Evaluating Alzheimer's special care units: reviewing the evidence and identifying potential sources of study bias.
Special Care Units (SCUs) for Alzheimer's disease have been proliferating in long-term care, but their effectiveness remains unproven. This review summarizes the published studies, presents and discusses the many potential sources of bias that pose special problems for SCU research, and proposes strategies for conducting and interpreting future outcome studies in this difficult research setting.


Milk production of Holstein heifers fed either alfalfa or corn silage diets at two rates of daily gain.
Seventy-five prepubertal heifers were fed diets based on either alfalfa silage or corn silage plus soybean meal for daily gains of either 725 or 950 g/d in a 2 x 2 factorial. Heifers were fed from 175 to 325 kg of body weight (BW). The alfalfa diet contained more digestible protein and less digestible energy than did the diet containing corn silage plus soybean meal. Actual gains were preexperimental BW gain, 633 g/d; lowest experimental BW gain, 785 g/d; highest experimental BW gain, 994 g/d; lowest postexperimental BW gain, 494 g/d; and highest postexperimental BW gain, 546 g/d. Compensatory postexperimental BW gains of heifers fed a common diet allowed the heifers to calve at 732 d of age. The postcalving BW was 508 kg, and precalving height at withers was 134 cm. A total mixed diet containing 17.1% CP and digestible energy at 3.12 Mcal/kg of dry matter was fed during lactation. Feed intake, milk and milk component production, and milk composition were not affected by either experimental diet or growth rate. As covariates, milk production was related to age at calving and was more strongly related to BW after calving, but no differences were observed among growth diets. Differences in protein and energy concentrations in experimental growth diets did not affect lactation performance. About 75% of total BW gains during the treatment period occurred before puberty, but rate of gain did not affect milk production. This lack of an effect of prepubertal growth rates on the milk production of primiparous heifers is consistent with six other similar studies that were conducted recently.


In vivo imaging of human vasculature in the chorioretinal complex using phase-variance contrast method with phase-stabilized 1-μm swept-source optical coherence tomography.
We present a noninvasive phase-variance (pv)–based motion contrast method for depth-resolved imaging of the human chorioretinal complex microcirculation with a newly developed phase-stabilized high speed (100-kHz A-scans/s) 1-μm swept- ource optical coherence tomography (SSOCT) system. Compared to our previous spectral-domain (spectrometer based) pv-spectral domain OCT (SDOCT) system, this system has the advantages of higher sensitivity, reduced fringe wash-out for high blood flow speeds and deeper penetration in choroid. High phase stability SSOCT imaging was achieved by using a computationally efficient phase stabilization approach. This process does not require additional calibration hardware and complex numerical procedures. Our phase stabilization method is simple and can be employed in a variety of SSOCT systems. Examples of vasculature in the chorioretinal complex imaged by pv-SSOCT from normal as well as diseased eyes are presented and compared to retinal images of the same subjects acquired with fluorescein angiography and indocyanine green angiography. Observations of morphology of vascular perfusion in chorioretinal complex visualized by our method are listed.


Levodopa Dependence and Hypersexuality in an Older Parkinson's Disease Patient.
The authors discuss the relationship between dopaminergic medication abuse and hypersexuality. Tin's is the first reported case of levodopa dependence mediated and reinforced by hypersexuality. The medication abuse started in an attempt to control parkinsonian symptoms but eventually led to high-risk, uncontrollable sexual behavior.


Complete eradication of squamous cell carcinoma of the esophagus with combined chemotherapy and radiotherapy.
Chemotherapy (with 5-fluorouracil and either mitomycin-C or cis-platinum) combined with radiotherapy was used either for palliation or as preoperative therapy in 67 patients with squamous cell carcinoma of the esophagus. In 25 patients having chemotherapy and 5000-6000 rads, good local palliation was obtained in 11 (49%) without surgery. In the remaining 25 patients, swallowing was restored with a variety of procedures (primarily Celestine tube or gastric bypass). The average survival time was seven months and two patients are still alive at 9 and 12.5 months. Of 42 patients receiving preoperative chemotherapy and radiotherapy, 35 had surgery. Of these, 13 (37%) had complete eradication of their tumors with no histologic evidence of carcinoma in the resected esophagus or associated lymph nodes. In another six (17%), the only evidence of tumor was small microscopic foci of cancer cells in the wall of the esophagus. The 6-, 12-, and 24-month survival rates for patients having surgery after the combined preoperative chemotherapy and radiotherapy were 83 per cent, 52 per cent, and 30 per cent, respectively. These results are far superior to those previously obtained.


Effects of haloperidol, clozapine and olanzapine on the survival of human neuronal and immune cells in vitro.
Cytotoxic effects on neuronal as well as on immune cells have been reported for both typical and atypical antipsychotic drugs. We evaluated the effects of different concentrations of a typical (haloperidol) and two atypical (clozapine, olanzapine) antipsychotics on the survival of human neuronal (SH-SY5Y cells) and immune cells (U937 cells) by determining the metabolic activity after 24 h of incubation by the modified tetrazolium method. The dopaminergic neuroblastoma SH-SY5Y and the lymphoma U-937 cell line are well established models for in vitro investigations. To further elucidate possible mechanisms of action we also determined the ATP content in the cultured cells. After experimental treatment, significant effects were detected by Kruskal Wallis test for all treatment conditions. Post-hoc tests (Dunn's method) showed that haloperidol and clozapine at the two highest concentrations (25 and 50 microg/ml) caused a significant decrease of metabolic activity in both cell systems, which was also detectable after treatment with clozapine at a concentration of 12.5 microg/ml in U937 cells. In contrast, olanzapine induced a significant increase in metabolic activity of SH-SY5Y cells at all concentrations except for the concentration of 3.1 microg/ml, whereas the metabolic activity in U937 cells was increased at concentrations of 1.6 and 6.25 microg/ml. For the determination of ATP content, the LD(50) values of the metabolic activity were used, except for olanzapine for which no distinct LD(50) value was available. Significant changes were detected for all treatments and post-hoc tests revealed that haloperidol caused a significant decrease compared to the control condition in both cell systems. These findings suggest that antipsychotic substances of different classes exert differential metabolic effects in both neuronal and immune cell systems.


Paclitaxel-carboplatin induced radiation recall colitis.
Some chemotherapeutic agents can "recall" the irradiated volumes by skin or pulmonary reactions in cancer patients who previously received radiation therapy. We report a recall colitis following the administration of paclitaxel-containing regimen in a patient who had been irradiated for a carcinoma of the uterine cervix. A 63-year-old woman underwent a Wertheim operation because of uterine cervix carcinoma. After 8 years of follow-up, a local recurrence was observed and she received curative external radiotherapy (45 Gy) to the pelvis. No significant adverse events were observed during the radiotherapy. Approximately one year later, she was hospitalized because of metastatic disease with multiple pulmonary nodules, and a chemotherapy regimen consisting of paclitaxel and carboplatin was administered. The day after the administration of chemotherapy the patient had diarrhea and rectal bleeding. Histological examination of the biopsy taken from rectal hyperemic lesions showed a radiation colitis. The symptoms reappeared after the administration of each course of chemotherapy and continued until the death of the patient despite the interruption of the chemotherapy. In conclusion, the probability of recall phenomena should be kept in mind in patients who received previously with pelvic radiotherapy and treated later with cytotoxic chemotherapy.


Transfer of ochratoxin A from raw black tea to tea infusions prepared according to the Turkish tradition.
Ochratoxin A (OTA) is a natural contaminant of food including tea with multiple toxic effects, which poses a threat to human health. In terms of lifestyle, the Turkish population is a frequent visitor of tearooms, and the traditional Turkish tea preparation is one of the most popular ways of preparing tea infusion. The aim of this study was to investigate OTA transfer from raw black tea to the tea infusion prepared according to the Turkish tradition. A high-performance liquid chromatography method with a limit of quantification of 0.35 ng g-1 was used for OTA determination. The OTA amount in raw black teas from Turkey ranged from ≤0.35 ng g-1 up to 56.7 ng g-1 . An homogenised sample of black tea naturally contaminated with 55.0 ng g-1 was used to prepare infusions. The OTA transfer from the black tea to the infusion was found to be 41.5% ± 7%. These data are important for the realisation of a 'Total Diet study' (TDS). The TDS can be a complementary tool to estimate the population dietary exposure to OTA across the entire diet by analysing main foods prepared 'as consumed' (tea infusions) and not 'as purchased' (raw tea). © 2017 Society of Chemical Industry.


Bioactive oligostilbenoids from the stem bark of Hopea exalata.
Hopeanolin (1), an unusual resveratral trimer with an ortho-quinone nucleus, was isolated and characterized from the stem bark of Hopea exalata. Also obtained were six known stibenoids, shoreaphenol (2), vaticanol G (3), alpha-viniferin (4), pauciflorol A (5), vaticanol A (6), and trans-3,5,4'-trihydroxystilbene 2-C-glucoside (7). The structure of 1 was determined by spectroscopic data interpretation. Compounds 1-7 were tested for antifungal activity and inhibitory effects against jack bean urease. Hopeanolin (1) demonstrated antifungal activity in the MIC value range 0.1-22.5 microg/mL.


LiNbO3 surfaces from a microscopic perspective.
A large number of oxides has been investigated in the last twenty years as possible new materials for various applications ranging from opto-electronics to heterogeneous catalysis. In this context, ferroelectric oxides are particularly promising. The electric polarization plays a crucial role at many oxide surfaces, and it largely determines their physical and chemical properties. Ferroelectrics offer in addition the possibility to control/switch the electric polarization and hence the surface chemistry, allowing for the realization of domain-engineered nanoscale devices such as molecular detectors or highly efficient catalysts. Lithium niobate (LiNbO3) is a ferroelectric with a high spontaneous polarization, whose surfaces have a huge and largely unexplored potential. Owing to recent advances in experimental techniques and sample preparation, peculiar and exclusive properties of LiNbO3 surfaces could be demonstrated. For example, water films freeze at different temperatures on differently polarized surfaces, and the chemical etching properties of surfaces with opposite polarization are strongly different. More important, the ferroelectric domain orientation affects temperature dependent surface stabilization mechanisms and molecular adsorption phenomena. Various ab initio theoretical investigations have been performed in order to understand the outcome of these experiments and the origin of the exotic behavior of the lithium niobate surfaces. Thanks to these studies, many aspects of their surface physics and chemistry could be clarified. Yet other puzzling features are still not understood. This review gives a résumé on the present knowledge of lithium niobate surfaces, with a particular view on their microscopic properties, explored in recent years by means of ab initio calculations. Relevant aspects and properties of the surfaces that need further investigation are briefly discussed. The review is concluded with an outlook of challenges and potential payoff for LiNbO3 based applications.


