrenergic agonists were similar (p > 0.05) in the treated and its control animals except that methoxamine caused a greater (p < 0.05) pressure response in the control group. The data obtained suggest that clonidine and AL-12 act possibly via vascular alpha1 and alpha2 adrenoceptors present at both pre- and postsynaptic locations.


Cortical pain processing in migraine.
Among painful disorders, migraine is distinguishable by its chronic pathology and episodic clinical manifestation. Only a small percentage of patients with migraine progress to a chronic form of migraine. Both peripheral and central portions of the trigeminal system are involved in the pathophysiology of migraine pain, as they are involved in the processes of peripheral and central sensitization, alongside various subcortical and cortical brain structures. This review focuses on clinical, neurophysiological, and neuroimaging data underscoring cortical pain processing in migraine. Data obtained from quantitative sensory testings are inconclusive and support the involvement of the peripheral portion of the trigeminovascular system as indirect evidence of peripheral sensitization, solely during the headache phase. The assessment of subjective pain intensity in response to several painful modalities has not been conclusive for the clear state of central sensitization in between migraine attacks but for the subclinical allodynia state that defines the boundary between behavioural responses and an irritable nervous state. Modulation of the brainstem and midbrain pain pathways, in conjunction with the thalamic and thalamocortical pathways, may be critical for the initiation and maintenance of migraine attacks. Several studies using different neuroimaging techniques have demonstrated that brains experiencing migraine undergo plastic changes in both microstructure and macrostructure and in the functioning of cortical networks, which may manifest early in the life of a patient with migraine. Further studies are required to understand how specific these results are to migraine relative to other painful disorders.


The Diabetes Health Coaching Randomized Controlled Trial: Rationale, Design and Baseline Characteristics of Adults Living With Type 2 Diabetes.
The Diabetes Health Coaching Trial was a single-blind, randomized controlled trial designed to evaluate the effect of a 1-year telephone-based diabetes health-coaching intervention for community-dwelling adults living with type 2 diabetes mellitus. It concerned glycated hemoglobin levels, self-care behaviours and cost-effectiveness. The purpose of this article is to describe the rationale, design and participants' characteristics. The eligibility criteria were: 1) adults ≥18 years of age; 2) a diagnosis of type 2 diabetes; 3) glycated hemoglobin levels of ≥7.5% 6 months before randomization; 4) the ability to read, write and understand English; and 5) having telephone access. Participants were randomized to either usual diabetes education or diabetes education plus diabetes health coaching. From May 2016 to December 2017, 365 participants were randomized into the trial. At baseline, the mean age was 57.9 (11.78) years, the mean duration of diabetes was 8.69 (8.54) years, the mean glycated hemoglobin level was 8.98 (1.58) %, and the mean body mass index was 35.03 (8.07) kg/m2. The baseline characteristics of the participants were equally distributed across the intervention and control groups. The Diabetes Health Coaching Trial is in a position to evaluate a potential treatment alternative and approach for type 2 diabetes and examined the effect of the intervention on clinical outcomes, self-care behaviours and cost-effectiveness.


Formation of singlet oxygen by urocanic acid by UVA irradiation and some consequences thereof.
Singlet oxygen-initiated decomposition of urocanic acid (UCA) (3-(1H-imidazol-4(5)-yl)-2-propenoic acid) was used to successfully confirm the report that UCA generates singlet oxygen when irradiated with ultraviolet A light (UVA). The UCA-generated singlet oxygen converts UCA to one or more products that then catalyze the further destruction of the UCA with UVA light by singlet oxygen formation. Some nicking of the phiX-174 supercoiled plasmid DNA was observed when UCA was irradiated with UVA to complete destruction of the starting material, and the product mixture was then mixed with the plasmid in the dark. More extensive nicking was seen when the photoproduct mixture and the plasmid were irradiated with UVA light. An "aged" (4 days) solution of UCA photoproduct no longer caused nicking in the dark but retained the capability to nick the plasmid when irradiated. There is evidence for the presence of hydroperoxides in the UCA photolysis product mixture, and the quenching studies with 2-propanol indicate that free radicals are involved in the plasmid-nicking photochemistry. Singlet oxygen does not appear to play a role in the nicking of the plasmid.


Managing an academic career.
Current predicaments that academic educators deal with, that is, the conflicts between teaching and research responsibilities, the competition within universities for promotion and tenure, and the importance of viewing the university as a complex social-political system are addressed. Recommendations for improvements in the development and education of new faculty members and suggestions for evaluative criteria for the documentation of a faculty member's performance are offered.


Palliative therapy of upper gastrointestinal malignancies using the Nd-YAG laser.
The principal role of the Neodymium yttrium aluminum garnet (Nd-YAG) laser has been to alleviate obstruction and to arrest hemorrhage secondary to metastatic or locally unresectable malignant lesions throughout the gastrointestinal (GI) tract. Between June 1985 and December 1988, 26 patients have been treated for advanced upper GI malignancy: 20 obstructing esophageal carcinomas (three proximal, eight middle, and nine distal third); two prepyloric obstructing and one bleeding gastric lesion; one bleeding pancreatic carcinoma eroding into the duodenum; and two primary duodenal lesions (one partially obstructing and one bleeding). The dysphagia grade improved in all patients with esophageal carcinoma, but less so for those with proximal tumors. The obstructing gastric lesions were recanalized and bleeding was arrested. The pancreatic and duodenal lesions were successfully managed with one treatment. There were no perforations or other laser-related complications. The approaches to palliation must be conceived in a fashion to improve the quality of life with minimal risk and discomfort. Although ultimate survival is determined by the stage of the disease, the Nd:YAG laser can restore gastrointestinal continuity and, in so doing, significantly palliate the patient.


Insights into the Mechanism of Installation of 5-Carboxymethylaminomethyl Uridine Hypermodification by tRNA-Modifying Enzymes MnmE and MnmG.
The evolutionarily conserved bacterial proteins MnmE and MnmG (and their homologues in Eukarya) install a 5-carboxymethylaminomethyl (cmnm5) or a 5-taurinomethyl (τm5) group onto wobble uridines of several tRNA species. The Escherichia coli MnmE binds guanosine-5'-triphosphate (GTP) and methylenetetrahydrofolate (CH2THF), while MnmG binds flavin adenine dinucleotide (FAD) and a reduced nicotinamide adenine dinucleotide (NADH). Together with glycine, MnmEG catalyzes the installation of cmnm5 in a reaction that also requires hydrolysis of GTP. In this letter, we investigated key steps of the MnmEG reaction using a combination of biochemical techniques. We show multiple lines of evidence supporting flavin-iminium FADH[N5═CH2]+ as a central intermediate in the MnmEG reaction. Using a synthetic FADH[N5═CD2]+ analogue, the intermediacy of the FAD in the transfer of the methylene group from CH2THF to the C5 position of U34 was unambiguously demonstrated. Further, MnmEG reactions containing the deuterated flavin-iminium intermediate and alternate nucleophiles such as taurine and ammonia also led to the formation of the anticipated U34-modified tRNAs, showing FAD[N5═CH2]+ as the universal intermediate for all MnmEG homologues. Additionally, an RNA-protein complex stable to urea-denaturing polyacrylamide gel electrophoresis was identified. Studies involving a series of nuclease (RNase T1) and protease (trypsin) digestions along with reverse transcription experiments suggest that the complex may be noncovalent. While the conserved MnmG cysteine C47 and C277 mutant variants were shown to reduce FAD, they were unable to promote the modified tRNA formation. Overall, this study provides critical insights into the biochemical mechanism underlying tRNA modification by the MnmEG.


Advanced spot quality analysis in two-colour microarray experiments.
Image analysis of microarrays and, in particular, spot quantification and spot quality control, is one of the most important steps in statistical analysis of microarray data. Recent methods of spot quality control are still in early age of development, often leading to underestimation of true positive microarray features and, consequently, to loss of important biological information. Therefore, improving and standardizing the statistical approaches of spot quality control are essential to facilitate the overall analysis of microarray data and subsequent extraction of biological information. We evaluated the performance of two image analysis packages MAIA and GenePix (GP) using two complementary experimental approaches with a focus on the statistical analysis of spot quality factors. First, we developed control microarrays with a priori known fluorescence ratios to verify the accuracy and precision of the ratio estimation of signal intensities. Next, we developed advanced semi-automatic protocols of spot quality evaluation in MAIA and GP and compared their performance with available facilities of spot quantitative filtering in GP. We evaluated these algorithms for standardised spot quality analysis in a whole-genome microarray experiment assessing well-characterised transcriptional modifications induced by the transcription regulator SNAI1. Using a set of RT-PCR or qRT-PCR validated microarray data, we found that the semi-automatic protocol of spot quality control we developed with MAIA allowed recovering approximately 13% more spots and 38% more differentially expressed genes (at FDR = 5%) than GP with default spot filtering conditions. Careful control of spot quality characteristics with advanced spot quality evaluation can significantly increase the amount of confident and accurate data resulting in more meaningful biological conclusions.


Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation.
Costimulation (signal 2) has been proposed to inhibit the induction of T cell clonal anergy by either directly antagonizing negative signals arising from TCR engagement (signal 1) or by synergizing with signal 1 to produce IL-2, which in turn leads to proliferation and dilution of negative regulatory factors. To better define the cellular events that lead to the induction of anergy, we used the immunosuppressive agent rapamycin, which blocks T cell proliferation in late G1 phase but does not affect costimulation-dependent IL-2 production. Our data demonstrate that full T cell activation (signal 1 plus 2) in the presence of rapamycin results in profound T cell anergy, despite the fact that these cells produce copious amounts of IL-2. Similar to conventional anergy (induction by signal 1 alone), the rapamycin-induced anergic cells show a decrease in mitogen-activated protein kinase activation, and these cells can be rescued by culture in IL-2. Interestingly, the rapamycin-induced anergic cells display a more profound block in IL-3 and IFN-gamma production upon rechallenge. Finally, in contrast to rapamycin, full T cell activation in the presence of hydroxyurea (which inhibits the cell cycle in early S phase) did not result in anergy. These data suggest that it is neither the direct effect of costimulation nor the subsequent T cell proliferation that prevents anergy induction, but rather the biochemical events that occur upon progression through the cell cycle from G1 into S phase.


Clinicopathologic features of a novel star-shaped transactive response DNA-binding protein 43 (TDP-43) pathology in the oldest old.
Transactive response DNA-binding protein 43 (TDP-43) pathology is categorized as type A-E in frontotemporal lobar degeneration and as type α-β in Alzheimer disease (AD) based on inclusion type. We screened amygdala slides of 131 cases with varying ages at death, clinical/neuroimaging findings, and AD neuropathologic changes for TDP-43 pathology using anti-phospho-TDP-43 antibodies. Seven cases (5%) only showed atypical TDP-43 inclusions that could not be typed. Immunohistochemistry and immunofluorescence assessed the atypical star-shaped TDP-43 pathology including its distribution, species, cellular localization, and colocalization with tau. All 7 had died at an extremely old age (median: 100 years [IQR: 94-101]) from nonneurological causes and none had dementia (4 cognitively unimpaired, 3 with amnestic mild cognitive impairment). Neuroimaging showed mild medial temporal involvement. Pathologically, the star-shaped TDP-43-positive inclusions were found in medial (subpial) amygdala and, occasionally, in basolateral regions. Hippocampus only showed TDP-43-positive neurites in the fimbria and subiculum while the frontal lobe was free of TDP-43 inclusions. The star-shaped inclusions were better detected with antibodies against N-terminal than C-terminal TDP-43. Double-labeling studies confirmed deposition of TDP-43 within astrocytes and colocalization with tau. We have identified a novel TDP-43 pathology with star-shaped morphology associated with superaging, with a homogeneous clinicopathologic picture, possibly representing a novel, true aging-related TDP-43 pathology.


Geothrix fermentans gen. nov., sp. nov., a novel Fe(III)-reducing bacterium from a hydrocarbon-contaminated aquifer.
In an attempt to understand better the micro-organisms involved in anaerobic degradation of aromatic hydrocarbons in the Fe(III)-reducing zone of petroleum-contaminated aquifers, Fe(III)-reducing micro-organisms were isolated from contaminated aquifer material that had been adapted for rapid oxidation of toluene coupled to Fe(III) reduction. One of these organisms, strain H-5T, was enriched and isolated on acetate/Fe(III) medium. Strain H-5T is a Gram-negative strict anaerobe that grows with various simple organic acids such as acetate, propionate, lactate and fumarate as alternative electron donors with Fe(III) as the electron acceptor. In addition, strain H-5T also oxidizes long-chain fatty acids such as palmitate with Fe(III) as the sole electron acceptor. Strain H-5T can also grow by fermentation of citrate or fumarate in the absence of an alternative electron acceptor. The primary end-products of citrate fermentation are acetate and succinate. In addition to various forms of soluble and insoluble Fe(III), strain H-5T grows with nitrate, Mn(IV), fumarate and the humic acid analogue 2,6-anthraquinone disulfonate as alternative electron acceptors. As with other organisms that can oxidize organic compounds completely with the reduction of Fe(III), cell suspensions of strain H-5T have absorbance maxima indicative of a c-type cytochrome(s). It is proposed that strain H-5T represents a novel genus in the Holophaga-Acidobacterium phylum and that it should be named Geothrix fermentans sp. nov., gen. nov.


A note on the frequency of consanguineous marriages in Reading, England in 1972/1973.
A random sample was taken of marriages celebrated in 1972/1973 in and around Reading, Berksshire, in order to investigate marital mobility and population structure. Respondents were asked whether they were related before marriage and isonymous marriages were noted. Eight consanguineous marriages were recorded. The inbreeding coefficient for the next generation is estimated to be 0.00017 from consanguineous marriages, 0.00021 from isonymy. These values are similar to those obtained from other modern Western societies.


The efficacy of a treatment program focusing on specific stabilizing exercises for pelvic girdle pain after pregnancy: a randomized controlled trial.
A randomized controlled trial with stratified block design. To evaluate a treatment program focusing on whether specific stabilizing exercises for patients with pelvic girdle pain after pregnancy reduce pain, improve functional status, and improve quality of life. SUMMARY OF BACKGROUND DATA. : The evidence of effectiveness of treatment for pelvic girdle pain is weak. Recent research has focused on the importance of activation of muscles for motor control and stability of the lumbopelvic region. To the authors' knowledge, the efficacy of applying these principles for pelvic girdle pain has not previously been evaluated in a randomized controlled trial. Eighty-one women with pelvic girdle pain were assigned randomly to two treatment groups for 20 weeks. One group received physical therapy with a focus on specific stabilizing exercises. The other group received individualized physical therapy without specific stabilizing exercises. Assessments were administered by a blinded assessor, at baseline, after intervention and 1 year post partum. Main outcome measures were pain, functional status and quality of life. There were no dropouts. After intervention and at 1 year post partum, the specific stabilizing exercise group showed statistically and clinically significant lower pain intensity, lower disability, and higher quality of life compared with the control group. Group difference in median values for evening pain after treatment was 30 mm on the Visual Analog Scale. Disability was reduced by more than 50% for the exercise group; changes were negligible in the control group. Significant differences were also observed for physical tests, in favor of the specific exercise group. An individualized treatment approach with specific stabilizing exercises appears to be more effective than physical therapy without specific stabilizing exercises for women with pelvic girdle pain after pregnancy.


Radionuclide scanning in the evaluation of Kaposi sarcoma.
A patient with Kaposi sarcoma showed increased uptake of sodium pertechnetate Tc 99m over both clinically evident and occult regions of involvement. The clinically negative but scan-positive regions showed pathologic lesions by biopsy. Gallium citrate Ga 67 and bleomycin sulfate labeled with indium 111 (111In) did not concentrate in the lesions, which suggest that Kaposi sarcoma, despite its resemblance to lymphoma, differs from lymphoma substantially with reference to raionuclide uptake. This report confirms that sodium pertechnetate Tc 99m is the most sensitive agent for diagnostic and therapeutic evaluation of patients with Kaposi sarcoma and suggests taht gallium citrate Ga 67 or bleomycin 111In may be useful in the differentiation of Kaposi sarcoma from lymphoma.


Enhancing CO2-Valorization Using Clostridium autoethanogenum for Sustainable Fuel and Chemicals Production.
Acetogenic bacteria can convert waste gases into fuels and chemicals. Design of bioprocesses for waste carbon valorization requires quantification of steady-state carbon flows. Here, steady-state quantification of autotrophic chemostats containing Clostridium autoethanogenum grown on CO2 and H2 revealed that captured carbon (460 ± 80 mmol/gDCW/day) had a significant distribution to ethanol (54 ± 3 C-mol% with a 2.4 ± 0.3 g/L titer). We were impressed with this initial result, but also observed limitations to biomass concentration and growth rate. Metabolic modeling predicted culture performance and indicated significant metabolic adjustments when compared to fermentation with CO as the carbon source. Moreover, modeling highlighted flux to pyruvate, and subsequently reduced ferredoxin, as a target for improving CO2 and H2 fermentation. Supplementation with a small amount of CO enabled co-utilization with CO2, and enhanced CO2 fermentation performance significantly, while maintaining an industrially relevant product profile. Additionally, the highest specific flux through the Wood-Ljungdahl pathway was observed during co-utilization of CO2 and CO. Furthermore, the addition of CO led to superior CO2-valorizing characteristics (9.7 ± 0.4 g/L ethanol with a 66 ± 2 C-mol% distribution, and 540 ± 20 mmol CO2/gDCW/day). Similar industrial processes are commercial or currently being scaled up, indicating CO-supplemented CO2 and H2 fermentation has high potential for sustainable fuel and chemical production. This work also provides a reference dataset to advance our understanding of CO2 gas fermentation, which can contribute to mitigating climate change.


Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease.
Liver biopsy is currently the most reliable way of evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Its inherent risks limit its widespread use. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has recently been shown to stratify patients in terms of fibrosis severity but requires access to liver tissue. The aim of this study was to assess whether DNA methylation of circulating DNA could be detected in human plasma and potentially used to stratify liver fibrosis severity in patients with NAFLD. Patients with biopsy-proven NAFLD and age-matched controls were recruited from the liver and gastroenterology clinics at the Newcastle upon Tyne Hospitals NHS Foundation Trust. Plasma cell-free circulating DNA methylation of PPARγ was quantitatively assessed by pyrosequencing. Liver DNA methylation was quantitatively assessed by pyrosequencing NAFLD explant tissue, subjected to laser capture microdissection (LCM). Patients with alcoholic liver disease (ALD) were also subjected to plasma DNA and LCM pyrosequencing. 26 patients with biopsy-proven NAFLD were included. Quantitative plasma DNA methylation of PPARγ stratified patients into mild (Kleiner 1-2) and severe (Kleiner 3-4) fibrosis (CpG1: 63% vs 86%, p<0.05; CpG2: 51% vs 65% p>0.05). Hypermethylation at the PPARγ promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis. Differential DNA methylation at the PPARγ promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARγ could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease.


