National Institutes of Health consensus statement. Health implications of smokeless tobacco use. NIH Consensus Development Panel.
National data indicate that at least 10 million persons have used smokeless tobacco within the past year. The human evidence that use of snuff causes cancer of the mouth is strong. Smokeless tobacco use increases the frequency of localized gum recession and leukoplakia where the snuff is usually placed. The presence of lead in smokeless tobacco may pose a special risk for the developing fetus. Use of smokeless tobacco releases nicotine into the bloodstream and produces blood levels of nicotine comparable to those produced by smoking tobacco. The primary behavioral consequence of regular use of smokeless tobacco is long-term nicotine dependence and its associated health risks.


Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction.
Left ventricular (LV) dysfunction caused by myocardial infarction (MI) is accompanied by endothelial dysfunction, most notably a loss of nitric oxide (NO) availability. We tested the hypothesis that endothelial dysfunction contributes to impaired tissue perfusion during increased metabolic demands as produced by exercise, and we determined the contribution of NO to regulation of regional systemic, pulmonary, and coronary vasomotor tone in exercising swine with LV dysfunction produced by a 2- to 3-wk-old MI. LV dysfunction resulted in blunted systemic and coronary vasodilator responses to ATP, whereas the responses to nitroprusside were maintained. Exercise resulted in blunted systemic and pulmonary vasodilator responses in MI that resembled the vasodilator responses in normal (N) swine following blockade of NO synthase with N(omega)-nitro-L-arginine (L-NNA, 20 mg/kg iv). However, L-NNA resulted in similar decreases in systemic (43 +/- 3% in N swine and 49 +/- 4% in MI swine), pulmonary (45 +/- 5% in N swine and 49 +/- 4% in MI swine), and coronary (28 +/- 4% in N and 35 +/- 3% in MI) vascular conductances in N and MI swine under resting conditions; similar effects were observed during treadmill exercise. Selective inhibition of inducible NO synthase with aminoguanidine (20 mg/kg iv) had no effect on vascular tone in MI. These findings indicate that while agonist-induced vasodilation is already blunted early after myocardial infarction, the contribution of endothelial NO synthase-derived NO to regulation of vascular tone under basal conditions and during exercise is maintained.


Knowing Groundlessness: An Enactive Approach to a Shift From Cognition to Non-Dual Awareness.
The enactive approach has become an influential paradigm in cognitive science. One of its most important claims is that cognition is sense-making: to cognize is to enact a world of meaning. Thus, a world is not pregiven but enacted through sense-making. Most importantly, sense-making is not a fixed process or thing. It does not have substantial existence. Instead, it is groundless: it springs from a dynamic of relations, without substantial ground. Thereby, as all cognition is groundless, this groundlessness is considered the central underlying principle of cognition. This article takes that key concept of the enactive approach and argues that it is not only a theoretical statement. Rather, groundlessness is directly accessible in lived experience. The two guiding questions of this article concern that lived experience of groundlessness: (1) What is it to know groundlessness? (2) How can one know groundlessness? Accordingly, it elaborates (1) how this knowing of groundlessness fits into the theoretical framework of the enactive approach. Also, it describes (2) how it can be directly experienced when certain requirements are met. In an additional reflexive analysis, the context-dependency and observer-relativity of those statements themselves is highlighted. Through those steps, this article exhibits the importance of knowing groundlessness for a cognitive science discourse: this underlying groundlessness is not only the "ground" of cognition, but it also can be investigated empirically through lived experience. However, it requires a methodology that is radically different from classical cognitive science. This article ends with envisioning a future praxis of cognitive science which enables researchers to investigate not only theoretically but empirically the "foundationless foundation" of cognition: groundlessness.


Follow your nose - Traveling the world of odorants in new cars.
Volatile organic compounds of the vehicle interior are well investigated, but only limited information is available on the odorants of the passenger cabin. To close this gap, we aimed at specifically elucidating the odor, as a general proof of principle, of two new cars with different seat upholstery in a controlled environment using a targeted odorant analysis. In a first step, odor profiles were evaluated by a descriptive sensory analysis. Then, potent odorants of the passenger cabins were characterized by gas chromatography-olfactometry and ranked according to their odor potency via odor extract dilution analysis. Using this approach, 41 potent odorants were detected, and 39 odorants were successfully identified by two-dimensional gas chromatography-mass spectrometry/olfactometry. In a third step, important odorants of the vehicle interior were quantified by means of internal standard addition. The most dominant odorants could be assigned to several specific substance classes comprising esters, saturated and unsaturated aldehydes, unsaturated ketones, rose ketones, phenolic and benzene derivatives, and pyrazines, occurring in a concentration range between 0.05 and 219 ng/L in air. Of these potent odorants, the aldehydes 2-butylhept-2-enal, 2-propyloct-2-enal, and (Z)-2-butyloct-2-enal are reported here for the first time as odorants in the environment of a passenger cabin.


Nanomaterial Production from Metallic Vapor Bubble Collapse in Liquid Nitrogen.
Nanomaterials with unique structural and properties can be synthesized by rapid transition of the thermodynamic state. One promising method is through electrical explosion, which possesses ultrafast heating/quenching rates (dT/dt~109 K/s) of the exploding conductor. In this study, experiments were performed with fine metallic wire exploding in liquid nitrogen (liq N2, 77 K) under different applied voltages. For the first time in the literature, the physical image of the electrical explosion dynamics in liq N2 is depicted using electro-physical diagnostics and spatial-temporal-resolved photography. Specifically, the pulsation and collapse processes of the vapor bubble (explosion products) have been carefully observed and analyzed. As a comparison, an underwater electrical explosion was also performed. The experimental results suggest that the vapor bubble behavior in liq N2 differs from that in water, especially in the collapse phase, characterized by secondary small-scale bubbles in liq N2, but multiple bubble pulses in water; correspondingly, the products' characteristics are discrepant.


Co9 S8 -Catalyzed Growth of Thin-Walled Graphite Microtubes for Robust, Efficient Overall Water Splitting.
Co9 S8 crystals can catalyze the growth of thin-walled graphite microtubes (GMTs) through a catalytic chemical vapor deposition (CCVD) process using thiourea as the precursor. The growth of GMTs follows a tip-growth mechanism with tube diameters up to a few micrometer. The hollow interiors of the GMTs are filled with carbon nanotubes and wrinkled graphene layers, which form a unique nanotube/graphene-in-microtube structure. As-formed GMTs are N,S-codoped with lots of Co9 S8 nanoparticles encapsulated in their inner walls. These GMTs are room-temperature ferromagnets and can be loaded on Ni foams to work as binder-free electrocatalysts with low overpotential (310 mV at 50 mA cm-2 for the oxygen evolution reaction (OER) and 284 mV at 50 mA cm-2 for the hydrogen evolution reaction (HER)) and long-term durability (continuous work for 120 h without loss in performance). Our research proves that metal sulfides can catalyze the growth of graphite microtubes and as-formed GMTs may potentially be used as functional building blocks to construct new kinds of electrochemical devices for various energy-related applications.


Raman-pumped Fourier-domain mode-locked laser: analysis of operation and application for optical coherence tomography.
We demonstrate a Raman-pumped Fourier-domain mode-locked (FDML) fiber laser and optical coherence tomography imaging with this source. The wavelength sweep range of only 30 nm centered around 1550 nm results in limited axial resolution, hence a nonbiological sample is imaged. An output power of 1.9 mW was achieved at a sweep rate of 66 kHz and a maximum ranging depth of ~2.5 cm. Roll-off characteristics are found to be similar to FDML lasers with semiconductor optical amplifiers as gain media. The application of Raman gain also enables unperturbed cavity ring-down experiments in FDML lasers for the first time, providing direct access to the photon lifetime in the laser cavity. Good agreement with nonswept cw operation is proof of the stationary operation of FDML lasers.


Alcohol dependence in adult children of alcoholics: longitudinal evidence of early risk.
This study investigates familial alcoholism effects and the comparative probability of risk for alcohol dependence in adult children of alcoholics (ACAs) with a control group of non-ACAs. A cohort of 12,686 young adults from the National Longitudinal Survey of Youth (NLSY) is examined over a five-year period and conventional and lineal intergenerational models of alcoholism transmission are assessed. The results of multivariate logistic regression analyses indicate that the risk is relatively greater for male ACAs; sons of alcoholics drink significantly more heavily, experience problems earlier, and develop alcohol dependence more extensively than female ACAs or non-ACAs of either gender. The extent of dependence found in subjects with a lineal history of alcoholism on the father's side of the family, as well as heavy drinking, cigarette smoking and drinking onset in adolescence should be considered as critical predisposing factors of high risk for dependence at later ages. These observations corroborate clinical studies and support a growing body of biopsychosocial research literature.


Surgical treatment of small hepatocellular carcinomas in cirrhosis.
Over the last five years a policy of systematic screening for small hepatocellular carcinomas (HCC) in patients at risk has led to an increasing number of resections in patients with cirrhosis. Remarkable progress in the surgery of HCC in cirrhosis has been accomplished through: (a) a better understanding of the surgical anatomy of the liver, (b) the definition of new types of liver resection aimed at reducing the amount of parenchyma removed while still being oncologically satisfactory, (c) the reduction of intraoperative blood loss by various techniques of clamping afferent and efferent vessels, (d) the systematic use of intraoperative ultrasonography, and (e) the prevention of postoperative variceal bleeding and the formation of ascites. Results of resection of small HCC in cirrhosis have been quite impressive in Japanese series, with a low operative mortality and above 50% three-year survivals. Results in the West have been somewhat less good. Differences in the pathology of these tumours and particularly in the rate of encapsulation could account for these differences. Clearly, surgical resection has become an established treatment for small HCC in cirrhosis. More information is needed on the results of surgery in operated patients and this should be compared with the natural history of small HCC in cirrhosis in order to better define the patients who will most benefit from these operations and which tests performed at which intervals, are most reliable in screening patients at risk.