Diffusion-controlled evolution of core-shell nanowire arrays into integrated hybrid nanotube arrays for Li-ion batteries.
Controlled integration of multiple semiconducting oxides into each single unit of ordered nanotube arrays is highly desired in scientific research for the realization of more attractive applications. We herein report a diffusion-controlled solid-solid route to evolve simplex Co(CO3)0.5(OH)0.11H2O@TiO2 core-shell nanowire arrays (NWs) into CoO-CoTiO3 integrated hybrid nanotube arrays (NTs) with preserved morphology. During the evolution procedure, the decomposition of Co(CO3)0.5(OH)0.11H2O NWs into chains of CoCO3 nanoparticles initiates the diffusion process and promotes the interfacial solid-solid diffusion reaction even at a low temperature of 450 °C. The resulting CoO-CoTiO3 NTs possess well-defined sealed tubular geometries and a special "inner-outer" hybrid nature, which is suitable for application in Li-ion batteries (LIBs). As a proof-of-concept demonstration of the functions of such hybrid NTs in LIBs, CoO-CoTiO3 NTs are directly tested as LIB anodes, exhibiting both a high capacity (~600 mA h g(-1) still remaining after 250 continuous cycles) and a much better cycling performance (no capacity fading within 250 total cycles) than CoO NWs. Our work presents not only a diffusion route for the formation of integrated hybrid NTs but also a new concept that can be employed as a general strategy to fabricate other oxide-based hybrid NTs for energy storage devices.


A full revolution: offering 360 degree library services to clinical clerkship students.
In their third year, medical students transition from the classroom to the hospital. Librarians can ease this transition from assignment-based to patient-based information needs, and at the University of Iowa this takes many forms. Preparation begins in the second year with foundational instruction. Customized electronic resource centers aid in selection of specialized resources; demonstrations at clerkship orientations promote these centers; attending morning reports show a librarian on the clinical team; and exercises assess the ability to find quality answers quickly. This combination has improved the students' searching facility and their comfort with library staff. Data show student resource selection became varied and appropriate, although understanding of study designs is suboptimal. Feedback has been positive from both students and faculty. While these techniques have been successful, they are only the first step in an evolving program.


[The study of the contamination and the levels of Campylobacter spp. during the processing of selected types of foods].
The purpose of the work was to study the nature of the Campylobacter spp. contamination during the processing of food products of plant and animal origin (raw poultry and beef meat, raw milk, leafy salads, sliced raw vegetables). In the study of 148 samples 50 strains of Campylobacter spp. (33.8%) were found. For the main phenotypic characteristics they were identified as C. jejuni spp. jejuni and C. jejuni spp. doylei (over 75%). The highest level of detection of campylobacteria (over 45%) was set for raw poultry, including the carcasses of chickens broilers, quails, turkeys and their semi-finished products. 19 of the 27 strains from poultry were identified as C. jejuni. Among the strains isolated from the environment, including swabs from equipment surfaces, 91% of the isolates were also presented by C. jejuni. It was found that the investigated foodstuffs were characterized by high levels of contamination with bacteria of the family Enterobacteriaceae, the content of which was comparable with the identified values of total viable bacteria (cfu). Salmonella was detected in 19% of the investigated poultry samples and in 14.3% of raw cow milk. In the study of swabs from surfaces of poultry processing equipment, the frequency of detection of Campylobacter strains was 38.7%, Salmonella - 12.9%. Most commonly Campylobacter and Salmonella were detected in the zones of primary processing of poultry: the frequency of isolation of Salmonella in slaughter corner was 25%, Campylobacter - 43%. When testing the swabs taken in the cooking zone of «fast food» restaurants Campylobacter and Salmonella were not detected. For studying the swabs from equipment surfaces and the environment for the presence of Campylobacter spp. a modified technique of sampling was developed. The method includes a comprehensive analysis in the test area with the use of three types of media for transportation and incubation of Campylobacter spp. (Preston broth with blood, Brucella broth, Cary-Blair medium), that increase the probability of detection of these pathogens.


[Chapter 5. Health and Big Data: the emergence of an infrastructure law in the digital space].
In the field of health, IoT devices, mobile apps, and online communities generate an enormous amount of data. However, health data benefit from a precise legal definition and protection as sensitive data, whereas well-being data have no specific legal regime. Since those data may contribute to identify individuals' health status, there are potential breaches to confidentiality and privacy. Recent European cases (ECHR and ECJ) reaffirms citizens' fundamental rights to privacy and family life, and to an effective remedy. Such decisions contribute to mitigate the misuse of big data broadly speacking, inclunding in the health sector.


Effects of diabetic neuropathy on body sway and slip perturbation detection in older population.
Postural control is a common mechanism to compensate for unexpected displacements of the body. In the older population, a slip or fall due to a failure of postural control is a common cause of morbidity and mortality. The ability of postural control decreases with aging or neuropathy. In this study, 2 groups, diabetics and non-diabetics in the older population, were compared to determine how patterns of postural sway during quiet standing were related to the detection of perturbation. The SLIP-FALLS system was applied to the measurement of sway and detection of perturbation. In phase 1 of the development of the predictive model, neural network algorithms were applied to find determinant variables for perturbation detection. In phase 2, a fuzzy logic inference system was developed to investigate the relationship between sway and perturbation detection. Results of this study may be applied to the design of floor mats or shoe insoles for preventing fatigue in workplaces.


Effects of housing, perches, genetics, and 25-hydroxycholecalciferol on keel bone deformities in laying hens.
Several studies have shown a high prevalence of keel bone deformities in commercial laying hens. The aim of this project was to assess the effects of perch material, a vitamin D feed additive (25-hydroxyvitamin D(3); HyD, DSM Nutritional Products, Basel, Switzerland), and genetics on keel bone pathology. The study consisted of 2 experiments. In the first experiment, 4,000 Lohmann Selected Leghorn hens were raised in aviary systems until 18 wk of age. Two factors were investigated: perch material (plastic or rubber-coated metal) and feed (with and without HyD). Afterward, the hens were moved to a layer house with 8 pens with 2 aviary systems. Daily feed consumption, egg production, mortality, and feather condition were evaluated. Every 6 wk, the keel bones of 10 randomly selected birds per pen were palpated and scored. In the second experiment, 2,000 Lohmann Brown (LB) hens and 2,000 Lohmann Brown parent stock (LBPS) hens were raised in a manner identical to the first experiment. During the laying period, the hens were kept in 24 identical floor pens but equipped with different perch material (plastic or rubber-coated metal). The same variables were investigated as in the first experiment. No keel bone deformities were found during the rearing period in either experiment. During the laying period, deformities gradually appeared and reached a prevalence of 35% in the first experiment and 43.8% in the second experiment at the age of 65 and 62 wk, respectively. In the first experiment, neither HyD nor the aviary system had any significant effect on the prevalence of keel bone deformities. In the second experiment, LBPS had significantly fewer moderate and severe deformities than LB, and rubber-coated metal perches were associated with a higher prevalence of keel bone deformities compared with plastic perches. The LBPS laid more but smaller eggs than the LB. Again, HyD did not affect the prevalence of keel bone deformities. However, the significant effect of breed affiliation strongly indicates a sizeable genetic component that may provide a basis for targeted selection.


Zinc biosorption by the purple non-sulfur bacterium Rhodobacter capsulatus.
This paper presents the first report providing information on the zinc (Zn) biosorption potentialities of the purple non-sulfur bacterium Rhodobacter capsulatus. The effects of various biological, physical, and chemical parameters on Zn biosorption were studied in both the wild-type strain B10 and a strain, RC220, lacking the endogenous plasmid. At an initial Zn concentration of 10 mg·L(-1), the Zn biosorption capacity at pH 7 for bacterial biomass grown in synthetic medium containing lactate as carbon source was 17 and 16 mg Zn·(g dry mass)(-1) for strains B10 and RC220, respectively. Equilibrium was achieved in a contact time of 30-120 min, depending on the initial Zn concentration. Zn sorption by live biomass was modelled, at equilibrium, according to the Redlich-Peterson and Langmuir isotherms, in the range of 1-600 mg Zn·L(-1). The wild-type strain showed a maximal Zn uptake capacity (Qm) of 164 ± 8 mg·(g dry mass)(-1) and an equilibrium constant (Kads) of 0.017 ± 0.00085 L·(mg Zn)(-1), compared with values of 73.9 mg·(g dry mass)(-1) and 0.361 L·mg(-1) for the strain lacking the endogenous plasmid. The Qm value observed for R. capsulatus B10 is one of the highest reported in the literature, suggesting that this strain may be useful for Zn bioremediation. The lower Qm value and higher equilibrium constant observed for strain RC220 suggest that the endogenous plasmid confers an enhanced biosorption capacity in this bacterium, although no genetic determinants for Zn resistance appear to be located on the plasmid, and possible explanations for this are discussed.


Uncertain future, non-numeric preferences, and the fertility transition: A case study of rural Mozambique.
In many high-fertility countries, and especially in sub-Saharan Africa, substantial proportions of women give non-numeric responses when asked about desired family size. Demographic transition theory has interpreted responses of "don't know" or "up to God" as evidence of fatalistic attitudes toward childbearing. Alternatively, these responses can be understood as meaningful reactions to uncertainty about the future. Following this latter approach, we use data from rural Mozambique to test the hypothesis that non-numeric responses are more common when uncertainty about the future is greater. We expand on previous research linking child mortality and non-numeric fertility preferences by testing the predictive power of economic conditions, marital instability, and adult mortality. Results show that uncertainty related to adult and child mortality and to economic conditions predicts non-numeric responses, while marital stability is less strongly related.


