Interleukin-8 is a chemo-attractant for eosinophils purified from subjects with a blood eosinophilia but not from normal healthy subjects.
Interleukin-8 (IL-8), a pro-inflammatory cytokine with potent neutrophil chemotactic activity, was studied for its effect on eosinophil migration responses, in vitro. Normal density eosinophils were isolated from healthy, non-atopic subjects (<0.35 x 10(9) eosinophils/l) and individuals with various diseases associated with a blood eosinophilia (range 0.56 x 10(9)-12.2 x 10(9) eosinophils/l). IL-8 produced a dose-dependent migrational response for eosinophils from subjects with an eosinophilia, optimal at 10(-8) M (P < 0.01) and the major component of the migrational response was chemokinesis. On a molar basis, IL-8 (EC50 approximately 10(10) M) was 100-fold more potent than platelet activating factor (PAF), although a comparison of the migrational responses showed that at optimal concentrations IL-8 (10(-8) M) produced only 30% maximal responses stimulated by PAF (10(-6) M). In contrast, IL-8 tested over a wide concentration range had a negligible effect on eosinophils from normal subjects. A direct correlation between the total blood eosinophil counts for all subjects and the absolute magnitude of the migrational response to IL-8 (r = 0.727, P < 0.01 at 10(-8) M), PAF (r = 0.551, P < 0.03 at 10(-6) M) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (r = 0.689, P < 0.02 at 10(-8) M), suggested that heightened eosinophil migrational responses to inflammatory mediators may arise as a consequence of in vivo priming mechanism(s) associated with the development of an eosinophilia. In this regard, eosinophils derived from human cord blood mononuclear cells cultured in the presence of eosinophilopoietic cytokines IL-3 and IL-5, produced migrational responses to IL-8 and PAF, that were comparable with that of eosinophils from eosinophilic subjects. Furthermore, incubation of eosinophils from normal donors with IL-5 (optimal concentration 10(-9) M), significantly enhanced the subsequent migrational responses to both IL-8 (10(-8) M, P < 0.01) and PAF (10(-8) M, P < 0.05). Therefore, the increased responsiveness of eosinophils from eosinophilic subjects may reflect in vivo priming by IL-5 and this phenomenon may contribute partly to the mechanism(s) by which eosinophils preferentially accumulate at sites of allergic inflammation.


Same day diagnosis of Down's syndrome and sex in single cells using multiplex fluorescent PCR.
The major reason for prenatal diagnosis lies in the detection of trisomies, particularly trisomy 21 (Down's syndrome). Current techniques require lengthy laboratory procedures and high costs. Furthermore, diagnosis is often not possible if the sample is of small size or is contaminated. An alternative method, quantitative fluorescent polymerase chain reaction (PCR) of short tandem repeats (STRs), can also be used to diagnose trisomies and it has the advantage that a result is obtained within five to eight hours. However, this method is currently limited to relatively large amounts of sample, which restricts diagnostic confidence and value. Recently, genetic diagnosis using fluorescent PCR has been applied at the single cell level but is limited to sex or single gene defect diagnosis. This study, using quantitative multiplex fluorescent PCR, provides for the first time simultaneous diagnosis and confirmation of sex and trisomy in single cells. Two markers for chromosome 21 increase diagnostic confidence, informativeness, and confirmation. This system is rapid (five hours), reliable, and accurate and we believe that it will be more cost effective than alternative methods. The technique has direct application to preimplantation genetic diagnosis, early prenatal diagnosis, and other diagnostic systems where sample size is limited.


[Trans-fatty acids--effects on coronary heart disease].
Trans-fatty acids (TFA) are formed during the industrial process of hydrogenation of vegetable oils. The consumption of hydrogenated fats has increased significantly over the last few decades. In Poland, the average daily intake of TFA for adults was estimated to be 2.8 to 6.9 g; which greatly exceeds the recommended daily maximum of 2 g/day (less than 1% of total energy intake). Increasing trans-fatty acid intake has detrimental effects on the lipid profile: TFA raise total cholesterol, LDL-cholesterol and triglyceride concentrations, and decrease HDL-cholesterol levels. Moreover, dietary trans-fatty acids may increase plasma levels of lipoprotein (a) and biomarkers of inflammation and endothelial dysfunction. Several studies have demonstrated that a high intake of TFA is associated with an increased risk of coronary heart disease. In addition, TFA consumption has been implicated as an independent risk factor for sudden cardiac arrest. It is therefore necessary to reduce the intake of hydrogenated fats rich in trans-fatty acids in order to minimize the adverse effects of TFA on health.


Atrial fibrillation in heart failure: stroke risk stratification and anticoagulation.
For an individual patient with both atrial fibrillation and heart failure, stroke risk is one of the most prominent mitigating factors for subsequent morbidity and mortality. Although the CHADS₂ stroke risk score is the most widely used score for risk stratification, it does not take into account the risk factors of vascular disease, female gender, or the age group 65-74 years, for which there is increasing evidence. There is also evidence that diastolic heart failure is as much a risk factor for stroke as systolic heart failure. The new oral anticoagulants dabigatran, rivaroxaban and apixaban appear to be appropriate agents in the heart failure population with atrial fibrillation and risk factors for stroke although there are dose-adjustments for renal insufficiency and these medications are contraindicated in advanced renal disease. As with the atrial fibrillation population as a whole, bleeding risk should be considered for every patient with heart failure prior to making recommendations regarding anticoagulation.


De novo adipose tissue generation through long-term, local delivery of insulin and insulin-like growth factor-1 by PLGA/PEG microspheres in an in vivo rat model: a novel concept and capability.
This study was undertaken to characterize the duration of long-term growth factor delivery by poly(lactic-co-glycolic-acid)-polyethylene glycol (PLGA/PEG) microspheres and to evaluate the potential of long-term delivery of insulin and insulin-like growth factor-1 (IGF-1) for the de novo generation of adipose tissue in vivo. PLGA/PEG microspheres containing insulin and IGF-1, separately, were produced by a double-emulsion solvent-extraction technique. In the first phase of the experiment, the in vitro release kinetics of the microspheres were evaluated for the optical density and polyacrylamide gel electrophoresis of solutions incubated with insulin-containing microspheres for four different periods of time (n = 1). The finding of increased concentrations of soluble insulin with increased incubation time confirmed continual protein release. In the second stage of the experiment, 16 rats were divided equally into four study groups (insulin, IGF-1, insulin + IGF-1, and blank microspheres) (n = 4). Insulin and IGF-1 containing microspheres were administered directly to the deep muscular fascia of the rat abdominal wall to evaluate the potential for de novo adipose tissue generation via adipogenic differentiation from native nonadipocyte cell pools in vivo. Animals treated with blank microspheres served as an external control group. At the 4-week harvest period, multiple ectopic islands of adipose tissue were observed on the abdominal wall of the animals treated with insulin, IGF-1, and insulin + IGF-1 microspheres. Such islands were not seen in the blank microsphere group. Hematoxylin and eosin-stained sections of the growth factor groups demonstrated mature adipocytes interspersed with fibrous tissue superficial to the abdominal wall musculature and continuous with the fascia. Oil-Red-O stained sections demonstrated that these cells contained lipid. Computer-aided image analysis of histologic sections confirmed that there were statistically significant increases in the amount of "ectopic" adipose neotissue developed on the abdominal wall of animals treated with growth factor microspheres. In conclusion, this study confirms the long-term release of proteins from PLGA/PEG microspheres up to 4 weeks and demonstrates the potential of long-term local insulin and IGF-1 to induce adipogenic differentiation to mature lipid-containing adipocytes from nonadipocyte cell pools in vivo at 4 weeks.


School-level factors associated with teacher connectedness: a multilevel analysis of the structural and relational school determinants of young people's health.
Conducting research on the antecedents of teacher connectedness (TC) is key to inform intervention and policy that can leverage the public health potential of teachers for young people's well-being. As part of the EU-funded Teacher Connectedness Project, this study aims to examine the contribution of a variety of school-level factors (including type of school, school size, student-teacher ratio, students per class and teacher gender). Sample consisted of 5335 adolescents aged 11, 13 and 15 years that had participated in the HBSC study in England. Multilevel multinomial regression was used to examine the contributions of sociodemographic and school-level factors to TC. TC was lower in older adolescents and those from less affluent families, but similar in boys and girls. Regarding school-level factors, it was not the size of the school but the ratio of students per teacher which was significantly associated to TC, with higher student-teacher ratio being significantly associated with lower odds of medium-to-high TC. Some differences between mixed and all-girls schools were also found. Health promotion strategies targeting student-teacher relationships need to consider how TC changes by age and SES and give attention to school-level factors, in particular the student-teacher ratio.


Early airway structural changes in cystic fibrosis pigs as a determinant of particle distribution and deposition.
The pathogenesis of cystic fibrosis (CF) airway disease is not well understood. A porcine CF model was recently generated, and these animals develop lung disease similar to humans with CF. At birth, before infection and inflammation, CF pigs have airways that are irregularly shaped and have a reduced caliber compared to non-CF pigs. We hypothesized that these airway structural abnormalities affect airflow patterns and particle distribution. To test this hypothesis we used computational fluid dynamics (CFD) on airway geometries obtained by computed tomography of newborn non-CF and CF pigs. For the same flow rate, newborn CF pig airways exhibited higher air velocity and resistance compared to non-CF. Moreover we found that, at the carina bifurcation, particles greater than 5-μm preferably distributed to the right CF lung despite almost equal airflow ventilation in non-CF and CF. CFD modeling also predicted that deposition efficiency was greater in CF compared to non-CF for 5- and 10-μm particles. These differences were most significant in the airways included in the geometry supplying the right caudal, right accessory, left caudal, and left cranial lobes. The irregular particle distribution and increased deposition in newborn CF pig airways suggest that early airway structural abnormalities might contribute to CF disease pathogenesis.


