Moyamoya syndrome in a splenectomized patient with beta-thalassemia intermedia.
We describe a 14-year-old Japanese girl with beta-thalassemia intermedia who developed moyamoya syndrome after splenectomy. This patient had compound heterozygous mutations of the beta-globin gene and received occasional transfusions. After splenectomy at 12 years of age, she transiently required partial exchange transfusions for leukoerythroblastosis but attained transfusion independence. Two years after the splenectomy, transient ischemic attacks occurred repeatedly with right hemiparesis or left paresthesia. Magnetic resonance imaging revealed bilateral stenosis of the internal carotid arteries and dilatation of the perforating branches with the formation of moyamoya vessels but not infarctions. The strict adherence to aspirin and dipyridamole has led to no stroke or progression of the vasculopathy for 8 years. Moyamoya disease has been reported in a patient with beta-thalassemia major. Cerebral vasculopathy can be a rare but grave consequence of the thromboembolic complications in beta-thalassemia major/intermedia. (J Child Neurol 2006;21:75-77).


Central command, but not muscle reflex, stimulates cutaneous sympathetic efferents of cats.
We determined the effects of stimulation of the mesencephalic locomotor region (MLR) and the muscle reflex, each evoked separately, on the discharge of cutaneous sympathetic fibers innervating the hairy skin of decerebrate cats. Electrical stimulation of the MLR was performed while the cats were paralyzed with vecuronium bromide. The muscle reflex was evoked while the cats were not paralyzed by electrical stimulation of the tibial nerve at current intensities that did not activate directly group III and IV muscle afferents. MLR stimulation increased, on average, the discharge of the 23 cutaneous sympathetic fibers tested (P < 0.05). The muscle reflex, in contrast, had no overall effect on the discharge of 21 sympathetic fibers tested (P > 0.05). Both maneuvers markedly increased mean arterial pressure and heart rate (P < 0.05). Prevention of the baroreceptor reflex with the alpha-adrenergic blocking agent phentolamine did not reveal a stimulatory effect of the muscle reflex on cutaneous sympathetic discharge. We conclude that the MLR is a more important mechanism than is the muscle reflex in controlling sympathetic discharge to hairy skin during dynamic exercise.


Oral zinc as an adjunct to dapsone in lepromatous leprosy.
Oral zinc was tried in 15 cases of multibacillary leprosy as an immunostimulant in addition to conventional antileprosy drugs. Results were compared with those in ten similar cases treated with dapsone alone. Cases treated with zinc showed faster clinical improvement, regrowth of eyebrows, rapid fall in the bacterial index (BI) and in the bacterial index in the granuloma (BIG), early and greater influx in lymphocytes in the granuloma, and neovascularization. Upgrading occurred in 6 out of 15 patients taking zinc, but in only 1 out of 10 patients in the control group. Five out of six patients who showed upgrading in the treated group became lepromin positive. Only one patient (BL) showed lepromin conversion in the control group.


A Prediction Tool to Facilitate Risk-Stratified Screening for Squamous Cell Skin Cancer.
Cutaneous squamous cell cancers (cSCCs) present an under-recognized health issue among non-Hispanic whites, one that is likely to increase as populations age. cSCC risks vary considerably among non-Hispanic whites, and this heterogeneity indicates the need for risk-stratified screening strategies that are guided by patients' personal characteristics and clinical histories. Here we describe cSCCscore, a prediction tool that uses patients' covariates and clinical histories to assign them personal probabilities of developing cSCCs within 3 years after risk assessment. cSCCscore uses a statistical model for the occurrence and timing of a patient's cSCCs, whose parameters we estimated using cohort data from 66,995 patients in the Kaiser Permanente Northern California healthcare system. We found that patients' covariates and histories explained approximately 75% of their interpersonal cSCC risk variation. Using cross-validated performance measures, we also found cSCCscore's predictions to be moderately well calibrated to the patients' observed cSCC incidence. Moreover, cSCCscore discriminated well between patients who subsequently did and did not develop a new primary cSCC within 3 years after risk assignment, with area under the receiver operating characteristic curve of approximately 85%. Thus, cSCCscore can facilitate more informed management of non-Hispanic white patients at cSCC risk. cSCCscore's predictions are available at https://researchapps.github.io/cSCCscore/.


Neuropathology associated with ventricular assist devices: an autopsy series of 33 patients.
The ventricular assist device (VAD) is a mechanical pump that has been shown to be an effective modality of cardiac support in patients with heart failure refractory to pharmacologic intervention and who are awaiting cardiac allograft transplantation. Neuropathologic findings in these patients have not been well described. We retrospectively reviewed 2,632 autopsy reports (between 1990 and 2000) and found 64 patients who received VADs. Of these 64 patients, brain and spinal cord tissue was available for review in 33 patients (25 males and eight females; age range, 4 to 69 years; mean age, 52 years). The study group was composed of these 33 patients. Ventricular assist devices were in place from one to 603 days (mean 49 days). Twenty-five patients had left VAD, three had right VAD, and five had biventricular VADs. Brain weights ranged from 928 g to 1,740 g (mean 1,325 g). The most common central nervous system pathologic findings included infarct (N = 23; 70%), acute neuronal necrosis (N = 22; 67% focal and N = 1; diffuse anoxic encephalopathy), hemorrhage (N = 14; 42%), and herniations (N = 7; 21%). Two patients had no neuropathologic findings at autopsy. Cause of death was central nervous system-related in eight patients (24%) including six with massive parenchymal hemorrhage and herniations, one with brainstem infarction, and one with air embolism (radiographically diagnosed). The most common causes of death in the remaining 25 patients included sepsis (n = 10; 30%), pneumonia (n = 4; 12%), and embolic events with widespread infarcts (n = 4; 12%). The most common neuropathologic findings in patients with VAD were related to ischemia and infarction. In a significant subset of patients, central nervous system pathology, particularly hemorrhage with herniation, was the primary cause of death. Ann Diagn Pathol 5:67-73, 2001.


Stromal Cells in the Pathogenesis of Inflammatory Bowel Disease.
Up till now, research on inflammatory bowel disease [IBD] has mainly been focused on the immune cells present in the gastrointestinal tract. However, recent insights indicate that stromal cells also play an important and significant role in IBD pathogenesis. Stromal cells in the intestines regulate both intestinal epithelial and immune cell homeostasis. Different subsets of stromal cells have been found to play a role in other inflammatory diseases [e.g. rheumatoid arthritis], and these various stromal subsets now appear to carry out also specific functions in the inflamed gut in IBD. Novel potential therapies for IBD utilize, as well as target, these pathogenic stromal cells. Injection of mesenchymal stromal cells [MSCs] into fistula tracts of Crohn's disease patients is already approved and used in clinical settings. In this review we discuss the current knowledge of the role of stromal cells in IBD pathogenesis. We further outline recent attempts to modify the stromal compartment in IBD with agents that target or replace the pathogenic stroma.


Competitive foods sales are associated with a negative effect on school finances.
It is widely presumed that competitive foods-foods offered for sale in schools in addition to reimbursable federal meals programs-provide revenue that is essential to maintain school foodservices. However, evidence is lacking to demonstrate whether competitive foods sales truly improve foodservice financial viability. The aim of this research was to assess whether or not competitive foods sales have an overall positive financial effect on school foodservice finances. DESIGN AND STATISTICAL ANALYSES: This observational study used a multivariate time series analysis of annual foodservice financial data from repeated observations of 344 Minnesota public school districts between 2001 and 2008 (N=2,695). First, revenue from competitive foods was assessed in terms of whether or not such revenue displaced or complemented revenue from reimbursable meals. Second, profit from competitive foods was assessed in terms of whether or not such profit displaced or increased total school foodservice profit. Fixed effects models indicated small but significant negative relationships between competitive foods sales and reimbursable meals revenue, as well as overall foodservice profit. A 10% increase in competitive foods revenue was associated with a 0.1% decrease in reimbursable meals revenue (P<0.05). A 10% increase in competitive foods profit was associated with a 0.7% decrease in overall foodservice profit among schools with profitable competitive sales (P<0.10). Study findings suggest that competitive foods can have a negative effect on school foodservice finances. Better understanding of foodservice finances could influence current approaches to improve school nutrition. Improved recordkeeping may be necessary to ensure that public funds are not used to subsidize schools' competitive offerings.


Analysis of microplastics of a broad size range in commercially important mussels by combining FTIR and Raman spectroscopy approaches.
Microplastic (MP) contamination is present in the entire marine environment from the sediment to the water surface and down to the deep sea. This ubiquitous presence of MP particles opens the possibility for their ingestion by nearly all species in the marine ecosystem. Reports have shown that MP particles are present in local commercial seafood species leading to the possible human ingestion of these particles. However, due to a lack of harmonized methods to identify microplastics (MPs), results from different studies and locations can hardly be compared. Hence, this study was aimed to detect, quantify, and estimate MP contamination in commercially important mussels originating from 12 different countries distributed worldwide. All mussels were obtained from supermarkets and were intended for human consumption. Using a combinatorial approach of focal plane array (FPA)-based micro- Fourier-transform infrared (FTIR) spectroscopy and micro-Raman spectroscopy allowed the detection and characterization of MP down to a size of 3 μm in the investigated mussels. Further, a gentle sample purification method based on enzymes has been modified in order to optimize the digestion of organic material in mussels. A random forest classification (RFC) approach, which allows a rapid discrimination between different polymer types and thus fast generation of data on MP abundance and size distributions with high accuracy, was implemented in the analytical pipeline for IR spectra. Additionally, for the first time we also applied a RFC approach for the automated characterization of Raman spectra of MPs.


