[Low-power Wireless Micro Ambulatory Electrocardiogram Node].
Ambulatory electrocardiogram (ECG) monitoring can effectively reduce the risk and death rate of patients with cardiovascular diseases (CVDs). The Body Sensor Network (BSN) based ECG monitoring is a new and efficien method to protect the CVDs patients. To meet the challenges of miniaturization, low power and high signal quality of the node, we proposed a novel 50 mmX 50 mmX 10 mm, 30 g wireless ECG node, which includes the single-chip an alog front-end AD8232, ultra-low power microprocessor MSP430F1611 and Bluetooth module HM-11. The ECG signal quality is guaranteed by the on-line digital filtering. The difference threshold algorithm results in accuracy of R-wave detection and heart rate. Experiments were carried out to test the node and the results showed that the pro posed node reached the design target, and it has great potential in application of wireless ECG monitoring.


Alcohol treatment research follow-up interviews and drinking behaviors.
This study, drawing upon data collected as part of a randomized clinical trial of alcohol treatment matching effects, investigates the relationship between research follow-up assessment interviews and subsequent drinking behaviors. Subjects (N = 188; 143 men) participated in a day hospital substance-use disorder treatment program at either a private psychiatric hospital (n = 151) or a community hospital (n = 37) and were classified into one of three research groups: regularly scheduled follow-up interviews, missed scheduled follow-up interviews, and delayed Year-2 follow-up interviews. Complete data relevant to the present study were collected on 157 subjects. Study results provided support for a subject reactivity effect related to the research follow-up interview; that is, those subjects classified within the regularly scheduled follow-up interviews condition had the better drinking outcomes. Furthermore, by the end of the second follow-up year, subjects classified within the delayed Year-2 follow-up interviews condition had the poorest drinking outcomes. There may be considerable potential for subject reactivity effects, specific to the research assessment interview, to confound study results. Therefore, the interpretation of data from alcohol treatment outcome studies that fail to control for such potential confounding effects must be viewed with caution. Researchers are advised to control for these potentially confounding effects via methodological and/or statistical mechanisms.


Lympho-epithelial interactions in the turtle Chrysemys scrypta elegans.
The morphological relationships present in the areas of lymphoid infiltration found in the esophagus in Chrysemys scripta elegans were studied by the use of light and transmission electron microscopy. These infiltrations are widespread and can be observed in the lamina propria and the covering epithelium. Electron microscopy reveals the presence of epithelial cells with differing characteristics at the apex of the lymphoid infiltrations. The introduction of horseradish peroxidase (HRP) into the esophageal lumen revealed that these cells possess a micropinocytotic activity. On the basis of the morphological and experimental results obtained, a hypothesis is advanced of the existence, also in the turtle, of a local system of uptake of extraneous material, which induces local and systemic immunological processes.


Patterns of pathologically confirmed metastasis to bone in Near East population.
Metastatic tumors to bone constitute the majority of bone malignancies. The site of metastasis to bone and the prognosis depend chiefly on the primary tumor. Despite all the advances in diagnostic techniques, identifying the primary tumor has not improved significantly. A total of 576 cases (Lebanon; n = 306, Pakistan; n = 270) presenting with microscopic evidence of metastasis to bone were reviewed between 1996 and 2016. Clinical and radiologic data were recorded. Out of 20 types of primary tumors, unknown primary (38.2%), followed by breast (23.8%), lung (10.4%) and thyroid (4.9%) tumors were the most commonly presenting with bone metastasis. The primary source of the tumor showed significant correlation with the site of metastasis, time lag to metastasis and radiologic presentation (p < 0.001). Interestingly, a significant variation was noted between the 2 observed populations. The patterns of pathologically confirmed metastasis to skeletal sites in Near East population showed a special distribution, and variation was even observed between the 2 studied centers. Understanding the biologic variations of the primary tumors in our population may further explain the variation in patterns of metastasis.


Multidomain Peptidyl Prolyl cis/trans Isomerases.
Peptidyl prolyl cis/trans isomerases (PPIases) assist the folding and restructuring of client proteins by catalysis of the slow rotational motion of peptide bonds preceding a proline residue. Catalysis is performed by relatively small, distinct protein domains of 10 to 18kDa for all PPIase families. PPIases are involved in a wide variety of physiological and pathophysiological processes like signal transduction, cell differentiation, apoptosis as well as viral, bacterial and parasitic infection. There are multidomain PPIases consisting of one to up to four catalytic domains of the respective PPIase family supplemented by N- or C-terminal extensions. This review examines the biochemical and functional properties of the members of the PPIase class of enzymes which contain additional protein domains with defined biochemical functions. The versatile domain architecture of multidomain PPIases is important for the control of enzyme specificity and organelle-specific targeting, the establishment of molecular connections and hence the coordination of PPIase functions across the cellular network. Accessory domains covalently linked to a PPIase domain supply an additional layer of control to the catalysis of prolyl isomerization in specific client proteins. Understanding these control mechanisms will provide new insights into the physiological mode of action of the multidomain PPIases and their ability to form therapeutic targets. This article is part of a Special Issue entitled Proline-directed Foldases: Cell Signaling Catalysts and Drug Targets.


Marked HDL deficiency and premature coronary heart disease.
Our purpose is to review recent publications in the area of marked human HDL deficiency, HDL particles, coronary heart disease (CHD), amyloidosis, the immune response, and kidney disease. Lack of detectable plasma apolipoprotein (apo) A-I can be due to DNA deletions, rearrangements, or nonsense or frameshift mutations within the APOA1 gene resulting in a lack of apoA-I secretion. Such patients have marked HDL deficiency, normal levels of triglycerides and LDL cholesterol, and can have xanthomas and premature CHD. ApoA-I variants with amino acid substitutions, especially in the region of amino acid residues 50-93 and 170-178, have been associated with amyloidosis. Patients with homozygous Tangier disease have defective cellular cholesterol efflux due to mutations in the adenosine triphosphate-binding cassette transporter A1, detectable plasma apoA-I levels and prebeta-1 HDL in their plasma. They have decreased LDL cholesterol levels and can develop neuropathy and premature CHD. Patients with lecithin: cholesterol acyltransferase deficiency have both prebeta-1 and alpha-4 HDL present in their plasma and develop corneal opacities, anemia, proteinuria, and kidney failure. Patients with marked HDL deficiency can have great differences in their clinical phenotype depending on the underlying defect.


The role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex on allodynia following spared nerve injury.
The present study examined the role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex (VLO) on allodynia induced by spared nerve injury (SNI) in the rat. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of noradrenaline (1, 2, 4 μg in 0.5 μl) into the VLO, contralateral to the site of nerve injury, reduced allodynia; PWT increased in a dose-dependent manner. Similar to noradrenaline, microinjection of selective α₂ adrenoceptor agonist clonidine into the same VLO site also reduced allodynia, and was blocked by selective α₂ adrenoceptor antagonist yohimbine. Furthermore, administration of γ-aminobutyric acid A (GABAA) receptor antagonist bicuculline or picrotoxin to the VLO significantly enhanced clonidine-induced inhibition of allodynia, while GABAA receptor agonist muscimol or THIP (2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride) attenuated clonidine-induced inhibition. These results suggest that noradrenaline acting in the VLO can potentially reduce allodynia induced by SNI, and this effect is mediated by α₂ adrenoceptor. Moreover, GABAergic disinhibition may participate in α₂ receptor mediating effects in neuropathic pain in the central nervous system.


Dental arch dimensions in primary dentition of children aged three to five years in Chennai and Hyderabad.
The purpose of this study was to assess the arch dimensions in primary dentition of 3-5 years old children in Chennai and Hyderabad. As no primary to the mixed dentition and determining the existence of sexual dimorphism. Children were selected fro various schools of both Chennai and Hyderabad, with complte set of primary dentition. Study casts were made and measurements of arch dimensions were made using digital sliding calipers. The data obtained was subjected to statistical analysis. The mean values and standard deviations of the various arch dimensions are given in the tables. Generally boys exhibited a greater arch dimensions than girls in both groups. Some of the dimensions showed a statistically significant mean values.


Assessment of diastolic function in normal and hypertrophied hearts: comparison of Doppler echocardiography and M-mode echocardiography.
Left ventricular (LV) filling was examined by Doppler and M-mode echocardiography in 24 patients with LV hypertrophy (five with aortic stenosis, six with hypertrophic cardiomyopathy, and 13 with LV hypertrophy secondary to systemic hypertension) and in 18 normal subjects. Patients with LV hypertrophy had significantly lower Doppler-determined peak filling rates (218 +/- 17 vs 288 +/- 66 cc/sec, p less than 0.01), but M-mode determined peak rate of chamber enlargement and normalized peak rate of chamber enlargement did not differ significantly between groups. Doppler measures of the ratio between early and late filling were significantly depressed in patients with LV hypertrophy and correlated inversely with age in the normal subjects. The M-mode derived normalized peak rate of chamber enlargement and the Doppler-derived normalized peak filling rate correlated weakly, but significantly, when both groups were combined (r = 0.56, p less than 0.01). Thus Doppler measurements can detect abnormalities of LV filling in patients with LV hypertrophy. These abnormalities are present when M-mode filling indices and systolic function are still normal.


Predictors of adherence to nicotine replacement therapy: Machine learning evidence that perceived need predicts medication use.
Nonadherence to smoking cessation medication is a frequent problem. Identifying pre-quit predictors of nonadherence may help explain nonadherence and suggest tailored interventions to address it. Identify and characterize subgroups of smokers based on adherence to nicotine replacement therapy (NRT). Secondary classification tree analyses of data from a 2-arm randomized controlled trial of Recommended Usual Care (R-UC, n = 315) versus Abstinence-Optimized Treatment (A-OT, n = 308) were conducted. R-UC comprised 8 weeks of nicotine patch plus brief counseling whereas A-OT comprised 3 weeks of pre-quit mini-lozenges, 26 weeks of nicotine patch plus mini-lozenges, 11 counseling contacts, and 7-11 automated reminders to use medication. Analyses identified subgroups of smokers highly adherent to nicotine patch use in both treatment conditions, and identified subgroups of A-OT participants highly adherent to mini-lozenges. Varied facets of nicotine dependence predicted adherence across treatment conditions 4 weeks post-quit and between 4- and 16-weeks post-quit in A-OT, with greater baseline dependence and greater smoking trigger exposure and reactivity predicting greater medication use. Greater quitting motivation and confidence, and believing that stop smoking medication was safe and easy to use were associated with greater adherence. Adherence was especially high in those who were more dependent and more exposed to smoking triggers. Quitting motivation and confidence predicted greater adherence, while negative beliefs about medication safety and acceptability predicted worse adherence. Results suggest that adherent use of medication may reflect a rational appraisal of the likelihood that one will need medication and will benefit from it.