Inferring Entropy Production from Short Experiments.
We provide a strategy for the exact inference of the average as well as the fluctuations of the entropy production in nonequilibrium systems in the steady state, from the measurements of arbitrary current fluctuations. Our results are built upon the finite-time generalization of the thermodynamic uncertainty relation, and require only very short time series data from experiments. We illustrate our results with exact and numerical solutions for two colloidal heat engines.


Testing the function of dromaeosaurid (Dinosauria, Theropoda) 'sickle claws' through musculoskeletal modelling and optimization.
Dromaeosaurids were a clade of bird-like, carnivorous dinosaurs that are well known for their characteristic morphology of pedal digit II, which bore an enlarged, sickle-shaped claw and permitted an extreme range of flexion-extension. Proposed functions for the claw often revolve around predation, but the exact manner of use varies widely. Musculoskeletal modelling provides an avenue to quantitatively investigate the biomechanics of this enigmatic system, and thereby test different behavioural hypotheses. Here, a musculoskeletal model of the hindlimb and pes of Deinonychus was developed, and mathematical optimization was used to assess the factors that maximize production of force at the claw tip. Optimization revealed that more crouched hindlimb postures (i.e., more flexed knees and ankles) and larger flexor muscle volumes consistently increased claw forces, although the optimal degree of digit flexion or extension depended on assumptions of muscle activity and fibre operating range. Interestingly, the magnitude of force capable of being produced at the claw tip was relatively small, arguing against regular transmission of a large proportion of body weight into a substrate principally via the claw tip. Such transmission would therefore likely have needed to occur via more proximal parts of the foot. Collectively, the results best support a grasping function for digit II (e.g., restraint of prey smaller than the dromaeosaurid's own body size), although other behaviours involving flexed hindlimbs cannot be excluded.


An experimental evaluation of the pharmacokinetics of fusidic acid in peritoneal dialysis.
Fusidic acid, an antimicrobial agent with activity against coagulase-positive and coagulase-negative staphylococci, has considerable potential for the management of staphylococcal peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Whether fusidic acid reaches therapeutic levels in the dialysate once therapeutic serum levels have been achieved is not known. An animal model of CAPD that reproduced essential features of the clinical procedure was used to investigate this issue. Although oral administration was the preferred route, fusidic acid is not absorbed from the gastrointestinal tract of laboratory rats, and a subcutaneous injection of diethanolamine fusidate was used to achieve serum levels of the agent equivalent to those achieved clinically in man. In this model, fusidic acid concentrations up to 28 times the MIC for staphylococci were found in the dialysate when therapeutic levels of the agent were reached in the serum. The data provide support for continued experimental and clinical evaluation of the role of fusidic acid in CAPD-associated peritonitis.


Pathogenic tau species drive a psychosis-like phenotype in a mouse model of Alzheimer's disease.
Psychotic Alzheimer's disease (AD+P) is a rapidly progressive variant of AD associated with an increased burden of frontal tau pathology that affects up to 50% of those with AD, and is observed more commonly in females. To date, there are no safe and effective medication interventions with an indication for treatment in this condition, and there has been only very limited exploration of potential animal models for pre-clinical drug development. Pathogenic tau is over represented in the frontal cortex in AD+P, especially in females. In order to develop a candidate animal model of AD+P, we employed a tau mouse model with a heavy burden of frontal tau pathology, the rTg(tauP301L)4510 mouse, hereafter termed rTg4510. We explored deficits of prepulse inhibition of acoustic startle (PPI), a model of psychosis in rodents, and the correlation between pathogenic phospho-tau species associated with AD+P and PPI deficits in female mice. We found that female rTg4510 mice exhibit increasing PPI deficits relative to littermate controls from 4.5 to 5.5 months of age, and that these deficits are driven by insoluble fractions of the phospho-tau species pSer396/404, pSer202, and pThr231 found to be associated with human AD+P. This preliminary data suggests the utility of the rTg4510 mouse as a candidate disease model of human female AD+P. Further work expanded to include both genders and other behavioral outcome measures relevant to AD+P is necessary.


Differential methylation in steroid 5 alpha-reductase isozyme genes in epididymis, testis, and liver of the adult rat.
DNA methylation has been largely involved in the regulation of tissue-specific gene expression. The aim of the study was to determine the methylation pattern of steroid 5 alpha-reductase genes 1 and 2 in two reproductive tissues (testis and epididymis) and a nonreproductive tissue (liver) that exhibit different contents of steroid 5 alpha-reductase isozymes. These isozymes induce the bioconversion of testosterone to dihydrotestosterone that in mammals is a key molecule for external genitalia development. Genomic DNA from the testis, the epididymis, and the liver from normal adult rats was used to determine cytosine and adenine methylation pattern of steroid 5 alpha-reductase genes 1 and 2 by restriction fragment length polymorphism (RFLP) analysis using restriction enzymes sensitive to adenine (Mbo I and Sau3A I) and cytosine (Hpa II and MSP I) methylation. We also evaluated the expression of both steroid 5 alpha-reductase genes by northern blot. When genomic DNA was digested with Hpa II or Msp I, we found that steroid 5 alpha-reductase gene 2 was less cytosine methylated in the epididymis and in the testis than in the liver. In contrast, when genomic DNA was digested with Mbo I or Sau3A I, we observed that gene 2 was more adenine methylated in the epididymis and in the testis than in the liver. 5 alpha-Reductase gene 1 presented the same adenine- and cytosine-methylation pattern in the studied tissues. We also found a differential expression of steroid 5 alpha-reductase genes. Gene 2 was expressed both in the testis and the epididymis but not in the liver; whereas gene 1 was only expressed in the latter. Our results suggest that the differential methylation pattern in 5 alpha-reductase gene 2 in reproductive and nonreproductive tissues should be involved in the regulation of its expression.


Assaying uptake of endocrine disruptor compounds in zebrafish embryos and larvae.
To study the effects of environmental endocrine disruptor compounds (EDCs) on aquatic animals, embryos and larvae are typically incubated in water containing defined concentrations of EDCs. However, the amount of EDC uptake into the animal is often difficult to determine. Using radiolabeled estradiol ([3H]E2), we previously developed a rapid, straightforward assay to measure estradiol uptake from water into zebrafish embryos and larvae. Here, we extend this approach to measure the uptake of two additional EDCs, bisphenol A (BPA) and ethinyl estradiol (EE2). As with E2, the uptake of each compound by individual larvae was low (<6%), and increased with increasing concentration, duration, and developmental stage. We found that E2 and EE2 had similar uptake under equivalent exposure conditions, while BPA had comparatively lower uptake. One application of this assay is to test factors that influence EDC uptake or efflux. It has been suggested that persistent organic pollutants (POPs) inhibit ABC transporters that may normally efflux EDCs and their metabolites, inducing toxicity in aquatic organisms. We measured [3H]E2 levels in zebrafish in the presence or absence of the POP PDBE-100, and cyclosporine A, a known inhibitor of ABC transporters. Neither chemical significantly affected [3H]E2 levels in zebrafish, suggesting that zebrafish maintain estradiol efflux in the presence of PDBE-100, independently of cyclosporine A-responsive transporters. These uptake results will be a valuable reference for EDC exposure studies in developing zebrafish, and provide a rapid assay to screen for chemicals that influence estrogen-like EDC levels in vivo.


Laparoscopic gastrectomy for remnant gastric cancer: A single-center retrospective study.
Laparoscopic gastrectomy (LG) for remnant gastric cancer (RGC) remains controversial because of its rarity and heterogeneity of clinical characteristics. Based on our experience, we posited that our established methodology in LG could be applied to the laparoscopic procedure for RGC surgery and introduced LG for RGC at our institution in 2004. This study enrolled 46 patients who underwent LG for RGC between January 2004 and December 2017. Data were obtained through a review of our prospectively maintained database. Laparoscopic total gastrectomy (LTG) was the standard surgical procedure for RGC. Laparoscopic subtotal gastrectomy (LsTG) was performed as an alternative procedure for patients with RGC located near the anastomotic site after primary gastrectomy. The technical and oncological feasibility and safety of LG for RGC were evaluated. LTG for RGC was performed on 36 patients. LsTG for RGC was performed on 10 patients. All patients completed LG procedure and succeeded R0 resection. Complications of Clavien-Dindo classification grade ≥ IIIa occurred in 4 (8.7%) patients. The retrospective video reviews showed that the time for adhesiotomy around the suprapancreatic area and the lesser curvature of the remnant stomach was significantly shorter in the primary-benign group than in the primary-malignant group. With the median follow-up period of 40 months, the 3-year recurrence-free survival and 3-year overall survival rates were 72.3% and 80.2%, respectively. LG for RGC represents a safe and feasible surgical option with favorable short-term and long-term outcomes in patients with RGC.


How fast is fisheries-induced evolution? Quantitative analysis of modelling and empirical studies.
A number of theoretical models, experimental studies and time-series studies of wild fish have explored the presence and magnitude of fisheries-induced evolution (FIE). While most studies agree that FIE is likely to be happening in many fished stocks, there are disagreements about its rates and implications for stock viability. To address these disagreements in a quantitative manner, we conducted a meta-analysis of FIE rates reported in theoretical and empirical studies. We discovered that rates of phenotypic change observed in wild fish are about four times higher than the evolutionary rates reported in modelling studies, but correlation between the rate of change and instantaneous fishing mortality (F) was very similar in the two types of studies. Mixed-model analyses showed that in the modelling studies traits associated with reproductive investment and growth evolved slower than rates related to maturation. In empirical observations age-at-maturation was changing faster than other life-history traits. We also found that, despite different assumption and modelling approaches, rates of evolution for a given F value reported in 10 of 13 modelling studies were not significantly different.


