The partitioning of phosphoramide mustard and its aziridinium ions among alkylation and P-N bond hydrolysis reactions.
NMR (1H and 31P) and HPLC techniques were used to study the partitioning of phosphoramide mustard (PM) and its aziridinium ions among alkylation and P-N bond hydrolysis reactions as a function of the concentration and strength of added nucleophiles at 37 degrees C and pH 7.4. With water as the nucleophile, bisalkylation accounted for only 10-13% of the product distribution given by PM. The remainder of the products resulted from P-N bond hydrolysis reactions. With 50 mM thiosulfate or 55-110 mM glutathione (GSH), bisalkylation by a strong nucleophile increased to 55-76%. The rest of the PM was lost to either HOH alkylation or P-N bond hydrolysis reactions. Strong experimental and theoretical evidence was obtained to support the hypothesis that the P-N bond scission observed at neutral pH does not occur in the parent PM to produce nornitrogen mustard; rather it is an aziridinium ion derived from PM which undergoes P-N bond hydrolysis to give chloroethylaziridine. In every buffer studied (bis-Tris, lutidine, triethanolamine, and Tris), the decomposition of PM (with and without GSH) gave rise to 31P NMR signals which could not be attributed to products of HOH or GSH alkylation or P-N bond hydrolysis. The intensities of these unidentified signals were dependent on the concentration of buffer.


Ecosystem-based management of a Mediterranean urban wastewater system: a sensitivity analysis of the operational degrees of freedom.
Urban wastewater systems discharge organic matter, nutrients and other pollutants (including toxic substances) to receiving waters, even after removing more than 90% of incoming pollutants from human activities. Understanding their interactions with the receiving water bodies is essential for the implementation of ecosystem-based management strategies. Using mathematical modeling and sensitivity analysis we quantified how 19 operational variables of an urban wastewater system affect river water quality. The mathematical model of the Congost system (in the Besòs catchment, Spain) characterizes the dynamic interactions between sewers, storage tanks, wastewater treatment plants and the river. The sensitivity analysis shows that the use of storage tanks for peak shaving and the use of a connection between two neighboring wastewater treatment plants are the most important factors influencing river water quality. We study how the sensitivity of the water quality variables towards changes in the operational variables varies along the river due to discharge locations and river self-purification processes. We demonstrate how to use the approach to identify interactions and how to discard non-influential operational variables.


A 12-month evaluation of the CMA-containing oral contraceptive Belara: efficacy, tolerability and anti-androgenic properties.
We conducted a postmarketing surveillance study to assess the long-term efficacy and tolerability of the oral contraceptive Belara (chlormadinone acetate 2.0 mg/ethinylestradiol 0.03 mg) in a normal outpatient setting. Another interest focused on changes in androgen-related skin and hair disorders. A total of 2620 women were enrolled in a 12-cycle clinical evaluation at 435 gynecological practices throughout Germany. An unadjusted Pearl index of 0.44 was calculated. At least 9 out of 10 pregnancies were attributable to user failure, thus resulting in an adjusted Pearl index of 0.04. More than two thirds (67.3%) of the women did not experience any bleeding disorder. Patients with intermenstrual bleeding or amenorrhea at study entry reported complete relief in 61.7% and 89.3%, respectively. Women who previously suffered from spots or bad skin showed significant improvement during the observation period (85.6%). Likewise, the percentage of patients with greasy or very greasy hair decreased markedly. The vast majority of women scored the tolerability of Belara as "very good" or "good." The results of this postmarketing study confirm that Belara is well tolerated and provides a high contraceptive efficacy, reliable cycle stability and beneficial effects on skin and hair.


Epidemiology and aetiology of cancer of the uterine cervix including the detection of carcinogenic N-nitrosamines in the human vaginal vault.
Cancer of the uterine cervix occurs with high frequency in black females of several populations of Southern Africa. It accounts for 40-50% of all cancers in Black females in the Johannesburg area and for over 40% of those in women in the rural lowveld area of the Transvaal. The aetiology of this cancer has several distinct features, almost all of which concern some or other aspect of coitus. Age at first coitus and at first marriage, and promiscuity, are very strongly associated with the development of the disease, and age, race, religion, culture, socio-economic status, extent of genital hygiene and venereal disease also play a major role. In spite of current belief, circumcision of the male partner is at best weakly associated with the development of the disease, and so are menstruation, coital habits and pregnancy. Certain aetiological features are selectively discussed; these include Herpesvirus type II, 'rogue' spermatozoa and the recent isolation of a group of potent carcinogens, the nitrosamines, in infected discharge samples taken from the vaginal vault of patients attending gynaecological clinics.


Operando Characterization of Organic Mixed Ionic/Electronic Conducting Materials.
Operando characterization plays an important role in revealing the structure-property relationships of organic mixed ionic/electronic conductors (OMIECs), enabling the direct observation of dynamic changes during device operation and thus guiding the development of new materials. This review focuses on the application of different operando characterization techniques in the study of OMIECs, highlighting the time-dependent and bias-dependent structure, composition, and morphology information extracted from these techniques. We first illustrate the needs, requirements, and challenges of operando characterization then provide an overview of relevant experimental techniques, including spectroscopy, scattering, microbalance, microprobe, and electron microscopy. We also compare different in silico methods and discuss the interplay of these computational methods with experimental techniques. Finally, we provide an outlook on the future development of operando for OMIEC-based devices and look toward multimodal operando techniques for more comprehensive and accurate description of OMIECs.


[Drug-induced immune tolerance to sheep erythrocytes in mice of different lines].
Immunological tolerance to sheep erythrocytes was induced in mice of the CBA, C57BL/6, CC57BR, C3H, DBA/2 lines by means of combined administration of a high dose of the antigen and cyclophosphamide. The count of 19S antibody-forming cells was determined in the mouse spleen after the test injection of erythrocytes, by local hemolysis in gel. The extent of the tolerance induced proved to depend on the genotype of the animals; mice of the DBA/2 line were found to be most "sensitive" to its induction. There was revealed no correlation between the level of the immunological reactivity to sheep erythrocytes in the intact mice of different lines and the extent of its suppression in tolerance induction


The effect of N-acetylcysteine on inflammation and oxidative stress in cisplatin-induced nephrotoxicity: a rat model
Cisplatin is a highly effective chemotherapeutic agent used in the treatment of solid organ cancers. Besides its chemotherapeutic effectiveness, cisplatin administration is associated with numerous side effects. Of those, the most clinically significant and common effect is nephrotoxicity. Recent studies reported that oxidative stress and inflammation are probably the most important mechanisms that contribute to the nephrotoxicity. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent. In the present study, the effects of NAC on cisplatin-induced nephrotoxicity were investigated. Rats were divided into four groups each including eight rats: CONT, NAC-250, CP, and CP+NAC. Rats in experimental groups were treated intraperitoneally (i.p.) with a single dose of cisplatin (10 mg/kg body weight) and i.p. with NAC (250 mg/kg body weight) for three consecutive days. Nephrotoxicity was determined by plasma BUN and creatinine levels. In tissue samples, myeloperoxidase (MPO), nuclear factor-kappa B (NF-kB), high mobility group box-1 (HMGB-1), total oxidant status (TOS), and total antioxidant status (TAS) levels were measured. Kidneys were analyzed histopathologically as well. It was revealed that cisplatin was not effective on MPO, HMGB-1 and NF-kB levels but did increase TOS levels and decrease TAS levels in tissue samples. Interestingly, NAC elevated MPO and HMGB-1 levels significantly. Nevertheless, NAC ameliorated histological and functional changes in kidney tissues. It is suggested that inflammation has a limited effect on cisplatin nephrotoxicity in this experimental design, and, as reflected by decreased BUN and creatinine levels, NAC can be used as an additional therapeutic agent in standard cisplatin treatment protocols.


Cocoa polyphenols enhance positive mood states but not cognitive performance: a randomized, placebo-controlled trial.
This study aimed to examine the acute and sub-chronic effects of cocoa polyphenols on cognition and mood. In a randomized, double-blind study, healthy middle-aged participants received a dark chocolate drink mix standardized to contain 500 mg, 250 mg or 0 mg of polyphenols (placebo) in a parallel-groups design. Participants consumed their assigned treatment once daily for 30 days. Cognition was measured with the Cognitive Drug Research system and self-rated mood with the Bond-Lader Visual Analogue Scale. Participants were tested at baseline, at 1, 2.5 and 4 h after a single acute dose and again after receiving 30 days of treatment. In total, 72 participants completed the trial. After 30 days, the high dose of treatment significantly increased self-rated calmness and contentedness relative to placebo. Mood was unchanged by treatment acutely while cognition was unaffected by treatment at all time points. This randomized controlled trial is perhaps the first to demonstrate the positive effects of cocoa polyphenols on mood in healthy participants. This provides a rationale for exploring whether cocoa polyphenols can ameliorate the symptoms associated with clinical anxiety or depression.


