Energetic and endocrine mediation of natal dispersal behavior in Belding's ground squirrels.
Natal dispersal, the permanent departure of an individual from its birth site, is sex biased in most mammals, with males dispersing at higher rates or over greater distances than do female conspecifics. Because dispersal movements may be energetically expensive, their occurrence should theoretically be influenced by energy availability. Moreover, the male bias typical of mammalian dispersal suggests that this behavior might be mediated by gonadal androgens. Using free-living Belding's ground squirrels (Spermophilus beldingi) as subjects, we provisioned juveniles with extra food to evaluate energetic influences on male dispersal behavior. Provisioning increased body mass and body fat of juvenile males and caused them to disperse at younger ages, but did not affect blood glucose levels. Dispersing males were fatter than same-aged males that had not yet dispersed. Moreover, body fat of provisioned and unprovisioned males did not differ when evaluated relative to the week during which they dispersed, suggesting that there may be a fat threshold for dispersal. In a second experiment, we measured plasma concentrations of testosterone (T) in provisioned and unprovisioned, free-living juveniles to evaluate the hypothesis that male dispersal behavior is activated by concurrent high levels of T. We observed no increase in plasma T associated with dispersal by juvenile males, no sex differences in circulating T among juveniles, and no effects of food provisioning on juvenile T levels. In a third experiment with free-living S. beldingi, we concurrently altered early androgen exposure by treating females with T at birth and manipulated energy availability by food provisioning. Perinatal T-treatment increased the likelihood of dispersal among juvenile females. Provisioning increased body mass and body fat of juveniles and caused males and T-treated females to disperse at significantly younger ages than either their unprovisioned counterparts or the few provisioned control females that dispersed. These results suggest that early T exposure in this species determines the probability of dispersal, whereas the amount of energy an individual has stored as fat strongly influences the timing of dispersal. Early T exposure also appears to cause the timing of dispersal to respond to energy availability and body fat in a male-typical way, possibly by organizing masculine mass and fat thresholds for dispersal.


7-Azidomethoxy-coumarins as profluorophores for templated nucleic acid detection.
Templated nucleic acid detection is an emerging bioanalytical method that makes use of the target DNA or RNA strand to initiate a fluorogenic reaction. The Staudinger reduction holds particular promise for templated sensing of nucleic acids because the involved functional groups are highly chemoselective. Here, the azidomethoxy group, which can be removed under Staudinger conditions, is used to cage 7-hydroxycoumarin fluorophores. Reduction by phosphines and subsequent loss of the azidomethoxy substituent induce a significant bathochromic shift of the major absorbance band in the near UV region. When excited at the appropriate wavelength, this change in the absorbance spectrum translates into a substantial fluorescence turn-on signal. The described profluorophores are readily conjugated to amino-modified DNAs and are rapidly uncaged by a triphenylphosphine-DNA probe under the control of a DNA template. In addition, turnover of the probes on the target strand occurs and yields substantial signal amplification.


Axonal sprouting following incomplete spinal cord injury: an experimental model.
Recovery of function following incomplete spinal cord injury may in part result from growth of new connections by spared descending pathways. It has been difficult to demonstrate such anatomical reorganization with traditional anatomic techniques. This study utilizes an immunocytochemical method to demonstrate axonal growth cones within the lumbar spinal cord in rats recovering from an incomplete midthoracic spinal cord injury. Adult rats underwent subtotal section of the midthoracic cord sparing the left lateral funiculus and a portion of the left ventral funiculus. Light microscope immunocytochemistry was performed on sections of lumbar spinal cord with antibodies to identify sprouting axons. These antibodies were used to determine the distribution of growth cones on both sides of the lumbar spinal cord in experimental and control animals. Growth cones were first observed three days after the spinal cord lesion. Specific labeling, similar in appearance to previous reports of growth cone identification, was apparent within the immediate gray and ventral horns on both sides of the cord. These data support the hypothesis of collateral sprouting distal to the lesion site following incomplete spinal cord injury. It further supports the idea that recovery of function following incomplete spinal cord injury is, in part, mediated by spared descending pathways.


