The influence of the call with a mobile phone on heart rate variability parameters in healthy volunteers.
It is possible that electromagnetic field (EMF) generated by mobile phones (MP) may have an influence on the autonomic nervous system (ANS) and modulates the function of circulatory system. The aim of the study was to estimate the influence of the call with a mobile phone on heart rate variability (HRV) in young healthy people. The time and frequency domain HRV analyses were performed to assess the changes in sympathovagal balance in a group of 32 healthy students with normal electrocardiogram (ECG) and echocardiogram at rest. The frequency domain variables were computed: ultra low frequency (ULF) power, very low frequency (VLF) power, low frequency (LF) power, high frequency (HF) power and LF/HF ratio was determined. ECG Holter monitoring was recorded in standardized conditions: from 08:00 to 09:00 in the morning in a sitting position, within 20 min periods: before the telephone call (period I), during the call with use of mobile phone (period II), and after the telephone call (period III). During 20 min call with a mobile phone time domain parameters such as standard deviation of all normal sinus RR intervals (SDNN [ms]--period I: 73.94+/-25.02, period II: 91.63+/-35.99, period III: 75.06+/-27.62; I-II: p<0.05, II-III: p<0.05) and standard deviation of the averaged normal sinus RR intervals for all 5-mm segments (SDANN [ms]--period I: 47.78+/-22.69, period II: 60.72+/-27.55, period III: 47.12+/-23.21; I-II: p<0.05, II-III: p<0.05) were significantly increased. As well as very low frequency (VLF [ms2]--period I: 456.62+/-214.13, period II: 566.84+/-216.99, period III: 477.43+/-203.94; I-II: p<0.05), low frequency (LF [ms(2)]--period I: 607.97+/-201.33, period II: 758.28+/-307.90, period III: 627.09+/-220.33; I-II: p<0.01, II-III: p<0.05) and high frequency (HF [ms(2)]--period I: 538.44+/-290.63, period II: 730.31+/-445.78, period III: 590.94+/-301.64; I-II: p<0.05) components were the highest and the LF/HF ratio (period I: 1.48+/-0.38, period II: 1.16+/-0.35, period III: 1.46+/-0.40; I-II: p<0.05, II-III: p<0.05) was the lowest during a call with a mobile phone. The tone of the parasympathetic system measured indirectly by analysis of heart rate variability was increased while sympathetic tone was lowered during the call with use of a mobile phone. It was shown that the call with a mobile phone may change the autonomic balance in healthy subjects. Changes in heart rate variability during the call with a mobile phone could be affected by electromagnetic field but the influence of speaking cannot be excluded.


Frequency- and orientation-dependent effects of mexiletine and quinidine on conduction in the intact dog heart.
Myocardial conduction depends on the magnitude of the fast inward sodium current as well as on cardiac fiber orientation, with more rapid propagation along myocardial fibers than across them. Although antiarrhythmic drugs depress the sodium current in a frequency-dependent fashion in vitro, their effects on conduction in the intact ventricle have been less well studied. We therefore evaluated the frequency- and orientation-dependent actions of mexiletine, quinidine, and their combination on epicardial conduction in 24 pentobarbital-anesthetized dogs. These interventions were chosen because the time constant of recovery from sodium-channel blockade by mexiletine in vitro is shorter than that from blockade by quinidine, and because we have previously shown that the combination of these drugs is often clinically effective when single-agent therapy fails. An electrode array that permitted measurement of conduction times in multiple orientations over short segments of epicardium without contamination by rapid Purkinje fiber propagation or by latency or virtual cathode effects at the stimulus site was developed for these studies. In all animals, the atrioventricular node was destroyed by injection of formalin to permit measurements over a wide range of cycle lengths (250 to 1500 msec). In the absence of drugs, conduction in any direction was frequency independent. In the presence of mexiletine, however, frequency-dependent increases in conduction times were found at cycle lengths of 600 msec or less; these changes were significantly greater in orientations for which baseline conduction was rapid. Quinidine, on the other hand, increased conduction times at all tested cycle lengths without significant orientation-dependent effects.(ABSTRACT TRUNCATED AT 250 WORDS)


Service innovation management practices in the telecommunications industry: what does cross country analysis reveal?
Service innovation management practice is currently being widely scrutinized mainly in the developed countries, where it has been initiated. The current study attempts to propose a framework and empirically validate and explain the service innovation practices for successful performance in the telecommunications industry of two developing countries, Malaysia and Bangladesh. The research framework proposes relationships among organisational culture, operating core (innovation process, cross-functional organisation, and implementation of tools/technology), competition-informed pricing, and performance. A total of 176 usable data from both countries are analysed for the purpose of the research. The findings show that organisational culture tends to be more influential on innovation process and cross-functional organisation in Malaysian telecommunication industry. In contrast, implementation of tools/technology plays a more instrumental role in competition-informed pricing practices in Bangladesh. This study revealed few differences in the innovation management practices between two developing countries. The findings have strategic implications for the service sectors in both the developing countries regarding implementation of innovative enterprises, especially in Bangladesh where innovation is the basis for survival. Testing the innovation management practices in the developing countries perhaps contains uniqueness in the field of innovation management.


The influence of maternal inflammatory bowel diseases on fetal cardiac functions: A case-control study.
The altered maternal inflammatory milieu and changes in maternal vascular structure (arterial stiffness) and function may affect the fetal heart in pregnant women diagnosed with inflammatory bowel disease (IBD). To investigate fetal cardiac functions in IBD pregnancies and to reveal the relationship between IBD duration and fetal cardiac functions. Prospective case-control study. The case group included 19 pregnant women with ulcerative colitis and seven with Crohn's disease who were in remission at the time of the study. The control group consisted of 52 healthy pregnant women matched for gestational age in the third trimester of pregnancy (at 32 to 33 weeks). Fetal cardiac functions. The assessment was blinded as to whether the patients were cases or controls. The right ventricular E', E'/A', S', and tricuspid annular plane systolic excursion (TAPSE) were significantly lower, and E/E', myocardial performance index (MPI'), and isovolumetric relaxation time (IVRT') were significantly higher in fetuses of IBD pregnancies. Diastolic functions (E/E', E', E'/A', and IVRT'), systolic functions (S' and TAPSE), and global function (MPI') were changed in the case group. A significantly strong correlation was between maternal disease duration and fetal right ventricle diastolic function parameters (E/E', E, E', E'/A') in the case group (r2 = 0.780; p ≤0.001, r2 = 0.570; p ≤0.001, r2 = 0.604; p ≤0.001, r2 = 0.638; p ≤0.001, respectively). Diastolic and systolic fetal cardiac functions changed in IBD pregnancies. As the disease duration increases, especially fetal cardiac diastolic functions may be affected.


Association of AKR1C3 Polymorphisms with Bladder Cancer.
Polymorphisms in the genes coding for the carcinogen metabolizing enzymes may affect enzyme activities and alter the activation and detoxification rates of the carcinogens. AKR1C3 is one of the very polymorphic xenobiotic metabolizing enzymes involved in the bioactivation process. Here we aimed to investigate the association of two single nucleotide polymorphisms in AKR1C3, rs12529 (c.15C > G) and rs1937920 (12259 bp 3' of STP A > G) with urinary bladder cancer (UBC). Two-hundred fifty UBC cases and 250 control subjects were genotyped using the Polymerase Chain Reaction and Restriction Fragment Length method. Associations of the genotypes with UBC risk and tumor characteristics were assessed using logistic regression and Fisher's exact test. The results are corrected for multiple testing. We identified strong associations between the studied AKR1C3 variants and UBC risk. The homozygous variant genotype of rs12529 was found to be inversely associated with UBC, and rs1937920 was shown to be associated with increased risk of UBC. None of the genotypes were found to be significantly associated with tumor characteristics. We provided evidence that rs12529 and rs1937920 are significant in the molecular pathogenesis of UBC. However, the results presented here should be regarded as preliminary and might represent a first step of future larger studies aiming to better elucidate the role of AKR1C3 polymorphisms in the susceptibility to bladder cancer.


Familial Poland anomaly.
The Poland anomaly is usually a non-genetic malformation syndrome. This paper reports two second cousins who both had a typical left sided Poland anomaly, and this constitutes the first recorded case of this condition affecting more than one member of a family. Despite this, for the purposes of genetic counselling, the Poland anomaly can be regarded as a sporadic condition with an extremely low recurrence risk.


Coordination of size and number of excitatory and inhibitory synapses results in a balanced structural plasticity along mature hippocampal CA1 dendrites during LTP.
Enlargement of dendritic spines and synapses correlates with enhanced synaptic strength during long-term potentiation (LTP), especially in immature hippocampal neurons. Less clear is the nature of this structural synaptic plasticity on mature hippocampal neurons, and nothing is known about the structural plasticity of inhibitory synapses during LTP. Here the timing and extent of structural synaptic plasticity and changes in local protein synthesis evidenced by polyribosomes were systematically evaluated at both excitatory and inhibitory synapses on CA1 dendrites from mature rats following induction of LTP with theta-burst stimulation (TBS). Recent work suggests dendritic segments can act as functional units of plasticity. To test whether structural synaptic plasticity is similarly coordinated, we reconstructed from serial section transmission electron microscopy all of the spines and synapses along representative dendritic segments receiving control stimulation or TBS-LTP. At 5 min after TBS, polyribosomes were elevated in large spines suggesting an initial burst of local protein synthesis, and by 2 h only those spines with further enlarged synapses contained polyribosomes. Rapid induction of synaptogenesis was evidenced by an elevation in asymmetric shaft synapses and stubby spines at 5 min and more nonsynaptic filopodia at 30 min. By 2 h, the smallest synaptic spines were markedly reduced in number. This synapse loss was perfectly counterbalanced by enlargement of the remaining excitatory synapses such that the summed synaptic surface area per length of dendritic segment was constant across time and conditions. Remarkably, the inhibitory synapses showed a parallel synaptic plasticity, also demonstrating a decrease in number perfectly counterbalanced by an increase in synaptic surface area. Thus, TBS-LTP triggered spinogenesis followed by loss of small excitatory and inhibitory synapses and a subsequent enlargement of the remaining synapses by 2 h. These data suggest that dendritic segments coordinate structural plasticity across multiple synapses and maintain a homeostatic balance of excitatory and inhibitory inputs through local protein-synthesis and selective capture or redistribution of dendritic resources.