Comparison of bronchial challenge with ultrasonic nebulized distilled water and hypertonic saline in children with mild-to-moderate asthma.
There is still controversy about the most suitable method to measure bronchial hyperresponsiveness in children. In epidemiological surveys, nonisotonic aerosols are being used increasingly for bronchial provocation testing. Our aim was to study the acceptability, safety and correlation between two published bronchial challenge tests. Two standardized protocols--the inhalation of hypertonic saline (HS) and ultrasonically-nebulized distilled water (UNDW)--were performed in 36 children: 19 patients with the clinical diagnosis of mild-to-moderate asthma (7-12 yrs of age), and 17 control subjects (8-18 yrs of age). HS challenge involved stepwise inhalation of 4.5% saline (for 0.5, 1, 2, 4 and 8 min), whereas challenge with UNDW was performed as a single step protocol with 10 min inhalation of cold UNDW. Asthma medication was withheld prior to challenge testing. Thirty five subjects completed both challenge tests (one asthmatic patient did not return after UNDW challenge) in random order within a 7 day time interval. For HS a > or = 15% reduction in forced expiratory volume in one second (FEV1) from baseline was considered a positive response, and for UNDW a > or = 10% decrease. In 13 of the 19 asthmatic patients, but in none of the controls, a positive response was observed for UNDW. Fifteen out of 18 patients and one control subject had a positive response to HS. Twelve out of 18 asthmatic children responded to both challenges, three responded only to HS and three had no response to either challenge. There was a negative correlation between log provocative dose causing a 15% reduction in FEV1 (PD15) after HS and the maximum fall in FEV1 after UNDW (rs = -0.63; p < 0.005). The HS challenge had a lower acceptability than challenge with UNDW due to the unpleasant salty taste of HS. However, this did not inhibit the completion of the tests in any subject. The results of this study suggest a good correlation between response to hypertonic saline and ultrasonically-nebulized distilled water in children with mild-to-moderate asthma. A multiple step protocol might be safer when applied in field studies involving children.


Diagnostic and therapeutic evaluation of 111In-vinorelbine-liposomes in a human colorectal carcinoma HT-29/luc-bearing animal model.
Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and (111)In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID mice to study the treatments with 6% polyethylene glycol (PEG) of (111)In-NanoX/VNB-liposomes. In vivo tumor growth tracing and BLI showed that tumor volume could be completely inhibited by the combination therapy with (111)In-VNB-liposomes and by chemotherapy with NanoX/VNB-liposomes (i.e., without Indium-111) (P<.01). The nuclear medicine images of gamma scintigraphy and WBAR also revealed the conspicuous inhibition of tumor growth by the combination therapy with (111)In-VNB-liposomes. Animal body weights, histopathology and biochemistry/hematology analyses were used to confirm the safety and feasibility of radiopharmaceuticals. A synergistic therapeutic effect on CRC xenografted SCID mice was proven by combining an Auger electron-emitting radioisotope (Indium-111) with an anticancer drug (VNB). This study further demonstrates the beneficial potential applications of multimodality molecular imaging as part of the diagnostic and therapeutic approaches available for the evaluation of new drugs and other strategic approaches to disease treatment.


The conjugation of tyramine with sulphate by liver and intestine of different animals.
Tyramine was conjugated with sulphate by extracts of monkey intestine and livers of monkey, rat, mouse, guinea pig and man. The activity measured in monkey intestine was almost three times that of monkey liver. Labelled tyramine sulphate synthesized from [14C] tyramine, [3H] tyramine or Na235SO4, on acid hydrolysis, released its radioactive precursor. Liver extracts of monkey, rat, mouse and guinea pig synthesized respectively 145,66,21 and 6 pmol of [14C] tyramine sulphate/min per mg of protein. Except with the monkey, intestine exhibited very low activity. trans-2-Phenylcyclopropylamine, a monoamine oxidase inhibitor, was added as a routine to the enzyme preparation, as its omission resulted in the production of p-hydroxyphenylacetic acid in appreciable amounts. This oxidative deamination of tyramine, however, did not decrease the sulpho-conjugation of tyramine. The low Km (9.1 muM) of sulphotransferase for tyramine is probably responsible.


What aspects of rehabilitation provision contribute to self-reported met needs for rehabilitation one year after stroke--amount, place, operator or timing?
To a large extent, people who have suffered a stroke report unmet needs for rehabilitation. The purpose of this study was to explore aspects of rehabilitation provision that potentially contribute to self-reported met needs for rehabilitation 12 months after stroke with consideration also to severity of stroke. The participants (n = 173) received care at the stroke units at the Karolinska University Hospital, Sweden. Using a questionnaire, the dependent variable, self-reported met needs for rehabilitation, was collected at 12 months after stroke. The independent variables were four aspects of rehabilitation provision based on data retrieved from registers and structured according to four aspects: amount of rehabilitation, service level (day care rehabilitation, primary care rehabilitation and home-based rehabilitation), operator level (physiotherapist, occupational therapist, speech therapist) and time after stroke onset. Multivariate logistic regression analyses regarding the aspects of rehabilitation were performed for the participants who were divided into three groups based on stroke severity at onset. Participants with moderate/severe stroke who had seen a physiotherapist at least once during each of the 1st, 2nd and 3rd-4th quarters of the first year (OR 8.36, CI 1.40-49.88 P = 0.020) were more likely to report met rehabilitation needs. For people with moderate/severe stroke, continuity in rehabilitation (preferably physiotherapy) during the first year after stroke seems to be associated with self-reported met needs for rehabilitation.


Can't Ignore-Distraction by Task-Irrelevant Sounds in Early and Middle Childhood.
Attention control abilities are relevant for learning success. Little is known about the development of audio-visual attention in early childhood. Four groups of children between the ages of 4 and 10 years and adults performed an audio-visual distraction paradigm (N = 106). Multilevel analyses revealed increased reaction times in a visual categorization task when task-irrelevant novel sounds were presented, demonstrating involuntary distraction of attention. This distraction effect decreased with age and significantly differed between age groups. In addition, the two youngest age groups responded with a delay in trials following a distractor trial, indicating delayed reallocation of attention to the task at hand. Results indicate a significant maturation of audio-visual attention control within a few years during early childhood that continues throughout middle childhood.


Electrochemical splitting of calcium carbonate to increase solution alkalinity: implications for mitigation of carbon dioxide and ocean acidity.
Electrochemical splitting of calcium carbonate (e.g., as contained in limestone or other minerals) is explored as a means of forming dissolve hydroxides for absorbing, neutralizing, and storing carbon dioxide, and for restoring, preserving, or enhancing ocean calcification. While essentially insoluble in water, CaCO3 can be dissolved in the presence of the highly acidic anolyte of a water electrolysis cell. The resulting charged constituents, Ca2+ and C03(2-), migrate to the cathode and anode, respectively, forming Ca(OH)2 on the one hand and H2CO3 (or H2O and CO2) on the other. By maintaining a pH between 6 and 9, subsequent hydroxide reactions with CO2 primarily produce dissolved calcium bicarbonate, Ca(HCO3)2aq. Thus, for each mole of CaCO3 split there can be a net capture of up to 1 mol of CO2. Ca(HCO3)2aq is thus the carbon sequestrant that can be diluted and stored in the ocean, in natural or artificial surface water reservoirs, or underground. The theoretical work requirement for the reaction is 266 kJe per net mole CO2 consumed. Even with inefficiencies, a realized net energy expenditure lower than the preceding quantity appears possible considering energy recovery via oxidation of the H2 produced. The net process cost is estimated to be <$100/tonne CO2 mitigated. An experimental demonstration of the concept is presented, and further implementation issues are discussed.


Caries-inhibiting effect of preventive measures during orthodontic treatment with fixed appliances. A systematic review.
A systematic review was performed of published data on the caries-inhibiting effect of preventive measures during orthodontic treatment with fixed appliances. The purpose was to develop evidence-based recommendations about the most effective means of preventing white spot lesions in orthodontic patients. The 15 studies included were divided into four groups based on comparable preventive measures: fluoride, chlorhexidine, sealants and bonding materials. The caries-inhibiting effect of the preventive measures was expressed by the prevented fraction (PF). The overall PF of the fluoride-releasing bonding materials was 20% (SEM 0.09). This effect was, however, not statistically significant. It was impossible to calculate an overall PF for the other preventive measures, but the tendency of their caries-inhibiting effect has been described. The use of toothpaste and gel with a high fluoride concentration of 1,500-5,000 ppm or of complementary chlorhexidine during orthodontic treatment showed a demineralisation-inhibiting tendency. The use of a polymeric tooth coating on the tooth surface around the brackets showed almost no demineralisation-inhibiting effect. Many publications had to be excluded from this systematic review because of improper research designs. Future clinical trials are needed to give evidence- based advice on the optimal caries-prevention strategy.


Beam configurations for 3D tomographic intensity modulated radiation therapy.
We extend the theory of three-dimensional (3D) tomographic intensity modulated radiation therapy (IMRT). The geometry consists of two-dimensional modulated beams on a sphere centred in the tumour. The theory provides an efficient algorithm for computing beam modulation patterns that approximately 'reconstruct' the prescribed dose function. In this paper optimum beam numbers are estimated from dose function spherical harmonics using the 3D projection-slice theorem. An extension to three dimensions of the 'Bow Tie' criterion for beam numbers is derived. The effects of insufficient beam front sampling and beam numbers are characterized with a configuration-dependent matrix. Factors that independently increase beam numbers, such as tumour size and shape, are related to the spherical harmonic content in the dose function. Examples of tomographic IMRT reconstruction with a 3D concave tumour are given.


Embolization of a renal artery aneurysm using ethylene vinyl alcohol copolymer (Onyx).
To report the embolization of a renal artery aneurysm using Onyx, a radiopaque nonadhesive liquid embolic agent. A 28-year-old woman with hypertension and fibromuscular dysplasia presented with a 20-mm renal artery aneurysm. In order to avoid any migration of embolic material into the parent vessel, a compliant balloon was inflated to exclude the aneurysm from the blood flow while injecting the liquid embolic agent. Complete aneurysm exclusion was achieved immediately, with no angiographic or duplex evidence of distal embolization or intra-aneurysmal flow. The Doppler ultrasound at 6 months confirmed aneurysm exclusion. The ease of use and nature of this material makes Onyx an effective and safe option in the treatment of wide-necked renal aneurysms.