[A method for measuring the strength of adhesion of Candida albicans on epithelial cells].
A method on estimation of Candida albicans adhesion to epitheliocytes is proposed. The principle consists in the fact that while centrifuging epitheliocytes (1000 cycles/min, 10 min) with adhered Candida albicans through phycoll-verografin (1.077 g/cm3 density), Candida albicans cells having poor adhesion are separated from epitheliocytes trying to rise to the surface of phycoll-verografin. Candida albicans strongly adhered to epitheliocytes settle down to the bottom of test tube. In experiments with buccal epitheliocytes of healthy donors the number of strongly adhered Candida albicans ranged from 13% to 50% and they amounted to 37.0 +/- 7.8% on an average.


Identification and characterization of the V3 promoter of the ST3GAL4 gene.
The ST3GAL4 gene encodes the enzyme Galβ1-4GlcNAc α2,3 sialyltransferase (ST3Gal IV). This enzyme participates in the synthesis of the sialyl Lewis x antigen. In different cancer types altered expression of this antigen has been reported. The transcriptional regulation of this gene is very complex, different mRNA variants (V1-V10) have been reported and are originated by the activity of different promoters and alternative splicing. Only the promoter that gives rise to the V3 variant has not been previously reported. The objective of this work was to identify and characterize the V3 promoter of the ST3GAL4 gene. For this, the putative V3 promoter of the ST3GAL4 gene was delimited by in silico analysis. The complete promoter and smaller versions were cloned in a reporter plasmid. The constructs were transfected in the HaCaT cells and the promoter activity was evaluated by luciferase reporter assays. The cloned region showed promoter activity, and the basal activity was not dependent on TATA boxes. However, the GC boxes, an initiator element (Inr) and downstream promoter element (DPE) could contribute to basal activity. The promoter contains several binding sites for the nuclear factor of activated T-cells (NFAT) that could participate in inducible activity during the immune response. The minimal promoter corresponds to a fragment of approximately 300 bp, located in the position -347 b to -40 b. The characterization of the V3 promoter of the ST3GAL4 gene completes the study of the four promoters of this gene, this contributes to the understanding of its complex transcription regulation.


Adjunct Nurse Faculty Demographics and Intent to Stay Teaching.
Adjunct nurse educators have become a primary facilitator of students' clinical learning in nursing education. However, studies are lacking as to variables that correlate with their intent to stay teaching. This study examined demographic variables that had an impact on adjunct clinical educators' decisions about whether to leave a teaching position in an associate degree nursing program. Full-time employment in addition to teaching as an adjunct faculty member predicted intent to leave the role. Measures to improve adjunct nurse faculty intent to stay are included.


Transcription-frequency-dependent modulation of an attenuator in a ribosomal protein-RNA polymerase operon requires an upstream site.
Although the attenuator located between the ribosomal protein and RNA polymerase gene domains of the Escherichia coli rplKAJLrpoBC operon has a maximum termination efficiency of 80%, the level of termination is diminished with decreasing transcription frequency. In this report, the use of transcriptional fusions to further investigate the mechanism of transcription-frequency-dependent regulation is described. The termination efficiency of two other weak terminators was assayed over a wide range of transcription frequencies programmed by different strength promoters. The results indicated that a decrease in termination efficiency with decreasing transcription frequency is not an inherent property of weak terminators. Deletion of the 165 bp segment located 439-274 bp upstream of the attenuator abrogated the difference in termination efficiency normally seen between high and low levels of transcription. This suggests that a cis-acting site located in this upstream region is necessary for transcription-frequency-dependent modulation of the attenuator's function. However, this site apparently works only in combination with the attenuator, since it did not cause transcription-frequency-dependent modulation when placed upstream of two other weak terminators. Analysis of the readthrough frequencies of single or tandem copies of the attenuator indicated that the transcription complexes which pass through the attenuator have not been converted to termination-resistant complexes in a manner analogous to the N-mediated antitermination system of lambda. Finally, an examination of termination efficiency in three nusA mutants suggested that although NusA increases readthrough at the attenuator it is not directly involved in transcription-frequency-dependent modulation.


Clinical correlations of grey matter reductions in the caudate nucleus of adults with attention deficit hyperactivity disorder.
Magnetic resonance imaging (MRI) studies have shown decreased caudate volumes in individuals with attention deficit hyperactivity disorder (ADHD). However, most of these studies have been carried out in male children. Very little research has been done in adults, and the results obtained in children are difficult to extrapolate to adults. We sought to compare the volume of the caudate of adults with ADHD with that of healthy controls; we also compared these volumes between men and women. We performed an MRI scan on 20 adults with ADHD (10 men and 10 women) aged 25-35 years and 20 healthy controls matched by age and sex. We used voxel-based morphometry with the DARTEL algorithm for image analyses. We used the specifically designed Friederichsen, Almeida, Serrano, Cortes Test (FASCT) to measure the severity of ADHD; both the self-reported (FASCT-SR) and the observer (FASCT-O) versions were used. The statistical parametric map showed a smaller region with low grey matter volume and a smaller concentration of grey matter in this region of the right caudate in ADHD patients than in health controls, both in the entire sample and within each sex. There was a significant correlation between the volume of this region of the caudate with the number of DSM IV-TR criteria, as well as with the total scores and most of the factors of the FASCT-SR and FASCT-O scales. A separate correlation analysis by sex gave similar results. The study design was cross-sectional. The region of the right caudate with low grey matter volume was smaller in adults with ADHD in both sexes and was correlated with ADHD severity.


Pathways of thymidine hypermodification.
The DNAs of bacterial viruses are known to contain diverse, chemically complex modifications to thymidine that protect them from the endonuclease-based defenses of their cellular hosts, but whose biosynthetic origins are enigmatic. Up to half of thymidines in the Pseudomonas phage M6, the Salmonella phage ViI, and others, contain exotic chemical moieties synthesized through the post-replicative modification of 5-hydroxymethyluridine (5-hmdU). We have determined that these thymidine hypermodifications are derived from free amino acids enzymatically installed on 5-hmdU. These appended amino acids are further sculpted by various enzyme classes such as radical SAM isomerases, PLP-dependent decarboxylases, flavin-dependent lyases and acetyltransferases. The combinatorial permutations of thymidine hypermodification genes found in viral metagenomes from geographically widespread sources suggests an untapped reservoir of chemical diversity in DNA hypermodifications.


Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease.
Previous studies have suggested a higher prevalence of thyroid abnormalities in persons with end-stage renal disease. However, little is known regarding the epidemiology of thyroid disorders in persons with less severe kidney dysfunction. We used data from the Third National Health and Nutrition Examination Survey to examine the prevalence of hypothyroidism (clinical and subclinical) at different levels of estimated glomerular filtration rate (GFR). We used multivariable logistic regression to evaluate the association between GFR and prevalent hypothyroidism. Among 14,623 adult participants with serum creatinine and thyroid function test results, the mean age was 48.7 years, and 52.6% were women. The prevalence of hypothyroidism increased with lower levels of GFR (in units of mL/min/1.73 m(2)), occurring in 5.4% of subjects with GFR >/=90, 10.9% with GFR 60-89, 20.4% with GFR 45-59, 23.0% with GFR 30-44, and 23.1% with GFR <30 (P < 0.001 for trend). Overall, 56% of hypothyroidism cases were considered subclinical. Compared with GFR >/=90 mL/min/1.73 m(2), reduced GFR was associated with an increased risk of hypothyroidism, after adjusting for age, gender, and race/ethnicity: adjusted odds ratio 1.07 (95% confidence interval: 0.86-1.32) for GFR 60-89, 1.57 (1.11-2.22) for GFR 45-59, 1.81 (1.04-3.16) for GFR 30-44, and 1.97 (0.69-5.61) for GFR <30 mL/min/1.73 m(2) (P= 0.008 for trend). Among a nationally representative sample of adults, reduced glomerular filtration rate was associated with a higher prevalence of hypothyroidism, with many subclinical cases. Future studies are needed to determine the potential adverse effects of subclinical and clinical hypothyroidism in persons with chronic kidney disease.


Effect of learning on slow gamma propagation between hippocampus and cortex in the wild-type and AD mice.
Slow gamma oscillations (20-50 Hz) have been suggested to coordinate information transfer between brain structures involved in memory formation. Whereas the involvement of slow gamma in memory processing was studied by means of correlation between the gamma power and the occurrence of a given event (sharp wave ripples (SWRs), cortical transients), our approach consists of the analysis of the transmission of slow gamma itself. We use the method based on Granger causality principle-direct Directed Transfer Function, which allows to determine directed propagation of brain activity, including bidirectional flows. Four cortical sites along with CA1 ipsi- and contralateral were recorded in behaving wild-type and APP/PS1 mice before and after learning session of a spatial memory task. During slow wave sleep propagation of slow gamma was bidirectional, forming multiple loops of interaction which involved both CA1 and some of cortical sites. In episodes coincident with SWRs the number and strength of connectivity pathways increased in both groups compared to episodes without SWRs. The effect of learning was expressed only in APP/PS1 mice and consisted in strengthening of the slow gamma transmission from hippocampus to cortex as well as between both CA1 which may serve more efficient transmission of information from impaired CA1.