Employment hardships and single mothers' self-rated health: evidence from the panel study of income dynamics.
Using a national sample of single mothers from the 2007 and 2009 waves of the Panel Study of Income Dynamics, this study examined the effects of multiple employment statuses on the selfrated health of single mothers during the recent economic recession. Unlike other studies, the current study minimized selection bias by controlling for prior self-rated health, in addition to other predisposing factors, enabling factors, and need factors. We found that underemployment, but not unemployment, is associated with lower levels of self-rated health of single mothers. Results further indicate that the 25-39 age range (compared to the 18-24 age range), lower family income, prior lower self-rated health, more chronic diseases, and binge drinking place single mothers at an increased risk of lower levels of self-rated health. In contrast, strength-building physical activity is significantly associated with higher levels of self-rated health. Implications for health care policy and social work practice are drawn from the results.


Genetic diversity of five Kobresia species along the eastern Qinghai-Tibet plateau in China.
Plants of the genus Kobresia are alpine grass species of high ecological and economic importance. Vegetative growth is the dominant means of reproduction for the Kobresia. Studies suggest that substantial vegetative growth can reduce genetic diversity and renders populations less able to buffer changing and extreme conditions. Kobresia are dominant species in the Qinghai-Tibet plateau in China where they face harsh conditions and frequent disturbance. The genetic diversity of five Kobresia species (K. humilis, K. royleana, K. kansuensis , K. tibetica and K. setchwanensis) from the Qinghai-Tibet plateau was assessed. The results reveal high genetic diversity at the population level for all of the species and there does not appear to be a relationship between altitude and genetic diversity. AMOVA analysis shows that most genetic variability resides among individuals within populations, whereas only a minor portion is found among populations. Of the five species, K. royleana and K. kansuensis have the highest levels of gene flow and the lowest genetic differentiation. While K. setchwanensis has the lowest gene flow and the greatest genetic differentiation. The level of gene flow between populations and the mating system play a critical role in the genetic structure of these Kobresia populations. Despite the predominance of vegetative growth enough sexual reproduction occurs to maintain the relatively high genetic diversity in Kobresia populations.


Cytotoxicity of hexahelicene and its effect on the aryl hydrocarbon receptor pathway.
Carbohelicenes are a group of helical-shaped polycyclic aromatic hydrocarbons. This study examined the effect of hexahelicene (or [6]helicene) and of its imidazolium derivative, 1-butyl-3-(2-methyl[6]helicenyl)-imidazolium bromide (I[6]H), on the activity of the aryl hydrocarbon receptor (AhR) and expression of cytochrome P450 1A1 (CYP1A1) in human hepatoma HepG2 cells. An MTT viability assay showed that both [6]helicene and I[6]H were cytotoxic to HepG2 cells after 24 h of exposure, with IC50 values of 0.9 and 8.4 μM, respectively. Using a gene reporter assay performed in transiently transfected HepG2 cells, we found that 1 μM [6]helicene, unlike I[6]H, significantly increased the activity of AhR to 2.1-fold compared to the control after 24 h of exposure. Moreover, [6]helicene induced a small but significant increase in the level of CYP1A1 mRNA. On the other hand, neither the protein level nor activity of CYP1A1 were affected by [6]helicene in HepG2 cells. The effect of [6]helicene on the AhR pathway was thus much lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, a potent AhR activator. We conclude that [6]helicene is a poor activator of the AhR pathway in HepG2 cells, and that the possible activation of the AhR pathway in vivo remains to be investigated.


Home initiation of chronic non-invasive ventilation in COPD patients with chronic hypercapnic respiratory failure: a randomised controlled trial.
Chronic non-invasive ventilation (NIV) has become evidence-based care for stable hypercapnic COPD patients. While the number of patients increases, home initiation of NIV would greatly alleviate the healthcare burden. We hypothesise that home initiation of NIV with the use of telemedicine in stable hypercapnic COPD is non-inferior to in-hospital NIV initiation. Sixty-seven stable hypercapnic COPD patients were randomised to initiation of NIV in the hospital or at home using telemedicine. Primary outcome was daytime arterial carbon dioxide pressure (PaCO2) reduction after 6 months NIV, with a non-inferiority margin of 0.4 kPa. Secondary outcomes were health-related quality of life (HRQoL) and costs. Home NIV initiation was non-inferior to in-hospital initiation (adjusted mean difference in PaCO2 change home vs in-hospital: 0.04 kPa (95% CI -0.31 to 0.38 kPa), with both groups showing a PaCO2 reduction at 6 months compared with baseline (home: from 7.3±0.9 to 6.4±0.8 kPa (p<0.001) and in-hospital: from 7.4±1.0 to 6.4±0.6 kPa (p<0.001)). In both groups, HRQoL improved without a difference in change between groups (Clinical COPD Questionnaire total score-adjusted mean difference 0.0 (95% CI -0.4 to 0.5)). Furthermore, home NIV initiation was significantly cheaper (home: median €3768 (IQR €3546-€4163) vs in-hospital: median €8537 (IQR €7540-€9175); p<0.001). This is the first study showing that home initiation of chronic NIV in stable hypercapnic COPD patients, with the use of telemedicine, is non-inferior to in-hospital initiation, safe and reduces costs by over 50%. NCT02652559.


Temperature field estimation using electrical impedance profiling methods. I. Reconstruction algorithm and simulated results.
Algorithmic methods for estimating complete temperature fields during hyperthermia treatments based on surface and internal electrical measurements are presented. The techniques utilized draw upon impedance imaging concepts, but rather than limit the measurements to positions on the body surface, internal impedance recording sites are allowed. Theoretical simulations show that this strategy improves the reconstructed image in the target region when either internal measurement locations are added to a given number of external recording sites or some external measurement locations are replaced by internal recording positions. The algorithms developed are tested on a set of problems with increasing levels of complexity. The culmination of these investigations is a complete simulation of a hyperthermia treatment and reconstruction of a thermal image for a body cross-section of an actual cancer patient. The results of this work suggest that the surface plus internal measurement approach holds some promise as a method for estimating temperature distributions during hyperthermia treatments. However, the simulations while promising are idealizations in that they are two-dimensional with modest levels of additive noise. In a companion paper, we explore the viability of this approach in several laboratory phantom experiments which include both static and heat-induced transient electrical property profiles.


[Study on visible-light curing soft resins consisting of fluoropolymers. 2. Effect of fluoroalkyl alpha-fluoroacrylate monomers].
New experimental visible-light cured soft resins were prepared by combining a vinylidene fluoride/hexafluoropropylene copolymer (2-6 F), or a vinylidene fluoride/tetrafluoroethylene/hexafluoropropylene copolymer (2-4-6 F) with 2,2,3,3-tetrafluoropropyl alpha-fluoroacrylate (4 FFA), 2,2,3,3,3-pentafluoropropyl alpha-fluoroacrylate (5 FFA), 2,2,3,3,4,4,5,5-octafluoropentyl alpha-fluoroacrylate (8 FFA), or 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoroheptyl alpha-fluoracrylate (12 FFA). Some properties of the resins prepared were measured to determine whether they would be candidate materials for the soft denture liner. Water contact angles increased with the increase in the number of fluorine atoms contained in the monomers: 85-90 degrees in 4 FFA, 90-93 degrees in 8 FFA, and 92-93 degrees in 12 FFA. Softer resins were obtained with 2-4-6 F, especially by the combination with 8 FFA giving the softest resin with a hardness of 43-46 (JIS A). Water sorption after 10 weeks was considerably low: 0.4-2%: 0.4-0.9% in 4 FFA/2-6 F and about 2% in 8 FFA/2-4-6 F. Solubility was 0.2-0.4% in the resins with 4 FFA and 1.0-1.4% with 8 FFA or 12 FFA. Amount of residual monomer was low, and the maximum was 0.4% in the resin with 12 FFA. Thus hardness and water sorption of the resins prepared were superior to those of the commercial soft materials.


Efficacy, safety, and effects on quality of life of salmeterol versus albuterol in patients with mild to moderate persistent asthma.
Salmeterol xinafoate is a long-acting, highly selective, beta2-adrenergic agonist that produces bronchodilation and clinically significant improvement in pulmonary function for up to 12 hours in patients with asthma. To evaluate the impact on asthma-specific quality of life, efficacy, and safety of salmeterol versus albuterol in adult patients with mild-to-moderate persistent asthma. A randomized, double-blind, double-dummy, parallel-group, multicenter study was conducted in 539 adult asthma patients over 12 weeks. Patients were randomized to receive either salmeterol 42 microg via metered-dose inhaler twice daily or albuterol 180 microg four times daily. Upon entry into the study, 46% of patients were being treated with an inhaled corticosteroid and were allowed to continue treatment throughout the study. Pulmonary function and asthma symptoms were monitored daily, and patients completed the Asthma Quality of Life Questionnaire (AQLQ) at baseline and after 4, 8, and 12 weeks of treatment. Treatment with salmeterol twice daily produced significantly greater improvements from baseline in all quality of life domain ("Activity Limitation," "Asthma Symptoms," "Emotional Function," "Environmental Exposure") scores and in the global AQLQ score at 12 weeks (P < or = .038) compared with albuterol treatment four times daily. Pulmonary function and asthma symptoms were also significantly improved with salmeterol compared with albuterol. Salmeterol 42 microg administered twice daily is significantly more effective than albuterol 180 microg four times daily for improving asthma-specific quality of life, controlling asthma symptoms, and improving pulmonary function in patients with mild-to-moderate persistent asthma. Furthermore, those improvements were maintained over a 12-week period.


Angelchik prosthesis complicates treatment of adenocarcinoma in Barrett's esophagus.
Indications for use of the Angelchik prosthesis remain controversial, and many surgeons actively involved in the treatment of reflux disease have not used the device. We describe a case that illustrates difficulties associated with resection of a tumor in the presence of this prothesis. Such experience suggests that patients known to have Barrett's esophagus might be better treated with standard antireflux procedures.


Juxtaglomerular cell tumor without hypertension.
Juxtaglomerular cell tumors are rare. This report presents a case of juxtaglomerular cell tumor without hypertension. All previously reported cases showed marked hypertension, whereas this is the first case of juxtaglomerular cell tumor without hypertension. The immunohistochemistry and ultrastructure of this case are discussed.