MXenes vs. clays: emerging and traditional 2D layered nanoarchitectonics.
Although MXene materials are considered an emerging research topic, they are receiving considerable interest because, like metals and graphene, they are good electronic conductors but with the particularity that they have a marked hydrophilic character. Having a structural organization and properties close to those of clay minerals (natural silicates typically with a lamellar morphology), they are sometimes referred to as "conducting clays" and exhibit colloidal, surface and intercalation properties also similar to those of clay minerals. The present contribution aims to inform and discuss the nature of MXenes in comparison with clay phyllosilicates, taking into account their structural analogies, outstanding surface properties and advanced applications. The current in-depth understanding of clay minerals may represent a basis for the future development of MXene-derived nanoarchitectures. Comparative examples of the preparation, and studies on the properties and applications of various nanoarchitectures based on clays and MXenes have been included in the present work.


Responses to conflicting stimuli in a simple stimulus-response pathway.
The "local bend response" of the medicinal leech (Hirudo verbana) is a stimulus-response pathway that enables the animal to bend away from a pressure stimulus applied anywhere along its body. The neuronal circuitry that supports this behavior has been well described, and its responses to individual stimuli are understood in quantitative detail. We probed the local bend system with pairs of electrical stimuli to sensory neurons that could not logically be interpreted as a single touch to the body wall and used multiple suction electrodes to record simultaneously the responses in large numbers of motor neurons. In all cases, responses lasted much longer than the stimuli that triggered them, implying the presence of some form of positive feedback loop to sustain the response. When stimuli were delivered simultaneously, the resulting motor neuron output could be described as an evenly weighted linear combination of the responses to the constituent stimuli. However, when stimuli were delivered sequentially, the second stimulus had greater impact on the motor neuron output, implying that the positive feedback in the system is not strong enough to render it immune to further input.


Remote Sensing-Based Quantification of the Impact of Flash Flooding on the Rice Production: A Case Study over Northeastern Bangladesh.
The northeastern region of Bangladesh often experiences flash flooding during the pre-harvesting period of the boro rice crop, which is the major cereal crop in the country. In this study, our objective was to delineate the impact of the 2017 flash flood (that initiated on 27 March 2017) on boro rice using multi-temporal Landsat-8 OLI and MODIS data. Initially, we opted to use Landsat-8 OLI data for mapping the damages; however, during and after the flooding event the acquisition of cloud free images were challenging. Thus, we used this data to map the cultivated boro rice acreage considering the planting to mature stages of the crop. Also, in order to map the extent of the damaged boro area, we utilized MODIS data as their 16-day composites provided cloud free information. Our results indicated that both the cultivated and damaged boro area estimates based on satellite data had strong relationships while compared to the ground-based estimates (i.e., r² values approximately 0.92 for both cases, and RMSE of 18,374 and 9380 ha for cultivated and damaged areas, respectively). Finally, we believe that our study would be critical for planning and ensuring food security for the country.


Overexpression of glucose-6-phosphate dehydrogenase extends the life span of Drosophila melanogaster.
The redox state of tissues tends to become progressively more prooxidizing during the aging process. The hypothesis tested in this study was that enhancement of reductive capacity by overexpression of glucose-6-phosphate dehydrogenase (G6PD), a key enzyme for NADPH biosynthesis, could protect against oxidative stress and extend the life span of transgenic Drosophila melanogaster. Overexpression of G6PD was achieved by combining a UAS-G6PD responder transgene at one of four independent loci with either a broad expression (armadillo-GAL4, Tubulin-GAL4, C23-GAL4, and da-GAL4) or a neuronal driver (D42-GAL4 and Appl-GAL4). The mean life spans of G6PD overexpressor flies were extended, in comparison with driver and responder controls, as follows: armadillo-GAL4 (up to 38%), Tubulin-GAL4 (up to 29%), C23-GAL4 (up to 27%), da-GAL4 (up to 24%), D42-GAL4 (up to 18%), and Appl-GAL4 (up to 16%). The G6PD enzymatic activity was increased, as were the levels of NADPH, NADH, and the GSH/GSSG ratio. Resistance to experimental oxidative stress was enhanced. Furthermore, metabolic rates and fertility were essentially the same in G6PD overexpressors and control flies. Collectively, the results demonstrate that enhancement of the NADPH biosynthetic capability can extend the life span of a relatively long-lived strain of flies, which supports the oxidative stress hypothesis of aging.


Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial.
Standard treatment of atopic dermatitis (AD) is based on topical glucocorticosteroids or calcineurin inhibitors to treat flares combined with moisturizer treatment to alleviate dry skin symptoms. Patients with AD have an abnormal skin barrier function, and strategies for reducing the risks for eczema would be to repair the barrier or prevent barrier dysfunction. The objective of this study was to explore the time to relapse of eczema during a 26-week maintenance treatment with a urea containing moisturizer compared to no treatment (neither medical nor non-medicated preparations) after successful clearing of atopic lesions. The moisturizer has previously been shown to improve skin barrier function. Patients applied betamethasone valerate (0.1%) on eczematous lesions during a 3-week period. Those with cleared eczema entered a 26-week maintenance phase, applying the moisturizer or left the previously affected area untreated. Upon eczema relapse, patients were instructed to contact the clinic and to have the relapse confirmed by the investigator. Fifty-five patients entered the study and 44 patients were included in the maintenance phase (22 using moisturizer twice daily and 22 using no treatment). Median time to relapse for patients treated with moisturizer was > 180 days (duration of the study) compared with 30 days for the no-treatment group. Sixty-eight per cent of the patients treated with the moisturizer and 32% of the untreated patients remained free from eczema during the observation period. Maintenance treatment with a barrier-improving urea moisturizer on previous eczematous areas reduced the risk of relapse to approximately one third of that of no treatment.


[The dentist as communicator: the law].
Communication with the patient in dentistry: what the law requires. What does the law require with respect to the communication of dentists with their patients? The answer is first of all to be found in the Act on the medical contract, which is incorporated in the Dutch Civil Code, and applies also to dentistry. In this article, that act is discussed with a view to dental practice. Particular attention is given to the content and extent of the duty to provide information, and to the liability of the dentist who acts negligently on this point.


Octopamine and cooperation: octopamine regulates the disappearance of cooperative behaviours between genetically unrelated founding queens in the ant.
We investigated whether octopamine (OA) is associated with the disappearance of cooperation in Polyrhachis moesta ant queens. Queens of P. moesta facultatively found the colony with genetically unrelated queens. The founding queens perform frequent food exchange with these non-related queens and partake in cooperative brood rearing, whereas single colony queens exclude non-related queens via aggressive behaviour. Thus, aggression is a factor that reduces cooperation. Given that aggression is generally associated with brain OA in insects, we hypothesized that OA controls the behavioural change in cooperation in the ant queen, via an increase in aggression. To test this hypothesis, we compared the amounts of OA and related substances in the brain between founding and colony queens, and observed the interaction of founding queens following oral OA administration. The brain OA levels in colony queens were significantly higher than those in founding queens. Oral administration of OA to founding queens caused significantly less trophallaxis and allogrooming behaviour than in the control founding queens, but with no significant increase in aggression. These results suggest that OA promotes the disappearance of cooperation in founding queens of P. moesta. This is the first study to reveal the neuroendocrine mechanism of cooperation in ant queens.


To NET or not to NET:current opinions and state of the science regarding the formation of neutrophil extracellular traps.
Since the discovery and definition of neutrophil extracellular traps (NETs) 14 years ago, numerous characteristics and physiological functions of NETs have been uncovered. Nowadays, the field continues to expand and novel mechanisms that orchestrate formation of NETs, their previously unknown properties, and novel implications in disease continue to emerge. The abundance of available data has also led to some confusion in the NET research community due to contradictory results and divergent scientific concepts, such as pro- and anti-inflammatory roles in pathologic conditions, demarcation from other forms of cell death, or the origin of the DNA that forms the NET scaffold. Here, we present prevailing concepts and state of the science in NET-related research and elaborate on open questions and areas of dispute.


Respiratory symptoms and lung function in alumina refinery employees.
Employees in alumina refineries are known to be exposed to a number of potential respiratory irritants, particularly caustic mist and bauxite and alumina dusts. To examine the prevalence of work related respiratory symptoms and lung function in alumina refinery employees and relate these to their jobs. 2964 current employees of three alumina refineries in Western Australia were invited to participate in a cross sectional study, and 89% responded. Subjects were given a questionnaire on respiratory symptoms, smoking, and occupations with additional questions on temporal relations between respiratory symptoms and work. Forced expiratory volume in 1 second (FEV(1)) and forced vital capacity (FVC) were measured with a rolling seal spirometer. Atopy was assessed with prick skin tests for common allergens. Associations between work and symptoms were assessed with Cox's regression to estimate prevalence ratios, and between work and lung function with linear regression. Work related wheeze, chest tightness, shortness of breath, and rhinitis were reported by 5.0%, 3.5%, 2.5%, and 9.5% of participants respectively. After adjustment for age, smoking, and atopy, most groups of production employees reported a greater prevalence of work related symptoms than did office employees. After adjustment for age, smoking, height, and atopy, subjects reporting work related wheeze, chest tightness, and shortness of breath had significantly lower mean levels of FEV(1) (186, 162, and 272 ml respectively) than subjects without these symptoms. Prevalence of most work related symptoms was higher at refinery 2 than at the other two refineries, but subjects at this refinery had an adjusted mean FEV(1) >60 ml higher than the others. Significant differences in FVC and FEV(1)/FVC ratio, but not FEV(1), were found between different process groups. There were significant differences in work related symptoms and lung function between process groups and refineries, but these were mostly not consistent. Undefined selection factors and underlying population differences may account for some of these findings but workplace exposures may also contribute. The differences identified between groups were unlikely to be clinically of note.