[An evaluation of diagnosis and treatment of acute sinusitis at three health care centers].
The objective of this study was to evaluate the diagnosis and treatment of acute sinusitis at three health care centers in northern and eastern Iceland. Information on all those diagnosed with acute sinusitis (ICD 10 J01.0, J01.9) in the year 2004 at the communal health care centers in Akureyri, Husavik and Egilsstadir was obtained retrospectively from computerized clinical records. Key factors used for diagnosis and treatment were recorded. In order to obtain an equal distribution in population size only about one-third of the diagnoses made in Akureyri were included in the search (the first ten days of every month). The search yielded a total of 468 individuals. The average incidence of acute sinusitis was found to be 3.4 per 100 inhabitants per year. Adherence to clinical guidelines (albeit from other countries) regarding diagnosis of bacterial sinusitis was nearly nonexistent. There were considerable differences found between health care centers as to whether x-rays were used for diagnostic purposes. Blood tests were hardly used at all. The disease was diagnosed over the telephone in 28% of the cases (Husavik 38%, Akureyri 32%, Egilsstadir 10%). Over 90% of all individuals diagnosed with acute sinusitis received antibiotics, regardless of symptom duration. The antibiotics most often prescribed were Doxycyclin and Amoxicillin. The incidence of acute sinusitis in these three communities seems to be similar to other western countries. Acute bacterial sinusitis seems to be overdiagnosed and the use of antibiotics is in no context with clinical guidelines. Our results support the hypothesis that physicians tend to regard acute sinusitis as a bacterial disease, and treat it accordingly.


Antibacterial role for natural killer cells in host defense to Bacillus anthracis.
Natural killer (NK) cells have innate antibacterial activity that could be targeted for clinical interventions for infectious disease caused by naturally occurring or weaponized bacterial pathogens. To determine a potential role for NK cells in immunity to Bacillus anthracis, we utilized primary human and murine NK cells, in vitro assays, and in vivo NK cell depletion in a murine model of inhalational anthrax. Our results demonstrate potent antibacterial activity by human NK cells against B. anthracis bacilli within infected autologous monocytes. Surprisingly, NK cells also mediate moderate antibacterial effects on extracellular vegetative bacilli but do not have activity against extracellular or intracellular spores. The immunosuppressive anthrax lethal toxin impairs NK gamma interferon (IFN-γ) expression, but neither lethal nor edema toxin significantly alters the viability or cytotoxic effector function of NK cells. Compared to human NK cells, murine NK cells have a similar, though less potent, activity against intracellular and extracellular B. anthracis. The in vivo depletion of murine NK cells does not alter animal survival following intranasal infection with B. anthracis spores in our studies but significantly increases the bacterial load in the blood of infected animals. Our studies demonstrate that NK cells participate in the innate immune response against B. anthracis and suggest that immune modulation to augment NK cell function in early stages of anthrax should be further explored in animal models as a clinical intervention strategy.


Critical thresholds: key to unlocking the door to the prevention and specific treatments for acute pancreatitis.
Acute pancreatitis (AP), an acute inflammatory disorder of the exocrine pancreas, is one of the most common gastrointestinal diseases encountered in emergency departments with no specific treatments. Laboratory-based research has formed the cornerstone of endeavours to decipher the pathophysiology of AP, because of the limitations of such study in human beings. While this has provided us with substantial understanding, we cannot answer several pressing questions. These are: (a) Why is it that only a minority of individuals with gallstones, or who drink alcohol excessively, or are exposed to other causative factors develop AP? (b) Why do only some develop more severe manifestations of AP with necrosis and/or organ failure? (c) Why have we been unable to find an effective therapeutic for AP? This manuscript provides a state-of-the-art review of our current understanding of the pathophysiology of AP providing insights into the unanswered clinical questions. We describe multiple protective factors operating in most people, and multiple stressors that in a minority induce AP, independently or together, via amplification loops. We present testable hypotheses aimed at halting progression of severity for the development of effective treatments for this common unpredictable disease.


Research Ethics Committees and clinical research in Italy: where are we going?
Italian Ethics Committees (ECs) have entered a new phase because of the recent Law no. 189 of November 8 2012 and the Ministry of Health Decree of February 8 2013. The new norms have introduced important changes. In fact, ECs are now established not to serve a single hospital or research institution but to serve even Regions. Moreover, they are established on the basis of the number of inhabitants, research sites and expected amount of clinical trials. The implementation of the news norms into practice have produced a drastic reduction in the number of ECs. This fact could raise some issues but it could obtain some benefits. The paper explains the main steps of ECs and clinical research development in Italy. Special attention will be paid to recent trends. Moreover, the new norms will be illustrated, showing possible issues and benefits connected to their implementation.


Protein selection and avoidance strategies of contemporary and ancestral foragers: unresolved issues.
During seasonal or inter-annual periods of food shortage and restricted total calorie intake, ethnographically and ethnohistorically documented human foragers, when possible, under-utilize foods that are high in protein, such as lean meat, in favour of foods with higher lipid or carbohydrate content. Nutritional studies suggest that one reason for this behaviour stems from the fact that pregnant women, particularly at times when their total calorie intake is marginal, may be constrained in the amount of energy they can safely derive from protein sources to levels below about 25% of total calories. Protein intakes above this threshold may affect pregnancy outcome through decreased mass at birth and increased perinatal morbidity and mortality. This paper briefly outlines the evidence for the existence of an upper safe limit to total protein intake in pregnancy, and then discusses several facets of the issue that remain poorly understood. The paper ends by raising two basic questions directed especially toward specialists in primate and human nutrition: is this protein threshold real and demographically significant in modern human foraging populations? If so, does an analogous threshold affect pregnant female chimpanzees? If the answer to both of these questions is yes, we can then begin to explore systematically the consequences such a threshold might have for the diet and behaviour of early hominids.


Effectiveness of Acceptance and Commitment Therapy (ACT) in Professional Dementia Caregivers Burnout.
To implement and assess the efficacy of a 6-week Acceptance and Commitment Therapy intervention to reduce anxiety and burnout in healthcare professionals working with dementia, and to increase their psychological flexibility and life satisfaction. A total of 105 workers from the CSSV Ricard Fortuny Hospital were randomly assigned to an intervention group (Acceptance and Commitment Therapy) or a wait list control group. Psychological Flexibility (AAQ-II), Life Satisfaction (SWLS), Anxiety (STAI-T), and Burnout (MBI) were measured before and after the intervention. Follow-up data were collected 3 months and 12 months post-intervention. Split-plot analyses were performed following intention to treat approach. No significant differences were found in baseline outcome measures. No time effects were found in wait list control group in any variable. In the intervention group, pre-post comparison showed a significant decrease in levels of MBI emotional exhaustion (p = .001) and anxiety (p < .001), and an increase in life satisfaction levels (p < .001) and MBI personal accomplishment (p < .001). These results were maintained at the 3- and 12-month follow-up periods. No significant intervention effects were observed in pre-post flexibility scores; however, data suggest slight progressive increase in flexibility at follow-up. Acceptance and Commitment Therapy showed positive effects in healthcare professionals working with dementia by reducing anxiety and burnout. The implementation of Acceptance and Commitment Therapy could help to increase the psychological well-being of healthcare professionals working with dementia.


Tailored oxido-vanadium(V) cage complexes for selective sulfoxidation in confined spaces.
Five sets of oxido-vanadium(V) complexes, which include both cages and open structures, were prepared and tested in the catalytic oxidation of sulfides. It was found that the hemicryptophane complexes, which are simultaneously comprised of cyclotriveratrylene (CTV), binaphthol and oxido-vanadium(V) moieties, are the most efficient supramolecular catalysts. The specific shape of the confined hydrophobic space above the metal center leads to a strong improvement in the yield, selectivity and rate of the reaction, compared to the other catalysts investigated herein. A remarkable turnover number (TON) of 10 000 was obtained, which can be attributed to both the high reactivity and stability of the catalyst. Similarly to enzymes, the kinetic analysis shows that the mechanism of oxidation with the supramolecular catalysts obeys the Michaelis-Menten model, in which initial rate saturation occurs upon an increase in substrate concentration. This enzyme-like behavior is also supported by the competitive inhibition and substrate size-selectivity observed, which underline the crucial role played by the cavity.


Closing the gap in mammogram screening: an experimental intervention among low-income Hispanic women in community health clinics.
A low rate of mammogram screening exists among low-income Hispanic women. To address this disparity, an experimental intervention containing audiovisual and written media was conducted using the health belief model as a framework. The purpose of this study was to determine if low-income Hispanic women, more than 40 years of age, who received targeted cancer prevention education (n = 105) had a significantly greater perceived threat of breast cancer, greater benefits and lower barriers to screening, and stronger intentions to obtain mammograms compared to a control group (n = 105). Intervention participants reported significantly greater perceived benefits, self-efficacy, and mammogram screening intentions than the control group. Predictors of mammogram screening intentions, when controlling for covariates, included receiving the intervention, and having greater perceived benefits, self-efficacy, and lower barriers. Results demonstrate the effectiveness of a low-cost, theory-based intervention aimed at increasing mammogram screening to assist in the monitoring of Healthy People 2020 objectives.


The influences of family environment on personality traits.
In order to clarify the influences of family environment on the development of personality traits, 150 children (104 males and 46 females, mean age 13.2 +/- 2.4 years) who had been interviewed at the Child Guidance Clinic in Osaka were investigated. From 13 behavioral characteristics (activity, talkativeness, sociability, social skills, rule-keeping, will, aggression, emotional control, imagination, anxiety, maturity, intelligence, and neuroticism), factor analysis identified three personality traits: extraversion, maturity, and intellect. The effects of family environment (maternal and paternal participation in child rearing before and after 4years of age, child-rearing style, parental relationship, sibling relationship, number of siblings, birth order, and socioeconomic status) on these personality traits were examined based on a structural equation model. The results found, first, that extraversion was negatively associated with overprotection/interference and with maternal participation in child rearing. Maturity correlated with high socioeconomic status, appropriate child-rearing style, and paternal participation in child rearing. Intellect was related to high socioeconomic status and maternal participation in child rearing. Second, path analysis with selected variables revealed that 8% of variance in extraversion, 14% in maturity, and 10% in intellect was due to family environment. Third, children with high introversion or high intellect had stronger influences from family environment than did those with high extraversion or low intellect.