A novel multiple-instance learning-based approach to computer-aided detection of tuberculosis on chest X-rays.
To reach performance levels comparable to human experts, computer-aided detection (CAD) systems are typically optimized following a supervised learning approach that relies on large training databases comprising manually annotated lesions. However, manually outlining those lesions constitutes a difficult and time-consuming process that renders detailedly annotated data difficult to obtain. In this paper, we investigate an alternative approach, namely multiple-instance learning (MIL), that does not require detailed information for optimization. We have applied MIL to a CAD system for tuberculosis detection. Only the case condition (normal or abnormal) was required during training. Based upon the well-known miSVM technique, we propose an improved algorithm that overcomes miSVM's drawbacks related to positive instance underestimation and costly iteration. To show the advantages of our MIL-based approach as compared with a traditional supervised one, experiments with three X-ray databases were conducted. The area under the receiver operating characteristic curve was utilized as a performance measure. With the first database, for which training lesion annotations were available, our MIL-based method was comparable to the supervised system ( 0.86 versus 0.88 ). When evaluating the remaining databases, given their large difference with the previous image set, the most appealing strategy was to retrain the CAD systems. However, since only the case condition was available, only the MIL-based system could be retrained. This scenario, which is common in real-world applications, demonstrates the better adaptation capabilities of the proposed approach. After retraining, our MIL-based system significantly outperformed the supervised one ( 0.86 versus 0.79 and 0.91 versus 0.85 , and p=0.0002 , respectively).


Influence of substituting steam-flaked corn for dry rolled corn on feedlot cattle growth performance when cattle are allowed either ad libitum or restricted access to the finishing diet.
The influence of substituting steam-flaked corn (SFC) for dry rolled corn (DRC) on feedlot cattle growth performance and dietary net energy when cattle are allowed either ad libitum or 2-h restricted access to the finishing diet was evaluated. Treatment effects were tested using 96 crossbred steers (251±2 kg) during the initial 56 d of the finishing phase. Cattle were blocked by weight and randomly assigned within blocks to 16 pens (4 pens/treatment). Bunk space was sufficient (41 cm/head) to allow all steers access to the feed bunk at the same time. Treatments consisted of two finishing diets containing (dry matter basis) 77.1% corn grain processed by dry rolling (density = 0.50 kg/L) or steam flaking (density = 0.36 kg/L). Cattle were fed twice daily at 06:00 and 14:00 h, allowing for approximately 5% residual. In the case of restricted feeding, steers were allowed access to feeders for 1 h following each feeding, after which residual feed was withdrawn. There were no treatment interactions on dry matter intake (DMI), average daily gain (ADG), gain efficiency (G:F), or dietary net energy (NE). Restricting feed access time reduced (p <0.01) feed intake, and hence, ADG. Substitution of SFC for DRC increased (p<0.01) ADG, feed efficiency (G:F), and estimated dietary NE, without affecting DMI. Based on tabular net energy of maintenance (NEm) value (2.18 Mcal/kg) for DRC, the estimated NEm value for SFC using the replacement technique, averaged 2.44 Mcal/kg; an improvement of 10.7%. The ratio of observed-to-expected dietary NE was not affected by feed access time. Substitution of SFC for DRC in finishing diets for feedlot cattle enhanced ADG, gain efficiency, and the NE value of the diet. Although restriction of feed access time depressed DMI and ADG, it did not affect the comparative benefit of steam flaking toward enhancement of ADG, G:F, and dietary NE.


Phenotypic stability and genome-wide association study of late blight resistance in potato genotypes adapted to the tropical highlands.
Potato genotypes from a breeding population adapted to tropical highlands were analyzed for the stability of late blight resistance and also for marker-phenotype association. We harmonized the historical evaluation data, consisting of observations spanning 6 years from two field sites utilizing a resistance scale constructed by comparing the area under the disease progress curve (AUDPC) values of 172 genotypes with that of susceptible control 'Yungay'. In total, 70 potato genotypes had a coefficient of variability <0.5 and were considered stable across the environments tested. A principal component analysis demonstrated that the ensemble of experiments formed two distinct groups that reflect the stability of genotype resistance to late blight. Phytophthora infestans isolates present in the experimental fields belonged to the EC-1 clonal lineage and showed variation in virulence beyond the concept of the avirulence determined by the conventionally used R1-R11 differential set. A single-nucleotide polymorphism (SNP) marker on chromosome 9 was associated with late blight resistance and linked to instability. Genotypes with either AACC or AAAC combinations for this SNP were highly resistant only in some environments, while the genotypes with the AAAA combination had more moderate levels of resistance but were stable across environments.


[Confidentiality, genetic counseling, and public health: a case study on sickle cell trait].
Sickle cell anemia is the most prevalent genetic disease in Brazil. Screening for sickle cell trait in blood donation centers has been recommended by the Brazilian government since 1976. This screening mechanism is one of most common forms of genetic screening for sickle cell disease in the country. This article is based on an ethnographic survey of individuals undergoing genetic counseling in a large blood donation center. The article contends that confidentiality should be a prerequisite for the broad dissemination of genetic information in public health. The ethical principle of confidentiality needs to be seen as a human right and public health issue.


Complications associated with revision of Sprint Fidelis leads: report from the Canadian Heart Rhythm Society Device Advisory Committee.
It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously. Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P=0.0008). The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.


Comparative performance of two drug interaction screening programmes analysing a cross-sectional prescription dataset of 84,625 psychiatric inpatients.
Clinical decision support software (CDSS) solutions can automatically identify drug interactions and thereby aim to improve drug safety. However, data on the comparative performance of different CDSS to detect and appropriately classify interactions in real-life prescription datasets is limited. The aim of this study was to compare the results from two different CDSS analysing the pharmacotherapy of a large population of psychiatric inpatients for drug interactions. We performed mass analyses of cross-sectional patient-level prescriptions from 84,625 psychiatric inpatients using two CDSS - MediQ and ID PHARMA CHECK(®). Interactions with the highest risk ratings and the most frequent ratings were reclassified according to the Zurich Interaction System (ZHIAS), a multidimensional classification that incorporates the OpeRational ClassificAtion of Drug Interactions (ORCA) and served as a reference standard. MediQ reported 6,133 unique interacting combinations responsible for 270,617 alerts affecting 63,454 patients. ID PHARMA CHECK(®) issued 5,400 interactions and 157,489 alerts in 48,302 patients. Only 2,154 unique interactions were identified by both programmes, but overlap increased with higher risk rating. MediQ reported high-risk interactions in 2.5 % of all patients, compared with 5 % according to ID PHARMA CHECK(®). The positive predictive value for unique major alerts to be (provisionally) contraindicated according to ORCA was higher for MediQ (0.63) than for either of the two ID PHARMA CHECK(®) components (0.42 for hospINDEX and 0.30 for ID MACS). MediQ reported more interactions, and ID PHARMA CHECK(®) tended to classify interactions into a higher risk class, but overall both programmes identified a similar number of (provisionally) contraindicated interactions according to ORCA criteria. Both programmes identified arrhythmia as the most frequent specific risk associated with interactions in psychiatric patients. CDSS can be used for mass-analysis of prescription data and thereby support quality management. However, in clinical practice CDSS impose an overwhelming alert burden on the prescriber, and prediction of clinical relevance remains a major challenge. Only a small subset of yet to be determined alerts appears suitable for automated display in clinical routine.


Absorption, psychological boundaries and attitude towards dreams as correlates of dream recall: two decades of research seen through a meta-analysis.
Many studies have reported positive correlations between dream recall frequency (DRF) and measures of absorption, psychological boundaries and attitude towards dreams. A majority of these studies, however, have relied exclusively on retrospective measures of DRF even though daily dream logs are generally considered to be more direct and valid measures of DRF. The first goal of the present meta-analysis was to evaluate the effect sizes of three variables (absorption, psychological boundaries and attitude towards dreams) as correlates of DRF. The second goal was to evaluate if these effect sizes varied as a function of how DRF was operationalized (i.e. retrospective measure versus dream log). Data from 24 studies were included in the analyses. For each of the three variables investigated, correlations with retrospective measures of DRF were of greater magnitude than those obtained with daily logs. These results indicate that scores on measures of absorption and psychological boundaries are not related to DRF per se, but rather to people's tendency to retrospectively underestimate or overestimate their DRF, while attitude towards dreams is related both to DRF per se and to people's retrospective estimation bias. Implications of these findings for dream research are discussed.


Methodological aspects of drug trials in migraine.
Treatment of migraine attacks and prophylactic treatment of migraine are each discussed under the four headings: patient selection, trial design, evaluation of results and statistics. Checklist of problems encountered in these trials are given in the tables. The unsuitability of currently used migraine definitions for scientific investigations is stressed. Operational diagnostic criteria for common and classic migraine are given. No clear separation of common migraine attacks and interval headaches is possible, but the problem can be reduced by setting an upper limit (4-6/month) on migraine attack frequency. For the treatment of migraine attacks, the crossover design should always be used. We suggest dose-response studies to solve the problem of equipotency of doses, when 2 drugs are compared. A prophylactic drug should be studied both with the crossover design and with the less powerful group comparison design. Evaluation of results should be based on patients' attack report forms and, in prophylactic studies, a headache diary. We suggest global rating of attack severity. A rather simple headache index (sum of severity scores for each day with migraine) and perhaps a sum of global scores should be used in prophylactic trials. Confidence limits and power should be given, particularly when statistically insignificant results are reported. Migraine frequency often decreases with time regardless of treatment, and this 'time effect' should be separated from the therapeutic effect by appropriate statistical methods.


[Thymocyte receptors reacting with red blood cells and Fc portion of immunoglobulin G].
Some properties of glycoprotein isolated from rat thymocytes were studied. The glycoprotein (its molecular weight is found to be about 12000 Daltons) has an affinity for autologous and xenogenous red blood cells as well as for Fc portion of IgG. It is shown that the glycoprotein belongs to the thymocyte plasma membrane receptors responsible for interaction with erythrocytes and possesses the Fe receptor properties. The data give reason to conclude that at least one of the Fc receptors has the affinity for SRBC, ARBC and Fe portion of IgG.