[Fractures of the dens in patients older than 65 years: direct osteosynthesis of the dens versus C1-C2 posterior fixation].
Surgical treatment is preferred in our department in all patients with type II and type III dens fractures, regardless of their age, with the exception of non-displaced or completely reduced fractures in young patients. The aim of this study was to evaluate patients over 65 years of age treated by direct osteosynthesis of the dens or posterior atlanto-axial fixation and spondylodesis. In the years 2001 to 2005, 28 patients aged 65 years and older were surgically treated for dens fracture. This included 13 men and 15 women between 65 and 90 years of age, with an average of 77.4 years. According to the treatment, i.e., direct dens osteosynthesis (1) or C1-C2 posterior fixation (2), two groups were evaluated, and two categories were considered by age, i.e., 65 to 74 years (8 patients) and 75 years and older (20 patients). In 23 patients, an isolated fracture of the dens was present and, in five patients, injury was part of a complex C1-C2 fracture. A Frankel grade D neurological deficit was found in three patients. In all patients, surgical treatment by direct osteosynthesis of the dens from the anterior approach, using two cannulated screws, was preferred as the method of choice. However, in the case of distinct osteoporosis, fragmented fracture of the dens base or tear of the ligamentum transversum atlantis, we used the Harms method of posterior fusion with polyaxial screw fixation as the primary treatment, or the Magerl transarticular fixation completed with the Gallie technique from the dorsal approach. The patients were followed up at 3, 6 and 12 weeks, at 6 and 12 months, and then at one-year intervals. X-ray and clinical examinations were made at the regular follow-ups and functional radiographs were taken at 12 months following the surgery. The whole group was evaluated in the range of 18 to 84 months (average, 37.3 months). Neurological deficit was assessed on the basis of the Frankel classification. The results were analysed using the Chi-square test. Of 20 patients still living at the time of this evaluation, 11 underwent direct osteosynthesis and nine were treated by posterior instrumented spondylodesis. In group 1, pseudoarthrosis of the dens or fibrous callus developed in one patient (9.1 %) and a line of fracture was evident in one patient of group 2 (11.1 %), which was not significant (p<0.05). However, a statistically significant difference in mortality was found when the two age categories were compared (p>0.05), with 0 % in the younger and 40 % in the older category. The overall mortality within 6 weeks of injury was 28.6 %. Mortality in group 1 and group 2 was 21.4 % and 35.7 %, respectively; this difference was not statistically significant (p<0.05). We use conservative treatment only in the patients who are able to stand up and move soon after injury. If this is not feasible, we prefer surgical treatment with the same aim achieved as soon as possible without rigid external fixation. In this study, surgery was associated with an acceptable number of minor complications due to poor bone quality or health state of the patient. The higher mortality in the higher age category was obviously related to generally poorer health of these patients. Surgical treatment can significantly improve the quality of life in elderly patients who have suffered a fracture of the dens. The surgical technique should be chosen to take bone quality, degenerative changes of the spine and overall health of the patient into consideration. Mortality after surgery is not related to the technique selected but to patient's age. Elderly patients with neurological deficit usually die due to co-morbidity, regardless of the therapy used.


Rapid and Efficient Identification of Caenorhabditis elegans Legacy Mutations Using Hawaiian SNP-Based Mapping and Whole-Genome Sequencing.
The production of viable embryos requires the coordination of many cellular processes, including protein synthesis, cytoskeletal reorganization, establishment of polarity, cell migration, cell division, and in Caenorhabditis elegans, eggshell formation. Defects in any of these processes can lead to embryonic lethality. We examined six temperature-sensitive mutants as well as one nonconditional mutant that were previously identified in genetic screens as either embryonic lethal (maternal-effect or zygotic lethal) or eggshell defective. The responsible molecular lesion for each had never been determined. After confirmation of temperature sensitivity and lethality, we performed whole-genome sequencing using a single-nucleotide polymorphism mapping strategy to pinpoint the molecular lesions. Gene candidates were confirmed by RNA interference phenocopy and/or complementation tests and one mutant was further validated by CRISPR (Clustered Regularly Interspaced Short Palidromic Repeats)/Cas9 gene editing. This approach identified new alleles of several genes that had only been previously studied by RNA interference depletion. Our identification of temperature-sensitive alleles for all of these essential genes provides an extremely useful tool for further investigation for the C. elegans community, such as the ability to address mutant phenotypes at various developmental stages and the ability to carry out suppressor/enhancer screens to identify other genes that function in a specific cellular process.


Comparison of flow diversion with clipping and coiling for the treatment of paraclinoid aneurysms in 115 patients.
OBJECTIVEParaclinoid aneurysms represent approximately 5% of intracranial aneurysms (Drake et al. [1968]). Visual impairment, which occurs in 16%-40% of patients, is among the most common presentations of these aneurysms (Day [1990], Lai and Morgan [2013], Sahlein et al. [2015], and Silva et al. [2017]). Flow-diverting stents, such as the Pipeline Embolization Device (PED), are increasingly used to treat these aneurysms, in part because of their theoretical reduction of mass effect (Fiorella et al. [2009]). Limited data on paraclinoid aneurysms treated with a PED exist, and few studies have compared outcomes of patients after PED placement with those of patients after clipping or coiling.METHODSThe authors performed a retrospective analysis of 115 patients with an aneurysm of the cavernous to ophthalmic segments of the internal carotid artery treated with clipping, coiling, or PED deployment between January 2011 and March 2017. Postoperative complications were defined as new neurological deficit, aneurysm rupture, recanalization, or other any operative complication that required reintervention.RESULTSA total of 125 paraclinoid aneurysms in 115 patients were treated, including 70 with PED placement, 23 with coiling, and 32 with clipping. Eighteen (14%) aneurysms were ruptured. The mean aneurysm size was 8.2 mm, and the mean follow-up duration was 18.4 months. Most aneurysms were discovered incidentally, but visual impairment, which occurred in 21 (18%) patients, was the most common presenting symptom. Among these patients, 15 (71%) experienced improvement in their visual symptoms after treatment, including 14 (93%) of these 15 patients who were treated with PED deployment. Complete angiographic occlusion was achieved in 89% of the patients. Complications were seen in 17 (15%) patients, including 10 (16%) after PED placement, 2 (9%) after coiling, and 5 (17%) after clipping. Patients with incomplete aneurysm occlusion had a higher rate of procedural complications than those with complete occlusion (p = 0.02). The rate of postoperative visual improvement was significantly higher among patients treated with PED deployment than in those treated with coiling (p = 0.01). The significant predictors of procedural complications were incomplete occlusion (p = 0.03), hypertension, (p = 0.04), and diabetes (p = 0.03).CONCLUSIONSIn a large series in which patient outcomes after treatment of paraclinoid aneurysms were compared, the authors found a high rate of aneurysm occlusion and a comparable rate of procedural complications among patients treated with PED placement compared with the rates among those who underwent clipping or coiling. For patients who presented with visual symptoms, those treated with PED placement had the highest rate of visual improvement. The results of this study suggest that the PED is an effective and safe modality for treating paraclinoid aneurysms, especially for patients who present with visual symptoms.


High, Anisotropic, and Substrate-Independent Mobility in Polymer Field-Effect Transistors Based on Preassembled Semiconducting Nanofibrils.
Achieving nanoscale control over the crystalline structure and morphology of electroactive polymer films and the possibility to transfer them onto any solid substrate are important tasks for the fabrication of high-performance organic/polymeric field-effect transistors (FETs). In this work, we demonstrate that ultrathin active layers preassembled at the water/air interface can possess high, anisotropic, and substrate-independent mobility in polymer FETs. By exploiting a modified approach to the Langmuir-Schaeffer technique, we self-assemble conjugated polymers in fibrillar structures possessing controlled thickness, nanoscale structure, and morphology; these highly ordered nanofibrils can be transferred unaltered onto any arbitrary substrate. We show that FETs based on these films possess high and anisotropic hole mobility approaching 1 cm2 V-1 s-1 along the nanofibrils, being over 1 order of magnitude beyond the state-of-the-art for Langmuir-Schaefer polymer FETs. Significantly, we demonstrate that the FET performances are independent of the chemical nature and dielectric permittivity of the substrate, overcoming a critical limit in the field of polymer FETs. Our method allows the fabrication of ultrathin films for low-cost, high-performance, transparent, and flexible devices supported on any dielectric substrate.


Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a Duchenne-like muscular dystrophy phenotype.
It recently was reported that Duchenne muscular dystrophy (DMD) patients and mdx mice have elevated levels of caveolin-3 expression in their skeletal muscle. However, it remains unknown whether increased caveolin-3 levels in DMD patients contribute to the pathogenesis of DMD. Here, using a genetic approach, we test this hypothesis directly by overexpressing wild-type caveolin-3 as a transgene in mice. Analysis of skeletal muscle tissue from caveolin-3- overexpressing transgenic mice reveals: (i) a dramatic increase in the number of sarcolemmal muscle cell caveolae; (ii) a preponderance of hypertrophic, necrotic, and immature/regenerating skeletal muscle fibers with characteristic central nuclei; and (iii) down-regulation of dystrophin and beta-dystroglycan protein expression. In addition, these mice show elevated serum creatine kinase levels, consistent with the myo-necrosis observed morphologically. The Duchenne-like phenotype of caveolin-3 transgenic mice will provide an important mouse model for understanding the pathogenesis of DMD in humans.


