Anaerobic co-digestion of sewage sludge and food waste using temperature-phased anaerobic digestion process.
This study was performed to overcome the low efficiency of anaerobic digestion of sewage sludge and food waste by combining temperature-phased digestion, sequencing batch operation, and co-digestion technology. It was demonstrated that the temperature-phased anaerobic sequencing batch reactor (TPASBR) system for the co-digestion of sewage sludge and food waste resulted in enhanced volatile solids (VS) reduction and methane production rate. At the organic loading rate (OLR) of 2.7 g VS/l/d, the TPASBR system showed the higher VS reduction (61.3%), CH4 yield (0.28 l/g VS(added)) and CH4 production rate (0.41 l CH4/l/d) than those (0.29 l CH4/l/d) of the mesophilic two-stage ASBR (MTSASBR). In the specific methanogenic activity (SMA) tests on thermophilic biomass of the TPASBR system, the average SMA of acetate (93 ml CH4/gVSS/d) was much higher than those of propionate (46 ml CH4/g VSS/d) and butyrate (76 ml CH4/g VSS/d). Also, higher specific hydrolytic activity (SHA, 217 mg COD/g VSS/d) of the biomass supported fast hydrolysis under thermophilic conditions. The track study revealed that the most active period of the 24 h cycle was between 6 and 12 h. The enhanced performance of the TPASBR system could be attributed to longer solids retention time, fast hydrolysis, higher CH4 conversion rate, and balanced nutrient condition of co-substrate. It was verified that this combination could be a promising and practical alternative for the simultaneous recycling of two types of organic fraction of municipal solid waste (OFMSW) with high stability.


[A case of extensor indicis brevis manus muscle].
The authors present one case of extensor indicis brevis muscle discovered accidentally during surgical operation for suspected synovial cyst of the left hand. They underlin the rarity and the facility of wrong diagnosis in the presence of such anomalous muscle.


An Exploratory Factor Analysis of the Scale Structure of the Patient Care Monitor Version 2.0.
The Patient Care Monitor (PCM), version 2.0, is an electronic patient-reported outcomes instrument designed to be embedded into oncology practices. One key psychometric component of an instrument is its factor structure. To validate the factor structure of the PCM. The PCM was administered within various oncology clinics at our institution from 2006 to 2011 as part of standard of care, yielding a large (n = 5624) and diverse data set. An exploratory factor analysis was performed. The PCM performed well in terms of missing values and floor and ceiling effects. The three scales postulated by the PCM developers exhibited high internal consistency (Cronbach alpha 0.94-0.95); the six subscales exhibited good internal consistency (Cronbach alpha 0.80-0.95). A three-factor model approximated simple structure and was consistent with the constructs of emotional function, physical function, and physical symptoms suggested by the PCM developers. However, a six-factor model did not support the division of these three constructs into subscales of despair, distress, ambulation, impaired performance, treatment side effects, and general physical symptoms. Instead, we observed an emotional factor, a physical functioning factor, a factor including many of the treatment side effects, and three factors consisting of various clusters of physical symptoms. Although six subscales postulated by its developers perform reasonably, allocation of the PCM items to three constructs is more accurate and likely more consistent with how symptoms and concerns are conceptualized by patients.


Primary spontaneous cerebrospinal fluid rhinorrhea: a symptom of idiopathic intracranial hypertension?
The authors aim to identify the characteristics of primary spontaneous CSF rhinorrhea and propose a hypothesis for its pathogenesis. Between 2003 and 2009, 21 patients diagnosed with primary spontaneous CSF rhinorrhea underwent surgery in the authors' hospital. The clinical aspects were retrospectively reviewed, and their characteristics were analyzed. There were 18 women and 3 men, whose ages ranged from 37 to 74 years (mean 53 years). Body mass index (BMI) ranged from 22 to 58.8 kg/m(2) (mean 31.2 kg/m(2)). Eighteen patients (85.7%) were overweight, and 18 (85.7%) suffered from headache or tinnitus before rhinorrhea. Radiological images revealed fully or partially empty sellae in 14 patients (66.7%). The preoperative intracranial pressure (ICP) ranged from 11 to 28 cm H(2)O (mean 17.6 cm H(2)O), while the postoperative ICP ranged from 21 to 32 cm H(2)O (mean 25.5 cm H(2)O, p < 0.01). An endoscope-assisted transnasal approach was chosen for the repair. Postoperatively, in 95.2% of patients a cure was achieved. Rhinorrhea recurred in only 1 patient, and a leakage from a new defect occurred in another patient 4 years after the operation. Both patients underwent additional surgery, which was successful. The follow-up period varied from 5 to 75 months with a mean of 34 months. All patients had direct or indirect evidence of elevated ICP, most patients presented with symptoms of idiopathic intracranial hypertension (IIH), and most patients were women and obese. Primary spontaneous CSF rhinorrhea may be due to IIH, and it is a rare symptom of IIH. When treating or monitoring these patients during follow-up, ICP should be controlled, and other symptoms of IIH should be noted.


Exposure of honey bees (Apis mellifera) to different classes of insecticides exhibit distinct molecular effect patterns at concentrations that mimic environmental contamination.
Pesticides are implicated in the decline of honey bee populations. Many insecticides are neurotoxic and act by different modes of actions. Although a link between insecticide exposure and changed behaviour has been made, molecular effects underlying these effects are poorly understood. Here we elucidated molecular effects at environmental realistic concentrations of two organophosphates, chlorpyrifos and malathion, the pyrethroid cypermethrin, and the ryanodine receptor activator, chlorantraniliprole. We assessed transcriptional alterations of selected genes at three exposure times (24 h, 48 h, 72 h) in caged honey bees exposed to different concentrations of these compounds. Our targeted gene expression concept focused on several transcripts, including nicotinic acetylcholine receptor α 1 and α 2 (nAChRα1, nAChRα2) subunits, the multifunctional gene vitellogenin, immune system related genes of three immune system pathways, genes belonging to the detoxification system and ER stress genes. Our data indicate a dynamic pattern of expressional changes at different exposure times. All four insecticides induced strong alterations in the expression of immune system related genes suggesting negative implications for honey bee health, as well as cytochrome P450 enzyme transcripts suggesting an interference with metabolism. Exposure to neurotoxic chlorpyrifos, malathion and cypermethrin resulted in up-regulation of nAChRα1 and nAChRα2. Moreover, alterations in the expression of vitellogenin occurred, which suggests implications on foraging activity. Chlorantraniliprole induced ER stress which may be related to toxicity. The comparison of all transcriptional changes indicated that the expression pattern is rather compound-specific and related to its mode of action, but clusters of common transcriptional changes between different compounds occurred. As transcriptional alterations occurred at environmental concentrations our data provide a molecular basis for observed adverse effects of these insecticides to bees.


Autogenous Particulate Dentin in Socket Site Preservation Procedures: Histologic and Histomorphometric Observations.
To evaluate the efficacy of autogenous particulate dentin as a bone substitute to maintain dimensional volume in human socket preservation procedures. Particulate dentin was used in socket site preservation procedures. The extracted natural tooth was ground to particles 250 to 1,200 μm in size to fill the socket site. At 6 months, during the implant placement stage, hard tissue biopsy specimens were harvested by a 2.5-mm cylindrical trephine bur for the histologic analysis. Histomorphometry was carried out with ImageJ software to calculate direct bone to grafted dentin particles contact, newly formed bone, and particulate dentin area fractions. Fifteen patients went through the socket preservation procedure using particulate dentin as the grafted bone substitute. De novo bone formation filled the entire grafted area. Newly formed bone was observed throughout the entire grafted area, particularly around the grafted dentin particles. The majority of particles were surrounded by direct contact with newly formed osseous tissue enriched by osteocytes. Newly formed bone ankylosed to particulate dentin and became a solid matrix preserving the ridge dimension. Histomorphometric measurements showed that the new bone formation area fraction was on average 38.4% ± 16.5%, while the residual particulate dentin showed an average of 29.9% ± 14.4%, and 31.7% ± 14.2% was captured by the connective tissue component. Particulate dentin was in direct contact with newly formed bone at an average rate of 69.1% ± 22.8%. Particulate dentin showed complete biocompatibility and high osteoconduction. Thus, it can be used as an appropriate grafting biomaterial to maintain socket site volume dimensionally for subsequent implant placement procedures.


Injection sclerotherapy for oesophageal varices: a prospective randomised trial of different treatment schedules.
A prospective randomised study to compare the efficacy and complications of injection sclerotherapy carried out at intervals of one week and three weeks up to the time obliteration of varices was achieved, was undertaken in 55 patients (48 cirrhosis, six portal vein thrombosis, one nodular regenerative hyperplasia). The number of courses of injection required for obliteration of the varices was not different in the two groups and despite a shorter time scale for obliteration in the weekly treated patients the frequency with which further episodes of bleeding occurred before that was not significantly less. Mucosal ulceration during the period required for obliteration was observed at endoscopy more frequently in the weekly treated patients but was not associated with a greater frequency of postinjection pain, dysphagia or of long term stricture formation.


The cost-effectiveness of cognitive behavioral therapy for bulimia nervosa in the Australian context.
This study was to model the cost-effectiveness of specialist-delivered cognitive behavioral therapy for bulimia nervosa (CBT-BN) compared to no intervention within the Australian context. An illness-death model was developed to estimate the cost per disability-adjusted life-year (DALY) averted of CBT-BN over 2 years from the healthcare perspective. Target population was adults aged 18-65 years with BN. Results are reported as incremental cost-effectiveness ratios (ICER) in 2013 Australian dollars per DALY averted. Uncertainty and sensitivity analyses were conducted to test the robustness of results. Primary analysis indicated that CBT-BN was associated with greater DALY averted (0.10 DALY per person) and higher costs ($1,435 per person) than no intervention, resulting the mean ICER of $14,451 per DALY averted (95% uncertainty interval [UI]: $8,762 to $35,650). Uncertainty analysis indicated CBT-BN is 99% likely to be cost-effective at a threshold of $50,000 per DALY averted. Including the patients' time and travel costs resulted in the mean ICER of $18,858 per DALY averted (95% UI: $11,235 to $46,026). Sensitivity analysis indicated the intervention was not cost-effective if over 80% people discontinued treatment. Other analyses including a reduced time horizon, increased remission rates, and 4-month effect size of CBT-BN increases the ICERs but these ICERs remained well below under a threshold of $50,000 per DALY averted. This study has demonstrated that CBT-BN for adults with BN is a cost-effective treatment intervention. Further research is required to investigate the practicability of CBT-ED and the cost-effectiveness of other formats of CBT-BN delivery.