Unified (3 + 1)-dimensional superspace description of the 2212-type stair-like [Bi2Sr3Fe2O9]m[Bi4Sr6Fe2O16] family of compounds.
The (3 + 1)-dimensional superspace approach is applied to describe and refine a series of sheared compounds related to layered high T(c) superconducting oxides. Two commensurate members (m = 4, 5) of the 2212 stair-like [Bi(2)Sr(3)Fe(2)O(9)](m)[Bi(4)Sr(6)Fe(2)O(16)] family of compounds, previously studied using single-crystal diffraction data, are analyzed. A common average unit cell has been identified and a composition-dependent modulation wavevector is proposed. The model is built using only three independent atomic domains, one for the metal atoms and two for the O atoms. The three Sr, Bi and Fe species are described using close-connected crenel-like functions forming a continuous atomic domain along the internal space. The two oxygen domains are represented by crenel functions and the displacive modulation functions are built up by Legendre polynomials recently implemented in the program JANA2006. Surprisingly, the results of the refinements show a striking similarity of the displacive modulations for the two compounds analyzed, indicating that a unique model can be used to describe the correlations between the atomic displacements of the 2212 stair-like series. This final model is then applied to predict the structure of new members of the family.


Economic Impact of Changes in Neonatal Intensive Care Unit Ventilation Strategies with the Advent of New Noninvasive Ventilation Techniques: A Review and Proposed Assessment Framework for High Flow Therapy as a Routine Respiratory Support Paradigm.
Background: High flow therapy (HFT) has been demonstrated to be a safe and effective noninvasive respiratory support technique for the treatment of pre-term infants in neonatal intensive care. Objectives: Our objective was to develop a quantitative framework based on available evidence to estimate the economic impact of adoption of a HFT respiratory support strategy compared to current standard of care. Methods: Model parameters were derived from a recent study comparing respiratory modality utilization between five US-based neonatal intensive care units (NICUs) adopting a HFT strategy and a larger pool of NICUs in the Vermont-Oxford Network (VON), and from single center experience. We computed the total cost difference between the respiratory support strategies based on published cost data. Parameter uncertainty was tested in sensitivity analyses. Results: The constructed model projected expected cost savings of $2,317 for the HFT strategy for the base case. Results were sensitive to length of HFT use, length of CMV, cost of HFT, and length of nCPAP support. Conclusions: Adoption of a HFT strategy appears to be associated with meaningful savings in total NICU episode of care costs, primarily because of reductions in the time of conventional mechanical ventilation. Further research is warranted to substantiate these findings.


Pharmacokinetics of Budesonide Administered with Surfactant in Premature Lambs: Implications for Neonatal Clinical Trials.
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of premature human infants, which may persist through adulthood. Airway inflammation has been firmly established in the pathogenesis of BPD. Previous studies to reduce airway inflammation with high-dose dexamethasone demonstrated adverse neurological outcomes, despite lower incidences of BPD. Instillation of budesonide and surfactant can facilitate early extubation and reduce the incidence of BPD and death among very low birth weight infants. However, the pharmacokinetics of budesonide and its distribution into the lung and brain are unknown. Therefore, 5 premature lambs were administered 0.25 mg/kg budesonide, with surfactant as the vehicle. Plasma and tissue samples were taken from the lambs for measurement of budesonide, 16α- hydroxy prednisolone, and budesonide palmitate using LC/MS/MS. Peak plasma budesonide concentrations were inversely correlated with the oxygenation index (correlation coefficient of -0.75). plasma budesonide concentrations were extremely low (~10% of expected) for two lambs that had high oxygenation indices and were excluded from further analyses. For the remaining 5 premature lambs, a non-compartmental analysis demonstrated an AUCinf of 148.77 ± 28.16 h*μg/L, half-life of 4.76 ± 1.79 h, and Cmax of 46.17 ± 17.71 µg/L. Using population pharmacokinetic methods, a onecompartment model with exponential residual error and first-order absorption adequately described the data. The apparent clearance and apparent volume of distribution of budesonide were estimated at 6.29 L/h (1.99 L/h/kg) and 29.1 L (9.2 L/kg), respectively. Budesonide and budesonide palmitate, but not 16α-hydroxy prednisolone, were detected in lung tissue. In this study, budesonide and its metabolites were not detected in the brain, which suggests that intratracheal instillation suggests that after local pulmonary deposition, there is no evidence of budesonide accumulation in the central nervous system. Overall, these results show that peak plasma budesonide concentrations are inversely correlated with the oxygenation index and that lung-specific delivery of budesonide avoids accumulation of budesonide in the brain.


Ultrasonography and ultrasound-guided fine-needle aspiration biopsy can predict a heavy nodal metastatic burden in early-stage breast cancer.
This study aimed to predict a heavy nodal burden (≥3 metastatic axillary lymph nodes [LNs]) using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) in patients with early-stage breast cancer. We retrospectively reviewed the medical records of 403 women (404 cancers) who underwent US-guided FNAB for axillary LN staging from January 2006 to December 2015. US findings and US-guided FNAB results were reviewed and compared using pathology results as the reference. Diagnostic performance was analyzed, and clinicopathological and radiological findings were compared between patients with <3 metastatic LNs and ≥3 metastatic LNs. The final pathology results revealed that 20.5% of cancers had heavy nodal metastases. US-guided FNAB showed significantly higher sensitivity (79.0% vs. 63.0%, P=0.009) and specificity (84.8% vs. 79.3%, P=0.036) in predicting heavy nodal metastases than did US. The presence of a larger number of suspicious LNs (two or more) on axillary US and positive FNAB results were significantly correlated with a heavy nodal burden in the multivariate analysis. The odds ratios were 4.20 (95% confidence interval [CI], 1.90 to 9.39) for two suspicious LNs, 9.40 (95% CI, 2.99 to 29.54) for three or more suspicious LNs, and 14.22 (95% CI, 6.78 to 29.82) for positive FNAB results. The number of suspicious LNs detected on axillary US and FNAB results can help predict a heavy axillary nodal burden in patients with early-stage breast cancer.


BENEFITS OF MULTIPLE MATES IN THE CRICKET GRYLLUS BIMACULATUS.
Despite the importance of polyandry for sexual selection, the reasons why females frequently mate with several males remain poorly understood. A number of genetic benefits have been proposed, based on the idea that by taking multiple mates, females increase the likelihood that their offspring will be sired by genetically more compatible or superior males. If certain males have intrinsically "good genes," any female mating with them will produce superior offspring. Alternatively, if some males have genetic elements that are incompatible with a particular female, then she may benefit from polyandry if the sperm of such males are less likely to fertilize her eggs. We examined these hypotheses in the field cricket Gryllus bimaculatus (Orthoptera: Gryllidae). By allocating females identical numbers of matings but different numbers of mates we investigated the influence of number of mates on female fecundity, and both short- and long-term offspring fitness. This revealed no effect of number of mates on number of eggs laid. However, hatching success of eggs increased with number of mates. This effect could not be attributed to nongenetic effects such as the possibility that polyandry reduces variance in the quantity or fertilizing ability of sperm females receive, because a control group receiving half the number of copulations showed no drop in hatching success. Offspring did not differ in survival, adult mass, size, or development time with treatment. When males were mated to several different females there were no repeatable differences between individual males in the hatching success of their mate's eggs. This suggests that improved hatching success of polyandrous females is not due to certain males having genes that improve egg viability regardless of their mate. Instead, our results support the hypothesis that certain males are genetically more compatible with certain females, and that this drives polyandry through differential fertilization success of sperm from more compatible males.


Assessment of drug-related problems in pediatric ward of Zewditu Memorial Referral Hospital, Addis Ababa, Ethiopia.
Background Although medications play a vital role in the cure, palliation, and inhibition of disease, they also expose patients to drug-related problems (DRPs). DRPs are common in hospitalized patients. Specifically, pediatrics population are easily affected by DRPs, as dynamic and kinetic behaviors of drugs in this population are usually different than in adults. Objectives To assess the prevalence of DRPs and associated factors in a pediatric setting in Ethiopia. Setting Pediatric ward of Zewditu Memorial Referral Hospital, Addis Abbeba, Ethiopia. Methods A cross-sectional study was conducted on 285 randomly selected patients. Data were obtained through review of physician medication orders and patient files. The prevalence and type of DRPs were studied and documented using the Pharmaceutical Care Network Europe Foundation classification system. The results were summarized using descriptive statistics including frequency, mean, and standard deviation. To identify the independent predicators of DRPs, logistic regression analysis was run and a P value ≤0.05 was considered as statistically significant. Main outcome measure DRPs, types of DRPs, drugs that are frequently involved in DRPs, and factors associated with DRPs. Main outcome measure Number of DRPs. Results Of the 1055 medication orders reviewed, a total of 106 DRPs were identified in 90 patients. This gives an overall rate of drug-related problems of 31.57%. The most frequently identified DRPs were dosing problems, with dose too low being 34.9% and dose too high being 7.5%. This was followed by drug-drug interactions (38.67%) and adverse drug reactions (8.49%). The number of prescribed drugs (AOR 2.3, 95% CI 1.3-4.3, P = 0.007) and total number of disease conditions (AOR 4.8, 95% CI 1.9, 12.1, P = 0.001) were potential risk factors for occurrence of DRPs. Conclusion The present study demonstrated that DRPs were common at the pediatric ward of Zewditu Memorial Referral Hospital and that it needs great attention. The most frequently identified DRPs were dosing problems, followed by drug-drug interactions and adverse drug reaction. Poly-pharmacy and number of disease conditions have been identified as important risk factors for occurrence of DRPs. The investigators recommend establishing a system for reporting DRPs in the pediatric ward of the hospital as it may facilitate appropriate measures for prospective interventions, such as training the healthcare team, as well as detail precautions to be followed by the practitioners. In addition to this, improving communication between the healthcare team members such as physicians, pharmacists, nurses, and other healthcare workers in the hospital is recommended.


Effects of a Nurse-Led, Stage-Matched, Tailored Program for Smoking Cessation in Health Education Centers: A Prospective, Randomized, Controlled Trial.
The purpose of this study was to examine the effectiveness of a stage-matched intervention performed at outpatient clinics. Participants were randomly assigned to an intervention group (IG) or usual care group (UCG). The trial was targeted on smoking patients with coronary heart disease or diabetes. After completing the 3-month intervention, both groups received a telephone follow-up at 6 months. This analysis showed that the outcomes of the IG for the 7-day point prevalence (PP) of abstinence (odds ratio [OR] = 2.00; p = .001) and 30-day PP (OR = 2.27; p = .004) at 6 months were significantly better than the UCG. Stage of change (OR = 4.06; p < .001) and decreased daily cigarette consumption by 50% at 6 months (OR = 2.26; p = .019) outcomes also improved significantly. The preliminary results showed that a nurse-led cessation intervention in clinics may be an effective approach to help outpatients quit smoking.