The effect of a short burst of exercise during the night on subsequent sleep.
When on-call workers wake during the night to perform work duties, they may experience reduced alertness and impaired performance as a result of sleep inertia. After performing their duties, on-call workers may have the opportunity to return to sleep. Thus, it is important that sleep inertia countermeasures do not affect subsequent sleep. Exercise may be a suitable countermeasure; however, the impact on subsequent sleep is untested. Healthy participants (n = 15) completed three conditions in a counterbalanced order: sedentary, low-intensity exercise or high-intensity exercise, performed for 2 min upon awakening. Sleep was recorded 2 hr later using polysomnography, the Karolinska Sleepiness Scale was administered to measure subjective sleepiness, and core body temperature was measured continuously. Results indicate there was no effect of condition on most sleep variables; however, three variables had small differences, with longer total sleep time (p = .006), higher sleep efficiency (p = .006) and shorter N3 latency (p < .001) in the low-intensity exercise condition. There was no difference in subjective sleepiness (p = .124) or core body temperature (p = .216) 90 min after the exercise intervention. These results indicate that using a short burst of exercise to counteract sleep inertia when woken during the night may be a suitable countermeasure for on-call workers who not only need to be alert upon waking but also need quality sleep when returning to bed. Future research could include participants of other ages and health statuses to investigate whether the results are generalizable.


Interferons: Success in anti-viral immunotherapy.
The interferons (IFNs) are glycoproteins with strong antiviral activities that represent one of the first lines of host defense against invading pathogens. These proteins are classified into three groups, Type I, II and III IFNs, based on the structure of their receptors on the cell surface. Due to their ability to modulate immune responses, they have become attractive therapeutic options to control chronic virus infections. In combination with other drugs, Type I IFNs are considered as "standard of care" in suppressing Hepatitis C (HCV) and Hepatitis B (HBV) infections, while Type III IFN has generated encouraging results as a treatment for HCV infection in phase III clinical trials. However, though effective, using IFNs as a treatment is not without the need for caution. IFNs are such powerful cytokines that affect a wide array of cell types; as a result, patients usually experience unpleasant symptoms, with a percentage of patients suffering system wide effects. Thus, constant monitoring is required for patients treated with IFN in order to reach the treatment goals of suppressing virus infection and maintaining quality of life.


Iraq and Afghanistan Veterans report symptoms consistent with chronic multisymptom illness one year after deployment.
Many Veterans returning from service in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) experience chronic pain. What is not known is whether for some OIF/OEF Veterans this pain is part of a larger condition of diffuse multisystem symptoms consistent with chronic multisymptom illness (CMI). We use data from a prospective longitudinal study of OIF/OEF Veterans to determine the frequency of CMI. We found that 1 yr after deployment, 49.5% of OIF/OEF Veterans met criteria for mild to moderate CMI and 10.8% met criteria for severe CMI. Over 90% of Veterans with chronic pain met criteria for CMI. CMI was not completely accounted for either by posttraumatic stress disorder or by predeployment levels of physical symptoms. Veterans with symptoms consistent with CMI reported significantly worse physical health function than Veterans who did not report symptoms consistent with CMI. This study suggests that the presence of CMI should be considered in the evaluation of OIF/OEF Veterans. Further, it suggests the pain management for these Veterans may need to be tailored to take CMI into consideration.


Risks and prevention of contamination of dairy products.
Consumers and regulatory officials are becoming increasingly aware of the human health risk of the presence of micro-organisms or chemicals in the agricultural environment. Providing 'on-farm food safety' programmes which address the daily management of the production unit with regard to animal health and well-being, public health and environmental health must be a top priority for agriculturalists and veterinarians. Developing critical control point management (CCPM) procedures for animal and human health concerns is a viable approach to aid in alleviating public concerns about dairy products and the food supply in general. Such CCPM programmes may be created for individual production units based upon risk analysis, total quality management and hazard analysis and critical control point principles. Implementation of these programmes will be essential both in addressing food safety concerns for the resident population of a nation and in developing or maintaining international markets for the export of animal products.


Transplantation of Nonexpanded Adipose Stromal Vascular Fraction and Platelet-Rich Plasma for Articular Cartilage Injury Treatment in Mice Model.
Stromal vascular fraction (SVF) combined with platelet-rich plasma (PRP) is commonly used in preclinical and clinical osteoarthritis as well as articular cartilage injury treatment. However, this therapy has not carefully evaluated the safety and the efficacy. This research aims to assess the safety and the efficacy of SVF combined with PRP transplantation. Ten samples of SVFs and PRPs from donors were used in this research. About safety, we evaluate the expression of some genes related to tumor formation such as Oct-4, Nanog, SSEA3, and SSEA4 by RT-PCR, flow cytometry, and tumor formation when injected in NOD/SCID mice. About efficacy, SVF was injected with PRP into murine joint that caused joint failure. The results showed that SVFs are negative with Oct-4, Nanog, SSEA-3, and SSEA-4, as well as they cannot cause tumors in mice. SVFs combined with PRP can improve the joint regeneration in mice. These results proved that SVFs combined with PRP transplantation is a promising therapy for articular cartilage injury treatment.


Imaging Atherosclerosis.
Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.


Structural studies on the core oligosaccharide of Phenylobacterium immobile strain K2 lipopolysaccharide. Chemical synthesis of 3-hydroxy-5c-dodecenoic acid.
The fatty acid composition of the bound lipids of 17 strains from Phenylobacterium immobile was investigated. Ester-linked 3-hydroxy-5c-dodecenoic acid was found to be the major substituent in the lipopolysaccharide. Therefore the occurrence of this unusual acid can be taken as a useful marker for the determination of P. immobile by simple fatty acid analysis. Lipid A backbone was found to consist of 2,3-diamino-2,3-dideoxy-D-glucose, which up to this time has only been detected in group I of purple nonsulfur bacteria and their non-phototrophic relatives. A convenient chemical synthesis for 3-hydroxy-5c-dodecenoic acid is described. The polysaccharide region of P. immobile strain K2 lipopolysaccharide was investigated. The methods used included gel filtration procedures, methylation analysis, periodate oxidation, Smith degradation, oxidation with chromium trioxide and enzymic degradations of the isolated oligosaccharide. We found that strain K2 has a rough-type lipopolysaccharide, devoid of an O-specific side chain. For the core oligosaccharide the following structure is proposed: (Formula: see text) beta-D-Glcp(1-3)-L-alpha-D-Hep rho(1-3)-L-alpha-D-Hep rho(1-3-L-alpha-D-Hep rho(1-4/5)dOclA.


Possible inflammatory pain biomarkers in postamputation pain.
Although chronic pain after amputation is frequent, the underlying mechanisms are still not well understood. It is widely accepted that the pathogenesis of postamputation pain is multifactorial, with both peripheral and central mechanisms playing an essential role. However, recent studies suggest that the immune system plays an important role in different neuropathic pain conditions, including postamputation pain. Eleven amputees were included in this clinical study. Information on the type and intensity of spontaneous postamputation pain was obtained and evoked pain responses for brush, cold, and warm allodynia and pinprick hyperalgesia were determined. In addition, skin biopsies were taken from the amputated site and a contralateral control site and analysed for possible markers of pain: IbA1 (macrophages), calcitonin gene-related peptide (CGRP), and substance P (SP). Irrespectively of the type and intensity of postamputation pain, no differences were found in IbA1, CGRP, and SP levels between the amputated site and the control site. Although no differences between the sites were seen in this study, this new method seems promising for our understanding of skin changes in amputees. In future studies, staining for other cytokines and inflammatory mediators in skin biopsies could provide new insight into the mechanisms of postamputation pain.


Survey of Listeria monocytogenes in ready-to-eat foods.
The purpose of this study was to develop data on the risk of listeriosis to support a science-based strategy for addressing Listeria monocytogenes in foods in the United States. Eight categories of ready-to-eat foods were collected over 14 to 23 months from retail markets at Maryland and northern California FoodNet sites. The product categories included luncheon meats, deli salads, fresh soft "Hispanic-style" cheeses, bagged salads, blue-veined and soft mold-ripened cheeses, smoked seafood, and seafood salads. The presence and levels of L. monocytogenes in the samples were determined by rapid DNA-based assays in combination with culture methods. Of 31,705 samples tested, 577 were positive. The overall prevalence was 1.82%. with prevalences ranging from 0.17 to 4.7% among the product categories. L. monocytogenes levels in the positive samples varied from <0.3 MPN (most probable number) per g to 1.5 x 10(5) CFU/g, with 402 samples having levels of <0.3 MPN/g, 21 samples having levels of >10(2) CFU/g, and the rest of the samples having intermediate levels. No obvious trends with respect to seasonality were observed. Significant differences (P < 0.05) between the sampling sites were found, with higher prevalences for threes categories in northern California and for two categories in Maryland. Significantly (P < 0.001) higher prevalences were found for in-store-packaged samples than for manufacturer-packaged samples of luncheon meats, deli salads, and seafood salads, while 16 of the 21 samples with higher counts were manufacturer packaged. The data collected in this study help to fill gaps in the knowledge about the occurrence of L. monocytogenes in foods, and this new information should be useful in the assessment of the risk posed by L. monocytogenes to consumers.


Centrohexaindane: six benzene rings mutually fixed in three dimensions - solid-state structure and six-fold nitration.
The solid-state molecular structure of centrohexaindane (), a unique hydrocarbon comprising six benzene rings clamped to each other in three dimensions around a neopentane core, and the molecular packing in crystals of ·CHCl3 are reported. The molecular Td-symmetry and the Cartesian orientation of the six indane wings of in the solid state have been confirmed. The course and limitation of electrophilic aromatic substitution of are demonstrated for the case of nitration. Based on nitration experiments of a lower congener of , tribenzotriquinacene , the six-fold nitrofunctionalisation of has been achieved in excellent yield, giving four constitutional isomers, two nonsymmetrical ( and ) and two C3-symmetrical ones ( and ), all of which contain one single nitro group in each of the six benzene rings. The relative yields of the four isomers (∼3 : 1 : 1 : 3) point to a random electrophilic attack of the electrophiles at the twelve formally equivalent outer positions of the aromatic periphery of , suggesting electronic independence of its six aromatic π-electron systems. In turn, the pronounced conformational rigidity of the centrohexacyclic framework of enables the unequivocal structural identification of the isomeric hexanitrocentrohexaindanes by (1)H NMR spectroscopy.