FDG-PET in thyroid cancer.
The most widely used diagnostic nuclear medicine technique in well-differentiated thyroid cancer (DTC) is radioiodine scintigraphy, either diagnostic or post-therapeutic, together with serum thyroglobulin (Tg) measurement; this combination is usually able to determine the presence or absence of cancer. FDG-PET has shown less sensitivity in DTC that retains the ability to trap 131I. Several alternative procedures with single photon emitting radiopharmaceuticals have been evaluated including whole body scan with 201Tl, 99mTc-sestamibi or tetrofosmin scan, with different sensitivity and specificity. The main advantage of these tests is that their results are not influenced by the levels of TSH, therefore they do not require a hypothyroid state in the patient. Recently positron emission tomography (PET) with FDG has been demonstrated to be highly useful in thyroid cancer patients with a negative 131I whole body scan but measurable Tg. According to reports in the literature FDG-PET in the follow-up of operated patients has a sensitivity ranging from 70% to 90% in identifying the source of Tg. The demonstration of lesions can lead to a change in treatment including surgery or external radiation instead of radioiodine treatment. In Europe, medullary thyroid cancer (MTC) is currently visualized by 99mTc pentavalent dimercaptosuccinic acid (DMSA) and 99mTc-sestamibi or tetrofosmin. Metaiodobenzylguanidine (MIBG) radiolabeled with 123I or 131I is another reliable radiopharmaceutical for medullary tumors. (111)In-pentetreotide scan is positive in a high percentage of patients because MTC expresses somatostatin receptors. FDG-PET has an interesting role to play in calcitonin-positive patients, where PET has been shown to correctly identify lesions in cervical and mediastinal lymph nodes as well as at distant sites. Furthermore, calcitonin-guided PET has been found to be superior to CT and MRI in many patients. Recent reports indicated that 18F-DOPA scan in MTC seems to be more accurate than FDG-PET.


Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated and Artemis for their repair.
Ataxia telangiectasia (ATM) mutated and Artemis, the proteins defective in ataxia telangiectasia and a class of Radiosensitive-Severe Combined Immunodeficiency (RS-SCID), respectively, function in the repair of DNA double strand breaks (DSBs), which arise in heterochromatic DNA (HC-DSBs) following exposure to ionizing radiation (IR). Here, we examine whether they have protective roles against oxidative damage induced and/or endogenously induced DSBs. We show that DSBs generated following acute exposure of G0/G1 cells to the oxidative damaging agent, tert-butyl hydroperoxide (TBH), are repaired with fast and slow components of similar magnitude to IR-induced DSBs and have a similar requirement for ATM and Artemis. Strikingly, DSBs accumulate in ATM(-/-) mouse embryo fibroblasts (MEFs) and in ATM or Artemis-defective human primary fibroblasts maintained for prolonged periods under confluence arrest. The accumulated DSBs localize to HC-DNA regions. Collectively, the results provide strong evidence that oxidatively induced DSBs arise in HC as well as euchromatic DNA and that Artemis and ATM function in their repair. Additionally, we show that Artemis functions downstream of ATM and is dispensable for HC-relaxation and for pKAP-1 foci formation. These findings are important for evaluating the impact of endogenously arising DNA DSBs in ATM and Artemis-deficient patients.


[Skeletal involvement in malignant lymphoma].
Of 114 patients with Hodgkin's disease reviewed, 13 (11%) had bone involvement. The typical osseous lesion in Hodgkin's disease is a secondary manifestation in the axial skeleton. The lesions are mainly lytic; there is no relation between the site of the affection and the character of the lesion. Of 261 patients with non-Hodgkin lymphoma, 19 (7.3%) had bone involvement. Non-Hodgkin lymphoma very rarely affects the bone primarily; these lesions are lytic. Involvement of the appendicular skeleton is reported to by typical; this cannot be confirmed by our study. Most secondary osseous lesions in non-Hodgkin lymphoma are found in the cranium, the spine and the sternum; this pattern of distribution as well as the mainly lytic appearance can be considered typical.


Adipose-Derived Stromal Cells and Mineralized Extracellular Matrix Delivery by a Human Decellularized Amniotic Membrane in Periodontal Tissue Engineering.
Periodontitis is a prevalent disease characterized by the loss of periodontal supporting tissues, bone, periodontal ligament, and cementum. The application of a bone tissue engineering strategy with Decellularized Human Amniotic Membrane (DAM) with adipose-derived stromal cells (ASCs) has shown to be convenient and valuable. This study aims to investigate the treatments of a rat periodontal furcation defect model with DAM, ASCs, and a mineralized extracellular matrix (ECM). Rat ASCs were expanded, cultivated on DAM, and with a bone differentiation medium for four weeks, deposited ECM on DAM. Periodontal healing for four weeks was evaluated by micro-computed tomography and histological analysis after treatments with DAM, ASCs, and ECM and compared to untreated defects on five consecutive horizontal levels, from gingival to apical. The results demonstrate that DAM preserves its structure during cultivation and healing periods, supporting cell attachment, permeation, bone deposition on DAM, and periodontal regeneration. DAM and DAM+ASCs enhance bone healing compared to the control on the gingival level. In conclusion, DAM with ASC or without cells and the ECM ensures bone tissue healing. The membrane supported neovascularization and promoted osteoconduction.


The effect of Medicaid premiums on enrollment: a regression discontinuity approach.
This paper estimates the effect that premiums in Medicaid have on the length of enrollment of program beneficiaries. Whether and how low income-families will participate in the exchanges and in states' Medicaid programs depends crucially on the structure and amounts of the premiums they will face. I take advantage of discontinuities in the structure of Wisconsin's Medicaid program to identify the effects of premiums on enrollment for low-income families. I use a 3-year administrative panel of enrollment data to estimate these effects. I find an increase in the premium from 0 to 10 dollars per month results in 1.4 fewer months enrolled and reduces the probability of remaining enrolled for a full year by 12 percentage points, but other discrete changes in premium amounts do not affect enrollment or have a much smaller effect. I find no evidence of program enrollees intentionally decreasing labor supply in order to avoid the premiums.


Short-term enzalutamide treatment for the potential remission of active surveillance or intermediate-risk prostate cancer: a case study, review, and the need for a clinical trial.
Active surveillance (AS) is a widely recognized and utilized option by which prostate cancer patients with less aggressive tumors on diagnosis defer immediate traditional conventional therapy (surgery, radiation) and undergo close monitoring by a physician for any clinical or pathologic changes. The juxtaposition of low- to intermediate-risk elderly patients between effective and conventional treatment with associated risks and monitoring without the opportunity for relief of anxiety and other psychological problems can be significant. Minimal and safe treatment over 6 months with the hope of eliminating the existing disease is of significant interest to prostate cancer patients. Unfortunately, dietary supplements have failed to improve and have sometimes even contributed to disease progression. In addition, the use of multiple medications is not always appropriate or safe. In this case study, we administered low doses of enzalutamide (80 mg/day-120 mg/day) in an AS patient during a 6 month period. Results showed a significant reduction in tumor size, as evidenced by magnetic resonance imaging and color Doppler, as well as a an undetectable level of prostate specific antigen during, and immediately following treatment. The use of an oral second-generation androgen-receptor signaling inhibitor was shown to be of benefit to patients unwilling to pursue AS and conventional treatment. Administration of enzalutamide did not reduce testosterone levels, but helped maintain good quality of life, was more cost effective at low doses, and was previously shown to be heart healthy and efficacious during early stages of castration-resistant prostate cancer. Although we do not advocate enzalutamide as a treatment approach in these situations, we believe that a clinical trial to evaluate short-term low-dose treatment using enzalutamide is warranted.


[Cellular immune response detected in blast transformation test with lymphocytes from rabbits immunized with nucleocapsid of herpes simplex type 2 virus].
A preparation of herpes simplex virus type 2 (HSV-2) nucleocapsid (NC) was obtained after treatment of intracellular virus with detergents followed by centrifugation in linear sucrose density gradient. Electron microscopic analysis revealed polymorphism of HSV-2 NC population. Three main types of capsid structures were found: empty capsids, NC containing various amounts of nucleoid material, and NC with complete nucleoid. Morphological heterogeneity correlated with heterogenous sedimentation profile of the total NC preparation of labeled virus represented by light, intermediate, and heavy structures. Specific blasttranformation tests with lymphocytes from rabbits immunized with HSV-2 NC demonstrated differences in the primary and secondary cellular immune responses. The secondary cellular immune response was characterized by a more rapid and strong increase in BTT values than the primary immune response.


Amplification of acetylcholine-binding catenanes from dynamic combinatorial libraries.
Directed chemical synthesis can produce a vast range of molecular structures, but the intended product must be known at the outset. In contrast, evolution in nature can lead to efficient receptors and catalysts whose structures defy prediction. To access such unpredictable structures, we prepared dynamic combinatorial libraries in which reversibly binding building blocks assemble around a receptor target. We selected for an acetylcholine receptor by adding the neurotransmitter to solutions of dipeptide hydrazones [proline-phenylalanine or proline-(cyclohexyl)alanine], which reversibly combine through hydrazone linkages. At thermodynamic equilibrium, the dominant receptor structure was an elaborate [2]-catenane consisting of two interlocked macrocyclic trimers. This complex receptor with a 100 nM affinity for acetylcholine could be isolated on a preparative scale in 67% yield.


Opioids prescriptions in pain therapy and risk of addiction: a one-year survey in Italy. Analysis of national opioids database.
An "epidemic use" of legal opioids in the USA and other countries has been reported in the last 15 years. We have analysed the database of the Italian Ministry of Health regarding the prescription of opioids for pain management to verify the trend of opioids uses in Italy. The amount of opioids prescribed for every single Italian patient in 2013 was anonymously recorded and transformed in daily MED (morphine equivalent dose). We considered every monthly percentage increase of MED during the entire period of chronic therapy for each patient. Classes of dosage increase for all patients in chronic therapy, distinguished between cancer and non-cancer ones, were created. We deduce that decreases or increases of small proportions prevailed in the observation period. The opioids "plague" that is striking the USA is not registered in Italy during the observation period. The reasons might be due to the innovative and effective law 38/2010 and a health care system able to guarantee appropriate prescriptions for major analgesics.