The selective anaplastic lymphoma receptor tyrosine kinase inhibitor ASP3026 induces tumor regression and prolongs survival in non-small cell lung cancer model mice.
Activation of anaplastic lymphoma receptor tyrosine kinase (ALK) is involved in the pathogenesis of several carcinomas, including non-small cell lung cancer (NSCLC). Echinoderm microtubule-associated protein like 4 (EML4)-ALK, which is derived from the rearrangement of ALK and EML4 genes, has been validated as a therapeutic target in a subset of patients with NSCLC. Here, we investigated the effects of ASP3026, a novel small-molecule ALK inhibitor, against ALK-driven NSCLC. ASP3026 inhibited ALK activity in an ATP-competitive manner and had an inhibitory spectrum that differed from that of crizotinib, a dual ALK/MET inhibitor. In mice xenografted with NCI-H2228 cells expressing EML4-ALK, orally administered ASP3026 was well absorbed in tumor tissues, reaching concentrations >10-fold higher than those in plasma, and induced tumor regression with a wide therapeutic margin between efficacious and toxic doses. In the same mouse model, ASP3026 enhanced the antitumor activities of paclitaxel and pemetrexed without affecting body weight. ASP3026 also showed potent antitumor activities, including tumor shrinkage to a nondetectable level, in hEML4-ALK transgenic mice and prolonged survival in mice with intrapleural NCI-H2228 xenografts. In an intrahepatic xenograft model using NCI-H2228 cells, ASP3026 induced continuous tumor regression, whereas mice treated with crizotinib showed tumor relapse after an initial response. Finally, ASP3026 exhibited potent antitumor activity against cells expressing EML4-ALK with a mutation in the gatekeeper position (L1196M) that confers crizotinib resistance. Taken together, these findings indicate that ASP3026 has potential efficacy for NSCLC and is expected to improve the therapeutic outcomes of patients with cancer with ALK abnormality.


CLPM: a cross-linked peptide mapping algorithm for mass spectrometric analysis.
Protein-protein, protein-DNA and protein-RNA interactions are of central importance in biological systems. Quadrapole Time-of-flight (Q-TOF) mass spectrometry is a sensitive, promising tool for studying these interactions. Combining this technique with chemical crosslinking, it is possible to identify the sites of interactions within these complexes. Due to the complexities of the mass spectrometric data of crosslinked proteins, new software is required to analyze the resulting products of these studies. We designed a Cross-Linked Peptide Mapping (CLPM) algorithm which takes advantage of all of the information available in the experiment including the amino acid sequence from each protein, the identity of the crosslinker, the identity of the digesting enzyme, the level of missed cleavage, and possible chemical modifications. The algorithm does in silico digestion and crosslinking, calculates all possible mass values and matches the theoretical data to the actual experimental data provided by the mass spectrometry analysis to identify the crosslinked peptides. Identifying peptides by their masses can be an efficient starting point for direct sequence confirmation. The CLPM algorithm provides a powerful tool in identifying these potential interaction sites in combination with chemical crosslinking and mass spectrometry. Through this cost-effective approach, subsequent efforts can quickly focus attention on investigating these specific interaction sites.


Leishmaniasis and malaria: new tools for epidemiologic analysis.
Parasitic diseases are still prevalent in many parts of the world, causing both human suffering and economic loss. Recent developments in biotechnology, such as the use of monoclonal antibodies and recombinant DNA, have the potential for providing both more extensive and detailed information on the parasite in the infected human and in insect vectors. New methods of detection, both in man and insect vectors, have been developed for two parasitic diseases, leishmaniasis and malaria. These new methodologies will be important in epidemiologic studies on the prevalence and transmission of these parasitic diseases.


Smoothing of Binary Codes, Uniform Distributions, and Applications.
The action of a noise operator on a code transforms it into a distribution on the respective space. Some common examples from information theory include Bernoulli noise acting on a code in the Hamming space and Gaussian noise acting on a lattice in the Euclidean space. We aim to characterize the cases when the output distribution is close to the uniform distribution on the space, as measured by the Rényi divergence of order α∈(1,∞]. A version of this question is known as the channel resolvability problem in information theory, and it has implications for security guarantees in wiretap channels, error correction, discrepancy, worst-to-average case complexity reductions, and many other problems. Our work quantifies the requirements for asymptotic uniformity (perfect smoothing) and identifies explicit code families that achieve it under the action of the Bernoulli and ball noise operators on the code. We derive expressions for the minimum rate of codes required to attain asymptotically perfect smoothing. In proving our results, we leverage recent results from harmonic analysis of functions on the Hamming space. Another result pertains to the use of code families in Wyner's transmission scheme on the binary wiretap channel. We identify explicit families that guarantee strong secrecy when applied in this scheme, showing that nested Reed-Muller codes can transmit messages reliably and securely over a binary symmetric wiretap channel with a positive rate. Finally, we establish a connection between smoothing and error correction in the binary symmetric channel.


Midlife physical activity engagement is associated with later-life brain health.
The relationship between midlife physical activity (PA), and cognition and brain health in later life is poorly understood with conflicting results from previous research. Investigating the contribution of midlife PA to later-life cognition and brain health in high-risk populations will propel the development of health guidance for those most in need. The current study examined the association between midlife PA engagement and later-life cognition, grey matter characteristics and resting-state functional connectivity in older individuals at high-risk for Alzheimer's disease. The association between midlife PA and later-life cognitive function was not significant but was moderated by later-life PA. Meanwhile, greater midlife moderate-to-vigorous PA was associated with greater grey matter surface area in the left middle frontal gyrus. Moreover, greater midlife total PA was associated with diminished functional connectivity between bilateral middle frontal gyri and middle cingulum, supplementary motor areas, and greater functional connectivity between bilateral hippocampi and right cerebellum, Crus II. These results indicate the potentially independent contribution of midlife PA to later-life brain health.


Dianthra[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DATT): synthesis, characterization, and FET characteristics of new π-extended heteroarene with eight fused aromatic rings.
A novel highly π-extended heteroarene with eight fused aromatic rings, dianthra[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DATT), was selectively synthesized via a newly developed synthetic strategy, fully characterized by means of single crystal X-ray structural analysis, and examined as an organic semiconductor in thin film transistors. Even with its highly extended acene-like π-system, DATT is a fairly air-stable compound with IP of 5.1 eV. Single crystal X-ray structural analysis revealed its planar molecular structure and the lamella-like layered structure with typical herringbone packing. Theoretical calculations of the solid state electronic structure based on the bulk single crystal structure suggest that DATT affords almost comparable intermolecular orbital couplings between HOMOs (t(HOMO)) with those of dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT), implying its good potential as an organic semiconductor for organic field-effect transistors. In fact, field-effect mobilities as high as 3.0 cm(2) V(-1) s(-1) were achieved with vapor-processed DATT-based devices, which is comparable with that of DNTT-based devices. The molecular ordering of DATT in the thin film state, however, turned out to be not completely uniform; as elucidated by in-plane and out-of-plane XRD measurements, the face-on molecular orientation was contaminated in the edge-on orientation, the former of which is not optimal for efficient carrier transport and thus could limit the mobility.


Prevalence of chronic prostatic inflammation based on clinical diagnostic criteria in a real-practice setting: a nation-wide observational study.
Chronic prostatic inflammation has a key role in the pathogenesis and progression of benign prostatic hyperplasia (BPH). Thus, the identification of patients with chronic inflammation is mandatory for Urologists. This study investigates which clinical, imaging and laboratory findings are used by Urologists in clinical practice to diagnose BPH and chronic prostate inflammation. This was a multicenter, non-interventional, observational study involving 30 Italian large-volume primary care urology centers. Patients were allocated into four diagnosis group: patients with BPH; patients with BPH and chronic prostate inflammation; patients with chronic prostate inflammation alone; and patients with lower urinary tract symptoms (LUTS) due to other causes. In total, 6134 patients were enrolled. BPH diagnosis with or without concomitant prostate inflammation was more frequent in older patients, while inflammation alone was prevalent in younger patients. Predictive factors for diagnosis of inflammation in all patients, regardless of age, were normal urinary flow (OR=2.73) and proved in-fection (OR=5.90), while in older patients (>61 years) diagnosis of chronic prostatic inflammation was specifically predicted by higher PSA values (≥4 ng/mL; OR=2.91), normal prostate volume (OR=10.23), mild symptoms (IPSS <8; OR=1.84), presence of intraprostatic calcifications (OR=4.55), and the combination of both infection and calcifications (OR=10.79). In daily practice, the presence of chronic prostatic inflammation is underestimated. A stricter application of established diagnostic criteria suggested would increase the detection rate of chronic prostatic inflammation and potentially change the therapeutic approach in many patients with LUTS.


Menthol pain relief through cumulative inactivation of voltage-gated sodium channels.
Menthol is a natural compound of plant origin known to produce cool sensation via the activation of the TRPM8 channel. It is also frequently part of topical analgesic drugs available in a pharmacy, although its mechanism of action is still unknown. Compelling evidence indicates that voltage-gated Na(+) channels are critical for experiencing pain sensation. We tested the hypothesis that menthol may block voltage-gated Na(+) channels in dorsal root ganglion (DRG) neurons. By use of a patch clamp, we evaluated the effects of menthol application on tetrodotoxin (TTX)-resistant Nav1.8 and Nav1.9 channel subtypes in DRG neurons, and on TTX-sensitive Na(+) channels in immortalized DRG neuron-derived F11 cells. The results indicate that menthol inhibits Na(+) channels in a concentration-, voltage-, and frequency-dependent manner. Menthol promoted fast and slow inactivation states, causing use-dependent depression of Na(+) channel activity. In current clamp recordings, menthol inhibited firing at high-frequency stimulation with minimal effects on normal neuronal activity. We found that low concentrations of menthol cause analgesia in mice, relieving pain produced by a Na(+) channel-targeting toxin. We conclude that menthol is a state-selective blocker of Nav1.8, Nav1.9, and TTX-sensitive Na(+) channels, indicating a role for Na(+) channel blockade in the efficacy of menthol as topical analgesic compound.


Self-Perception Of Malocclusion And Barriers To Orthodontic Care: A Cross-Sectional Study In Al-Madinah, Saudi Arabia.
This study was conducted to assess adult levels of knowledge, awareness of malocclusion and barriers to the uptake of orthodontic care alongside the associated factors (sex and gender). A convenience sample aged 18 years and above, residing in Al-Madinah Al-Munawwarah, Saudi Arabia, was recruited. A self-administrated validated questionnaire was used to collect the data, and data descriptive and inferential statistical analysis were performed. Of the 700 distributed questionnaires, 554 usable were returned (response rate = 79%). The mean±SD age of participants was 26.40 (±7.87) years and 55.2% were females. Over 60% of the participants reported high oral health knowledge with respect to the alignment of teeth being important for esthetics and neglected malocclusion had consequences, eg, caries. Likewise, high percentages were having knowledge that thumb sucking (80%) contributed to malocclusion although early extraction of primary teeth and genetics was reported by just 52% and 40%, respectively. Awareness of the importance of teeth alignment was reported by 81.6%; however, 37.7% were only advised for orthodontic treatment. Notably, most of the aforementioned knowledge and awareness was statistically significantly higher among females compared to counterpart males (p < 0.05). As for barriers, high orthodontic treatment fees were the barrier for 80% of the total participants irrespective of age and gender. Females were statistically significantly more likely to report barriers for orthodontic care, eg, accessibility and length of treatment (p < 0.05). The majority of the participants scored high levels of knowledge and awareness of oral health-specific conditions in relation to malocclusion. Although females were significantly knowledgeable and aware of malocclusion compared to males, social and orthodontic treatment factors were perceived as barriers to uptake of orthodontic care.