Varus derotation osteotomy for the treatment of hip subluxation and dislocation in GMFCS level III to V patients with unilateral hip involvement. Follow-up at skeletal maturity.
Hip displacement is common in children with cerebral palsy (CP). The risk of hip displacement is related to gross motor function level as graded with the Gross Motor Function Classification System (GMFCS). Most clinicians agree that surgical treatment is indicated for progressive hip subluxation in patients with CP. However, it is unclear whether unilateral bony surgery and musculotenduous release is effective in cases in which the contralateral hip is well seated. The purpose of this study is to describe the fate of the original and the contralateral hip of severely involved patients with CP, GMFCS III to V, with unilateral hip subluxation or dislocation treated by unilateral femoral osteotomy with or without pelvic osteotomy along with unilateral or bilateral soft tissue release when the contralateral hip was well seated followed to skeletal maturity. A continuous group of GMFCS III to V CP patients with unilateral hip subluxation or dislocation who underwent soft tissue release (adductor and iliopsoas) and unilateral intertrochanteric varus, rotation and shortening osteotomy with or without pelvic osteotomy are included. All patients were clinically and radiologically followed from the time of presentation until skeletal maturity. Twenty-seven children and adolescents with GMFCS level III, IV, and V met the inclusion criteria. Two patients (7.4%) were GMFCS III, 5 (18.5%) were GMFCS IV and 20 (74.1%) GMFCS V. The male:female ratio was almost 1 (13 boys and 14 girls). At the time of chart and radiograph review, the average age of this patient group was 20.4 years (range: 14 to 25 y). Twelve patients (44%) required subsequent bony surgical management of the contralateral hip for subluxation or dislocation after the index procedure. Initially, in all cases there was pelvic obliquity with the operative side higher, which reversed in cases in which the contralateral hip deteriorated, and did not reverse when the contralateral hip remained stable. Nine of them were treated with femoral varus osteotomy alone and 3 underwent a combination of femoral and pelvic osteotomy. Three of these 12 (25%) patients had revision of the first hip and bony correction of the contralateral hip. Age at surgery did not seem to have a significant effect on maintaining reduction or in preventing the contralateral hip to deteriorate. The rates of recurrence of the original hip and contralateral hip subluxation and dislocation after unilateral bony surgery in GMFCS III to V spastic patients are higher than those of other earlier series. However, in this series patients were followed until skeletal maturity. It is prudent to warn families of the possibility of long-term subluxation or dislocation of the original hip and development of the hip dysplasia requiring surgery on the contralateral side. Consideration should be given to adductor and iliopsoas release and bony surgery on the contralateral side in a GMFCS level III to V child undergoing surgery for hip displacement, even when the hip seem radiologically normal. If unilateral bony surgery is carried out, close radiological follow-up of both hips is recommended. It also seems that unilateral hip surgery alters the forces maintaining pelvic alignment, which can lead to destabilization of the contralateral hip. Case series. Level IV.


Preoperative serum C- reactive protein: a prognostic marker in patients with upper urinary tract urothelial carcinoma.
To analyse the prognostic significance of preoperative C-reactive protein (CRP) serum level in patients with upper urinary tract urothelial carcinoma (UUT-UC). We evaluated 158 UUT-UC patients who had undergone surgery in the University Hospital of Hannover (MHH). 143 (89.4%) suffered from cancer in the renal pelvis, 13 (8.1%) patients presented with tumour located in the ureter. A preoperative CRP value was available for 115 patients. The mean (median) follow-up for these patients was 28.3 (15.1) months. The median (mean) CRP value of all evaluable patients was 10.0 (40.7) mg/l. The CRP-level, stratified into two subgroups (CRP ≤5 vs. >5 mg/l), correlated significantly with muscle invasive tumour stage (36.4 vs. 78.9%; p<0.001), the risk of presenting nodal disease (4.5 vs. 26.8%; p=0.002) and distant metastasis (2.3 vs. 16.9%; p<0.016). The Kaplan-Meier 5-year cancer specific survival (CSS) rates were 54.2 and 26.4% for patients with preoperative CRP levels ≤ and >5 mg/l, respectively (p<0.006). Next to age and the presence of metastasis, multivariate analysis also identified CRP as a continuous variable as an independent prognosticator for CSS. A high preoperative serum CRP level is associated with locally advanced and metastatic disease in patients with UUT-UC. Its routine use could allow better risk stratification and risk-adjusted follow-up of UUT-UC patients.


Pseudohyponatremia in acute hyperlipemic pancreatitis. A potential pitfall in therapy.
Six patients had apparent hyponatremia associated with hyperlipidemia and acute pancreatitis. To our knowledge, only one such patient with acute pancreatitis has previously been described, although the association of hyperlipidemia with "pseudohyponatremia" had been well documented. One of the above patients, whose condition was hemodynamically unstable on admission, developed dangerous symptoms of hyperosmolarity and cerebral dysfunction following aggressive resuscitation with hypertonic saline solution. The pseudohyponatremia results from displacement of water in the serum by the lipids, with sodium existing only in the aqueous phase. This volume displacement results in errors of sodium measurement when the latter is determined by flame photometry or indirect potentiometry, but not when determined by ultracentrifugation and direct potentiometry.


Use of wireless phones and the risk of salivary gland tumours: a case-control study.
The last decades of increasing use of wireless phones, including mobile as well as cordless desktop phones, have led to concerns about the potential carcinogenic effects of radiofrequency electromagnetic fields. Among the most exposed areas of the body when the phone is used for talking are the salivary glands, mainly the parotid gland, located in front of the ear. The objective of this case-control study was to assess whether the use of wireless phones is associated with an increased risk of tumour at this site. Sixty-nine patients with salivary gland tumours (63 with a parotid gland tumour) and 262 randomly recruited controls were included. Unconditional logistic regression - adjusted for age at diagnosis, sex, year of diagnosis and socioeconomic index - was used to produce odds ratios and 95% confidence intervals. The use of wireless phones was not associated with an overall increased risk of salivary gland tumours, odds ratio 0.8, 95% confidence interval 0.4-1.5. Neither was there an increased risk for the different phone types when calculated separately nor was there an increased risk for different latencies or when cumulative use was divided into three groups (1-1000, 1001-2000 and >2000 h). The overall results were similar for the risk of parotid gland tumours. In conclusion, our data add to the evidence against there being an increased risk for parotid gland tumours associated with light-to-moderate use of wireless phones and for less than 10 years of use but offers little information on risk related to more prolonged and/or heavy use.


Distribution of the ACME-arcA gene among methicillin-resistant Staphylococcus aureus from England and Wales.
The ST8-SCCmecIVa (USA300) methicillin-resistant Staphylococcus aureus (MRSA) clone can harbour the arginine catabolic mobile element (ACME). The arc gene cluster within the ACME may function as a virulence or strain survival factor. We determined the distribution of the ACME-associated arcA gene among genetically diverse MRSA from around England and Wales. MRSA isolates (n = 203) of diverse genetic types, referred to the England and Wales Staphylococcus reference laboratory, were tested for the presence of the ACME-arcA gene. ACME-arcA-positive isolates were characterized by toxin gene profiling, PFGE and spa sequence typing. MICs of a range of antimicrobials were also determined. The ACME-arcA gene was detected in 17 isolates. Twelve were related to known ST8-MRSA-SCCmecIVa isolates of the USA300 lineage by pulsotype and were resistant to oxacillin, with variable ciprofloxacin and erythromycin resistance. Outside the USA300 lineage, four of the remaining five ACME-arcA isolates were closely related ST97-MRSA-SCCmecV, Panton-Valentine leucocidin (PVL)-negative, resistant to oxacillin and variously resistant to erythromycin, ciprofloxacin, clindamycin, gentamicin, tetracycline and fusidic acid. The remaining isolate was ST1, PVL-positive and resistant to fusidic acid as well as oxacillin. Thirteen out of the 17 isolates were associated with skin and soft tissue infections. The detection of ACME-arcA in diverse MRSA types highlights the mobility of the elements encoding ACME-arcA genes. The diversity of strain types and resistance profiles among ACME-arcA-encoding MRSA is a cause for public-health concern and demands continued surveillance and close monitoring.


The modified vaccination technique designed to prevent and cure acute and chronic disorders.
In spite of enormous efforts there have been no solutions to date for preventing/terminating certain acute and chronic disorders of humans by vaccination or drugs. Yet it is well understood that if the target antigen (ag) could be presented appropriately to the cells of the immune system then solutions could be found. Recently, the Barabas research group has introduced and described the third vaccination method - called modified vaccination technique (MVT) - which has the ability to provide a corrective immune response in experimental animals with an autoimmune kidney disease. Injections of immune complexes - made up of the target ag and specific non-pathogenic IgM antibodies directed against the target ag - achieved downregulation of pathogenic immune responses and tolerance to self was regained. Utilizing the immune system's natural abilities to respond to corrective information, the MVT technique was able to prevent an autoimmune kidney disease from occurring (prophylactic effect) in experimental animals, and when present, terminating it (therapeutic effect) specifically and without measurable side effects.It is predicted that the application of the MVT will have the potential in the future to revolutionize the preventative and therapeutic options for dealing with chronic disorders in humans (such as autoimmune disease, cancer and acute chronic infections) and achieve cures.