Protonation-Initiated Cyclization by a Class II Terpene Cyclase Assisted by Tunneling.
Terpenes represent one of the most diversified classes of natural products with potent biological activities. The key to the myriad of polycyclic terpene skeletons with crucial functions in organisms from all kingdoms of life are terpene cyclase enzymes. These biocatalysts enable stereospecific cyclization of relatively simple, linear, prefolded polyisoprenes by highly complex, partially concerted, electrophilic cyclization cascades that remain incompletely understood. Herein, additional mechanistic light is shed on terpene biosynthesis by kinetic studies in mixed H2 O/D2 O buffers of a class II bacterial ent-copalyl diphosphate synthase. Mass spectrometry determination of the extent of deuterium incorporation in the bicyclic product, reminiscent of initial carbocation formation by protonation, resulted in a large kinetic isotope effect of up to seven. Kinetic analysis at different temperatures confirmed that the isotope effect was independent of temperature, which is consistent with hydrogen tunneling.


The health needs of women prisoners: an Italian field survey.
Health care in prisons represents an important part of public health due to the interaction between prisons and society. Women prisoners have needs that distinguish them from male prisoners, however little is known about how those needs are met. The aim of the study was to gather information about the needs of women in prison and to identify which of their needs are the most or the least met. This study investigated the needs of detained women using a newly developed Questionnaire based on Gordon's model. In this descriptive study, data were collected from a convenient sample of women recruited from two Italian prisons. Data analysis used descriptive statistics. Fifty-five women (response rate = 92%) completed the self-reported questionnaire. Our findings showed that physical needs are met worse than psychological and social needs. The majority of physical needs were related to the inability to meet food preferences and the difficulty in respecting food requirements related to disease and by religion. The women experienced a loss of privacy, and they need more time for improving the quality of their relationships. The majority of the participants (65%) declared that they suffer from psychological disorders with an alarming percentage (29%) stating that they had thoughts of self-harm. They commonly consume tobacco (87.3%), and abuse substances (20%). The recognition of multi-dimensional women's needs is of primary importance to create opportunities to support incarcerated women and to build health-promoting gender-sensitive interventions.


Discovery of sodium and potassium vapor in the atmosphere of the moon.
Spectra of the region just above the bright limb of the Moon show weak emission features that are attributed to resonant scattering of sunlight from sodium and potassium vapor in the lunar atmosphere. The maximum omnidirectional emission flux above the bright limb is 3.8 +/- 0.4 kilorayleighs for sodium and 1.8 +/- 0.4 kiloray-leighs for potassium. The zenith column densities above the subsolar point are estimated to be 8 +/- 3 x 10(8) atoms cm(-2) for sodium 1.4 +/- 0.3 x 10(8) atoms cm(-2) for potassium. Corresponding surface densities are 67 +/- 12 atoms cm(-3) and 15 +/- 3 atoms cm(-3), respectively. The scale height for the sodium atmosphere is 120 +/- 42 kilometers, and for potassium 90 +/- 20 kilometers, which implies that the effective temperature of the sodium and potassium is close to the lunar surface temperature. The sodium density at the south polar region was found to be similar to that at the subsolar point, indicating wide-spread distribution of sodium vapor over the lunar surface. The ratio of the density of sodium to the density of potassium is (6 +/- 3) to 1, which is close to the sodium to potassium ratio in the lunar surface, suggesting that the atmosphere originates from the vaporization of surface minerals.


Childhood arterial ischemic stroke: a review of etiologies, antithrombotic treatments, prognostic factors, and priorities for future research.
Childhood arterial ischemic stroke (AIS) is a rare, but serious, medical condition, which is fatal in approximately 3% and associated with both acute and long-term neurologic impairment in over 70% of cases. Common etiologies include sickle cell disease, congenital heart disease, arterial dissection, prothrombotic conditions, and preceding viral infections; however, one in four cases is considered idiopathic. To date, no randomized controlled clinical trials (RCTs) have been conducted to establish evidence for current therapeutic strategies outside of sickle cell disease, thus, treatment strategies are largely shaped by consensus-based guidelines, in which, beyond the acute period, aspirin is the mainstay of therapy and anticoagulation is reserved for select circumstances. In recent years, evidence on prognostic factors has accumulated, helping to inform the future design of prognostically stratified RCTs. In this narrative review, we discuss the current understanding of etiologies, consensus-based treatment recommendations, contemporary treatment data, and prognostic factors in childhood AIS. We also identify priorities for future research.


Minimizing hemorrhagic complications in dialysis patients.
Renal failure is associated with an increased incidence of hemorrhage from a variety of sites, particularly in patients undergoing surgical procedures. The primary factors in the pathogenesis of bleeding in renal failure are platelet biochemical abnormalities and alterations in platelet vessel wall interactions. Hemodialysis improves hemostatic abnormalities in uremia, but the need for heparinization during the procedure may increase the bleeding risk. The risk of bleeding may be minimized by using peritoneal dialysis or alternative means to routine heparinization to prevent clotting in the extracorporeal circulation during hemodialysis. These include use of minimal heparin, prostacyclin, regional citrate anticoagulation, and no anticoagulation. Continuous arteriovenous hemodialysis may also be performed with regional citrate anticoagulation. There are several nondialytic therapies that may be used to prevent or treat hemorrhage in renal failure patients. These include administration of cryoprecipitate, 1-deamino-8-arginine vasopressin, estrogens, red blood cells, and erythropoietin. A clinical strategy to minimize bleeding complications in dialysis patients is presented.


Arabidopsis ROOT UVB SENSITIVE2/WEAK AUXIN RESPONSE1 is required for polar auxin transport.
Auxin is an essential phytohormone that regulates many aspects of plant development. To identify new genes that function in auxin signaling, we performed a genetic screen for Arabidopsis thaliana mutants with an alteration in the expression of the auxin-responsive reporter DR5rev:GFP (for green fluorescent protein). One of the mutants recovered in this screen, called weak auxin response1 (wxr1), has a defect in auxin response and exhibits a variety of auxin-related growth defects in the root. Polar auxin transport is reduced in wxr1 seedlings, resulting in auxin accumulation in the hypocotyl and cotyledons and a reduction in auxin levels in the root apex. In addition, the levels of the PIN auxin transport proteins are reduced in the wxr1 root. We also show that WXR1 is ROOT UV-B SENSITIVE2 (RUS2), a member of the broadly conserved DUF647 domain protein family found in diverse eukaryotic organisms. Our data indicate that RUS2/WXR1 is required for auxin transport and to maintain the normal levels of PIN proteins in the root.


Effect of Segment Types on Characterization of Soft Sensing Textile Actuators for Soft Wearable Robots.
The use of textiles in soft robotics is gaining popularity because of the advantages textiles offer over other materials in terms of weight, conformability, and ease of manufacture. The purpose of this research is to examine the stitching process used to construct fabric-based pneumatic bending actuators as well as the effect of segment types on the actuators' properties when used in soft robotic glove applications. To impart bending motion to actuators, two techniques have been used: asymmetry between weave and weft knit fabric layers and mechanical anisotropy between these two textiles. The impacts of various segment types on the actuators' grip force and bending angle were investigated further. According to experiments, segmenting the actuator with a sewing technique increases the bending angle. It was discovered that actuators with high anisotropy differences in their fabric combinations have high gripping forces. Textile-based capacitive strain sensors are also added to selected segmented actuator types, which possess desirable properties such as increased grip force, increased bending angle, and reduced radial expansion. The sensors were used to demonstrate the controllability of a soft robotic glove using a closed-loop system. Finally, we demonstrated that actuators integrated into a soft wearable glove are capable of grasping a variety of items and performing various grasp types.


Counseled women's perspectives on their interactions with lay health advisors: a feasibility study.
Although the use of lay health advisors (LHAs) has become a popular intervention in public health promotion projects, few programs have conducted evaluations demonstrating program impact by interviewing people actually counseled by LHAs. This study used semistructured, in-person interviews with 29 older, black women to elicit their perceptions of their interactions with the North Carolina Breast Cancer Screening Program's LHAs, and the ways in which these interactions affected their mammography attitudes and behavior. Interview data indicate that a majority of the respondents felt that LHAs had helped them in some way; most said that talking to advisors made them think more positively about mammograms and/or consider getting one. LHAs influenced the women they counseled because the women knew the advisors well, felt comfortable talking to advisors about private issues, considered advisors to be credible sources of information about mammography and because advisors offered women support with respect to their mammography behavior. These results elucidate some of the mechanisms through which LHAs affect the attitudes and behavior of individuals in their social networks.


Recent advances in the supramolecular assembly of cyclophosphazene derivatives.
Cyclophosphazenes are a fascinating group of inorganic heterocyclic compounds whose rings are constituted by the repetition of phosphorus and nitrogen atoms. They have received particular attention due to their easy functionalization and thermal stability and as an excellent core for the preparation of advanced materials. Rigid trispirocyclic derivatives of cyclophosphazenes afford numerous supramolecular structures that are suitable for the formation of host-guest complexes with a variety of guest molecules such as gas molecules and molecular rotor compounds. Also, the donor nitrogen atoms of the cyclophosphazene ring can participate in non-covalent interactions such as hydrogen bonding and metal coordination. It can also be used in the construction of supramolecular dendrimeric or polymeric systems as either the starting compound or the carrier of supramolecular groups. Thus, cyclophosphazenes have been employed in the preparation of supramolecular systems for about past 30 years. This review focuses on the state of recent advances in the construction of cyclotriphosphazene-based supramolecular systems built by non-covalent interactions and their applications such as host-guest complexes, liquid crystals, coordination polymers and nanostructures. The future perspective of cyclophosphazene supramolecular assemblies is also discussed.