The Mg(2+)-ATPase of rabbit skeletal-muscle transverse tubule is a highly glycosylated multiple-subunit enzyme.
The Mg(2+)-ATPase present in rabbit skeletal-muscle transverse tubules is an integral membrane enzyme which has been solubilized and purified previously in this laboratory [Kirley (1988) J. Biol. Chem. 263, 12682-12689]. The present study indicates that, in addition to the approx. 100 kDa protein (distinct from the sarcoplasmic-reticulum Ca(2+)-ATPase) seen previously to co-purify with the Mg(2+)-ATPase activity, there are also proteins having molecular masses of 160, 70 and 43 kDa. The 70 and 43 kDa glycosylated proteins (50 and 31 kDa after deglycosylation) are difficult to detect by SDS/PAGE before deglycosylation, owing to the broadness of the bands. Additional purification procedures, cross-linking studies and chemical and enzymic deglycosylation studies were undertaken to determine the structure and relationship of these proteins. Both the 97 and 160 kDa proteins were demonstrated to be N-glycosylated at multiple sites, the 97 kDa protein being reduced to a peptide core of 84 kDa and the 160 kDa protein to a peptide core of 131 kDa after deglycosylation. Although the Mg(2+)-ATPase activity is resistant to a number of chemical modification reagents, cross-linking inactivates the enzyme at low concentrations. This inactivation is accompanied by cross-linking of two 97 kDa molecules to one another, suggesting that the 97 kDa protein is involved in ATP hydrolysis. The existence of several proteins along with the inhibition of ATPase activity by cross-linking is consistent with the interpretation of the susceptibility of this enzyme to inactivation by most detergents as being due to the disruption of a protein complex of associated subunits by the inactivating detergents. The 160 kDa glycoprotein can be partially resolved from the Mg(2+)-ATPase activity, and is identified by its N-terminal amino acid sequence as angiotensin-converting enzyme.


Control of intracellular pH. Predominant role of oxidative metabolism, not proton transport, in the eukaryotic microorganism Neurospora.
Recessed-tip microelectrodes were used to measure internal pH (pHi) in the fungus Neurospora, and to examine the response of pHi to several kinds of stress: changes of extracellular pH (pHo), inhibition of the principal proton pump in the plasma membrane, and inhibition of respiration. Under control conditions, at pHo = 5.8, pHi in Neurospora is 7.19 +/- 0.04. Changes of pHo between 3.9 and 9.3 affect pHi linearly but with a slope of only approximately 0.1 unit pHi per unit pHo, stable pHi being reached within 3 min of changed pHo. Despite a postulated high passive permeability of the Neurospora membrane to protons (Slayman, 1970), neither active nor passive H+ transport appears critical to pHi because (alpha) specific inhibition of the proton pump by orthovanadate has little effect on pHi, and (b) cytoplasmic acidification produced by respiratory blockade is unaffected by the size or direction of proton gradient. To convert measured changes in pHi into net proton fluxes, intracellular buffering capacity (beta i) was measured by the weak acid/weak base technique. At pHi = 7.2, beta i was (-) 35 mmol H+ (liter cell water)-1 (pH unit)-1, but beta i increased substantially in both the acid and alkaline directions, which suggests that amino acid side chains are the principal source of buffer.


MR evaluation of sinonasal angiomatous polyp.
SAP is a rare lesion of the sinonasal cavity, which may be misdiagnosed as a benign or malignant neoplasm. The purpose of our study was to comprehensively evaluate the MR imaging features of SAP. Forty patients with SAP confirmed pathologically were retrospectively reviewed. Of the 40 patients undergoing MR imaging, 39 had postcontrast T1WI; 30, DCE MR imaging; and 17, DWI. The image features assessed included the location, shape, margin, size, signal intensity, and enhancement pattern on DCE MR imaging and ADC maps. All 40 SAPs originated from the maxillary sinus, but the lesions frequently extended into the ipsilateral nasal cavity (38/40), toward the choana (19/40), and into the nasopharynx (8/40). The lesions demonstrated hypointensity on T1WI and heterogenous hyperintensity on T2WI. All 40 lesions showed a peripheral hypointense rim on T2WI. Postcontrast MR imaging revealed marked heterogeneous nodular and patchy enhancement. Progressive enhancement was found on DCE MR imaging in 30 cases. The TIC showed a steady enhancement pattern in 3 cases, a rapidly enhancing and slow washout pattern in 6 cases, and a rapidly enhancing and rapid washout pattern in 21 cases. On DWI, the mean ADC value was (1.40 ± 0.20) × 10(-3) mm(2)/s. Distinctive features of SAP on conventional MR imaging include internal heterogeneous hyperintensity and a peripheral hypointense rim on T2WI, as well as strong nodular and patchy enhancement on postcontrast MR images. The progressive enhancement on DCE MR imaging can also suggest the diagnosis.


Dietary soy and tea mitigate chronic inflammation and prostate cancer via NFκB pathway in the Noble rat model.
Chronic inflammation and nuclear factor-kappa B (NFκB) have been implicated in prostate cancer development; thus, dietary factors that inhibit NFκB may serve as effective chemo-preventative agents. Prostate cancer risk is significantly lower in Asian countries compared to the United States, which has prompted interest in the potential chemopreventative action of Asian dietary components such as soy and green tea. This study examined the effects of dietary soy and tea on NFκB activation and inflammation in vivo using a hormone-induced rat model for prostate cancer. Male Noble rats implanted with estradiol and testosterone were divided into 4 dietary groups: control, soy, tea, or soy+tea. NFκB activation and inflammatory cytokines were measured post implantation. The combination of soy and tea suppressed NFκB p50 binding activity and protein levels via induction of IκBα. Soy and tea also decreased prostate inflammatory infiltration, increased Bax/BcL2 ratio and decreased protein expression of tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1β compared to control. Soy and tea attenuated prostate malignancy by decreasing prostate hyperplasia. These effects were not apparent in groups treated with soy or tea alone. The ongoing in vivo studies thus far suggest that combination of foods, such as soy and tea, may inhibit hormone-induced proinflammatory NFκB signals that contribute to prostate cancer development.


Review of criteria used to measure library effectiveness.
This article reports the results of a survey of literature on measures of library effectiveness. This survey led to the formulation of six criterion concepts (accessibility, cost, user satisfaction, response time, cost/benefit ratio, and use). The advantages and disadvantages of each method of measurement are discussed. Several points which became clear during the analysis are discussed. First, there is a relative lack of concern with the rationale behind the evaluation process, although the results invariably lead to a confused interpretation when there is no clear understanding of the purpose of an evaluation. Second, the total library system is rarely considered; instead, each evaluation criterion is taken in isolation rather than as part of the whole. Third, the library's preservation function has not been considered at all.


Clustered-Dot Screen Design for Digital Multitoning.
Digital multitoning is an extension of halftoning for rendering more than two tones at each pixel for higher image quality. Although a lot of effort has been put in generating dispersed dots previously, the blue-noise feature can hardly be achieved for those printers utilizing the electrophotography (EP) process to avoid the physically unstable isolated dots. To overcome this issue, Chandu et al. proposed a screening method for yielding green-noise dot clusters, yet noisy multitone texture was accompanied. This degrades the visual quality and the stability of tone rendering. In this paper, a significantly improved homogeneity of clustered dots can be achieved by the proposed screening method based upon the new inter-iterative clustered-dot direct multi-bit search algorithm. Compared with the former approaches, the inter-iteration design leads to less error by the updated initial multitone patterns. As demonstrated in the experimental results, both of the high homogenous multitone texture and less noisy perception at all absorptance levels are offered in contrast to the former Chandu et al.'s results. The high-quality output proves it as a very competitive candidate for EP printers, e.g., laser printers.


Simulation Fellowship Programs: An International Survey of Program Directors.
To report on the evolution of simulation-based training (SBT) by identifying the composition and infrastructure of existing simulation fellowship programs, describing the current training practices, disclosing existing program barriers, and highlighting opportunities for standardization. Investigators conducted a cross-sectional survey study among English-speaking simulation fellowship program directors (September 2014-September 2015). They identified fellowships through academic/institutional Web sites, peer-reviewed literature, Web-based search engines, and snowball sampling. They invited programs to participate in the Web-based questionnaire via e-mail and follow-up telephone calls. Forty-nine programs met the inclusion criteria. Of these, 32 (65%) responded to the survey. Most programs were based in the United States, but others were from Canada, England, and Australia. Over half of the programs started in or after 2010. Across all 32 programs, 186 fellows had graduated since 1998. Fellows and directors were primarily departmentally funded; programs were primarily affiliated with hospitals and/or medical schools, many of which had sponsoring centers accredited by governing bodies. Fellows were typically medical trainees; directors were typically physicians. The majority of programs (over 90%) covered four core objectives, and all endorsed similar educational outcomes. Respondents identified no significant universal barriers to program success. Most directors (18/28 [64%]) advocated standardized fellowship guidelines on a national level. Paralleling the fast growth and integration of SBT, fellowship training opportunities have grown rapidly in the United States, Canada, and beyond. This study highlights potential areas for standardization and accreditation of simulation fellowships which would allow measurable competencies in graduates.


The value of studying gene-environment interactions in culturally diverse populations.
Cardiovascular disease (CVD) is the leading cause of death and disability in the world. It is anticipated that CVD will reach pandemic proportions by the year 2020. Although the major causes of CVD are well documented and explain the majority of cardiovascular deaths, the prevalence of conventional cardiovascular risk factors vary substantially across diverse cultural groups. These differences are attributed to cultural or genetic differences or to interactions between genes and environmental factors. Substantial efforts have been invested in determining the genetic influences on CVD development, and it is unlikely that a single gene is responsible for the development of atherosclerotic CVD or its classical risk factors such as blood pressure or plasma lipids. It is more plausible that multiple genes, acting either alone or in concert with one another, which display effect modification in the presence of certain environmental factors, are modestly associated with CVD or its main risk factors. Following this hypothesis, studying populations with diversity in environmental factors may increase the discovery potential of gene-environmental interactions. In this brief review, the advantage of studying gene-environment interactions across heterogeneous groups with diverse lifestyles is discussed.