Nuclear Cytometry: Analysis of the Patterns of DNA Synthesis and Transcription Using Flow Cytometry, Confocal Microscopy, and RNA Sequencing.
Eukaryotes are defined by cells that contain a nucleus and other membrane-bound organelles. Cytometric analysis in situ, utilizing imaging, provides a useful understanding of the structure and function of the various subcellular components, particularly when combined with methods that preserve the living state. In terms of information provided by the observation of eukaryotic nuclei, imaging has provided a wealth of information about cellular multiplication. When organisms are present in multicellular form (tissues and organs), this property does not generally confound imaging cytometry. Multicellular eukaryotic species present immediate problems when being considered for analysis using flow cytometry which requires suspensions of single particles. Although some eukaryotic cell types exist as natural single cell suspensions (cf. the erythropoietic system), for other tissues and organs, strategies are required to produce single particle suspensions. This chapter illustrates the application of flow cytometry combined with confocal microscopy to analyze complex organs, focusing on properties of the plant nucleus, and then goes on to describe how suspensions of nuclei can be prepared from tissues and organs, and used for flow cytometric analysis of cellular and transcriptional states. The application of these techniques to animal species is also discussed with the implication that this strategy is universally applicable for the characterization of nuclei within tissues that cannot readily be converted into suspensions of cells.


Keyhole limpet hemocyanin (KLH): a biomedical review.
In this review we present a broad survey of fundamental scientific and medically applied studies on keyhole limpet hemocyanin (KLH). Commencing with the biochemistry of KLH, information on the biosynthesis and biological role of this copper-containing respiratory protein in the marine gastropod Megathura crenulata is provided. The established methods for the purification of the two isoforms of KLH (KLH1 and KLH2) are then covered, followed by detailed accounts of the molecular mass determination, functional unit (FU) structure, carbohydrate content, immunological analysis and recent aspects of the molecular genetics of KLH. The transmission electron microscope (TEM) has contributed significantly to the understanding of KLH structure, primarily from negatively stained images. We give a brief account of TEM studies on the native KLH oligomers, the experimental manipulation of the oligomeric states, together with immunolabelling data and studies on subunit reassociation. The field of cellular immunology has provided much relevant biomedical information on KLH and has led to the expansion of use of KLH in experimental immunology and clinically as an immunotherapeutic agent; this area is presented in some detail. The major clinical use of KLH is specifically for the treatment of bladder carcinoma, with efficacy probably due to a cross-reacting carbohydrate epitope. KLH also has considerable possibilities for the treatment of other carcinomas, in particular the epithelially derived adenocarciomas, when used as a carrier for carcinoma ganglioside and mucin-like epitopes. The widespread use of KLH as a hapten carrier and generalised vaccine component represent other major on-going aspects of KLH research, together with its use for the diagnosis of Schistosomiasis, drug assay and the treatment of drug addiction. Immune competence testing, assessment of stress and the understanding of inflammatory conditions are other areas where KLH is also making a useful contribution to medical research.


Factors Associated With Quality of Life in Subjects With Stable COPD.
The purpose of this study was to assess the impact of bronchiectasis, anxiety and depression, and parameters of disease severity on health-related quality of life (HRQOL) in subjects with COPD. Sixty-two subjects with stable COPD were selected for the study. The presence of bronchiectasis in all subjects with COPD was investigated by high-resolution computed tomography. Pulmonary function tests were performed. Dyspnea was assessed using the Modified Medical Research Council (MMRC) dyspnea scale. Psychological disorders were investigated using the Hospital Anxiety and Depression Scale (HADS), and the HRQOL was examined using the St George Respiratory Questionnaire (SGRQ). High-resolution computed tomography revealed that 44 of 62 (70.9%) subjects with COPD had bronchiectasis. There were no differences in pulmonary function tests, symptoms, activities, impact, SGRQ total scores, and HADS scores between COPD subjects with and without bronchiectasis. Pearson correlation analyses showed that there was no significant association between the presence of bronchiectasis, bronchial wall thickness, or severity of bronchial dilatation and all subscales of the SGRQ or HADS scores. Additionally, HADS scores showed significant positive association with all subscales of the SGRQ in all subjects. In linear regression analysis, a statistically significant relationship was found between the SGRQ total score and percent-of-predicted FEV1, percent-of-predicted diffusing capacity of the lung for carbon monoxide, MMRC score, and anxiety score, but the SGRQ total score was not associated with age, body mass index, total number of hospitalizations, PaO2 , or depression score. The presence of bronchiectasis in subjects with COPD does not impact HRQOL and psychological disorders. However, disease severity, dyspnea levels, and anxiety scores predict poor HRQOL.


Experimental myocardial infarction in dogs with normal coronary arteries. Angiographic resolution of coronary arterial emboli.
Percutaneous transcatheter embolization of the coronary arteries with autologous clot was performed in six dogs. The occlusions resolved completely within 14 days in the four surviving dogs. Postmortem examination revealed transmural myocardial infarction in two dogs and subendocardial infarcts in the other two. Histological sections showed no residual emboli in three dogs and a recanalized thrombus in an epicardial vessel in the fourth. These findings indicate that myocardial infarction can be produced by multiple occlusions of the distal coronary arterial branches, provided that common or contiguous myocardium is affected. The recanalized thrombus in one dog suggests that the thrombolytic process need not be complete for return to a normal angiographic appearance.


Radiative-surface plasmon resonance for the detection of apolipoprotein E in medical diagnostics applications.
Surface plasmon resonance (SPR)-based sensors enable the rapid, label-free and highly sensitive detection of a large range of biomolecules. We have previously shown that, using silver-coated optical fibers with a high surface roughness, re-scattering of light from the surface plasmons is possible, turning SPR into a radiative process. The efficacy of this platform has proven for the detection of large biomolecules such as viruses, proteins and enzymes. Here, we demonstrate that by bringing together this novel emission-based fiber SPR platform with an improved surface functionalization process aimed at properly orienting the antibodies, it is possible to rapidly and specifically detect the regulation of human apolipoprotein E (apoE), a low-molecular-weight protein (~39 kDa) known to be involved in cardiovascular diseases, Alzheimer's disease and gastric cancer. The results obtained clearly show that this new sensing platform has the potential to serve as a tool for point-of-decision medical diagnostics. In this study, a novel emission-based surface plasmon resonance platform using silver-coated optical fibers is described. Properly orienting antibodies on the surface enables rapid and specific detection of human apolipoprotein E (apoE).


Bioidentical hormones: an evidence-based review for primary care providers.
Since 2002, when the US Food and Drug Administration (FDA) placed a black box warning on women's hormone replacement products, women and their providers have been struggling with whether to proceed with hormone replacement therapy. Out of the controversy has grown a popular movement promoting the use of bioidentical hormones. Many providers are still unsure if they want to recommend these products and, if so, how to use them appropriately. To inform primary care providers (eg, physicians, physician assistants, nurse practitioners) about current data on the safety and efficacy of bioidentical hormone replacement therapy and to provide a context for patient perceptions. Literature published between 1999 and 2009 was reviewed through MD Consult's Medline and Ovid search engines. A Google search of popular media was also performed using the same terms. Randomized clinical trial data are sufficient to support the prescription of only estropipate, estradiol, and progesterone for the relief of menopausal symptoms. Estropipate is approved by the FDA for the management of menopausal symptoms. 17β-Estradiol is FDA approved for menopausal symptoms, may have cardioprotective effects, and may have fewer adverse effects on blood pressure than conjugated equine estrogens. Estriol is not FDA approved but is widely used in Europe and is effective for relieving menopausal symptoms. Progesterone is approved by the FDA for the management of menopausal symptoms and for the prevention of endometrial hyperplasia; it should be used orally to oppose estrogen. Testosterone is FDA approved in combination with estrogen for the management of vasomotor symptoms. Dehydroepiandrosterone is not FDA approved, but small-scale studies indicate it may improve bone mineral density. Data are conflicting about efficacy in improving sexual dysfunction. There is an abundance of misleading information available in the media and on the Internet for our patients. Compounded bioidenticals and salivary hormone testing are unnecessary, are not standardized, and should be avoided. Bioidentical hormones that are approved by the FDA may be preferred over standard hormone replacement because of their physiologic benefits and safety profile.


Investigating macromolecules inside cultured and injected cells by in-cell NMR spectroscopy.
The noninvasive character of NMR spectroscopy, combined with the sensitivity of the chemical shift, makes it ideally suited to investigate the conformation, binding events and dynamics of macromolecules inside living cells. These 'in-cell NMR' experiments involve labeling the macromolecule of interest with a nonradioactive but NMR-active isotope (15N or 13C). Cellular samples are prepared either by selectively overexpressing the protein in suitable cells (e.g., bacterial cells grown on isotopically labeled media), or by injecting isotopically labeled proteins directly into either cells or cell extracts. Here we provide detailed protocols for in-cell NMR experiments in the prokaryotic organism Escherichia coli, as well as eukaryotic cells and extracts employing Xenopus laevis oocytes or egg extracts. In-cell NMR samples with proteins overexpressed in E. coli can be produced within 13-14 h. Preparing Xenopus oocyte samples for in-cell NMR experiments takes 6-14 h depending on the oocyte preparation scheme and the injection method used.


Identifying and assisting low-literacy patients with medication use: a survey of community pharmacies.
Nearly one-half of adult Americans have limited functional literacy skills. Low patient literacy is associated with poor medication adherence and health outcomes. However, little is known about how pharmacies address literacy-related needs among patrons. To determine the frequency with which pharmacies identify and provide appropriate assistance to patients with limited literacy skills and provide specific recommendations to help improve pharmacists' recognition of low health literacy, as well as strategies to improve adherence in this population. Through a telephone-based survey of Atlanta-area pharmacies, we obtained information on (1) whether the pharmacy attempted to identify patients with limited literacy skills, (2) what measures were taken by the pharmacy to optimize the health care of low-literacy patients, especially with regard to medication adherence, and (3) what services the pharmacy offered to improve adherence in general. The response rate among eligible pharmacies was 96.8% (N = 30). Only 2 (7%) pharmacies reported attempting to identify literacy-related needs among their patrons. One of these facilities provided additional verbal counseling to assist low-literacy patients, and the other pharmacy involved family members, provided verbal counseling, and had patients repeat instructions to confirm comprehension. Most pharmacies reported availability of adherence aids that could help low-literacy patients if such patients were identified and targeted to receive additional assistance. These included verbal and written counseling (offered at 73% of pharmacies), packaging or organizing aids (27%), refill services (17%), and graphic or multimedia aids (13%). Pharmacies infrequently attempt to identify and assist patients with limited literacy skills.