p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group.
To evaluate the safety and efficacy of p55 tumor necrosis factor receptor fusion protein, a recombinant chimeric protein of human p55 (type I) tumor necrosis factor receptor (CD120a) extracellular domain and IgG1 sequences (referred to as p55-IgG), in the treatment of patients with severe sepsis or septic shock. Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. Forty-four community and university-affiliated hospitals in the United States and Europe. There were 498 patients enrolled in this clinical trial. Patients prospectively stratified within each site into refractory shock or severe sepsis groups were randomized to receive a single infusion of p55-IgG, 0.083 mg/kg, 0.042 mg/kg, or 0.008 mg/kg, or placebo. Patients received standard aggressive medical/surgical care during the 28-day postinfusion period. Twenty-eight-day all-cause mortality. The distribution of variables describing demographics, organ system dysfunction or failure, infecting microorganisms, predicted mortality, plasma interleukin 6 levels, and plasma tumor necrosis factor alpha (TNF-alpha) levels were similar among patients in the p55-IgG and placebo treatment arms. A planned interim analysis was performed after 201 patients were enrolled. Because a statistically nonsignificant trend toward increased mortality was present in patients who had received 0.008 mg/kg, this treatment arm was discontinued, and the study continued with 3 arms. Among all infused patients, there was a statistically nonsignificant trend toward reduced 28-day all-cause mortality in those who received p55-IgG compared with placebo-treated patients (5% reduction, 0.042 mg/kg vs placebo; 15% reduction, 0.083 mg/kg vs placebo; P=.30). However, in patients with severe sepsis and early septic shock (n=247), therapy with p55-IgG, 0.083 mg/kg, was associated with a 36% reduction in 28-day all-cause mortality compared with placebo (P=.07): 20 (23%) of 87 patients died among those treated with p55-IgG, 0.083 mg/kg; 30 (37%) of 82 among those treated with p55-IgG, 0.042 mg/kg; and 28 (36%) of 78 in the placebo group. A prospectively planned logistic regression analysis to assess treatment effect on 28-day all-cause mortality by means of predicted mortality and serum interleukin 6 levels as continuous covariates demonstrated a significant improvement in outcome for the patients with severe sepsis treated with p55-IgG, 0.083 mg/kg, compared with placebo (P=.01). Serious adverse events, including death and the development of new organ system dysfunction, were reported in 65% of patients infused with placebo, with no increased frequency (56%) present in the 2 p55-IgG treatment arms. There were no reports of immediate hypersensitivity reactions caused by p55-IgG. In this dose-finding study, there was no decrease in mortality between placebo and p55-IgG in all infused patients. In the prospectively defined population of patients with severe sepsis who received p55-IgG, 0.083 mg/kg, there was a trend toward reduced mortality at day 28 that became significant when predicted mortality and plasma interleukin 6 levels were included in a logistic regression analysis.


A transcultural ethos underpinning curriculum development: a master's programme in disaster relief nursing.
This article discusses the development and implementation of a masters' degree programme in disaster relief nursing by cooperating partners in European countries. It aims to enhance the provision of aid by endorsing the role of nurses at the forefront of health care in disaster-stricken areas around the world. As an attempt to address the implications of globalization in health care, the programme was established as a recognition of the rapidly developing specialty of transcultural/transnational nursing. Innovative teaching and learning strategies used include e-learning, simulation exercises, and competency portfolio development. A rigorous evaluation of programme outcomes is ongoing.


Unprecedented formation of 3-(tetrahydrofuran-2-yl)-4H-chromen-4-one in a reaction between 3,3a-dihydro-9H-furo[3,4-b]chromen-9-one and malononitrile.
Chromone skeletons are widespread among natural products as well as bioactive molecules. Here, we describe an unprecedented reaction of furo[3,4-b]chromen-9-one with malononitrile to afford 3-(tetrahydrofuran-2-yl)-4H-chromen-4-ones. Experimental data suggest that a sequence of Michael/retro-Michael/nucleophilic addition is involved in this unprecedented transformation.


The role of systemic and topical fatty acids for dry eye treatment.
Dry eye is a prevalent condition and one of the main reasons for patients to seek ophthalmic medical care. A low systemic level of omega fatty acids is a risk factor for dry eye disease (DED). There are two groups of essential fatty acids (EFAs): the omega-6 (n-6) family and the omega-3 (n-3) family. Humans evolved on a diet in which the n-6:n-3 ratio was approximately 1:1, however the current Western diet tends to be deficient in n-3 EFAs and this ratio is typically much higher (approaching 17:1). The metabolism of EFAs generates four new families of local acting mediators: lipoxins, resolvins, protectins, and maresins. These molecules have anti-inflammatory and pro-resolution properties. We present a critical overview of animal model studies and human clinical trials that have shown that dietary modification and oral supplementation could be complementary therapeutic strategies for the treatment of dry eye. Furthermore, we discuss preliminary results of the topical application of n-3 and n-6 EFAs because these molecules may act as natural anti-inflammatory agents with positive changes of the entire ocular surface system.