Development and Validation of a Method for the Analysis of Bisoprolol and Atenolol in Human Bone.
A method based on gas chromatography-mass spectrometry (GC-MS) is described for the determination of bisoprolol and atenolol in human bone. After the addition of lobivolol as internal standard, pulverized samples were incubated in acetonitrile for 1 h under ultrasounds. After adjusting the pH of the samples to 6, they were centrifuged, and the supernatants were subjected to solid phase extraction. Elution was achieved by using 3 mL of 2% ammonium hydroxide in 80:20 dichloromethane:isopropanol solution. Eluted samples were evaporated and derivatized. Chromatography was performed on a fused silica capillary column and analytes were determined in the selected-ion-monitoring (SIM) mode. The assay was validated in the range 0.1-0.3 ng/mg (depending on the drug) to 150 ng/mg, the mean absolute recoveries were 60% for bisoprolol and 106% for atenolol, the matrix effect was 69% for bisoprolol and 70% for atenolol and process efficiency was 41% for bisoprolol and 80% for atenolol. The intra- and inter-assay accuracy values were always better than 12%. The validated method was then applied to bone samples from two real forensic cases in which toxicological analysis in blood were positive for atenolol in the first case (0.65 µg/mL) and bisoprolol in the second case (0.06 µg/mL). Atenolol was found in bone samples from the corresponding case at the approximate concentration of 148 ng/mg and bisoprolol was found at 8 ng/mg.


Validation of a picture book to be used in a pan-European dietary survey.
To validate a picture book for estimation of food portion sizes using two approaches: (i) 'perception' of food portions by comparison with a series of food photos; and (ii) 'conceptualization and memory', using the same photos to estimate the amount of served food one hour after self-served food portions. Each partner developed a country-specific picture book based on the so-called EPIC-Soft picture book. Representative and common photo series were chosen achieving approximately 25 % of the original picture book (n 23). Three portions from each photo series were randomly selected. The study was performed within the Pilot study in the view of a Pan-European dietary survey - Adolescents, adults and elderly (PILOT-PANEU) project. A sample of adolescents and adults was recruited in five countries: Bulgaria (n 103), Finland (n 34), Germany (n 69), Hungary (n 62) and Portugal (n 77). Among the portions of the corresponding photo series and depending on the type of food, from 18 % (cheese) to 96 % (ratatouille) of participants chose the correct portions. In the perception study, agreement between the portions shown and reported was substantial (intraclass correlation coefficient (ICC)=0·805) and the mean difference was very low. In the memory study, agreement between the served and reported portions was lower than in the perception study (ICC=0·536). Agreement also seemed to decrease as the appearance of food on the plate differed from food in the picture. Overall, the picture series selected can be applied in future intake surveys to quantify foods similar to those depicted in the pictures.


Determining Gaps in Current Physiatric Tele-Physical Assessments via a Needs Assessment Survey.
Physical examinations are essential for in-person patient visits but remain difficult to replicate during virtual encounters. This work aims to identify gaps in the current state of telemedicine-based physical assessments by surveying physical medicine and rehabilitation physicians who perform physical examinations. A survey of 29 Likert-scale questions and five open-ended questions was distributed to practicing physical medicine and rehabilitation physicians. The Likert-scale questions covered remote physical assessment, access, perception/engagement, implementation/effectiveness, and administrative concerns. Fifty-three participants completed the survey. More than 80% of respondents suggested that while telemedicine was universally well accepted, they could not effectively perform telemedicine-based physical assessments, especially the musculoskeletal and neurological components. Remote assessment of upper and lower limb strength, reflexes, and sensation were examples of key unmet needs. Responses to open-ended questions suggested that telemedicine-based physical assessments can reduce the burden of travel and increase adherence to follow-up visits, but complex technology setup can pose difficulty for older patients and patients with cognitive deficits. These findings suggest that current telemedicine technology is insufficient to meet physical medicine and rehabilitation physicians' telemedicine-based physical assessments needs. Despite high levels of provider and patient engagement with telemedicine, numerous deficits remain in performing musculoskeletal and neurological examinations. These results can inform future technology developments that address these identified telemedicine-based physical assessments gaps.


Aromatic Side Chain Water-to-Lipid Transfer Free Energies Show a Depth Dependence across the Membrane Normal.
Quantitating and understanding the physical forces responsible for the interactions of biomolecules are fundamental to the biological sciences. This is especially challenging for membrane proteins because they are embedded within cellular bilayers that provide a unique medium in which hydrophobic sequences must fold. Knowledge of the energetics of protein-lipid interactions is thus vital to understand cellular processes involving membrane proteins. Here we used a host-guest mutational strategy to calculate the Gibbs free energy changes of water-to-lipid transfer for the aromatic side chains Trp, Tyr, and Phe as a function of depth in the membrane. This work reveals an energetic gradient in the transfer free energies for Trp and Tyr, where transfer was most favorable to the membrane interfacial region and comparatively less favorable into the bilayer center. The transfer energetics follows the concentration gradient of polar atoms across the bilayer normal that naturally occurs in biological membranes. Additional measurements revealed nearest-neighbor coupling in the data set are influenced by a network of aromatic side chains in the host protein. Taken together, these results show that aromatic side chains contribute significantly to membrane protein stability through either aromatic-aromatic interactions or placement at the membrane interface.


[Pharmacoeconomic analysis of using mirabegron to treat overactive bladder in the setting of the Russian Federation health care].
The present paper presents, for the first time in Russia, a comparative pharmacoeconomic analysis of using mirabegron (Betmiga) to treat overactive bladder (OAB). Three medical technologies were evaluated: treatment of OAB with mirabegron 50 mg/day, solifenacin 5 mg/day and solifenacin 10 mg/day. In addition, the strategies of mirabegron and botulinum toxin type A were analyzed as a result of simulating the second-line treatment. When modeling for 1-year horizon, the lowest cost was found in mirabegron strategy, which was 16% lower than with solifenacin. When comparing the second line strategies using mirabegron and botulinum toxin type A, costs of mirabegron group were 61% lower. According to the selected performance criteria, mirabegron was more effective in comparison with other strategies. The findings of the budget impact analysis revealed that using mirabegron was preferable compared with solifenacin as the first line treatment, and compared with botulinum toxin type A as the second-line treatment. The analysis of cost-effectiveness and availability of technology showed growth when using mirabegron strategy; there was an increase in the efficiency of mirabegron strategy relative to solifenacin strategy, accompanied by cost reduction and, as a consequence, reducing the burden on the budget. Thus, using mirabegron to treat OAB both as the first and the second line treatment is absolutely cost-effective and profitable medical technology.


An evaluation of commercial school health software for use in multisite research studies.
Multisite research studies are an ideal way to help specialty nursing organizations move toward evidence-based practice. A necessary requisite of such studies, the ability to collect data efficiently and accurately, can be addressed by adapting commercially available software to the research. This article reviews six commercial software packages designed for school nurses as to their appropriateness for use with multisite studies. The three major criteria considered were (a) whether the software is sophisticated enough to meet the demands of research, (b) whether it is user-friendly, and (c) whether it has reasonable technical specifications. The strengths, weaknesses, appropriateness, and costs of each of the products are reviewed.


Lack of evidence for an unmet need to treat Clostridium difficile infection in infants aged <2 years: expert recommendations on how to address this issue.
The role of Clostridium difficile in causing disease in infants is unclear, and the existence of C. difficile infection (CDI) in this population is controversial. As part of the drug licensing process for new CDI therapies, a pediatric investigation plan is required to define studies in infants aged <2 years. This assumes an unmet medical need, even though clinical trials in this age group may not be feasible. Three pharmaceutical companies developing CDI treatments came together to seek advice from a panel of experts. Our unanimous opinion is that the existence of CDI is questionable in infants, and if it exists, is rare. There is therefore no unmet need for CDI treatment in this population. Interventional studies are not feasible with the current level of knowledge, and studies should be limited to noninterventional studies or open-label pharmacokinetic and safety studies to better define CDI in infants.


Management of acquired cholesteatoma in the pediatric population.
This review focuses on the most recent literature pertaining to pediatric acquired cholesteatoma and aims to integrate findings into a comprehensive management approach. Pediatric acquired cholesteatoma has been shown to differ from the adult variety secondary to anatomy and physiologic factors. Whereas the goals of therapeutic management are ultimately similar in adult and pediatric patients, special considerations must be taken into account when deciding on a treatment plan for a child. Although avoidance of an unstable mastoid cavity is an important consideration in this population, successful management has been reported with canal wall-up, canal wall-down, and hybrid techniques. Second-look procedures are also important when concern of recurrence exists. Newer innovations include endoscopic ear surgery and diffusion-weighted imaging. The principal goal of pediatric cholesteatoma management is eradication of disease. An individualized approach is paramount in yielding superior results in these patients. Special consideration should be given to anatomical and social factors.


Cannabinoid modulation of backpropagating action potential-induced calcium transients in layer 2/3 pyramidal neurons.
Endocannabinoids (eCBs) play a prominent role in regulating synaptic signaling throughout the brain. In layer 2/3 of the neocortex, eCB-mediated suppression of GABA release results in an enhanced excitability of pyramidal neurons (PNs). The eCB system is also involved in spike timing-dependent plasticity that is dependent on backpropagating action potentials (bAPs). Dendritic backpropagation plays an important role in many aspects of neuronal function, and can be modulated by intrinsic dendritic conductances as well as by synaptic inputs. The present studies explored a role for the eCB system in modulating backpropagation in PN dendrites. Using dendritic calcium imaging and somatic patch clamp recordings from mouse somatosensory cortical slices, we found that activation of type 1 cannabinoid receptors potentiated bAP-induced calcium transients in apical dendrites of layer 2/3 but not layer 5 PNs. This effect was mediated by suppression of GABAergic transmission, because it was prevented by a GABAA receptor antagonist and was correlated with cannabinoid suppression of inhibitory synaptic activity. Finally, we found that activity-dependent eCB release during depolarization-induced suppression of inhibition enhanced bAP-induced dendritic calcium transients. Taken together, these results point to a potentially important role for the eCB system in regulating dendritic backpropagation in layer 2/3 PNs.