Metronidazole versus anaerobes. In vitro data and initial clinical observations.
Metronidazole, a systemic trichomonicide which has been used extensively since 1960, has recently been shown to be active against various anaerobic bacteria in vitro and in experimental infections. In the present study, metronidazole showed significant activity against virtually all of 54 strains of anaerobic and microaerophilic bacteria tested, including Bacteroides fragilis. Since this organism is the anaerobe most commonly isolated from human infections and has demonstrated significant resistance to many antimicrobial agents, metronidazole may prove to be very useful. Our initial clinical evaluation of metronidazole in human anaerobic infections is presented. Because of metronidazole's in vitro activity, its low incidence of toxic reactions, and this initial favorable clinical trial, the drug deserves further evaluation in the management of anaerobic infections.


Plasma metabolomics study reveals the critical metabolic signatures for benzene-induced hematotoxicity.
Metabolomics has been used to explore the molecular mechanism and screen biomarkers. However, the critical metabolic signatures associated with benzene-induced hematotoxicity remain elusive. Here, we performed a plasma metabolomics study in 86 benzene-exposed workers and 76 healthy controls, followed by a validation analysis in mice, to investigate the dynamical change of the metabolic profile. We found that 8 fatty acids were significantly altered in both benzene-exposed worker and benzene-exposed animal models. These metabolites were significantly associated with S-phenylmercapturic acid and WBC, and they mediated the benzene-induced WBC decline. Furthermore, in vivo results confirm that fatty acid levels were dynamically altered, characterized by a decrease at 15 days and then sharp increases at 30 and 45 days. Following these identified fatty acids, the potential metabolic pathways were investigated. Fatty acids, as precursors for fatty acid oxidation, may disturb the balance of fatty acid biosynthesis and degradation. Our results reveal that fatty acid metabolism was strongly reprogrammed after benzene exposure. This abnormal change of fatty acids might be the key metabolic signature associated with benzene-induced hematotoxicity.


A rat model of chronic gastric sensorimotor dysfunction resulting from transient neonatal gastric irritation.
Although several pathophysiologic abnormalities have been noted in functional dyspepsia (FD), their pathogenesis is poorly understood. We hypothesized that chronic gastric hypersensitivity and gastric motor dysfunction seen in FD patients can be modeled in rats by transient gastric irritation during the neonatal period, a time of known neuronal vulnerability to long-term plasticity. Ten-day-old male rats received 0.2 mL 0.1% iodoacetamide (IA) in 2% sucrose daily by oral gavages for 6 days; controls received 2% sucrose. Rats in both groups were then followed to adulthood (8-10 weeks) at which point behavioral, visceromotor, and great splanchnic nerve responses to graded gastric balloon distention (GD; 20-80 mm Hg) and gastric motor function were tested. IA-treated rats exhibited hypersensitivity to GD in a dose-dependent manner, as compared with the control group. The threshold of afferent nerve activation was lower and nerve responses to GD were significantly increased in IA-treated rats. Although IA-treated rats ingested food at a lower rate, gastric emptying was not significantly different between IA and control groups. However, gastric accommodation was significantly reduced in the IA group. No significant gastric pathology was seen in hypersensitive adult rats compared with controls. These studies demonstrate that gastric irritation in the neonatal period can result in chronic gastric hypersensitivity and gastric motor dysfunction in adults even in the absence of significant detectable gastric pathology. Our results offer insight into the pathogenesis of chronic functional dyspepsia and provide a potential model for further study to this important clinical problem.


Active Aging through Volunteerism: A Longitudinal Assessment of Perceived Neighborhood Safety as a Predictor among Older Adults, 2008-2018.
Volunteering can play an important role in active aging. The resource theory of volunteering posits that volunteerism depends on human, social, and cultural capital. Benefits of volunteering have been documented at the micro-, meso-, and macrolevels, positively affecting individual older people as well as their local communities and society at large. Taking a process-oriented theoretical approach, this study focused on the mesolevel factor of the environment with the purpose of determining the relationship between perceived neighborhood safety and volunteerism over the course of a decade and the extent to which this relationship differs by gender and race. Longitudinal data from the Health and Retirement Study in the United States of America between 2008 and 2018 were used (N = 72,319 adults 60 years and older). Generalized estimating equations (GEE) with robust standard errors were employed while controlling for a number of covariates. A third of the sample volunteered in the past year (33%). The probability of volunteering among older adults who rated their perceived neighborhood safety as excellent was greater compared with those who rated their perceived neighborhood safety as fair/poor after controlling for all other model covariates (ME: 0.03, 95% CI: 0.02, 0.05). Among males rating their perceived neighborhood safety as excellent, the probability of volunteering was higher (ME: 0.04, 95% CI: 0.02, 0.07). Among females, the probability of volunteering was higher among those who perceived their neighborhood safety to be excellent (ME: 0.03, 95% CI: 0.01, 0.05) or very good (ME: 0.02, 95% CI: 0.00, 0.04). White respondents who rated their neighborhood safety as excellent (ME: 0.05, 95% CI: 0.03, 0.07) or very good (ME: 0.04, 95% CI: 0.02, 0.06) had a higher probability of volunteerism. Results were not significant among Black respondents and those who described their race as "other." This study's process-oriented theoretical approach indicates that initiatives aimed at improving neighborhood safety and older adults' perceptions of neighborhood safety could increase social capital and lead older adults to engage in more volunteering, providing benefits at micro-, meso-, and macrolevels-to older individuals, their local communities, and society at large.


Derivative matrix isopotential synchronous fluorescence spectroscopy for the direct determination of 1-hydroxypyrene as a urinary biomarker of exposure to polycyclic aromatic hydrocarbons.
Urinary 1-hydroxypyrene is a biomarker in the measurement of human exposure to polycyclic aromatic hydrocarbons. A rapid and simple derivative isopotential synchronous fluorescence method was developed for the direct determination of 1-hydroxypyrene in urine. A length of iso-intensity route was scanned on the three-dimensional fluorescence spectrum of urine and this result was combined with that from derivative technique. Thus the strong background signals of urine were removed and the 1-hydroxypyrene can be determined directly in urine without tedious pre-separation. The derivative isopotential synchronous fluorescence spectrum was directly obtained from a single scan on a spectrofluorometer, which further simplified isopotential synchronous fluorescence technique. The recoveries of 93% to 115% were obtained for 1-hydroxypyrene added to urine.


[Technics for the functional evaluation of the thoracic cage].
A study of lung volumes offers an overall index of thoracic mobility. The techniques of magnetometry and respiratory plethysmography by induction allow studies of thoracic wall movements to be separated into two compartments by measuring thoracic and abdominal movements. These techniques enable a quantitative evaluation of thoraco-abdominal incoordination seen notably in patients with chronic airflow obstruction and in cases of respiratory muscle fatigue. Similar information is obtained by measuring variations in inspiratory pleural and abdominal pressure, using oesophageal and gastric balloons. The maximal force of respiratory muscles is an important index of the functional reserve at a patient's disposal and may be assessed by measuring maximal inspiratory and expiratory pressures at the mouth against an occlusion. Diaphragmatic force is assessed by the maximal trans-diaphragmatic pressure. Respiratory muscle fatigue appears when their contraction is sustained above a certain threshold of tension and duration. This phenomenon may be detected by a diminution of maximal pressures. For example, the fatigue of inspiratory muscles is accompanied by a fall of maximal inspiratory and trans-diaphragmatic pressures. The fatigue process can also be detected early by changes in the pattern of the diaphragmatic electromyogram. The principles and limitations of different techniques of assessment of respiratory muscle fatigue are analysed. The use of one or several of these techniques accompanied by an awareness of the clinical signs of respiratory muscle fatigue ought to enable an early detection of this condition.


Atrial natriuretic peptide elevation in congestive heart failure in the human.
A sensitive radioimmunoassay for atrial natriuretic peptide was used to examine the relation between circulating atrial natriuretic peptide and cardiac filling pressure in normal human subjects, in patients with cardiovascular disease and normal cardiac filling pressure, and in patients with cardiovascular disease and elevated cardiac filling pressure with and without congestive heart failure. The present studies establish a normal range for atrial natriuretic peptide in normal human subjects. These studies also establish that elevated cardiac filling pressure is associated with increased circulating concentrations of atrial natriuretic peptide and that congestive heart failure is not characterized by a deficiency in atrial natriuretic peptide, but with its elevation.


Analysis of piroxicam in pharmaceutical formulation and human urine by dispersive liquid-liquid microextraction combined with spectrophotometry.
Piroxicam, is non-steroidal anti-inflammatory and analgesic agent, which is widely used in the treatment of patients with rheumatologic disorders. A new analytical approach based on the dispersive liquid-liquid microextraction (DLLME) has been developed for the extraction and determination of PX in pharmaceutical preparation and human urine. From the PX standard solution or solutions prepared from real samples, aliquot volumes were pipetted into centrifuge tubes and mixed with acetate buffer at pH 3.0 and NaCl solution. The contents were subjected to the DLLME, so 700 µL of methanol containing 70 µL of chloroform was injected rapidly into a sample solution. A cloudy solution was rapidly produced and the PX extracted into dispersed fine droplets. The mixture was centrifuged, thus these fine droplets of chloroform were settled. The supernatant aqueous phase was readily decanted, then the remained organic phase was diluted with ethanol and the absorbance measured at 355 ± 3 nm against a reagent blank. The main factors affecting the extraction efficiency such as pH, extraction and disperser solvent types and etc. were studied and optimized systematically. Under optimized conditions, the calibration graphs were linear over the range of 0.2 to 4.8 µg/mL. The limit of detection and relative standard deviation were found to be 0.058 µg/mL and 2.83%, respectively. Relative recoveries in the spiked samples ranged from 97 to 110%. Using the developed method PX can be analyzed in pharmaceutical formulation and human urine sample in a simpler, cheaper and more rapid manner.


A flowchart to analyze protease activity in plant mitochondria.
Proteases are one of the most abundant classes of enzymes and are involved in a plethora of biological processes in many cellular compartments, including the mitochondria. To understand the role of proteases is essential to determine their substrate repertoire, preferably in an in vivo setting. In this chapter we describe general guidelines to analyze protease activity using several strategies, from in-gel analysis to mass spectrometry mapping of the cleavage site(s) and fluorogenic probes that can easily be used in vivo. To exemplify this flowchart, we used the recently characterized organellar oligopeptidase of Arabidopsis (Arabidopsis thaliana), an enzyme that takes part in degradation of short peptides within mitochondria and chloroplasts.