Tetranectin Binds to the Kringle 1-4 Form of Angiostatin and Modifies Its Functional Activity.
Tetranectin is a plasminogen kringle 4 domain-binding protein present in plasma and various tissue locations. Decreased plasma tetranectin or increased tetranectin in stroma of cancers correlates with cancer progression and adverse prognosis. A possible mechanism through which tetranectin could influence cancer progression is by altering activities of plasminogen or the plasminogen fragment, angiostatin. Tetranectin was found to bind to the kringle 1-4 form of angiostatin (AST $;{\text{K1-4}}$ ). In addition, tetranectin inhibited binding of plasminogen or AST $;{\text{K1-4}}$ to extracellular matrix (ECM) deposited by endothelial cells. Finally, tetranectin partially counteracted the ability of AST $;{\text{K1-4}}$ to inhibit proliferation of endothelial cells. This latter effect of tetranectin was specific for AST $;{\text{K1-4}}$ since it did not counteract the antiproliferative activities of the kringle 1-3 form of angiostatin (AST $;{\text{K1-3}}$ ) or endostatin. These findings suggest that tetranectin may modulate angiogenesis through interactions with AST.


A method of reducing background radiance for emissivity-compensated radiation thermometry of silicon wafers.
We studied the spectral and directional emissivities of silicon wafers using an optical polarization technique. Based on simulation and experimental results, we developed two radiation thermometry methods for silicon wafers: one is based on the polarized emissivity-invariant condition and the other is based on the relationship between the ratio of the p- and s-polarized radiance and the polarized emissivity. These methods can be performed at temperatures above 600 °C and over a wide wavelength range (0.9-4.8 μm), irrespective of the dielectric film thickness and the substrate resistivity, which depends on the dopant concentration. The temperature measurements were estimated to have expanded uncertainties (k = 2) of less than 5 °C. With a view to practically applying these methods, we investigated a method to reduce the intense background radiance produced by high-intensity heating lamps. We found that the background radiance can be greatly reduced by using a radiometer that is sensitive to wavelengths of 4.5 or 4.8 μm and suitable geometrical arrangements of a quartz plate. This opens up the possibility of using the two proposed radiation thermometry methods in practical applications.


Comparison of segmental-dependent permeability in human and in situ perfusion model in rat.
Nowadays, alternative methods have been developed to predict intestinal permeability values in human as in vitro, in situ or ex vivo methods. They were developed by the necessity to avoid the problems of the human permeability experiments. However, determination of human permeability is needed to properly validate the alternative methods. For this reason, recently, Dahlgren et al. published an indirect method based on a deconvolution technique to estimate the human permeability in different gastrointestinal segments (jejunum, ileum and colon). Therefore, the objective of this research was to demonstrate that Doluisio technique is a useful method to predict the human permeability in different gastrointestinal segments. To achieve this goal, the rat permeability in different segments, of the same drugs studied by Dahlgren et al. (atenolol, metoprolol and ketoprofen), have been compared with the human data obtained by the deconvolution method. The results obtained in this work show that the Doluisio method is a reliable tool to predict segmental human permeability. Consequently, the deconvolution method can be employed to build an extensive database of human permeability, overall from ileum and colon, because there is a lack of human permeability data of these distal segments. Once there are enough human data available, the Doluisio technique will be a valuable alternative method to predict the permeability of new molecules with therapeutic activity without the requirement of human experiments.


A full-configuration interaction "nuclear orbital" method to study doped 3HeN clusters (N< or =4).
An efficient full configuration interaction (FCI) treatment, based on the Jacobi-Davidson algorithm, is developed in order to study small doped (3)He(N) clusters. The state of each He atom in a given cluster is described by a set of wave-functions which by extention of the quantum-chemistry notation are caller here "nuclear orbitals". The FCI treatment is applied to the calculation of binding energies and helium natural orbitals of (3)He(N)...Br(2)(X) complexes. In agreement with our previous calculations using a Hartree-Fock approach [Phys. Rev. Lett. 93, 053401 (2004)], in which the He-He interaction is modified at small distances to account for short-range correlation effects, the lowest-energy states of each multiplet are found to be very close in energy. The natural orbital analysis, in turn, indicates the adequacy of the "nuclear orbital" approach in these systems.