Predator olfactory cues generate a foraging-predation trade-off through prey apprehension.
Most animals are faced with the challenge of securing food under the risk of predation. This frequently generates a trade-off whereby animals respond to predator cues with reduced movement to avoid predation at the direct cost of reduced foraging success. However, predators may also cause prey to be apprehensive in their foraging activities, which would generate an indirect 'apprehension cost'. Apprehension arises when a forager redirects attention from foraging tasks to predator detection and incurs a cost from such multi-tasking, because the forager ends up making more mistakes in its foraging tasks as a result. Here, we test this apprehension cost hypothesis and show that damselflies miss a greater proportion of their prey during foraging bouts in response to both olfactory cues produced by conspecifics that have only viewed a fish predator and olfactory cues produced directly by fish. This reduced feeding efficiency is in addition to the stereotypical anti-predator response of reduced activity, which we also observed. These results show that costs associated with anti-predator responses not only arise through behavioural alterations that reduce the risk of predation, but also from the indirect costs of apprehension and multi-tasking that can reduce feeding efficiency under the threat of predation.


Identifying pain in children with CHARGE syndrome.
Background and aims The objective was to conduct the first investigation to identify the frequency and intensity of pain experiences for individuals with CHARGE syndrome and to review the use of two established non-vocal pain assessments with children with CHARGE, the NCCPC-R (Non-Communicating Children's Pain Checklist-Revised) and the PPP (Pediatrics Pain Profile). Methods Parents of children with CHARGE were enrolled. Participants completed a pain questionnaire and the NCCPC-R and PPP twice, once for a baseline measure and second during a painful experience for their child. Results A moderate negative correlation between the mean intensity of pain and the mean duration of pain among individuals with CHARGE was found, ρ=-0.34. There was a tendency for intensity of pain to increase for sources of pain that were of shorter duration. The NCCPC-R and PPP were found to identify pain when compared to baseline performance (no pain) with a large effect, d=1.3. For the NCCPC-R, the difference between these ratings was significant beyond the 0.05 level, t (40)=8.15, p=0.000, 95% CI [16.93, 28.10]. Similarly, for the PPP, the mean pain ratings were significantly greater than the mean ratings for no pain, with significance beyond the 0.05 level, t (51)=9.59, p=0.000, CI 95% [11.74, 17.96]. Conclusions Evidence exists that children with CHARGE experience pain. While the NCCPC-R and PPP were found to identify pain; future research should consider the development of a pain assessment individualized to pain behaviors present in CHARGE syndrome, given this population's unique expression of pain.


Novel, bilateral, two-bellied muscles span the extensor forearm, thenar eminence to insert on the proximal phalanx of the thumb: clinical and embryological significance.
Muscle and tendon variations in the forearm, wrist and hand are commonly reported in the anatomical and surgical literature. They are frequently the source of inflammatory conditions such as de Quervain's tenosynovitis or carpal tunnel syndrome. During academic dissection, a cadaver presented with bilateral, additional muscles running parallel to the abductor pollicis longus muscles (APL) in the extensor compartment of the forearm. Both additional muscles had two bellies, one proximal and one distal, with an intervening tendon. The proximal bellies were separate and distinct from the adjacent APLs. The tendons traversed the first dorsal compartments with the tendons of the APLs and the extensor pollicis brevis muscles (EPB). The distal bellies lay adjacent to the abductor pollicis brevis (APB) muscles in the thenar compartments, and inserted onto the volar base of the proximal phalanges of the thumbs. Following a thorough search of the literature, we determined that these additional muscles constitute a previously unreported variation. This report details the variation, compares it with other reported variations, presents the related embryology, and reviews the significance of this variation as it relates to inflammatory conditions and surgical procedures.


Physical characterization of wax/oil crystalline networks.
The objective of this research was to evaluate the physical properties of different types of wax/oil systems. Olive (OO), corn (CO), soybean (SBO), sunflower (SFO), safflower (SAFO), and canola (CAO) oils were mixed with sunflower oil wax (SFOW), paraffin wax (PW), and beeswax (BW) at different concentrations (1% to 10%). Results from this study show that the physical properties of wax/oil systems is affected not only by the concentration and type of wax used, but also by the type of oil used. In general, wax/oil systems formulated with SFOW generated crystalline networks with high enthalpies (1 to 22 J/g) and high G' values (2 to 6 × 10(6) Pa) compared with the values obtained for BW and PW. SFOW crystalline networks were characterized by needle-like crystals independently of the wax concentrations and type of oil used. BW crystalline networks, however, were characterized by different crystal morphologies (needle-like or spherulites) depending on the wax concentration and type of oil used. PW samples were characterized by a crystalline network formed by needle- and platelet-like crystals. Enthalpy values of BW and PW samples were similar (0.3 to 20 J/g), but BW samples resulted in significantly higher (P < 0.05) G' values in the 5% and 10% samples with values of 3.9 × 10(6) and 6.1 × 10(5) Pa for 10% BW and PW, respectively.


[Recognition of conventional and emotional facial expressions in patients with cortical lesions (author's transl)].
Recognition of facial expressions was studied in a group of patients with cortical lesions. The test which was used consists in designating 30 expressions upon verbal command. Fifteen items had an emotional characteristic, and fifteen had a conventional characteristic (with an intentional communicative aspect). Results showed that right hemisphere patients had a elective deficit for emotional expressions. Left hemisphere patients had a elective deficit for conventional expressions. Analysis of correlations with associated clinical deficits showed further, that the deficit was associated, in right hemisphere patients, with lesions giving rise to Unilateral Spatial Agnosia. In left hemisphere patients it was associated with posterior lesions outside of the language area.


[The European Directive 96/29/Euratom through the history of radiation protection].
The new european directive concerning the radiation protection 96/29/Euratom is currently being transposed in national regulations. This directive is registered in a historical context. This context allows us to understand how it is realised and what philosophy underlies the actual structure and its possible shortcomings. Current developments of the radiobiology and the radio-epidemiology, notably important modifications of our knowledge about natural irradiation, the attention for genetic fragile populations and relationships between irradiation and cancer are likely to modify our perception of the radiation protection.


Interactions between race/ethnicity and anthropometry in risk of incident diabetes: the multi-ethnic study of atherosclerosis.
This study examined how adiposity influences racial/ethnic differences in diabetes incidence by exploring whether relations between anthropometric measures and incident diabetes vary by race/ethnicity. Data from the Multi-Ethnic Study of Atherosclerosis initiated in 2000 (n = 5,446 US men and women aged 45-84 years) were analyzed by using proportional hazards and Poisson regression. The diabetes incidence rate was 2/100 person-years (n = 479 cases). Interactions were present between race and anthropometry (P-interaction((race x body mass index)) = 0.002). The slope of incident diabetes per anthropometric unit was greatest for Chinese, less for whites and Hispanics, and still less for blacks. For small waist, risk of incident diabetes was <1/100 person-years for all racial/ethnic groups. At intermediate waist levels, Chinese had the highest and whites the lowest rates of incident diabetes. At the respective 95th percentiles of waist circumference, risk of incident diabetes per 100 person-years was 3.9 for Chinese (104 cm), 3.5 for whites (121 cm), 5.0 for blacks (125 cm), and 5.3 for Hispanics (121 cm). Adiposity influenced relative diabetes occurrence across racial/ethnic groups, in that Chinese had a steeper diabetes risk per unit of adiposity. However, the generally low level of adiposity in Chinese led to a relatively low diabetes occurrence.


Bromelain plus peroxidase reduces non-Hodgkin lymphoma progression in invivo via up-regulation of antioxidant enzymes and modulating apoptotic protein expression.
Aim: Pineapple (Ananas comosus (L.) Merr.) is a good source of bromelain (B) and also contain peroxidase. The objective of this study is isoaltion of bromelain plus peroxidase (BP) from the pineapple fruit to evaluate the anticancer activity of BP from the pineapple fruit of Tripura, compared to commercial bromelain against ascitic Dalton's lymphoma cells (DLA) in mice. Methods: By acetone precipitation BP was isolated from the pineapple. Animals bearing DLA, receive B and BP orally for 15 alternative days. Apoptotic proteins are assayed using western blot. Results: BP treated mice showed recover of hemoglobin and WBC count compared to control lymphoma animal. The animal showed significant reduction of body weight due to reduced tunor load and elevated reactive oxygen species (ROS) production, elevated levels of vitamin C and vitamin E and other antioxidants in blood after BP treatment. Histology of liver and kidney also shows restored architecture in BP treated animal compared to only B treated group. BP treatment upregulates the cytochrome C, BAD, and BAX protein and downregulates the Bcl-2 and NF-kβ occuring upon BP treatment in the DLA cells collected from lymphoma animal. This induce the apoptosis of DLA cells in lymphoma animal and reduce the tumor load. Conclusion: The present findings suggest that BP from pineapple improves the survival of the induced lymphoma animal compared to only B which may be used as therapeutic target.


Spontaneous regression of hepatic inflammatory pseudotumor with primary biliary cirrhosis: case report and literature review.
Hepatic inflammatory pseudotumor (IPT) is a rare benign non-neoplastic lesion characterized by proliferating fibrous tissue infiltrated by inflammatory cells. The exact etiology of IPT remains unclear. Although the association of IPT with systemic inflammatory disorders has been well established, a specific relationship with cholangitis is distinctly rare. We report a case of spontaneous regression of hepatic IPT with primary biliary cirrhosis (PBC). To date, only two cases of IPT with PBC have been reported. In our case, however, IPT developed during the course of improvement of cholangitis of PBC induced by effective treatment, differing from two previously reported cases. Our case indicates that the development of IPT does not also relate to the activity of cholangitis and/or hyper gamma-globulinemia, since our case was confirmed radiologically to be free of IPT when biliary enzymes and immunoglobulins were much higher than the corresponding values on admission. Comparison of our case with the two previously reported cases suggests that IPT occurring with PBC does not represent the same disease entity or be a bystander for PBC.