K(+)-stimulated amino acid release from cultured cerebellar neurons: comparison of static and dynamic stimulation paradigms.
The release of several endogenous amino acids and adenosine from rat cerebellar neuronal cultures following elevated K+ exposure in the presence and absence of added Ca2+ was studied. The amino acids aspartate (ASP), glutamate (GLU) and GABA were released from the cultures in a dose- and Ca(2+)-dependent manner. Taurine (TAU) and the nucleoside adenosine (ADN) efflux rates were dose-dependent but Ca(2+)-independent, and basal levels increased in the absence of Ca2+. The K+ depolarization induced release of serine (SER), alanine (ALA) and proline (PRO), was not dose-dependent and in the absence of extracellular Ca2+ (with added Mg2+) higher basal release of SER and ALA, but not PRO, was noted. These findings demonstrate that in addition to known cerebellar neurotransmitters, other neuroactive and neutral amino acids are released from cultured cerebellar neurons in response to K+ depolarization. Their observed efflux suggests they may have as yet unidentified roles in neuronal function with different classes of efflux corresponding to: neurotransmitter-type release (ASP, GLU, GABA), an osmoregulatory, possibly neuromodulatory-type release (TAU), a Ca(2+)-insensitive, possibly neuromodulatory-type release (ADN), and a depolarization-sensitive release (SER, ALA, PRO) of which SER and ALA are partially Ca(2+)-sensitive.


[Bacteriologic and clinical analysis of nosocomial infections in patients from the intensive care unit].
The aim of this study is to evaluate what pathogens are mainly responsible for infection among all hospitalised at our ITU patients, to define the influence of antibiotic use on the aetiology of nosocomial infection. The research was conducted on a six-bedded surgical ITU in a 700-bed teaching hospital from January 1995 till June 1996. In August 1995 we changed infection control protocols (more stress on: handwashing with antiseptic soaps and routine microbiological culture for early prediction of infection) and antibiotic guidelines on our ITU (third generation cephalosporins, fluoroquinolones and Vancomycin were used only as the last option and never in prevention). 1276 samples for microbiological culture were obtained in routine manner. From 60% positive cultures 1216 strains were isolated (Tab. 1) and resistance to antibiotics were defined (Tab. 3). Monthly antibiotic consumption was expressed in defined daily dose (DDD) for 1000 hospitalisation-days. DDD = (X/Y)/Z x x 1000, were: X-cumulative antibiotic consumption during analysed period (g), Y-standard daily dose (g/24 h), Z-number of hospitalisation-days during analysed period (Tab. 2). Values were expressed as the mean +/- standard error (SE). Relationships between variables were analysed using linear correlation. All data were categorised for the frequency table. Statistically significant differences were considered to exist when calculated p values were less than 0.05. There were no statistically significant differences in the number of treated patients, length of stay and mortality rate on our ITU in 18 months. 58% of isolated strains were Gram-negative bacteria especially Pseudomonas aeruginosa (22%) and Acinetobacter spp. (16%) and Proteus spp. (9%). The commonly isolated Gram-positive bacteria were Enterococcus faecalis (14%), Staphylococcus aureus (12%)--of which 90% were MRSA. In 8% of cases we have isolated Candida spp. Monthly antibiotic consumption was displayed in table 2. Trend analysis confirmed reduction in Ofloxacin, fluoroquinolones and Colistin consumption over 18 months period (Fig. 2). We observed statistically significant decrease in amount of isolated Proteus spp. strains from 70 in I'95 to 31 in II'95 (p < 0.05) and 10 in I'96 (p < 0.005). This observation was confirmed in trend analysis (Fig. 1). We have observed in analysed period improvement in activities of third generation cephalosporins and fluoroquinolones (Tab. 3). We have analysed the influence of antibiotic use on the aetiology of nosocomial infection. Table 4 shows statistically significant correlation between Acinetobacter spp., MRSA, MRSE isolates and antibiotics consumption. Crosstabulated variables analyses confirm MRSE outbreaks in periods when excessive amount of Amikacin (p < 0.05 for chi 2 test, D Somer rate 0.59, V Cramer rate 0.67), aminoglicosides (p < 0.05 for chi 2 test, D Somer rate 0.57, V Cramer rate 0.59), imipenem (p < 0.05 for chi 2 test, D Somer rate 0.44, V Cramer rate 0.60) and total antibiotics consumption were high (p < 0.005 for chi 2 test, D Somer rate 0.67, V Cramer rate 0.81) (Fig. 3). This study illustrates the influence of antimicrobial therapy on the species and the resistance of strains isolated in nosocomial infection. Restrictive antibiotics policy does not affect ITU outcome. Better strategies for antibiotic administration in the ITU setting may improve their efficacy and control the spread of nosocomial infection caused by multi-resistant organisms. Therefore, restrictive antibiotic policy would be mandatory in each hospital and department.


Significance of simultaneous determination of serum and seminal plasma alpha-tocopherol and retinol in infertile men by high-performance liquid chromatography.
High-performance liquid chromatography was used for the simultaneous determination of alpha-tocopherol and retinol in serum and semen of 40 subfertile men. The serum levels of the two vitamins were significantly higher in serum than in semen (3- to 10-fold) (P < 0.001). The mean alpha-tocopherol levels were higher in the serum and semen of men with normal sperm parameters (20 +/- 5 and 5 +/- 4 mumol L-1) than those with oligozoospermia (10 +/- 4 and 3 +/- 2 mumol L-1), azoospermia (8 +/- 3 and 3 +/- 1 mumol L-1) and asthenozoospermia (9 +/- 6 and 3 +/- 2 mumol L-1) (P < 0.002). Mean retinol levels in serum were similar in men with normal sperm parameters (2.4 +/- 2 mumol L-1) as in those with defective sperm parameters such as oligozoospermia (2.5 +/- 2 mumol L-) and asthenozoospermia (2.1 +/- 1.0 mumol L-) (P = 0.15), but significantly lower in men with azoospermia (1.3 +/- 0.3 mumol L-1) (P < 0.05). The alpha-tocopherol:retinol ratio was significantly higher in semen than in serum of men with normal sperm parameters (11.5) and those with asthenozoospermia (10.3) compared with ratios in those with oligozoospermia (8.3) and azoospermia (6.3). This may be related to reduced antioxidant activity in sperm dysfunction as a result of lipid peroxidation, from increased generation of reactive oxygen species.


Partial purification of mare early pregnancy factor.
Early pregnancy factor (EPF) is an immunosuppressive protein detected in the serum in early pregnancy. We have already reported the development of the rosette inhibition test for mare EPF and have detected EPF in thoroughbreds and ponies. Here, we attempted to purify equine EPF from pregnant mare serum. Mare EPF was purified by ultrafiltration and ion-exchange chromatography. Purified EPF was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting and a neutralization test. EPF activity was estimated as the rosette inhibition titer (RIT) by the rosette inhibition test. Purified EPF bound to carboxymethyl (CM) sepharose and did not adsorb to diethylaminoethyl (DEAE) sepharose. SDS-PAGE revealed that in the final purified fraction there were many proteins. In the immunoblotting analysis, a protein band of 25.8 kDa was detected as the pregnancy-specific band. Further, antibody gained from the 20 to 30 kDa protein band of the final purified fraction neutralized the RIT activity of pregnant mare serum. Mare EPF was detected in the final purified fraction and had a molecular weight of 25.8 kDa. EPF in the mare is similar to that obtained from the serum of pregnant cows.


Differential regulation of components of the focal adhesion complex by heregulin: role of phosphatase SHP-2.
Heregulin (HRG) has been implicated in the progression of breast cancer cells to a malignant phenotype, a process that involves changes in cell motility and adhesion. Here we demonstrate that HRG differentially regulates the site-specific phosphorylation of the focal adhesion components focal adhesion kinase (FAK) and paxilin in a dose-dependent manner. HRG at suboptimal doses (0.01 and 0.1 nM) increased adhesion of cells to the substratum, induced phosphorylation of FAK at Tyr-577, -925, and induced formation of well-defined focal points in breast cancer cell line MCF-7. HRG at a dose of 1 nM, increased migratory potential of breast cancer cells, selectively dephosphorylated FAK at Tyr-577, -925, and paxillin at Tyr-31. Tyrosine phosphorylation of FAK at Tyr-397 remained unaffected by HRG stimulation. FAK associated with HER2 only in response to 0.01 nM HRG. In contrast, 1 nM HRG induced activation and increased association of tyrosine phosphatase SHP-2 with HER2 but decreased association of HER2 with FAK. Expression of dominant-negative SHP-2 blocked HRG-mediated dephosphorylation of FAK and paxillin, leading to persistent accumulation of mature focal points. Our results suggest that HRG differentially regulates signaling from focal adhesion complexes through selective phosphorylation and dephosphorylation and that tyrosine phosphatase SHP-2 has a role in the HRG signaling.


Somatomedin-like activity in plasma after foetal hypophysectomy or nephrectomy and in experimental intra-uterine growth retardation in sheep.
Plasma samples from pregnant ewes and their foetuses during the last quarter of gestation were assayed for somatomedin-like activity (SLA) using the procine costal cartilage assay. In maternal plasma, the mean potency (compared with pooled serum from six sheep) was 0.84 +/- 0.05 (S.E.M.) units/ml (n = 15). Somatomedin-like activity in the plasma of five control foetuses (0.91 +/- 0.1 units/ml) was similar to the maternal levels and did not change with gestational age. After foetal hypophysectomy the SLA in foetal plasma (0.37 +/- 0.05 units/ml, n = 4) was significantly less than in control animals. In two nephrectomized foetuses, the mean SLA in plasma (0.08 and 0.51 units/ml respectively) was less than in control animals. Retardation of intra-uterine foetal growth was induced by removal of endometrial caruncles before pregnancy in four sheep. The SLA in plasma from these foetuses was 0.38 +/- 0.05 units/ml (P less than 0.01 v. control animals). The results suggest that SLA in the foetus may be important in the regulation of foetal growth, but they also indicate that factors other than growth hormone may be important in the control of SLA in foetal plasma.