Circulating Retinol-Binding Protein 4 Is Inversely Associated With Pancreatic β-Cell Function Across the Spectrum of Glycemia.
The aim of this study was to examine the association of circulating retinol-binding protein 4 (RBP4) levels with β-cell function across the spectrum of glucose tolerance from normal to overt type 2 diabetes. A total of 291 subjects aged 35-60 years with normal glucose tolerance (NGT), newly diagnosed impaired fasting glucose or glucose tolerance (IFG/IGT), or type 2 diabetes were screened by a standard 2-h oral glucose tolerance test (OGTT) with the use of traditional measures to evaluate β-cell function. From these participants, 74 subjects were recruited for an oral minimal model test, and β-cell function was assessed with model-derived indices. Circulating RBP4 levels were measured by a commercially available ELISA kit. Circulating RBP4 levels were significantly and inversely correlated with β-cell function indicated by the Stumvoll first-phase and second-phase insulin secretion indices, but not with HOMA of β-cell function, calculated from the 2-h OGTT in 291 subjects across the spectrum of glycemia. The inverse association was also observed in subjects involved in the oral minimal model test with β-cell function assessed by both direct measures and model-derived measures, after adjustment for potential confounders. Moreover, RBP4 emerged as an independent factor of the disposition index-total insulin secretion. Circulating RBP4 levels are inversely and independently correlated with β-cell function across the spectrum of glycemia, providing another possible explanation of the linkage between RBP4 and the pathogenesis of type 2 diabetes.


Health Related Quality of Life in Japanese Patients with Localized Prostate Cancer: Comparative Retrospective Study of Robot-Assisted Laparoscopic Radical Prostatectomy Versus Radiation Therapy.
Radical prostatectomy and radiotherapy are standard treatments for localized prostate cancer. When making decisions about treatment, it is important to not only consider medical information such as the patient's age, performance status, and complications, but also the impact on quality of life (QOL) after treatment. Our purpose was to compare health related quality of life (HRQOL) after robot-assisted laparoscopic radical prostatectomy (RARP) versus radiation therapy in Japanese patients with localized prostate cancer retrospectively. Patients with localized prostate cancer receiving RARP or radiotherapy at Tottori University Hospital between October 2010 and December 2014 were enrolled in a retrospective observational study with follow-up for 24 months to December 2016. The Medical Outcome Study 8-Item Short-Form Health Survey was performed before treatment and 1, 3, 6, 12, and 24 months post-treatment. Complete responses to the questionnaire were obtained from 154/227 patients receiving RARP, 41/67 patients receiving intensity-modulated radiation therapy, 35/82 patients receiving low dose rate brachytherapy, and 18/28 patients given low dose rate brachytherapy plus external beam radiation therapy. The median physical component summary score of the Medical Outcome Study 8-Item Short-Form Health Survey was significantly lower at 1 month after prostatectomy than radiotherapy, but was similar for both treatments at 3 months, and was significantly higher at 6, 12 and 24 months after prostatectomy. The median mental component summary score was also significantly lower in the prostatectomy group at 1 month, but not from 3 months onwards. Our study suggested that HRQOL was inferior at 1 month after RARP, however, recovered at 3 months after RARP and was better than after radiotherapy at 6, 12, and 24 months.


Treatment of common ailments by plant-based remedies among the people of District Attock (Punjab) of northern Pakistan.
District Attock is one of the resource-based areas of medicinal plants in the north of Punjab province of Pakistan. The local people of the area have always used medicinal plants for their common ailments by traditional methods. Indigenous knowledge of local people about medicinal plants is directly linked to their culture and history. It is therefore felt worthwhile to record the indigenous knowledge about the plant-based remedies. The present communication deals with the common diseases treated by plant based remedies such as abdominal pain and worms, asthma, cough and bronchitis, cold, flu, influenza, diabetes, diarrheoa, dysentery, digestive disorders, ear infections and eye complaints. 25 species belonging to 25 genera were used for common ailments. It was found that plant based remedies were used in effective prescriptions, which are simple, inexpensive, and acceptable among the local inhabitants of the area.


Evaluation of the Aromatase Inhibition Potential of Freeze-Dried Grape Powder.
To determine the role of freeze-dried grapes as a potential aromatase inhibitor by testing of plasma hormone levels. A six-week study was conducted involving postmenopausal women during which 94 g of freeze-dried grape powder was consumed in addition to their usual diet. Plasma hormones were measured before and after the treatment. Of the 18 women involved in the study, average age and body mass index were 61.4 years and 24.4 respectively. For the hormone levels studied, the following median (interquartile range) percentage changes from baseline to six-week values were found: estradiol +11.8% (-34.4%, +44.2%), p = .42; estrone +3.4% (-15.7%, +12.9%), p = .64; estrone sulfate +5.3% (-19.9%, +56.3%), p = .35; testosterone -1.5% (-14.7%, +10.7%), p = .97; and androstenedione +12.6% (-17.1%, +49.1%), p = .15. The hormone levels did not significantly change between baseline and six weeks. Further, the changes that were observed did not tend to go in the hypothesized direction (estrogens and conjugates increased slightly, and testosterone decreased slightly). Only androstenedione showed a trend toward change in the hypothesized direction. In this study, there was no evidence that plasma hormone levels are altered by six weeks of daily consumption of 94 g of freeze-dried grape powder.


Femoral nerve repair using an H-type nerve regeneration chamber in rats.
Peripheral nerve injury in surgical trauma patients is very common. The femoral nerve can be divided into two branches: one regarding the quadricep muscles, and one the skin. After nerve transection and suture, the motor axons have an equal opportunity to regenerate into the original muscle branch, or regenerate into the sensory skin nerves. These anatomical features of femoral nerve have made it important in nerve regeneration research. Thus, this study was designed to examine the effects of an H-type nerve regeneration chamber on motor nerve regeneration after femoral nerve injury. We performed femoral nerve injuries in adult rats and assessed nerve recovery over a 4-week post-operative period. Additionally, we evaluated nerve regeneration in the same animals anatomically, using several histological staining methods to provide structure analyses. We found that H-type nerve regeneration chamber provided enhanced improvement in nerve regeneration without nerve anastomosis, as compared with nerve anastomosis. Furthermore, incorrect nerve anastomosis reduced the nerve fiber diameter and thickness of myelin sheaths in regenerated nerve fibers. Finally, H-type nerve regeneration chamber provided enhanced functional recovery of nerve fibers, particularly for motor nerves. Together, our results suggest that direct nerve suture cannot effectively improve the functional recovery of damaged nerves, and nerve chemotaxis coupled with nerve regeneration chamber can effectively improve the effects of nerve regeneration, and enhance the prognosis of nerve injury repair.


Assessment of the Long-term Diagnostic Performance of a New Serological Screening Scheme in Large-scale Nasopharyngeal Carcinoma Screening.
Background: Nasopharyngeal carcinoma (NPC) remains as a major public health burden in Southern China. Over the last decade, Epstein-Barr virus (EBV) serological detection has been the most promising tool used for NPC screening. The present study aims to evaluate the long-term diagnostic performance of a new NPC screening scheme (probability of NPC units [logit P], PROB≥0.65), and compare this with other EBV seromarkers used within 2009-2015. Methods: Enzyme-linked immunosorbent assay (ELISA) for EBV capsid antigen (VCA/IgA) and nuclear antigen-1 (EBNA1/IgA) was performed in 16,712 subjects, who were within 30-59 years old.All subjects were followed up for six years. The area under the receiver operating characteristic curve (AUC) and correlation analyses were preformed to evaluate the diagnostic value of different measures. Furthermore, the rates of early diagnosis in NPC patients were statistically analyzed. Results: The new NPC screening scheme (PROB≥0.65) and the four strategies (VCA/IgA, EBNA1/IgA, VCA/IgA and EBNA1/IgA, and VCA/IgA or EBNA1/IgA) had comparable rates of early diagnosis for NPC (no significant difference was found), but the sensitivity of the new scheme (95.7%) was higher than that of the others. The top three seromarkers with the largest AUC were PROB≥0.65 (AUC:0.926, 95% CI: 0.885-0.966), VCA/IgA or EBNA1/IgA (AUC:0.883, 95% CI:0.824-0.942), and EBNA1/IgA (AUC: 0.866, 95% CI: 0.794-0.938). Conclusion: The new NPC screening scheme (PROB≥0.65) based on VCA/IgA and EBNA1/IgA outperforms the other seromarkers, and making it the preferred serodiagnostic strategy for long-term NPC screening in high-incidence areas.


[Interspecies differences of co-orientation of primary polytene chromosomes in ovarian nurse cells in Drosophila melanogaster, D. simulans and D. mauritiana].
Essential differences in the architecture of primary polytene chromosomes in ovarian nurse cells between Drosophila melanogaster, D. simulans and D. mauritiana were discovered. The individual chromosomes of D. melanogaster (as well as their arms) are separated significantly from each other and are attached to the nuclear envelope by the centromeric (and the XL arm--by the telomeric) sites. D. simulans has the combination of the centromeric parts of the chromosomes X, 2, 3 into the "elongated" chromocentre, and in addition, the arms of chromosomes are also separated and attached to the nuclear envelope. Unlike the rest of the chromosomes, D. mauritiana has the chromosome 3 with firm combinated arms and the large heterochromatic block in the centromere, without being attached to the nuclear envelope.