The potential protective effect of monoclonal antibodies to gonococcal outer membrane protein IA.
Hybrid cell lines were derived which produced monoclonal antibodies directed against gonococcal outer membrane protein IA. One antibody, SM101, recognized 24 P.IA-expressing strains out of 25 tested--the rest exhibited relatively less cross-reactivity. Competitive radioimmunoassays revealed that each antibody could effectively inhibit binding of the others, suggesting close proximity of the epitopes recognized. The antibodies were used in assays in vitro to investigate their potential efficacy in protection against gonococcal infection. In a cytotoxicity assay, the antibodies afforded some protection to epithelial cells challenged with gonococci. They were very effective at bactericidal killing in the presence of complement and, in addition, were opsonic for homologous and heterologous strains. The cross-reacting antibody, SM101, was one of the most effective in both assays. The results show that the conserved epitope on P.IA recognized by antibody SM101 is potentially an effective target on the gonococcal surface for immunoprophylaxis.


[Geometrical property of navigation].
There is a tendency that a blind or a blind-folded subject fails to return to a starting point within the range of errors when he or she walks to a place, next turns to right or left, and then comes back to the starting point. We studied this tendency from a non-Euclidean geometrical point of view. In Experiment 1, total of 28 blind-folded subjects walked to construct a square, a regular triangle and a circle. The result showed that the location of the final reaching point was on the fronto-right side of the starting point in the square and triangle conditions and went over the starting point in the circle condition. In Experiment 2, 15 subjects judged visual properties (angles and distances) of a triangle and constructed the triangle by walking. The walking loci were compared with the visual properties. It was found that the walking loci were curved, differing from the visual properties. These results implied that the walking loci agree with the nature of elliptic geometry.


Percutaneous injuries among health care workers. The real value of human immunodeficiency virus testing of 'donor' blood.
A decision analysis was conducted to examine whether health care workers should receive short-term (42 days) zidovudine treatment following percutaneous exposure to blood, as well as to determine the value of testing "donor" (patient's) blood. Three alternative options were analyzed: treat all, treat none, and test. In the treat all option, all health care workers receive short-term zidovudine therapy immediately after exposure; in the treat none option, no one receives zidovudine; and in the test option, donor blood is tested, and if it is human immunodeficiency virus (HIV) positive, zidovudine is given. Baseline variables were obtained from the literature. Each outcome was expressed as a utility; this is a method of quantifying the values that persons place on different health states. The results showed that the test option was preferred. Sensitivity analyses indicated that even if the risk of seroconversion were zero or the effectiveness of zidovudine were zero or the drug were withheld, this option was preferred, thus indicating some value of testing other than merely identifying health care workers who should receive zidovudine. In the baseline analysis, this was derived from the fact that approximately 95% of the health care workers would be reassured by a negative test; ie, only approximately 5% of donors are HIV positive. If the prevalence of HIV seropositivity exceeded 42%, the treat none option was preferred. This was found to be due to the fact that increased numbers of health care workers would be told that they were exposed to HIV-positive blood. The "worrying factor" associated with such an exposure was such that above 42% HIV seropositivity, the treat none option was preferred overall. Thus, the real value of testing donor blood is in identifying those persons (greater than 95%) who could be told that they were exposed to HIV-negative blood, that is, reducing their worrying factor to zero. Because acquired immunodeficiency syndrome is a fatal disease, and given that zidovudine is the only available therapeutic option at present, the drug has an important role to play if its effectiveness is greater than zero.


Incidence, aetiology, and outcome of non-traumatic coma: a population based study.
To determine the incidence, presentation, aetiology, and outcome of non-traumatic coma in children aged between 1 month and 16 years. In this prospective, population based, epidemiological study in the former Northern NHS region of the UK, cases were notified following any hospital admission or community death associated with non-traumatic coma. Coma was defined as a Glasgow Coma Score below 12 for more than six hours. The incidence of non-traumatic coma was 30.8 per 100 000 children under 16 per year (6.0 per 100 000 general population per year). The age specific incidence was notably higher in the first year of life (160 per 100 000 children per year). CNS specific presentations became commoner with increasing age. In infants, nearly two thirds of presentations were with non-specific, systemic signs. Infection was the commonest overall aetiology. Aetiology remained unknown in 14% despite extensive investigation and/or autopsy. Mortality was highly dependent on aetiology, with aetiology specific mortality rates varying from 3% to 84%. With follow up to approximately 12 months, overall series mortality was 46%.


Spinal Versus General Anesthesia for Cesarean Delivery in Pregnant Women With Moyamoya Disease: A Retrospective Observational Study.
Moyamoya disease, a rare chronic cerebrovascular disease with a fragile vascular network at the base of the brain, can cause ischemic or hemorrhagic strokes or seizures. Precise blood pressure control and adequate analgesia are important for patients with moyamoya disease to prevent neurological events such as ischemia and hemorrhage. This study aimed to compare the intraoperative mean arterial pressure of pregnant women with moyamoya disease according to the mode of anesthesia (general anesthesia versus spinal anesthesia) used during cesarean delivery. We retrospectively reviewed the medical records of 87 cesarean deliveries in 74 patients who had been diagnosed with moyamoya disease before cesarean delivery. The primary outcome, intraoperative maximum mean arterial pressure during anesthesia, was compared according to the type of anesthesia administered (general versus spinal anesthesia). Other perioperative hemodynamic data (lowest mean arterial pressure, incidence of hypotension, vasopressor use, and antihypertensive agent use), maternal neurologic symptoms, neonatal outcomes (Apgar scores <7, ventilatory support, and intensive care unit admission), maternal and neonatal length of stay, postoperative pain scores, and rescue analgesic use were assessed as secondary outcomes. While the lowest blood pressure during anesthesia and incidence of hypotension did not differ between the 2 groups, the maximum mean arterial pressure during anesthesia was lower in the spinal anesthesia group than that in the general anesthesia group (104.8 ± 2.5 vs 122.0 ± 4.6; P = .002). Study data did not support the claim that maternal neurologic symptoms differ according to the type of anesthesia used (5.6% vs 9.3%; P = .628); all patients recovered without any sequelae. The postoperative pain scores were lower, and fewer rescue analgesics were used in the spinal anesthesia group than in the general anesthesia group. Other maternal and neonatal outcomes were not different between the 2 groups. Compared with general anesthesia, spinal anesthesia mitigated the maximum arterial blood pressure during cesarean delivery and improved postoperative pain in patients with moyamoya disease.


Suppressing the Intrinsic Photoelectric Response of Organic Semiconductors for Highly-Photostable Organic Transistors.
Suppressing the photoelectric response of organic semiconductors (OSs) is of great significance for improving the operational stability of organic field-effect transistors (OFETs) in light environments, but it is quite challenging because of the great difficulty in precisely modulating exciton dynamics. In this work, photostable OFETs are demonstrated by designing the micro-structure of OSs and introducing an electrical double layer at the OS/polyelectrolyte dielectric interface, in which multiple exciton dynamic processes can be modulated. The generation and dissociation of excitons are depressed due to the small light-absorption area of the microstripe structure and the excellent crystallinity of OSs. At the same time, a highly efficient exciton quenching process is activated by the electrical double layer at the OS/polyelectrolyte dielectric interface. As a result, the OFETs show outstanding tolerance to the light irradiation of up to 306 mW·cm-2 , which far surpasses the solar irradiance value in the atmosphere (≈138 mW·cm-2 ) and achieves the highest photostability ever reported in the literature. The findings promise a general and practicable strategy for the realization of photostable OFETs and organic circuits.


Intracranial saccular aneurysm in a child with only persistent headache.
Headache is one of the common symptoms of intracranial aneursym. A 5-year-old child lately presented to our pediatric emergency department with persistent headache. Brain magnetic resonance imaging revealed a 7×8 mm rounded lesion with slowly heterogeneous low signal in T2 sequence consistent with a partial occluded aneurysm, in the right medial frontal lobe that close to anterior cerebral artery. Intracranial aneurysms are rare in children and they are noncommon without complications as our case.


Power scaling of semiconductor laser pumped Praseodymium-lasers.
We report on efficient lasing of Pr-doped fluoride materials with cw output powers up to 600 mW in the visible spectral range. Praseodymium doped LiYF(4) and LiLuF(4) crystals were pumped either by an intracavity frequency doubled optically pumped semiconductor laser with output powers up to 1.6 W and nearly diffraction limited beam quality or by a multimode GaN-laser diode with an output power of about 370 mW. Furthermore, intracavity frequency doubling of the red Pr-laser radiation to 320 nm reaching output powers of more than 360 mW with a conversion efficiency of 61% and an optical-to-optical efficiency of 22% are presented.


Glucocorticoid regulation of beta-adrenergic receptors in 3T3-L1 preadipocytes.
Treatment of 3T3-L1 preadipocytes (fibroblasts) with 250 nM dexamethasone for 48 hr caused a doubling of total beta-adrenergic receptors and an increase in beta 2-adrenergic receptor subtype proportion from approximately 50% in controls to 85% in treated cells. The responses to epinephrine and norepinephrine in a whole cell cAMP accumulation assay reflected these changes. The effects of dexamethasone on beta-adrenergic receptors were mediated through the glucocorticoid receptor and were time and dose dependent with an EC50 of 2.77 +/- 0.73 nM for an increase in the proportion of beta 2-adrenergic receptors. The rank order of potency of steroids to effect these changes (betamethasone = dexamethasone greater than fludrocortisone greater than hydrocortisone = triamcinolone greater than aldosterone) correlated with their glucocorticoid potency. [3H]Dexamethasone binding to intact cells yielded a KD value of 3.47 +/- 0.38 nM for binding to the glucocorticoid receptor which correlated well with the EC50 for dexamethasone to alter beta-adrenergic receptors. Inhibition of [3H]dexamethasone binding by other steroids confirmed that the ability of steroids to regulate beta-adrenergic receptors correlated with the affinity of each compound for the 3T3-L1 glucocorticoid receptor. Progesterone, which can bind to the glucocorticoid receptor but has only weak agonist activity, competitively inhibited the ability of dexamethasone to alter beta-adrenergic receptors. Protein synthesis, RNA synthesis, and N-linked glycosylation appeared to be necessary for the change in receptor subtype expression and the increase in beta-adrenergic receptor number induced by dexamethasone. The present study suggests that regulation of beta-adrenergic receptor expression in 3T3-L1 preadipocytes by dexamethasone is a glucocorticoid-specific effect which may require gene activation.