Biological responses to environmental heterogeneity under future ocean conditions.
Organisms are projected to face unprecedented rates of change in future ocean conditions due to anthropogenic climate-change. At present, marine life encounters a wide range of environmental heterogeneity from natural fluctuations to mean climate change. Manipulation studies suggest that biota from more variable marine environments have more phenotypic plasticity to tolerate environmental heterogeneity. Here, we consider current strategies employed by a range of representative organisms across various habitats - from short-lived phytoplankton to long-lived corals - in response to environmental heterogeneity. We then discuss how, if and when organismal responses (acclimate/migrate/adapt) may be altered by shifts in the magnitude of the mean climate-change signal relative to that for natural fluctuations projected for coming decades. The findings from both novel climate-change modelling simulations and prior biological manipulation studies, in which natural fluctuations are superimposed on those of mean change, provide valuable insights into organismal responses to environmental heterogeneity. Manipulations reveal that different experimental outcomes are evident between climate-change treatments which include natural fluctuations vs. those which do not. Modelling simulations project that the magnitude of climate variability, along with mean climate change, will increase in coming decades, and hence environmental heterogeneity will increase, illustrating the need for more realistic biological manipulation experiments that include natural fluctuations. However, simulations also strongly suggest that the timescales over which the mean climate-change signature will become dominant, relative to natural fluctuations, will vary for individual properties, being most rapid for CO2 (~10 years from present day) to 4 decades for nutrients. We conclude that the strategies used by biota to respond to shifts in environmental heterogeneity may be complex, as they will have to physiologically straddle wide-ranging timescales in the alteration of ocean conditions, including the need to adapt to rapidly rising CO2 and also acclimate to environmental heterogeneity in more slowly changing properties such as warming.


The rachitic tooth: The use of radiographs as a screening technique.
This study investigates morphological changes in pulp chambers of living and archaeological individuals with past vitamin D deficiency. Living individuals (n=29), four with detailed medical and dental records and three groups of archaeological individuals (n=25) were radiographed; selected individuals were further evaluated histologically for the presence of incremental interglobular dentin (IIGD), indicative of deficiency (28 living; 17 archaeological). Measurements of pulp horns/chambers from radiographs were conducted to quantify morphological observations. One group had clear skeletal evidence of rickets from St. Matthew, Quebec (n=1) and St. Jacques, France (n=4); a second group had slight skeletal indicators from Bastion des Ursulines, Quebec (n=6); and a third group lacked both skeletal and radiological evidence of deficiency from St. Antoine (n=6) and Pointe-aux-Trembles (n=4). Results showed archaeological individuals with clear and slight skeletal evidence of past deficiency displayed constricted or chair shaped pulp horns. Living individuals with deficiency exhibited similar pulp chamber morphology. Radiographic pulp horn/chamber measurements corroborated morphological findings and significant differences were found in pulp horn/chamber measurements between those with and without deficiency. Results suggest that radiograph assessment of teeth can be used as a screening technique to elucidate patterns of deficiency and select individuals for microCT or histological assessment.


[Role of heat-shock proteins of Hsp70 family in changes of narcotic activity of hyperbaric nitrogen during increasing hypoxic stimulus].
The spontaneous motor activity and pose reflexes of male adult rats (Wistar) were observed in the course of high pressure nitrogen compression up to 4,1 MPa. The experiments were carried out under normoxic and hypoxic conditions. Stabile rat motor cortex oxygen tension was recording during the nitrogen compression up to 7,1 MPa under normoxic condition. Sensitivity to nitrogen high pressure to be on the increase under hypoxic conditions. In its turn, resistibility to nitrogen high pressure to be on the decrease under hypoxic conditions (oxygen partial pressure from 0,012 to 0,004 MPa). Quantity of high dencity heat shock proteins (Hsp70) rats motor cortex neurons was 3,44 times higher after course of high pressure nitrogen compression up to 4,1 MPa. For hypoxic exposure (6% O2) the difference was less pronounced - 2,2 times. Data about rat motor cortex neurons Hsp70 concentration under high nitrogen pressure and low oxygen pressure may turn to be a clear base for explanation hypoxic influence on processes of nitrogen narcosis.


Exercise Mode Specificity for Preserving Spine and Hip Bone Mineral Density in Prostate Cancer Patients.
Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with an array of adverse effects, including reduced bone mineral density (BMD) predisposing patients to increased fracture risk. Our purpose was to examine the effects of targeted exercise modes on BMD in men with PCa undergoing ADT. Between 2009 and 2012, 154 PCa patients 43-90 yr old on ADT were randomized to exercise targeting the musculoskeletal system (impact loading + resistance training [ImpRes], n = 57) supervised for 12 months, cardiovascular and muscular systems (aerobic + resistance training, n = 50) supervised for 6 months followed by a 6-month home-based program, or delayed aerobic exercise (DelAer, n = 47) received exercise information for 6 months followed by 6 months of supervised aerobic exercise (stationary cycling). End points were lumbar spine, hip and whole-body BMD measured by dual-energy x-ray absorptiometry with secondary end points of lean and fat mass, appendicular skeletal muscle mass, and neuromuscular strength. ANOVA was used to compare the exercise groups with DelAer at 6 and 12 months. There was a between-group difference in BMD for ImpRes and DelAer at the spine (6 months, P = 0.039; 12 months, P = 0.035) and femoral neck (6 months, P = 0.050), with decline attenuated in ImpRes (~-1.0% vs ~-2.0%). Compared with DelAer, ImpRes increased appendicular skeletal muscle at 6 months (0.3 kg, P = 0.045) and improved muscle strength at 6 and 12 months (P ≤ 0.012) by 9%-34%. A limitation was inclusion of well-functioning patients. Combined impact loading and resistance exercise attenuates bone loss at the spine and enhances overall musculoskeletal function in PCa patients undergoing ADT.


Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration.
To evaluate the functional effect of short-term supplementation of saffron, a spice containing the antioxidant carotenoids crocin and crocetin, in early age-related macular degeneration (AMD). Twenty-five patients with AMD were randomly assigned to oral saffron 20 mg/d or placebo supplementation over a 3-month period and then reverted to placebo or saffron for a further 3 months. Focal electroretinograms (fERGs) and clinical findings were recorded at baseline and after 3 months of saffron or placebo supplementation. fERGs were recorded in response to a sinusoidally modulated (41 Hz), uniform field presented to the macular region (18°) at different modulations between 16.5% and 93.5%. Main outcome measures were fERG amplitude (in microvolts), phase (in degrees), and modulation thresholds. After saffron, patients' fERGs were increased in amplitude, compared with either baseline or values found after placebo supplementation (mean change after saffron, 0.25 log μV; mean change after placebo, -0.003 log μV; P < 0.01). fERG thresholds were decreased after saffron supplementation but not placebo, compared with baseline (mean change after saffron, -0.26 log units; mean change after placebo, 0.0003 log units). The results indicate that short-term saffron supplementation improves retinal flicker sensitivity in early AMD. Although the results must be further replicated and the clinical significance is yet to be evaluated, they provide important clues that nutritional carotenoids may affect AMD in novel and unexpected ways, possibly beyond their antioxidant properties. (ClinicalTrials.gov number, NCT00951288.).


Barriers to CT Dose Optimization: The Challenge of Organizational Change.
The use of diagnostic imaging with computed tomography (CT) has risen significantly, increasing cumulative life-time exposure to ionizing radiation for patients and raising concerns about increased cancer risk. Lowering the doses would reduce concerns about associated cancer risks. To determine organizational leaders' perceptions of barriers to optimizing radiation dose in CT. An observational study using semistructured interviews conducted with 26 organizational leaders from 19 health care systems in the United States, Europe, and Japan. Interviews focused on approaches the organizations used to optimize radiation dose and barriers encountered. Data were analyzed using a directed content analysis approach. Analysis identified six primary barriers to dose optimization: (1) resistance to change, (2) limited time and resources, (3) complex organizational structure, (4) lack of leadership support, (5) variations in CT equipment, and (6) variability in CT protocols. Barriers to optimizing CT dose across diverse health care organizations were described by organizational leaders tasked with implementing and improving CT imaging. They identified six consistent themes that reflected barriers to optimizing radiation dose at the organizational level. These barriers impeded efforts by health care organizations to optimize radiation doses to patients from CT imaging. Identifying barriers early in any improvement process is an important first step in making meaningful and sustained change.


Disruption of oligosaccharide processing in murine tumor cells inhibits their susceptibility to lysis by activated mouse macrophages.
The components of tumor cell surfaces that participate in the recognition and lysis of these cells by activated macrophages have not been identified. One plausible hypothesis is that these components are specific carbohydrate structures. As an initial test of this hypothesis, I have made use of the oligosaccharide processing inhibitors 1-deoxynojirimycin (dNM) and 1-deoxymannojirimycin (dMM). dNM is an inhibitor of the glucosidases involved in the initial steps of oligosaccharide processing. dMM inhibits mannosidase I. P815 cells incubated in the presence of 1-2 mM dNM for 24 hr synthesized mature glycoproteins that contained glucosylated high-mannose asparagine-linked oligosaccharides instead of complex forms. The glucosylated oligosaccharides were present in trypsin digests of the cell surface. The dNM treatment resulted in a diminution in the amount of surface galactose residues as evidenced by neuraminidase/galactose oxidase/NaB3H4 labeling of surface glycopeptides. It did not, however, inhibit protein synthesis or alter the surface polypeptide profile of the tumor cells. P815 and R1- cells incubated in the presence of 1-3 mM dNM for 24 hr were considerably less sensitive to lysis by interferon-gamma-activated macrophages than were cells incubated in control medium. At a dNM concentration of 3 mM, a 71% inhibition of P815 cell lysis was observed. Similarly, P815 and R1- cells incubated in the presence of 2 mM dMM were also less sensitive to macrophage-mediated lysis than were control cells. The inhibitors did not affect cell viability, growth, or gross morphology. These observations suggest that complex asparagine-linked oligosaccharides on tumor cell surfaces may participate in recognition and lysis by activated macrophages.


Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis.
Defective apoptosis renders immortalized epithelial cells highly tumorigenic, but how this is impacted by other common tumor mutations is not known. In apoptosis-defective cells, inhibition of autophagy by AKT activation or by allelic disruption of beclin1 confers sensitivity to metabolic stress by inhibiting an autophagy-dependent survival pathway. While autophagy acts to buffer metabolic stress, the combined impairment of apoptosis and autophagy promotes necrotic cell death in vitro and in vivo. Thus, inhibiting autophagy under conditions of nutrient limitation can restore cell death to apoptosis-refractory tumors, but this necrosis is associated with inflammation and accelerated tumor growth. Thus, autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing death by necrosis.


Developing promiscuous glycosidases for glycoside synthesis: residues W433 and E432 in Sulfolobus solfataricus beta-glycosidase are important glucoside- and galactoside-specificity determinants.
Two residues that have been implicated in determining the substrate specificity of the thermophilic beta-glycosidase from the archaeon Sulfolobus solfataricus (SsbetaG), a member of the glycosyl hydrolase family 1, have been mutated by site-directed mutagenesis so as to create more versatile catalysts for carbohydrate chemistry. The wild-type and mutated sequences were expressed in E. coli with a His(7)-tag to allow one-step chromatographic purification. The E432C and W433C mutations removed key interactions with the OH-4 and OH-3 of the sugar substrates, thus reducing the discrimination of glucose, galactose and fucose with respect to other glycosides. This resulted in two glycosidases with greatly broadened substrate specificities. Observed changes include a 24-fold increase in Man:Gal activity and an 18-fold increase in GalA:Gal activity. This promiscuous substrate tolerance was further illustrated by the parallel synthesis of a beta-glycoside library of glucose, galactose, xylose and mannose in one pot at 50 degrees C, in organic solvent. The synthetic potential of the catalysts was further evaluated through alkyl glycoside transglycosylation yields, including the first examples of synthesis of beta-mannosides and beta-xylosides with SsbetaG.


Fusarium Solani Infection Following Burn Injury: A Case Report.
Fungal infections are becoming increasingly recognized among burn patients. Infection with Fusarium, a filamentous mold, is rarely encountered and mainly seen in immunocompromised patients. High mortality and morbidity were reported with these virulent infections. We present a rare case of refractory septic shock from upper extremity fungal infection with Fusarium solani in a burn patient. Multiple operative debridements and below elbow amputation caused resolution of septic shock. Closure was achieved with a split thickness skin graft. Aggressive approach should be adopted in managing burn patients with Fusarium infection. Serial debridements and extremity amputation should be considered in attempts to improve survival.


[Ultrastructure of cells of the lateral field of the hypothalamus of the cat after exposure to electromagnetic radiation].
Under the effect of electromagnetic radiation not any specific changes are revealed in the neural system unequivocally characterizing disturbances in its structure as a result of an excess absorption of electromagnetic energy. The ultrastructural changes revealed in the lateral fields of the cat hypothalamus are suitable for a well known scheme demonstrating the course of the pathological process, where three phases are distinguished: reactive, destructive and restorative. The pathological process develops gradually. The reactive changes in neurons and synapses, observed immediately after withdrawal of the electromagnetic action. increase during the following three months and result in coarse destructive disorders and in death of some neurons and synapses. In 6 months certain signs of restoration of the structures are observed. Under the effect of electromagnetic radiation water redistribution between the structures takes place, the sympathetic terminals loosing their fluid. Thus, certain conditions are produced for sticking together the synaptic vesicles. Possibly that deficiency of Ca++ ions contributes to it.


Cross-species behavior analysis with attention-based domain-adversarial deep neural networks.
Since the variables inherent to various diseases cannot be controlled directly in humans, behavioral dysfunctions have been examined in model organisms, leading to better understanding their underlying mechanisms. However, because the spatial and temporal scales of animal locomotion vary widely among species, conventional statistical analyses cannot be used to discover knowledge from the locomotion data. We propose a procedure to automatically discover locomotion features shared among animal species by means of domain-adversarial deep neural networks. Our neural network is equipped with a function which explains the meaning of segments of locomotion where the cross-species features are hidden by incorporating an attention mechanism into the neural network, regarded as a black box. It enables us to formulate a human-interpretable rule about the cross-species locomotion feature and validate it using statistical tests. We demonstrate the versatility of this procedure by identifying locomotion features shared across different species with dopamine deficiency, namely humans, mice, and worms, despite their evolutionary differences.


Surgonomics: the identifier concept. Hospital charges in general surgery and surgical specialties under prospective payment systems.
Surgical care is entering a new payment era for inhospital care using the diagnostic related group (DRG) mechanism for Medicare. A study at The Long Island Jewish-Hillside Medical Center showed that a majority of its surgical DRGs would be unprofitable under the proposed reimbursement scheme. This study was undertaken to develop a method of allowing the hospital to group patients with each DRG that would show a difference in hospital charges and be clinically meaningful to surgeons. The study implementors tested the hypothesis that entities called identifiers, arbitrarily chosen as mode of admission [emergency (+ER vs. nonemergency (-ER)] and presence (+T) or absence (-T) of blood transfusion, would show a difference in charges (mean hospital charge exclusive of physician fees) within a DRG. Nine hundred five patients in nine DRGs encompassing general surgery, thoracic surgery, cardiac surgery, neurosurgery, orthopedics, urology, and head and neck surgery were studied. For ER identifier, eight of nine DRGs were found to be positive (greater than 20% difference in charges between positive and negative identifier); for T identifier, all DRGs (9) were positive. These findings demonstrate that these identifiers may enable teaching institutions to disaggregate each DRG and, in this way, propose more equitable reimbursement rates.


Use of radioreceptor assay and cell superfusion system for in vitro screening of analogs of growth hormone-releasing hormone.
In the search for more active agonists and antagonists of human growth hormone-releasing hormone (hGH-RH), various analogs are being synthesized. In order to follow the binding affinity of these analogs, we have developed a sensitive in vitro radioreceptor assay for GH-RH based on binding of labeled [His1,Nle27]hGH-RH(1-32)NH2 to rat anterior pituitary membrane homogenates by adapting and modifying earlier methods. Scatchard analysis of saturation binding data demonstrated the presence of a single class of specific binding sites for GH-RH in membranes of rat anterior pituitaries with a Bmax of 33.3 +/- 5.2 fmol/mg protein and an apparent Kd of 0.19 +/- 0.02 nM. In displacement analyses, we compared the binding affinity of [His1,Nle27]hGH-RH(1-32)NH2 with its iodinated derivative. No significant differences were detected in IC50 concentrations ranging from 0.97 to 3.4 nM between labeled and nonlabeled hGH-RH analogs. These findings demonstrate the validity of the radioreceptor assay. To evaluate the biological activities of hGH-RH derivatives, we applied a sensitive, dispersed rat pituitary cell superfusion system. This dynamic in vitro system eliminates the drawbacks of the static pituitary cell culture. No differences were observed in biological activities of the iodinated and noniodinated hGH-RH analogs. GH-releasing activity obtained from the superfusion assay correlated well with GH-RH receptor binding affinity for all nonlabeled and labeled hGH-RH analogs examined. These two methods are fast, simple, and relatively inexpensive, and provide quantitative data on receptor affinities, biological activities, and hence structure-affinity and structure-activity relationships. Joint use of these two in vitro systems appears to be suitable for screening newly synthesized GH-RH analogs.


Assessment of the geometric profile of the Amplatzer and Cardioseal septal occluders by three dimensional echocardiography.
To apply three dimensional echocardiography to describe the geometric profile of the Amplatzer and Cardioseal occluders after deployment for closure of atrial septal defect. 20 patients (mean (SD) age, 14 (5) years) were enrolled for transcatheter closure of a secundum atrial septal defect with the Amplatzer occluder (10) or with the Cardioseal occluder (10). The two populations were matched for the stretched diameter of the defect (mean 18 (6) mm). The profile of the two occluders was examined. Transoesophageal echocardiography did not show any residual shunts after Amplatzer occluder deployment, whereas three patients had a small residual leak after Cardioseal deployment. One patient had transient atrioventricular block with the Amplatzer device. The mean surface area of the Amplatzer occluder was 6.9 (2) cm(2), and that of the Cardioseal device 5.4 (3) cm(2) (p = 0.03). The mean volume of the Amplatzer occluder was 9.2 (1) cm(3), while that of the Cardioseal occluder was 3.5 (1) cm(3) (p < 0.0001). From the three dimensional views, the Cardioseal occluder looked like a flat square after deployment whereas the Amplatzer occluder took up a ball shape in the atrial cavity. Three dimensional views by multiplane transoesophageal echocardiography allow a realistic in vivo description of atrial septal occluders. The Amplatzer occluder, with its high geometric profile, allows complete closure of large atrial septal defects but with some risk of mechanical complications. Use of the Cardioseal device, with its small surface coverage and high residual shunt rate, should be limited to transcatheter closure of a patent foramen ovale or small atrial septal defects.


Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer.
Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX-2) plays a critical role in DMBA/TPA-induced skin tumor induction. Although many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell type-specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared with littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2-expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell type-specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biologic responses. Cox-2 gene deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes is a principal driver of skin carcinogenesis; lipidomic analysis identifies likely prostanoid effectors.


A synergistic decline in humoral and cellular immunity of diabetic mice on exposure to polluted air.
It is clinically known that diabetic patients are more prone to infectious diseases, due to low immune status. Since, some of the common air pollutants are reported to suppress immune system, how exposure to artificially polluted air influences the immune responses in experimental diabetic mice was studied. A diabetic state was induced by alloxan and mice were exposed to artificially polluted air for 30 days. During the period of exposure, the humoral (antibody titer) and cellular (foot and swelling) immune responses to antigenic challenges with sheep RBC were investigated. The exposure to polluted air produced a significant decline in the immune responses in non-diabetic mice whereas a synergistic decline was observed in diabetic group. Since, daily oral treatment with vitamin E (150 mg/kg) significantly prevented the pollution induced immunosuppression, the involvement of free radicals is suggested.