Classification images for localization performance in ramp-spectrum noise.
This study investigates forced localization of targets in simulated images with statistical properties similar to trans-axial sections of x-ray computed tomography (CT) volumes. A total of 24 imaging conditions are considered, comprising two target sizes, three levels of background variability, and four levels of frequency apodization. The goal of the study is to better understand how human observers perform forced-localization tasks in images with CT-like statistical properties. The transfer properties of CT systems are modeled by a shift-invariant transfer function in addition to apodization filters that modulate high spatial frequencies. The images contain noise that is the combination of a ramp-spectrum component, simulating the effect of acquisition noise in CT, and a power-law component, simulating the effect of normal anatomy in the background, which are modulated by the apodization filter as well. Observer performance is characterized using two psychophysical techniques: efficiency analysis and classification image analysis. Observer efficiency quantifies how much diagnostic information is being used by observers to perform a task, and classification images show how that information is being accessed in the form of a perceptual filter. Psychophysical studies from five subjects form the basis of the results. Observer efficiency ranges from 29% to 77% across the different conditions. The lowest efficiency is observed in conditions with uniform backgrounds, where significant effects of apodization are found. The classification images, estimated using smoothing windows, suggest that human observers use center-surround filters to perform the task, and these are subjected to a number of subsequent analyses. When implemented as a scanning linear filter, the classification images appear to capture most of the observer variability in efficiency (r2 = 0.86). The frequency spectra of the classification images show that frequency weights generally appear bandpass in nature, with peak frequency and bandwidth that vary with statistical properties of the images. In these experiments, the classification images appear to capture important features of human-observer performance. Frequency apodization only appears to have a significant effect on performance in the absence of anatomical variability, where the observers appear to underweight low spatial frequencies that have relatively little noise. Frequency weights derived from the classification images generally have a bandpass structure, with adaptation to different conditions seen in the peak frequency and bandwidth. The classification image spectra show relatively modest changes in response to different levels of apodization, with some evidence that observers are attempting to rebalance the apodized spectrum presented to them.


Highly Efficient Visible Light Active Doped ZnO Photocatalysts for the Treatment of Wastewater Contaminated with Dyes and Pathogens of Emerging Concern.
Water is obligatory for sustaining life on Earth. About 71% of the Earth's surface is covered in water. However, only one percent of the total water is drinkable. The presence of contaminants in wastewater, surface water, groundwater, and drinking water is a serious threat to human and environmental health. Their toxic effects and resistance towards conventional water treatment methods have compelled the scientific community to search for an environmentally friendly method that could efficiently degrade toxic contaminants. In this regard, visible light active photocatalysts have proved to be efficient in eliminating a wide variety of water toxins. A plethora of research activities have been carried out and significant amounts of funds are spent on the monitoring and removal of water contaminants, but relatively little attention has been paid to the degradation of persistent water pollutants. In this regard, nanoparticles of doped ZnO are preferred options owing to their low recombination rate and excellent photocatalytic and antimicrobial activity under irradiation of solar light. The current article presents the roles of these nanomaterials for wastewater treatment from pollutants of emerging concern.


Transcatheter closure of various types of defects within the oval fossa using the double umbrella device (CardioSEAL)--feasibility and echocardiographic follow-up.
Data on long-term follow-up for closure of so-called secundum type" atrial septal defects within the oval fossa using recently developed devices are limited, and results focused on presence of residual shunting. The purpose of our study was to report the experience from a single center establishing the effectiveness of transcatheter closure in patients with various types of defect other than those located centrally within the oval fossa. A total of 72 patients was included in this study. On transesophageal echocardiography, the size of the defects varied from 6 to 18 mm, with estimation of the stretched diameter from 11 to 21 mm. The ratio of stretched diameter to the extent of the residual septum ranged from 0.28 to 0.54. Mean follow-up was 30.5+7.4 months, with a range from 13 to 42 months. The rate of closure using devices with diameters from 28 to 40 mm increased from 80% immediately after implantation to 93% in the 57 patients examined 24 months after implantation. For further analysis, we compared the 44 patients with a solitary, centrally located, defect to 28 having morphological variations, including superiorly located defects with deficient superior and aortic rims, multifenestrated and aneurysmal defects, or isolated additional defects. There was no incidence of formation of thrombus, sustained atrial arrhythmia, or infective endocarditis. Residual shunting was not influenced by location or morphology of the defects, but increased with size, stretched diameter, and the ratio of pulmonary to systemic flows. Serial transthoracic echocardiographic findings revealed malposition of one right-sided superior arm of the device in 8 patients, while protrusion of one left-sided arm onto the right atrial aspect was observed in 3 patients. Fluoroscopy showed fatigue fracture of a single arm in 7 patients (9.7%) within the first 6 months after implantation. These results demonstrate that transcatheter closure with the non self-centering double umbrella device was effective and safe on medium-term follow-up, and could be extended to defects within the oval fossa having various morphologies. Residual shunting resolved with time, and was not related to either morphology or the position of the device.


A brief primary care intervention to reduce fear of movement in chronic low back pain patients.
Fear avoidance model of chronic pain-based interventions are effective, but have not been successfully implemented into primary care. It was hypothesized that speed walking times and key measures of the fear avoidance model would improve following the brief intervention delivered in primary care. A brief primary care-based intervention (PCB) that included a single educational session, speed walking (an in vivo desensitization exposure task), and visual performance feedback was designed to reduce fear avoidance beliefs and improve function in 4 patients with chronic low back pain. A multiple baseline across subjects with a changing criterion design indicated that speed walking times improved from baseline only after the PCB intervention was delivered. Six fear avoidance model outcome measures improved from baseline to end of study and five of six outcome measures improved from end of study to follow-up. This study provides evidence for the efficacy of a brief PCB fear avoidance intervention that was successfully implemented into a busy clinic for the treatment of chronic pain.


What is new in atopic dermatitis/eczema?
Atopic eczema (AE) is a chronic relapsing inflammatory skin condition and one of the most common, potentially debilitating diseases with increasing incidence. The complex etiology of AE with multiple systemic and local immunologic and inflammatory responses and interactions between susceptibility genes and environmental factors leading to defects in skin barrier function and eczematous skin lesions is presented. Knowledge of pathogenesis is important for understanding the more innovative treatment approaches discussed. Basic therapy consists of hydrating topical treatment and avoidance of specific and unspecific provocation factors. For acute eczematous skin lesions, anti-inflammatory treatment consists mainly of topical glucocorticoids and topical calcineurin inhibitors. Microbial colonization and superinfection may induce skin exacerbation, which can be treated by either topical or systemic antimicrobial treatment. Systemic anti-inflammatory therapy is limited to severe cases and consists of systemic steroids, cyclosporine A or mycophenolate mofetil. Novel anti-inflammatory concepts that go beyond corticosteroids are in the early phases of development. There are targeted therapeutic approaches, such as cytokine and chemokine modulators, and it remains to be investigated how effective they will be and what side effects they may carry. Existing treatment modalities such as barrier repair therapy, topical immunosuppressive agents, antiseptic treatment as well as systemic treatment options are discussed.


Ropinirole treatment for restless legs syndrome.
Restless legs syndrome (RLS) is a chronic neurological disorder associated with sleep disturbance. Prepare a drug evaluation of the non-ergot dopamine agonist ropinirole in RLS. Review of scientific literature on RLS, particularly focusing on treatment with ropinirole. Ropinirole has been studied for treatment of moderate to severe primary RLS in a comprehensive clinical development program. Ropinirole significantly improved symptoms of RLS, versus placebo, in patients with primary RLS. These improvements are supported by data from individual studies and pooled analyses. Significant improvements in RLS symptoms were observed within two nights of treatment. Ropinirole also produced significant benefits on objective measures of RLS motor symptoms, such as periodic leg movements, and subjective measures of sleep. Ropinirole was generally well tolerated.


Sexuality in Patients with Hidradenitis Suppurativa: Beliefs, Behaviors and Needs.
Little is known about the impact of hidradenitis suppurativa (HS) on patients' sexuality. The aim of this research is to investigate the impact of HS on several previously unexplored aspects of sexuality. In March 2018, we conducted a crowd-sourced cross-sectional online survey hosted by the Spanish association of patients with HS (ASENDHI) and available in Spanish. A panel of experts and patients from ASENDHI designed various questions in order to explore the extent to which HS influenced participants' sex lives. The final sample consisted of 386 participants, 79.27% (306/386) of which were women and 20.73% (80/306) of which were men. Seventy-seven point one percent (236/306) of women and 67.5% (54/80) of men were in stable relationships; the rest of the participants were single. Forty-seven point nine percent (185/386) admitted to feeling fear of rejection. Pain was the symptom that most interfered with sexual relations in women and suppuration in men. Forty-four point three percent (171/386) of the participants considered themselves to be less attractive than average. Considering the participants in a stable relationship, women described receiving more emotional support from their partners, while men received more help with lesion dressing in intimate areas. Seventy-one point four percent (207/290) of participants stated that HS negatively affected their relationship. Among single patients, women experienced greater fear of rejection and were less willing to meet new people because of HS. Ninety-four point three percent (66/70) of women and 80.8% (21/26) of men stated that HS had a negative influence on their chances of having a relationship or sexual relations. In conclusion, HS has a significant, unrecognized and misunderstood impact on sexuality which must be addressed.