[The prospective assessment of the influence of duration of untreated psychosis (DUP) on the course of schizophrenia].
This study is a part of a prospective schizophrenia research project run in Krak6w. The general objective of the project is a long-time observation of people with schizophrenia, starting from the first episode through the years of living with the illness, the assessment of treatment results and predictors. The goal of this study was to investigate whether the level of DUP before the first admission may have a prognostic value in regard to the further course of the illness. Four indicators of treatment results were observed: the number of relapses, the overall time of inpatient hospitalisations, the number of inpatient hospitalisations and the severity of psychopathological symptoms assessed in 3, 7 and 12 years since the first hospitalisation. DUP was estimated during a clinical interview with a patient and his/her family at the index admission. The severity of symptoms was assessed with BPRS-SA, the UCLA version. The increase of the number of relapses in follow-up assessments was more prominent in the group with longer DUP (p < 0.001). The decrease of the results of BPRS (symptom improvement) was more prominent in patients with short DUP. They had significantly lower results compared to patients with long DUP at each assessment except the index hospitalisation (p equaled respectively: 0.449; 0.002; 0.012; 0.034 and 0.014). The decrease of positive symptoms was larger in patients with short DUP - significant in all except the 7-year follow-up (p equaled respectively: 0.230; < 0.001, 0.011; 0.214; <0.001). (1) A relationship was found between the duration of untreated psychosis and the dynamics of general and positive symptoms and the number of relapses. (2) There was no significant relationship between the duration of untreated psychosis and the dynamics of negative symptoms, whereas the relationship between the time and number of re-hospitalisations was on the brink of statistical significance. (3) A replication of some and the lack of confirmation of other long-time results observed by other researchers prompts us to conclude that there still is a need for further studies concerning the duration of untreated psychosis


Short-term Internet search using makes people rely on search engines when facing unknown issues.
The Internet search engines, which have powerful search/sort functions and ease of use features, have become an indispensable tool for many individuals. The current study is to test whether the short-term Internet search training can make people more dependent on it. Thirty-one subjects out of forty subjects completed the search training study which included a pre-test, a six-day's training of Internet search, and a post-test. During the pre- and post- tests, subjects were asked to search online the answers to 40 unusual questions, remember the answers and recall them in the scanner. Un-learned questions were randomly presented at the recalling stage in order to elicited search impulse. Comparing to the pre-test, subjects in the post-test reported higher impulse to use search engines to answer un-learned questions. Consistently, subjects showed higher brain activations in dorsolateral prefrontal cortex and anterior cingulate cortex in the post-test than in the pre-test. In addition, there were significant positive correlations self-reported search impulse and brain responses in the frontal areas. The results suggest that a simple six-day's Internet search training can make people dependent on the search tools when facing unknown issues. People are easily dependent on the Internet search engines.


S-nitrosylation of VASP at cysteine 64 mediates the inflammation-stimulated increase in microvascular permeability.
We tested the hypothesis that platelet-activating factor (PAF) induces S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S-nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of endothelial nitric oxide synthase (eNOS) subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosylation of VASP in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Reconstitution of VASP knockout myocardial endothelial cells with cysteine mutants of VASP demonstrated that S-nitrosylation of cysteine 64 is associated with PAF-induced hyperpermeability. We propose that regulation of VASP contributes to endothelial cell barrier integrity and to the onset of hyperpermeability. S-nitrosylation of VASP inhibits its function in barrier integrity and leads to endothelial monolayer hyperpermeability in response to PAF, a representative proinflammatory agonist.NEW & NOTEWORTHY Here, we demonstrate that S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) on C64 is a mechanism for the onset of platelet-activating factor-induced hyperpermeability. Our results reveal a dual role of VASP in endothelial permeability. In addition to its well-documented function in barrier integrity, we show that S-nitrosylation of VASP contributes to the onset of endothelial permeability.


Health-related quality of life (HRQOL) measures: there are still many unanswered questions about human life.
Health-related quality of life (HRQOL) measures are used to assess the multifaceted impact of disease, and determine the utility and associated disability. In addition, the impact of medical interventions must be assessed by psychometrically robust HRQOL measures based on a comprehensive and dynamic model. To develop such a model, the concepts of life, its quality, domains, essence, and purpose must be properly and clearly understood. The correct understanding of these entities is specifically important for patient-centered medicine and has universal implications for all fields of human endeavor. Therefore, in order to explore questions about life and quality of life adequately, every necessary field of knowledge should be employed. A multilinguistic and etymological appraisal reveals that life is related to medicine, freedom, being, soul,and spirit, all of which must therefore be considered in its conceptualization.


Low-Intensity swimming training after weaning improves glucose and lipid homeostasis in MSG hypothalamic obese mice.
Low-intensity swimming training, started at an early age, was undertaken to observe glycemic control in hypothalamic obese mice produced by neonatal monosodium l-glutamate (MSG) treatment. Although swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, this event was not observed when exercise training is applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Current work verifies whether, besides reducing fat tissue accumulation, low-intensity swimming in MSG-weaned mice also improves glycemic control. Although MSG and control mice swam for 15 min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Retroperitonial fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Mice were also submitted to ipGTT. MSG obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance and insulin resistance. However, the exercise was able to block MSG treatment effects. Higher total cholesterol and triglycerides observed in MSG mice were normalized by exercise after weaning. Exercised MSG animals had higher HDLc than the sedentary group. Data suggest that early exercise training maintains normoglycemia, insulin tissue sensitivity, and normal lipid profile in mice programmed to develop metabolic syndrome.


Menstrual disturbances in the athlete.
Women should be encouraged to exercise. Those who develop menstrual problems should be thoroughly evaluated to detect any serious causes and should be treated to prevent any serious results. The importance of exercise in the lifestyle of female athletes should be respected.


Toward the Automation of Diagnostic Conversation Analysis in Patients with Memory Complaints.
The early diagnosis of dementia is of great clinical and social importance. A recent study using the qualitative methodology of conversation analysis (CA) demonstrated that language and communication problems are evident during interactions between patients and neurologists, and that interactional observations can be used to differentiate between cognitive difficulties due to neurodegenerative disorders (ND) or functional memory disorders (FMD). This study explores whether the differential diagnostic analysis of doctor-patient interactions in a memory clinic can be automated. Verbatim transcripts of conversations between neurologists and patients initially presenting with memory problems to a specialist clinic were produced manually (15 with FMD, and 15 with ND). A range of automatically detectable features focusing on acoustic, lexical, semantic, and visual information contained in the transcripts were defined aiming to replicate the diagnostic qualitative observations. The features were used to train a set of five machine learning classifiers to distinguish between ND and FMD. The mean rate of correct classification between ND and FMD was 93% ranging from 97% by the Perceptron classifier to 90% by the Random Forest classifier.Using only the ten best features, the mean correct classification score increased to 95%. This pilot study provides proof-of-principle that a machine learning approach to analyzing transcripts of interactions between neurologists and patients describing memory problems can distinguish people with neurodegenerative dementia from people with FMD.


A Rare Case of Lambert-Eaton Myasthenia Syndrome Associated with Non-Hodgkin's Lymphoma: A Case Report and Review of the Literature.
Lambert-Eaton myasthenia syndrome (LEMS) is a rare autoimmune disorder characterized by autoantibodies targeting presynaptic neuromuscular junctions. It results in muscle weakness and autonomic dysfunction. LEMS can be idiopathic or associated with neoplastic diseases, often small-cell lung cancer. This case report describes a rare instance of paraneoplastic LEMS in a man with non-Hodgkin lymphoma. A 57-year-old male with non-Hodgkin lymphoma presented with progressive muscle weakness, diminished reflexes, and autonomic symptoms. Diagnosis revealed LEMS with autoantibodies against voltage-gated calcium channels. Immunosuppressive therapy and lymphoma treatment led to significant improvement in his condition. This case highlights the rare occurrence of paraneoplastic LEMS in a patient with non-Hodgkin lymphoma. Recognition and timely management of LEMS alongside lymphoma treatment can lead to significant clinical improvement, emphasizing the need for increased awareness of such complex associations.


Equicrestal and subcrestal dental implants: a histologic and histomorphometric evaluation of nine retrieved human implants.
Stability of peri-implant crestal bone plays a relevant role relative to the presence or absence of interdental papilla. Several factors can contribute to the crestal bone resorption observed around two-piece implants, such as the presence of a microgap at the level of the implant-abutment junction, the type of connection between implant and prosthetic components, the implant positioning relative to the alveolar crest, and the interimplant distance. Subcrestal positioning of dental implants has been proposed to decrease the risk of exposure of the metal of the top of the implant or of the abutment margin, and to get enough space in a vertical dimension to create a harmoniously esthetic emergence profile. The present retrospective histologic study was performed to evaluate dental implants retrieved from human jaws that had been inserted in an equicrestal or subcrestal position. A total of nine implants were evaluated: five of these had been inserted in an equicrestal position, whereas the other four had been positioned subcrestally (1 to 3 mm). In all subcrestally placed implants, preexisting and newly formed bone was found over the implant shoulder. In the equicrestal implants, crestal bone resorption (0.5 to 1.5 mm) was present around all implants. The subcrestal position of the implants resulted in bone located above the implant shoulder.


Adaptation and Feasibility of the interRAI Family Carer Needs Assessment in a Pediatric Setting.
Family carers of children with serious illness contribute many hours of medical care in addition to usual daily care. Assessing the needs and supports of family carers is not routine practice. This study is the first to utilize the interRAI Family Carer Needs Assessment in carers of children, seeking to evaluate and improve its ability to capture their needs. This is a prospective pilot study of family carers of children with serious illness receiving care at a pediatric hospice. Thirty carers completed the self-assessment form. Additional feedback was sought inquiring about the appropriateness of questions and missing information relevant to the pediatric setting. All participants reported the assessment captured important information across multiple domains. Additional questions surrounding extra costs, home and school supports, as well as direct impacts of caregiving activities on pain and relationships were identified as important adaptations. The most common unmet needs in carers and care recipients were episodic relief from caregiving (n=17) and housing adaptation (n=17), respectively. Overall, a comprehensive assessment form is feasible in identifying the diverse needs of family carers of children. Future research should focus on using pediatric specific interRAI tools to guide improvements in policy and practice that can address unmet needs.