Low Body Weight Is Associated With the Incidence of Stroke in Atrial Fibrillation Patients - Insight From the Fushimi AF Registry.
Japanese patients with atrial fibrillation (AF) are generally small and lean, but knowledge of the clinical characteristics of those with low body weight (LBW: ≤50 kg) is limited. The Fushimi AF Registry is a community-based prospective survey of AF patients who visited the participating medical institutions in Fushmi-ku, Japan. The BW and follow-up data were available for 2,945 patients. We compared the background and the incidence of clinical events during a median follow-up of 746 days between a LBW and non-LBW group. Patients in the LBW group accounted for 26.8% (788 patients) of the total. The LBW group was more often female, older, and had higher CHADS2score. The incidence of stroke/systemic embolism (SE) during follow-up was higher in the LBW group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.57-3.04; P<0.01), whereas that of major bleeding was comparable (HR: 1.05, 95% CI: 0.64-1.68; P=0.84). This trend was consistently observed in the subgroups stratified by age, sex, and oral anticoagulant prescription at baseline. Multivariate analysis as well as propensity-score matching analysis further supported the significance of LBW as a risk of stroke/SE. Patients in the LBW group had high risk profiles and showed a higher incidence of stroke/SE, but the incidence of major bleeding was not particularly high.


Immediate Soft-Tissue Reconstruction for Chronic Infected Tibia Nonunions Treated with an Ilizarov Frame.
There are multiple options available for the management of large tibial defects. The Ilizarov frame is one of the most widely used techniques due to the physiological bone growth and the symmetrical distribution of axial forces permitting adequate bone distribution. However, disadvantages still remain including obtaining additional soft-tissue access for defect coverage. We present our experience with soft-tissue reconstruction for chronic infected tibial nonunions using free tissue transfers simultaneously with Ilizarov device placement. A retrospective review was performed from 2014 to 2016 of patients presenting with a chronically infected tibia nonunion and treated by our senior orthopedic and plastic surgeons. Demographic data, comorbidities, intraoperative details and postoperative outcomes were collected. A total of 6 patients were identified with a mean age of 46.2 ± 11.6 years. Complete flap survival and resolved active infection were achieved in 5 of our patients, 4 demonstrated body union on imaging, and all of them reached complete ambulance. Flap revisions with allografting for partial flap loss were performed in 1 patient. Preoperative planning is critical for immediate lower extremity reconstruction in the setting of an Ilizarov frame. From our institutional experience, free tissue transfer can safely be placed after frame placement.


The Effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-Analysis.
The effects of ketoanalogues (KA) on chronic kidney disease (CKD) deterioration have not yet been fully confirmed. To strengthen the evidence of the role of KA in CKD, PubMed and Embase were searched for studies published through February 2019. Effect sizes from ten randomized control trials (RCTs) and two non-RCTs comprising a total of 951 patients were pooled and analyzed. A restricted protein diet supplemented with ketoanalogues (RPKA) was found to significantly delay the progression of CKD (p = 0.008), particularly in patients with an estimated glomerular filtration rate (eGFR) > 18 mL/min/1.73 m2 (p < 0.0001). No significant change in eGFR was found when comparing a very-low-protein diet and a low-protein diet (p = 0.10). In addition, compared with the placebo, RPKA did not cause malnutrition (albumin: p = 0.56; cholesterol: p = 0.50). Moreover, RPKA significantly decreased phosphorous levels (p = 0.001), increased calcium levels (p = 0.04), and decreased parathyroid hormone (PTH) levels (p = 0.05) in patients with eGFR < 18 mL/min/1.73 m2. In conclusion, RPKA could slow down the progression of CKD in patients with eGFR > 18 mL/min/1.73 m2 without causing malnutrition and reverse CKD-MBD in patients with eGFR < 18 mL/min/1.73 m2.


Patient satisfaction: examine your practice through their eyes.
In an environment of constant change, effective management decisions are harder to make. Physicians and clinic managers often miss valuable information from one key group--the patients. Their input builds a framework for sound solutions. The most efficient, unbiased collection method is a patient satisfaction study. With guidance from some one who is experienced in survey design and handling, physicians and managers will find these studies are easy to administer, are tools for learning and help build patient loyalty. Effectively designed studies give proportion to issues raised by patients. This information helps physicians and managers make good decisions on practice style, operations and service delivery. In the two case studies of primary care practices included in this article, the physician partners had very different issues of concern than the patients did. Without the studies, the physicians might have made poor decisions on the future of their clinics. Insurance providers recommend regular satisfaction studies to measure quality improvements, a clinic's strengths and weaknesses, and the patients' expectations. Patients are your lifetime partners and have valuable information for the survival of a practice. They help define where a practice is and where it should be.


Molecular diagnosis of known recessive ataxias by homozygosity mapping with SNP arrays.
The diagnosis of rare inherited diseases is becoming more and more complex as an increasing number of clinical conditions appear to be genetically heterogeneous. Multigenic inheritance also applies to the autosomal recessive progressive cerebellar ataxias (ARCAs), for which 14 genes have been identified and more are expected to be discovered. We used homozygosity mapping as a guide for identification of the defective locus in patients with ARCA born from consanguineous parents. Patients from 97 families were analyzed with GeneChip Mapping 10K or 50K SNP Affymetrix microarrays. We identified six families homozygous for regions containing the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) gene, two families homozygous for the ataxia-telangiectasia gene (ATM), two families homozygous for the ataxia with oculomotor apraxia type 1 (AOA1) gene, and one family homozygous for the AOA type 2 (AOA2) gene. Upon direct gene testing, we were able to identify a disease-related mutation in all families but one of the two kindred homozygous at the ATM locus. Although linkage analyses pointed to a single locus on chromosome 11q22.1-q23.1 for this family, clinical features, normal levels of serum alpha-foetoprotein as well as absence of mutations in the ATM gene rather suggest the existence of an additional ARCA-related gene in that interval. While the use of homozygosity mapping was very effective at pointing to the correct gene, it also suggests that the majority of patients harbor mutations either in the genes of the rare forms of ARCA or in genes yet to be identified.


New fundamental and applied mechanisms in exercise hemorheology.
The present article summarizes recent data presented at the Exercise and Hemorheology symposium during the 15th Conference of the European Society for Clinical Hemorheology and Microcirculation (June 28-July 1, Pontresina, Switzerland, 2009). The review starts with several unresolved paradoxes in exercise hemorheology. Then, we focus on the potential hemorheological and immunological mechanisms involved in the adverse events sometimes reported in exercising sickle cell trait carriers, and the role of habitual physical activity. In a fourth part, new results on the effects of acute hypoxia on blood rheology are presented. Finally, we will discuss recent experimental evidences on the role of exercise on the regulation of nitric oxide synthesizing mechanisms in red blood cell.


Differences in knee joint stabilization between children and adults and between the sexes.
Differences in knee joint stabilization between children and adults and between the sexes are not fully understood. To compare the knee laxity and the dynamic tibial translation between (1) children and adults, (2) girls and boys, and (3) women and men. Controlled laboratory study. Sixty-seven children (aged 8-13 years) and 63 adults (aged 18-30 years) without previous knee injuries participated. Sagittal tibial translation was measured during the instrumented Lachman test at 90 N and 134 N (knee laxity) and during gait (dynamic translation). Tibial translation was recorded with an electrogoniometer. Knee laxity was greater in children than in adults (Lachman test at 90 N: 9.1 ± 2.9 vs 7.3 ± 2.7, respectively; P < .001). In contrast, dynamic tibial translation during gait did not differ between children and adults. Girls and boys did not differ in knee laxity or maximum anterior tibial translation during gait, and men and women did not differ in knee laxity. Women had greater dynamic tibial translation during gait than men (7.8 ± 2.7 vs 5.7 ± 3.0, respectively; P = .004). Children had greater knee laxity than adults, whereas the dynamic tibial translation did not differ. In adults, knee laxity did not differ between the sexes, but dynamic tibial translation was greater in women. Children and men had less dynamic tibial translation during gait in proportion to their maximum knee laxity. The observed less dynamic tibial translation in children and adult men might be related to their reduced risk of sustaining an anterior cruciate ligament injury.


Endosomal vacuoles of the prepupal salivary glands of Drosophila play an essential role in the metabolic reallocation of iron.
In the recent past, we demonstrated that a great deal is going on in the salivary glands of Drosophila in the interval after they release their glycoprotein-rich secretory glue during pupariation. The early-to-mid prepupal salivary glands undergo extensive endocytosis with widespread vacuolation of the cytoplasm followed by massive apocrine secretion. Here, we describe additional novel properties of these endosomes. The use of vital pH-sensitive probes provided confirmatory evidence that these endosomes have acidic contents and that there are two types of endocytosis seen in the prepupal glands. The salivary glands simultaneously generate mildly acidic, small, basally-derived endosomes and strongly acidic, large and apical endosomes. Staining of the large vacuoles with vital acidic probes is possible only after there is ambipolar fusion of both basal and apical endosomes, since only basally-derived endosomes can bring fluorescent probes into the vesicular system. We obtained multiple lines of evidence that the small basally-derived endosomes are chiefly involved in the uptake of dietary Fe3+ iron. The fusion of basal endosomes with the larger and strongly acidic apical endosomes appears to facilitate optimal conditions for ferrireductase activity inside the vacuoles to release metabolic Fe2+ iron. While iron was not detectable directly due to limited staining sensitivity, we found increasing fluorescence of the glutathione-sensitive probe CellTracker Blue CMAC in large vacuoles, which appeared to depend on the amount of iron released by ferrireductase. Moreover, heterologous fluorescently-labeled mammalian iron-bound transferrin is actively taken up, providing direct evidence for active iron uptake by basal endocytosis. In addition, we serendipitously found that small (basal) endosomes were uniquely recognized by PNA lectin, whereas large (apical) vacuoles bound DBA lectin.