Selinexor for the treatment of patients with previously treated multiple myeloma.
Multiple myeloma (MM) is an increasingly treatable but still incurable hematologic malignancy. Prognosis has improved significantly over recent years, although further advances remain urgently needed, especially for patients with heavily pre-treated and resistant disease for whom there are limited options. Selinexor is a first-in-class, oral, selective inhibitor of nuclear export (SINE) compound that triggers apoptosis in malignant cells by inducing nuclear retention of oncogene messenger RNAs (mRNAs) and reactivation of tumor suppressor proteins (TSPs). In clinical studies of patients with relapsed and/or refractory MM, selinexor has demonstrated both manageable toxicity and encouraging efficacy. This review will provide an overview of the mechanism of action of selinexor as well as the efficacy and safety data from clinical studies using selinexor for the treatment of multiple myeloma. Long-term outcomes for patients with MM will continue to improve due to numerous recent and imminent therapeutic advances, although critical areas of unmet need remain. Oral selinexor is likely to contribute to the meeting of these needs and the further advancement of MM therapy in a meaningful way.


Membrane morphology determines diacylglycerol kinase α substrate acyl chain specificity.
Diacylglycerol kinases catalyze the ATP-dependent phosphorylation of diacylglycerol (DAG) to produce phosphatidic acid (PA). In humans, the alpha isoform (DGKα) has emerged as a potential target in the treatment of cancer due to its anti-tumor and pro-immune responses. However, its mechanism of action at a molecular level is not fully understood. In this work, a systematic investigation of the role played by the membrane in the regulation of the enzymatic properties of human DGKα is presented. By using a cell-free system with purified DGKα and model membranes of variable physical and chemical properties, it is shown that membrane physical properties determine human DGKα substrate acyl chain specificity. In model membranes with a flat morphology; DGKα presents high enzymatic activity, but it is not able to differentiate DAG molecular species. Furthermore, DGKα enzymatic properties are insensitive to membrane intrinsic curvature. However, in the presence of model membranes with altered morphology, specifically the presence of physically curved membrane structures, DGKα bears substrate acyl chain specificity for palmitic acid-containing DAG. The present results identify changes in membrane morphology as one possible mechanism for the depletion of specific pools of DAG as well as the production of specific pools of PA by DGKα, adding an extra layer of regulation on the interconversion of these two potent lipid-signaling molecules. It is proposed that the interplay between membrane physical (shape) and chemical (lipid composition) properties guarantee a fine-tuned signal transduction system dependent on the levels and molecular species of DAG and PA.


Inhibition of microsomal lipid peroxidation and protein oxidation by extracts from plants used in Bamun folk medicine (Cameroon) against hepatitis.
The antioxidant activities of 53 medicinal plants used in Bamun folk medicine for the management of jaundice and hepatitis were investigated. The studies were done using rat hepatic microsomes for lipid peroxidation and bovine serum albumin (BSA) for carbonyl group formation. Silymarine was used as reference compound. Fifteen different extracts were effective at a dose of 200 microg/ml in both experiments. Specifically, 25 extracts inhibited lipid peroxidation initiated non-enzymatically by ascorbic acid while 18 inhibited peroxidation as determined by reduced Nicotinamide Adenine Dinucleotide Phosphate (NADPH). The inhibitory concentration 50 (IC(50)) of 23 different plant extracts was lower than 200 microg/ml in the microsomal lipid peroxidation inhibition study. Fifteen of the 23 extracts were active in preventing protein oxidation by inhibiting the formation of the carbonyl group on BSA with an IC(50) value less than 200 microg/ml. The results suggest that the antioxidant activity of the extracts, may be due to their ability to scavenge free radicals involved in microsomal lipid peroxidation or in protein oxidation. These biochemical processes are involved in the aetiology of toxic hepatitis.


Continuous flow organic synthesis under high-temperature/pressure conditions.
Microreactor technology and continuous flow processing in general are key features in making organic synthesis both more economical and environmentally friendly. When preformed under a high-temperature/pressure process intensification regime many transformations originally not considered suitable for flow synthesis owing to long reaction times can be converted into high-speed flow chemistry protocols that can operate at production-scale quantities. This Focus Review summarizes the state of the art in high-temperature/pressure microreactor technology and provides a survey of successful applications of this technique from the recent synthetic organic chemistry literature.


Venoarterial Extracorporeal Membrane Oxygenation After Autologous Stem Cell Transplantation With Pancytopenia: JACC Patient Care Pathways.
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) provides temporary mechanical circulatory support and simultaneous extracorporeal gas exchange for acute cardiorespiratory failure. By providing circulatory support, VA-ECMO gives treatments time to reach optimal efficacy or may be used as a bridge to a more durable mechanical solution for patients with acute cardiopulmonary failure. It is commonly used when a readily reversible etiology of decompensation is identified with very strict inclusion criteria for extracorporeal cardiopulmonary resuscitation use. We present a unique case in which VA-ECMO/extracorporeal cardiopulmonary resuscitation was used after cardiac arrest with pulseless electrical activity in a patient with recurrent lymphoma of the left thigh with recent autologous stem cell transplant.


Evaluation of a ferroelectric tunnel junction by ultraviolet-visible absorption using a removable liquid electrode.
Ferroelectric memristors offer a significant alternative to their redox-based analogs in resistive random access memory because a ferroelectric tunnel junction (FTJ) exhibits a memristive effect that induces resistive switching (RS) regardless of the operating current level. This RS results from a change in the ferroelectric polarization direction, allowing the FTJ to overcome the restriction encountered in redox-based memristors. Herein, the memristive effect of an FTJ was investigated by ultraviolet-visible (UV-Vis) absorption spectroscopy using a removable mercury (Hg) top electrode (TE), BaTiO3 (BTO) ferroelectric tunnel layer, La0.7Sr0.3MnO3 (LSMO) semiconductor bottom electrode, and wide-bandgap quartz (100) single-crystal substrate to determine the low-resistance state (LRS) and high-resistance state (HRS) of the FTJ. A BTO (110)/LSMO (110) polycrystal memristor involving a Hg TE showed a small memristive effect (switching ratio). This effect decreased with increasing read voltage because of a small potential barrier height. The LRS and HRS of the FTJ showed quasi-similar UV-Vis absorption spectra, consistent with the small energy difference between the valence-band maximum of BTO and Fermi level of LSMO near the interface between the LRS and HRS. This energy difference stemmed from the ferroelectric polarization and charge-screening effect of LSMO based on an electrostatic model of the FTJ.


Utility of neurological smears for intrasurgical brain cancer diagnostics and tumour cell percentage by DESI-MS.
Analysis of neurological smears by desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging diagnostic strategy for intraoperative consultation in brain tumor resection. DESI-MS allows rapid sampling while providing accurate diagnostic information. We assess the chemical homogeneity of neurological smears using DESI-MS imaging and the quality of rapid DESI-MS diagnosis.


Identification of largemouth bass virus in the introduced Northern Snakehead inhabiting the Chesapeake Bay watershed.
The Northern Snakehead Channa argus is an introduced species that now inhabits the Chesapeake Bay. During a preliminary survey for introduced pathogens possibly harbored by these fish in Virginia waters, a filterable agent was isolated from five specimens that produced cytopathic effects in BF-2 cells. Based on PCR amplification and partial sequencing of the major capsid protein (MCP), DNA polymerase (DNApol), and DNA methyltransferase (Mtase) genes, the isolates were identified as Largemouth Bass virus (LMBV). Nucleotide sequences of the MCP (492 bp) and DNApol (419 pb) genes were 100% identical to those of LMBV. The nucleotide sequence of the Mtase (206 bp) gene was 99.5% identical to that of LMBV, and the single nucleotide substitution did not lead to a predicted amino acid coding change. This is the first report of LMBV from the Northern Snakehead, and provides evidence that noncentrarchid fishes may be susceptible to this virus.


Installation of the pyrrolyl-2-carboxyl pharmacophore by CouN1 and CouN7 in the late biosynthetic steps of the aminocoumarin antibiotics clorobiocin and coumermycin A1.
The 5-methyl-2-pyrrolylcarbonyl moiety of the aminocoumarin antibiotics clorobiocin and coumermycin A1 is the key pharmacophore for targeting the ATP-binding site of GyrB for inhibition of the bacterial type-II topoisomerase DNA gyrase. During the late stage of clorobiocin and coumermycin A1 biosynthesis, the pyrrolyl-2-carboxyl group is transferred from the peptidyl carrier proteins Clo/CouN1 to the 3'-hydroxyl of the 4-methoxy-L-noviosyl scaffold by the action of the acyltransferases Clo/CouN7. CouN1 and CouN7 have now been heterologously expressed and purified from Escherichia coli. The apo form of CouN1 is converted to the acyl-holo form by loading with pyrrolyl-2-carboxyl-S-pantetheinyl moieties from synthetic pyrrolyl- and 5-methylpyrrolyl-CoAs by the action of the phosphopantetheinyl transferase Sfp. CouN7 acts as an acyltransferase, moving the pyrrole acyl moieties from CouN1 to the noviose sugar of descarbamoylnovobiocin. When the 5-methylpyrrolyl-2-carboxyl-thioester of CouN1 is the cosubstrate, the in vitro product differs from clorobiocin only in a CH3 for Cl group change on the coumarin ring. Double transfer of this acyl moiety by CouN7 to the penultimate intermediate in coumermycin A1 assembly completes that antibiotic biosynthetic pathway.


Localization of the site of ventricular preexcitation with body surface maps in patients with Wolff-Parkinson-White syndrome.
Forty-nine patients with Wolff-Parkinson-White syndrome, ages 7 weeks to 51 years, were studied with isopotential body surface maps during normal sinus rhythm, atrial pacing or induced atrial fibrillation. The location of the accessory pathway was determined by multicather electrophysiologic study or surgical ablation of the accessory pathway. When fusion was minimized and ventricular activation primarily controlled by a single accessory pathway, the distribution of positive and negative potentials on the anterior and posterior torso during QRS (observed at 40 msec) and the ST segment were an excellent index of the location of the site of the accessory pathway. The relationship between a specific sequence of QRS-T wave body surface maps and a specific preexcitation site was similar from patient to patient in the presence of marked differences in age, size, and different cardiac status due to structural congenital cardiac defects. The localization of the site of the accessory pathway using distributions too early in QRS (before 40 msec) was unreliable because the early distributions varied from patient to patient for the same preexcitation site; however, the potential distributions during the ST segment were both stable and consistent from patient to patient for the same preexcitation site. The presence of significant fusion of ventricular activation initiated via a single accessory pathway and the normal conduction system or via multiple accessory pathways complicated the interpretation of body surface distributions. Thus, one can predict accurately at least seven preexcitation sites by the combined use of QRS and ST-segment body surface maps.