The psychiatrist and the pain clinic.
The author discusses the difficulties inherent in the role of the psychiatrist in a pain clinic as well as some of the recurring problems that he has seen in this setting. He states that the psychiatrist brings to the understanding of pain a multidimensional approach, which is hard for nonpsychiatrist clinicians to accept, and valuable psychophysical methods for evaluating and quantifying pain. He discusses aspects of the interplay between intrapsychic and interpersonal factors in the pain experience, particularly the relationship between pain and guilt, and illustrates these aspects with case reports.


Is high dose therapy superior to conventional dose therapy as initial treatment for relapsed germ cell tumors? The TIGER Trial.
Metastatic germ cell tumours (GCTs) are usually cured with cisplatin based chemotherapy and standard treatment algorithms are established. However when this treatment fails and the disease relapses, standard treatment is much more uncertain. Both conventional dose therapy (CDT) and high dose therapy (HDT) are widely used, due to the lack of conclusive data supporting one specific approach. A recent retrospective analysis focusing on this population suggested a significant benefit for HDT. Retrospective analyses are prone to bias, and therefore while this data is provocative it is by no mean conclusive. For this reason the international community is supporting a prospective randomised trial in this area comparing CDT(TIP) with sequential HDT (TICE). The planned open labelled randomised phase III study (TIGER) is due to open in 2011 and will recruit 390 patients to detect a 13% difference in 2 year progression free survival (primary endpoint). It is hoped that this large study will conclusively resolve the uncertainty which currently exists.


Definitive chemoradiation at high volume facilities is associated with improved survival in glioblastoma.
The standard of care for glioblastoma (GBM) is maximal safe resection followed by concurrent chemoradiation (CRT). For several neoplasms, receipt of radiation treatment at high-volume facilities has been associated with improved overall survival (OS). The purpose of the present investigation was to determine if there was an association between receipt of CRT for GBM at facilities with a higher case volume and improved OS. The National Cancer Data Base was queried for patients with GBM diagnosed between 2006 and 2012 that received full-course CRT. Statistics included Kaplan-Meier analysis to compare OS between patients treated facilities with the highest quartile volume (HVF) to those treated at lower case volume facilities, multivariate logistic regression to determine factors associated with treatment at a HVF, and Cox proportional hazards modeling to determine variables associated with OS. A total of 4892 patients met the specified criteria. Fourteen facilities (9.9%) treated the highest quartile volume of patients, while 69 (48.6%) treated the lowest quartile volume (LVF) of patients. Treatment at the HVF was associated with improved median OS (16.5 vs. 14.1 months, p < 0.001). Treatment at a LVF also independently predicted for worse OS on multivariate analysis, along with age >70 years, and a resection limited to a biopsy. This is the first study to demonstrate that treatment of GBM with CRT at a HVF is associated with improved survival. Major goals of future oncologic care should be to achieve greater standardization of quality of treatment across facilities with different case volumes.


Glucocorticoids in the cat.
Glucocorticoids are one of the two main classes of hormones, along with mineralocorticoids, which are secreted from the adrenal cortex. Since the discovery of the anti-inflammatory properties of the natural glucocorticoid hydrocortisone, a large number of artificial glucocorticoids have been synthesized to attempt to increase efficacy and decrease side effects. These drugs are now considered one of the most commonly prescribed agents in veterinary practice. The effect of these drugs has been shown to vary significantly between species. Cats appear to tolerate glucocorticoids well, resulting in these drugs being recommended for a wide variety of conditions; however, there are few studies on the effects of glucocorticoids in cats. In this paper we review some of the available literature on glucocorticoid use in the cat.


[Biochemical wound monitoring. PMN elastase in different healing stages after trauma surgery-orthopedic interventions].
Laboratory parameters are of proven value in the diagnosis of early postsurgical infections, since clinical aspects cannot always be clearly defined. Neutrophil granulocytes (PMN) are major inflammatory cells taking effect following ingestion and degradation of foreign material, such as bacteria and cell debris, for example after mechanical trauma. In patients who had undergone surgery we monitored the course of plasma PMN elastase in uncomplicated wound healing (n = 22), in uncomplicated wound healing associated with secondary infections (n = 6), and in defective wound healing (manifestation of a bacterial wound infection: n = 3; wound infection already manifest at the time of entry on study: n = 11). Surgical trauma was accompanied by an increase in PMN elastase and C-reactive protein (CRP) in all patients studied, reaching a maximum within the first 3 postsurgical days. When a bacterial wound infection became manifest during the course of healing there was a highly significant difference on the 4th postsurgical day (p < 0.01) compared with the group with uncomplicated healing. Since PMN elastase can now be determined automatically with an autoanalyser and a commercial kit and its discriminatory time point is as soon as 4-5 days after surgery, it is suggested that this marker should be determined routinely together with CRP in traumatology.


[Actual problems of brain pathology in cerebral microangiopathy].
Cerebral microangiopathy (small vessels disease) is a cause of diffuse changes of brain tissue (encephalopathy) denoted in Russian literature by the term dyscirculatory encephalopathy (DE). The main cause of microangiopathy leading to encephalopathy is arterial hypertension, less frequently - cerebral amyloid angiopathy and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. The diagnosis of encephalopathy in patients with microangiopathy is based on the combination of clinical manifestations (mainly, cognitive impairment of varying severity and disorders of gait) with the neuroimaging changes (white matter hyperintensity, multiple lacunar infarcts on MRI). The causes of DE hyperdiagnosis in Russia, its differential diagnosis with the consequences of recurrent strokes as well as the question of the terminology are considered. The term 'microangioencephalopathy' (instead of DE) to denote encephalopathy in patients with the cerebral small vessel disease is proposed, as more fully reflecting morphological changes of the brain.


Virus epidemics can lead to a population-wide spread of intragenomic parasites in a previously parasite-free asexual population.
Sexual reproduction is problematic to explain due to its costs, most notably the twofold cost of sex. Yet, sex has been suggested to be favourable in the presence of proliferating intragenomic parasites given that sexual recombination provides a mechanism to confine the accumulation of deleterious mutations. Kraaijeveld et al. compared recently the accumulation of transposons in sexually and asexually reproducing lines of the same species, the parasitoid wasp Leptopilina clavipes. They discovered that within asexually reproducing wasps, the number of gypsy-like retrotransposons was increased fourfold, whereas other retrotransposons were not. Interestingly, gypsy-like retrotransposons are closely related to retroviruses. Endogenous retroviruses are retroviruses that have integrated to the germ line cells and are inherited thereafter vertically. They can also replicate within the genome similarly to retrotransposons as well as form virus particles and infect previously uninfected cells. This highlights the possibility that endogenous retroviruses could play a role in the evolution of sexual reproduction. Here, we show with an individual-based computational model that a virus epidemic within a previously parasite-free asexual population may establish a new intragenomic parasite to the population. Moreover and in contrast to other transposons, the possibility of endogenous viruses to maintain a virus epidemic and simultaneously provide resistance to individuals carrying active endogenous viruses selects for the presence of active intragenomic parasites in the population despite their deleterious effects. Our results suggest that the viral nature of certain intragenomic parasites should be taken into account when sex and its benefits are being considered.


[A Case of Multiple Tumor Neurosurgery for Brain Metastasis of Colorectal Cancer].
We report a patient with brain metastasis of rectal cancer who underwent metastatic tumor resection 3 times. In March 2012, a 76-years-old man, diagnosed with Stage III a rectal cancer, underwent Hartmann's operation. The lung metastasis was confirmed in July and November 2013, surgical resection for pulmonary metastasis was performed 2 times. In January 2016, he had difficulty of speaking, and isolated brain tumor was found. We performed surgical resection of brain metastasis in February 2016. In March and July 2016, the gamma knife radiosurgery was performed for other brain metastasis. In July 2016, he occurred nausea, headache and right identity hemi-blindness. Two new brain tumors were revealed. We performed surgical resection again. Three months after second brain surgery, he had dysarthria and a solitary brain tumor was confirmed. We performed third neurosurgical resection. All tumors of brain were found to be metastasis from rectal cancer in histological study. Currently, 16 months have passed since the first diagnosis of brain metastasis of this patient, and the quality of life was good relatively. The prognosis of the patients with brain metastasis is poor generally. However, this case suggested that multiple surgical resection of brain metastasis could improve prognosis and quality of life of patients. Accumulation of further cases is needed.


The effect of human immunodeficiency virus-1 protease inhibitors on the toxicity of a variety of cells.
Protease inhibitors in combination with other antiretroviral drugs have been shown to be efficacious in treating human immunodeficiency virus-1 (HIV-1) infection. The side effects of such a treatment usually involve perturbations of fat metabolism and insulin responsiveness. This has led to a number of studies on the adverse effects of these drugs in vitro. The concentrations of various protease inhibitors used in many of these studies were >20 microM. Although some investigators did address the toxicity of protease inhibitors, no overall effort was made to examine this effect during differentiation of fat or muscle. In this study, we assessed the toxicity of HIV-1 protease inhibitors over a range of concentrations (i.e., 0 to 100 microM) in nondifferentiating (e.g., human fibroblasts, 3T3-L1 preadipocytes, and L6 myoblasts) and differentiated cells (e.g., L6 myotubes). The most toxic protease inhibitor in all cell types was Saquinavir (sqv), whereas the least toxic protease inhibitor was Indinavir (idv). Ritonavir (rtv) and Amprenavir (apv) were more toxic than idv but not quite as toxic as sqv. In 3T3-L1 preadipocytes, treatment with sqv, rtv, and apv resulted in toxicity, whereas idv was not toxic even at the highest concentration used. Indinavir was not toxic to L6 myoblasts or L6 myotubes; however, sqv, rtv, and apv caused toxicity in L6 myoblasts. Saquinavir decreased L6 myotube viability in a dose-dependent manner. Human immunodeficiency virus-1 protease inhibitors were shown to be toxic in a variety of cell types. These effects on human fibroblasts and muscle cells have not been reported previously.