Characterization of Chlorhexidine-Loaded Calcium-Hydroxide Microparticles as a Potential Dental Pulp-Capping Material.
This study explores the delivery of novel calcium hydroxide [Ca(OH)₂] microparticles loaded with chlorhexidine (CHX) for potential dental therapeutic and preventive applications. Herein, we introduce a new approach for drug-delivery to deep dentin-surfaces in the form of drug-loaded microparticles. Unloaded Ca(OH)₂ [Ca(OH)₂/Blank] and CHX-loaded/Ca(OH)₂ microparticles were fabricated by aqueous chemical-precipitation technique. The synthesized-microparticles were characterized in vitro for determination of surface-morphology, crystalline-features and thermal-properties examined by energy-dispersive X-ray scanning and transmission electron-microscopy (EDX-SEM/TEM), Fourier-transform infrared-spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and differential scanning-calorimetry (DSC). Time-related pH changes, initial antibacterial/biofilm-abilities and cytotoxicity of CHX-loaded/Ca(OH)₂ microparticles were evaluated. Microparticles were delivered to dentin-surfaces with subsequent SEM examination of treated dentin-substrates. The in vitro and ex vivo CHX-release profiles were characterized. Ca(OH)₂/Blank were hexagonal-shaped with highest z-average diameter whereas CHX-inclusion evidenced micro-metric spheres with distinguishable surface "rounded deposits" and a negative-shift in diameter. CHX:Ca(OH)₂/50 mg exhibited maximum encapsulation-efficiency with good antibacterial and cytocompatible properties. SEM examination revealed an intact layer of microparticles on exposed dentin-surfaces with retention of spherical shape and smooth texture. Microparticles loaded on dentin-surfaces showed prolonged release of CHX indicating substantial retention on dentin-substrates. This study validated the inherent-applicability of this novel drug-delivery approach to dentin-surfaces using micro-metric CHX-loaded/Ca(OH)₂ microparticles.


Mapping the literature of health education.
Health education is a relatively new multidisciplinary field concerned with educational programs that empower individuals and communities to play active roles in achieving, protecting, and sustaining their health. Its practitioners have bachelor's, master's, or doctoral degrees and work in educational, worksite, health facility, or agency settings. This bibliometric study was part of the Medical Library Association (MLA) Nursing and Allied Health Resources Section's Project for Mapping the Literature of Allied Health. It sought to identify the core journals in health education and to determine the extent to which these titles are covered by the standard indexing sources. Cited references appearing from 1991 through 1993 in articles of four journals published by the major professional associations in the field were analyzed. It was found that only thirteen journals supply one-third of all references in the study. Another eighty journals provide the second third. MEDLINE gives the best indexing coverage with nearly 69% of the journals receiving indexing for at least half of their articles, followed by EMBASE (52%) and PsycINFO (43%). Limited coverage is given by the Cumulative Index to Nursing and Allied Health Literature (16%) and ERIC (14%). The findings name titles that should be added by indexing services and those that should have more complete coverage.


Supersymmetry-inspired non-Hermitian optical couplers.
Supersymmetry has been shown to provide a systematic and effective framework for generating classes of isospectral optical structures featuring perfectly-phase-matched modes, with the exception of one (fundamental) mode which can be removed. More recently, this approach has been extended to non-Hermitian scenarios characterized by spatially-modulated distributions of optical loss and gain, in order to allow the removal of higher-order modes as well. In this paper, we apply this approach to the design of non-Hermitian optical couplers with higher-order mode-selection functionalities, with potential applications to mode-division multiplexing in optical links. In particular, we highlight the critical role of the coupling between non-Hermitian optical waveguides, which generally induces a phase transition to a complex eigenspectrum, thereby hindering the targeted mode-selection functionality. With the specific example of an optical coupler that selects the second-order mode of a given waveguide, we illustrate the aforementioned limitations and propose possible strategies to overcome them, bearing in mind the practical feasibility of the gain levels required.


The use of the eating disorder examination with children: a pilot study.
This article describes the use of a slightly modified version of the Eating Disorders Examination (EDE) in children. Sixteen children aged between 7 and 14 years attending an eating disorders clinic over a 5-month period were recruited to the study. The two main modifications to the EDE were (A) the inclusion of a sort task to assess overvalued ideas about weight and shape and (B) the reformulation of certain items to assess intent rather than actual behavior. The existing EDE scoring system was used, resulting in item, subscale, and global scores. Of the 16 children (10 F 6 M), 11 had a diagnosis of anorexia nervosa, and 5 of eating disorder not otherwise specified (EDNOS). There were interesting differences in responses on items assessing core overvalued ideas, with weight and/or shape concerns emerging as of great importance in terms of self-evaluation in the majority of children with anorexia nervosa. Results suggest that this may be a useful assessment tool in children, with some children obtaining global and subscale scores consistent with adult norms for females with eating disorders. Problems of the administration of the EDE to this patient group are discussed and details of the modifications used are outlined.


Genetic diseases of renal phosphate handling.
Renal control of systemic phosphate homeostasis is critical as evident from inborn and acquired diseases causing renal phosphate wasting. At least three transport proteins are responsible for renal phosphate reabsorption: NAPI-IIa (SLC34A1), NAPI-IIc (SLC34A3) and PIT-2 (SLC20A2). These transporters are highly regulated by various cellular mechanisms and factors including acid-base status, electrolyte balance and hormones such as dopamine, glucocorticoids, growth factors, vitamin D3, parathyroid hormone and fibroblast growth factor 23 (FGF23). Whether renal phosphate wasting is caused by inactivating mutations in the NAPI-IIa transporter is controversial. Mutations in the NAPI-IIc transporter cause hereditary hypophosphatemic rickets with hypercalciuria. Besides the primary inherited defects, there are also inherited defects in major regulators of phosphate homeostasis that lead to alterations in phosphate handling. Autosomal dominant hypophosphatemic rickets is due to FGF23 mutations leading to resistance against its own degradation. Similarly, inactivating mutations in the PHEX gene, which causes FGF23 inactivation, cause X-linked hypophosphatemia due to renal phosphate losses. In contrast, mutations in galactosamine:polypeptide N-acetyl-galactosaminyltransferase, responsible for O-glycosylation of FGF23, or in klotho, a cofactor for FGF23 signalling result in hyperphosphatemia. Acquired syndromes of renal phosphate wasting, hypophosphatemia and osteomalacia (tumour-associated osteomalacia) can be due to the excessive synthesis or release of phosphaturic factors (FGF23, FGF-7, MEPE and sFRP4) from mesenchymal tumours. bone, FGF23, kidney, phosphate, PTH.


Alternatives to the isomerase-dependent pathway for the beta-oxidation of oleic acid are dispensable in Saccharomyces cerevisiae. Identification of YOR180c/DCI1 encoding peroxisomal delta(3,5)-delta(2,4)-dienoyl-CoA isomerase.
Fatty acids with double bonds at odd-numbered positions such as oleic acid can enter beta-oxidation via a pathway relying solely on the auxiliary enzyme Delta(3)-Delta(2)-enoyl-CoA isomerase, termed the isomerase-dependent pathway. Two novel alternative pathways have recently been postulated to exist in mammals, and these additionally depend on Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase (di-isomerase-dependent) or on Delta(3,5)-Delta(2,4)-dienoyl-CoA isomerase and 2,4-dienoyl-CoA reductase (reductase-dependent). We report the identification of the Saccharomyces cerevisiae oleic acid-inducible DCI1 (YOR180c) gene encoding peroxisomal di-isomerase. Enzyme assays conducted on soluble extracts derived from yeast cells overproducing Dci1p using 3,5,8,11,14-eicosapentenoyl-CoA as substrate demonstrated a specific di-isomerase activity of 6 nmol x min(-1) per mg of protein. Similarly enriched extracts from eci1Delta cells lacking peroxisomal 3,2-isomerase additionally contained an intrinsic 3,2-isomerase activity that could generate 3, 5,8,11,14-eicosapentenoyl-CoA from 2,5,8,11,14-eicosapentenoyl-CoA but not metabolize trans-3-hexenoyl-CoA. Amplification of this intrinsic activity replaced Eci1p since it restored growth of the eci1Delta strain on petroselinic acid for which di-isomerase is not required whereas Eci1p is. Heterologous expression in yeast of rat di-isomerase resulted in a peroxisomal protein that was enzymatically active but did not re-establish growth of the eci1Delta mutant on oleic acid. A strain devoid of Dci1p grew on oleic acid to wild-type levels, whereas one lacking both Eci1p and Dci1p grew as poorly as the eci1Delta mutant. Hence, we reasoned that yeast di-isomerase does not additionally represent a physiological 3,2-isomerase and that Dci1p and the postulated alternative pathways in which it is entrained are dispensable for degrading oleic acid.


Virulent bacteriophage of Edwardsiella ictaluri isolated from kidney and liver of striped catfish Pangasianodon hypophthalmus in Vietnam.
Striped catfish Pangasianodon hypophthalmus farmed in the Mekong Delta, Vietnam, represents an important contribution to Vietnamese aquaculture exports. However, these fish are affected by frequent disease outbreaks across the entire region. One of the most common infections involves white spots in the internal organs, caused by the bacterium Edwardsiella ictaluri. In this study, a virulent phage specific to E. ictaluri, designated MK7, was isolated from striped catfish kidney and liver samples and characterized. Morphological analysis indicates probable placement in the family Myoviridae with a 65 nm icosahedral head and a 147 %%CONV_ERR%% 19 nm tail. A double-stranded DNA genome of approximately 34 kb was predicted by restriction fragment analysis following digestion with SmaI. The adsorption affinity (ka) of the MK7 phage was estimated as 1.6 %%CONV_ERR%% 10-8 ml CFU-1 min-1, and according to a 1-step growth curve, its latent period and burst size were ~45 min and ~55 phage particles per infected host cell, respectively. Of the 17 bacterial strains tested, MK7 only infected E. ictaluri, although other species of Edwardsiella were not tested. E. ictaluri was also challenged in vitro, in both broth and water from a striped catfish pond and was inactivated by MK7 for 15 h in broth and 51 h in pond water. Thus, initial characterization of phage MK7 indicates its potential utility as a biotherapeutic agent against E. ictaluri infection in striped catfish. This is the first report of a lytic phage specific to an important striped catfish pathogen.