How many electrocardiographic leads are required for exercise treadmill tests?
Forty-four consecutive patients who had perfusion defects on thallium-201 scanning and positive exercise treadmill tests were prospectively studied. Thirty-eight (86%) subjects had diagnostic ST segment changes in lead V5, 37 (84%) in lead V4, and 44 (100%) in either lead V4, V5 or both. Thirty patients had ST segment changes in the inferior leads, 20 in lead aVR, and only four in lead I and/or aVL. All of these latter subjects had diagnostic ST segments in lead V4 and/or V5. It is concluded that: combined electrocardiographic leads V4 and V5 detect the vast majority of ischemic changes during exercise treadmill testing, regardless of the site of perfusion defects detected by thallium-201 scanning; and monitoring the inferior and lateral leads rarely provides more diagnostic information.


Diagnostic and therapeutic approach to acute pulmonary embolism in an emergency department.
Pulmonary embolism (PE) is the obstruction of the pulmonary arteries by the dislodging and embolization of thrombotic material coming in most cases from the deep veins of the leg. PE is a relatively common disease with an estimated annual incidence up to 37 cases diagnosed per 100,000 persons it is the third cause of death in the United States. Clinical signs and symptoms are non specific and in the 70% of cases there isn't a correct diagnosis. The aim of this review is to summarize the state of the art of the diagnostic and treatment algorithms of PE in the evidence based medicine in order to minimize the "clinician gestalt" by the only guide for the early diagnosis and treatment of the disease. A correct diagnosis based on pre test probability, the use of computed tomographic pulmonary angiography, early anticoagulation/fibrinolysis started in the Emergency Department can change the natural history of the disease. In perspective, a combined approach of localyzed fibrinolysis and mechanical fragmentation could improve the overall outcome of these patients.


Chromatin Immunoprecipitation in Skeletal Myoblasts.
Chromatin immunoprecipitation (ChIP) is a powerful and sensitive technique that is widely used to study DNA-protein interactions. It enables an unbiased genome-wide analysis of transcriptional changes during several biological processes including cellular differentiation. Here, we describe a step-by-step protocol to identify histone modifications, transcription factor, and co-factor binding to chromatin in skeletal myoblasts. We discuss critical steps during cell harvesting, sonication, and immunoprecipitation and provide notes to evade common pitfalls.


Image annotation for conveying automated lung nodule detection results to radiologists.
The author investigated the ability of automated techniques to convey the results of an automated lung nodule detection method for human visualization. Automated nodule detection begins with gray-level thresholding techniques to create a segmented lung volume within which nodule candidates are identified. Morphologic and gray-level features are computed for each candidate. To distinguish between candidates that represent actual nodules and those that represent non-nodules, a rule-based scheme is combined with linear discriminant analysis. For output visualization, final detection results are represented as circles around computer-detected structures in a single section in which each structure appears. Consequently, an inappropriate choice of section could result in an actual nodule detected by the computer but not properly indicated to the radiologist, thus reducing the potential positive impact of that detection on the radiologist's decision-making process. The automated nodule detection method achieved 71% sensitivity with 0.5 false positives per section on 38 CT scans; however, when these results were converted to annotations on the images output for human visualization, only 91% of the computer-detected true-positive nodules received annotations that encompassed a portion of the actual nodule. Thus, the "effective sensitivity" of the automated detection method was reduced. The "effective sensitivity" of an automated lung nodule detection system considers the eventual human interaction with system output. Differences between reported computer sensitivity and "effective sensitivity" may be reduced through proper consideration of the assessment of "truth," of the manner in which computer results are scored, and of the complete segmentation of candidates for automated nodule detection.


Effects of insulin-like growth factor I and insulin on proliferation and on basal and luteinizing hormone-induced steroidogenesis of bovine thecal cells: involvement of glucose and receptors for insulin-like growth factor I and luteinizing hormone.
The objective of the present study was to determine the effects of IGF-I and insulin on cell proliferation, LH receptors, and basal and LH-induced progesterone and androstenedione production by bovine thecal cells. Cells from large (> or = 8mm) bovine follicles were cultured for 1 or 2 d in medium containing 10% fetal calf serum (FCS) and treated for 1 or 2 d in serum-free medium with IGF-I, insulin, and(or) LH. Treatment with 30 and 100 ng/mL of IGF-I for 1 or 2 d increased thecal cell numbers in the absence of LH regardless of whether treatments were initiated after 1 or 2 d of exposure to 10% FCS. Co-treatment with LH reduced the stimulatory effect of IGF-I on thecal cell numbers. Insulin at 10 and 100 ng/mL increased cell numbers in the presence of LH. Both IGF-I and insulin were ineffective at stimulating thecal cell progesterone or androstenedione production in the absence of LH. However, IGF-I and insulin increased (P < .05) androstenedione and progesterone production in the presence of LH. Alone, LH had little or no effect on androstenedione and progesterone production, whereas in the presence of 30 and 100 ng/mL IGF-I or 1 to 100 ng/mL insulin, LH stimulated (P < .05) androstenedione production. The stimulatory effects of IGF-I on cell proliferation and progesterone production were not detected in the presence of 100 ng/mL insulin. However, co-treatment with various doses of IGF-I and 100 ng/mL insulin further increased androstenedione production above that seen with insulin alone. In glucose-deficient medium, 25 to 75 mg/dL of glucose increased (P < .05) thecal cell proliferation, progesterone production, and androstenedione production. In the absence or presence of glucose, insulin (100 ng/mL) increased (P < .05) thecal cell proliferation, progesterone production, and androstenedione production. Treatment with 3, 10, or 100 ng/mL LH had no effect (P > .10) on the numbers of IGF-I binding sites on thecal cells but increased (P < .05) androstenedione production. Treatment with 10 and 100 ng/mL IGF-I increased (P <.01) numbers of LH/hCG binding sites. These results indicate that IGF-I and insulin may each play a significant role in thecal cell mitogenesis and LH-induced thecal cell steroidogenesis during follicular development in cattle and that glucose enhances these effects. Furthermore, the synergism between IGF-I and LH on increasing steroidogenesis does not seem to be mediated through increased binding sites for IGF-I in bovine thecal cells but rather, in part, through increased binding sites for LH.


Aberrant reflexes and function of the pelvic organs following spinal cord injury in man.
Spinal cord injuries can be devastating on quality of life and lost opportunities due to their impact on bladder, bowel and sexual functions. Supra-sacral spinal lesions can cause incontinence by interrupting those pathways, which normally coordinate the bladder, bowel and sphincters. From a scientific perspective, neural control of the pelvic organs is one of the most intriguing in the body, involving both somatic and autonomic pathways participating in an exquisitely fine integration of lumbo-sacral reflexes. This review details the interactions of somatic and autonomic lumbo-sacral pathways responsible for coordinating the bladder and sphincters, the nature of their aberration post-injury and those aspects of neural control of the pelvic organs that are amenable to neurophysiological examination in man. It will focus in greater detail on how measurement of pelvic floor and sphincter reflexes can be used to assess the modulatory effects of sacral autonomic pathways on sacral somatic reflexes and vice versa including the so called "guarding reflex" and vesical inhibitory reflexes. The effects of volitional modulation of these reflexes will be discussed in relation to people with both complete and incomplete lesions. Finally the possible utility of such neurophysiological measures for complementing the established neurological classification and the assessment of somatic sensory-motor impairment in spinal cord injury will be discussed.


Community pharmacists' opinions on skill-mix and delegation in England.
Following the 2005 contractual framework amendment, the expanding role of community pharmacy team members required a shift in entrenched views on roles and duties. This study aimed to report on community pharmacists' opinions on skill mix and explore how they can be addressed so that skill mix may be optimised. An invitation to complete an online questionnaire was distributed via email, marked for the attention of the lead pharmacist. Following a low response, a paper-based questionnaire was sent to all community pharmacies in England (n = 11,816). Questions elicited data about the respondent, the pharmacy (including staffing profile) and opinions on skill mix. A total of 1154 returns were received, representing a 10% response rate. Of these, most were pharmacy chains (76%; n = 877), with 5-9 staff (54%; n = 600); commonly open 40-49 hours (42%; n = 487), dispensing <6000 prescriptions per week (41%, n = 533). From 26 statements on skill mix, three factors were identified by principal-components factor analysis: 'working well', 'feeling the pressure' and 'open to development'. Characteristics associated with 'working well': pharmacy owners, single businesses, with pharmacy technician(s), dispensing fewer prescriptions and open shorter hours. Characteristics associated with 'feeling the pressure': pharmacy chains, open longer hours, large numbers of prescriptions and relief pharmacists. Characteristics associated with 'open to development': recently qualified, second pharmacists, working longer hours, chains and dispensing lower numbers of prescriptions. Although limited by a low response, results suggest being in a position to influence (more experienced, business owners) may be associated with more positive opinions. Further training (including about legalities and leadership) could contribute to optimising skill mix in community pharmacies.


On the evolutionary origin of the chaperonins.
An analysis of the apical domain of the Group-I and Group-II chaperonins shows that they have structural similarities to two different protein folds: a "swivel-domain" phosphotransferase and a thioredoxin-like peroxiredoxin. There is no significant sequence similarity that supports either similarity and the degree of similarity based on structure is comparable but weak for both relationships. Based on possible evolutionary transitions, we deduced that a phosphotransferase origin would require both a large insertion and deletion of structure whereas a peroxiredoxin origin requires only a peripheral rearrangement, similar to an internal domain-swap. We postulate that this change could have been triggered by the insertion of a peroxiredoxin into the ATPase domain that led to the modern chaperonin domain arrangement. The peroxidoxin fold is the most highly embellished member of the thioredoxin super-family and the insertion event may have "overloaded" the core, leading to a rearrangement. A peroxiredoxin origin for the domain also provides a functional explanation, as the peroxiredoxins can act as chaperones when they adopt a multimeric ring complex, similar to the chaperonin subunit configuration. In addition, several of the GroEL apical domain hydrophobic residues which interact with the unfolded protein are located in a position that corresponds to the protein substrate binding region of the peroxiredoxin fold. We suggest that the origin of the ur-chaperonin from a thioredoxin/peroxiredoxin fold might also account for the number of thioredoxin-fold containing proteins that interact with chaperonins, such as tubulin and phosducin-like proteins.


Optical aberration correction by real-time holography in liquid crystals.
We present results of experiments that use nematic-phase liquid crystal as a real-time holographic recording medium. Plane-wave gratings were written with as little as 10 mJ/cm(2) of incident write-beam energy from a pulsed Nd:YAG laser, and diffraction efficiencies greater than 25% were measured at 633 nm. Grating decay times were observed to fall within two distinct time regimes: a rapid-decay time of 60 to 100 microsec and a slower-decay time of 6 to 30 msec. The rapid-decay regime was used to demonstrate real-time correction of severely aberrated images by degenerate four-wave mixing.