Human type VII collagen: genetic linkage of the gene (COL7A1) on chromosome 3 to dominant dystrophic epidermolysis bullosa.
Epidermolysis bullosa (EB) is a heterogeneous group of heritable blistering disorders affecting the skin and the mucous membranes. Previous ultrastructural studies on the dystrophic (scarring) forms of EB have demonstrated abnormalities in the anchoring fibrils, morphologically distinct structures below the basal lamina at the dermal/epidermal basement membrane zone. Type VII collagen is the major collagenous component of the anchoring fibrils, and it is therefore a candidate gene for mutations in some families with dystrophic forms of EB. In this study, we performed genetic linkage analyses in a large kindred with dominant dystrophic EB. A 1.9-kb type VII collagen cDNA clone was used to identify a PvuII RFLP to follow the inheritance of the gene. This RFLP cosegregated with the EB phenotype in this family, strongly supporting genetic linkage (Z = 5.37; theta = .0). In addition, we assigned the type VII collagen gene (COL7A1) to chromosome 3 by hybridization to a panel of human x rodent somatic cell hybrids. These data demonstrate very close genetic linkage between the clinical phenotype in this family and the polymorphism in the type VII collagen gene mapped to chromosome 3. The absence of recombination between EB and the type VII collagen gene locus, as well as the observed abnormalities in the anchoring fibrils, strongly suggest that this collagen gene is the mutant locus in this kindred.


Mastoid vibration affects dynamic postural control during gait in healthy older adults.
Vestibular disorders are difficult to diagnose early due to the lack of a systematic assessment. Our previous work has developed a reliable experimental design and the result shows promising results that vestibular sensory input while walking could be affected through mastoid vibration (MV) and changes are in the direction of motion. In the present paper, we wanted to extend this work to older adults and investigate how manipulating sensory input through mastoid vibration (MV) could affect dynamic postural control during walking. Three levels of MV (none, unilateral, and bilateral) applied via vibrating elements placed on the mastoid processes were combined with the Locomotor Sensory Organization Test (LSOT) paradigm to challenge the visual and somatosensory systems. We hypothesized that the MV would affect sway variability during walking in older adults. Our results revealed that MV significantly not only increased the amount of sway variability but also decreased the temporal structure of sway variability only in anterior-posterior direction. Importantly, the bilateral MV stimulation generally produced larger effects than the unilateral. This is an important finding that confirmed our experimental design and the results produced could guide a more reliable screening of vestibular system deterioration.


Use of creatine in the elderly and evidence for effects on cognitive function in young and old.
The ingestion of the dietary supplement creatine (about 20 g/day for 5 days or about 2 g/day for 30 days) results in increased skeletal muscle creatine and phosphocreatine. Subsequently, the performance of high-intensity exercise tasks, which rely heavily on the creatine-phosphocreatine energy system, is enhanced. The well documented benefits of creatine supplementation in young adults, including increased lean body mass, increased strength, and enhanced fatigue resistance are particularly important to older adults. With aging and reduced physical activity, there are decreases in muscle creatine, muscle mass, bone density, and strength. However, there is evidence that creatine ingestion may reverse these changes, and subsequently improve activities of daily living. Several groups have demonstrated that in older adults, short-term high-dose creatine supplementation, independent of exercise training, increases body mass, enhances fatigue resistance, increases muscle strength, and improves the performance of activities of daily living. Similarly, in older adults, concurrent creatine supplementation and resistance training increase lean body mass, enhance fatigue resistance, increase muscle strength, and improve performance of activities of daily living to a greater extent than resistance training alone. Additionally, creatine supplementation plus resistance training results in a greater increase in bone mineral density than resistance training alone. Higher brain creatine is associated with improved neuropsychological performance, and recently, creatine supplementation has been shown to increase brain creatine and phosphocreatine. Subsequent studies have demonstrated that cognitive processing, that is either experimentally (following sleep deprivation) or naturally (due to aging) impaired, can be improved with creatine supplementation. Creatine is an inexpensive and safe dietary supplement that has both peripheral and central effects. The benefits afforded to older adults through creatine ingestion are substantial, can improve quality of life, and ultimately may reduce the disease burden associated with sarcopenia and cognitive dysfunction.


Impact of medical education program on COPD patients: a cohort prospective study.
The main objective of this study was to assess the effects of intensive medical education courses on chronic obstructive pulmonary disease (COPD)-related rehospitalizations and emergency department visits and the secondary aim was to monitor quality of life. This cohort prospective study included 76 group D COPD patients (pts.). Patients from the intervention group (IG, 52 pts.) underwent a program comprising two components: a comprehensive medical education program (1h/day for 5 days) and a specific drug therapy. Control group (CG, 24 pts.) received only drug therapy. Patients underwent spirometry and completed St. George's Respiratory Questionnaire (SGRQ) at the time of inclusion and at periodical evaluations performed every three months for a year. Patients included in a medical education program showed significant decrease of exacerbation rate compared with the CG. Patients from the IG group had fewer emergency department visits within a year compared with the CG. Patients from the IG had significantly better quality of life scores (both at 3 and 6 months) compared with the CG. This study reveals that an adequate medical education program is associated with a decreased rate of COPD-related hospitalizations. The implementation of a medical education program as an integrated part of therapy could lead to a more accurate self-management of the disease.


Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease.
We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound. Patients had greater carotid IMT (0.779 +/- 0.164 mm) than did controls (0.699 +/- 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 +/- 0.116 mm) than those without plaques (0.739 +/- 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease. The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.


ERK Dephosphorylation through MKP1 Deacetylation by SIRT1 Attenuates RAS-Driven Tumorigenesis.
The role of Situin 1 (SIRT1) in tumorigenesis is still controversial due to its wide range of substrates, including both oncoproteins and tumor suppressors. A recent study has demonstrated that SIRT1 interferes in the Kirsten rat sarcoma viral oncogene homolog (KRAS)-driven activation of the Raf-mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway, thereby inhibiting tumorigenesis. However, the molecular mechanism of SIRT1 as a tumor suppressor in RAS-driven tumorigenesis has been less clearly determined. This study presents evidence that the ectopic expression of SIRT1 attenuates RAS- or MEK-driven ERK activation and reduces cellular proliferation and transformation in vitro. The attenuation of ERK activation by SIRT1 results from prompt dephosphorylation of ERK, while MEK activity remains unchanged. We identified that MKP1, a dual specific phosphatase for MAPK, was deacetylated by SIRT1. Deacetylation of MKP1 by direct interaction with SIRT1 increased the binding affinity to ERK which in turn facilitated inactivation of ERK. Taken together, these results suggest that SIRT1 would act as a tumor suppressor by modulating RAS-driven ERK activity through MKP1 deacetylation.


How stable is the photon?
Yes, the photon. While a nonzero photon mass has been under experimental and theoretical study for years, the possible implication of a finite photon lifetime lacks discussion. The tight experimental upper bound of the photon mass restricts the kinematically allowed final states of photon decay to the lightest neutrino and/or particles beyond the standard model. We discuss the modifications of the well-measured cosmic microwave background spectrum of free streaming photons due to photon mass and lifetime and obtain model-independent constraints on both parameters--most importantly a lower direct bound of 3 yr on the photon lifetime, should the photon mass be at its conservative upper limit. In that case, the lifetime of microwave photons will be time-dilated by a factor order 10(15).


Anxiety symptom interpretation in high-anxious, defensive high-anxious, low-anxious and repressor sport performers.
For the first time in a sport setting this study examined the intensity and direction of the competitive state anxiety response in collegiate athletes as a function of four different coping styles: high-anxious, defensive high-anxious, low-anxious and repressors. Specifically, the study predicted that repressors would interpret competitive state anxiety symptoms as more facilitative compared to high-anxious, defensive high-anxious, and low-anxious performers. Separate Multivariate Analyses of Variance (MANOVA) were performed on the intensity and direction subscales of the modified Competitive State Anxiety Inventory-2 (CSAI-2). A significant main effect was identified for trait worry revealing that low trait anxious athletes reported lower intensities of cognitive and somatic anxiety and higher self-confidence and interpreted these as more facilitative than high trait anxious athletes. The prediction that performers with a repressive coping style would interpret state anxiety symptoms as more facilitative than performers with non-repressive coping styles was not supported.


Food for thought: endocannabinoid modulation of lipogenesis.
An emerging body of evidence implicates peripheral and central endocannabinoid pathways in the regulation of feeding behavior and body weight. A report in this issue of the JCI demonstrates the presence of a common endocannabinoid-regulated molecular pathway for peripheral lipogenic and central appetitive regulation. This pathway involves the activation of the transcription factor SREBP-1c and its associated enzymes, acetyl-CoA carboxylase-1 and fatty acid synthase, in the liver and hypothalamus. Activation of cannabinoid receptor 1 (CB(1)) in liver plays a key role in increased serum lipid production, fatty liver, and possibly diet-induced obesity. Conversely, stimulation of these receptors in the hypothalamus may lead to an increase in food consumption. Thus, targeting both of these pathways with CB(1) antagonists could promote sustained weight loss and favorable serum lipid profiles in obese patients.


PhotoCloud: Interactive remote exploration of joint 2D and 3D datasets.
PhotoCloud is a real-time client-server system for interactive visualization and exploration of large datasets comprising thousands of calibrated 2D photographs of a scene and a complex 3D description of the scene. The system isn't tailored to any specific data acquisition process; it aims at generality and flexibility. PhotoCloud achieves scalability through a multiresolution dynamic hierarchical representation of the data, which is remotely stored and accessed by the client through an efficient cache system. The system includes a compact image browser and a multiresolution model renderer. PhotoCloud employs iconic visualization of the images in the 3D space and projects images onto the 3D scene on the fly. Users can navigate the 2D and 3D spaces with smooth, integrated, seamless transitions between them. A study with differently skilled users confirms PhotoCloud's effectiveness and communication power. The Web extras at http://www.youtube.com/playlist?list=PLHJB2bhmgB7cmYD0ST9CEDMRv1JlX4xPH are videos demonstrating PhotoCloud, a real-time client-server system for interactive exploration of large datasets comprising 2D photos and 3D models.