Effect of Mycobacterium bovis BCG vaccination on Mycobacterium-specific cellular proliferation and tumor necrosis factor alpha production from distinct guinea pig leukocyte populations.
In this study, we focused on three leukocyte-rich guinea pig cell populations, bronchoalveolar lavage (BAL) cells, resident peritoneal cells (PC), and splenocytes (SPC). BAL cells, SPC, and PC were stimulated either with live attenuated Mycobacterium tuberculosis H37Ra or with live or heat-killed virulent M. tuberculosis H37Rv (multiplicity of infection of 1:100). Each cell population was determined to proliferate in response to heat-killed virulent H37Rv, whereas no measurable proliferative response could be detected upon stimulation with live mycobacteria. Additionally, this proliferative capacity (in SPC and PC populations) was significantly enhanced upon prior vaccination with Mycobacterium bovis BCG. Accordingly, in a parallel set of experiments we found a strong positive correlation between production of antigen-specific bioactive tumor necrosis factor alpha (TNF-alpha) and prior vaccination with BCG. A nonspecific stimulus, lipopolysaccharide, failed to induce this effect on BAL cells, SPC, and PC. These results showed that production of bioactive TNF-alpha from mycobacterium-stimulated guinea pig cell cultures positively correlates with the vaccination status of the host and with the virulence of the mycobacterial strain.


Tyrosine Kinase Inhibitors Display Potent Activity against Cryptosporidium parvum.
The protozoan parasite Cryptosporidium is a leading cause of diarrheal disease (cryptosporidiosis) and death in young children. Cryptosporidiosis can be life-threatening in individuals with weak immunity such as HIV/AIDS patients and organ transplant recipients. There is currently no effective drug to treat cryptosporidiosis in the pediatric and immunocompromised population. Therefore, there is an urgent need to expedite the drug discovery process in order to develop new and effective therapies to reduce the global disease burden of cryptosporidiosis. In this study, we employed a drug repurposing strategy to screen a library of 473 human kinase inhibitors to determine their activity against Cryptosporidium parvum. We have identified 67 new anti-cryptosporidial compounds using phenotypic screening based on a transgenic C. parvum strain expressing a luciferase reporter. Further, dose-response assays led to the identification of 11 hit compounds that showed potent inhibition of C. parvum at nanomolar concentration. Kinome profiling of these 11 prioritized hits identified compounds that displayed selectivity in targeting specific families of kinases, particularly tyrosine kinases. Overall, this study identified tyrosine kinase inhibitors that hold potential for future development as new drug candidates against cryptosporidiosis. IMPORTANCE The intestinal parasite Cryptosporidium parvum is a major cause of diarrhea-associated morbidity and mortality in children, immunocompromised people, and young ruminant animals. With no effective drug available to treat cryptosporidiosis in humans and animals, there is an urgent need to identify anti-parasitic compounds and new targets for drug development. To address this unmet need, we screened a GSK library of kinase inhibitors and identified several potent compounds, including tyrosine kinase inhibitors, that were highly effective in killing C. parvum. Overall, our study revealed several novel compounds and a new family of kinases that can be targeted for anti-cryptosporidial drug development.


Reliable DNA histogram interpretation. Number of nuclei requiring measurement with flow cytometry.
The reasons for conflicting prognostic results as to DNA ploidy and cell cycle variables (DNA index, percent S (%S) phase) may be found mainly at different levels of the flow cytometric methodology used. The present study concentrated on how many nuclei have to be measured with flow cytometry for reliable DNA histogram interpretation. Twenty-three samples of fresh frozen and 22 samples of paraffin-embedded material from different sites were used. For each sample, 5, 10, 15, 20, 25, 30, 35, 40, 45 and 50 (x1,000) events were cumulatively measured. The resulting DNA histograms were analyzed with the MultiCycle computer program using a highly reproducible interpretation protocol. No disagreements about DNA ploidy classification were found in samples with 10,000 or more events for the fresh frozen and 40,000 or more events for the paraffin-embedded material. Excluding DNA ploidy disagreements, the DNA index was stable in all cases. To obtain a %S-phase cell measurement within 20% of the reference value, at least 20,000 and 40,000 events were needed for, respectively, DNA diploid and DNA nondiploid cases for the fresh frozen material and, respectively, 40,000 and 50,000 events for the paraffin-embedded material. For reliable combined determination of DNA ploidy, DNA index and %S-phase cells, at least 40,000 and 50,000 events are necessary for fresh frozen and paraffin-embedded material, respectively.


Gender role across development in adults with 46,XY disorders of sex development including perineoscrotal hypospadias and small phallus raised male or female.
Self-rated degree of femininity and masculinity across development were evaluated for 40 adults affected by 46,XY disorders of sex development (DSDs) who presented at birth with a small phallus and perineoscrotal hypospadias, raised either male (n = 22) or female (n = 18). Most participants were confirmed or presumed to be affected by partial androgen insensitivity syndrome (n = 14), partial gonadal dysgenesis (n = 11), or were considered to have a poorly defined case of 46,XY DSD including ambiguous external genitalia (n = 15). Participants retrospectively evaluated their degree of masculinity and femininity during their childhood, adolescence, adulthood, and in the past 12 months of filling out a questionnaire pertaining to their psychosexual development. Participants raised male reported more masculinity than those raised female due to an increase in masculinization during adolescence and adulthood. Participants raised male also reported less femininity than those raised female throughout development. Participants raised female reported more femininity than those raised male due to an increase in feminization during adolescence and adulthood. Participants raised female also reported less masculinity than those raised male throughout development. These data support the proposition that some aspects of gender role (GR), such as masculinity and femininity, are capable of proceeding along female- or male-typic patterns depending on sex of rearing among individuals affected by specific types of 46,XY DSD. Furthermore, regardless of male or female rearing, GR increasingly corresponds with assigned sex as individuals proceed through sexual maturity and into adulthood. These results are consistent with the idea that socialization/learning contributes to GR development in humans in addition to data from others demonstrating endocrine influences.


[Use of the method of pulsed thermopuncture in the treatment of patients with chronic alcoholism during therapeutic remission].
The paper is concerned with pulse thermopuncture, a new method of reflexotherapy. Its modes and parameters, indications for clinical use are based. The method is especially indicated in the treatment of patients with vegetovascular and neurotic disorders. It provided a beneficial effect in the treatment of chronic alcoholics in a state of therapeutic remission in order to correct the above-indicated disorders and prevent the disease relapses.


Body morphometry appropriate computational phantoms for dose and risk optimization in pediatric renal imaging with Tc-99m DMSA and Tc-99m MAG3.
Current guidelines for administered activity (AA) in pediatric nuclear medicine imaging studies are based on a 2016 harmonization of the 2010 North American Consensus guidelines and the 2007 European Association of Nuclear Medicine pediatric dosage card. These guidelines assign AA scaled to patient body mass, with further constraints on maximum and minimum values of radiopharmaceutical activity. These guidelines, however, are not formulated based upon a rigor-ous evaluation of diagnostic image quality. In a recent study of the renal cortex imaging agent 99mTc-DMSA (Li Y et al 2019), body mass-based dosing guidelines were shown to not give the same level of image quality for patients of differing body mass. Their data suggest that patient girth at the level of the kidneys may be a better morphometric parameter to consider when selecting AA for renal nuclear medicine imaging. The objective of the present work was thus to develop a dedicated series of computational phantoms to support image quality and organ dose studies in pediatric renal imaging using 99mTc-DMSA or 99mTc-MAG3. The final library consists of 50 male and female phantoms of ages 0 to 15 years, with percentile variations (5th to 95th) in waist circumference (WC) at each age. For each phantom, nominal values of kidney volume, length, and depth were incorporated into the phantom design. Organ absorbed doses, detriment-weighted doses, and stochastic risks were assessed using ICRP reference biokinetic models for both agents. In Monte Carlo radiation transport simulations, organ doses for these agents yielded detriment-weighted dose coefficients (mSv/MBq) that were in general larger than current ICRP values of the effective dose coefficients (age and WC-averaged ratios of eDW/e were 1.40 for the male phantoms and 1.49 for the female phantoms). Values of risk index (ratio of radiation-induced to natural background cancer incidence risk x 100) varied between 0.062 (newborns) to 0.108 (15-year-olds) for 99mTc-DMSA and between 0.026 (newborns) to 0.122 (15-year-olds) for 99mTc-MAG3. Using tallies of photon exit fluence as a rough surrogate for uniform image quality, our study demonstrated that through body region-of-interest optimization of AA, there is the potential for further dose and risk reductions of between factors of 1.5 to 3.0 beyond simple weight-based dosing guidance.


Studies on the surface properties of hybrid cells. III. A membrane glycoprotein found on the surface of a wide range of malignant cells.
We report here the presence of a glycoprotein of apparent molecular mass 90000 daltons on the surface of membranes of malignant cells, which is absent or very much reduced on the surface of non-malignant cells. This glycoprotein is rich in sialic acid and appears to be sensitive to the concentration of cAMP under certain conditions. Analysis of the labelled sugars present in the glycoproteins of cells metabolically labelled with [14C]glucosamine suggests that all the enzymes necessary for the conversion of the tracer precursor into the sugars normally found to be labelled are present in both the malignant and the non-malignant cells.