Elevated Temperature Reduces Overwintering Survival of an Avian Ectoparasite, the Swallow Bug (Hemiptera: Cimicidae: Cimex vicarius).
The survival of insects that are dormant in winter may either increase or decrease as a consequence of elevated winter temperatures under climate change. Warming can be deleterious when metabolism of the overwintering life stages increases to the point that energy reserves are exhausted before postoverwintering reemergence. We examined experimentally how overwintering survival of swallow bugs (Hemiptera: Cimicidae: Cimex vicarius Horvath), an ectoparasite primarily of cliff swallows (Passeriformes: Hirundinidae: Petrochelidon pyrrhonota Vieillot), was affected by a 3°C rise in mean daily temperature for populations in Oklahoma, Nebraska, and North Dakota. Adult and nymphal swallow bugs exposed to elevated temperature had an average reduction of approximately 31% in overwintering survival (from July/August to April/May), relative to controls exposed to current region-specific ambient-like conditions. Adult males in both groups survived less well in Nebraska and North Dakota than adult males in Oklahoma, but there was no consistent latitudinal effect of the elevated heat treatment. Our results indicate that projected increases in mean temperature in the Great Plains by 2050 could result in fewer swallow bugs surviving the winter and thus a reduced population size upon the arrival of their primary host in the spring, potentially affecting cliff swallow reproductive success, site use, and breeding phenology. Global climate change may alter the dynamics of host-parasite systems by reducing overall parasite abundance.


Local co-delivery of rhBMP-2 and cathepsin K inhibitor L006235 in poly(d,l-lactide-co-glycolide) nanospheres.
Cathepsin K inhibitors (CKIs) are an emerging class of drugs that are potent antagonists of osteoclastic activity. We speculated that they may be beneficial in bone tissue engineering, where a stress shielded environment can lead to rapid resorption of new bone. Most CKIs require frequent dosing, so to achieve a sustained release we manufactured polymer nanoparticles encapsulating the CKI L006235 (CKI/nP). CKI/nP and the collagen matrices that were used to deliver them were characterized by electron microscopy and fluorescent confocal microscopy, and data indicated that the particles were evenly distributed throughout the collagen. Elution studies indicated a linear release of the inhibitor from the CKI/nP, with approximately 2% of the drug being released per day. In an in vivo study, mice were implanted with collagen scaffolds containing rhBMP-2 that were loaded with the CKI/nP. Measurement of bone volume (BV) by microCT showed no significant increase with CKI/nP incorporation, and other parameters similarly showed no statistical differences. Cell culture studies confirmed the activity of the drug, even at low concentrations. These data indicate that polymer nanoparticles are an effective method for sustained drug delivery of a CKI, however, this may not be readily translatable to substantively improved bone tissue engineering outcomes. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 136-144, 2017.


[Bacteremias after bone marrow grafts in a protected environment: effects, various aspects and prognosis].
We evaluated retrospectively the incidence and prognosis of bacteremias after bone marrow transplantation treated in protected environment with intestinal decontamination. Bacteremias are more frequent during the extreme granulopenia (55% of the patients) than during recovery of granulocyte counts greater than 500/mm3 (35% of the patients). Gram + organisms are more frequently responsible of bacteremias (80%), mainly Staphylococcus epidermidis and Streptococci. Mortality is low (7%) and related to additional factors like GVH, resistant leukemia. These data invite to develop new approaches of prevention of bacterial infection, with measures possibly efficient on Gram + organisms.


[Evaluation of 196 patients with chronic myeloid leukemia based on a standard prognosis model].
The clinical course of 196 patients with chronic myelocytic leukemia (CML) was studied. Prognostic factors were analyzed using a standard prognostic model. From a univariate analysis of patients with nonblastic Philadelphia chromosome-positive CML, splenomegaly, bone marrow fibrosis, percentage of blasts and promyelocytes in the peripheral blood and LDH activity were shown to be factors with a significant negative influence on survival. However, age and the platelet count did not influence survival. The standard prognostic model, generated with the 4 variables (1) percentage of blasts and promyelocytes, (2) spleen size, (3) platelet count and (4) age did not provide a useful representation of risk status in this heterogenous patient population. However, the addition of further variables (LDH, additional chromosomal aberrations, percentage of basophiles/eosinophiles and percentage of bone marrow blasts) to the standard model allowed a separation into 2 patient groups: one with low and the other with intermediate to high risk. Our data support the general validity of the prognostic model; however, the applicability of the model may be compromised in hematologic centers with a heterogenous CML population due to the selection of high-risk patients. In this situation additional risk factors may have to be added to the prognostic formula.


[Interscalene brachial plexus block for shoulder surgery].
This study evaluates the clinical efficacy of interscalene brachial plexus block (according to G. Meier) for shoulder surgery. Seventy-three patients, scheduled for the elective shoulder surgery, were included in this study. All patients received an interscalene block before surgery and a standard analgesia protocol after it. Minimal stimulating current, block performance time, the onset of sensory and motor blocks, duration of surgery and surgery type were recorded. The quality of nerve block was also evaluated by a surgeon. The duration of postoperative analgesia resulting from residual local anesthetic effect was expressed as the time to first requirement for post-operative pain medication. Satisfaction scores with a visual analog scale, side effects, circulatory and respiratory parameters were assessed. The success rate was 97%. For the nerve location a minimal stimulating current of 0.1 mA had been achieved. The median onset time of both motor and sensory blockade was <4 min. A complete muscle paralysis was observed after 21 (16-30) min. Duration of sensory blockade was 420 (240-840) min. The time from the block placement to the first request for pain medication was 8 (4-32) hours. Side effects were minor. Patient satisfaction was high. Single injection interscalene brachial plexus block is a reliable anesthetic and effective method of providing postoperative pain relief after shoulder surgery.


Deprescribing in the Pharmacologic Management of Delirium: A Randomized Trial in the Intensive Care Unit.
Benzodiazepines and anticholinergics are risk factors for delirium in the intensive care unit (ICU). We tested the impact of a deprescribing intervention on short-term delirium outcomes. Multisite randomized clinical trial. ICUs of three large hospitals. Two hundred adults aged 18 years or older and admitted to an ICU with delirium, according to the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the ICU (CAM-ICU). Participants had a contraindication to haloperidol (seizure disorder or prolonged QT interval) or preference against haloperidol as a treatment for delirium, and were excluded for serious mental illness, stroke, pregnancy, or alcohol withdrawal. Participants were randomized to a deprescribing intervention or usual care. The intervention included electronic alerts combined with pharmacist support to deprescribe anticholinergics and benzodiazepines. Primary outcomes were delirium duration measured by the CAM-ICU and severity measured by the Delirium Rating Scale Revised-98 (DRS-R-98) and the CAM-ICU-7; secondary outcomes included adverse events and mortality. Participants had a mean age of 61.8 (SD = 14.3) years, 59% were female, and 52% were African American, with no significant differences in baseline characteristics between groups. No differences between groups were identified in the number exposed to anticholinergics (P = .219) or benzodiazepines (P = .566), the median total anticholinergic score (P = .282), or the median total benzodiazepine dose in lorazepam equivalents (P = .501). Neither median delirium/coma-free days (P = .361) nor median change in delirium severity scores (P = .582 for DRS-R-98; P = .333 for CAM-ICU-7) were different between groups. No differences in adverse events or mortality were identified. When added to state-of-the-art clinical services, this deprescribing intervention had no impact on medication use in ICU participants. Given the age of the population, results of clinical outcomes may not be easily extrapolated to older adults. Nonetheless, improved approaches for deprescribing or preventing anticholinergics and benzodiazepines should be developed to determine the impact on delirium outcomes. J Am Geriatr Soc 67:695-702, 2019.


Supporting Latine children's informal engineering learning through tinkering and oral storytelling.
Providing equitable informal science, technology, engineering, and mathematics (STEM) learning opportunities to young children from diverse backgrounds may be a way to increase access and interest in STEM and can help to address the broader goal of increasing representation. Importantly, these learning experiences must be meaningful and engage everyday cultural practices. Guided by a strengths-based approach, the current study examines how oral stories as a cultural resource can be harnessed to support Latine children's engagement in a tinkering activity. The project explores whether and how setting an at-home tinkering activity within a story context engenders rich parent-child conversations that provide engineering learning opportunities for young children. Fifty-two Latine parents and children (Mage = 7.69 years; 23 girls; 90.4% Mexican heritage) were randomly assigned to either hear a story as a frame for a hands-on tinkering activity or to engage in the same tinkering activity without the story. After families finished tinkering, a researcher elicited the children's reflections about their tinkering experience. Approximately 2 weeks after the activity, children were asked to share their tinkering reflections with a second researcher. Parents and children in the story condition talked more about engineering during tinkering, and these children also talked more about engineering during both reflections than did children in the no-story condition. These findings suggest that integrating oral storytelling into tinkering activities is a promising future direction for the creation of more equitable informal engineering learning opportunities for Latine children and families. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Simple reaction time in 8-9-year old children environmentally exposed to PCBs.
Simple reaction time (SRT) has been studied in children exposed to polychlorinated biphenyls (PCBs), with variable results. In the current work we examined SRT in 146 boys and 161 girls, aged 8.53 ± 0.65 years (mean ± SD), exposed to PCBs in the environment of eastern Slovakia. We divided the children into tertiles with regard to increasing PCB serum concentration. The mean ± SEM serum concentration of the sum of 15 PCB congeners was 191.15 ± 5.39, 419.23 ± 8.47, and 1315.12 ± 92.57 ng/g lipids in children of the first, second, and third tertiles, respectively. We created probability distribution plots for each child from their multiple trials of the SRT testing. We fitted response time distributions from all valid trials with the ex-Gaussian function, a convolution of a normal and an additional exponential function, providing estimates of three independent parameters μ, σ, and τ. μ is the mean of the normal component, σ is the standard deviation of the normal component, and τ is the mean of the exponential component. Group response time distributions were calculated using the Vincent averaging technique. A Q-Q plot comparing probability distribution of the first vs. third tertile indicated that deviation of the quantiles of the latter tertile from those of the former begins at the 40th percentile and does not show a positive acceleration. This was confirmed in comparison of the ex-Gaussian parameters of these two tertiles adjusted for sex, age, Raven IQ of the child, mother's and father's education, behavior at home and school, and BMI: the results showed that the parameters μ and τ significantly (p ≤ 0.05) increased with PCB exposure. Similar increases of the ex-Gaussian parameter τ in children suffering from ADHD have been previously reported and interpreted as intermittent attentional lapses, but were not seen in our cohort. Our study has confirmed that environmental exposure of children to PCBs is associated with prolongation of simple reaction time reflecting impairment of cognitive functions.