Comparison of absorption and excretion of cefazolin with cephalothin and cephapirin.
Since the discovery of cephalothin in 1962, many semi-synthetic cephalosporins have appeared. To choose the most suitable drug for the clinical treatment of infections, the characteristics of these antibiotics must be sufficiently understood. When cephalosporins which are or will be commercially available are divided into two categories, one consists of cephaloridine, cefazolin and cephalexin which are comparatively stable in the living body; and the other cephalothin, cephaloglycin, cephapirin and cephacetrile which are metabolized into desacetyl compounds with low antibacterial activity. In this study, the author compared the absorption, excretion and some other properties of cefazolin and cephalothin, (widely used clinically), and cephapirin (still under study in Japan).


Virtual histology and color flow intravascular ultrasound in peripheral interventions.
The quality and interpretation of intravascular ultrasound (IVUS) imaging has been revolutionized in recent years by two new and major advances: virtual histology and color flow IVUS. Virtual histology intravascular ultrasound (VHIVUS) is a catheter-based technology where IVUS is generated from the transducer on the catheter tip and the reflected signals from the artery wall produce a color-coded map of the arterial disease. Different histological constituents of the plaque produce different reflected signals and these are assigned different colors (dark green, fibrous; yellow/green, fibrofatty; white, calcified; red, necrotic lipid core plaque). This color-coded map assists the interventionalist in understanding more fully how the lesion will behave at the moment of treatment, whether it will resist complete stent deployment or be liable to embolization. Originally introduced for coronary interventions, VHIVUS is now being applied to peripheral situations. Because it provides a detailed and close-proximity view of plaque, its potential to improve the safety and efficacy of carotid endoluminal repair is stimulating substantial interest. Similarly, color flow IVUS provides greater understanding for the operator of blood flow, and the interface between the vessel wall and the blood stream, lumen size, and success of treatment. Color flow IVUS does not use the Doppler effect, but creates real-time images that resemble color flow Doppler ultrasound. These two technological advances in IVUS have greatly improved the ability of the endovascular specialist to understand the arterial disease they are treating and to assess the completion of treatment.


Parametric modulation of cortical activation during smooth pursuit with and without target blanking. an fMRI study.
Smooth pursuit eye movements (SPEM) are performed to track slowly moving visual targets and are accompanied by saccades whenever foveal representation is lost. In the present study, we correlated the cerebral activation as assessed by functional magnetic resonance imaging with parameters of eye movement performance in order to determine the cortical areas involved in the retinal and extraretinal processing of maintaining smooth pursuit velocity (SPV) and generating saccades in 16 healthy males. The stimulus consisted of a target moving at a constant velocity of 10 degrees/s with and without target blanking. During constant target presentation, SPV was positively correlated with the BOLD signal in the right V5 complex and negatively correlated with the BOLD response in the left dorsolateral prefrontal cortex (DLPFC). In the condition with target blanking, additional negative correlations with SPV were found in the left frontal eye field (FEF), the left parietoinsular vestibular cortex (PIVC) and the left angular gyrus. Saccadic frequency was negatively correlated with activations of the right mesial intraparietal sulcus (IPS) during both conditions and the right premotor area during continuous target presentation. We conclude that V5 is directly related to the maintenance of an optimal smooth pursuit velocity during visual feedback, whereas the FEF, PFC, angular gyrus and PIVC are involved in reconstitution and prediction whenever SPV decreases, especially during maintenance of smooth pursuit in the absence of a visual target. Furthermore, we suggest that parietal areas are related to the suppression of saccades during smooth pursuit.


Evaluation of vision in slow-stream wards.
Two hundred and twenty-one patients in slow-stream geriatric wards in the Portsmouth district were questioned about their vision; 159 of these were examined. It was possible to give help with vision to 21 per cent of patients and to give a further 6 percent help with other eye problems. Eighteen months later, when half the patients examined had died, 14 per cent of those still alive were continuing to enjoy their improved vision, and 6 per cent were benefitting from the help they had received with other eye problems. As a result, we recommend that all admissions should be assessed with regard to their visual ability and that all those with adequate mental faculties should be examined by an ophthalmologist or an optician on admission and when necessary therafter.


[Invasive mycosis, immunocompromise and fever of unknown origin].
fungal invasive infections are frequent in patients with immunosuppression. A common clinical feature is the presence of fever of unknown origin (FUO) in any of its several presentations. The aim of this study was to know the frequency of FUO associated to invasive mycosis in hospitalized patients. samples from 34 patients were studied by immunological and microbiological procedures in order to investigate candidiasis, cryptococcosis, aspergillosis and Pneumocystis infection. fungal infection diagnosis was established in 12 (35 %) from 34 patients who full criterion. The fungal species isolated were Candida albicans (six), Aspergillus fumigates (four) and Cryptococcus sp. (two). All candidiasis cases were diagnosed only by microbiological studies, aspergillosis by immunological and microbiological studies, and cryptococcosis only by immunological studies. we concluded that is important the searching of mycosis in immunocompromised patients with fever of unknown origin by microbiological and immunological procedures.