Smoking and drinking habits of women in subsequent pregnancies after specific advice about the dangers of these exposures during pregnancy.
Although women are informed about the dangers of drinking and smoking during pregnancy when they book for antenatal care, it is uncertain whether this advice is accepted, or whether attempts are made to apply it in subsequent pregnancies. To assess how pregnant women respond to the advice to refrain from smoking and drinking during pregnancy in subsequent pregnancies. Research staff were trained to obtain accurate prospective information on smoking and drinking during pregnancy in a prospective study, using well-standardised methods. Care was taken to inform participants about the dangers of smoking and drinking during pregnancy. They were also given pamphlets on these dangers in their own language and a list of telephone numbers where they could find help to quit should they need it. This information was repeated at subsequent study visits (ranging from 1 to 3, depending on the gestational age at which they enrolled). Gestational age was determined by early ultrasound. Z-scores of birthweight for gestational age were determined according to the INTERGROWTH-21st study. Pregnancy outcomes of women who enrolled twice (n=888) or three times (n=77) in the Safe Passage Study were compared with those of women in the first enrolment (n=889). The proportion of drinkers did not change significantly (p=0.058) from the first to the second and third enrolments (63.8%, 59.0% and 54.6%, respectively). A similar trend was found for smokers (73.3%, 72.2% and 68.4%, respectively). Cannabis use was reported by 15.1%, 9.7% and 12.0% (p<0.005) of women, respectively, and use of methamphetamine by 10.1%, 6.6% and 12.7% (p<0.005). There was an increase in the rate of preterm births from 15.5% to 17.5% and 24.7%, respectively, but the increase was not significant. Although mean birthweight was lower in the third enrolment compared with the second, the difference was not significant. The z-score of birthweight for gestational age was significantly lower in the second enrolment compared with the first. Detailed information on the adverse effects of smoking and drinking during pregnancy was not effective in the population studied. Other methods to reduce or stop these toxic exposures should therefore be investigated. A short inter-pregnancy interval, as demonstrated by three enrolments in 7.5 years, is associated with preterm labour and fetal growth restriction, and is probably indicative of the role played by confounders such as poor socioeconomic conditions and drug exposure during pregnancy.


Congenital lacrimal sac fistula: a case report and review.
The lacrimal system is crucial for vision and comprises the lacrimal glands, which produce tears, and the lacrimal drainage system, which drains tears away from the eyes. While various disease processes affect the lacrimal glands, the lacrimal drainage system is commonly prone to congenital abnormalities such as lacrimal sac fistula. We describe a case with classic findings and review dermatologic manifestations of this entity.


Components of the plasma membrane of growing axons. III. Saxitoxin binding to sodium channels.
The density of sodium channels was measured in growing and mature axons of the olfactory nerve of the bullfrog, using as a probe the drug saxitoxin (STX). The toxin binds to control nerves from adult animals in a saturable manner with a dissociation constant of approximately 23 nM at 4 degrees C and a capacity of 72 fmol/mg wet weight, equivalent to about five sites per square micrometer of axolemma. In growing nerves, obtained from adult frogs 4-5 wk following removal of the original nerve, the STX-binding capacity per wet weight of tissue is markedly reduced, to approximately 25% of control values, and appears to decrease in the proximodistal direction. STX-binding data, expressed as STX/mg wet weight, was converted to STX/micron 2 of axolemma using stereologically derived values of membrane area per milligram wet weight of nerve. The axolemmal content (area/mg wet weight) of all regions of growing nerve is substantially decreased compared to controls, but increases in the proximodistal direction by 60%. These changes in axolemmal area result in calculated STX receptor densities (per unit axolemmal area) which, in distal regions, are approximately at the level of the mature nerve and, in proximal regions, are actually increased above controls by 50 to 70%. Upon comparing the axolemmal density of intramembrane particles, reported in the companion paper, with the calculated density of STX receptors in both mature and growing nerves, we find a correlation between STX receptors and intramembrane particles with diameters of 11.5-14.0 nm. The growing axon's gradient of sodium channels and the shift from this gradient to a uniform distribution in the mature axon suggest (a) that sodium channels are inserted into the perikaryal plasmalemma and diffuse from there into the growing axolemma, and (b) that the axolemma undergoes functional maturation during growth.


Effects of the surface mobility on the oxidation of adsorbed CO on platinum electrodes in alkaline media. The role of the adlayer and surface defects.
The oxidation of adsorbed CO on Pt single crystal electrodes has been studied in alkaline media. The surfaces used in this study were the Pt(111) electrode and vicinal stepped and kinked surfaces with (111) terraces. The kinked surfaces have either (110) steps broken by (100) kinks or (100) steps broken by (110) kinks and different kink densities. The voltammetric profiles for the CO stripping on those electrodes show peaks corresponding to the oxidation of CO on the (111) terraces, on the (100) steps/kinks and on the (110) steps/kinks at very distinctive potentials. Additionally, the stripping voltammograms always present a prewave. The analysis of the results with the different stepped and kinked surfaces indicates that the presence of the prewave is not associated with defects or kinks in the electrode surface. Also, the clear separation of the CO stripping process in different peak contributions indicates that the mobility of CO on the surface is very low. Using partial CO stripping experiments and studies at different pH, it has been proposed that the low mobility is a consequence of the negative absolute potential at which the adlayers are formed in alkaline media. Also, the surface diffusion coefficient for CO in these media has been estimated from the dependence of the stripping charge of the peaks with the scan rate of the voltammetry.


Predator discrimination error and the benefits of Müllerian mimicry.
Müllerian mimicry has traditionally been thought to benefit both unpalatable mimic and model species but recently its existence has been questioned. Even if both mimic and model species are unpalatable, they are unlikely to be equally unpalatable. It has been argued that the more unpalatable species will suffer a cost of increased predation because the presence of the more palatable mimic will increase its perceived palatability (by the predator), similar to that experienced by a model in Batesian mimicry. Yet, previous models of Müllerian mimicry have assumed that a predator can discriminate perfectly between available prey. We argue that this is not the case and that discrimination error is an important factor in determining the nature of mimetic relationships. Using computer simulations we show that the nature of a mimetic relationship will depend on the trade-off between the cost of an increase in perceived palatability and the benefits of a reduction in predator discrimination error. We show that mimicry can be unequivocally Müllerian, with both species benefiting, and propose that palatability should no longer be used as the sole defining characteristic of a mimetic relationship. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.


Prostatic ultrasonography: applicability in a small hospital.
This paper reports the results of a prospective study undertaken to assess the applicability of prostatic ultrasonography in a small community hospital, and to determine the accuracy and technical feasibility of sonographic imaging using contact scanning technique.


A tool for gene expression based PubMed search through combining data sources.
We present a new tool for the semi-automated querying of PubMed using a batch of tens to thousands of GenBank accession numbers or UniGene cluster ids. By combining information from UniGene and SWISS-PROT, microGENIE obtains information on the biological relevance of expressed genes, as identified by micro-array experiments, with minimal user intervention and time investment. microGENIE is freely available from http://www.cs.vu.nl/microgenie The web site above supplies examples of input and output files.


A new RNASeq-based reference transcriptome for sugar beet and its application in transcriptome-scale analysis of vernalization and gibberellin responses.
Sugar beet (Beta vulgaris sp. vulgaris) crops account for about 30% of world sugar. Sugar yield is compromised by reproductive growth hence crops must remain vegetative until harvest. Prolonged exposure to cold temperature (vernalization) in the range 6 °C to 12 °C induces reproductive growth, leading to bolting (rapid elongation of the main stem) and flowering. Spring cultivation of crops in cool temperate climates makes them vulnerable to vernalization and hence bolting, which is initiated in the apical shoot meristem in processes involving interaction between gibberellin (GA) hormones and vernalization. The underlying mechanisms are unknown and genome scale next generation sequencing approaches now offer comprehensive strategies to investigate them; enabling the identification of novel targets for bolting control in sugar beet crops. In this study, we demonstrate the application of an mRNA-Seq based strategy for this purpose. There is no sugar beet reference genome, or public expression array platforms. We therefore used RNA-Seq to generate the first reference transcriptome. We next performed digital gene expression profiling using shoot apex mRNA from two sugar beet cultivars with and without applied GA, and also a vernalized cultivar with and without applied GA. Subsequent bioinformatics analyses identified transcriptional changes associated with genotypic difference and experimental treatments. Analysis of expression profiles in response to vernalization and GA treatment suggested previously unsuspected roles for a RAV1-like AP2/B3 domain protein in vernalization and efflux transporters in the GA response. Next generation RNA-Seq enabled the generation of the first reference transcriptome for sugar beet and the study of global transcriptional responses in the shoot apex to vernalization and GA treatment, without the need for a reference genome or established array platforms. Comprehensive bioinformatic analysis identified transcriptional programmes associated with different sugar beet genotypes as well as biological treatments; thus providing important new opportunities for basic scientists and sugar beet breeders. Transcriptome-scale identification of agronomically important traits as used in this study should be widely applicable to all crop plants where genomic resources are limiting.


Biological and clinical features of acute lymphoblastic leukaemia with cytoplasmic granules or inclusions: description of eight cases.
We describe eight patients (four children and four adults) with an acute lymphoblastic leukaemia (ALL) with cytoplasmic granules or inclusions. The incidence of this variant of acute leukaemia in our whole series of patients with ALL is 1.8%. The granules or inclusions were usually positive for aspecific esterases (ANAE) and/or acid phosphatase, and the immunophenotype was in all cases typical of a CALLA positive B-lineage ALL (CD10+, CD19+ and/or CD24+, DR+, TdT+, anti-T-, anti-My-, SIg-). In one paediatric case, CD33 was unusually coexpressed. Ultrastructural investigations were performed in one case and demonstrated large granules containing vesicles, usually membrane bound, in the majority of blast cells. In the two cases analysed, Ig heavy chain gene rearrangement was detected. In this series of patients prognosis was poor since three never achieved a complete remission, four relapsed and only one is still in first continuous remission.