Decrease in calcium carbimide (calcium cyanamide)-induced inhibition of rat hepatic aldehyde dehydrogenases by multiple ethanol administration.
Ethanol (0.3 g/kg) was administered intravenously to adult, male rats at 3 h or at 1 and 3 h after gastric intubation of 7 mg/kg calcium carbimide (CC). For animals administered CC and two ethanol doses, blood ethanol concentration was similar for the two doses; however, blood acetaldehyde concentration was significantly less for the second ethanol dose compared with the first dose as determined by the area-under-curve data. Hepatic aldehyde dehydrogenase activity was determined over the 3.5- to 5-h interval after CC pretreatment. The inhibition of low Km and high Km aldehyde dehydrogenase activity in liver homogenate and in hepatic mitochondrial, cytosolic, and microsomal fractions was significantly less for rats administered CC followed by two ethanol doses compared with that for animals administered CC alone or CC followed by one ethanol dose. The data demonstrate that increased acetaldehyde concentration, produced during the CC - ethanol interaction, can augment the recovery of hepatic aldehyde dehydrogenase activity following CC pretreatment and indicate the existence of a displaceable enzyme inhibitor derived from CC.


Veterinary Expert Opinion on Potential Drivers and Opportunities for Changing Antimicrobial Usage Practices in Livestock in Denmark, Portugal, and Switzerland.
Reducing antimicrobial use (AMU) in livestock is requested by Public Health authorities. Ideally, this should be achieved without jeopardizing production output or animal health and welfare. Thus, efficient measures must be identified and developed to target drivers of AMU. Veterinarians play a central role in the identification and implementation of such efficient interventions. Sixty-seven veterinarians with expertise in livestock production in Denmark, Portugal, and Switzerland participated in an expert opinion study aimed at investigating experiences and opinions of veterinarians about the driving forces and practices related to AMU in the main livestock sectors (broiler, dairy cattle, fattening/veal calf, and pig industry) of the aforementioned countries. Opinions on potential factors influencing the choice of antimicrobials and opportunities to reduce AMU were collected. Antibiograms are seldom used, mainly due to the time lag between testing and obtaining the results. The perceived percentage of treatment failures varied between countries and livestock sectors; however, little changes were reported over time (2005-2015). The animal health problems of each livestock sector most frequently leading to AMU did not vary substantially between countries. Mandatory official interventions (i.e., binding measures applied by national or international authorities) were highlighted as having the biggest impact on AMU. There was a variation in the experts' opinion regarding feasibility and impact of interventions both between countries and livestock sectors. Nevertheless, improved biosecurity and education of veterinarians frequently received high scores. Most veterinarians believed that AMU can be reduced. The median potential reduction estimates varied from 1% in Swiss broilers to 50% in Portuguese broilers and veal/fattening calves in all countries. We hypothesize that the differences in views could be related to disease epidemiology, animal husbandry, and socio-economic factors. A profound investigation of these disparities would provide the required knowledge for developing targeted strategies to tackle AMU and consequently resistance development. However, experts also agreed that mandatory official interventions could have the greatest impact on antimicrobial consumption. Furthermore, improvement of biosecurity and education of veterinarians, the use of zinc oxide (in pigs), improving vaccination strategies, and the creation of treatment plans were the measures considered to have the largest potential to reduce AMU. This paper can inform policymakers in Europe and countries with a similar animal production regarding their AMU policy.


Contribution of cell wall degrading enzymes to pathogenesis of Fusarium graminearum: a review.
Plant-pathogenic fungi produce an array of extracellular hydrolytic enzymes that enable them to penetrate and infect the host tissue; these enzymes are collectively called cell wall-degrading enzymes (CWDE). They may contribute to pathogenesis by degrading wax, cuticle and cell walls, thus aiding tissue invasion and pathogen dissemination. Furthermore, they can act as elicitors of host defense reaction.Fusarium head blight (FHB) is a disease caused principally by Fusarium graminearum on crops, occurring all over the world. Important economic losses on wheat-growing areas have been registered by altering quality parameters of grains. Significant progress has been made in understanding the infection process from F. graminearum on wheat, based on genomic technologies. The virulence degree of this phytopathogen on crops could arise from differences in the production of extracellular enzymes, factors controlling the establishment of infection.Fusarium graminearum isolates from different geographical areas have been examined, and a combination of morphological and molecular data allowed the division of fungi in diverse groups, which have been related to the variation in pathogenicity. In most studied cases there is a correlation between the presence of pectic enzymes, disease symptom and virulence, being also their production decisive in the infection process.


[Attitudes, knowledge and use of complementary and alternative medicine among perioperative healthcare professionals].
Perioperative healthcare professionals' attitudes towards non-conventional treatments have not been explored in Hungary yet. Our goal was to survey healthcare professionals' attitude and knowledge towards naturopathy in six clinics of the Semmelweis University that provide perioperative care. An anonymous, paper-based questionnaire was used. With an 82% response rate, the data was gained from 119 questionnaires and was processed using statistical analysis and chi-squared test. Only 25.2% of those surveyed considered themselves to be well-informed in this field. 68.1% of the participants had an interest in naturopathy and 60.5% would have liked to learn about naturopathy. 70.6% would be willing to use non-conventional treatments in their daily work, predominantly those who have used these methods in the case of their own illness, p = 0.0027. The most popular treatment methods included homeopathy, alternative massage and movement therapy, acupuncture and manual therapy. As anticipated based on international literature in this field, those Hungarian healthcare professionals who took part in our survey showed openness and interest towards naturopathy. Orv. Hetil., 2017, 158(10), 368-375.


[Men and violence, a subject little known by general practitioners].
Violence in men represents a global health burden and a serious problem of public health, with severe repercussions on physical, psychic and social health. The cost is very high for society. Men are often the authors of violence, but they also can be victims or witnesses. Violence presents itself under diverse forms and differently affects women and men in the various phases of their life and also depends from specific features, such as social status, sexual orientation and morbidities. We propose an overview of several points concerning violence in men that are relevant for general practice.


'Theory of Mind' I: a theory of knowledge?
'Theory of mind' is a cognitive notion introduced by Simon Baron-Cohen and colleagues to explain certain deficits in autistic disorders. It has, however, been extended beyond this, and applied more broadly. It proposes a means of knowing the mind of others, and suggests that this means fails in autism. The epistemological basis of 'theory of mind' will be examined critically, not just in terms of its endeavour as a theory of knowledge, but also in regard to the principles that underlie it. The proponents of 'theory of mind' eschew the rich field of psychological and phenomenological research, privileging only the biological sciences into which they endeavour to place their theorizations. In doing this, they fail to recognize the epistemological problems involved. This leads to the theory remaining hamstrung by the very Cartesian ontological problems that it seeks to avoid. For some, 'theory of mind' is but an artefact of the cognitive approach that it employs. It is argued that these difficulties are compounded by the failure of 'theory of mind' to take account of the place of language in the interpersonal encounters it attempts to describe.


Isolation of hepatocyte-like cells from mouse embryoid body cells.
We previously reported that embryoid body (EB) cells derived from embryonic stem (ES) cells are capable of differentiating into functional hepatocyte-like cells both in vitro and in vivo. Because transplantation of EB-derived cells into the liver via the spleen resulted in a low incidence of teratoma formation, purification of hepatocyte-like cells is required to prevent teratoma formation. The aim of this study was to purify hepatocyte-like cells from cultured EBs. For the isolation of hepatocyte-like cells, EBs cultured for 15 days were treated with trypsin-EDTA. The disaggregated cells were plated on a gelatin-coated dish as a monolayer. These cells were separated by Percoll gradient centrifugation, enriched by magnetic cell sorting, and purified by FACS. The purified hepatocyte-like cells in monolayer cultures were positive for immunostaining for albumin and expressed albumin mRNA, but not Oct3/4 mRNA. Transplantation of the purified hepatocyte-like cells derived from mouse ES cells might be an effective treatment for liver failure.


Mobile phone middleware architecture for energy and context awareness in location-based services.
The disruptive innovation of smartphone technology has enabled the development of mobile sensing applications leveraged on specialized sensors embedded in the device. These novel mobile phone applications rely on advanced sensor information processes, which mainly involve raw data acquisition, feature extraction, data interpretation and transmission. However, the continuous accessing of sensing resources to acquire sensor data in smartphones is still very expensive in terms of energy, particularly due to the periodic use of power-intensive sensors, such as the Global Positioning System (GPS) receiver. The key underlying idea to design energy-efficient schemes is to control the duty cycle of the GPS receiver. However, adapting the sensing rate based on dynamic context changes through a flexible middleware has received little attention in the literature. In this paper, we propose a novel modular middleware architecture and runtime environment to directly interface with application programming interfaces (APIs) and embedded sensors in order to manage the duty cycle process based on energy and context aspects. The proposed solution has been implemented in the Android software stack. It allows continuous location tracking in a timely manner and in a transparent way to the user. It also enables the deployment of sensing policies to appropriately control the sampling rate based on both energy and perceived context. We validate the proposed solution taking into account a reference location-based service (LBS) architecture. A cloud-based storage service along with online mobility analysis tools have been used to store and access sensed data. Experimental measurements demonstrate the feasibility and efficiency of our middleware, in terms of energy and location resolution.


Progress and opportunities in EELS and EDS tomography.
Electron tomography using energy loss and X-ray spectroscopy in the electron microscope continues to develop in rapidly evolving and diverse directions, enabling new insight into the three-dimensional chemistry and physics of nanoscale volumes. Progress has been made recently in improving reconstructions from EELS and EDS signals in electron tomography by applying compressed sensing methods, characterizing new detector technologies in detail, deriving improved models of signal generation, and exploring machine learning approaches to signal processing. These disparate threads can be brought together in a cohesive framework in terms of a model-based approach to analytical electron tomography. Models incorporate information on signal generation and detection as well as prior knowledge of structures in the spectrum image data. Many recent examples illustrate the flexibility of this approach and its feasibility for addressing challenges in non-linear or limited signals in EELS and EDS tomography. Further work in combining multiple imaging and spectroscopy modalities, developing synergistic data acquisition, processing, and reconstruction approaches, and improving the precision of quantitative spectroscopic tomography will expand the frontiers of spatial resolution, dose limits, and maximal information recovery.