Normal ascent of the conus medullaris: a post-mortem foetal MRI study.
The position of the conus medullaris is considered abnormal if it ends below lumbar vertebrae three (L3) at birth. We used magnetic resonance imaging (MRI) to measure the position of the conus in post-mortem foetuses, to investigate the timing of normal ascent. The position of the conus in 84 post-mortem foetuses (mean gestation 26.3 weeks; range 14-41 weeks) was identified using 3D MRI datasets. A numerical scale was used for vertebral levels, from 1 (S2) to 15 (T12). There was significant ascent of the conus medullaris with increasing gestation. At 20 weeks gestation, an estimated 84.2% (95% confidence interval (CI): 72.9, 93.2%) of foetuses have a conus position of L4/5 or higher, but only 22.8% (95% CI 11.7, 34.9%) at L3 or higher. By 26 weeks, an estimated 50.7% (95% CI 34.1, 67.5) will have reached L3, and 94.8% (95% CI 87.0, 98.5%) reach L3 by 40 weeks. There is regular ascent of the conus throughout foetal life. Although growth for each individual foetus may be non-linear, most foetuses have a conus level within the normal adult range by 33 weeks gestation.


Biomechanical analysis of tibial strength after harvesting unicortical tibial grafts of two different lengths.
It is not known whether the use of the proximal tibia as a source of strut graft compromises the strength of the tibia. Our hypothesis was that unicortical proximal tibial grafts in two different sizes would not significantly decrease the torsional strength of the tibia. Ten matched pairs of human cadaver tibiae were stripped of all soft tissues. One tibia in each pair was randomly assigned to receive an osteotomy of 2 x 1.5 cm or 6 x 1.5 cm placed 1 cm dorsal to the tibial crest with the proximal graft edge 6 cm from the tibial plateau. Specimens were loaded at 720 N and in external rotational torque at 5 degrees per second to failure. Axial force or torque at failure were analyzed via T-test (p < or = 0.05). There was no significant difference in torque to failure between specimens with an osteotomy of 1.5 x 2 cm versus the matched intact specimens. Torque to failure for specimens with an osteotomy 1.5 x 6 cm was lower than that of the matched intact specimens (28.69 Nm +/- 4.2 Nm versus 60.95 Nm +/- 9.49 Nm; p = 0.01) and lower than that found in the 2-cm osteotomy group (p = 0.04). Torque to failure was significantly decreased with the larger 6-cm graft as compared with the intact tibia and with the graft 1.5 x 2 cm. The smaller graft did not result in a significant change in torsional strength of the tibia. Though this study cannot be extrapolated directly to the clinical setting, the longer graft tested in this study may raise concerns regarding the strength of the tibia after graft removal.


Hematopoietic progenitor cells of transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to tumor necrosis factor.
The mechanism of growth inhibition mediated by tumor necrosis factor (TNF) is unclear. Since recent data strongly suggested that generation of superoxide is a key step in cytotoxicity of TNF, we reasoned that cells expressing high levels of enzymes that degrade superoxide radicals would be resistant to TNF. Therefore, we examined the TNF-sensitivity of bone marrow progenitor cells of transgenic mice that expressed the gene for human copper zinc-superoxide dismutase (CuZn-SOD). The CuZn-SOD is a key enzyme in the metabolism of superoxide radicals. Heterozygous and homozygous transgenic mice had 3- and 5-fold increased levels of CuZn-SOD activity, respectively. Bone marrow cells of transgenic and nontransgenic mice were plated in soft gel culture with TNF (0.01-100 ng/ml). TNF inhibited myeloid colony formation supported by either granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF from nontransgenic mice in a dose-dependent manner. In contrast, the myeloid clonal growth of homozygote transgenic mice was not inhibited by TNF at concentrations up to 100 ng/ml. As expected, the effects of TNF on erythroid clonogenic cells, which do not produce superoxide, and the action of transforming growth factor-beta on myeloid progenitor cells, were similar in both transgenic and nontransgenic mice. These results suggest that the mechanism of TNF-mediated growth inhibition of hematopoietic cells occurs through production of superoxide.


Flexible granulocyte colony-stimulating factor dosing in ovarian cancer patients who receive dose-intense taxol therapy.
As has been reported with other chemotherapeutic agents, evidence is emerging to suggest that increased taxol dose intensity is associated with improved therapeutic efficacy. Granulocyte colony-stimulating factor (G-CSF) effectively protects the bone marrow from taxol-induced neutropenia and allows for higher taxol dose administration. This report addresses the optimal use of G-CSF as a supportive agent for dose-intense taxol therapy. Forty-seven patients were evaluated. Each ovarian cancer patient received taxol with G-CSF support, with starting doses of 250 mg/m2 per 21 days and 10 micrograms/kg/d, respectively. Five patients were treated with the same dose of G-CSF for multiple cycles. Forty-two patients were given "flexible" G-CSF dosing. Instead of reducing taxol dose after a cycle of therapy complicated by febrile neutropenia (F+N+), the G-CSF dose was increased. Only after a second episode of F+N+ was the taxol dose reduced. The initial 5 patients who developed F+N+ after taxol (250 mg/m2) and G-CSF (10 micrograms/kg/d) were retreated at the same doses of both drugs; subsequently, 4 of 5 patients had another episode of F+N+. With flexible G-CSF dosing, taxol dose intensity could be maintained at the target level in 34 of 42 patients (81% of the cohort). Sixteen of these patients (38% of the cohort) would have required taxol dose reductions for F+N+ if flexible G-CSF dosing had not been used. By increasing the G-CSF dose when indicated, patients at high risk for recurrence of F+N+, because they had already experienced one episode, appeared to have a lower risk of developing a recurrent episode. These data suggest that flexible G-CSF dosing may have merit and may allow the administration of more dose-intense taxol. A prospective, randomized, controlled clinical trial of flexible G-CSF dosing versus fixed-dose G-CSF appears warranted.


Interspecific plasmid transfer and modification of heat-stable enterotoxin expression by Klebsiella pneumoniae from infants with diarrhea.
We have previously described two heat-stable enterotoxins (ST) produced by Citrobacter freundii and by Klebsiella pneumoniae. To see whether transfer of toxigenic ability may occur between different bacterial species, conjugal mating experiments were performed using strains isolated from children. Donors and recipients were incubated together. ST production by the recipients was tested by the suckling mouse assay, which is the standard biologic method for detecting ST, and also by an ELISA test. The latter is based on MAb directed to Escherichia coli 18- or 19-amino acid toxin. Citrobacter and E. coli strains producing an ELISA-positive ST were used as plasmid donors. Recipients were E. coli, Klebsiella P89, and Klebsiella AL55. The latter had been previously shown to be capable of producing an ELISA-negative ST, but had spontaneously lost this ability. After conjugation, all strains gave positive results in the suckling mouse assay. However, E. coli and Klebsiella P89 ST were positive in the ELISA test, whereas Klebsiella AL55 ST was negative. The same three strains were transformed by inserting the plasmid pSLM004 encoding an ELISA-positive ST. Klebsiella P89 and E. coli became capable of producing an ELISA-positive ST, whereas Klebsiella AL55 cells were positive in the suckling mouse assay but negative in the ELISA. To assess whether the toxigenicity acquired was itself transmissible, the new ST-producing strains were incubated with a nontoxigenic Citrobacter strain. The latter became capable of producing an ELISA-positive ST in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Are interatrial band myocytes maximally hypertrophied in normal canine hearts?
In canine right atrial hypertrophy, the cross-sectional area (Axs) of right atrial myocytes increases, whereas the Axs of the broader interatrial band myocytes does not. In the current study, myocyte reconstructions showed that right atrial myocyte length increased in proportion to Axs in right atrial hypertrophy. On the other hand, mean interatrial band myocyte length in both normal and right atrial hypertrophy dogs was roughly inversely proportional to mean Axs, as expected if interatrial band myocyte volume was constant. Plotting mean Axs vs. myocyte length for individual interatrial band myocytes revealed a distribution whose border defined a maximal volume curve; many myocytes were well beneath that curve. Mononuclear myocytes (generally diploid) were limited by a 65,000-micrometer 3 curve, which many binuclear myocytes (generally tetraploid) surpassed; myocyte ploidy thus constrained myocyte volume. However, because many mononuclear and binuclear myocytes had lower volumes, their failure to hypertrophy cannot be attributed to attainment of the maximal volume possible for their ploidy.


[Cytogenetic study of peripheral lymphocyte culture in couples with habitual abortion].
We report on a cytogenetic investigation of lymphocytes in 241 couples and six women with at least three abortions. We found a balanced reciprocal translocation three times (1.2% of couples) and a balanced Robertsonian translocation twice (0.8% of couples). Four numerical aberrations of the gonosomes were detected (three of them as a mosaic), and one deletion Xq- as a mosaic. The heterochromatic region of the chromosomes 1, 9 or 16 was enlarged in 12 couples (4.9%). There was no couple with a pericentric inversion of the chromosomes 1 or 9. The enlarged Y-chromosome (five males) according to our results does not play any important role for the reproduction. Five translocations and one supernumerary chromosome each in one cell only indicate an enlarged frequency of breakage events in couples with habitual abortion.


[Guideline 'Radiotherapy in non-small-cell lung carcinoma. Working Group, National Organization for Quality Assurance in Hospitals, Netherlands].
8000-9000 new patients with lung cancer are diagnosed yearly in the Netherlands. Of these 10-30% can be treated by surgery, which because of co-morbidity or the extent of the disease is impossible in the others. There is agreement on the terms 'curative', 'radical' and 'palliative' radiotherapy: curative radiotherapy aims at cure through destruction of all tumour cells, on the assumption that the neoplasia has not metastasized (this applies to patients with tumours in stage I and II and sometimes in stage III); radical radiotherapy aims at postponement of locoregional tumour growth; this has a positive effect on the patient's duration of survival and quality of life, but it is to be expected that the patient will die from distant metastases (this treatment is indicated for patients with stage IIIA disease); palliative radiotherapy aims at improvement of the quality of life rather than on prolonging the duration of survival. Patients with a stage III tumour (locoregional invasion making surgical treatment impossible but without distant metastases) without complaints should receive radiotherapy, because these patients are candidates for prolonged survival. In the future the best therapy for these patients could be a combined modality (chemotherapy in combination with radiotherapy). Lung cancer patients with an irresectable tumour should be included as often as possible in clinical trials. During treatment checking quality of life, taking into account the objective and the side effects of the treatment, is important. All medical experts who look after the patient, should inform each other on the actual state of health of the patient and any appointments made. A personal file with this information, kept by the patient himself, has been advocated for this purpose.