Assembled Structures of Perfluorosulfonic Acid Ionomers Investigated by Anisotropic Modeling and Simulations.
Nafion, a classic of perfluorosulfonic acid ionomers, has broad applications in proton conduction, attributed from the unique structures. However, a satisfactory structure model from theoretical calculation and simulation that can match with the well-known experimental observations is still absent. We performed GPU-accelerated molecular dynamics simulations to investigate the assembled structures of Nafion at different water contents based on an anisotropic coarse-grained model equipped with Gay-Berne potential. Accurate parameters for the coarse-grained model are collected by matching energy profiles based on density functional theory calculations. The results show that the hydrophilic phase in Nafion assemblies undergoes a crossover from isolated spherical clusters to interconnected cluster/channel networks with the increase of water content. We found the crystalline domains in polymer matrix and they are suppressed at elevated water content. These microphase-separated structures achieve quantitative agreement with existing experimental observations, including morphologies from electron microscopy and intensity profiles from scattering experiments. This work suggests that accurate consideration of the anisotropy is a key to reveal the formation of unique assembled structures of perfluorosulfonic acid ionomers at different water contents.


Vpr-mediated incorporation of UNG2 into HIV-1 particles is required to modulate the virus mutation rate and for replication in macrophages.
Human immunodeficiency virus type 1 is able to infect nondividing cells, such as macrophages, and the viral Vpr protein has been shown to participate in this process. Here, we investigated the impact of the recruitment into virus particles of the nuclear form of uracil DNA glycosylase (UNG2), a cellular DNA repair enzyme, on the virus mutation rate and on replication in macrophages. We demonstrate that the interaction of Vpr with UNG2 led to virion incorporation of a catalytically active enzyme that is directly involved with Vpr in modulating the virus mutation rate. The lack of UNG in virions during virus replication in primary monocyte-derived macrophages further exacerbated virus mutant frequencies to an 18-fold increase compared with the 4-fold increase measured in actively dividing cells. Because the presence of UNG is also critical for efficient infection of macrophages, these observations extend the role of Vpr to another early step of the virus life cycle, e.g. viral DNA synthesis, that is essential for replication of human immunodeficiency virus type 1 in nondividing cells.


Tyrosine residues 239 and 240 of Shc are phosphatidylinositol 4,5-bisphosphate-dependent phosphorylation sites by c-Src.
In the previous study (Sato K.-I. et al. (1997) FEBS Lett. 410, 136-140), we showed that the phosphorylation of Shc protein by c-Src is dependent on the binding of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to the PTB domain of Shc. In this study, we demonstrate that, in contrast to c-Src, v-Src and epidermal growth factor (EGF) receptor can phosphorylate Shc in a PtdIns(4,5)P2-independent manner and at different phosphorylation sites. To determine the phosphorylation sites in Shc, we used mutant Shc proteins in which tyrosine residues (Y) 317 and/or 239 and 240 were replaced by phenylalanine residues (F). We found that Y317F Shc but not Y239/240F or Y239/240/317F Shc was phosphorylated by c-Src. The reaction was PtdIns(4,5)P2-dependent and inhibited by the addition of PTB domain of Shc. On the other hand, v-Src and EGF receptor were able to phosphorylate both Y317F and Y239/240F but not Y239/240/317F Shc in a PtdIns(4,5)P2-independent manner. These results highlight the difference between c-Src and v-Src or EGF receptor and suggest that c-Src can phosphorylate predominantly on Tyr239/240 of Shc only when Shc PTB domain is bound to PtdIns(4,5)P2.


Cutting edge: innate immune response triggered by influenza A virus is negatively regulated by SOCS1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway.
Influenza A virus (IAV) triggers a contagious respiratory disease that produces considerable lethality. Although this lethality is likely due to an excessive host inflammatory response, the negative feedback mechanisms aimed at regulating such a response are unknown. In this study, we investigated the role of the eight "suppressor of cytokine signaling" (SOCS) regulatory proteins in IAV-triggered cytokine expression in human respiratory epithelial cells. SOCS1 to SOCS7, but not cytokine-inducible Src homology 2-containing protein (CIS), are constitutively expressed in these cells and only SOCS1 and SOCS3 expressions are up-regulated upon IAV challenge. Using distinct approaches affecting the expression and/or the function of the IFNalphabeta receptor (IFNAR)1, the viral sensors TLR3 and retinoic acid-inducible gene I (RIG-I) as well as the mitochondrial antiviral signaling protein (MAVS, a RIG-I signaling intermediate), we demonstrated that SOCS1 and SOCS3 up-regulation requires a TLR3-independent, RIG-I/MAVS/IFNAR1-dependent pathway. Importantly, by using vectors overexpressing SOCS1 and SOCS3 we revealed that while both molecules inhibit antiviral responses, they differentially modulate inflammatory signaling pathways.


[Role of vascular endothelial growth factor and monocyte chemoattractant protein-1 in the development of endothelial dysfunction in types 1 and 2 diabetes mellitus complicated by diabetic retinopathy].
The paper presents the results of a study of the serum levels of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) in 120 patients with types 1 and 2 diabetes mellitus complicated by diabetic retinopathy. All the patients with diabetes have been ascertained to show a rise in the levels of MCP-1 and VEGF. Calculation of VEGF/MCP-1 ratio is proposed to evaluate vascular bed lesion in diabetic patients.


Benzodiazepine Use and Dependence in Relation to Chronic Pain Intensity and Pain Catastrophizing.
Benzodiazepines (BZDs), a class of sedative-hypnotic medications, generated concern as their popularity grew, with particular alarm regarding elevated rates of BZD use among chronic pain populations. Consistent with negative reinforcement/motivational models of substance use, desire for pain alleviation may motivate BZD use. Yet, little is known about relations between pain and addiction-relevant BZD use processes. This cross-sectional survey study aimed to: a) test associations between pain intensity and clinically relevant BZD use patterns, and b) examine the role of pain catastrophizing in hypothesized pain-BZD relations. Participants included 306 adults with chronic musculoskeletal pain and a current BZD prescription who completed an online survey study (Mage = 38.7, 38.9% female). Results indicated that pain intensity was positively associated with past-month BZD use frequency, BZD dependence severity, and likelihood of endorsing BZD misuse behaviors (ps < .05). Pain catastrophizing was positively associated with BZD dependence/likelihood of BZD misuse, covarying for pain intensity (P < .05). These findings build upon an emerging literature by highlighting positive covariation of pain intensity and pain catastrophizing with addiction-relevant BZD use behaviors. Results underscore the need to further investigate high-risk BZD use among individuals with chronic pain, with and without concurrent opioid use, to inform prevention/intervention efforts. PERSPECTIVE: This article presents findings on cross-sectional associations of pain intensity and pain catastrophizing with clinically relevant benzodiazepine (BZD) use outcomes, including dependence and misuse, among individuals with chronic pain. Findings help elucidate the higher burden of BZD misuse/dependence in chronic pain populations and suggest that pain relief may be a common, yet under recognized, self-reported motivation for taking BZDs.


When Emotions Matter: Focusing on Emotion Improves Working Memory Updating in Older Adults.
Research indicates that emotion can affect the ability to monitor and replace content in working memory, an executive function that is usually referred to as updating. However, it is less clear if the effects of emotion on updating vary with its relevance for the task and with age. Here, 25 younger (20-34 years of age) and 25 older adults (63-80 years of age) performed a 1-back and a 2-back task, in which they responded to younger, middle-aged, and older faces showing neutral, happy or angry expressions. The relevance of emotion for the task was manipulated through instructions to make match/non-match judgments based on the emotion (i.e., emotion was task-relevant) or the age (i.e., emotion was task-irrelevant) of the face. It was found that only older adults updated emotional faces more readily compared to neutral faces as evidenced by faster RTs on non-match trials. This emotion benefit was observed under low-load conditions (1-back task) but not under high-load conditions (2-back task) and only if emotion was task-relevant. In contrast, task-irrelevant emotion did not impair updating performance in either age group. These findings suggest that older adults can benefit from task-relevant emotional information to a greater extent than younger adults when sufficient cognitive resources are available. They also highlight that emotional processing can buffer age-related decline in WM tasks that require not only maintenance but also manipulation of material.


Novel approaches to HIV prevention and sexual health promotion among Guatemalan gay and bisexual men, MSM, and transgender persons.
The burden of HIV is disproportionate for Guatemalan sexual minorities (e.g., gay and bisexual men, men who have sex with men [MSM], and transgender persons). Our bi-national partnership used authentic approaches to community-based participatory research (CBPR) to identify characteristics of potentially successful programs to prevent HIV and promote sexual health among Guatemalan sexual minorities. Our partnership conducted Spanish-language focus groups with 87 participants who self-identified as male (n=64) or transgender (n=23) and individual in-depth interviews with ten formal and informal gay community leaders. Using constant comparison, an approach to grounded theory, we identified 20 characteristics of potentially successful programs to reduce HIV risk, including providing guidance on accessing limited resources; offering supportive dialogue around issues of masculinity, socio-cultural expectations, love, and intimacy; using Mayan values and images; harnessing technology; increasing leadership and advocacy skills; and mobilizing social networks. More research is clearly needed, but participants reported needing and wanting programming and had innovative ideas to prevent HIV exposure and transmission.


Bovine milk glycome.
Bovine milk oligosaccharides have several potentially important biological activities including the prevention of pathogen binding to the intestinal epithelial and as nutrients for beneficial bacteria. It has been suggested that milk oligosaccharides are an important source of complex carbohydrates as supplements for the food and the pharmaceutical industries. However, only a small number of structures of bovine milk oligosaccharides (bMO) are known. There have been no systematic studies on bMO. High-performance mass spectrometry and separation methods are used to evaluate bMO, and nearly 40 oligosaccharides are present in bovine milk. Bovine milk oligosaccharides are composed of shorter oligomeric chains than are those in human milk. They are significantly more anionic with nearly 70%, measured abundances, being sialylated. Additionally, bMO are built not only on the lactose core (as are nearly all human milk oligosaccharides), but also on lactose amines. Sialic acid residues include both N-acetyl and N-glycolylneuraminic acid, although the former is significantly more abundant.