Analysis of volatile organic compounds of bacterial origin in chronic gastrointestinal diseases.
The aim of this study was to determine whether volatile organic compounds (VOCs) present in the headspace of feces could be used to diagnose or distinguish between chronic diseases of the gastrointestinal tract and apparently healthy volunteers. A total of 87 people were recruited, divided between 4 categories: healthy volunteers (n = 19), Crohn's disease (n = 22), ulcerative colitis (n = 20), and irritable bowel syndrome (n = 26). They each supplied fecal samples before, and except for the healthy volunteers, after treatment. Fecal samples were incubated in a sample bag with added purified air at 40°C and headspace samples were taken and concentrated on thermal sorption tubes. Gas chromatography-mass spectrometry then desorbed and analyzed these. The concentrations of a selection of high-abundance compounds were determined and assessed for differences in concentration between the groups. Crohn's disease samples showed significant elevations in the concentrations of ester and alcohol derivates of short-chain fatty acids and indole compared with the other groups; indole and phenol were elevated in ulcerative colitis and irritable bowel syndrome but not at a statistically significant level. After treatment, the levels of many of the VOCs were significantly reduced and were more similar to those concentrations in healthy controls. The abundance of a number of VOCs in feces differs markedly between Crohn's disease and other gastrointestinal conditions. Following treatment, the VOC profile is altered to more closely resemble that of healthy volunteers.


Electrochemical characterization of Escherichia coli adaptive response protein AidB.
When exposed to known DNA-damaging alkylating agents, Escherichia coli cells increase production of four DNA repair enzymes: Ada, AlkA, AlkB, and AidB. The role of three enzymes (Ada, AlkA, and AlkB) in repairing DNA lesions has been well characterized, while the function of AidB is poorly understood. AidB has a distinct cofactor that is potentially related to the elusive role of AidB in adaptive response: a redox active flavin adenine dinucleotide (FAD). In this study, we report the thermodynamic redox properties of the AidB flavin for the first time, both for free protein and in the presence of potential substrates. We find that the midpoint reduction potential of the AidB flavin is within a biologically relevant window for redox chemistry at -181 mV, that AidB significantly stabilizes the flavin semiquinone, and that small molecule binding perturbs the observed reduction potential. Our electrochemical results combined with structural analysis allow for fresh comparisons between AidB and the homologous acyl-coenzyme A dehydrogenase (ACAD) family of enzymes. AidB exhibits several discrepancies from ACADs that suggest a novel catalytic mechanism distinct from that of the ACAD family enzymes.


Neuroendocrine, Autonomic, and Metabolic Responses to an Orexin Antagonist, Suvorexant, in Psychiatric Patients with Insomnia.
Aim: The aim of this study was to investigate the neuroendocrine, autonomic, and metabolic system responses to suvorexant in psychiatric subjects with insomnia. Design: This prospective study was conducted in Kusatsu Hospital in Hiroshima, Japan and included 40 psychiatric inpatients treated with suvorexant from December 2014 to April 2016. Methods: Questionnaire of Pittsburgh Sleep Quality Index (PSQI), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scores were checked at baseline, Week 2, and Week 4, and fasting serum levels of prolactin, insulin, cortisol, noradrenaline, white blood cell count, and average pulse rate were measured at baseline and Week 4 and Week 8 after suvorexant initiation. Sequential change of the values were compared against baseline respectively. Results: Subjective sleep quality scores were significantly decreased at Weeks 2 and 4, and sleep duration, habitual sleep efficacy, and global scores were significantly decreased at Week 4 from baseline. Total scores on the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-9 significantly decreased at Week 4 from baseline. The levels of cortisol and white blood cell count were decreased, significantly at Week 8, and the levels of pulse rate were significantly decreased at Week 4 from baseline. The levels of noradrenaline decreased, although not significantly. The prolactin levels remained unchanged, and no trend was found in the insulin levels. Conclusion: Suvorexant treatment resulted in overall improvement in the quality of sleep and the severity of anxiety and depression. This dual orexin antagonist may be related to autonomic functions and neuroendocrine systems, especially in the hypothalamus-pituitary-adrenal axis in psychiatric subjects.


Classification-by-Analogy: Using Vector Representations of Implicit Relationships to Identify Plausibly Causal Drug/Side-effect Relationships.
An important aspect of post-marketing drug surveillance involves identifying potential side-effects utilizing adverse drug event (ADE) reporting systems and/or Electronic Health Records. These data are noisy, necessitating identified drug/ADE associations be manually reviewed - a human-intensive process that scales poorly with large numbers of possibly dangerous associations and rapid growth of biomedical literature. Recent work has employed Literature Based Discovery methods that exploit implicit relationships between biomedical entities within the literature to estimate the plausibility of drug/ADE connections. We extend this work by evaluating machine learning classifiers applied to high-dimensional vector representations of relationships extracted from the literature as a means to identify substantiated drug/ADE connections. Using a curated reference standard, we show applying classifiers to such representations improves performance (+≈37%AUC) over previous approaches. These trained systems reproduce outcomes of the manual literature review process used to create the reference standard, but further research is required to establish their generalizability.


[The prevalence of single and synchronous multiple tumours in autopsy series and its dependence on age (author's transl)].
The present study reports the age specific prevalence rate of tumors in autopsies of the years 1958--1969, registered in the Medical Academy "Carl Gustav Carus" Dresden. The results refer to the total of all malignant tumors, to several tumor sites as well as to multiple simultaneous tumors. In many neoplasms highest prevalence occurs in presenile age (malignancies of lung, uterus, ovar, brain, and bone marrow). On the other side prevalence of carcinoma of breast, urinary bladder, kidney, prostate, and large intestine increases up to the oldest age-groups. With respect to the population the prevalence of cancer increases permanently up to the age of eighty and decreases only in the following age-groups. The age-specific prevalence of simultaneous multiple tumors referred to cases of single tumors in the post-mortem findings reveals an analogous age distribution curve. The prevalence of simultaneous cancer is discussed concerning the influence of age and duration of the malignancy.


Examining the health care payment reforms in Abu Dhabi.
The purpose of this paper is to provide an overview of the current health care payment reforms in Abu Dhabi and discuss the potential impact of these reforms on health care consumers and providers as we all as long-term sustainability of the mandatory health care insurance system. A focused literature review was conducted to systematically identify and summarize relevant literature published on the recent payments reforms in Abu Dhabi along with a secondary review and analysis of existing related government documents, technical reports, and press releases by the Health Authority-Abu Dhabi (HAAD) and other relevant research groups. The implementation of the mandatory health insurance system allowed all UAE nationals and foreign workings in Abu Dhabi to have access to medical care insurance and access to care. Prospective payment reforms represent critical sustainability interventions for health care funding in Abu Dhabi. The full impact of payment reforms on affordability, system efficiency, and patient outcomes is yet to be documented. Given the Government of Abu Dhabi has identified the sustainability of healthcare funding as a key governmental policy, more research is needed to systematically examine the impact of the current payment reforms on multiple stakeholders.


Adverse pathological outcomes of patients with de novo muscle invasive bladder cancer in Northern Ontario.
This study aimed to investigate the clinical and pathological characteristics of patients with de novo muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy in Northern Ontario. This is a retrospective cross-sectional study of patients with de novo T2 MIBC who underwent radical cystectomy over a 2-year-period in Thunder Bay Regional Health Sciences Centre. Clinical and pathological characteristics of Trans Urethral Resection of Bladder Tumors and cystectomy specimens were analyzed. Of the 59 patients aged 67 ± 8.8 years, predominated by males (80%), 27.1% were younger than age 60. After surgery, upstaging was noted in 59.3% (T3 in 27.1% and T4 in 32.2%) while node positive was noted in 36% of patients. Prostate adenocarcinoma was incidentally discovered in 20 (34%) of patients with 50% considered significant (Gleason score ≥ 7). Downstaging was found in those who had neoadjuvant chemotherapy (p = 0.001). The high prevalence of younger ages (less than 60), a high rate of upstaging, the presence of high-grade incidental prostate cancer, and lymph node positives in T2 de novo MIBC in Northern Ontario, warrants further investigation of potential causes and risk factors at individual, public, and population health levels in the region.


Surveys of Stroke Patients and Their Next of Kin on Their Opinions towards Decision-Making and Consent for Stroke Thrombolysis.
Early initiation of stroke thrombolysis is associated with improved outcomes. Procurement of consent is a key factor in prolonging the door-to-needle duration. This study aimed to determine the attitudes and preferences of stroke patients and their next of kin (NOK) towards decision-making for stroke thrombolysis in Singapore. We surveyed acute ischaemic stroke patients (n = 171) who presented beyond the 4.5-hour therapeutic window and their NOK (n = 140) using a questionnaire with scenarios on obtaining consent for intravenous thrombolysis. In the patient survey, 83% were agreeable for their NOK to decide on their behalf if mentally incapacitated and 74% were agreeable for the doctor to decide if the NOK was absent. In the NOK survey, the majority (81%) wanted to be consulted before mentally capacitated patients made their decision; 72% and 74%, meanwhile, were willing to decide on behalf of a mentally capacitated and mentally incapacitated patient, respectively. In the scenario where a doctor recommended a mentally incapacitated stroke patient to undergo thrombolysis but the family declined, there was a near equal split in preference to follow the family's or doctor's decision in both the patient and NOK surveys. The survey found that in the decision-making process for stroke thrombolysis, there was no clear consensus on the preference for the decision maker of the mentally incapacitated patient. In Singapore, there is a strong influence of the NOK in decision-making for thrombolysis.