Antibacterial electrospun zein nanofibrous web encapsulating thymol/cyclodextrin-inclusion complex for food packaging.
Thymol (THY)/γ-Cyclodextrin(γ-CD) inclusion complex (IC) encapsulated electrospun zein nanofibrous webs (zein-THY/γ-CD-IC-NF) were fabricated as a food packaging material. The formation of THY/γ-CD-IC (1:1 and 2:1) was proved by experimental (X-ray diffraction (XRD), thermal gravimetric analysis (TGA), 1H NMR) and computational techniques. THY/γ-CD-IC (2:1) exhibited higher preservation rate and stability than THY/γ-CD-IC (1:1). It is worth mentioning that zein-THY/γ-CD-IC-NF (2:1) preserved much more THY as observed in TGA and stability of THY/γ-CD-IC (2:1) was higher, as shown by a modelling study. Therefore, much more THY was released from zein-THY/γ-CD-IC-NF (2:1) than zein-THY-NF and zein-THY/γ-CD-IC-NF (1:1). Similarly, antibacterial activity of zein-THY/γ-CD-IC-NF (2:1) was higher than zein-THY-NF and zein-THY/γ-CD-IC-NF (1:1). It was demonstrated that zein-THY/γ-CD-IC-NF (2:1) was most effective in inhibiting the growth of bacteria on meat samples. These webs show potential application as an antibacterial food packaging material.


Evaluation of a new method for identification of Cryptococcus neoformans which uses serologic tests aided by selected biological tests.
A new method for identifying Cryptococcus neoformans isolates and their serotypes by the slide agglutination test using five kinds of factor sera, with the aid of nitrate reduction, phenol oxidase, and growth at 37 degrees C tests was evaluated by using 36 reference strains and 75 clinical isolates of C. neoformans. The results showed that the reference strains were identified exactly as they were labeled, and clinical isolates were identified as C. neoformans serotypes A, D, and AD. C. neoformans could be distinguished from other Cryptococcus species that cross-reacted with factor sera by their ability to grow at 37 degrees C. These results indicate that the slide agglutination test combined the use of factor sera for isolates which grow at 37 degrees C is a useful method for identification of C. neoformans and their serotypes and that the nitrate reduction test (negative in 100% of the isolates) and the phenol oxidase test (positive in approximately 95% of the isolates) can be used to confirm that the species is C. neoformans.


The food craving experience: Thoughts, images and resistance as predictors of craving intensity and consumption.
The Elaborated-Intrusion Theory of Desire (Kavanagh, Andrade, & May, 2005) suggests that cravings are made up of two distinct stages whereby an initial, seemingly spontaneous craving-related thought is sufficiently intrusive and pleasant for it then to be elaborated with vivid mental imagery. Previous questionnaire studies have investigated the craving experience with a particular focus on the role of imagery. The present study sought to provide a fuller account of the craving process by investigating the role of craving-related thoughts alongside imagery in predicting craving intensity. Further, the present study sought to investigate predictors of craving-related consumption, including spontaneous strategies used to resist cravings. Two-hundred and forty-nine women completed an online questionnaire which asked about their most recent food craving experience. Results showed that around a third of participants reported craving-related thoughts and about half reported craving-related imagery. Craving-related imagery appeared to be a more important predictor of craving intensity than craving-related thoughts; however, neither predicted craving-related consumption. One resistance strategy, 'recognised it was just a thought', was successful in decreasing the likelihood of eating in response to craving. Theoretical and practical implications are discussed in the context of the Elaborated-Intrusion Theory.


Retinal pigment epithelial tears associated with trauma.
Two previously healthy patients, a 66-year-old man with blunt trauma to the right eye, and a 28-year-old man with head trauma from a motorcycle accident, were observed to have parafoveal retinal pigment epithelial tears after injury. In both patients, fluorescein angiography demonstrated mottled window defects in the areas of the tears, and blocked fluorescence in the areas of the rolled-up pigment epithelium. Neither eye had evidence of pigment epithelial detachments. We hypothesize that this unusual phenomenon is caused by an acute tractional force oriented tangentially to the macular plane, the result of a rapid spherically expansile deformation of the globe during trauma.


Genome-wide analysis of FOXO3 mediated transcription regulation through RNA polymerase II profiling.
Forkhead box O (FOXO) transcription factors are key players in diverse cellular processes affecting tumorigenesis, stem cell maintenance and lifespan. To gain insight into the mechanisms of FOXO-regulated target gene expression, we studied genome-wide effects of FOXO3 activation. Profiling RNA polymerase II changes shows that FOXO3 regulates gene expression through transcription initiation. Correlative analysis of FOXO3 and RNA polymerase II ChIP-seq profiles demonstrates FOXO3 to act as a transcriptional activator. Furthermore, this analysis reveals a significant part of FOXO3 gene regulation proceeds through enhancer regions. FOXO3 binds to pre-existing enhancers and further activates these enhancers as shown by changes in histone acetylation and RNA polymerase II recruitment. In addition, FOXO3-mediated enhancer activation correlates with regulation of adjacent genes and pre-existence of chromatin loops between FOXO3 bound enhancers and target genes. Combined, our data elucidate how FOXOs regulate gene transcription and provide insight into mechanisms by which FOXOs can induce different gene expression programs depending on chromatin architecture.


Alteration of disc vacuum contents during prolonged supine positioning: evaluation with MR image.
Consecutive study. To investigate the changes of disc signal in intradiscal vacuum phenomenon during prolonged supine MR imaging. Increased T2 signal on MR imaging in intravertebral vacuum cleft during prolonged supine positioning has been described, but no sequential observation of the intervertebral discal signal change in intervertebral disc vacuum. Six women and 4 men (age range, 49-89 years; mean, 77 years) with low back pain and more than one level of intradiscal vacuum phenomenon underwent MR examinations at 0 minute, 1 hour, and 2 hours while remaining continuously supine. We recorded the original T2 signal intensity in the vacuum disc and subsequent alterations in the disc signals; they were scored 0 for signal void, 1 for equivocal or mild fluid intensity, or 2 for fluid signal intensity. Vacuum phenomena affected 31 of 60 intervertebral discs (T11-T12 to L5-S1). In 9 patients, the signal intensity of the vacuum content progressively replaced by hyperintense fluid occurred in 25 discs (81%) after prolonged supine positioning, mostly from L3 to S1 levels. The location of fluid signal was central in 20 discs (65%), anterior in 4 (13%), and posterior in 1 (3%). Signal intensity was unchanged in 6 discs (19%). Fluid signal intensity was linear shape in 9 discs (29%), homogeneous in 5 (16%), and mixed in 11 (35%). Overall scores were 8, 26, and 38 at 0, 71, and 161 minutes, respectively. After prolonged supine positioning, fluid-like signal could be identified among the intradiscal vacuum by using T2 MR images. This in vivo observation suggested the possible pathway of fluid diffusion from surrounding tissues into degenerative discs.


An Updated Review on Implications of Autophagy and Apoptosis in Tumorigenesis: Possible Alterations in Autophagy through Engineered Nanomaterials and Their Importance in Cancer Therapy.
Most commonly recognized as a catabolic pathway, autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components, i.e., organelles, by means of certain membranous vesicles or lysosomes filled with degrading enzymes. Upon exposure to external insult or internal stimuli, the cell might opt to activate such a pathway, through which it can gain control over the maintenance of intracellular components and thus sustain homeostasis by intercepting the formation of unnecessary structures or eliminating the already present dysfunctional or inutile organelles. Despite such appropriateness, autophagy might also be considered a frailty for the cell, as it has been said to have a rather complicated role in tumorigenesis. A merit in the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. In fact, several investigations on tumorigenesis have reported diminished levels of autophagic activity in tumor cells, which might result in transition to malignancy. On the contrary, autophagy has been suggested to be a seemingly favorable mechanism to progressed malignancies, as it contributes to survival of such cells. Based on the recent literature, this mechanism might also be activated upon the entry of engineered nanomaterials inside a cell, supposedly protecting the host from foreign materials. Accordingly, there is a good chance that therapeutic interventions for modulating autophagy in malignant cells using nanoparticles may sensitize cancerous cells to certain treatment modalities, e.g., radiotherapy. In this review, we will discuss the signaling pathways involved in autophagy and the significance of the mechanism itself in apoptosis and tumorigenesis while shedding light on possible alterations in autophagy through engineered nanomaterials and their potential therapeutic applications in cancer. SIGNIFICANCE STATEMENT: Autophagy has been said to have a complicated role in tumorigenesis. In the early stages of tumor formation, autophagy appears to be salutary because of its tumor-suppressing effects. On the contrary, autophagy has been suggested to be a favorable mechanism to progressed malignancies. This mechanism might be affected upon the entry of nanomaterials inside a cell. Accordingly, therapeutic interventions for modulating autophagy using nanoparticles may sensitize cancerous cells to certain therapies.


On the Selective Packaging of Genomic RNA by HIV-1.
Like other retroviruses, human immunodeficiency virus type 1 (HIV-1) selectively packages genomic RNA (gRNA) during virus assembly. However, in the absence of the gRNA, cellular messenger RNAs (mRNAs) are packaged. While the gRNA is selected because of its cis-acting packaging signal, the mechanism of this selection is not understood. The affinity of Gag (the viral structural protein) for cellular RNAs at physiological ionic strength is not much higher than that for the gRNA. However, binding to the gRNA is more salt-resistant, implying that it has a higher non-electrostatic component. We have previously studied the spacer 1 (SP1) region of Gag and showed that it can undergo a concentration-dependent conformational transition. We proposed that this transition represents the first step in assembly, i.e., the conversion of Gag to an assembly-ready state. To explain selective packaging of gRNA, we suggest here that binding of Gag to gRNA, with its high non-electrostatic component, triggers this conversion more readily than binding to other RNAs; thus we predict that a Gag-gRNA complex will nucleate particle assembly more efficiently than other Gag-RNA complexes. New data shows that among cellular mRNAs, those with long 3'-untranslated regions (UTR) are selectively packaged. It seems plausible that the 3'-UTR, a stretch of RNA not occupied by ribosomes, offers a favorable binding site for Gag.