A new device in the treatment of hyperhidrosis by iontophoresis.
All participants with a baseline print score of greater than 1 demonstrated reduced sweating for up to six weeks following treatment with the Drionic device. Because of experimental design flaw, similar results were not obtained from those participants producing a baseline sweat print of 1. Therefore, the impression from these results is that, while not completely supported by objective data, it is possible to substantiate the subjective information related by patients in the control of hyperhidrosis.


Greatly Intensified Guest Exchange Strategy for Highly-Efficient Activation of Metal-Organic Frameworks.
The preservation and accessibility of pores are prerequisites to the application of metal-organic frameworks (MOFs). Activation is a key step to eliciting rich features of pores, but it needs a repeated solvent-exchange process which is tedious and time/cost-consuming. Herein, a facile strategy for highly-efficient activation of MOFs utilizing rotating packed bed is proposed. With the tremendous enhancement of molecular mixing and mass transfer in high-gravity and strong-shearing surrounding, nine representative MOFs are completely activated within 2 h without structural change. Compared with conventional process, this activation displays surprising efficiency by accelerating the diffusion of solvents and redissolution of residual reactants in the pores. The complete activation time can be significantly shortened by over 90%. As a proof-of-concept, the methane storage of as-activated UiO-66 is five times that of as-synthesized UiO-66. This strategy provides a potential platform with industrial worth for the activation of MOF materials with ultra-high efficiency and versatility.


A controlled chamber study of effects of exposure to diesel exhaust particles and noise on heart rate variability and endothelial function.
Adverse cardiovascular effects are associated with both diesel exhaust and road traffic noise, but these exposures are hard to disentangle epidemiologically. We used an experimental setup to evaluate the impact of diesel exhaust particles and traffic noise, alone and combined, on intermediary outcomes related to the autonomic nervous system and increased cardiovascular risk. In a controlled chamber 18 healthy adults were exposed to four scenarios in a randomized cross-over fashion. Each exposure scenario consisted of either filtered (clean) air or diesel engine exhaust (particle mass concentrations around 300 µg/m3), and either low (46 dB(A)) or high (75 dB(A)) levels of traffic noise for 3 h at rest. ECG was recorded for 10-min periods before and during each exposure type, and frequency-domain heart rate variability (HRV) computed. Endothelial dysfunction and arterial stiffness were assessed after each exposure using EndoPAT 2000. Compared to control exposure, HRV in the high frequency band decreased during exposure to diesel exhaust, both alone and combined with noise, but not during noise exposure only. These differences were more pronounced in women. We observed no synergistic effects of combined exposure, and no significant differences between exposure scenarios for other HRV indices, endothelial function or arterial stiffness. Three-hour exposure to diesel exhaust, but not noise, was associated with decreased HRV in the high frequency band. This indicates activation of irritant receptor-mediated autonomic reflexes, a possible mechanism for the cardiovascular risks of diesel exposure. There was no effect on endothelial dysfunction or arterial stiffness after exposure.


Distinct maturation of, but not migration between, human monocyte-derived dendritic cells upon ingestion of apoptotic cells of early or late phases.
Cell death via apoptosis is a normal physiological process. Rapid, but silent, removal of apoptotic cells (ACs) plays an essential role in maintaining homeostasis in the immune system. Defective clearance of ACs allows ACs to accumulate and undergo late phase apoptosis, also known as secondary necrosis, which may generate danger signals, leading to inflammation or autoimmunity. In this study we investigate the outcome of dendritic cells (DCs), which are potent APCs, on the interaction with ACs of early or late phase. Immature DCs internalized ACs of both early and late phases with similar efficiency. However, DCs that had taken up ACs of early phase acquired a non-fully mature DC phenotype, expressing low MHC class II complex, costimulatory molecule CD40, and mature DC-restricted marker CD83, and had a low capacity to stimulate allogeneic CD4+ T cell proliferation, whereas DCs that had taken up ACs of late phase acquired a mature DC phenotype with enhanced T cell stimulatory capacity. Ingestion of either early or late ACs induced minimal production of IL-12 and modulated CC chemokine and CCR expression in DCs. In particular, there was down-regulation of CCR5 and up-regulation of CCR7, resulting in switches in responsiveness from inflammatory to lymphoid chemokines. We conclude from these data that after taking up ACs of either early or late phases, DCs acquire the capability of homing to draining lymph nodes, and the distinct maturation between DCs taking up early or late ACs may contribute to DC function in the induction of T cell tolerance or Ag-specific T cell response, respectively.


Cost of long-distance energy transmission by different carriers.
This paper compares the relative cost of long-distance, large-scale energy transmission by electricity, gaseous, and liquid carriers (e-fuels). The results indicate that the cost of electrical transmission per delivered MWh can be up to eight times higher than for hydrogen pipelines, about eleven times higher than for natural gas pipelines, and twenty to fifty times higher than for liquid fuels pipelines. These differences generally hold for shorter distances as well. The higher cost of electrical transmission is primarily because of lower carrying capacity (MW per line) of electrical transmission lines compared to the energy carrying capacity of the pipelines for gaseous and liquid fuels. The differences in the cost of transmission are important but often unrecognized and should be considered as a significant cost component in the analysis of various renewable energy production, distribution, and utilization scenarios.


Effective Calibration of Low-Cost Soil Water Content Sensors.
Soil water content is a key variable for understanding and modelling ecohydrological processes. Low-cost electromagnetic sensors are increasingly being used to characterize the spatio-temporal dynamics of soil water content, despite the reduced accuracy of such sensors as compared to reference electromagnetic soil water content sensing methods such as time domain reflectometry. Here, we present an effective calibration method to improve the measurement accuracy of low-cost soil water content sensors taking the recently developed SMT100 sensor (Truebner GmbH, Neustadt, Germany) as an example. We calibrated the sensor output of more than 700 SMT100 sensors to permittivity using a standard procedure based on five reference media with a known apparent dielectric permittivity (1 < Ka < 34.8). Our results showed that a sensor-specific calibration improved the accuracy of the calibration compared to single "universal" calibration. The associated additional effort in calibrating each sensor individually is relaxed by a dedicated calibration setup that enables the calibration of large numbers of sensors in limited time while minimizing errors in the calibration process.


Effect of cimetidine on hepatic vitamin D metabolism in humans.
Cimetidine inhibits the action of vitamin D-hydroxylase (a hepatic mixed-function oxidase) in the rat. Therefore, the hypothesis was tested that this H2 receptor antagonist would affect vitamin D metabolism in humans. Nine adult patients were treated with 400 mg cimetidine orally twice daily during a period from winter to summer, when days were becoming longer. Serum levels of 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D were monitored before treatment, after 4 weeks of treatment, and 1 month after cessation of treatment. No seasonal increase in the level of 25-hydroxyvitamin D was observed during the period of treatment, but the level rose significantly after withdrawal of the drug. The other hydroxylates of vitamin D were not affected. Levels of albumin, total calcium, phosphorus and alkaline phosphatase remained normal. The data suggest that short-term treatment with cimetidine could potentially perturb vitamin D metabolism in man.


Loss of disialyl Lewis(a), the ligand for lymphocyte inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) associated with increased sialyl Lewis(a) expression on human colon cancers.
Expression of sialyl Lewis(a) is known to be increased in cancers of the digestive organs. The determinant serves as a ligand for E-selectin and mediates hematogenous metastasis of cancers. In contrast, disialyl Lewis(a), which has an extra sialic acid attached at the C6-position of penultimate GlcNAc in sialyl Lewis(a), is expressed preferentially on nonmalignant colonic epithelial cells, and its expression decreases significantly on malignant transformation. Introduction of the gene for an alpha2-->6 sialyl-transferase responsible for disialyl Lewis(a) synthesis to colon cancer cells resulted in a marked increase in disialyl Lewis(a) expression and corresponding decrease in sialyl Lewis(a) expression. This was accompanied by the complete loss of E-selectin binding activity of the cells. In contrast, the transfected cells acquired significant binding activity to sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7)/p75/adhesion inhibitory receptor molecule-1, an inhibitory receptor expressed on lymphoid cells. These results indicate that the transition of carbohydrate determinants from disialyl Lewis(a)-dominant status to sialyl Lewis(a)-dominant status on malignant transformation has a dual functional consequence: the loss of normal cell-cell recognition between mucosal epithelial cells and lymphoid cells on one hand and the gain of E-selectin binding activity on the other. The transcription of a gene encoding the alpha2-->6 sialyltransferase was markedly down-regulated in cancer cells compared with nonmalignant epithelial cells, which is in line with the decreased expression of disialyl Lewis(a) and increased expression of sialyl Lewis(a) in cancers. Treatment of cancer cells with butyrate or 5-azacytidine induced strongly disialyl Lewis(a) expression, suggesting that histone deacetylation and/or DNA methylation may be involved in the silencing of the gene in cancers.


Quercetin-phenylalanine 3d-transition metal-based {Co(II), Ni(II) & Cu(II)} intercalative therapeutic agents: DNA & BSA interaction studies in vitro and cleavage activity.
New Quercetin-phenylalanine metal-based therapeutic agents of the formulation [Qu(Phe)M(II).(H2O)2].NO3 where M(II) = Co(II) and Ni(II) and [Qu(Phe)Cu(II).(H2O)2] were synthesized and their structure was predicted by IR, UV-vis, EPR and ESI-MS spectroscopic techniques. The bio-molecular interaction studies of the Quercetin-phenylalanine complexes, 1-3 with ct-DNA and BSA were performed using a battery of complimentary biophysical techniques. The corroborative results of these experiments revealed strong binding propensity via electrostatic interactions probably through minor grove binding towards ct-DNA, therapeutic target. The binding affinity of Quercetin-phenylalanine complexes 1-3 was quantified by determining binding constants values, Kb, Ksv, and the magnitude of binding propensity followed the order 3 > 1 > 2, implicating the preferential binding of Cu(II) complex 3 with ct-DNA. The cleavage studies were performed with complexes using gel electrophoretic mobility assay. The complexes 1-3 demonstrated efficient cleaving ability by the hydrolytic cleavage pathway involving hydroxyl (OH) radicals. BSA binding profile of Quercetin-phenylalanine metal therapeutics 1-3 was studied in order to understand the drug carrier potential of these compounds and found that complex 3 was capable of binding preferentially with BSA as compared to other complexes.