Evaluation of Weight Loss Indicators and Laparoscopic One-Anastomosis Gastric Bypass Outcomes.
Mini-gastric bypass/One-anastomosis gastric bypass (MGB-OAGB) is an effective bariatric technique for treating overweight and obesity, controlling and improving excess-weight-related comorbidities. Our study evaluated OAGB characteristics and resulting weight evolution, plus surgical success criteria based on various excess weight loss indicators. A prospective observational study of 100 patients undergoing OAGB performed by the same surgical team (two-year follow-up). Surgical characteristics were: surgery duration, associated complications, bowel loop length, hospital stay, and weight loss at 6 postoperative points. 100 patients were treated (71 women, 29 men); mean initial age was 42.61 years and mean BMI, 42.61 ± 6.66 kg/m2. Mean surgery duration was 97.84 ± 12.54 minutes; biliopancreatic loop length was 274.95 ± 23.69 cm. Average hospital stay was 24 hours in 98% of patients; no surgical complications arose. Weight decreased significantly during follow-up (P < 0.001). Greatest weight loss was observed at 12 months postsurgery (68.56 ± 13.10 kg). Relative weight loss showed significant positive correlation, with greatest weight loss at 12 months and %excess BMI loss > 50% achieved from the 3-month follow-up in 92.46% of patients. OAGB seems to be effective in treating obesity, with short hospital stays. Relative weight loss correlates optimally with absolute outcomes, but both measures should be used to evaluate surgical results.


Outcomes for depressed and anxious inpatients discharged before or after group cognitive behavior therapy: a naturalistic comparison.
Treatment outcomes for psychiatric inpatients with a primary diagnosis of a depressive or anxiety disorder who completed a cognitive behavior therapy (CBT) program while inpatients or when discharged were examined. Of 340 inpatients, 197 had been discharged to day patient status before the end of the CBT program, and 143 remained as inpatients. Data were collected before and after the CBT program and at 3-month follow-up. There was a significant improvement by posttreatment in self-esteem, locus of control, anxiety, depression, and stress, and these gains were maintained at 3-month follow-up. In addition, anxious, but not depressed, patients who completed CBT as day patients demonstrated greater improvements from after the CBT program to follow-up than those treated as inpatients. Possible reasons for the beneficial effects of completing the CBT as a day patient rather than an inpatient are discussed, and threats to the validity of this naturalistic study are considered.


Growth and development of the exocrine pancreas in newborn pigs: the effect of colostrum feeding.
This study examined the growth and development of the pancreas in naturally suckled piglets during the first 3 postnatal days and the effects of colostrum feeding on the pancreatic development. The results showed that in naturally suckled piglets, the absolute weight of the pancreas increased 51% during the first day and 86% by the 3rd day, and the relative weight per unit body weight increased 37% during the first day and 47% by the 3rd day. Associated with the rapid weight gain was a significant increase in pancreatic DNA content and enlargement of pancreatic exocrine acinar units, the latter apparently resulted from an increase in number rather than size of acinar cells. It was further shown that the rapid pancreatic growth was related to colostrum ingestion as significant pancreatic weight gain was observed in piglets bottle-fed porcine colostrum or trypsinized porcine colostrum but not in piglets bottle-fed 5% lactose solution. Trypsinized porcine colostrum was apparently more potent than native porcine colostrum in stimulating pancreatic growth in newborn pigs. It is speculated that colostrum-borne growth factors and/or postnatal surge of gut hormones following onset of oral feeding are the major factors responsible for the rapid postnatal pancreatic growth in newborns.


[Treatment of bone cyst by transplantation of autologous bone marrow combined with allograft bone].
To investigate the clinical result of treatment of bone cyst by transplantation of the autologous bone marrow combined with the allograft bone. From February 2004 to March 2006, 13 patients with bone cyst were treated by transplantation of the autologous bone marrow combined the the allograft bone. Among the 13 patients, 6 were males and 7 were females, ranging in age from 5 to 16 years, averaged 11.5 years. In the patients, 5 lesions were located in the proximal humerus, 2 in the femoral neck, 3 in the femoral shaft, 2 in the proximal tibia, and 1 in the distal tibia. Among the patients, 5 had a complication of pathologic fracture. All the patients underwent an erasion of the bone cyst, and then the transplantation of the autologous bone marrow combined with the allograft bone, and 8 of them were also given an instrument fixation. The follow-up for 6 months to 2 years after operation revealed that 5 of the patients had an incision healing by the first intention, 5 had an effusion in the incision site, and 3 had a delayed healing of the incision. According to the Capanne criteria, the postoperative X-ray findings indicated that 10 patients had Grade I healing, and 3 had Grade II healing. The complete healing took 3.5-8 months, averaged 5. 2 months. There was no recurrence. When the fixation instrument was removed, no pathologic fracture occurred. The function of the upper and lower limbs recovered. Transplantation of the autologous bone marrow combined with the allograft bone is an effective and safe procedure for treatment of bone cyst.


Attachment of streptavidin to beta-cyclodextrin molecular printboards via orthogonal host-guest and protein-ligand interactions.
Streptavidin (SAv) is attached to beta-cyclodextrin (beta-CD) self-assembled monolayers (SAMs) via orthogonal host-guest and SAv-biotin interactions. The orthogonal linkers consist of a biotin functionality for binding to SAv and adamantyl functionalities for host-guest interactions at beta-CD SAMs. SAv complexed to excess monovalent linker in solution and then attached to a beta-CD SAM could be removed by rinsing with a 10 mM beta-CD solution. When SAv was attached to the beta-CD SAM via the divalent linker, it was impossible to remove SAv from the surface by the same rinsing procedure. This is interpreted by assuming that two SAv binding pockets are oriented towards the beta-CD SAM resulting in (labile) divalent and (stable) tetravalent beta-CD-adamantyl interactions for the mono- and divalent linkers, respectively. This was confirmed by experiments at varying beta-CD concentrations. When the [linker]/[SAv] ratio is reduced, a clear trend in the divalent-linker case is seen: the less linker the more protein could be removed from the surface. It is proven that the orthogonality of the binding motifs and the stability of the divalent linker at the beta-CD SAM allows the stepwise assembly of the complex at the beta-CD SAM by first adsorbing the linker, followed by SAv. This stepwise assembly allows the controlled heterofunctionalization of surface-immobilized SAv.


An equivalent-square formula for head-scatter factors.
A simple formula is evaluated for calculating the equivalent square collimator setting that gives the same headscatter factor as a given rectangular field. The expression requires that one parameter is determined experimentally. It is found that one single value of this parameter can be used for the six x-ray beams studied (two accelerators, two energies, with and without wedge).


Excitatory amino acid receptors in the dorsomedial hypothalamus mediate prostaglandin-evoked thermogenesis in brown adipose tissue.
We determined whether the dorsomedial hypothalamus (DMH) plays a role in the thermogenic, metabolic, and cardiovascular effects evoked by centrally administered PGE2. Microinjection of PGE2 (170 pmol/60 nl) into the medial preoptic area of the hypothalamus in urethane-chloralose-anesthetized, artificially ventilated rats increased brown adipose tissue (BAT) sympathetic nerve activity (SNA; +207 +/- 18% of control), BAT temperature (1.5 +/- 0.2 degrees C), expired CO2 (0.9 +/- 0.1%), heart rate (HR; 106 +/- 12 beats/min), and mean arterial pressure (22 +/- 4 mmHg). Within 5 min of subsequent bilateral microinjections of the GABAA receptor agonist muscimol (120 pmol.60 nl-1.side-1) or the ionotropic excitatory amino acid antagonist kynurenate (6 nmol.60 nl-1.side-1) into the DMH, the PGE2-evoked increases were, respectively, attenuated by 91 +/- 3% and 108 +/- 7% for BAT SNA, by 73 +/- 12% and 102 +/- 28% for BAT temperature, by 100 +/- 4% and 125 +/- 21% for expired CO2, by 72 +/- 11% and 70 +/- 16% for HR, and by 84 +/- 19% and 113 +/- 16% for mean arterial pressure. Microinjections outside the DMH within the dorsal hypothalamic area adjacent to the mamillothalamic tracts or within the ventromedial hypothalamus were less effective for attenuating the PGE2-evoked thermogenic, metabolic, and cardiovascular responses. These results demonstrate that activation of excitatory amino acid receptors within the DMH is necessary for the thermogenic, metabolic, and cardiovascular responses evoked by microinjection of PGE2 into the medial preoptic area.


The female and pupa of Uranotaenia (Pseudoficalbia) bhutanensis (Diptera: Culicidae).
Uranotaenia bhutanensis Somboon, Namgay & Harbach was recently described as a new species of the Bimaculata Series of the subgenus Pseudoficalbia Theobald based on larvae collected from a log hole at high altitude in Bhutan. The adult female and pupa are described in this article based on the subsequent discovery of 2 paratype females with associated pupal exuviae.


HSV Encephalomyelitis in an Immunocompetent Patient With Prior Splenectomy.
A 44-year-old male with history of asplenia, provoked PE, and hyperlipidemia presented with ascending paralysis, bowel and bladder incontinence and altered mental status, and progressively developed acute hypoxic respiratory failure. Initial workup including CT head, magnetic resonance imaging (MRI) brain, and lumbar puncture which was concerning for herpes simplex virus (HSV) meningoencephalitis; out of caution he was started on multiple antibiotics consequently resulting in the development of Clostridium difficile (C.diff). He also received two doses of IVIG. He was transferred to our institution and after interval re-imaging via MRI brain and spinal surveys and repeat lumbar punctures, he was found to have a high CSF HSV titer and positive GAD 65 antibody, the latter likely a false positive due to IVIG administration. IVIG was not continued from the outside hospital due to the development of deep vein thrombosis (DVT), and the risks of plasmapheresis outweighed the benefits. The patient gradually improved after a prolonged course of acyclovir and was downgraded out of the Neuroscience ICU (NSICU), however decompensated due to rectal bleeding, and subsequently went into cardiac arrest. Though this patient underwent a splenectomy, his relative immunocompetency towards non-encapsulated organisms should have been preserved. It has not been clearly described in the literature how and why HSV encephalomyelitis takes a fulminant course in immunocompetent patients, including our asplenic patient. Furthermore, definitive treatment and management of this condition remains unclear. Severity of HSV encephalomyelitis has not been clearly described in the literature, particularly in immunocompetent patients (such as this asplenic patient).