Conformational preferences and binding to neurophysins of oxytocin analogs with sarcosine or N-methylalanine in position 7.
The 600 MHz proton n.m.r. spectra of (sarcosyl7)-oxytocin and (N-methylalanyl7) oxytocin in 2H2O solution have been recorded and completely assigned. In each case the spectrum indicates the presence of two slowly interconverting conformers, which are the cis-trans isomers about the peptide bond between residues six and seven. The trans isomer is energetically favored in both cases. When neurophysin is added to a solution of (N-methylalanyl7) oxytocin or (sacrosyl7)-oxytocin at pH 3.0, the proportion of minor conformer remains constant, indicating that the cis and trans conformers are equally tightly bound to the protein.


[The homosexual as a "molesting personality". Nikolaus Jensch and his psychiatric-genetic studies].
For the first time ever, this study presents facts on the biography of Nikolaus Jensch (1913 - 1964), who worked in Wroclav, Leipzig, Strasbourg and Bremen, and on his psychiatric-genetic studies on homosexuality during the Nazi regime. Jensch tried, under methodologically rather doubtful presuppositions, to separate "genuine" from so-called "pseudo-homosexuals", who for him were receptive to psychotherapeutic and educational intervention. Ultimately he aimed to establish an empiric prediction as to the heredity of homosexuality, although even that would not exculpate homosexuals from prosecution. In a different study he analysed the curing effects of castration for homosexuality and other sexual deviances. Although acknowledging the mutilating character of castration and its due to high recrudescence rates rather poor therapeutic outcome, he never pleaded to refrain from this intervention.


Insulinlike growth factor 1 production is inhibited in human sepsis.
We studied the response of 14 normal volunteers and five septic patients to a 48-hour course of exogenous biosynthetic human growth hormone (hGH) or placebo. Six normal controls (group 1) received saline, eight normal controls received hGH (group 2), and five septic patients also received biosynthetic hGH (group 3). Urinary urea excretion declined, and splanchnic amino acid uptake was maintained only in group 2 subjects. Septic patients exhibited changes in amino acid and urea dynamics comparable to those of subjects receiving placebo. Insulinlike growth factor 1 (IGF-1) production and plasma concentrations increased in group 2 in a fashion corresponding to the changes in nitrogen exchange, whereas septic patients exhibited no change in IGF-1 level. Therefore, in this septic patient group, exogenous hGH was ineffective in attenuating nitrogen losses and stimulating IGF-1 production. This supports the hypothesis that IGF-1 is a mediator of the anabolic effect of hGH.


Barriers Associated With Evidence-Based Practice Among Nurses in Low- and Middle-Income Countries: A Systematic Review.
Evidence-based practice (EBP) is both a goal and an approach that requires a combination of clinical experience with the most credible recent research evidence when making decisions in healthcare practice. The approach has been widely embraced; however, an evidence-to-practice gap still exists. To assess barriers to EBP among nurses in low- and middle-income countries. This review conforms to the PRISMA statement. Databases PubMed, Scopus, EMBASE, and Web of Science/Knowledge were searched using a combination of keywords that included "barriers," "evidence-based practice," and "nurses." The references of the selected articles were also hand-searched to obtain additional relevant articles. Studies published in peer-reviewed journals in English between 2000 and 2018 were included in the review. Sixteen articles were included in the analysis, with a total number of 8,409 participants. Both qualitative and quantitative studies were included in the review. Three main themes emerged from eight categories found. The three main themes were institutional-related barriers, interdisciplinary barriers, and nurse-related barriers. The theme of institutional-related barriers emerged from four categories, which included scant resources, limited access to information, inadequate staffing, and lack of institutional support. The theme of interdisciplinary barriers emerged from subcategories that included lack of communication between academic and clinical practice environments, inconsistency between education and practice in the nursing discipline, lack of teamwork, and the public's negative image about the nursing profession. Finally, the theme of nurse-related barriers emerged from categories including perceived limitations in the scope of nurses' practice, time, knowledge of EBP, and individual-related barriers. These findings may guide the design of future interventions aimed at fostering EBP. Implementing EBP in practice should be systematic and requires institutional will and interdisciplinary and individual commitment. It should be a collective goal and a win-win situation for nurses, clinicians, and healthcare organizations.


[Comparative morphofunctional research on the individual resistance of animals to hypoxia].
It has been shown in experiments on white male rats that there is a correlation between hypoxia tolerance and the rate of metabolism in brain tissue. Animals with varying tolerance to hypoxia differed also in the acid-base balance of venous blood outflowing from the brain. While adapting to hypoxia animals with high individual tolerance developed the main metabolic changes in the reticular formation and those with low tolerance in the cerebral cortex. During adaptation to hypoxia animals with high and low tolerance had varying changes in acid-base balance. The data obtained allow the conclusion that there is a correlation between the rate of brain tissue metabolism, acid-base balance of jugular vein blood and individual animals' tolerance to hypoxia.


Orthopedic history and examination in the etiology of overuse injuries.
Overuse injuries, and stress fractures in particular, afflict many runners and military recruits. This investigation sought to identify pretraining factors which may predispose to overuse injuries. Orthopedic and running history questionnaires and an orthopedic examination were administered to 505 trainees entering an intensive military training school. A novel method for evaluating ankle dorsiflexion was developed, and alignment measures, in units of centimeters rather than degrees, were obtained. Over 10% of the trainees were removed from the school for overuse-related injuries, and over half of these were tibial stress fractures. The incidence of clinically diagnosed stress fractures was 6.3%. No single orthopedic history question or combination of questions could discriminate between trainees who did or did not subsequently incur overuse injuries. Results from the running history indicated that those running 25 or more miles.wk-1 (mpw) had a significantly (P less than 0.027) lower incidence of stress fractures (3.0%) than those running 4 or fewer mpw over the previous year (11.5%). The orthopedic examination did not identify any predisposing alignment characteristics, perhaps due to the low incidence of overuse injuries. Population means are presented for future use in comparative studies.


Activation of nuclear factor-kappaB p50 homodimer/Bcl-3 complexes in nasopharyngeal carcinoma.
EBV latent infection is associated with the development of lymphoid and epithelial malignancies such as nasopharyngeal carcinoma (NPC). The EBV latent membrane protein 1 (LMP1) acts as a constitutively active tumor necrosis factor receptor and activates cellular signaling pathways such as c-Jun-NH(2)-terminal kinase, cdc42, Akt, and nuclear factor (NF)-kappaB. In epithelial cells, two regions of LMP1 induce specific forms of NF-kappaB. COOH-terminal activating region 2 only activates p52/p65 dimers, whereas COOH-terminal activating region 1 activates p50/p50, p50/p52, and p52/p65 dimers and also uniquely up-regulates the epidermal growth factor receptor (EGFR) at the mRNA level. Deregulation of specific NF-kappaB members is associated with the development of many cancers. In this study, the status of NF-kappaB activation was investigated in NPC to determine which NF-kappaB dimers may contribute to the development of NPC. Electrophoretic mobility shift assay, immunoblot, ELISA, and immunohistochemistry data demonstrate that in NPC, NF-kappaB p50 homodimers are specifically activated, and this activation is not dependent on LMP1 expression. Coimmunoprecipitation assays indicate that homodimers are bound to the transcriptional coactivator Bcl-3, and chromatin immunoprecipitation indicates that this complex is bound to NF-kappaB consensus motifs within the egfr promoter in NPC. The discrete yet striking NF-kappaB p50 activation in NPC suggests that p50/p50 homodimers may be important factors in the development of NPC and may contribute to oncogenesis through transcriptional up-regulation of target genes through their interaction with Bcl-3.


[Laparoscopic radical prostatectomy: initial 17 case report].
We report our early experience of laparoscopic radical prostatectomy for clinically localized prostatic cancer. Between April and December 2000, 17 patients with clinical stage T1c to T2b prostatic cancer underwent laparoscopic radical prostatectomy. The median age was 70.9 year old, the median preoperative PSA and the median Gleason score of biopsy specimens was 7.1 ng/ml, 6, respectively. We followed the operation technique from the "Montsouris technique". Briefly, we used five trocars (two 10-mm and three 5-mm trocars) and the operation was performed transperitoneally. Pelvic lymph node dissection was performed in only one patient (case 3). Urethrovesical anastomosis was performed with 6 to 9 interrupted 3-0 absorbable sutures. No conversion to open surgery or reoperation was required in all cases. Median operation time was 450 minutes (range 290 to 750) and median intraoperative bleeding (including urine) was 600 ml (range 100 to 3,135). Only one case (case 3) needed homologous blood transfusion. Median postoperative Foley catheterization period was 9 days (range 5 to 19). Intraoperative complications related to operation procedure were one rectal injury and three vesical injuries, which were treated by absorbable suturing laparoscopically. Major complication was one complete A-V block (case 3) who was required a transient discontinuance of the procedure. Surgical margins were negative in 13 cases. Postoperative pathological evaluation was one pT0, five pT2a, seven pT2b and four pT3a. PSA value decreased less than 0.2 ng/ml after surgery in all patients. Although six months have passed after the surgery in only 4 patients, all of them were fully continent. Although the operation time is still longer than that of conventional open procedures, intraoperative magnified vision allows a more precise and safer dissection, especially for apical dissection. We believe that operative time will decrease with more experience. These results show that laparoscopic radical prostatectomy can be an acceptable treatment option for localized prostatic cancer.


High-energy electrons used to inhibit experimental intraocular proliferation and detachment.
Irradiation of rabbit eyes with high-energy electrons was used to test the inhibition of experimental intraocular proliferation and retinal detachment, produced by intravitreal implantation of 250,000 homologous fibroblasts. After irradiation with 2,000 rad, started 5 days after implantation, 45% of eyes (9 of 20) still manifested traction detachment. When the dose was increased to 3,000 rad and radiation treatment was started 1 day after implantation, proliferation and traction detachment were observed in only 10% of eyes (2 of 20). No acute damage to retinal tissue or nerve fibers was observed. Because it is easily available, simple in application and dose adjustment, and without toxic side effects, radiation therapy should be considered as an effective alternative to drug treatment for the inhibition of intraocular proliferation and detachment. Statistically significant results of this investigation suggest its use combined with surgery in certain reproliferative cases in man.


Rh(II) catalysed intramolecular C-H insertion of diazo substrates in water: a simple and efficient approach to catalyst reuse.
Water is an efficient solvent for the Rh2(OAc)4 catalysed intramolecular C-H insertion of a range of diazo substrates without competitive water insertion. Due to the high solubility and stability of the catalyst in water, the catalyst can be efficiently reused.