[Comparative evaluation of the effectiveness of vaccination of newborn infants with BCG and BCG-M vaccines].
A comparative effectiveness of the newborn BCG- and BCG-M vaccination was analysed as to the indices of primary infection, morbidity and its structure. The rate of postvaccination complications in 1,645,360 children, aged under 3 years, and living in the areas with different epidemiological situations for tuberculosis was studied too. 2,142,292 and 799486 healthy newborns were BCG- and BCG-M-vaccinated, respectively. The studies were carried out in Moscow, Kiev, Vilnius++ and Tashkent. The obtained results indicate that the number of complications in the form of regional lymphadenitis induced by BCG-M vaccine is 5 times less frequent than those caused by BCG. Under favourable epidemiological conditions, the primary infection and morbidity are alike, while under unfavourable ones the former is higher, particularly in infants in their first year as compared to the BCG-vaccinated. On the basis of the available data BCG-M can be recommended for the vaccination of all the newborns living in the areas with a favourable epidemiological situation for tuberculosis, thus increasing the newborn vaccination coverage and bringing the morbidity down.


Clinical curative effect of acupuncture therapy on xerophthalmia.
This study observes changes in symptoms of xerophthalmia pre- and post-acupuncture therapy and compares the results of the acupuncture therapy (AT) group and the artificial tear control (ATC) group. Parallel comparative studies were carried out on 44 patients with xerophthalmia, who were divided into the AT group (n = 20) and the ATC group (n = 24). A 10-session acupuncture therapy program was performed for the AT group while Dextran 70 was used for the ATC group with each course of treatment lasting 21 day. Examinations were made on the day when a patient was chosen to join the study, 1 hour after completion of treatment, and 3 weeks after stopping treatment. There was no statistically significant difference in terms of the reduction of the symptoms and sign score (SSS) 1 hour after completion of treatment between the AT group and the ATC group. Three weeks after completion of treatment, the reduction of SSS for the AT group was larger than that of the ATC group, with the difference achieving statistical significance. Both acupuncture therapy and artificial tear therapy have an immediate positive effect on the symptoms of xerophthalmia, but acupuncture therapy has a longer continuous effect than that of artificial tears.


LOMA: a fast method to generate efficient tagged-random primers despite amplification bias of random PCR on pathogens.
Pathogen detection using DNA microarrays has the potential to become a fast and comprehensive diagnostics tool. However, since pathogen detection chips currently utilize random primers rather than specific primers for the RT-PCR step, bias inherent in random PCR amplification becomes a serious problem that causes large inaccuracies in hybridization signals. In this paper, we study how the efficiency of random PCR amplification affects hybridization signals. We describe a model that predicts the amplification efficiency of a given random primer on a target viral genome. The prediction allows us to filter false-negative probes of the genome that lie in regions of poor random PCR amplification and improves the accuracy of pathogen detection. Subsequently, we propose LOMA, an algorithm to generate random primers that have good amplification efficiency. Wet-lab validation showed that the generated random primers improve the amplification efficiency significantly. The blind use of a random primer with attached universal tag (random-tagged primer) in a PCR reaction on a pathogen sample may not lead to a successful amplification. Thus, the design of random-tagged primers is an important consideration when performing PCR.


Characteristics of cerebrospinal fluid associated with canine granulomatous meningoencephalomyelitis: a retrospective study.
Cerebrospinal fluid of 22 dogs with histologically confirmed granulomatous meningoencephalomyelitis was analyzed, retrospectively. Seventeen dogs had cisternal CSF analysis, 4 dogs had lumbar CSF analysis, and 1 dog had both. For cisternal CSF, the mean +/- SEM total WBC count was 800.8 +/- 300.9 cells/microliter. The WBC differential count was predominantly lymphoplasmacytic cells, but 13 of the 18 cisternal CSF had polymorphonuclear (PMN) cells, and the mean +/- SEM PMN cell percentage was 18.6 +/- 5.3%. The mean +/- SEM total protein content of cisternal CSF was 255.8 +/- 98 mg/dl. Of 5 cisternal CSF pressures measured, 4 were within the normal range. The mean +/- SEM total WBC count and total protein content of lumbar CSF were 533.4 +/- 256.5 cells/mu/microliter and 163.2 +/- 25 mg of protein/dl, respectively. As with cisternal CSF, the WBC differential count of lumbar CSF was predominantly lymphoplasmacytic cells. Of 5 lumbar CSF, 4 contained PMN cells, but the percentage was less than the PMN cell percentage of cisternal CSF. Although variable, the general pattern of CSF abnormality associated with granulomatous meningoencephalomyelitis was different from the CSF abnormalities commonly seen with viral, bacterial, or mycotic encephalitides.


Escherichia coli MoeA and MogA. Function in metal incorporation step of molybdenum cofactor biosynthesis.
Escherichia coli MoeA and MogA are required for molybdenum cofactor biosynthesis and are believed to function in the addition of molybdenum to the dithiolene of molybdopterin to form molybdenum cofactor. Here we show that moeA(-) and mogA(-) cells are able to synthesize molybdopterin, but both are deficient in molybdenum incorporation and, as a consequence, are deficient in the formation of molybdopterin-guanine dinucleotide. Human sulfite oxidase expressed in E. coli moeA(-) could be activated in vitro in the presence of MoeA and low concentrations of molybdate. Sulfite oxidase purified from the moeA(-) lysate was also activated, although to a lesser extent than observed in the presence of lysate. MogA was incapable of activating sulfite oxidase expressed in E. coli mogA(-). These results demonstrate that molybdenum insertion into molybdopterin is required for molybdopterin-guanine dinucleotide formation, and that MoeA facilitates molybdenum incorporation at low levels of molybdate, but MogA has an alternative function, possibly as a carrier for molybdopterin during molybdenum incorporation.


Mode of the excitatory and inhibitory actions of ciguatoxin in the guinea-pig vas deferens.
Ciguatoxin (CTX), one of the most potent known toxic substances among marine toxins, causes a contraction in the isolated guinea-pig vas deferens at the concentration of above 3 x 10(-7) g/ml. The CTX-induced contraction of the vas deferens was inhibited or abolished by a treatment with phentolamine or guanethidine, but not affected in the presence of atropine or mecamylamine. Furthermore, this contraction was blocked by a treatment with tetrodotoxin, procaine or cold storage and incubation in a low Na+ medium. On the other hand, CTX markedly potentiated the contraction of vas deferens which was induced by norepinephrine (NE), acetylcholine or high-K, whereas it inhibited the contractile response to transmural stimulation. CTX caused a marked release of NE from the adrenergic nerves, which was blocked after treatment with tetrodotoxin or incubation in a Ca-free medium. On the basis of these results, it is suggested that the CTX-induced contraction is the result of an indirect action mediated through the NE release from the adrenergic nerve terminals and that the effect of NE released from the presynaptic sites is potentiated by CTX at the postsynaptic sites. The inhibitory effect of CTX on the contractile response to transmural stimulation may be due to decreasing the transmitter release caused by stimulation.


Patterns of myocardial fibrosis in idiopathic cardiomyopathies and chronic Chagasic cardiopathy.
To study the fibrillar nature and structural features of the collagenous interstitium of the myocardium in normal and cardiomyopathic human hearts, employing the picrosirius red technique and polarization microscopy. A survey, case series study. Referral autopsy service at a university medical centre (Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto). A total of 46 adult hearts obtained at autopsy were used: five control hearts without evidence of cardiac disease, nine hearts with dilated cardiomyopathy, five with hypertrophic cardiomyopathy, four with endomyocardial fibrosis affecting the left ventricle, and 23 with chronic Chagasic cardiopathy. Fragments of myocardial tissue were obtained from the equator of the left ventricular free wall, fixed in formalin, dehydrated, and embedded in paraffin. Sections were stained with a modification of the picrosirius red technique and examined using direct light and polarization microscopy. The findings in the control myocardium did not differ from those reported in the literature. The myocardium in both dilated and hypertrophic cardiomyopathies showed diffuse fibrosis varying in degree from one case to another, but present in all cases. The basic pattern was characterized by a diffuse increase in both endomysial and perimysial collagen thick fibres, particularly surrounding individual myocytes (endomysial sheath). The microscopic study of the cases of endomyocardial fibrosis showed a thickened fibrotic endocardium consisting predominantly of thick collagen fibres extending as a septum, corresponding to broad perimysial sheaths, into the myocardium. In the superficial muscle fibre bundles usually composed of atrophic fibres, there was an increase in thickness of collagen fibres in both the perimysial and endomysial connective tissue matrix. To a variable degree (but present in all cases) interstitial and diffuse fibrosis could be observed in the chronic myocarditis of Chagas's disease. This was manifested by a diffuse increase in the amount of thick collagen fibres surrounding muscle fibre bundles (perimysial matrix), varying in intensity from one area to another, and around intramural coronary vessels, combined with a less pronounced increase in the endomysial collagen matrix. These findings extend knowledge of the various expressions of interstitial myocardial fibrosis in the idiopathic cardiomyopathies and chronic Chagasic cardiopathy and perhaps provide insight into pathogenesis. Further research into the patterns and pathogenesis of myocardial fibrosis are needed in order to offer prevention and corrective forms of therapy of the fibrotic process.


Fundus magnification produced during direct ophthalmoscopy of the corrected eye.
The clinical significance of fundus magnification produced during direct ophthalmoscopy of the corrected eye has not been fully established. Based on paraxial ray tracing, fundus magnification (M) can be defined by a simple equation, M = (K'/4) x (Fs/K), where K' is the dioptric axial power of the eye, Fs is the correcting thin lens power and K is the ocular ametropia. Refractive myopes produce greater fundus magnification than axial myopes, whereas refractive hyperopes produce lower fundus magnification than axial hyperopes. If we assume 15 x fundus magnification as our standard magnification for an emmetropic reduced eye, then wearing glasses or putting the focusing lens at or close to the anterior focus of the eye is able to achieve the standard magnification for axial myope and axial hyperope, whereas wearing contact lenses is able to achieve the standard magnification for refractive myope and refractive hyperope. Vertex distance has greater influence on fundus magnification produced during direct ophthalmoscopy than other funduscopic techniques. In conclusion, the newly defined formula has clinical applications during direct ophthalmoscopy.