The Function, Underlying Mechanism and Clinical Potential of Exosomes in Colorectal Cancer.
Colorectal cancer (CRC) is a lethal malignancy worldwide. Exosomes are extracellular vesicles derived from the endosomal pathway of nearly all cells and can be found in body fluids. They can be considered an intercellular system in the human body that can mediate near- and long-distance intercellular communication due to their features and functions. Investigations have revealed that exosomes are participated in different processes, physiologically and pathologically, especially in cancer. However, the clinical value of exosomes and their mechanisms of action in CRC are unclear and have not been systematically assessed. The purpose of this review is to discuss how exosomes play a role in the occurrence and development of CRC, with a particular focus on the functions and underlying mechanisms of tumor-derived exosomes as well as non-tumor-derived exosomes. We also describe the evidence that exosomes can be used as diagnostic and prognostic markers for CRC. In addition, the possibilities of exosomes in CRC clinical transformation are also discussed.


Effects of organophosphate pesticides and other drugs on subcortical mechanisms of visual integration.
Atropine, scopolamine, mevinphos, and eserine selectively block directional sensitivity of visual integrative neurones in the thalamus. Cholinergic drugs that do not penetrate the blood-brain barrier are without effect. The neurones studied are important links in reflex brain systems controlling visual attention and eye movements. The results suggest that any cholinergic drug that can get into the brain will disturb visual functions. Since the changes are qualitative and the system is reflex, the affected individual may be unaware of dysfunction. The resultant dangers to aerial applicator personnel are discussed, particularly with respect to atropine, which is necessary in the therapy of organophosphate and carbamate poisoning but is potentially harmful if self-administered for either pro-phylaxis or treatment.


Neurotrophins, inflammation and oxidative stress as illness activity biomarkers in bipolar disorder.
Recent studies highlight the presence of systemic toxicity as an integral dimension of bipolar disorder pathophysiology, possibly linking this mood disorder with other medical conditions and comorbidities. This review summarizes recent findings on possible peripheral biomarkers of illness activity, with a focus on neurotrophins, inflammation and oxidative stress. The possible mechanisms underlying the systemic toxicity associated with acute episodes in bipolar disorder are also discussed. Finally, the authors outline novel therapies that emerge from this new research and the assessment of multiple biomarkers as a potential approach to improving management strategies in bipolar disorder.


Vascular endothelial growth factor receptor-2 expression is induced by 17beta-estradiol in ZR-75 breast cancer cells by estrogen receptor alpha/Sp proteins.
Vascular endothelial growth factor receptor-2 kinase insert domain receptor (VEGFR2/KDR) is critical for angiogenesis, and VEGFR2 mRNA and protein are expressed in ZR-75 breast cancer cells and induced by 17beta-estradiol (E2). Deletion analysis of the VEGFR2 promoter indicates that the proximal GC-rich region is required for both basal and hormone-induced transactivation, and mutation of one or both of the GC-rich motifs at -58 and -44 results in loss of transactivation. Electrophoretic mobility shift and chromatin immunoprecipitation assays show that Sp1, Sp3, and Sp4 proteins bind the GC-rich region of the VEGFR2 promoter. Results of the chromatin immunoprecipitation assay also demonstrate that ERalpha is constitutively bound to the VEGFR2 promoter and that these interactions are not enhanced after treatment with E2, whereas ERalpha binding to the region of the pS2 promoter containing an estrogen-responsive element is enhanced by E2. RNA interference studies show that hormone-induced activation of the VEGFR2 promoter constructs requires Sp3 and Sp4 but not Sp1, demonstrating that hormonal activation of VEGFR2 involves a nonclassical mechanism in which ERalpha/Sp3 and ERalpha/Sp4 complexes activate GC-rich sites where Sp proteins but not ERalpha bind DNA. These results show for the first time that Sp3 and Sp4 cooperatively interact with ERalpha to activate VEGFR2 and are in contrast to previous results showing that several hormone-responsive genes are activated by ERalpha/Sp1 in breast cancer cell lines.


The Hypotensive and Vasodilatory Effects Observed in Rats Exposed to Chiranthodendron pentadactylon Larreat Flowers Can Be Attributed to Cyanidin 3-O-Glucoside.
Chiranthodendron pentadactylon Larreat is a tree native to southeastern Mexico and Guatemala. Its flower is used in Mexican folk medicine to treat a variety of diseases, including conditions of blood pressure. However, scientific information on its usefulness in this pathology is lacking. The present study evaluates the effect of a methanolic extract (ME) from the flower and its active constituents on heart rate (HR) and mean arterial pressure (MAP) in anesthetized rats (MAPHR). The study also analyzed the effects on rat-isolated aortic rings (RIAR) and the rat mesenteric arterial bed (MABR). Active fractions were chromatographed, which led to the isolation of cyanidin 3-O-glucoside (C3G) identified through HPLC. The Chiranthodendron pentadactylon flowers produced hypotensive and vasorelaxant effects associated with C3G. The vasorelaxant effect is a mechanism underlying the synthesis and release of nitric oxide (NO). Neither cholinergic receptors nor prostaglandins are involved. ME and C3G cause cardiovascular depression in anesthetized rats via cholinergic and prostanoid mechanisms. Our research expands the scientific understanding of the flowers on the rat cardiovascular system. This amplifies the appreciation of the flower's ethnomedicine employed to control blood pressure. However, researchers need to conduct toxicity studies to determine the safety of this plant.


Response to a urate-lowering diet according to polymorphisms in the apolipoprotein AI-CIII-AIV cluster.
The apolipoprotein AI-CIII-AIV cluster has been associated with the response to a urate-lowering diet, and polymorphisms in the apolipoprotein CIII gene have been associated with hyperuricemia and hypertriglyceridemia. We assessed the influence of polymorphisms in the apolipoprotein AI-CIII-AIV cluster on the response to a urate-lowering diet in patients with hyperuricemia. A urate-lowering diet was followed for 2 weeks by 64 men with hyperuricemia. Plasma concentrations of triglycerides, cholesterol, glucose, and uric acid, and the uric acid clearance and 24-hour uric acid urinary excretory fraction were measured before and after the diet. The data were analyzed in association with the polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster. After the urate-lowering diet, the plasma levels of triglycerides, cholesterol, glucose, and uric acid and 24-hour uric acid excretion all fell significantly. Paired sample ANOVA showed that the decrease was mainly due to the diet, except for the plasma triglycerides, which were influenced by allele X2 of the XmnI polymorphism of the apolipoprotein AI gene. The response of the biological variables to a urate-lowering diet was mainly influenced by diet. Changes in triglycerides were also influenced by the apolipoprotein AI XmnI polymorphism (p = 0.04), suggesting a gene-diet interaction (p = 0.03).


Dietary intake estimated using different methods in two Italian older populations.
Most of the tools used to assess nutritional intake in large epidemiological studies were originally developed to be used in young and middle-aged subjects and, therefore, their validity and reliability when employed in older subjects remain uncertain. We conducted this study to verify whether the questionnaire developed in the context of the European Prospective Investigation into Cancer and nutrition (EPIC) could be used to assess dietary intake in the participants of InCHIANTI, an epidemiological study of risk factors for disability in late life, performed in 633 men (78% aged, > or =65 years) and 802 women (81% aged, > or =65 years) randomly sampled from the general population. In particular, the aim of this project was to collect preliminary information that could support a future study of concurrent validity. Data on food consumption assessed using the EPIC questionnaire from the InCHIANTI participants were compared with those collected using a 7-day diary in the National Nutritional Investigation into Dietary Behavior (INN-CA), a study conducted in 15 Italian centres aimed at assessing Italian households' and individuals' dietary intake. In spite of different populations and different methods used in data collection, the distributions of dietary intake from the two studies were remarkably similar for most macro- and micro-nutrients, both in men and women and according to age groups. At a population level, a food frequency questionnaire and a costly and time-consuming objective method provided similar estimates of dietary intake. Future study should attempt to generalize these findings at an individual level by collecting data with both instruments in the same subjects.


Minimally invasive plate fixation in femoral shaft fractures.
Bridge-plating with its advantages in terms of vascularity and bone healing is a well established procedure today in the treatment of comminuted femoral fractures. Bridge-plating means that the fracture site is not interfered with during the operative procedure. This paper introduces a surgical technique in which the plate is inserted through isolated proximal and distal incisions only, behind the vastus lateralis. Alignment is secured by the plates, the fracture site remains untouched, fixation and screw insertion is restricted to the proximal and distal main fragments. Longitudinal femoral fractures extending right into the trochanteric and or condylar areas are the main indication for minimally invasive plate fixations with angled blade plates or condylar screws since fractures which are restricted to the diaphyseal area are mostly treated by nailing today. The surgical trauma resulting from plating by proximal and distal incisions only is less than that associated with conventional techniques. Indirect reduction of femoral fragments is much easier since the integrity of the surrounding muscles and soft tissue is preserved, the fragments often being reduced simply by traction. Adjustment of rotation is an essential aspect requiring careful attention. For special indications, namely comminuted fractures affecting a large part of the femur and extending into the trochanteric or condylar areas, insertion of the plate via proximal and distal incisions only is a further development in bridge-plating which minimizes surgical trauma and operation time.


[A radioautographic study of changes in the intensity of total protein synthesis in the limb tissues of anuran amphibia during loss of regenerating capacity].
The intensity of total protein synthesis was estimated by 3H-lysine incorporation in the hind limb tissues of mesodermal origin in the common frog tadpoles. In the course of limb development and loss of regenerative ability, the intensity of 3H-lysine incorporation in the differentiating muscle tissue and cartilage epiphysis increased; the cartilage diaphysis is characterized by the low level of 3H-lysine incorporation. At the stage Ia of regeneration after the limb amputation the intensity of labeling in the tissues of organ residue descreases until the stage of regeneration blastema formation and then, during the formation of limb rudiment, rapidly increases. The blastema cells are characterized by the high intensity of 3H-lysine incorporation. At the stage IIIa of wound healing after the limb amputation, the intensity of 3H-lysine incorporation in the differentiated muscles and cartilage epiphysis gradually decreases. The intensity of labeling in the scar cells is high enough.


Development of novel pea protein-based nanoemulsions for delivery of nutraceuticals.
A novel pea protein-based emulsifier was used in the production of oil in water (O/W) nanoemulsions. The regions of kinetically stabilized O/W emulsions were individuated in a pseudoternary diagram containing different pea protein, sunflower oil, and water fractions. The stable O/W emulsion region was widened by the addition of NaCl to the aqueous phase or, to a more significant extent, by high pressure homogenization (HPH) processing. The HPH treatment caused the formation of very fine emulsions in the nanometric range (<200 nm), with extremely high stability over time. HPH treatment affected the protein properties, resulting in a reduced water surface tension. Changes in protein structure, which were characterized by light scattering and SDS-PAGE, suggest the occurrence of the disruption of disulfide bonds, thus changing the exposition and availability of hydrophobic groups.