Superparamagnetic sub-5 nm Fe@C nanoparticles: isolation, structure, magnetic properties, and directed assembly.
A method for isolating single crystalline sub-5 nm carbon coated iron nanoparticles (Fe@C NPs) from a carbon nanotube matrix has been developed. The isolation of such particles allows for their characterization by high resolution electron microscopy methods and SQUID magnetometry. While the NPs are superparamagnetic at room temperature, at 10 K they exhibit a coercivity nearly 30 times greater than that of commercial Fe3O4 NPs of comparable size. A novel nanotemplate directed assembly method for manipulating the particles at the individual particle level is also reported.


Development of a balanced detector with biased synchronous detection and application to near shot noise limited noise cancelling of supercontinuum pulse light.
We report on the development of a balanced detector suited for multicolor imaging. The source pulsed light is split into probe and reference pulsed light. The reference pulse is delayed through an optical path and the probe and reference pulses are detected by a single photodetector. The signs of the detected signals of the probe and reference pulses are flipped based on a signal synchronous to the light source. Then, the signals are averaged through a low-pass filter. The output signal is proportional to the intensity difference between the probe and the reference. This balanced detector has two features: (1) both the probe and reference pulsed lights are detected by a single photodetector and (2) a voltage bias on the sign flipping compensates for the optical-intensity unbalance between the probe and reference pulsed lights. The first feature enables the probe and reference pulses to travel along a common optical path from a sample through a spectrograph to the photodetector, which minimizes the intensity unbalance between the probe and reference pulses during imaging and spectroscopy. The second feature ensures the complete balanced-detection in whole wavelength range by compensating for the optical unbalance created by deviations in the splitting ratios of the probe and reference lights at different wavelengths. Although a higher signal to noise ratio (SNR) reached to near shot noise limited SNR is attained by attaching a resonator to the photodetector for pulse repetition, the electrical bias cannot compensate for the optical balance. This unbalance is, however, corrected by adjusting the phase of the synchronous signal. We applied the present balanced detection to a stimulated Raman microscope with supercontinuum probe light and demonstrated its noise cancelling performance through capturing polystyrene beads.


Are bile bacteria relevant to septic complications following biliary surgery?
Bile bacteriology, wound sepsis and the effect of prophylactic antibiotics have been studied in a controlled prospective double blind randomized trial on 375 patients undergoing elective cholecystectomy at a district general hospital. We have examined the overall prevalence of bacteria in bile and have identified several factors associated with an increased incidence. The identity of organisms isolated from a total of 21 patients with infected wound swabs was compared with isolates from the bile at operation, and in only two instances was there a correlation. Cephazolin, given either pre-operatively, or into the wound, reduced wound infection rates compared with a control group (from 11.8 to 2.4 per cent, P less than 0.005). We conclude that the majority of wound infections in this series were caused by organisms from the patients' skin or exogenous sources, rather than by bacteria from the biliary system.


[Stability of beta-HCG in old blood stains].
Pregnancy was diagnosed from old blood stains by means of radioimmunoassay of beta-HCG. Up to 45 days, the age of the blood stains did not influence values, and extraction by ultrasound did not improve the results.


Diphenhydramine for Acute Extrapyramidal Symptoms After Propofol Administration.
Extrapyramidal symptoms are an uncommon but well-recognized side effect after the administration of general anesthesia in patients without a significant neurologic history. Several case reports implicate propofol as the likely causative agent producing these symptoms, which include ballismus, dystonia, choreoathetosis, and opisthotonus. Currently, there is no clear consensus on first-line treatment of these symptoms. In each of the published cases, anticholinergic medications and benzodiazepines were central to initial management, although the speed and extent of symptom resolution were variable. Here we present a case of a 17-year-old boy with ulcerative colitis who presented with ballismus, torticollis, tongue thrusting, and oculogyric movements after colonoscopy under general anesthesia with propofol. The patient responded promptly to treatment with diphenhydramine. This is the first reported case in which diphenhydramine was successfully used as the primary treatment of severe extrapyramidal symptoms in a pediatric patient after propofol administration.


The expression of metallothionein (MT) and proliferation intensity in ovarian cancers treated with cisplatin and paclitaxel.
Metallothioneins (MT) represent low molecular weight proteins that are supposed to fulfil several functions. They participate in the cell cycle, protect cells from oxidative stress, control levels of heavy metals and participate in multidrug resistance processes, particularly in cases of alkylating drugs. The present study aimed at evaluation of proliferation intensity (Ki67, PCNA) in ovarian cancers treated using cisplatin and paclitaxel, as related to expression of MT. The experiments were performed on samples originating from 10 patients operated on due to ovarian cancer. The material originated from the first operations or second-look operations. All the patients were treated with cisplatin and paclitaxel. Immunocytochemical reactions using antibodies to MT, Ki67 and PCNA were performed in paraffin sections originating from the cases studied. Statistical analysis was performed using Statistica software. The studies demonstrated no relation between expression of MT on the one hand and intensity of proliferation before or after chemotherapy on the other hand (gamma correlation, p > 0.05). The results indicate that expression of MT is not related to resistance to treatment using cisplatin and paclitaxel.


Infection with GB virus C (GBV-C) in patients with fulminant hepatitis.
There appear to be hepatitis viruses other than hepatitis A, B, C, D and E. One of these has been proposed with a designation of GB virus C. Sera from 44 patients with fulminant hepatitis were tested for RNA of GB virus C by reverse-transcription polymerase chain reaction with nested primers deduced from the putative non-structural 3 (helicase) region. RNA of GB virus C was detected in three (20%) of 15 patients with hepatitis B virus infection and three (12%) of 25 patients without markers of hepatitis A-E virus infection. Overall, GB virus C RNA was detected in six (14%) of the 44 patients with fulminant hepatitis, at a frequency significantly higher (p < 0.001) than that in three (0.9%) of 326 blood donors matched for age with the patients. These results indicate a role of GB virus C in inducing fulminant hepatitis either by itself or in concert with the other hepatitis viruses.


Salicylic acid and its location in response to biotic and abiotic stress.
Salicylic acid (SA) is an important signal involved in the activation of plant defence responses against abiotic and biotic stress. SA may derive from the phenylpropanoid pathway or via isochorismate synthase as demonstrated in Nicotiana benthamiana, tomato and Arabidopsis thaliana. The phenylpropanoid pathway as well as isochorismate synthase are localized in the chloroplasts but it remains unknown if the end product SA is in the same organelle. We have studied the localization of SA in A. thaliana using the salicylate hydroxylase (NahG) gene expressed with a chloroplast targeting sequence. Plants expressing NahG in the chloroplasts are unable to accumulate SA induced after pathogen or UV exposure. Our data infer that SA is initially located in the chloroplasts.


Gasohol: Does It or Doesn't It Produce Positive Net Energy?
A detailed analysis of energy inputs and outputs is performed on grain-based gasohol (10 percent grain-based ethanol, 90 percent gasoline). Existing differences of opinion on the energy balance derive mainly from variations in interpretation which are several examples of inherent methodological problems in energy analysis. The result is strongly dependent on assumptions about use of crop residues for fuel and the miles-per-gallon rating of gasohol. In terms of total nonrenewable energy, gasohol is close to the energy break-even point. On the other hand, in terms of petroleum or petroleum-substitutable energy, gasohol is an unambiguous energy producer, since most energy inputs to the process can be supplied by nonpetroleum sources such as coal.


Characterization of AIDS-associated tumors in Italy: report of 435 cases of an IVDA-based series.
The Italian Cooperative Group on AIDS-related tumors has collected 435 cases of HIV-associated tumors since December 1986. The following conclusions can be drawn from this IVDA-based series: (1) at least 15% of AIDS cases are associated with tumors; (2) the number of malignant lymphomas (high-grade non-Hodgkin's lymphoma [NHL], Hodgkin's disease [HD] is comparable to that of Kaposi's sarcoma (KS) (188 vs. 198); (3) KS among AIDS patients is less common than in countries where homosexual men are the main group affected by AIDS. However, KS also affects intravenous drug abusers (IVDA) almost exclusively males, with characteristics similar to those observed among homosexual men; (4) HD is associated with an aggressive course; (5) anal and oral primary tumors as well as oral and anal involvement of NHL are very rare; (6) testicular cancers occur in patients mainly with early HIV infection, without adversely affecting the dosage of radiotherapy and chemotherapy; (7) cervical cancer successfully treated with conization suggests that PAP test screening in young IVDA women is warranted; (8) lung cancer occurs in a young age group with rapid progression and death.


Tumor cells with neuronal intermediate progenitor features define a subgroup of 1p/19q co-deleted anaplastic gliomas.
The integrated diagnosis of anaplastic oligodendroglioma, IDH mutant and 1p/19q co-deleted, grade III (O3id ) is a histomolecular entity that WHO 2016 classification distinguished from other diffuse gliomas by specific molecular alterations. In contrast, its cell portrait is less well known. The present study is focused on intertumor and intratumor, cell lineage-oriented, heterogeneity in O3id . Based on pathological, transcriptomic and immunophenotypic studies, a novel subgroup of newly diagnosed O3id overexpressing neuronal intermediate progenitor (NIP) genes was identified. This NIP overexpression pattern in O3id is associated with: (i) morphological and immunohistochemical similarities with embryonic subventricular zone, (ii) proliferating tumor cell subpopulation with NIP features including expression of INSM1 and no expression of SOX9, (iii) mutations in critical genes involved in NIP biology and, (iv) increased tumor necrosis. Interestingly, NIP tumor cell subpopulation increases in O3id recurrence compared with paired newly diagnosed tumors. Our results, validated in an independent cohort, emphasize intertumor and intratumor heterogeneity in O3id and identified a tumor cell subpopulation exhibiting NIP characteristics that is potentially critical in oncogenesis of O3id . A better understanding of spatial and temporal intratumor cell heterogeneity in O3id will open new therapeutic avenues overcoming resistance to current antitumor treatments.


[Cyberstalking].
The term cyberstalking appears in the media with increasing frequency. So far epidemiological studies are sparse. Since researchers have used different definitions and study samples for cyberstalking, widely varying prevalence rates have been published. We report here a case of cyberstalking and discuss available empirical data. Cyberstalking may cause psychological distress similar to that of real world stalking. The need for a scientific definition of cyberstalking and for future studies is presented. Since it is likely that psychiatrists will encounter victims of cyberstalking they should have knowledge of this phenomenon.