Exenatide: a novel approach for treatment of type 2 diabetes.
Exenatide (synthetic exendin-4) is the analog of glucagon-like peptide 1 (GLP-1), the major physiologic incretin. The latter is an intestinal hormone that enhances glucose-induced insulin secretion after meals. In addition, GLP-1 stimulates insulin synthesis, inhibits glucagon secretion, delays gastric emptying, and may promote satiety. These glucoregulatory actions help control plasma glucose in the postprandial period. However, in diabetes, the GLP-1 response to nutrient intake is impaired, leading to exacerbation of postprandial hyperglycemia. Exenatide was recently approved as adjunctive therapy in diabetic patients failing sulfonylureas and/or metformin. In clinical trials lasting 30 weeks, exenatide therapy was associated with moderate reduction in mean hemoglobin A1c (HbA1c) levels of approximately 0.8%, and an average weight loss of approximately 2 kg compared with baseline. Hypoglycemia was generally mild and occurred more commonly when exenatide was used in conjunction with sulfonylureas. The requirement of subcutaneous injections twice a day, and the frequent occurrence of nausea and vomiting, represent the main limitations of exenatide. Nevertheless, this agent may be a useful add-on therapy in obese diabetic patients with suboptimal control as a result of continuing weight gain and/or severe postprandial hyperglycemia. The introduction of GLP-1-based antidiabetic drugs is a novel and promising strategy to treat diabetes.


Pulmonary nodules causing false-positive liver scans. Preoperative and postoperative scintigraphic findings in three cases.
False-positive liver scans may occur due to intrinsic hepatic anatomy, extrinsic impression on the liver from adjacent structures, or external attenuation of gamma rays. However, reports of false-positive scans due to external attenuation by pulmonary nodules are very few, and postoperative changes in liver scintigraphy have not been reported. We experienced three such cases. In each case, a pulmonary mass was located in the right posterior basal segment. The preoperative liver scan showed a focal "cold" area in the upper portion of the right lobe. This "cold" area was seen only in the posterior view, and after resection of the tumor it usually disappeared promptly unless direct liver invasion was present.


Calf and colostrum management practices on New Zealand dairy farms and their associations with concentrations of total protein in calf serum.
To gather information on management practices and farmer attitudes to management of cows and calves during the immediate post-partum period on dairy farms in New Zealand, and to assess these practices for associations with concentrations of total protein (TP) in serum of calves 1-8 days-old. Between July and September 2015 blood samples were collected from calves aged between 24 hours and 7 days, from dairy farms (n=105) in nine areas in New Zealand, on three occasions throughout the calving period. Concentrations of TP were determined in all serum samples. At each visit technicians collected 1 L of the pooled colostrum that was intended for feeding to newborn calves that day. These samples were assessed for Brix, coliform and total bacterial counts. After the last sampling visit, the calf rearer or farm manager were asked to complete a questionnaire describing calf and colostrum management practices on the farm. Potential farm-level variables associated with concentrations of TP in serum of sampled calves were identified using univariable and multivariable linear mixed models. Mean concentration of TP in serum of calves across all farms was 59.8 (95% CI=59.4-60.2) g/L, and was associated with region and herd size in the final multivariable model. Concentrations of TP were lower in calves from farms in Otago (56.2 (95% CI=53.4-58.9) g/L) and Southland (56.9 (95% CI=54.1-59.7) g/L) compared to calves on farms in the Far North (62.6 (95% CI=59.8-65.3) g/L), and were lower in calves from farms with a herd size >600 (58.3 (95% CI=56.7-59.8) g/L) than ≤600 (61.3 (95% CI=60.1-62.5) g/L) cows. After accounting for fixed effects, farm accounted for only 8.4% of the unexplained variation. There was no association between any of the measures of colostrum quality and concentrations of TP in serum (p>0.2). Very few herd-level variables were associated with concentrations of TP in serum. Risk factors that have been shown to be of importance in previous studies outside New Zealand were not identified as important in the current study. It is possible that, in the situation where calves are kept at pasture with their dams for prolonged periods, variables which influence how well a cow can feed its calf in the first 12-24 hours have a larger influence on concentrations of TP in serum than the collection and management of calves once they reach the rearing shed.