The phosphorylation state and expression of soybean BiP isoforms are differentially regulated following abiotic stresses.
The mammalian BiP is regulated by phosphorylation, and it is generally accepted that its unmodified form constitutes the biologically active species. In fact, the glycosylation inhibitor tunicamycin induces dephosphorylation of mammalian BiP. The stress-induced phosphorylation state of plant BiP has not been examined. Here, we demonstrated that soybean BiP exists in interconvertible phosphorylated and nonphosphorylated forms, and the equilibrium can be shift to either direction in response to different stimuli. In contrast to tunicamycin treatment, water stress condition stimulated phosphorylation of BiP species in soybean cultured cells and stressed leaves. Despite their phosphorylation state, we demonstrated that BiP isoforms from water-stressed leaves exhibit protein binding activity, suggesting that plant BiP functional regulation may differ from other eukaryotic BiPs. We also compared the induction of the soybean BiP gene family, which consists of at least four members designated soyBiPA, soyBiPB, soyBiPC, and soyBiPD, by tunicamycin and osmotic stress. Although all soybean BiP genes were induced by tunicamycin, just the soyBiPA RNA was up-regulated by osmotic stress. In addition, these stresses promoted BiP induction with different kinetics and acted synergistically to increase BiP accumulation. These results suggest that the soybean BiP gene family is differentially regulated by abiotic stresses through distinct signaling pathways.


MiR-25 promotes gastric cancer cells growth and motility by targeting RECK.
Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. Recently, accumulating evidence suggests that microRNAs (miRNAs) play prominent roles in tumorigenesis and metastasis. Here, we confirmed that miR-25 was significantly increased in human GC tissues and cell lines. Forced expression of miR-25 remarkably enhanced cell proliferation, migration, and invasion in GC cells, whereas inhibition of miR-25 by inhibitor caused significant suppression of proliferation and significant increase of apoptosis. Moreover, inhibition of miR-25 significantly decreased migration and invasion of GC cells. Finally, reversion-inducing-cysteine-rich protein with kazal motifs (RECK) was found to be a target of miR-25. Overexpression of RECK could significantly reverse the oncogenic effect of miR-25. Taken together, miR-25 might promote GC cells growth and motility partially by targeting RECK.


Osteomyelitis treated with gentamicin-PMMA beads: 100 patients followed for 1-12 years.
We treated 100 patients having osteomyelitis with debridement and gentamicin-PMMA beads and followed them for 5 (1-12) years. 66 of the infections were chronic, in 18 cases combined with arthritis and in 3 cases with pseudarthrosis. They underwent 117 "treatment periods", consisting of one or more operations (total 152), in most cases with an interval of 2 weeks. No systemic antibiotics were necessary besides the local antibiotic treatment in 52 of the treatment periods. Healing was achieved in 92 patients, in 78 after a single treatment period which included 1-5 operations, in 14 after two or three treatment periods. Healing was more difficult to achieve when the infection was chronic, especially with a duration of more than 6 years or when caused by elective surgery. Local antibiotic treatment with gentamicin PMMA beads has the advantage that the wound can be closed primarily and that a higher local antibiotic concentration in the tissues can be achieved, often making systemic antibiotic treatment unnecessary.


The use of long-acting drugs in the treatment of rheumatoid arthritis.
Experience to date strongly indicates that long-acting drugs currently used in treatment of rheumatoid arthritis are very potent antiinflammatory agents which act in most cases by completely unknown mechanisms. All of them have built in but recognizable toxicity which can usually be prevented by appropriate monitoring. Although most of them offer relatively short term (up to 3 years) benefits, with the probable exception of methotrexate, nonetheless they can offer for a period of time improved function and relief of pain for many individuals. Thus, even though they do not dramatically affect the long-range outcome of the disease, they continue to offer useful benefit for patients with rheumatoid arthritis who are not responding to conservative therapy. Some of the long-acting agents are only slightly more toxic than the widely nonsteroidal antiinflammatory drugs which do have a definite risk of serious upper gastrointestinal bleeding. Currently the use of combinations as well as the continued introduction of new drugs in this class, offer hope that greater benefit than we can currently provide is within reach over the next few years.


The Risk of Oral Cancer among Different Categories of Exposure to Tobacco Smoking in Sri Lanka
Background: The global incidence of oral squamous cell carcinoma (OSCC) is on the rise with no improvement seen in survival rates. Tobacco consumption varies depending on geographic location, ethnicity and culture. The present case-controlled study aimed to determine the relative risk of OSCC for different tobacco consumption patterns in a selected Sri Lankan population. Methods: One hundred and five patients with histopathologically confirmed OSCC attending the National Cancer Institute (Apeksha Hospital) of Sri Lanka and 210 age and gender-matched controls from the community responded to an interviewer-administered questionnaire regarding their smoking and betel-quid chewing (with/ without smokeless tobacco) habits were included in the study. The odds ratios (OR) and 95% confidence intervals (CI) were calculated. p<0.05 was considered as statistically significant. Results: The overall risk of OSCC increased 2.93-fold for smokers. Those smoking two packets of cigarettes or more per day (OR=5.56; 95% CI-2.822- 10.984; p=0.000) had more than double the risk of OSCC than those smoking 1-2 packets per day. Smoking for more than 20 years had a 3.4-fold risk of OSCC. Consumption of betel quid containing tobacco (smokeless tobacco) had a 4.26-fold higher risk for OSCC (OR=4.26; 95% CI-2.21-8.21; p=0.000), and the risk increased when all four ingredients (betel leaf, slaked lime, areca nut, and tobacco) were consumed together (OR=4.26; 95% CI-2.34-7.74; p=0.000). The combined effect from concurrent smoking and betel chewing emerged as the highest risk for OSCC (OR=15.34) which significantly exceeded the risks evident for the two habits practised in isolation from each other. Conclusions: Use of smokeless tobacco, consumption of all four ingredients together, duration of smoking, the number of cigarettes smoked per day and combined consumption of betel quid and smoking are significant risk factors in the development of OSCC among Sri Lankans.


Phosphoglycerate Kinases Are Co-Regulated to Adjust Metabolism and to Optimize Growth.
In plants, phosphoglycerate kinase (PGK) converts 1,3-bisphosphoglycerate into 3-phosphoglycerate in glycolysis but also participates in the reverse reaction in gluconeogenesis and the Calvin-Benson cycle. In the databases, we found three genes that encode putative PGKs. Arabidopsis (Arabidopsis thaliana) PGK1 was localized exclusively in the chloroplasts of photosynthetic tissues, while PGK2 was expressed in the chloroplast/plastid of photosynthetic and nonphotosynthetic cells. PGK3 was expressed ubiquitously in the cytosol of all studied cell types. Measurements of carbohydrate content and photosynthetic activities in PGK mutants and silenced lines corroborated that PGK1 was the photosynthetic isoform, while PGK2 and PGK3 were the plastidial and cytosolic glycolytic isoforms, respectively. The pgk1.1 knockdown mutant displayed reduced growth, lower photosynthetic capacity, and starch content. The pgk3.2 knockout mutant was characterized by reduced growth but higher starch levels than the wild type. The pgk1.1 pgk3.2 double mutant was bigger than pgk3.2 and displayed an intermediate phenotype between the two single mutants in all measured biochemical and physiological parameters. Expression studies in PGK mutants showed that PGK1 and PGK3 were down-regulated in pgk3.2 and pgk1.1, respectively. These results indicate that the down-regulation of photosynthetic activity could be a plant strategy when glycolysis is impaired to achieve metabolic adjustment and optimize growth. The double mutants of PGK3 and the triose-phosphate transporter (pgk3.2 tpt3) displayed a drastic growth phenotype, but they were viable. This implies that other enzymes or nonspecific chloroplast transporters could provide 3-phosphoglycerate to the cytosol. Our results highlight both the complexity and the plasticity of the plant primary metabolic network.


Characterized polysaccharides from black soybean induce granulocyte colony-stimulated factor gene expression in a phosphoinositide 3-kinase-dependent manner.
Black soybean (Glycine max L. merr.) is an edible Chinese medicine for nourishment spleen. In the present study, effects of characterized polysaccharides from black soybean (PGM) on granulocyte colony-stimulated factor (G-CSF) production in human peripheral blood mononuclear cells (PBMC) were determined and their action mechanisms were examined. The results indicated that PGM concentration-dependently enhanced G-CSF production in PBMC through modulation of mRNA expression. Data from Western blotting showed that PGM significantly induced the extracellular signal-regulated protein kinase (ERK) activation in PBMC. The nuclear factor (NF)-κB activation in PBMC was increased with PGM by modulation of IκB degradation and PKC θ activation. The levels of G-CSF mRNA in PGM-treated PBMC could be reduced by ERK inhibitor U0126 and NF-κB inhibitor pyrrolidine dithiocarbamate, respectively. Furthermore, the data showed that PGM stimulated phosphoinositide 3-kinase (PI3K)-regulated Akt phosphorylation. The PI3K inhibitor, Ly294002, blocked ERK, NF-κB, and PKC θ activation and G-CSF mRNA expression in PBMC induced by PGM. Thus, we first proved that the enhancement mechanisms of PGM on G-CSF production, appeared to be mediated, at least in part, through activation of PI3K, ERK, PKC θ, and NF-κB signaling pathways in PBMC. We suggest that PGM from black soybean is a potential G-CSF stimulator.