Central Venous Catheter Placement in the Left Internal Jugular Vein Complicated by Perforation of the Left Brachiocephalic Vein and Massive Hemothorax: A Case Report.
An elderly male presented for emergent repair of a ruptured abdominal aortic aneurysm. For anticipated volume resuscitation, vasopressor administration, and hemodynamic monitoring, a large-bore central venous catheter was placed in the left internal jugular vein under ultrasound guidance before surgical incision. Initially, there were no readily apparent signs of venous perforation. However, a massive left hemothorax developed because of perforation of the brachiocephalic vein and violation of the pleural space. This case report discusses both prevention and management of such a complication.


White matter hyperintensities and medial temporal lobe atrophy in clinical subtypes of mild cognitive impairment: the DESCRIPA study.
Clinical subtypes of mild cognitive impairment (MCI) may represent different underlying aetiologies. This European, multicentre, memory clinic based study (DESCRIPA) of non-demented subjects investigated whether MCI subtypes have different brain correlates on MRI and whether the relation between subtypes and brain pathology is modified by age. Using visual rating scales, medial temporal lobe atrophy (MTA) (0-4) and white matter hyperintensities (WMH) (0-30) were assessed. Severity of MTA differed between MCI subtypes (p<0.001), increasing from a mean of 0.8 (SD 0.7) in subjective complaints (n = 77) to 1.3 (0.8) in non-amnestic MCI (n = 93), and from 1.4 (0.9) in single domain amnestic MCI (n = 70) to 1.7 (0.9) in multiple domain amnestic MCI (n = 89). The association between MCI subtype and MTA was modified by age and mainly present in subjects >70 years of age. Severity of WMH did not differ between MCI subtypes (p = 0.21). However, the combination of MTA and WMH differed between MCI subtypes (p = 0.02) We conclude that MCI subtypes may have different brain substrates, especially in older subjects. Isolated MTA was mainly associated with amnestic MCI subtypes, suggesting AD as the underlying cause. In non-amnestic MCI, the relatively higher prevalence of MTA in combination with WMH may suggest a different pathophysiological origin.


The occurrence of cardiovascular disease during 5-year follow-up in patients with idiopathic atrial fibrillation.
Idiopathic atrial fibrillation (AF) may be an expression of as yet undetected underlying heart disease. We found it useful for clinical practice to study the long-term development of cardiovascular disease (CVD) in patients diagnosed with idiopathic AF. Forty-one consecutive idiopathic AF patients (56 ± 10 years, 66% male) were compared with 45 healthy control patients in permanent sinus rhythm. Patients were free of hypertension, antihypertensive and antiarrhythmic drugs, diabetes, congestive heart failure, coronary artery or peripheral vascular disease, previous stroke, thyroid, pulmonary and renal disease, and structural abnormalities on echocardiography. Baseline characteristics and echocardiographic parameters were equal in AF cases and controls. During a mean follow-up of 66 ± 11 months, CVD occurred significantly more often in idiopathic AF patients compared with controls (49 vs. 20%, P= 0.006). Patients with idiopathic AF were significantly younger at the time of their first CV event compared with controls (59 ± 9 vs. 64 ± 5 years, P= 0.027), and had more severe disease. Multivariable Cox regression analysis revealed that age, a history of AF, and echocardiographic left ventricular wall width were significant predictors of CVD development. Patients originally diagnosed with idiopathic AF develop CVD more often, at younger age, and with a more severe disease profile compared with healthy sinus rhythm control patients. The detection and treatment of CVD in an early stage could improve the prognosis of these patients. At present it seems prudent to regularly check idiopathic AF patients for the insidious development of CVD.


Polyamine metabolism and cancer.
Polyamines are aliphatic cations present in all cells. In normal cells, polyamine levels are intricately controlled by biosynthetic and catabolic enzymes. The biosynthetic enzymes are ornithine decarboxylase, S-adenosylmethionine decarboxylase, spermidine synthase, and spermine synthase. The catabolic enzymes include spermidine/spermine acetyltransferase, flavin containing polyamine oxidase, copper containing diamine oxidase, and possibly other amine oxidases. Multiple abnormalities in the control of polyamine metabolism and uptake might be responsible for increased levels of polyamines in cancer cells as compared to that of normal cells. This review is designed to look at the current research in polyamine biosynthesis, catabolism, and transport pathways, enumerate the functions of polyamines, and assess the potential for using polyamine metabolism or function as targets for cancer therapy.


The spread and control of norovirus outbreaks among hospitals in a region: a simulation model.
Because hospitals in a region are connected via patient sharing, a norovirus outbreak in one hospital may spread to others. We utilized our Regional Healthcare Ecosystem Analyst software to generate an agent-based model of all the acute care facilities in Orange County (OC), California and simulated various norovirus outbreaks in different locations, both with and without contact precautions. At the lower end of norovirus reproductive rate (R0) estimates (1.64), an outbreak tended to remain confined to the originating hospital (≤6.1% probability of spread). However, at the higher end of R0 (3.74), an outbreak spread 4.1%-17.5% of the time to almost all other OC hospitals within 30 days, regardless of the originating hospital. Implementing contact precautions for all symptomatic cases reduced the probability of spread to other hospitals within 30 days and the total number of cases countywide, but not the number of other hospitals seeing norovirus cases. A single norovirus outbreak can continue to percolate throughout a system of different hospitals for several months and appear as a series of unrelated outbreaks, highlighting the need for hospitals within a region to more aggressively and cooperatively track and control an initial outbreak.


Cheyne-Stokes respiration in patients with congestive heart failure: causes and consequences.
Cheyne-Stokes respiration is a form of periodic breathing in which central apneas and hypopneas alternate with periods of hyperventilation, producing a waxing and waning pattern of tidal volume. This review focuses on the causes and consequences of Cheyne-Stokes respiration in patients with congestive heart failure, in whom the prevalence is strikingly high and ranges from 30% to 50%. Several factors have been implicated in the genesis of Cheyne-Stokes respiration, including low cardiac output and recurrent hypoxia. The key pathophysiological mechanism triggering Cheyne-Stokes respiration is hyperventilation and low arterial CO2 (PaCO2) that when below the apneic threshold triggers a central apnea. Hyperventilation is associated with pulmonary congestion, and Cheyne-Stokes respiration is more prone to occur during sleep, when the respiratory system is mainly dependent on chemical control. It is associated with recurrent dips in oxygen saturation and arousals from sleep, with oscillations in blood pressure and heart rate, sympathetic activation and increased risk of ventricular tachycardia. Cheyne-Stokes respiration is an independent marker of poor prognosis and may participate in a vicious cycle, further stressing the failing heart.


Chromoome mapping of asteurella pseudotuberculosis by interrupted mating.
Pasteurella pseudotuberculosis, containing the Escherichia coli plasmid F'lac, transferred its chromosome in an oriented manner to each of five multiply auxotrophic strains of P. pseudotuberculosis. In a mating system containing gelatin, glucose, and phosphate buffer, a maximum of 0.02% of the donor cells transferred lead markers. The donor population was counterselected with nalidixic acid. We established the entry time of seven markers as follows: proline (11 min); arginine (14 min); histidine (14 min); threonine (25 min); lysine (50 min); tyrosine (67 min); and tryptophan (77 min). However, an analysis of the inheritance of unselected markers did not support the simplest assumption that the chromosome was transferred as Origin... pro... arg his... thr... lys... tyr... trp.... The markers common to all five recipients, arg and his, were closely linked, but of the five other markers, each unique to a different recipient strain, only trp was linked to arg and his. Our data suggest that the Pasteurella chromosome is transferred in more than one linkage group.


Demonstration of a two-line Kr PLIF thermometry technique for gaseous combustion applications.
Experiments were performed to demonstrate a dual-wavelength excitation krypton planar laser-induced fluorescence (Kr PLIF)-based 2D temperature imaging technique in a laminar non-sooting CH4/N2 diffusion flame. The technique exploits the thermochemical dependence of the overlap integral arising from Kr absorption and excitation laser spectra to yield the temperature without the need to know the local mixture composition. The choice of the two excitation wavelengths is made using the knowledge of the fuel mixture and pressure. The two excitation wavelengths lie within the same 4p6S01→→5p[32]2 transition, and their selection is informed such that the resulting Kr PLIF signal ratio depends primarily on the temperature and negligibly on local composition. Mean temperature fields show excellent agreement when compared to Fluent simulations across different regions of the combustion domain, while the single-shot temperature field exhibits slightly degraded accuracy. Overall, the technique provides very similar figures of merit compared to conventional composition-dependent thermometry approaches and showcases a promising scope for application in complex reacting flows.


[The experience in postoperative administration of alpha-adrenoblockers].
The study of efficacy of alpha-blocker alfuzosine (dalphaz CP) in a dose 10 mg/day for treatment of postoperative complications after transurethral resection (TUR) of the prostate and open adenomectomy (OAE) and in quality of life (QoL) improvement enrolled 22 patients after TUR of the prostate and 18 patients after OAE. Examination of the patients was carried out before the operation 10 days and 1 month after surgery. The assessment was performed according to IPSS, QoL index, V and RU. It is shown that patients treated without the alpha-blocker had more urination defects. Administration of alpha-blocker on day 1 after surgical treatment of prostatic adenoma leads to earlier regress of urination disorders. This improves the course of the postoperative period, lowers the risk of urogenital infection and risk of acute urine retention. Therefore QoL rises significantly.


Modulation of Subcellular Redox Homeostasis with Trialkylphosphines.
Redox homeostasis is essential for cell function and its disruption is associated with multiple pathologies. Redox balance is largely regulated by the relative concentrations of reduced (GSH) and oxidized (GSSG) glutathione. In eukaryotic cells, this ratio is different in each cell compartment. There is a lack of chemical probes able to modulate GSH/GSSG in order to study the impact of redox stress in an organelle specific manner. Here, we highlight the importance of trialkylphosphines to induce reductive stress and how it can be targeted to a specific organelle. Our probe is selectively activated by endogenous nitroreductases, and releases tributylphosphine to trigger redox stress in mitochondria. Mechanistic studies revealed that the induced stress activates a cellular response orchestrated by transcription factor ATF4, which upregulates genes involved in glutathione catabolism.