Opbp is a new architectural/insulator protein required for ribosomal gene expression.
A special class of poorly characterized architectural proteins is required for chromatin topology and enhancer-promoter interactions. Here, we identify Opbp as a new Drosophila architectural protein, interacting with CP190 both in vivo and in vitro. Opbp binds to a very restrictive set of genomic regions, through a rare sequence specific motif. These sites are co-bound by CP190 in vivo, and generally located at bidirectional promoters of ribosomal protein genes. We show that Opbp is essential for viability, and loss of opbp function, or destruction of its motif, leads to reduced ribosomal protein gene expression, indicating a functional role in promoter activation. As characteristic of architectural/insulator proteins, the Opbp motif is sufficient for distance-dependent reporter gene activation and enhancer-blocking activity, suggesting an Opbp-mediated enhancer-promoter interaction. Rather than having a constitutive role, Opbp represents a new type of architectural protein with a very restricted, yet essential, function in regulation of housekeeping gene expression.


Variability and host density independence in inductions-based estimates of environmental lysogeny.
Temperate bacterial viruses (phages) may enter a symbiosis with their host cell, forming a unit called a lysogen. Infection and viral replication are disassociated in lysogens until an induction event such as DNA damage occurs, triggering viral-mediated lysis. The lysogen-lytic viral reproduction switch is central to viral ecology, with diverse ecosystem impacts. It has been argued that lysogeny is favoured in phages at low host densities. This paradigm is based on the fraction of chemically inducible cells (FCIC) lysogeny proxy determined using DNA-damaging mitomycin C inductions. Contrary to the established paradigm, a survey of 39 inductions publications found FCIC to be highly variable and pervasively insensitive to bacterial host density at global, within-environment and within-study levels. Attempts to determine the source(s) of variability highlighted the inherent complications in using the FCIC proxy in mixed communities, including dissociation between rates of lysogeny and FCIC values. Ultimately, FCIC studies do not provide robust measures of lysogeny or consistent evidence of either positive or negative host density dependence to the lytic-lysogenic switch. Other metrics are therefore needed to understand the drivers of the lytic-lysogenic decision in viral communities and to test models of the host density-dependent viral lytic-lysogenic switch.


Malignant melanoma metastatic to the gastrointestinal tract.
Malignant melanoma, a common malignancy whose prevalence is increasing, represents 1-3% of cancers in the United States [1]. At autopsy, metastatic deposits to the gut are frequently found, but less than 9% of melanoma patients are diagnosed with gastrointestinal metastases while living [2]. Modern management includes aggressive surgical therapy to prolong survival and to palliate the disease [3]. Therefore, imaging of metastatic melanoma is clinically important to detect extent and determine whether the patient would benefit by surgery. Gastrointestinal metastases may manifest as mucosal or submucosal masses, serosal implants, or carcinomatosis [4]. They arise more commonly in the mesentery or distal small bowel than the proximal gastrointestinal tract or colon. The purpose of this essay is to illustrate the appearance of melanoma metastatic to the gastrointestinal tract on luminal contrast studies and on CT and to emphasize the importance of early investigation of gastrointestinal symptoms in a patient with a history of malignant melanoma.


Assexon: Assembling Exon Using Gene Capture Data.
Exon capture across species has been one of the most broadly applied approaches to acquire multi-locus data in phylogenomic studies of non-model organisms. Methods for assembling loci from short-read sequences (eg, Illumina platforms) that rely on mapping reads to a reference genome may not be suitable for studies comprising species across a wide phylogenetic spectrum; thus, de novo assembling methods are more generally applied. Current approaches for assembling targeted exons from short reads are not particularly optimized as they cannot (1) assemble loci with low read depth, (2) handle large files efficiently, and (3) reliably address issues with paralogs. Thus, we present Assexon: a streamlined pipeline that de novo assembles targeted exons and their flanking sequences from raw reads. We tested our method using reads from Lepisosteus osseus (4.37 Gb) and Boleophthalmus pectinirostris (2.43 Gb), which are captured using baits that were designed based on genome sequence of Lepisosteus oculatus and Oreochromis niloticus, respectively. We compared performance of Assexon to PHYLUCE and HybPiper, which are commonly used pipelines to assemble ultra-conserved element (UCE) and Hyb-seq data. A custom exon capture analysis pipeline (CP) developed by Yuan et al was compared as well. Assexon accurately assembled more than 3400 to 3800 (20%-28%) loci than PHYLUCE and more than 1900 to 2300 (8%-14%) loci than HybPiper across different levels of phylogenetic divergence. Assexon ran at least twice as fast as PHYLUCE and HybPiper. Number of loci assembled using CP was comparable with Assexon in both tests, while Assexon ran at least 7 times faster than CP. In addition, some steps of CP require the user's interaction and are not fully automated, and this user time was not counted in our calculation. Both Assexon and CP retrieved no paralogs in the testing runs, but PHYLUCE and Hybpiper did. In conclusion, Assexon is a tool for accurate and efficient assembling of large read sets from exon capture experiments. Furthermore, Assexon includes scripts to filter poorly aligned coding regions and flanking regions, calculate summary statistics of loci, and select loci with reliable phylogenetic signal. Assexon is available at https://github.com/yhadevol/Assexon.


Extracellular polymeric substances from Bacillus subtilis associated with minerals modify the extent and rate of heavy metal sorption.
Extracellular polymeric substances (EPS) are an important source of organic matter in soil. Once released by microorganisms, a portion may be sorbed to mineral surfaces, thereby altering the mineral̀s ability to immobilize heavy metals. EPS from Bacillus subtilis were reacted with Ca-saturated bentonite and ferrihydrite in 0.01 M KCl at pH 5.0 to follow the preferential uptake of EPS-C, -N, and -P. The sorption kinetics of Pb(2+), Cu(2+), and Zn(2+) to the resulting EPS-mineral composites was studied in single and binary metal batch experiments ([metal](total) = 50 μM, pH 5.0). Bentonite sorbed much more EPS-C (18.5 mg g(-1)) than ferrihydrite (7.9 mg g(-1)). During sorption, EPS were chemically and size fractionated with bentonite favoring the uptake of low-molecular weight components and EPS-N, and ferrihydrite selectively retaining high-molecular weight and P-rich components. Surface area and pore size measurements by N(2) gas adsorption at 77 K indicated that EPS altered the structure of mineral-EPS associations by inducing partial disaggregation of bentonite and aggregation of ferrihydrite. Whereas mineral-bound EPS increased the extent and rate of Pb(2+), Cu(2+), and Zn(2+) sorption for bentonite, either no effect or a decrease in metal uptake was observed for ferrihydrite. The extent of sorption always followed the order Pb(2+) > Cu(2+) > Zn(2+), which also prevailed in binary Pb(2+)/Cu(2+) systems. In consequence, sorption of EPS to different minerals may have contrasting consequences for the immobilization of heavy metals in natural environments by inducing mineral-specific alterations of the pore size distribution and, thus, of available sorption sites.


Long-term outcome of early steroid withdrawal after kidney transplantation in African American recipients monitored by surveillance biopsy.
Generally chronic steroid therapy is standard care for African American (AA) kidney recipients because of their higher incidence of rejections and lower long-term graft survival. This prospective study evaluated the long-term safety and efficacy of early steroid withdrawal (ESW) in AA recipients. A total of 206 recipients were studied; 103 AA and 103 non-AA recipients monitored by serial surveillance biopsies from 1 to 60 months posttransplantation to evaluate subclinical acute rejections (SCAR) and chronic allograft injury (CAI). Biopsy-proven clinical acute rejections (BPAR) and SCAR were treated. Primary end point was BPAR and secondary end points were 5-year SCAR, CAI and survival. Incidences of BPAR was 16% versus 14% (p = 1.0), prevalence of CAI due to hypertension was 48% versus 30% (p = 0.05) and interstitial fibrosis/tubular atrophy was 47% versus 32% (p = 0.05) and the mean serum creatinine levels were 2.1 versus 1.8 mg/dL (p = 0.05) at 5-years in AA versus non-AA recipients. The incidence of SCAR was 23% versus 11% at 1 month (p = 0.04), 12% versus 3% at 3 years (p = 0.04) and 10% versus 1% at 5 years (p = 0.04) in AA and non-AA recipients, respectively. Five-year patient survivals were 81% and 88% (p = 0.09) and graft survivals were 71% and 73%(p = 0.19) in AA and non-AA groups, respectively. After early steroid withdrawal AA kidney recipients have significantly lower renal function and higher SCAR and CAI but 5-year graft survival are comparable to non-AA recipients.


Endometriomas: their ultrasound characteristics.
To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas. All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated. Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was 'an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable. Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy.


CARMAweb: comprehensive R- and bioconductor-based web service for microarray data analysis.
CARMAweb (Comprehensive R-based Microarray Analysis web service) is a web application designed for the analysis of microarray data. CARMAweb performs data preprocessing (background correction, quality control and normalization), detection of differentially expressed genes, cluster analysis, dimension reduction and visualization, classification, and Gene Ontology-term analysis. This web application accepts raw data from a variety of imaging software tools for the most widely used microarray platforms: Affymetrix GeneChips, spotted two-color microarrays and Applied Biosystems (ABI) microarrays. R and packages from the Bioconductor project are used as an analytical engine in combination with the R function Sweave, which allows automatic generation of analysis reports. These report files contain all R commands used to perform the analysis and guarantee therefore a maximum transparency and reproducibility for each analysis. The web application is implemented in Java based on the latest J2EE (Java 2 Enterprise Edition) software technology. CARMAweb is freely available at https://carmaweb.genome.tugraz.at.


Cerebral circulation and EEG alpha frequency in relation to daily fluctuations in psychotic behavior.
Aspects of the cerebral circulation were monitored daily by cerebral electrical impedance plethysmography in one chronic schizophrenic girl for 9 months and seven other chronic schizophrenic patients for a period of 8 months. An additional manic-depressive patient was monitored while in a remission phase over 2 months. Simultaneous electroencephalogram (EEG) recordings were made on the schizophrenic patients. Daily Malamud-Sands (MS) psychiatric rating scales were completed by trained nursing staff on all patients. Correlation coefficients were obtained between this behavioral variable and the EEG-measured alpha frequency. Correlations were also run between the dimensions of the MS rating scale and three indices of the cerebral circulation and between two indices of cervical blood flow. Results indicated significant correlations between the "stuporous" scores of the MS scale and the cerebrovascular measurements in one catatonic patient. EEG alpha frequency correlated significantly with "excitement" scores in the same patient. The manic-depressive patient monitored in her remission phase showed no correlations with MS scores but relatively unchanging normal cerebral hemodynamics. The remaining seven chronic schizophrenic patients were followed daily for 8 months during a drug regimen in which phenelzine and L-tryptophan were administered. Significant relationships were found between the daily fluctuations of behavior and cerebral circulatory variables in a majority of the patients, and the extent of these correlations appeared to be increased by the addition of the metabolically active agents. Only a minority of correlations between MS scores and EEG dominant frequency were found in this group of patients. It is concluded that the MS scale affords a useful ethological monitor of psychotic behavior and that cerebral electrical impedance plethysmography and EEG alpha frequency correlate significantly with the fluctuations it records.