Bone Ingrowth Around an Uncemented Femoral Implant Using Mechanoregulatory Algorithm: A Multiscale Finite Element Analysis.
The primary fixation and long-term stability of a cementless femoral implant depend on bone ingrowth within the porous coating. Although attempts were made to quantify the peri-implant bone ingrowth using the finite element (FE) analysis and mechanoregulatory principles, the tissue differentiation patterns on a porous-coated hip stem have scarcely been investigated. The objective of this study is to predict the spatial distribution of evolutionary bone ingrowth around an uncemented hip stem, using a three-dimensional (3D) multiscale mechanobiology-based numerical framework. Multiple load cases representing a variety of daily living activities, including walking, stair climbing, sitting down, and standing up from a chair, were used as applied loading conditions. The study accounted for the local variations in host bone material properties and implant-bone relative displacements of the macroscale implanted FE model, in order to predict bone ingrowth in microscale representative volume elements (RVEs) of 12 interfacial regions. In majority RVEs, 20-70% bone tissue (immature and mature) was predicted after 2 months, contributing toward a progressive increase in average Young's modulus (1200-3000 MPa) of the interbead tissue layer. Higher bone ingrowth (mostly greater than 60%) was predicted in the anterolateral regions of the implant, as compared to the posteromedial side (20-50%). New bone tissue was formed deeper inside the interbead spacing, adhering to the implant surface. The study helps to gain an insight into the degree of osseointegration of a porous-coated femoral implant.


Absolute risk or relative risk? A study of intraspecies and interspecies extrapolation of chemical-induced cancer risk.
We have used the CBDS database of the National Toxicology Program to study the difference between absolute risk and relative risk models for interspecies and intersex predictions of cancer risk. For no combination (class) of tumor and site is the prediction good for all chemicals. The variation in predicted risk between chemicals exceeds the difference in risks resulting from application of these two models. On the whole, it appears that relative risk is a better model.


Measurement of driving force of catalytic nanomotors in dilute hydrogen peroxide by torsion balance.
A simple torsion balance is designed to directly determine the force generated by catalytic nanomotor nanorods. A 1 cm1 silicon substrate coated with approximately 3.1 x 10(8) nanomotors was attached to a balancing weight and submerged into different concentrations of hydrogen peroxide. The force generated through the catalytic reaction leads to a measurable torque applied to the torsion balance. The force is on the order of 10(-14)-10(-13) N per individual nanomotor and has a linear concentration dependence with a slope of 4.82 x 10(-14) N per percentage of hydrogen peroxide in agreement with previous studies.


HEart and BRain interfaces in Acute ischemic Stroke (HEBRAS)--rationale and design of a prospective oberservational cohort study.
An effective diagnostic work-up in hospitalized patients with acute ischemic stroke is vital to optimize secondary stroke prevention. The HEart and BRain interfaces in Acute ischemic Stroke (HEBRAS) study aims to assess whether an enhanced MRI set-up and a prolonged Holter-ECG monitoring yields a higher rate of pathologic findings as compared to diagnostic procedures recommended by guidelines (including stroke unit monitoring for at least 24 h, echocardiography and ultrasound of brain-supplying arteries). Prospective observational single-center study in 475 patients with acute ischemic stroke and without known atrial fibrillation. Patients will receive routine diagnostic care in hospital as wells as brain MRI, cardiac MRI, MR angiography of the brain-supplying arteries and Holter-monitoring for up to 10 days. Study patients will be followed up for cardiovascular outcomes at 3 and 12 months after enrollment. By comparing the results of routine diagnostic care to the study-specific MRI/ECG approach, the primary outcome of HEBRAS is the proportion of stroke patients with pathologic diagnostic findings. Predefined secondary outcomes are the association of stroke localization, autonomic dysbalance and cardiac dysfunction as well as the effect of impaired heart-rate-variability on long-term clinical outcome. The investigator-initiated HEBRAS study will assess whether an enhanced MRI approach and a prolonged ECG monitoring yield a higher rate of pathological findings than current standard diagnostic care to determine stroke etiology. These findings might influence current diagnostic recommendations after acute ischemic stroke. Moreover, HEBRAS will determine the extent and clinical impact of stroke-induced cardiac damage. Clinicaltrials.gov NCT02142413.


Electron transport through YBa2Cu3O7-delta grain boundary interfaces between 4.2 and 300 K.
The current-induced dissipation in YBa(2)Cu(3)O(7-delta) grain boundary tunnel junctions has been measured between 4.2 and 300 K. It is found that the resistance of 45 degrees (100)/(110) junctions decreases linearly by a factor of 4 when their temperature is increased from 100 to 300 K. At the superconducting transition temperature T(c) the grain boundary resistance of the normal state and of the superconducting state extrapolates to the same value.


Can ovarian aging be delayed by pharmacological strategies?
Aging has been regarded as a treatable condition, and delaying aging could prevent some diseases. Ovarian aging, a special type of organ senescence, is the earliest-aging organ, as ovaries exhibit an accelerated rate of aging with characteristics of gradual declines in ovarian follicle quantity and quality since birth, compared to other organs. Ovarian aging is considered as the pacemaker of female body aging, which drives the aging of multiple organs of the body. Hence, anti-ovarian aging has become a research topic broadly interesting to both biomedical scientists and pharmaceutical industry. A marked progress has been made in exploration of possible anti-ovarian agents or approaches, such as calorie restriction mimetics, antioxidants, autophagy inducers etc., over the past years. This review is attempted to discuss recent advances in the area of anti-ovarian aging pharmacology and to offer new insights into our better understanding of molecular mechanisms underlying ovarian aging, which might be informative for future prevention and treatment of ovarian aging and its related diseases.


Robust shrinking ellipsoid model predictive control for linear parameter varying system.
In this paper, a new off-line model predictive control strategy is presented for a kind of linear parameter varying system with polytopic uncertainty. A nest of shrinking ellipsoids is constructed by solving linear matrix inequality. By splitting the objective function into two parts, the proposed strategy moves most computations off-line. The on-line computation is only calculating the current control to assure the system shrinking into the smaller ellipsoid. With the proposed formulation, the stability of the closed system is proved, followed with two numerical examples to demonstrate the proposed method's effectiveness in the end.


Bacterial colonization of nasal mucosa induces expression of siderocalin, an iron-sequestering component of innate immunity.
Host-microbe interactions often begin with colonization of mucosal surfaces. These relationships are highly specific, as certain microbial species are found only in particular microenvironments. Transcriptional microarrays were used to screen host genes whose expression in the murine nasal mucosa was affected by colonization with the Gram-positive bacterium Streptococcus pneumoniae. Siderocalin (Scn, or lipocalin 2 or neutrophil gelatinase-associated lipocalin) expression was increased up to 65-fold during colonization by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western analysis showed that Scn was secreted into airway surface fluid in colonized animals. Immunohistochemical analysis localized Scn expression primarily to secretory Bowman's glands. Similar results were observed during colonization with the Gram-negative bacterium Haemophilus influenzae, suggesting that Scn secretion is a general response. Western analysis of human nasal secretions also demonstrated secretion of Scn at potentially bacteriostatic levels. This is a previously unrecognized response that may have a role in determining the establishment or maintenance of mucosal colonization. Scn contributes to antimicrobial defence by sequestration of a subset of microbial siderophores. As neither S. pneumoniae nor H. influenzae are known to produce or utilize siderophores, successful colonizers of the nasal passages may have evolved siderophore-independent mechanisms to acquire essential iron and to evade the inhibitory effects of Scn.


Automated prescription of oblique brain 3D magnetic resonance spectroscopic imaging.
Two major difficulties encountered in implementing Magnetic Resonance Spectroscopic Imaging (MRSI) in a clinical setting are limited coverage and difficulty in prescription. The goal of this project was to automate completely the process of 3D PRESS MRSI prescription, including placement of the selection box, saturation bands and shim volume, while maximizing the coverage of the brain. The automated prescription technique included acquisition of an anatomical MRI image, optimization of the oblique selection box parameters, optimization of the placement of outer-volume suppression saturation bands, and loading of the calculated parameters into a customized 3D MRSI pulse sequence. To validate the technique and compare its performance with existing protocols, 3D MRSI data were acquired from six exams from three healthy volunteers. To assess the performance of the automated 3D MRSI prescription for patients with brain tumors, the data were collected from 16 exams from 8 subjects with gliomas. This technique demonstrated robust coverage of the tumor, high consistency of prescription and very good data quality within the T2 lesion.


A collaborative clinical and population-based curriculum for medical students to address primary care needs of the homeless in New York City shelters : Teaching homeless healthcare to medical students.
Background Millions of Americans experience homelessness annually. Medical providers do not receive adequate training in primary care of the homeless.Methods Starting in 2012, a comprehensive curriculum was offered to medical students during their family medicine or ambulatory clerkship, covering clinical, social and advocacy, population-based, and policy aspects. Students were taught to: elicit specific social history, explore health expectations, and assess barriers to healthcare; evaluate clinical conditions specific to the homeless and develop plans for care tailored toward patients' medical and social needs; collaborate with shelter staff and community organizations to improve disease management and engage in advocacy efforts. A mixed methods design was used to evaluate students' knowledge, attitudes, and skills including pre- and post-curriculum surveys, debriefing sessions, and observed clinical skills.Results The mean age of the students (n = 30) was 26.5 years; 55 % were female. The overall scores improved significantly in knowledge, attitude, and self-efficacy domains using paired t‑test (p < 0.01). Specific skills in evaluating mental health, substance abuse, and risky behaviours improved significantly (p < 0.05). In evaluation of communication skills, the majority were rated as having 'outstanding rapport with patients.'Conclusions Comprehensive and ongoing clinical component in shelter clinics, complementary teaching, experienced faculty, and working relationship and collaboration with community organizations were key elements.