Herpes simplex virus phosphoproteins. I. Phosphate cycles on and off some viral polypeptides and can alter their affinity for DNA.
We report on phosphorylation, the stability of the bound phosphate, and the properties of several phosphorylated infected-cell polypeptides (ICPs) synthesized in cells infected with herpes simplex virus 1 and 2. Our results and conclusions are as follows. (i) Phosphorylation of ICPs occurs by at least two different pathways. Thus, the 4a and 4c electrophoretic forms of ICP 4 were labeled with 32P during a pulse concurrently with their synthesis, whereas ICP 22 and ICP 27 were labeled with 32P only during a subsequent chase in the presence of unlabeled phosphate. (ii) Pulse chase studies with [35S]methionine and 32P indicate that whereas most polypeptides are stable, the bound phosphate with few exceptions cycles on and off. Of special interest is the observation that the phosphate bound to ICP 4a and 4c cycles on and off, whereas that bound to ICP 4b is stably associated. Similar cycling was observed for ICP 6, 11, 22, and 27. The observation that 4a and 4c can be phosphorylated as late as 24 h after infection, i.e., long after their synthesis ceases, suggests that all three forms may have defined functions that persist throughout the reproductive cycle. (iii) All three forms of ICP 4 can be the translational products of only one of two copies of the ICP 4 gene in the viral genome. (iv) Analyses of the distribution of the viral proteins within the cell indicate that phosphorylation is not a major determinant in the compartmentalization of most viral phosphoproteins. (v) Comparisons of the binding to DNA-cellulose of artificial mixtures of 32P- and [35S]methionine-labeled proteins from infected cells indicate that phosphorylation in some instances enhances (e.g., ICP 29) and in other instances decreases (e.g., ICP 6) binding affinity for DNA. In light of previous reports that some of the proteins identified as phosphoproteins have regulatory functions, the data suggest that phosphorylation may modify the activity of regulatory proteins in herpes simplex virus-infected cells.


Emotional dysfunction in avoidant personality disorder and borderline personality disorder: A cross-sectional comparative study.
According to the literature, avoidant personality disorder (APD) is often overlooked in research on personality disorders. In the present study, patients with APD were compared to patients with borderline personality disorder (BPD) with respect to emotional dysfunction. Emotional dysfunction was operationalized through the Affect Integration Inventory. Sixty-one patients receiving treatment at specialized outpatient hospital facilities for either BPD (n = 25) or APD (n = 36) (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) were included in a cross-sectional study. Supporting our expectations of no difference in the global capacity for affect integration between groups, the estimated difference was 0.00 (95% confidence interval [CI] [-0.53, 0.53]). On the other hand, the expected increased dysfunction in APD regarding Expression could not be confirmed. Furthermore, problems with specific affects distinguished the groups; integration of Interest was worse in APD (p = 0.01), whereas integration of Jealousy was worse in BPD (p = 0.04). In terms of prototypical modes of experiencing affects, APD was characterized by decreased access to the motivational properties of Interest (p < 0.01), while BPD was more driven by Interest (p < 0.01), Anger (p < 0.01), and Jealousy (p = 0.01). In conclusion, even though the two disorders are characterized by similar overall levels of emotional dysfunction, they differ systematically and predictably regarding specific affects and modes of experiencing. These findings carry implications for the understanding of emotional dysfunction in APD and BPD, suggesting specific areas of emotional dysfunction that could be targeted in tailored psychotherapeutic interventions.


Rare event selection of fetal nucleated erythrocytes in maternal blood by flow cytometry.
A noninvasive method of prenatal genetic diagnosis requires fetal cell selection from the maternal circulation that allows efficient recovery for analysis by fluorescence in situ hybridization (FISH). We have solved several problems that negatively affect the isolation and FISH analysis of fetal nucleated red blood cells (nRBCs) in the maternal circulation. The use of glycophorin A (Gly A) antibodies (Abs) for selection is problematic because all five monoclonal antibodies (mAbs) tested caused agglutination of non-nRBCs, thereby changing both light scatter and fluorescence properties of cells by flow cytometry. Because the number of non-nRBCs is variable after Ficoll separation, isolation of nRBCs could be compromised severely by agglutination of nucleated cells with nonnucleated cells, causing them to shift light scatter and fluorescence properties. Several methods for the removal of unwanted maternal white blood cells with CD45 mAbs were also evaluated. Magnetic bead depletion was found to interfere with FISH detection because of residual bead debris after sorting. By contrast, removal of CD45+ cells by a panning technique eliminated this problem. Positive selection methods based on CD71, CD45, and LDS-751 staining and detection of fetal cells by gamma globin expression were also analyzed. Fetal cells were detected by FISH in 11 of 19 (CD71 selection) and in 13 of 15 (gamma selection) random pregnancies. These data support the possibility of a noninvasive method for isolation and analysis of fetal cells for prenatal diagnosis.


Aerococcus viridans native valve endocarditis.
Aerococcus viridans is an infrequent human pathogen and few cases of infective endocarditis have been reported. A case involving a 69-year-old man with colon cancer and hemicolectomy 14 years previously, without recurrence, is reported. A diagnosis of native mitral valve endocarditis was established on the basis of clinical presentation, characteristic echocardiographic findings and pathological specimen examination after urgent valve replacement. A viridans endocarditis appears to be particularly virulent, requiring a surgical approach in four of 10 cases reported and death in one of nine. Given the aggressive nature of A viridans endocarditis and the variable time to diagnosis (a few days to seven months), prompt recognition of symptoms and echocardiography, in addition to blood cultures, should be performed when symptoms persist.


Water and solutions at negative pressure: Raman spectroscopic study to -80 megapascals.
Microscopic inclusions of aqueous fluids trapped in interstices in quartz and other crystals provide novel systems for the deliberate study of liquids under tension. Liquids under tension should differ in interesting ways from those at ambient pressure or compressed liquids because attractive, rather than repulsive, forces should dominate their behavior. Static tensions in excess of 100 megapascals (~1000 atmospheres) have been obtained reproducibly. Video-recorded observations of the final liquid rupture process, coupled with extrapolations of data at positive pressure, suggest that the homogeneous vapor nucleation point was reached in two of the cases studied. Raman spectra of the fluids at -80 megapascals show that an isothermal volume stretch of -5 percent by volume has only a weak effect on the spectral features and is similar to the effect of isobaric heating.


MicroRNA‑146a inhibits the inflammatory responses induced by interleukin‑17A during the infection of Helicobacter pylori.
Helicobacter pylori (H. pylori) infection is the major cause of chronic active gastritis and peptic ulcer disease. Upregulation of IL‑17A is associated with H. pylori infection in the gastric mucosa; however, the factors involved in the regulation of interleukin (IL)‑17A‑induced inflammatory responses in H. pylori‑associated gastritis remain unknown. MicroRNAs (miRNAs) serve as key post‑transcriptional regulators of gene expression and are associated with the H. pylori infection. The present study aimed to analyze the effects of IL‑17A on the expression of miR‑146a upon infection with H. pylori, as well as to identify the possible impact of miR‑146a dysregulation on the inflammatory response in vivo and in vitro. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the expression levels of miR‑146a in gastric epithelial cells upon IL‑17A stimulation. The effects of miR‑146a mimics on IL‑17A‑induced inflammatory responses in SGC‑7901 cells were evaluated. The effects of miR‑146a mimics on the expression levels of IL‑1 receptor‑associated kinase 1 (IRAK1) and tumor necrosis factor receptor‑associated factor 6 (TRAF6) upon IL‑17A treatment were analyzed, and the IL‑17A‑stimulated inflammation following the silencing of IRAK1 and TRAF6 was observed. In addition, the correlation between miR‑146a and IL‑17A in human gastric mucosa with H. pylori was examined. The results indicated that IL‑17A‑induced miR‑146a may regulate the inflammatory response during the infection of H. pylori in a nuclear factor‑κB‑dependent manner. Furthermore, the expression of miR‑146a and IL‑17A are positively correlated in human gastric mucosa infected with H. pylori. These data suggested that miR‑146a may serve as a biomarker or therapeutic target in gastritis therapy.


Elg1, the major subunit of an alternative RFC complex, interacts with SUMO-processing proteins.
PCNA is a homotrimeric ring with important roles in DNA replication and repair. PCNA is loaded and unloaded by the RFC complex, which is composed of five subunits (Rfc1-5). Three additional complexes that share with RFC the small subunits (Rfc2-5) and contain alternative large subunits were found in yeast and other eukaryotes. We have recently reported that one of these, the Elg1-RFC complex, interacts with SUMOylated PCNA and may play a role in its unloading during DNA repair. Here we report that a yeast-two-hybrid screen with the N terminus of Elg1(which interacts with SUMOylated PCNA) uncovered interactions with proteins that belong to the SUMO pathway, including Slx5 and Slx8, which form an E3 ubiquitin ligase that ubiquitinates SUMOylated proteins. Mutations in SLX5 result in a genomic instability phenotype similar to that of elg1 mutants. The physical interaction between the N terminus of Elg1 and Slx5 is mediated by poly-SUMO chains but not by PCNA modifications, and requires Siz2, but not Siz1, activity. Thus our results highlight the many important roles played by Elg1, some of which are PCNA-dependent and some PCNA-independent.


Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.
The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. Ondansetron rdf is effective for the prophylaxis of rinv.


Role of water channel AQP-CD in water retention in SIADH and cirrhotic rats.
We determined whether aquaporin of collecting duct (AQP-CD) is involved in pathogenesis of water retention in rats with experimental models of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and liver cirrhosis. SIADH rats were made by administering 1-desamino-8-D-arginine vasopressin (DDAVP) subcutaneously and providing them with a liquid diet. Serum Na levels decreased to < 120 meq/l on day 2, and hyponatremia persisted throughout the rest of observation period. Six hours after the DDAVP infusion, the expression of AQP-CD mRNA significantly increased by 198%, followed by > 144% increases in its expression during the 14-day observation period. On day 7, the increased expression of AQP-CD mRNA was abolished after the administration of an antidiuretic, nonpeptide arginine vasopressin (AVP) antagonist, OPC-31260, which was closely related to a marked diuresis and a prompt normalization of serum Na levels in SIADH rats. Rats were made cirrhotic by injecting a mixture of carbon tetrachloride and olive oil subcutaneously for 3 mo. The expression of AQP-CD mRNA was increased by 164% in the decompensated cirrhotic rats. The blockade of AVP action by OPC-31260 significantly diminished its expression. These results indicate that water channel AQP-CD plays an important role in water retention in pathological states of SIADH and liver cirrhosis.