Identification of anaerobic arsenite-oxidizing and arsenate-reducing bacteria associated with an alkaline saline lake in Khovsgol, Mongolia.
Microbial arsenic transformation pathways associated with a saline lake located in northern Mongolia were examined using molecular biological and culturing approaches. Bacterial 16S rRNA gene sequences recovered from saline lake sediments and soils were affiliated with haloalkaliphiles, including Bacillus and Halomonas spp. Diverse sequences of arsenate respiratory reductase (arrA) and a new group of arsenite oxidase (arxA) genes were also identified. Pure cultures of arsenate-reducing Nitrincola strain and anaerobic arsenite-oxidizing Halomonas strain were isolated. The chemoorganotrophic Halomonas strain contains arxA gene similar to that of a chemoautotrophic arsenite-oxidizing Alkalilimnicola ehrlichii strain MLHE-1. These results revealed the diversity of arsenic transformation pathways associated with a geographically distinct saline system and the potential contribution of arx-dependent arsenite oxidation by heterotrophic bacteria.


Relationship between computer segmentation performance and computer classification performance in breast CT: A simulation study using RGI segmentation and LDA classification.
Many computer aided diagnosis (CADx) tools for breast cancer begin by fully or semiautomatically segmenting a given breast lesion and then classifying the lesion's likelihood of malignancy using quantitative features extracted from the image. It is often assumed that better segmentation will result in better classification. However, this has not been thoroughly evaluated. The purpose of this study is to evaluate the relationship between computer segmentation performance and computer classification performance. We used 85 breast lesions (32 benign, 56 malignant) from breast computed tomography (CT) cases of 82 women. We prepared one smooth and one sharp iterative image reconstructions (IIR) and a clinical reconstruction for each of the 82 breast CT scans. For each reconstruction, we created 15 segmentation outcomes by applying 15 different segmentation algorithms. Specifically, we simulated 15 segmentation algorithms by changing parameters in a single segmentation algorithm. We then created 15 classification outcomes by conducting quantitative image feature analysis on the segmented image results. Using a 10-fold cross-validation, we evaluated the relationship between segmentation and classification performances. We found a low positive correlation between segmentation and classification performances for the smooth IIR (median Pearson's rho = 0.18), while a moderate positive correlation (median Pearson's rho = 0.4-0.43) was found between the two performances for the sharp IIR and clinical reconstruction. However, we found large variations in both segmentation and classification performances for the sharp IIR and clinical reconstruction. There were cases where segmentation algorithms resulted in similar segmentation performances, but the corresponding classification performances were different. These results indicate that an improvement in segmentation performance does not guarantee an improvement in the corresponding classification performance. Computer segmentation is an indirect variable affecting the computer classification. As better segmentation does not guarantee better classification, we should report both segmentation and classification performances when comparing segmentation algorithms.


Applying tobacco carcinogen and toxicant biomarkers in product regulation and cancer prevention.
Tobacco carcinogen and toxicant biomarkers are metabolites or protein or DNA adducts of specific compounds in tobacco products. Highly reliable analytical methods, based mainly on mass spectrometry, have been developed and applied in large studies of many of these biomarkers. A panel of tobacco carcinogen and toxicant biomarkers is suggested here, and typical values for smokers and nonsmokers are summarized. This panel of biomarkers has potential applications in the new and challenging area of tobacco product regulation and in the development of rational approaches to cancer prevention by establishing carcinogen and toxicant uptake and excretion in people exposed to tobacco products.


International science--an overview.
Scientific projects that succeed as international cooperative efforts are those related to subjects that transcend national frontiers, are costly, have long-range objectives rather than short-term commercial aims, and correspond with the political objectives of the countries involved. Yet the best context for the all science is the global community, which is also the best hope for humanity. The global community is still generations away and scientists must continue to work for it, by seeking the international dimensions of science as individuals and participating in governmental as well as nongovernmental international scientific organizations.


[Pre-primary prophylaxis of variceal bleeding].
Portosystemic collateral formation, particularly at the gastroesophageal junction, is a most serious consequence of portal hypertension. Increased portal pressure is the most significant force underlying gastroesophageal variceal formation, to which end portal pressure (estimated from the hepatic venous pressure gradient) must reach at least 10 mmHg. Subsequently, splanchnic hyperemia also contributes to variceal development. Portoystemic collaterals result from repermeabilization of pre-extant vessels, vascular remodeling, and angiogenesis. The goal of pre-primary prophylaxis is preventing or delaying the formation of gastroesophageal varices. In experimental models of portal hypertension, early administration of splanchnic vasoconstrictors such as beta-blockers, nitric oxide synthesis inhibitors, or antiangiogenic substances inhibits portosystemic collateral formation. However, clinical trials of beta-blockers in patients with cirrhosis and no varices to delay variceal formation have failed to yield expected results.


Breast cancer registry in Palermo and its Province: incidence in 1999.
The incidence of breast cancer in the city of Palermo and its Province was investigated. The cancer rate was higher in the city of Palermo (100.8/100,000/year), a great southern urban area, than in the 81 municipalities of the Province (79.2/100,000/year). Rates were also compared with those in other geographic areas of Italy, showing a smaller than expected negative north-south gradient in incidence, especially in the young age group, as shown by the cumulative risk observed in the 0-54-year-old group. These findings confirm the role of recent life style changes in the cancer risk distribution.


Clonidine in congestive heart failure: a vasodilator with negative inotropic effects.
Fourteen patients with moderately severe congestive heart failure (CHF) were given clonidine orally (0.2 and 0.4 mg doses) to determine the hemodynamic effects of a typical centrally acting vasodilator. The 0.2 mg dose significantly reduced mean systemic (15%) and mean pulmonary artery (20%) pressure; the corresponding reductions in vascular resistance were not as great because of a diminished cardiac output. Pulmonary capillary wedge pressure decreased significantly (27%). Heart rate decreased 11% and stroke volume remained unchanged. At a higher dose (0.4 mg), clonidine augmented these reductions but increased stroke volume modestly (15%). Isovolumic developed pressure/duration of isovolumic contraction and the duration of the preejection period were used as indexes of inotropy. After both doses, isovolumic developed pressure/duration of isovolumic contraction decreased dramatically (greater than or equal to 33%) and the preejection period increased substantially (greater than or equal to 18%) (both p less than 0.05). Compared with currently employed vasodilating agents, the centrally acting agent clonidine appears unique in that the drug-induced systemic and pulmonary arterial vasodilation are not accompanied by a commensurate improvement in ventricular systolic function. This lack of improvement appears to be a result of negative inotropic effects.


Challenging a surgical dictum: results from a 10-year experience on the safety of open inguinal herniorrhaphy in patients on chronic warfarin therapy.
Previous reports document the safety of open inguinal herniorrhaphy in patients on chronic warfarin therapy; however, the practice remains controversial. This study is a 10-year update of our experience. A retrospective review of 1,839 consecutive patients undergoing open inguinal hernia repair was conducted from 2000 to 2010. All patients on chronic warfarin therapy were included. Three groups: continuation (CW), discontinuation (DW) and case-matched control (C) not on warfarin therapy were compared for operative details and postoperative complications. One hundred and fifty-eight patients were on chronic warfarin therapy. Of these, 40 patients (25%) continued on warfarin during the perioperative period (CW). Average preoperative international normalized ratio (INR) was 2.15 ± 0.76 for CW and 1.38 ± 0.42 for DW, p < 0.001. Mean operative times were equivalent between all three groups (88 min CW vs. 85 min DW vs. 79 min C, p = 0.518). Although CW patients experienced higher incidences of both hematoma and urinary retention overall, no statistically significant differences in complication rates were seen between the three groups (hematoma = 10 vs. 8% DW vs. 5% C, p = 0.703; urinary retention = 15 vs. 10% DW vs. 8% C, p = 0.541). Comparing patients by INR, there were no statistically different postoperative complication rates, particularly for hematoma (8% INR <2 vs. 9.5% INR = 2-3 vs. 20% INR >3, p = 0.65). Maintenance of warfarin therapy during the perioperative period for open inguinal herniorrhaphy results in equivalent operative times and postoperative complications as discontinuation.


Crystal growth kinetics of triblock Janus colloids.
We measure the kinetics of crystal growth from a melt of triblock Janus colloids using non-equilibrium molecular dynamics simulations. We assess the impact of interaction anisotropy by systematically varying the size of the attractive patches from 40% to 100% coverage, finding substantially different growth behaviors in the two limits. With isotropic particles, the interface velocity is directly proportional to the subcooling, in agreement with previous studies. With highly anisotropic particles, the growth curves are well approximated by using a power law with exponent and prefactor that depend strongly on the particular surface geometry and patch fraction. This nonlinear growth appears correlated to the roughness of the solid-liquid interface, with the strongest growth inhibition occurring for the smoothest crystal faces. We conclude that crystal growth for patchy particles does not conform to the typical collision-limited mechanism, but is instead an activated process in which the rate-limiting step is the collective rotation of particles into the proper orientation. Finally, we show how differences in the growth kinetics could be leveraged to achieve kinetic control over polymorph growth, either enhancing or suppressing metastable phases near solid-solid coexistence lines.