Sublexical components in implicit memory for novel words.
Five experiments investigated the role of sublexical components in implicit memory for novel words. Priming on an implicit word judgement task occurred consistently for nonwords formed out of familiar linguistic components (morphemes and syllables) but minimally for nonwords formed out of unfamiliar pseudosyllabic components. This effect was dissociable from explicit memory and insensitive to changes in the surface features of the stimuli. Moreover, it depended on unitization of stimulus components as opposed to priming of individual components. Results are interpreted in terms of the activation and integration of prior linguistic knowledge and as evidence against the role of new (perceptual or episodic) representations in implicit memory for new information.


Effects of rat bile infusion on renal function in rats.
The influence of rat bile infusion on renal function in rats and the possible role of bile-induced hemolysis in these effects were examined. The hemolytic action of rat bile and some bile salts were determined in vitro. After the i.v. infusion of rat bile (70 mg freeze-dried powder/2.55 ml) into pentobarbitone-anesthetized rats, the urine, sodium and potassium excretion rates were reduced more than half, which was due to the decrease of glomerular filtration rate and increase of tubular water and sodium reabsorption. A fall in blood pressure, a rise in hematocrit, and hemolysis were also found. Infusion of hemolysed (30 microliters RBC) solution produced by distilled water and then made isotonic caused a short-duration increase in renal excretion and glomerular filtration rate, and the blood pressure was unchanged. Infusion of a rat bile-hemolysed solution after removal of bile acids with cholestyramine increased renal excretions at first with reduction thereafter. Infusion of the rat bile-hemolysed solution treated with barium sulfate produced a renal response very similar to rat bile alone. It is proposed that two factors are involved in the renal response after bile infusion, namely bile acid-induced hemolysis producing diuresis with natriuresis, and bile acid-induced antidiuresis and antinatriuresis, possibly due to a direct renal effect.


Differential Electrochemical Conductance Imaging at the Nanoscale.
Electron transfer in proteins is essential in crucial biological processes. Although the fundamental aspects of biological electron transfer are well characterized, currently there are no experimental tools to determine the atomic-scale electronic pathways in redox proteins, and thus to fully understand their outstanding efficiency and environmental adaptability. This knowledge is also required to design and optimize biomolecular electronic devices. In order to measure the local conductance of an electrode surface immersed in an electrolyte, this study builds upon the current-potential spectroscopic capacity of electrochemical scanning tunneling microscopy, by adding an alternating current modulation technique. With this setup, spatially resolved, differential electrochemical conductance images under bipotentiostatic control are recorded. Differential electrochemical conductance imaging allows visualizing the reversible oxidation of an iron electrode in borate buffer and individual azurin proteins immobilized on atomically flat gold surfaces. In particular, this method reveals submolecular regions with high conductance within the protein. The direct observation of nanoscale conduction pathways in redox proteins and complexes enables important advances in biochemistry and bionanotechnology.


Modeling and minimizing interference from corneal birefringence in retinal birefringence scanning for foveal fixation detection.
Utilizing the measured corneal birefringence from a data set of 150 eyes of 75 human subjects, an algorithm and related computer program, based on Müller-Stokes matrix calculus, were developed in MATLAB for assessing the influence of corneal birefringence on retinal birefringence scanning (RBS) and for converging upon an optical/mechanical design using wave plates ("wave-plate-enhanced RBS") that allows foveal fixation detection essentially independently of corneal birefringence. The RBS computer model, and in particular the optimization algorithm, were verified with experimental human data using an available monocular RBS-based eye fixation monitor. Fixation detection using wave-plate-enhanced RBS is adaptable to less cooperative subjects, including young children at risk for developing amblyopia.


Towards a national patient card system in Japan.
Patient Card Systems (PCS) have been applied on a regional level to improve access to patient information. However, current projects lack a vision of future integration on a national level. In addition, Integrated Circuit cards and optical cards were introduced without considering that their cost and capacity limits impose significant constraints for future integration. The major arguments against PCS are the huge costs incurred by such a system and the limitations of the card capacities. In addition, standards and legislation have not been sufficiently developed. In this study, we propose a new model of PCS that employs recent communication and card technologies as a key to access a national medical information center. We demonstrate that PCS are feasible if implemented in several distinct phases and if the acceptance and cooperation of physicians and patients are achieved. However, political consensus about the necessity of reform in the health care sector must be established so that the necessary legislation can be enacted.


Tumor Site-Specific Cleavage Improves the Antitumor Efficacy of Antibody-Drug Conjugates.
Antibody-drug conjugates (ADCs) play important roles in tumor therapy. However, traditional ADCs are limited by the extremely large molecular weight of the antibody molecules, which results in low permeability into solid tumors. The use of small ADCs may be expected to alleviate this problem, but this switch brings the new limitation of a greatly shortened blood circulation half-life. Here, we propose a new cleavable ADC design with excellent tumor tissue permeability and a long circulation half-life by fusing the small ADC ZHER2-MMAE with the Fc domain of the antibody for circulation half-life extension, and inserting a digestion sequence between them to release the small ADC inside tumors for better tumor penetration. The experimental results showed that the designed molecule Fc-U-ZHER2-MMAE has a significantly increased blood circulation half-life (7.1 h, 59-fold longer) compared to the small ADC ZHER2-MMAE, and significantly improved drug accumulation ability at tumor sites compared to the conventional full-length antibody-coupled ADC Herceptin-MMAE. These combined effects led to Fc-U-ZHER2-MMAE having significantly enhanced tumor treatment ability, as shown in mouse models of NCI-N87 gastric cancer and SK-OV-3 ovarian cancer, where Fc-U-ZHER2-MMAE treatment achieved complete regression of tumors in all or a portion of animals with no obvious side effects and an MTD exceeding 90 mg/kg. These data demonstrate the therapeutic advantages of this cleavable ADC strategy, which could provide a new approach for ADC design.


[The peak flow meter: limited role in the diagnosis and follow-up of children with asthma].
The peak flow meter is commonly used to diagnose and follow up asthma in children and adults. This practice, however, is not supported by evidence from the literature. The amount of overlap in peak flow level and variation between healthy and asthmatic subjects precludes the use of peak flow diaries as a reliable tool in diagnosing asthma. It has also become clear that the correlation between peak flow variation and other indices of asthma severity is inconsistent. Moreover, children and adults have been shown to be unreliable in keeping peak flow diaries: 20-40% of all recorded values in a peak flow diary are invented, and another 25% are recorded inaccurately. Finally, self-management programmes for asthma have been shown to be effective, whether they incorporate peak flow monitoring or not. Therefore, peak flow registration cannot be recommended for the routine diagnosis and follow-up of asthma. In isolated cases however, such as patients who poorly perceive a deterioration of their asthma, or when it is unclear what triggers asthmatic symptoms, the peak flow meter can be useful.


Meta-analysis comparing doublet and single cytotoxic agent therapy as first-line treatment in elderly patients with advanced nonsmall-cell lung cancer.
To perform a systematic review and meta-analysis comparing doublet versus single agent therapy in elderly patients with advanced nonsmall-cell lung cancer (NSCLC). PubMed® and Cochrane databases, and American Society of Clinical Oncology, World Congress of Lung Cancer, and European Society of Medical Oncology abstracts were searched. Endpoints were overall survival (OS), 1-year survival rate (1-year SR), overall response rate (ORR), and grade 3/4 adverse events. Subgroup analyses were based on chemotherapy regimens and race. Out of 11 studies (13 randomized trials; n = 2782), doublet therapy was associated with significantly increased OS (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.83, 0.95), 1-year SR (risk ratio [RR] 1.15, 95% CI 1.04, 1.28), and ORR (RR 1.39, 95% CI 1.39, 1.86) versus single-agents. Chemotherapy regimen-based subgroup analyses favoured platinum-based doublet therapy for OS (RR 0.71, 95% CI 0.60, 0.84), 1-year SR (RR 1.28, 95% CI 1.11, 1.47), and ORR (RR 1.88, 95% CI 1.49, 2.38). Race-based subgroup analyses revealed increased benefit from doublet therapy in Asian populations for ORR (RR 1.70, 95% CI 1.29, 2.23) but not increased survival benefit. Higher incidences of grade 3/4 anaemia (RR 2.23, 95% CI 1.61, 3.09), thrombocytopenia (RR 2.47, 95% CI 1.17, 5.20), and fatigue (RR 1.36, 95% CI 1.06, 1.74) were observed with doublet versus single-agent therapy. Doublet therapy was associated with significantly increased OS, 1-year SR and ORR compared with single agent therapy. Race may be considered when choosing doublet versus single-agent therapy as first-line treatment of NSCLC in elderly patients.


Serum glucose and electrolyte levels in alcohol-intoxicated adolescents on admission to the emergency department: an unmatched case-control study.
Aimed at examining serum glucose and electrolytes concentrations in adolescents with acute alcohol intoxication (AAI) on admission to the pediatric Emergency Department (ED), a retrospective unmatched, case-control study was conducted. Two cohorts of adolescents were compared, patients presenting with AAI and patients presenting with non-alcohol intoxication. The study group included ED patients aged 12-18 years with AAI. The control group included ED patients aged 12-18 years who had poisoning from a non-illicit drug. Demographic characteristics and glucose and electrolyte blood levels were extracted from the medical files. The records of patients who were admitted between January 2007 and December 2009 were analyzed. The study group and the control group included 106 subjects and 27 subjects, respectively. The study subjects had serum ethanol levels in the range of 55.6-297 mg/dL. No case of hypoglycemia was recorded. The study subjects had higher glucose levels and lower potassium levels compared to the controls (p < 0.005 and p < 0.0001, respectively). No such difference was found when the levels of sodium and bicarbonate were compared (p = 0.3 and p = 0.14, respectively). In conclusion, the findings of this study suggest that at presentation to the ED adolescents with AAI are at low risk for hypoglycemia.


Potential application of a low-viscosity and high-transparency xanthan gum produced from Xanthomonas campestris CCTCC M2015714 in foods.
Xanthan gum is commonly used as a thickener in food industry, while the usage of xanthan gum as a dietary fiber is restricted for its low additive volume. Herein, the potential use of a low-viscosity and high-transparency xanthan gum as a dietary fiber was evaluated in vitro. This new xanthan shows better transparency and faster dissolution rate than most commercial products, and its viscosity increases along with the treatment of freeze-thaw cycles at -20°C. Moreover, this new xanthan can absorb heavy metals (Pb, Cd, Cu) and retard starch digestion by glucoamylase. In summary, this new xanthan could be potentially used as a dietary fiber or fiber ingredient for preventing and treating diabetes, hyperlipemia, heavy metal poisoning, and cardiovascular diseases effectively.