Novel astroviruses in insectivorous bats.
Bats are increasingly recognized to harbor a wide range of viruses, and in most instances these viruses appear to establish long-term persistence in these animals. They are the reservoir of a number of human zoonotic diseases including Nipah, Ebola, and severe acute respiratory syndrome. We report the identification of novel groups of astroviruses in apparently healthy insectivorous bats found in Hong Kong, in particular, bats belonging to the genera Miniopterus and Myotis. Astroviruses are important causes of diarrhea in many animal species, including humans. Many of the bat astroviruses form distinct phylogenetic clusters in the genus Mamastrovirus within the family Astroviridae. Virus detection rates of 36% to 100% and 50% to 70% were found in Miniopterus magnater and Miniopterus pusillus bats, respectively, captured within a single bat habitat during four consecutive visits spanning 1 year. There was high genetic diversity of viruses in bats found within this single habitat. Some bat astroviruses may be phylogenetically related to human astroviruses, and further studies with a wider range of bat species in different geographic locations are warranted. These findings are likely to provide new insights into the ecology and evolution of astroviruses and reinforce the role of bats as a reservoir of viruses with potential to pose a zoonotic threat to human health.


Environmental regulation of fimbrial gene expression in Porphyromonas gingivalis.
Porphyromonas gingivalis fimbriae are an important virulence factor involved in attachment and invasion. Fimbrillin, encoded by the fimA gene, is the major subunit protein of the fimbriae. To elucidate the influence of environmental signals on the expression of the fimA gene, a strain of P. gingivalis (designated PLE) containing a chromosomal transcriptional fusion between a promoterless lacZ gene and the fimA promoter region was constructed. Promoter activity was assessed by measurement of beta-galactosidase activity of PLE. An 11-fold increase in activity of fimA promoter was found as growth temperature declined from 39 to 34 degrees C. Promoter activity decreased by approximately 50% in response to hemin limitation and upon culture on solid medium. In addition, the presence of serum or saliva in the growth medium decreased fimA promoter activity by similar amounts. A correlation between fimA promoter activity and phenotypic properties dependent upon fimbriae was established. P. gingivalis grown at 34 degrees C, compared to 39 degrees C, showed an increased ability to adhere to Streptococcus gordonii and to invade primary cultures of gingival epithelial cells. These studies indicate that expression of the P. gingivalis fimA gene is regulated at the transcriptional level in response to several environmental conditions and that altered fimA expression can also modulate the adherence and invasion abilities of P. gingivalis.


Nickel-Catalyzed Stereoselective Coupling Reactions of Benzylic and Alkyl Alcohol Derivatives.
ConspectusNickel-catalyzed reactions of alkyl alcohol derivatives leverage the high prevalence of hydroxyl groups in natural products, medicinal agents, and synthetic intermediates to provide access to C(sp3)-rich frameworks. This Account describes our laboratory's development of stereospecific and stereoconvergent C-C bond forming reactions employing C(sp3)-O and C(sp3)-N electrophiles. In the context of development of new transformations, we also define fundamental characteristics of the nickel catalysts.Part I details the nickel-catalyzed cross-coupling reactions developed by our group which hinges on stereospecific formation of stable π-benzyl intermediates. Acyclic and cyclic ethers, esters, carbamates, lactones, and sulfonamides undergo Kumada-, Suzuki-, and Negishi-type coupling reactions to produce enantioenriched products with high fidelity of stereochemical information. We describe extension to include ring-opening reactions of saturated heterocycles to afford acyclic 1,3-fragments in high diastereomeric ratios. We also describe our advances in stereospecific nickel-catalyzed cross-electrophile coupling reactions. Tethered C-O and C-X electrophiles proved fruitful for construction of a variety of carbocyclic frameworks. We report an intramolecular cross-electrophile coupling of benzylic pivalates with aryl bromides for the synthesis of indanes and tetralins. We found that 4-halotetrahydropyrans and 4-halopiperidines readily undergo stereospecific ring contraction to afford substituted cyclopropanes. Mechanistic investigations are consistent with closed-shell intermediates, a Ni(0)/Ni(II) cycle, and an intramolecular SN2-type reaction of a key organonickel intermediate to form the cyclopropane. Building toward more complex cascade reactions, we have demonstrated that 2-alkynyl piperidines incorporate MeMgI in a dicarbofunctionalization of the alkyne to afford highly substituted vinyl cyclopropanes.In Part II we present our development of stereoconvergent reactions of alkyl alcohol derivatives. In order to expand the utility of the intramolecular XEC reaction, we sought to employ unactivated alkyl electrophiles. Specifically, alkyl dimesylates engage in intramolecular XEC reactions to form alkyl cyclopropanes. In contrast to our previous work, these reactions proceed through open-shell intermediates and favor stereoconvergent formation of the trans-cyclopropane. Enantioselective aldol reactions can be employed in syntheses of 1,3-diols which furnish enantioenriched cyclopropanes in high ee. Experimental and computational evidence reveals that MeMgI mediates formation of alkyl iodides in situ. The coupling reaction initiates with halogen atom abstraction at the secondary alkyl iodide. The alkyl Ni(II) complex then proceeds through a stereospecific SN2-type ring closure to form cyclopropane. In an effort to increase functional group compatibility in the synthesis of cyclopropanes from alkyl dimesylates we developed a zinc-mediated reaction of 1,3-dimesylates prepared from medicinal analogues. In challenging nickel-catalyzed intramolecular cross-electrophile coupling we were also able to show that vicinal carbocycles can be prepared under similar conditions, affording vicinal cyclopentyl-cyclopropyl motifs in high yield.In Part III we discuss our recent findings on the role of ligand identity in catalyst selectivity for stereospecific vs stereoablative mechanisms for oxidative addition. We demonstrate multivariable control of mechanism, where the choice of substrate and ligand work together to promote open- or closed-shell intermediates. In divergent reactions of 4-halotetrahydropyrans we observe distinct ligand preference for reactions at the C(sp3)-O center or the C(sp3)-Cl center. These findings are the source of continued investigations in our laboratory.


Meaningful outcome measures in cardiac surgery.
The most common cardiac surgical procedures are coronary artery bypass graft surgery and aortic or mitral valve repair or replacement. Underlying conditions include coronary artery disease and heart failure, manifesting as exertional angina, dyspnea, and poor exercise tolerance. The major goals of surgery are to alleviate symptoms and improve patient survival. These, therefore, should inform the choice of primary outcome measures in clinical studies enrolling patients undergoing cardiac surgery. Studies focusing on surrogate outcome measures are relied on all too often. Many are of questionable significance and often have no convincing relationship with patient outcome. Traditional "hard endpoint" outcome measures include serious complications and death with the former including myocardial infarction (MI) and stroke. Such serious adverse outcomes are commonly collected in registries, but because they occur infrequently, they need to be large to reliably detect true associations and treatment effects. For this reason, some investigators combine several outcomes into a single composite endpoint. Cardiovascular trials commonly use major adverse cardiac events (MACEs) as a composite primary endpoint. However, there is no standard definition for MACE. Most include MI, stroke, and death; others include rehospitalization for heart failure, revascularization, cardiac arrest, or bleeding complications. An influential trial in noncardiac surgery found that perioperative beta-blockers reduced the risk of MI but increased the risk of stroke and death. Such conflicting findings challenge the veracity of such composite endpoints and raise a far more important question: which of these endpoints, or even others that were unmeasured, are most important to a patient recovering from surgery? Given the primary aims of cardiac surgery are to relieve symptoms and improve good quality survival, it is disability-free survival that is the ultimate outcome measure. The question then becomes: what is disability and how should it be quantified after cardiac surgery?


Is Induced Sputum A Useful Noninvasive Tool in the Diagnosis of Pulmonary Sarcoidosis?
In patients with pulmonary sarcoidosis, the provocation of sputum expectoration through the inhalation of hypertonic saline has been investigated as an alternative diagnostic tool for invasive procedures. We aimed to assess the diagnostic value of induced sputum (IS) by observing its cell distribution in patients with a confirmed histopathological diagnosis of sarcoidosis. In this prospective, cross-sectional study, we compared the IS results of 20 patients with a histopathologically confirmed pulmonary sarcoidosis diagnosis and 24 healthy volunteers. The percentages of macrophages, lymphocytes, neutrophils, and eosinophils in IS and the CD4/CD8 ratio were compared. The percentage of lymphocytes in IS was significantly higher in the pulmonary sarcoidosis patients compared to the control group (41.6% vs 8.9%, p<0.001). There were no significant differences in the other IS cell percentages and CD4+/CD8+ ratio between the groups. Sputum induction was well tolerated. Sputum induced by the inhalation of hypertonic saline is a safe, inexpensive, less invasive, and easily repeated method and can be a valuable alternative to other invasive methods in the diagnosis of pulmonary sarcoidosis.


[Not Available].
R. Mssrouri, S. Benamr, A. Essadel, J. Mdaghri, El H. Mohammadine, M.-K. Lahlou, A. Taghy, A. Belmahi, B. Chad Objective: To evaluate the incidence of thyroid carcinoma in patients operated on for Graves' disease, to identify criteria which may predict malignancy, and to develop a practical approach to determine the extensiveness of thyroidectomy. Retrospective study of all patients who underwent thyroidectomy for Graves' disease between 1995 and 2005. 547 patients underwent subtotal thyroidectomy for Graves' disease during this period. Post-operative pathology examination revealed six cases of thyroid cancer (1.1%). All six cases had differentiated thyroid carcinoma (papillary carcinoma in 3 cases, follicular carcinoma in 2 cases and papillo-follicular carcinoma in 1 case). The indication for initial thyroidectomy was a palpable thyroid nodule in 3 cases (50%), failure of medical treatment for Grave's disease in 2 cases (33%), and signs of goiter compression in 1 case (17%). Five patients underwent re-operative total thyroidectomy. This study shows that while malignancy in Grave's disease is uncommon, the presence of thyroid nodule(s) in patients with Grave's disease may be considered as an indication for radical surgery. The most adequate radical surgery in this situation is to perform a total thyroidectomy.