Hepatic monooxygenase (CYP1A and CYP3A) and UDPGT enzymatic activities as biomarkers for long-term carbofuran exposure in tench (Tinca tinca L).
The effect of a long-term exposure of tenchs to different concentrations (10 and 100 micro g/L) of the pesticide carbofuran has been evaluated. Microsomal hepatic cytochrome P450 subfamily 1A (CYP1A) and 3A (CYP3A) activities, as well as the phase II enzyme uridine diphospho-glucuronosyltransferase (UDPGT) activity were evaluated as adequate biomarkers of fish exposure to environmentally relevant concentrations of the pesticide carbofuran in freshwater ecosystems. A clear time-dependent inhibition of both CYP1A and UDPGT activities was observed in fish exposed to the highest dose of carbofuran with respect to controls, whereas in the case of CYP3A activity, values of exposed animals did not show a clear pattern of alteration during the experiment. The results of the present study demonstrated that hepatic CYP1A and UDPGT activities from tench could be considered as sensitive biomarkers for carbamate pesticides in polluted water, thus allowing future and ecologically relevant biomonitoring studies with this species.


CADASIL: how to avoid the unavoidable?
All three siblings (one female/two males) of a family presented successively with cerebrovascular events at the ages of 55, 63 and 65. The first one manifested extensive left subcortical haemorrhage and both the second and third patient, showed left lacunar ischemic stroke. Their mother had died from vascular dementia at the age of 60 after several subcortical ischaemic strokes. Their maternal grandfather had died in his fifties from haemorrhagic stroke. All of them showed extensive white matter involvement. The genetic study revealed a mutation in exon 11 of the Notch3 gene in two family members. They were diagnosed with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Although CADASIL is a well-established disease, little is known about this disorder. The fact that all three siblings presented with CADASIL successively may appear disheartening, further studies are needed in order to control the clinical course of this devastating and unavoidable disorder.


Time-dependent inactivation of immobilized glucose oxidase and catalase.
Homogeneous membranes containing immobilized glucose oxidase and catalase were stored in buffered solutions at 37 degrees C to determine the mechanisms and rates of catalyst inactivation. The experiments were designed so that inactivation occurred homogeneously throughout the membrane, thereby simplifying the analysis. The mechanism of inactivation is consistent with the reaction of hydrogen peroxide and certain catalytic intermediates of both enzymes. Based on this information, numerical simulations were developed that incorporate spatially heterogeneous catalytic and inactivation processes.


Ginsenoside Rh2 reverses sleep deprivation-induced cognitive deficit in mice.
Sleep deprivation (SD) negatively caused cognitive deficit, which was associated with oxidative stress induced damage. Ginsenoside Rh2 had the ability to protect against damage caused by reactive oxygen species in vitro, showing antioxidant property. Therefore, it was hypothesized that Ginsenoside Rh2 could prevent SD-induced cognitive deficit via its antioxidant properties. In this study, the effect of Ginsenoside Rh2 on memory impairment induced by sleep deprivation was investigated. The mice were sleep deprived continuously for 14 days using our self-made Sleep Interruption Apparatus (SIA). Ginsenoside Rh2 was administered intraperitoneally at two doses (20 and 40 μmol/kg) for 20 days. Thereafter, behavioral studies were conducted to test the learning and memory ability using object location recognition (OLR) experiment and passive avoidance (PA) test. Additionally, the oxidative stress parameters in the serum and the brain tissues (cortex and hippocampus) were assessed, including the superoxide dismutase (SOD) enzyme activity, the total antioxidant reactivity (TAR), the malondialdehyde (MDA) level, the glutathione (GSH) level, and the lipid peroxidation (LPO) content. The results revealed that SD impaired both spatial and non-spatial memory (P < 0.05). Treatment with Ginsenoside Rh2 at both doses prevented memory impairment induced by SD. Moreover, Ginsenoside Rh2 normalized the reduction of SOD and TAR activities in the serum (P < 0.01) and the decrease of GSH content in both the cortex and hippocampus (P < 0.05) induced by SD. Furthermore, Ginsenoside Rh2 significantly decreased the MDA level in the serum (P < 0.05) and the LPO content in both the cortex and hippocampus (P < 0.05) compared to SD group. In conclusion, sleep deprivation impaired both spatial and non-spatial memory and Ginsenoside Rh2 reversed this impairment, probably by preventing the oxidative stress damage in the body, including the serum and brain during sleep deprivation.