Isolation of the kernel for respiratory rhythm generation in a novel preparation: the pre-Bötzinger complex "island".
The pre-Bötzinger complex (pre-BötC), a bilaterally distributed network of rhythmogenic neurons within the ventrolateral medulla, has been proposed to be the critical locus for respiratory rhythm generation in mammals. To date, thin transverse medullary slice preparations that capture the pre-BötC have served as the optimal experimental model to study the region's inherent cellular and network properties. We have reduced the thin slices to isolated pre-BötC "islands" to further establish whether the pre-BötC has intrinsic rhythmicity and is the kernel for rhythmogenesis in the slice. We recorded neuron population activity locally in the pre-BötC with macroelectrodes and fluorescent imaging of Ca(2+) activities with Calcium Green-1AM dye before and after excising the island. The isolated island remained rhythmically active with a population burst profile similar to the inspiratory burst in the slice. Rhythmic population activity persisted in islands after block of GABA(A)ergic and glycinergic synaptic inhibition. The loci of pre-BötC Ca(2+) activity imaged in thin slices and islands were similar, and imaged pre-BötC neurons exhibited synchronized flashing after blocking synaptic inhibition. Population burst frequency increased monotonically as extracellular potassium concentration was elevated, consistent with mathematical models consisting entirely of an excitatory network of synaptically coupled pacemaker neurons with heterogeneous, voltage-dependent bursting properties. Our results provide further evidence for a rhythmogenic kernel in the pre-BötC in vitro and demonstrate that the islands are ideal preparations for studying the kernel's intrinsic properties.


Artificial neural networks can predict trauma volume and acuity regardless of center size and geography: A multicenter study.
Trauma has long been considered unpredictable. Artificial neural networks (ANN) have recently shown the ability to predict admission volume, acuity, and operative needs at a single trauma center with very high reliability. This model has not been tested in a multicenter model with differing climate and geography. We hypothesize that an ANN can accurately predict trauma admission volume, penetrating trauma admissions, and mean Injury Severity Score (ISS) with a high degree of reliability across multiple trauma centers. Three years of admission data were collected from five geographically distinct US Level I trauma centers. Patients with incomplete data, pediatric patients, and primary thermal injuries were excluded. Daily number of traumas, number of penetrating cases, and mean ISS were tabulated from each center along with National Oceanic and Atmospheric Administration data from local airports. We trained a single two-layer feed-forward ANN on a random majority (70%) partitioning of data from all centers using Bayesian Regularization and minimizing mean squared error. Pearson's product-moment correlation coefficient was calculated for each partition, each trauma center, and for high- and low-volume days (>1 standard deviation above or below mean total number of traumas). There were 5,410 days included. There were 43,380 traumas, including 4,982 penetrating traumas. The mean ISS was 11.78 (SD = 6.12). On the training partition, we achieved R = 0.8733. On the testing partition (new data to the model), we achieved R = 0.8732, with a combined R = 0.8732. For high- and low-volume days, we achieved R = 0.8934 and R = 0.7963, respectively. An ANN successfully predicted trauma volumes and acuity across multiple trauma centers with very high levels of reliability. The correlation was highest during periods of peak volume. This can potentially provide a framework for determining resource allocation at both the trauma system level and the individual hospital level. Care Management, level IV.


[The non-etherifying and free fatty acids of blood plasma. Pathogenesis of arterial hypertension and symptoms of syndrome of overeating-metabolic syndrome: a lecture].
From point of view of physiology, the metabolic syndrome is a syndrome of overeating when an optimal by the content of fatty acids in food is too much a physologically. This condition forms an omental variant of increase of body mass. The oleic triglycerides cumulate in fatty cells of omentum and after activation of lypolisis at the level of paracrinically regulating associations of cells and organs release into blood many non-etherifying fatty acids. The albumin has no possibilities to bind them all. The polar fatty acids-free fatty acids which are not bind by albumin form in blood direct heterogeneous micelles which spontaneously incorporate into plasmatic membrane of monolayer of endothelium. At that, the hydrophilic lipid pores are formed through which Ca2+, Na+ and water get into cytosol and K+ gets out. The hydration of cytosol and hypercalcinemia increase dimensions, thickness of monolayer of epithelium, narrow lumen of arterioles of muscular type and increase resistance to blood flow in distal section of arterial channel. The hydrodynamic pressure increases compensatory in proximal section of arterial channel along with the development of arterial hypertension. The late in phylogenesis insulin has no possibilities to block lipolysis in fatty cells of omentum hence these cells have no receptors to this insulin. While in blood plasma the concentration of non-etherifying acids is increased the cell will not absorb and oxidize glucose. The non-etherifying form the resistance too late in phylogenesis insulin, hyperglycemia and hyperinsulinemia. The concentration of oleic triglycerides increases in blood. The increase in omentum of number of fatty cells of loose connective tissue forms biological reaction of inflammation right up to destruction of overloaded oleic triglycerides cells on the type of apoptosis. This occurrence increases the concentration of C-reactive protein in blood plasma. All symptoms of syndrome of overeating (metabolic syndrome) are formed in the framework of integrated pathogenesis.


Ayahuasca's entwined efficacy: An ethnographic study of ritual healing from 'addiction'.
A range of studies has demonstrated the efficacy of the psychoactive Amazonian brew ayahuasca in addressing substance addiction. These have revealed that physiological and psychological mechanisms are deeply enmeshed. This article focuses on how interactive ritual contexts support the healing effort. The study of psychedelic-assisted treatments for addiction has much to gain from ethnographic analyses of healing experiences within the particular ecologies of use and care, where these interventions are rendered efficacious. This is an ethnographically grounded, qualitative analysis of addiction-recovery experiences within ayahuasca rituals. It draws on long-term fieldwork and participant observation in ayahuasca communities, and in-depth, semi-structured interviews of participants with histories of substance misuse. Ayahuasca's efficacy in the treatment of addiction blends somatic, symbolic and collective dimensions. The layering of these effects, and the direction given to them through ritual, circumscribes the experience and provides tools to render it meaningful. Prevailing modes of evaluation are ill suited to account for the particular material and semiotic efficacy of complex interventions such as ayahuasca healing for addiction. The article argues that practices of care characteristic of the ritual spaces in which ayahuasca is collectively consumed, play a key therapeutic role. The ritual use of ayahuasca stands in strong contrast to hegemonic understandings of addiction, paving new ground between the overstated difference between community and pharmacological interventions. The article concludes that fluid, adaptable forms of caregiving play a key role in the success of addiction recovery and that feeling part of a community has an important therapeutic potential.


Regulation of protein phosphorylation in pancreatic acini. Distinct effects of Ca2+ ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate.
Regulation of protein phosphorylation in isolated pancreatic acini by the intracellular messengers Ca2+ and diacylglycerol was studied by using the Ca2+ ionophore A23187 and the tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate. As assessed by two-dimensional polyacrylamide-gel electrophoresis, the phorbol ester (1 microM) and Ca2+ ionophore (2 microM) altered the phosphorylation of distinct sets of proteins between Mr 83,000 and 23,000 in mouse and guinea-pig acini. The phorbol ester increased the phosphorylation of four proteins, whereas the ionophore increased the phosphorylation of two proteins and, in mouse acini, decreased the phosphorylation of one other protein. In addition, the phorbol ester and ionophore each caused the dephosphorylation of two proteins, of Mr 20,000 and 20,500. Administered together, these agents reproduced the changes in phosphorylation induced by the cholinergic agonist carbamoylcholine. The effects of the phorbol ester and ionophore on acinar amylase release were also studied. In mouse pancreatic acini, a maximally effective concentration of phorbol ester (1 microM) produced a secretory response that was only 28% of that produced by a maximally effective concentration of carbamoylcholine, whereas the ionophore (0.3 microM) stimulated amylase release to two-thirds of the maximal response to carbamoylcholine. In contrast, in guinea-pig acini, the phorbol ester and carbamoylcholine evoked similar maximal secretory responses, whereas the maximal secretory response to the ionophore was only 35% of that to carbamoylcholine. Combination of phorbol ester and ionophore resulted in a modest synergistic effect on amylase release in both species. It is concluded that cholinergic agonists act via both diacylglycerol and Ca2+ to regulate pancreatic protein phosphorylation, but that synergism between these intracellular messengers is of limited importance in stimulating enzyme secretion.


Quantification of acylfulvene- and illudin S-DNA adducts in cells with variable bioactivation capacities.
Illudin S and its semisynthetic analogue acylfulvene (AF) are structurally similar but elicit different biological responses. AF is a bioreductive alkylating anticancer agent with a favorable therapeutic index, while illudin S is in general highly toxic. AF toxicity is dependent on the reductase enzyme prostaglandin reductase 1 (PTGR1) for activation to a cytotoxic reactive intermediate. While illudin S can be metabolized by PTGR1, available data suggest that its toxicity does not correspond with PTGR1 function. The goal of this study was to understand how drug cytotoxicity relates to cellular bioactivation capacity and the identity and quantity of AF- or illudin S-DNA adducts. The strategy involved identification of novel illudin S-DNA adducts and their quantitation in a newly engineered SW-480 colon cancer cell line that stably overexpresses PTGR1 (PTGR1-480). These data were compared with cytotoxicity data for both compounds in PTGR1-480 versus normal SW-480 cells, demonstrating that AF forms more DNA adducts and is more cytotoxic in cells with higher levels of PTGR1, whereas illudin S cytotoxicity and adduct formation are not influenced by PTGR1 levels. Results are discussed in the context of an overall model for how changes in relative propensities of these compounds to undergo cellular processes, such as bioactivation, contributes to DNA damage, and cytotoxicity.