Sonography of small renal masses with indeterminant density characteristics on computed tomography.
Nine small renal masses with attenuation coefficients greater than 20 HU on computed tomography (CT) were termed indeterminate for cyst or renal cell carcinoma. Correlative sonography identified the fluid-filled internal architecture in four of five cysts and correctly characterized as solid four small renal cell carcinomas. The sonogram was particularly valuable in assessing masses that were indeterminate on CT when enhancement was equivocal or when intravenous contrast could not be administered. We conclude that sonography is extremely useful as a noninvasive procedure in evaluating the occasional small renal mass with CT number greater than 20 HU.


[Polysaccharide of Atractylodis Macrocephalae Rhizoma inhibits expression of immune checkpoint PD-L1 by targeting miR-34a in esophageal carcinoma cells].
The immune checkpoint programmed cell death-ligand 1(PD-L1)-mediated immunosuppression is among the important features of tumor. PD-L1, an immunosuppressant, can induce T cell failure by binding to programmed cell death-1(PD-1). Thus, the key to restoring the function of T cells is inhibiting the expression of PD-L1. The Chinese medicinal Atractylodis Macrocephalae Rhizoma(AMR) has the anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic activities, and the polysaccharide in AMR(PAMR) plays a crucial role in immunoregulation, but the influence on the immune checkpoints which are closely related to immunosuppression has not been reported. MicroRNA-34 a(miR-34 a) expression in esophageal carcinoma tissue is significantly lower than that in normal tissue. This study aims to investigate the inhibitory effect of PAMR on esophageal carcinoma cells, and the relationship between its inhibitory effect on PD-L1 expression and miR-34 a, which is expected to clarify the anti-tumor mechanism of PAMR. Firstly, different human esophageal carcinoma cell lines(EC9706, EC-1, TE-1, EC109 cells) were screend out, and expression of PD-L1 was determined. Then, EC109 cells, with high expression of PD-L1, were selected for further experiment. The result showed that PAMR suppressed EC109 cell growth. According to the real-time quantitative PCR(qPCR) and Western blot, it significantly suppressed the mRNA and protein expression of PD-L1, while promoting the expression of tumor suppressor miR-34 a. The confocal microscopy and luci-ferase assay proved that PAMR alleviated the inhibitory effect of PD-L1 while blocked miR-34 a. Additionally, the expression of PD-L1 was controlled by miR-34 a, and the combination of miR-34 a inhibitor with high-dose PAMR reversed the inhibitory effect of PAMR on PD-L1 protein expression. Thus, the PAMR may inhibit PD-L1 by increasing the expression of miR-34 a and regulating its downstream target genes. In conclusion, PAMR inhibits the expression of PD-L1 mainly by inducing miR-34 a.


Evaluation of five imidazopyrazinone-type chemiluminescent superoxide probes and their application to the measurement of superoxide anion generated by Listeria monocytogenes.
Superoxide-triggered chemiluminescence of five new imidazopyrazinone derivatives was investigated using the hypoxanthine-xanthine oxidase system as the source of superoxide anion. The results showed that they are highly sensitive and have favorable properties in measuring superoxide anion. With those new probes, the generation of superoxide anion from the bacteria Listeria monocytogenes was examined. The results confirmed the previous report that L. monocytogenes is an unusual organism that extracellularly and continuously generates a high level of superoxide anion in the presence of acetaldehyde. The data indicated that two of the probes, 3,7-dihydro-2-methyl-6-phenylethynylimidazo[1,2-a]pyrazin-3- one (4) and its methoxy derivative (5), are highly sensitive and useful in the measurements of superoxide anion and are clearly superior to 3,7-dihydro-2-methyl-6-(4-methoxyphenyl)imidazo[1,2-a]pyrazin-3-on e (MCLA), which-has been generally considered the most sensitive superoxide probe in the past. When tested at a probe concentration of 3.3 microM, the luminescence response and the signal-background ratio of compound 4 were 1.5 and 2.5 times those of MCLA, respectively, and the signal-background ratio of compound 5 was almost 15 times that of MCLA, though the luminescence response of this compound was slightly lower than that of MCLA. The low probe concentration used enhances the usefulness of probes in the measurements of superoxide in functioning biological systems.


An interactive program to calculate the treatment time for 60Co single beam, opposing beam, and rotational beam radiation therapy.
An interactive computer program for calculating treatment times for 60Co single beam, opposing beam, or rotational beam radiation therapy is described. The program allows the user to enter parameters specific to his machine. Analytic expressions are used to represent the depth dose, backscatter factor, tissue-air ratio, collimator factor, and beam attenuation of a block-carrying tray.


Contribution of diacylglycerol lipase β to pain after surgery.
Metabolism of the endocannabinoid 2-arachidonoylglycerol (2-AG) yields arachidonic acid (AA), the precursor to proalgesic eicosanoids including prostaglandin E2 (PGE2). Diacylglycerol lipase β (DAGLβ) is an enzyme that synthesizes 2-AG and its inhibition reduces eicosanoid levels and produces antinociceptive effects in models of inflammatory pain. Here we test whether inhibition of DAGLβ produces antinociceptive effects in a model of postoperative pain. Rats were administered the selective DAGLβ inhibitor KT109 or vehicle and underwent plantar incision. Postsurgical pain/disability was examined using evoked (mechanical hyperalgesia), functional (incapacitance/weight bearing), and functional/spontaneous (locomotion) modalities. Activity-based protein profiling confirmed that KT109 inhibited DAGLβ in the lumbar spinal cord (LSC) and brain, confirming that it is a systemically active DAGLβ inhibitor. Treatment with KT109 reduced basal 2-AG, AA, and PGE2 levels in the liver but not the brain, indicating that DAGLβ activity does not significantly contribute to basal PGE2 production within the central nervous system. Plantar incision elevated the levels of 2-AG and PGE2 in the LSC. Although KT109 did not alter postsurgical 2-AG levels in the LSC, it slightly reduced PGE2 levels. In contrast, the clinically efficacious cyclooxygenase inhibitor ketoprofen completely suppressed PGE2 levels in the LSC. Similarly, KT109 had no significant effect upon postsurgical 2-AG, AA, or PGE2 levels at the incision site, while ketoprofen abolished PGE2 production at this location. KT109 and ketoprofen reversed the weight bearing imbalance induced by plantar incision, yet neither KT109 nor ketoprofen had any significant effect on mechanical hyperalgesia. Treatment with ketoprofen partially but significantly rescued the locomotor deficit induced by incision while KT109 was without effect. DAGLβ is not the principal enzyme that controls 2-AG derived AA and PGE2 production after surgery, and inhibitors targeting this enzyme are unlikely to be efficacious analgesics superior to those already approved to treat acute postoperative pain.


Soil enzyme responses to land use change in the tropical rainforest of the Colombian Amazon region.
Soil enzymes mediate key processes and functions of the soils, such as organic matter decomposition and nutrient cycling in both natural and agricultural ecosystems. Here, we studied the activity of five extracellular soil enzymes involved in the C, N, and P-mineralizing process in both litter and surface soil layer of rainforest in the northwest region of the Colombian Amazon and the response of those soil enzymes to land use change. The experimental study design included six study sites for comparing long-term pasture systems to native forest and regeneration practices after pasture, within the main landscapes of the region, mountain and hill landscapes separately. Results showed considerable enzymatic activity in the litter layer of the forest, highlighting the vital role of this compartment in the nutrient cycling of low fertility soils from tropical regions. With the land use transition to pastures, changes in soil enzymatic activities were driven by the management of pastures, with SOC and N losses and reduced absolute activity of soil enzymes in long-term pastures under continuous grazing (25 years). However, the enzyme activities expressed per unit of SOC did not show changes in C and N-acquiring enzymes, suggesting a higher mineralization potential in pastures. Enzymatic stoichiometry analysis indicated a microbial P limitation that could lead to a high catabolic activity with a potential increase in the use of SOC by microbial communities in the search for P, thus affecting soil C sequestration, soil quality and the provision of soil-related ecosystem services.


Magnetic Resonance Imaging Findings and Their Association with Electroencephalogram Data in Children with Partial Epilepsy.
Background It is important to identify the neuroimaging features that are associated with partial epilepsy in children. Advances in technology have recently been made to localize focal epileptogenic lesions, especially high-resolution structural imaging with magnetic resonance imaging (MRI). The recommendation that electroencephalography (EEG) should be the gold standard and that MRI should be optional has been questioned. The present study aims to evaluate the efficacy of MRI in children with partial epilepsy and to compare the diagnostic yields of MRI and EEG data. Methods The present study was conducted among one hundred twelve 1- to 6-year-old children with partial epilepsy. All patients underwent EEG and brain MRI. The epileptogenic lesions were identified on the basis of the signal intensities and morphological abnormalities seen on MRI. The correlation between MRI and EEG abnormal findings was analyzed using a chi-square test. Results Abnormal MRI findings were present in 34.8% (n = 39) of the sample. The EEG and MRI data agreed with respect to classifications into abnormal or normal in 48.2% of the sample (n = 54). Of the 27 patients with normal EEG findings, six (22.2%) had abnormal MRI findings. Inter-rater agreement showed the compatibility between EEG and MRI not significant (weighted Kappa = 0.105). Conclusion A number of MRI abnormalities were found in our study of otherwise normal children, although the correlation between these results was not clear. The follow-up of these children will help us identify the important abnormalities. Despite the small sample size, our results showed that normal EEG findings do not predict normal brain MRI data in children with partial epilepsy.