Continuation of Renin-Angiotensin-Aldosterone Inhibitors Does Not Impact Renal Function Among Patients Undergoing Percutaneous Nephrolithotomy.
In the perioperative period, renin-angiotensin-aldosterone system (RAAS) inhibitors may result in cardiovascular and renal functional changes. We sought to determine the acute and chronic renal functional and blood pressure effects of continuing or withdrawing angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) after percutaneous nephrolithotomy (PCNL). This was a retrospective review of all patients undergoing PCNL at our institution from 2002 to 2013. Patients on either an ACE-I and/or ARB who received an ACE-I and/or ARB during their surgical hospitalization were matched based on sex, age, and body mass index to patients who had their medication withheld during the postoperative period. The two groups were compared. A total of 2784 patients underwent PCNL during the study period. At the time of PCNL, 15.2% (423/2784) of patients and 6.5% (181/2784) were prescribed an ACE-I and an ARB, respectively. Fifty-nine percent (248/423) of patients on an ACE-I and 66.9% (121/181) on an ARB received their medication during their postoperative hospitalization. There was no significant difference in average length of stay (2 days vs 2 days), perioperative change in glomerular filtration rate, glomerular filtration rate (GFR) (-0.50 mL/min/1.73 m2 vs -2.34 mL/min/1.73 m2, p = 0.267), change in GFR at 1 month postoperatively (-4.63 mL/min/1.73 m2 vs -5.90 mL/min/1.73 m2, p = 0.748), or change in GFR at 1 year (-2.08 mL/min/1.73 m2 vs -0.13 mL/min/1.73 m2, p = 0.267) between patients who received vs withheld their medication during the postoperative stay. It is safe to continue RAAS inhibitors in patients undergoing PCNL during their operative hospitalization.


Contribution of Poststent Irregular Protrusion to Subsequent In-Stent Neoatherosclerosis after the Second-Generation Drug-Eluting Stent Implantation.
Previous optical coherence tomography (OCT) study reported that irregular protrusion (IP) post drug-eluting stent (DES) implantation was an independent predictor of clinical outcome; however, the relationship between IP and the presence of subsequent in-stent neoatherosclerosis remains unclear. This study aimed to assess the relationship between IP and in-stent neoatheroscrerosis formation using OCT. We evaluated 83 patients (101 lesions) who underwent second-generation DES implantation and 8-month follow-up (8M-FU) using OCT. Lesions were divided into two groups in presence of IP (IP: n = 43, non-IP: n = 58). At prepercutaneous coronary intervention (pre-PCI), lipid-rich plaque, lesions with positive remodeling, and in-stent thrombus formation were more frequent in IP than in non-IP. On multivariate analysis, the thrombus at pre-PCI and the lesions with positive remodeling were independent predictors of IP. At 8M-FU, heterogeneous neointima, microvessel, lipid-laden neointima, and thin-cap fibro-atheroma like neointima were more frequent in IP than in non-IP (respectively, P < 0.05). On multivariate analysis, IP was associated with heterogeneous neointima. Binary restenosis was more frequent and late lumen loss tended to be larger in IP than in non-IP (19% versus 5%, P = 0.04; 1.25 ± 1.24 mm versus 0.91 ± 0.63 mm, P = 0.09); however, the target lesion revascularization rate was similar in both groups at 8M-FU. In conclusion, our study suggested that poststent IP was associated with subsequent neoatherosclerosis formation at 8M-FU after the second-generation DES implantation.


Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant alpha-interferon.
In a randomized controlled trial, 41 chronic hepatitis B virus carriers were allocated, by opening numbered computerized randomization envelopes, to receive recombinant interferon-alpha 2A at three different doses: 2.5; 5.0, and 10.0 mU per m2. Thirty-two patients received treatment (6 for 3 months, 26 for 6 months), and 9 patients were controls (received no treatment). Ninety-three per cent of our patients were homosexual, and 41% had anti-HTLV-III in their serum. None of the control patients lost HBeAg. In contrast, six of the anti-HTLV-III-negative patients (33%) responded to treatment (p less than 0.02): five of these responders were homosexual (p less than 0.05). The response rate was greatest (44%) in the anti-HTLV-III-negative patients who received 10 mU per m2 of recombinant interferon-alpha 2A. None of the anti-HTLV-III-positive patients responded to treatment. The percentage reduction of hepatitis B virus DNA was significantly less in the anti-HTLV-III-positive group in comparison to the anti-HTLV-III-negative group at 1 and 4 months of treatment and at 3 months after the end of treatment (p less than 0.05). These patients were younger (33 vs. 42 years, p less than 0.02), had lower mean baseline AST values (42 vs. 80 IU per liter, p less than 0.02) and tended to have milder histological disease. Homosexual men with HBeAg-positive chronic liver disease who are anti-HTLV-III-positive appear to be less responsive to the direct antiviral and immunomodulatory effects of recombinant interferon-alpha 2A. This may be due to the subclinical immunosuppressive effects of co-infection with HTLV-III.


A Novel Method for Direct Assessment of Everyday Competence Among Older Adults.
Recent findings indicate that impairments in functional performance do occur among individuals diagnosed with mild cognitive impairment (MCI). Most assessment strategies for everyday competence are associated with challenges with reliability, are typically in paper and pencil format, or require in-person administration by a trained professional. This paper reports on a novel technology-based assessment battery of everyday competence that includes ecologically valid simulations of daily activities important to independence. The sample included 85 non-cognitively impaired older adults aged 65+ and 62 older adults diagnosed with amnestic MCI (aMCI). Participants completed standard measures of cognitive abilities and the computerized battery of everyday tasks, which included simulations of a doctor's visit; and medication and financial management tasks. The older adults with aMCI performed significantly poorer on all three tasks in the everyday task battery. Performance on these measures were also moderately correlated with standard measures of cognitive abilities and showed good test-retest reliability. The results show that it is feasible to use a technology-based assessment battery of everyday tasks with both non-cognitively impaired older adults and older adults with MCI. The use of this type of battery can overcome many of the logistic constraints associated with current functional assessment protocols.


Application of host-specific bacteriophages to the surface of chicken skin leads to a reduction in recovery of Campylobacter jejuni.
Retail poultry products are widely purported as the major infection vehicle for human campylobacteriosis. Numerous intervention strategies have sought to reduce Campylobacter contamination on broiler carcasses in the abattoir. This study reports the efficacy of bacteriophage in reducing the number of recoverable Campylobacter jejuni cells on artificially contaminated chicken skin.


Impaired coordination of nucleophile and increased hydrophobicity in the +1 subsite shift levansucrase activity towards transfructosylation.
Bacterial levansucrases produce β(2,6)-linked levan-type polysaccharides using sucrose or sucrose analogs as donor/acceptor substrates. However, the dominant reaction of Bacillus megaterium levansucrase (Bm-LS) is hydrolysis. Single domain levansucrases from Gram-positive bacteria display a wide substrate-binding pocket with open access to water, challenging engineering for transfructosylation-efficient enzymes. We pursued a shift in reaction specificity by either modifying the water distribution in the active site or the coordination of the catalytic acid/base (E352) and the nucleophile (D95), thus affecting the fructosyl-transfer rate and allowing acceptors other than water to occupy the active site. Two serine (173/422) and two water-binding tyrosine (421/439) residues located in the first shell of the catalytic pocket were modified. Library variants of S173, Y421 and S422, which coordinate the position of D95 and E352, show increased transfructosylation (30-200%) and modified product spectra. Substitutions at position 422 have a higher impact on sucrose affinity, while changes at position 173 and 421 have a strong effect on the overall catalytic rate. As most retaining glycoside hydrolases (GHs) Bm-LS catalyzes hydrolysis and transglycosylation via a double displacement reaction involving two-transition states (TS1 and TS2). Hydrogen bonds of D95 with the side chains of S173 and S422 contribute a total of 2.4 kcal mol-1 to TS1 stabilization, while hydrogen bonds between invariant Y421, E352 and the glucosyl C-2 hydroxyl-group of sucrose contribute 2.15 kcal mol-1 stabilization. Changes at Y439 render predominantly hydrolytic variants synthesizing shorter oligosaccharides.


Improvement in laboratory diagnosis of wound botulism and tetanus among injecting illicit-drug users by use of real-time PCR assays for neurotoxin gene fragments.
An upsurge in wound infections due to Clostridium botulinum and Clostridium tetani among users of illegal injected drugs (IDUs) occurred in the United Kingdom during 2003 and 2004. A real-time PCR assay was developed to detect a fragment of the neurotoxin gene of C. tetani (TeNT) and was used in conjunction with previously described assays for C. botulinum neurotoxin types A, B, and E (BoNTA, -B, and -E). The assays were sensitive, specific, rapid to perform, and applicable to investigating infections among IDUs using DNA extracted directly from wound tissue, as well as bacteria growing among mixed microflora in enrichment cultures and in pure culture on solid media. A combination of bioassay and PCR test results confirmed the clinical diagnosis in 10 of 25 cases of suspected botulism and two of five suspected cases of tetanus among IDUs. The PCR assays were in almost complete agreement with the conventional bioassays when considering results from different samples collected from the same patient. The replacement of bioassays by real-time PCR for the isolation and identification of both C. botulinum and C. tetani demonstrates a sensitivity and specificity similar to those of conventional approaches. However, the real-time PCR assays substantially improves the diagnostic process in terms of the speed of results and by the replacement of experimental animals. Recommendations are given for an improved strategy for the laboratory investigation of suspected wound botulism and tetanus among IDUs.


Development and initial testing of a Health Confidence Score (HCS).
Patients need to feel confident about looking after their own health. This is needed to improve patient outcomes and clinical support. With few suitable tools available to measure self-care health confidence, we developed and validated a short, generic survey instrument for use in evaluation and quality improvement. The Health Confidence Score (HCS) was developed through literature review, patient and expert focus groups and discussions. This paper reports an initial survey (n = 1031, study 1) which identified some issues and a further face-to-face survey (n = 378, study 2) to test the construct and concurrent validity of the final version. Scores were correlated against the My Health Confidence (MHC) rating scale, howRu (health status measure) and relevant demographics. The HCS is short (50 words) with good readability (reading age 8). It has four items covering health knowledge, capability to self-manage, access to help and shared decision-making; each has four response options (strongly agree, agree, neutral disagree). Items are reported independently and as a summary score.The mean summary score was 76.7 (SD 20.4) on 0-100 scale. Cronbach's alpha = 0.82. Exploratory factor analysis suggested that the four items relate to a single dimension. Correlation of the HCS summary score with MHC was high (Spearman r = 0.76). It was also associated with health status (Spearman r = 0.49), negatively with number of medications taken (r=-0.29) and age (r=-0.22) and not with ethnicity, having children or education level. The HCS is short, easy to use, with good psychometric properties and construct validity. Each item is meaningful independently and the summary score gives an overall picture of health confidence.