A pediatric surgery study: parent usage of the Internet for medical information.
The goal of this study was to (1) determine parents access to and use of the Internet for information relating to their child's health; (2) investigate parents methods of searching for such information; and (3) evaluate the information found in relation to its readability, accuracy, and influence. A study was conducted of 150 parents of outpatients in the Pediatric Surgery Clinic of a local Children's Hospital. Parents completed study surveys over a 6-week time frame. All parents (150 of 150, 100%) completed the surveys. The median age of the parents was 35 years, 83% (124 of 150) were mothers, and most (32%) attained a high school diploma. Of the 128 parents having Internet access, 71% used the Internet to search for health-related information. A majority of parents, 98%, agreed or somewhat agreed that the information they found was comprehensible and helpful. All respondents at least somewhat trusted information found, and 52% were at least somewhat influenced by online information when making a medical decision. Many parents use the Internet for additional medical information, but they do not access this information frequently. The overwhelmingly positive impression of online health information suggests parents are unaware of the dangers of encountering misleading sources, an issue of special concern when considering the amount of influence this information carries. A movement must be made to create uniform guidelines for health information on the Internet. In the meantime, pediatric surgeons must take a role in guiding parents toward accurate online sources and becoming more Internet proficient themselves.


Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose.
A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C'-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.


Current bacterial speciation and antibiotic resistance in deep infections after operative fixation of fractures.
Infection after fracture fixation is a major source of morbidity. Information regarding bacterial speciation and antibiotic resistance is lacking. We attempted to determine the speciation and drug resistance profiles associated with fracture fixation infections. Retrospective study. Level I trauma center. Two hundred eleven patients with 214 infections underwent surgery for postoperative infection from December 2006 to December 2010. Deep postoperative infections within 12 months of fixation were included. None. Incidence of each bacterial species and rate of clinically relevant resistance in Staphylococcus aureus, gram-negative rod (GNR), and Enterococcus species. The effect of timing of infection presentation and location of fracture on bacterial speciation was also investigated. Fifty-six percent of infections had S. aureus present, with 58% of those (32% of all infections) being methicillin-resistant S. aureus. Thirty-two percent of infections had at least one GNR present, with only 4% of those being multidrug resistant. We found a marked increase in the rate of GNR infections of the pelvis, acetabulum, and proximal femur (63%) compared with other locations (27%), which was statistically significant (P = 0.0002). At our center, S. aureus and GNR are most often found in deep postoperative infections after fixation. Methicillin-resistant S. aureus is common in this population. Our GNR rate is high, but resistance in this group was low. The proportion of GNR infections in the pelvis, acetabulum, and proximal femur was high even in closed fractures. These data provide a modern snapshot of orthopaedic infections after fracture fixation and might be useful in designing future studies and protocols for antibiotic prophylactic treatment. We are considering the use of aminoglycosides in the treatment of closed fractures of the pelvis, acetabulum, and proximal femur. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Modification of Cellulose with Succinic Anhydride in TBAA/DMSO Mixed Solvent under Catalyst-Free Conditions.
Homogeneous modification of cellulose with succinic anhydride was performed using tetrabutylammonium acetate (TBAA)/dimethyl sulfoxide (DMSO) mixed solvent. The molar ratio of succinic anhydride (SA) to free hydroxyl groups in the anhydroglucose units (AGU), TBAA dosage, reaction temperature, and reaction time were investigated. The highest degree of substitution (DS) value of 1.191 was obtained in a 10 wt% TBAA/DMSO mixed solvent at 60 °C for 60 min, and the molar ratio of SA/AGU was 6/1. The molar ratio of SA/AGU and the TBAA dosage showed a significant influence on the reaction. The succinoylated cellulose was characterized by ATR-FTIR, TGA, XRD, solid state CP/MAS 13C NMR spectroscopy (CP/MAS 13C NMR), and SEM. Moreover, the modified cellulose was applied for the adsorption of Cu2+ and Cd2+, and both the DS values of modified cellulose and pH of the heavy metal ion solutions affected the adsorption capacity of succinylated cellulose. The highest capacity for Cu2+ and Cd2+ adsorption was 42.05 mg/g and 49.0 mg/g, respectively.


Effects of multidisciplinary education on outcomes in patients with irritable bowel syndrome.
The impact of education on irritable bowel syndrome (IBS) is not well known. This study evaluated the effect of a onetime group education program on patient-based outcomes in IBS. All adults referred by Mayo Clinic physicians to the Gastroenterology Division with a diagnosis of IBS between May 1997 and March 1998 were asked to participate. Questionnaires were administered at baseline and 6 months. Symptom resolution, change in pain severity, quality of life, Health-Promoting Lifestyle Profile score, overall patient satisfaction, and health care utilization were compared among those patients who attended the multidisciplinary class and those who did not. Of the 506 patients approached, 403 (80%) agreed to participate. The clinical diagnosis was confirmed in 344 patients (85%) on chart review; 211 patients (61%) subsequently completed a follow-up questionnaire. Overall, 29% of class attendees who met Rome criteria for IBS at baseline no longer met Rome criteria at follow-up, compared with 7% of nonattendees. By multivariate analysis, class attendance predicted higher odds of not meeting Rome criteria at follow-up in individuals meeting Rome criteria at baseline (odds ratio, 7.91; 95% confidence interval, 0.97-64.41) than in nonattendees, but the opposite effect was seen with class attendance in those not meeting Rome criteria at baseline. This interaction between baseline Rome status and class attendance was significant (P < 0.05). Class attendance was associated with improvement in Health-Promoting Lifestyle Profile scores (P < 0.05) but not with change in pain, quality of life, satisfaction, or health care utilization. A onetime, multidisciplinary class for patients with IBS was associated with improvement in symptoms and health-promoting lifestyle behavior.


Virus population extinction via ecological traps.
Populations are at risk of extinction when unsuitable or when sink habitat exceeds a threshold frequency in the environment. Sinks that present cues associated with high-quality habitats, termed ecological traps, have especially detrimental effects on net population growth at metapopulation scales. Ecological traps for viruses arise naturally, or can be engineered, via the expression of viral-binding sites on cells that preclude viral reproduction. We present a model for virus population growth in a heterogeneous host community, parameterized with data from populations of the RNA bacteriophage Phi6 presented with mixtures of suitable host bacteria and either neutral or trap cells. We demonstrate that viruses can sustain high rates of population growth in the presence of neutral non-hosts as long as some host cells are present, whereas trap cells dramatically reduce viral fitness. In addition, we demonstrate that the efficacy of traps for viral elimination is frequency dependent in spatially structured environments such that population viability is a nonlinear function of habitat loss in dispersal-limited virus populations. We conclude that the ecological concepts applied to species conservation in altered landscapes can also contribute to the development of trap cell therapies for infectious human viruses.


Theoretical study on molecular design and optical properties of organic sensitizers.
A series of organic sensitizers based on different configurations such as D-π-A, D-[π]n-A, D-π-[A]n, [D]n-π-A, D-π-A-π-D, D-π-[A]n-π-D and D-[π-A]n-π-D (where n = 1-4) are designed using theoretical methods. The effects of repeating π-linker, donor-acceptor moieties and the substitution of additional donor-acceptor moieties on the optoelectronic properties have been addressed. Our results show that the strength of the acceptor units changes the mono band absorption into dual band absorption in all the considered strategies. We found that repeating π-linker/donor moieties in the D-π-A series enhances the intensity of the absorption and can tune their absorption spectra from UV-to-visible and visible to near IR regions by repeating acceptor units. Also, the present results indicate that the D-π-A-π-D configuration shows improved optical properties than the conventional D-π-A structure. This theoretical study explores the new configurations and design strategies of organic dyes for developing efficient light harvesting devices working in the whole visible and near IR regions.


A Six-Year Study on Epidemiology of Electrical Burns in Northern Iran: Is It Time to Pay Attention?
Although electrical burns are less prevalent than other types, they put socioeconomic burden on communities, yielding higher mortalities. Therefore, the frequency and causes of electrical burns in the largest burn center in northern Iran were studied. All patients with electrical burn injuries admitted to Velayat Hospital, Rasht, Iran participated in this descriptive cross-sectional study. The data collection tool was a checklist including demographic data, damage mechanism, voltage classification (high or low), injured organ, ICU need, length of stay (LOC), electrical burn severity (degree and area of burns based on TBSA), surgical interventions, and return to work. All data were gathered through HIS system and analyzed. Most electrical burns occurred in men (99.4%) and most of whom had electricity-related jobs (26%). The majority of victims had third-degree burns (63%), and electrical current-induced burns in entry points occurred in the upper and lower extremities, head and other organs ranked the first to fourth, respectively. Most burns happened due to abrupt contact with electrical current (83.33%) in routine home activities (52.78%). The mean LOC was 8.73 days, suggesting that LOC increased significantly, if the electrical current entered the body through lower extremities, while it decreased significantly, if the electrical current exited through lower extremities. The majority of electrical burn victims were men. Most burns occurred in urban communities in summer. Most people were affected by high voltage electricity.


Tryptophan degradation in women with breast cancer: a pilot study.
Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy. Blood samples were collected from women with a recent diagnosis of breast cancer (n = 33) before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (n = 24) provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP) was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (p = 0.036), which remained elevated in women with breast cancer throughout the treatment trajectory. The findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.