Postmortem Fetal Temperature Estimation with Magnetic Resonance Imaging: Apparent Diffusion Coefficient Measurements in the Vitreous Body and Cerebrospinal Fluid.
Magnetic resonance imaging (MRI) is increasingly used in postmortem fetal imaging. Several factors influence the quality of MRI in this setting, such as small size, autolytic and maceration changes, and temperature. Knowing the fetal temperature at the time of scanning can improve the MRI interpretation. Temperature can be calculated using diffusion-weighted imaging with measurements of the apparent diffusion coefficient (ADC) in the cerebrospinal fluid (CSF). However, this is complicated by small ventricle size and hemorrhage and, therefore, may be unreliable in postmortem imaging. The current study evaluated the feasibility and reliability of using the ADC for temperature measurements of the vitreous body compared to that of CSF. Two lambs were scanned postmortem at five different time points over 28 hours. Furthermore, 10 stillborn fetuses were scanned once, at 4 to 62 hours after birth. The temperature was measured with a digital thermometer and calculated using the ADCs of the vitreous body (lambs and fetuses) and CSF (fetuses). There was an excellent correlation between measured and calculated temperatures in vitreous bodies of lambs (r = 0.997, P < 0.001) and fetuses (r = 0.970, P < 0.001). The correlation between measured and calculated temperatures in the CSF was poor (r = 0.522, P = 0.122). The calculation of the temperature based on the ADC of the vitreous body is feasible and reliable for postmortem fetal imaging.


Caffeine stimulates locomotor activity in the mammalian spinal cord via adenosine A1 receptor-dopamine D1 receptor interaction and PKA-dependent mechanisms.
Caffeine is a potent psychostimulant that can have significant and widely variable effects on the activity of multiple neuronal pathways. The most pronounced caffeine-induced behavioral effect seen in rodents is to increase locomotor activity which has been linked to a dose-dependent inhibition of A1 and A(2A) receptors. The effects of caffeine at the level of the lumbar spinal central pattern generator (CPG) network for hindlimb locomotion are lacking. We assessed the effects of caffeine to the locomotor function of the spinal CPG network via extracellular ventral root recordings using the isolated neonatal mouse spinal cord preparation. Addition of caffeine and of an A1 receptor antagonist significantly decreased the cycle period accelerating the ongoing locomotor rhythm, while decreasing burst duration reversibly in most preparations suggesting the role of A1 receptors as the primary target of caffeine. Caffeine and an A1 receptor antagonist failed to stimulate ongoing locomotor activity in the absence of dopamine or in the presence of a D1 receptor antagonist supporting A1/D1 receptor-dependent mechanism of action. The use of caffeine or an A1 receptor blocker failed to stimulate an ongoing locomotor rhythm in the presence of a blocker of the cAMP-dependent protein kinase (PKA) supporting the need of this intracellular pathway for the modulatory effects of caffeine to occur. These results support a stimulant effect of caffeine on the lumbar spinal network controlling hindlimb locomotion through the inhibition of A1 receptors and subsequent activation of D1 receptors via a PKA-dependent intracellular mechanism.


Identification of metastasis-associated genes in colorectal cancer through an integrated genomic and transcriptomic analysis.
Identification of colorectal cancer (CRC) metastasis genes is one of the most important issues in CRC research. For the purpose of mining CRC metastasis-associated genes, an integrated analysis of microarray data was presented, by combined with evidence acquired from comparative genomic hybridization (CGH) data. Gene expression profile data of CRC samples were obtained at Gene Expression Omnibus (GEO) website. The 15 important chromosomal aberration sites detected by using CGH technology were used for integrated genomic and transcriptomic analysis. Significant Analysis of Microarray (SAM) was used to detect significantly differentially expressed genes across the whole genome. The overlapping genes were selected in their corresponding chromosomal aberration regions, and analyzed by using the Database for Annotation, Visualization and Integrated Discovery (DAVID). Finally, SVM-T-RFE gene selection algorithm was applied to identify metastasis-associated genes in CRC. A minimum gene set was obtained with the minimum number [14] of genes, and the highest classification accuracy (100%) in both PRI and META datasets. A fraction of selected genes are associated with CRC or its metastasis. Our results demonstrated that integration analysis is an effective strategy for mining cancer-associated genes.


Increasing rate of angiotensin-converting enzyme inhibitor-related upper airway angio-oedema.
The objective of this study was to evaluate whether the increased use of angiotensin-converting enzyme inhibitors (ACEI) has affected the rate of upper airway angio-oedema (AE). In addition, we evaluated the presentation and treatment of patients with upper airway AE. This was a ten-year retrospective study of 112 patients presenting with upper airway AE at The Department of Otorhinolaryngology, Aarhus University Hospital, Denmark. Incidence, presentation and treatment in the 2000-2004-period were compared to those of the 2005-2009-period. In the ten-year period, we found 112 AE patients of whom 39% were using ACEI. The relative risk of AE was 7.7 (p < 0.0001) among ACEI users. We found a 67% increase in AE in 2005-2009 compared with 2000-2004 which corresponds to a similar increase in ACEI use in the Danish population. The most frequent anatomic sites of involvement were the floor of the mouth and/or oropharynx including the base of the tongue. Two patients required intubation upon their arrival to the hospital. None progressed in airway obstruction requiring intubation later. None died. We found an increasing rate of ACEI-related upper airway AE over a ten-year period corresponding to greater use of ACEI in the population. With a relative risk of 7.7 and continuously increasing ACEI consumption, this condition will certainly require future attention and resources as almost one third of patients are admitted to an intensive care unit.


Thunderstorm Cloud-Type Classification from Space-Based Lightning Imagers.
The organization and structure of thunderstorms determines the extent and severity of their hazards to the general public and their consequences for the Earth system. Distinguishing vigorous convective regions that produce heavy rain and hail from adjacent regions of stratiform or overhanging anvil clouds that produce light-to-no rainfall is valuable in operations and physical research. Cloud type algorithms that partition convection from stratiform regions have been developed for space-based radar, passive microwave, and now Geostationary Operational Environmental Satellites (GOES) Advanced Baseline Imager (ABI) multi-spectral products. However, there are limitations for each of these products including temporal availability, spatial coverage, and the degree to which they based on cloud microphysics. We have developed a cloud type algorithm for GOES Geostationary Lightning Mapper (GLM) observations that identifies convective / non-convective regions in thunderstorms based on signatures of interactions with non-convective charge structures in the lightning flash data. The GLM sensor permits a rapid (20-s) update cycle over the combined GOES-16 / GOES-17 domain across all hours of the day. Storm regions that do not produce lightning will not be classified by our algorithm, however. The GLM cloud type product is intended to provide situational awareness of electrified anvils and to complement other cloud type retrievals by providing a contemporary assessment tied to lightning physics. We propose that a future combined ABI / GLM cloud type algorithm would be a valuable product that could draw from the strengths of each instrument and approach.


Inducement in research.
Opposition to inducement payments for research subjects is an international orthodoxy amongst writers of ethics committee guidelines. We offer an argument in favour of these payments. We also critically evaluate the best arguments we can find or devise against such payments, and except in one very limited range of circumstances, we find these unconvincing.


Developmental timing of hair follicle and dorsal skin innervation in mice.
The innervation of hair follicles offers an intriguing, yet hardly studied model for the dissection of the stepwise innervation during cutaneous morphogenesis. We have used immunofluorescence and a panel of neuronal markers to characterize the developmental choreography of C57BL/6 mouse backskin innervation. The development of murine skin innervation occurs in successive waves. The first cutaneous nerve fibers appeared before any morphological evidence of hair follicle development at embryonic day 15 (E15). Stage 1 and 2 developing hair follicles were already associated with nerve fibers at E16. These fibers approached a location where later in development the follicular (neural) network A (FNA) is located on fully developed pelage hair follicles. Prior to birth (E18), some nerve fibers had penetrated the epidermis, and an additional set of perifollicular nerve fibers arranged itself around the isthmus and bulge region of stage 5 hair follicles, to develop into the follicular (neural) network B (FNB). By the day of birth (P1), the neuropeptides substance P and calcitonin gene-related peptide became detectable in subcutaneous and dermal nerve fibers first. Newly formed hair follicles on E18 and P1 displayed the same innervation pattern seen in the first wave of hair follicle development. Just prior to epidermal penetration of hair shafts (P5), peptide histidine methionine-IR nerve fibers became detectable and epidermal innervation peaked; such innervation decreased after penetration (P7- P17). Last, tyrosine hydroxylase-IR and neuropeptide Y-IR became readily detectable. This sequence of developing innervation consistently correlates with hair follicle development, indicating a close interdependence of neuronal and epithelial morphogenesis.


Placental pathology of recurrent spontaneous abortion: the role of histopathological examination of products of conception in routine clinical practice: a mini review.
Histopathological examination of products of conception from miscarriages is part of routine clinical practice. The extent of additional clinically relevant information provided by this investigation in the setting of recurrent spontaneous abortion remains uncertain. Review of the literature was performed to identify studies reporting on findings of histological examination of routinely obtained products of conception in the setting of recurrent spontaneous abortion. The initial search identified 312 potential references, but 300 were excluded on further examination due to lack of data on specific histopathological findings in routine products of conception specimens from patients with recurrent spontaneous abortion. The 12 included studies indicated that such examination may identify hydatidiform moles, villous dysmorphic features suggesting fetal aneuploidy, chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition and impaired trophoblast invasion. However, in most cases, morphological assessment cannot reliably determine the cause of the miscarriage or distinguish recurrent from sporadic miscarriage. Studies reporting on the use of additional immunohistochemical methods do not currently provide additional clinically useful diagnostic or prognostic information. Routine histological examination of products of conception in the setting of recurrent spontaneous abortion can provide important clinical information in a minority of cases.


Composite matrix for large, non-wedgeable Class III or Class IV preparations with gingival or subgingival margins.
Dentists sometimes are required to place a matrix to restore large Class III or Class IV preparations that have gingival or subgingival margins or are prepared in rotated or malposed teeth. In these situations, dentists sometimes cannot place a wedge between the prepared tooth and a neighboring tooth because the wedge cannot engage enough interproximal tooth structure to firmly anchor both itself and a matrix strip. This article presents a technique for placing a matrix around such large, non-wedgeable Class III or Class IV preparations.