Hypoxia-induced cleavage of caspase-3 and DFF45/ICAD in human failed cardiomyocytes.
It has been proposed that the hemodynamic deterioration associated with heart failure (HF) may be due in part to ongoing loss of viable cardiac myocytes through apoptosis. Hypoxia has been shown to promote apoptosis in normal cardiomyocytes. Adaptation and maladaptations inherent to heart failure can modify the susceptibility of cells to different stress factors. We hypothesized that HF modifies the threshold of cardiomyocytes to hypoxia-induced apoptosis. Cardiomyocytes were isolated from 18 human hearts explanted at the time of cardiac transplantation due to either ischemic cardiomyopathy (ICM) (n = 9) or idiopathic dilated cardiomyopathy (IDC) (n = 9). Tissue from five normal donor hearts (NL) for whom no suitable recipient was available was used as control. Cardiomyocytes were incubated for 3 h under normoxic (95% air-5% CO(2)) or hypoxic (95% N(2)-5% CO(2)) conditions. Expression of caspase-3 and DNA fragmentation factor-45 (DFF45)/inhibitor of caspase-3-activated DNase (ICAD) was detected by Western blot analysis. Three hours of hypoxia did not affect the expression of these proteins in NL cardiomyocytes. In contrast, hypoxia led to cleavage of caspase-3 and DFF45/ICAD both in ICM and IDC. In conclusion, failing cardiomyocytes exhibit increased susceptibility to hypoxia-induced apoptosis.


Radioimmunoassay of 15alpha-hydroxyestriol (estetrol) in pregnancy serum.
A more specific antisera against 15alpha-hydroxyestriol (estetrol) was produced in rabbits by immunization with 6-oxoestetrol-6-carboxy-methyloximino-bovine serum albumin. The synthesis of estetrol tetraacetate was greatly improved. Characterization of estetrol antisera revealed that it is more specific than those formerly obtained. A simple method of extraction of estetrol with alcohol from serum with high recovery is described. A radioimmunoassay method for pregnancy serum is characterized in regard to its specificity, accuracy, sensitivity and precision. The method is able to measure as little as 50 pg/tube or 167 pg/ml of serum. The intraassay coefficient of variation is 7.8% and that for interassay including personnel variation is 14.2%. Accuracy of the method, as determined by the recovery of non-radioactive estetrol (1 ng/ml) added to non-pregnancy serum, is found to be 89 +/- 8 (SD)%, CV = 8.7%, without correction for experimental losses. One hundred twelve pregnancy sera were analysed; the values obtained from normal subjects in the third trimester ranged from 240-950 pg/ml. The values obtained by this method are somewhat lower than those reported previously, presumably due to the higher specificity of the antibody.


The Efficacy of Lavender Aromatherapy in Reducing the Overcrowding-Related Anxiety in Health Care Workers.
In general, emergency departments (EDs) are stressful workplaces with excessive workloads and time pressures. Crowding, which is an important problem worldwide disrupting ED functions, leads further increases in the stressors which health care workers are exposed to. Long-term exposure to stressors can lead to anxiety in health care workers. The aim of this study was to determine the effect of aromatherapy on crowding-related anxiety in ED health care workers. Crowding was measured simultaneously with the National Emergency Department Overcrowding Scale objectively and the Health Care Workers' Crowding Perception Evaluation Form subjectively. The state-trait anxiety level was measured at each crowding level according to the health care workers' perception. When perceived crowding was at severely overcrowding level, lavender oil aromatherapy was applied. Anxiety level was measured before and after aromatherapy. Aromatherapy was repeated 3 times on different days. A significant positive correlation was found between state anxiety level and perceived crowding (r = 0.415, p < 0.001). Aromatherapy was found to have a significant correlation in reducing the overcrowding-related anxiety in health care workers (p < 0.05). This study showed that there is a significant correlation between anxiety level and perceived crowding, and aromatherapy is related to a decrease in overcrowding-related anxiety. In EDs, lavender oil aromatherapy can be used as a complementary method in reducing the overcrowding-related anxiety. But further researches are needed to verify that aromatherapy has a causative effect on reducing overcrowding-related anxiety.


USP6 rearrangement in pediatric nodular fasciitis.
Nodular fasciitis (NF) is a myofibroblastic proliferation that is uncommonly present in pediatric patients. These benign neoplasms can masquerade as more insidious sarcomatous proliferations on both clinical exam and initial histopathologic review, often prompting undue concern in patients, parents, and providers. While immunohistochemical analysis of NF can be variable, adding to the diagnostic uncertainty, molecular analysis documenting ubiquitin-specific protease 6 (USP6) gene rearrangement can help confirm the diagnosis as an association between NF and USP6 overexpression was first identified 10 years ago in an analysis that found rearrangements of the involved locus in over 90% of studied samples. In this report, we review one case of NF located on the chin of a nine-year-old girl in which molecular testing was essential to secure the correct diagnosis, and provide a summary of documented cases of USP6 overexpression in transient pediatric neoplasms.


A bacterial mutation blocking P2 phage late gene expression.
A mutant of Escherichia coli strain C has been isolated, called gro109, that blocks bacteriophage P2 propagation by interfering with late gene expression. DNA replication proceeds normally in P2+-infected gro109 cells, but late phage proteins are not made. Early P2 mRNA is made in normal amounts, but very little late mRNA can be detected. P2 mutants (P2 ogr) able to overcome the gro109 block have been isolated in which synthesis of late P2 mRNA and phage proteins Is restored. The gro109 mutation is closely linked to the cluster of ribosomal genes at 64 min and is recessive to the wild-type (gro+) allele. A P2 ogr mutation has been mapped on the left arm of the P2 genome, between the right-most known late gene (D) and the phage attachment site. P2 ogr can complement P2+ in gro109 cells, indicating that ogr codes for a diffusible product.


Comparison of unipedicular and bipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures: a prospective randomised study.
This is a prospective randomised study comparing the clinical and radiological outcomes of uni- and bipedicular balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures. A total of 44 patients were randomised to undergo either uni- or bipedicular balloon kyphoplasty. Self-reported clinical assessment using the Oswestry Disability Index, the Roland-Morris Disability questionnaire and a visual analogue score for pain was undertaken pre-operatively, and at three and twelve months post-operatively. The vertebral height and kyphotic angle were measured from pre- and post-operative radiographs. Total operating time and the incidence of cement leakage was recorded for each group. Both uni- and bipedicular kyphoplasty groups showed significant within-group improvements in all clinical outcomes at three months and twelve months after surgery. However, there were no significant differences between the groups in all clinical and radiological outcomes. Operating time was longer in the bipedicular group (p < 0.001). The incidence of cement leakage was not significantly different in the two groups (p = 0.09). A unipedicular technique yielded similar clinical and radiological outcomes as bipedicular balloon kyphoplasty, while reducing the length of the operation. We therefore encourage the use of a unipedicular approach as the preferred surgical technique for the treatment of osteoporotic vertebral compression fractures.


Recurrence and treatment of urinary bladder cancer after failure in radiotherapy.
One hundred fifty-five patients with urinary bladder cancer who were not suitable for radical surgery were treated with full-course radiotherapy, 6600 cGy in 9 weeks, split-course. After the treatment recurrences were observed in 94 patients (60%), 49 (53%) were treated with transurethral surgery and intravesical cytostatics, local surgery, systemic cytostatics, or palliative radiotherapy. The median survivals for the patients were 33, 10, 4, and 2.4 months, respectively. The outcome of treatment for radiotherapy failures was related to the nature of the failure, ureteric obstruction, the recurrence rate, and the mode of treatment. Shrinkage of the bladder was observed in 15 patients (16%). The occurrence of bladder shrinkage was related to the increase in frequency of recurrences and of different types of treatments.


Contrast-Based Real-Time Assessment of Microcirculatory Changes in a Fatty Liver After Ischemia Reperfusion Injury.
A fatty liver is known to have impairment of microcirculation, which is worsened after ischemia reperfusion injury (IRI). This makes most fatty grafts unsuitable for transplantation, and in the absence of real time assessment of microcirculation this selection has been at best, random. The aim of this study was to demonstrate the utility of a contrast enhanced ultrasound model in quantitative assessment of the microcirculation of a fatty liver. We subjected fatty mice to IRI, and blood flow dynamics were assessed before and after the injury. There was a significant increase in the resistive and pulsatility index of the extrahepatic artery and a significant decrease in velocity of the portal vein. There was also a quantifiable decrease in the intrahepatic blood volume, blood flow, time to peak flow, and perfusion index of mice with fatty liver, suggesting that a fatty liver develops hemodynamic abnormalities after IRI, leading to increased hepatocellular injury. Hemodynamic abnormalities in liver can be reliably quantified using a contrast, enhanced Doppler ultrasound, which is an inexpensive technique with multiple clinical applications. It can be used to assess the quality of the fatty liver donor graft before organ retrieval; for determining live donor candidacy, for making post-IRI recovery prognosis, and for assessing the effectiveness of therapeutic interventions.


Endoscopic ultrasound-guided fine needle aspiration biopsy: equipment and technique.
Endoscopic ultrasound-guided fine needle aspiration biopsy (EUS-FNA) is currently performed on a routine basis at many endoscopic centers and it is evident that this procedure has a major impact on the therapeutic management of patients by obtaining a definite tissue diagnosis from lesions outlined by endosonography. The reported yield of EUS-FNA is about 90-95%, with an overall sensitivity and specificity of 90% and 100%, respectively. Moreover, even minute lesions down to a size of 5 mm may be imaged and consequently biopsied. This Review describes the technique of EUS-FNA in detail, based on a literature review and the authors' extensive experience with this method. The endoscopes and needle systems available on the market are presented in detail. The biopsy procedure is carefully explained, as well as the preparation of the cytology smears. Finally, the limitations and complications of the procedure are reviewed in brief, stressing the low rate of complications (below 1-2%), most of them being minor and self-limiting. Currently endosonography has strengthened its position as a diagnostic and staging method, especially after establishing the method of FNA biopsy. Thus, EUS-FNA is very useful to establish an initial tissue diagnosis of malignancy, but also to accurately stage the patients preoperatively, influencing the decision-making process and reducing the morbidity and mortality that accompanies inappropriate surgical interventions in patients with advanced cancer.