Microsphere Embolization of Hypervascular Posterior Fossa Tumors.
Preoperative embolization of highly vascular tumors of the posterior fossa can decrease morbidity and operative blood loss. No clear consensus exists for the embolization agent of choice for optimal devascularization of these tumors. The purpose of this study was to assess effectiveness of microsphere embolization in reducing tumor hypervascularity before surgical resection. We retrospectively reviewed medical records of patients with hypervascular posterior fossa tumors who were treated at a single institution from 2009 to 2016. Four of 9 patients with hypervascular posterior fossa tumors underwent embolization with 300-500 μm microspheres before surgical resection. Patients selected for embolization had large tumors with large feeding vessels evident on brain magnetic resonance imaging. Surgical resection was performed within 24 hours of embolization in all 4 patients. Mean (SD) patient age was 42.5 years (18.4), and mean (SD) tumor size was 4.3 cm (1.4) in greatest dimension. All patients presented with symptoms related to mass effect. Gross total tumor resection was achieved in all patients. There were no intraoperative complications related to the embolization or craniotomy; mean (SD) blood loss was 350 mL (208). Preoperative embolization with microspheres can effectively reduce vascularity of the hypervascular posterior fossa tumor bed. This technique helped achieve complete resection, particularly for patients with recurrence after previous resection.


Testing the efficacy and toxicity of adenylyl cyclase inhibitors against enteric pathogens using in vitro and in vivo models of infection.
Enterotoxigenic Escherichia coli (ETEC) produces the ADP-ribosyltransferase toxin known as heat-labile enterotoxin (LT). In addition to the toxic effect of LT resulting in increases of cyclic AMP (cAMP) and disturbance of cellular metabolic processes, this toxin promotes bacterial adherence to intestinal epithelial cells (A. M. Johnson, R. S. Kaushik, D. H. Francis, J. M. Fleckenstein, and P. R. Hardwidge, J. Bacteriol. 191:178-186, 2009). Therefore, we hypothesized that the identification of a compound that inhibits the activity of the toxin would have a suppressive effect on the ETEC colonization capabilities. Using in vivo and in vitro approaches, we present evidence demonstrating that a fluorenone-based compound, DC5, which inhibits the accumulation of cAMP in intoxicated cultured cells, significantly decreases the colonization abilities of adenylyl cyclase toxin-producing bacteria, such as ETEC. These findings established that DC5 is a potent inhibitor both of toxin-induced cAMP accumulation and of ETEC adherence to epithelial cells. Thus, DC5 may be a promising compound for treatment of diarrhea caused by ETEC and other adenylyl cyclase toxin-producing bacteria.


Presentation of a nationwide multicenter registry of intestinal failure and intestinal transplantation.
Exact data on Dutch patients with chronic intestinal failure (CIF) and after intestinal transplantation (ITx) have been lacking. To improve standard care of these patients, a nationwide collaboration has been established. Objectives of this study were obtaining an up-to-date prevalence of CIF and characterizing these patients using the specially developed multicenter web-based Dutch Registry of Intestinal Failure and Intestinal Transplantation (DRIFT). Cross-sectional study. CIF was defined as type 3 intestinal failure in which >75% of nutritional requirements were given as home parenteral nutrition (HPN) for ≥ 4 weeks in children and >50% for ≥3 months in adults. All patients with CIF receiving HPN care by the three Dutch specialized centers on January 1, 2013 and all ITx patients were registered in DRIFT (https://drift.darmfalen.nl). In total, 195 patients with CIF (158 adults, 37 children) were identified, of whom 184 were registered in DRIFT. The Dutch point prevalence of CIF was 11.62 per million (12.24 for adults, 9.56 for children) on January 1, 2013. Fifty-seven patients (31%) had one or more indications for ITx, while 12 patients actually underwent ITx since its Dutch introduction. Four patients required transplantectomy of their intestinal graft and 3 intestinal transplant patients died. The multicenter registry DRIFT revealed an up-to-date prevalence of CIF and provided nationwide insight into the patients with CIF during HPN and after ITx in the Netherlands. DRIFT will facilitate the multicenter monitoring of individual patients, thereby supporting multidisciplinary care and decision-making.


Enzyme immunoassay of the capsular polysaccharide of Streptococcus pneumoniae type III in cerebrospinal fluid in experimental meningitis.
An enzyme immunoassay (EIA) for the capsular polysaccharide of Streptococcus pneumoniae type III was developed and applied to the measurement of this antigen in cerebrospinal fluid (CSF) in an experimental model of pneumococcal meningitis. EIA was performed by a single-antibody sandwich technique in which the globulin fraction of pneumococcal type-specific antiserum (antiserum-globulin) was used to coat the solid phase before antigen attachment and to conjugate with the labelling enzyme, horseradish peroxidase. Under optimum assay conditions EIA detected purified pneumococcal type-III capsular polysaccharide in concentrations as low as 0.15 ng/ml in aqueous buffer. Assayed by EIA, the mean concentration of type-III capsular polysaccharide in CSF of rabbits with pneumococcal meningitis increased exponentially from 24 h to 96nh of infection (range 13.9 ng/ml--62 500 ng/ml). Effective antimicrobial therapy of rabbits with meningitis was associated with a rapid decrease in the CSF concentration of the capsular antigen, although it was still detected in concentration in the range 1--10 ng/ml in 100% of animals treated for 4 days. Thus EIA provides a quantitative and extremely sensitive method of measuring type-III pneumococcal capsular polysaccharide in CSF.


[Generation of membrane potential by aerobic bacteria Micrococcus lysodeikticus. Correlation between coupled and uncoupled respiration].
The effects of cyanide and nonylhydroxyquinoline-N-oxide on membrane potential generation and oxidase activities in intact cells and membrane particles of M. lysodeikticus were studied. Low concentrations of the inhibitors interacting with the components of one branch of a branched respiratory chain of M. lysodeikticus strongly inhibit the membrane potential generation and only slightly reduce the total respiration rate. It was assumed that the generation of delta psi takes place in the b-c locus of the respiratory chain branch terminated with cytochrome oxidase; over 90% of total O2 uptake provides for the uncoupled respiration via cytochrome omicron. Inside the b-c locus two sites responsible for delta psi generation were singled out; these sites differ in their sensitivities towards nonylhydroxyquinoline-N-oxide. Based on the data obtained and the effect of "extra-reduction" of cytochrome b566 a hypothetical model of the respiratory chain of M. lysodeikticus was developed, which includes the branching of the electron flux to two terminal pathways and redox equivalent transport cyclization via the menaquinone cycle. The physiological role of uncoupled respiration through cytochrome omicron is discussed.


Occupational risk assessment of exposure to metals in chrome plating workers.
Inhalation of xenobiotics during manufacture process in chrome plating bath produce hazards to workers' health. Chromium (Cr) is a metal widely used by industry, and its hexavalent (VI) form has been classified as mutagenic and carcinogenic. This study aimed to evaluate the occupational risk of exposure to metals in chrome plating workers. Biological monitoring was performed through quantification of Cr, Pb, As, Ni, and V in blood by ICP-MS in 50 male chrome-plating workers from the exposed group and 50 male non-exposed workers. The inflammatory parameters assessed were β-2 integrin, intercellular adhesion molecule-1 (ICAM-1), and L-selectin expression in lymphocytes. The genotoxicity was evaluated with comet and micronucleus (MN) assays and as a biomarker of oxidative damage the lipid peroxidation (MDA) and protein carbonyl (PCO). The results demonstrated that Cr levels in blood and urine were increased in the exposed group compared to the non-exposed group. Although the biomarkers of exposure proved to be within the levels considered safe in exposed individuals, chrome plating workers presented significantly increase in the percentage of lymphocytes expressing β-2 integrin, ICAM-1, and L-selectin as well as DNA damage (comet assay) and plasmatic MDA and PCO levels. Therefore, it is possible also assign the injuries caused to lipids, proteins, and DNA assessed due to the increased presence of other metals such as Pb, As, Ni, and V in exposed subjects. These results suggest that exposure to xenobiotics present in the occupational environment in chrome plating industry could play a crucial role toward the inflammation, genetic, and oxidative damage.


Identification and cloning of GCA1, a gene that encodes a cell surface glucoamylase from Candida albicans.
Adherence of yeast cells of Candida albicans to human oesophageal cells is greater when cells are grown in 500 mM D-galactose in comparison to D-glucose at the same concentration. Moreover, a 190 kDa mannoprotein (MP190) from a yeast cell wall preparation is highly expressed when cells are grown in the presence of galactose but less so in glucose. We now report on the identification of the MP190 and the isolation of its encoding gene. MP190 was purified, and three internal peptides were isolated and sequenced. Each of the three peptides showed significant homology (65-85%) with a glucoamylase (GAM1) from the yeast, Schwanniomyces occidentalis. In order to isolate the C. albicans homologue of GAM1 (GCA1), we probed a genomic library with a 0.9-kb internal fragment of the S. occidentalis GAM1 and isolated a 2.3-kb clone that corresponded to the 5' region of the gene. Polymerase chain reaction (PCR) amplification was used to isolate the remainder of the open reading frame. GCA1 encodes a 946 amino acid protein containing three putative hydrophobic, membrane-spanning domains and 15 potential N-glycosylation sites. Both Gca1p and GAM1 are novel to the family of glycosyl hydrolases. Northern analysis indicated that GCA1 is transcribed to a greater extent in galactose than in sucrose or glucose. Also, using reverse transcriptase (RT)-PCR, we observed expression of GCA1 in a rat model of oral candidiasis, indicating that Gca1p is expressed during disease development.


Ankyrin-1 Gene Exhibits Allelic Heterogeneity in Conferring Protection Against Malaria.
Allelic heterogeneity is a common phenomenon where a gene exhibits a different phenotype depending on the nature of its genetic mutations. In the context of genes affecting malaria susceptibility, it allowed us to explore and understand the intricate host-parasite interactions during malaria infections. In this study, we described a gene encoding erythrocytic ankyrin-1 (Ank-1) which exhibits allelic-dependent heterogeneous phenotypes during malaria infections. We conducted an ENU mutagenesis screen on mice and identified two Ank-1 mutations, one resulting in an amino acid substitution (MRI95845), and the other a truncated Ank-1 protein (MRI96570). Both mutations caused hereditary spherocytosis-like phenotypes and confer differing protection against Plasmodium chabaudi infections. Upon further examination, the Ank-1(MRI96570) mutation was found to inhibit intraerythrocytic parasite maturation, whereas Ank-1(MRI95845) caused increased bystander erythrocyte clearance during infection. This is the first description of allelic heterogeneity in ankyrin-1 from the direct comparison between two Ank-1 mutations. Despite the lack of direct evidence from population studies, this data further supported the protective roles of ankyrin-1 mutations in conferring malaria protection. This study also emphasized the importance of such phenomena in achieving a better understanding of host-parasite interactions, which could be the basis of future studies.