Imaging Appropriateness for Neck Pain.
Imaging of neck pain contributes to a significant proportion of health care costs and is expected to increase with current practices that heavily use radiologic studies as a diagnostic tool. Though consensus guidelines are available to assist physicians in selection of appropriate imaging examinations for neck pain, it is unclear if current ordering practices reflect their use and understanding. To investigate this, we analyzed the number and types of imaging examinations performed for neck pain at a university medical center over the past year. Current trends at our institution suggest that clinicians use consensus imaging guidelines, but there is still controversy in the cervical spine for when not to image. To promote appropriate imaging utilization, we developed an algorithm to guide imaging of neck pain, based upon clinical presentation, referral patterns for neck pain, and a review of the literature.


Chronic ventricular tachyarrhythmias in the conscious dog: prevention by UM-272 (dimethylpropranolol).
The ability of chronic UM-272 (dimethylpropranolol) treatment to prevent the induction of reentrant ventricular tachyarrhythmias was assessed in the conscious dog subjected to serial programmed electrical stimulation on days 3--5 after myocardial infarction. In 20 untreated control animals, programmed electrical stimulation produced nonsustained ventricular tachycardia in 6 animals (30%), sustained ventricular tachycardia in 8 animals (40%), and ventricular fibrillation in 6 animals (30%) on the third day after occlusion and reperfusion of the left anterior descending coronary artery. On day 4, programmed electrical stimulation produced nonsustained ventricular tachycardia in 5 animals (36%), sustained ventricular tachycardia in 7 animals (50%), and ventricular fibrillation in 2 animals (14%). UM-272, 5 or 10 mg/kg, i.v., was administered every 12 hr to a separate group of 8 dogs after the induction of ischemic myocardial injury. Programmed electrical stimulation on day 3 after myocardial infarction failed to elicit ventricular arrhythmias in 4 animals (50%, p = 0.014), with acute administration of the next UM-272 dose preventing the induction of ventricular tachyarrhythmias in 7 animals (88%, p less than 0.0001). On day 4, programmed electrical stimulation failed to elicit ventricular arrhythmias in 5 aminals (63%, p = 0.0021). Thirty-six hours after the withdrawal of UM-272, programmed electrical stimulation produced ventricular fibrillation in 5 animals (63%) and sustained ventricular tachycardia which degenerated to ventricular fibrillation in 3 animals (37%). UM-272 significantly (p less than 0.05) depressed conduction in both normal and ischemically injured myocardium while also increasing (p less than 0.05) ventricular effective refractory periods. The results of these investigations suggest that UM-272 may be effective in preventing reentrant ventricular rhythms in hearts subjected to chronic myocardial ischemic damage and, therefore, may be of potential value in preventing reentrant ventricular arrhythmias in man.


Laryngeal fractures in lacrosse due to high speed ball impact.
Men's lacrosse is a fast-paced, high-collision sport with ball speeds in excess of 90 mph. Laryngeal fractures in lacrosse are a rarely reported injury. To increase awareness of this potential injury, we describe 3 male lacrosse players who sustained laryngeal fractures from lacrosse ball trauma to the neck. The first patient sustained a minimally displaced, paramedian thyroid cartilage fracture and was managed with observation alone. The second patient sustained a depressed fracture of the left thyroid ala and was managed with closed reduction. The third case sustained a mildly displaced transcricoid fracture. He was managed with open reduction and internal fixation. All 3 patients returned to regular activities with near normal voice results by final follow-up. This is the first report of laryngeal fractures following lacrosse ball trauma to the neck. Lacrosse players are at risk for laryngeal injuries, and neck protection is only worn by the goalie. It is our hope that this series will raise awareness of this potentially lethal injury and prompt the sport to consider mandatory neck protection for all players.


Eosinophils are a major intravascular location for tissue factor storage and exposure.
Blood cell progenitors were scanned for the presence of the coagulation starter protein tissue factor (TF) by immunoelectron microscopy. Thereby, substantial TF expression was observed in the precursor cells of eosinophils. TF levels were lower in basophil precursors and barely detectable in neutrophil progenitors. In peripheral blood immediately processed to avoid activation of the TF gene, mature eosinophils were found to considerably express TF, unique among the granulocyte and monocyte fractions. TF was preferentially located in the specific granules in resting eosinophils. Platelet-activating factor (PAF), and more pronounced, granulocyte-macrophage colony-stimulating factor (GM-CSF) plus PAF, caused translocation of preformed TF to the eosinophil cell membrane. GM-CSF/PAF also increased the TF transcript levels. The activated eosinophils exhibited procoagulant activity that was abrogated by TF inhibition. Targeting the extracellular domain of TF with specific antibodies markedly suppressed the initial phase of the eosinophil passage across the IL-4-activated endothelium. Eosinophil rolling and firm adhesion remained unaffected. This suggests that TF specifically facilitates the early transendothelial migration of the eosinophils. In summary, eosinophils maintain a high TF expression during maturation, providing a main source of preformed TF in blood, which might be relevant for the thrombogenesis promoted by hypereosinophilic conditions.


Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis.
Hormonal therapy to the brain-dead potential organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), corticosteroids, antidiuretic hormone, and insulin. Data on 66,629 donors (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in 63,593 (study 1), but 23,469 had incomplete documentation of other hormones. In 40,124, details of all four hormones were recorded (study 2). In this cohort, group A (received T3/T4) consisted of 23,022, and group B (no T3/T4) consisted of 17,102 donors. A multivariate analysis was performed to determine whether age, sex, ethnicity, cause of death, body mass index, Organ Procurement Organization region, or other hormonal therapy influenced procurement. Posttransplantation organ graft survival at 1 and 12 months was compared. In study 1, 30,962 (48.69%) received T3/T4, providing a mean of 3.35 organs per donor, and 32,631 (51.31%) did not receive T3/T4, providing a mean of 2.97 organs per donor, an increase of 12.8% of organs from T3/T4-treated donors (P<0.0001). In study 2, group A provided a mean of 3.31 organs per donor and group B provided a mean of 2.87 organs per donor, an increase of 15.3% in group A (P<0.0001). T3/T4 therapy was associated with procurement of significantly greater numbers of hearts, lungs, kidneys, pancreases, and intestines, but not livers. Multivariate analysis indicated a beneficial effect of T3/T4 independent of other factors (P<0.0001). T3/T4 therapy of the donor was associated with improved posttransplantation graft survival or no difference in survival, except for pancreas recipient (but not graft) survival at 12 months in study 2. T3/T4 therapy results in more transplantable organs, with no detriment to posttransplantation graft survival.


Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine.
The aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response. Patients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E-headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS-D and CES-D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti-CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables. In total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti-CGRP medication was positively associated with a reduction in the HADS-D (β = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES-D (β = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09). Anti-CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab.


[Osteocalcin in chronic hemodialysis patients as an additional parameter in the diagnosis of advanced secondary hyperparathyroidism].
Osteocalcin (OC), also called Bone Gla Protein (BGP), is a bone matrix protein of 5800 MW synthesized by osteoblasts. Since OC is mainly metabolized in the kidney, its blood concentration is altered in renal failure. The relationship between OC and the calcium-phosphorus regulating hormones (parathyroid hormone, calcitonin) and the biochemical parameters of bone metabolism (serum calcium, serum phosphorus and serum alkaline phosphatase) was studied in 30 patients on chronic hemodialysis (mean age: 51 years; mean duration of dialysis treatment: 39 months). OC levels were significantly elevated in all patients on chronic hemodialysis (34.7 +/- 31.5 ng/ml) when compared to healthy subjects (6.25 +/- 1.39 ng/ml, p less than 0.001). In 2 patients the OC levels were excessively high (127.54 ng/ml; 148.02 ng/ml), which was associated with severe renal osteodystrophy due to secondary hyperparathyroidism. When divided into 2 groups in the patients with secondary hyperparathyroidism the mean OC value was markedly elevated (50.5 +/- 12.7 ng/ml) compared to the patients without secondary hyperparathyroidism (24.1 +/- 2.8 ng/ml) (p less than 0.05). 70 per cent of the patients on chronic hemodialysis with OC levels greater than 30 ng/ml showed moderate to severe scintigraphic findings of bone disease. In neither of the 2 groups could a correlation between OC and serum alkaline phosphatase be demonstrated. The results indicate, that OC levels could be useful additional parameter in hemodialyzed patients with secondary hyperparathyroidism and OC levels could reflect bone formation in these patients.


Group B streptococcal disease: a life-threatening infection in the newborn.
Group B streptococcal (GBS) disease, a life-threatening infection in newborns in the United States, causes considerable neonatal morbidity and mortality. GBS is also a major source of maternal infection. Screening during pregnancy leads to early identification. Intrapartal treatment of affected mothers can prevent harmful neonatal effects. Implementation of screening and treatment protocols is recommended for the protection of all obstetric and neonatal patients.


Seasonal variation in the balance and strength of cooperative and competitive behavior in patches of blue mussels.
Aggregation into groups may affect performance of individuals through the balance and strength of facilitative versus competitive interactions. We studied in situ how seasonal variation in abiotic environment affects this balance for blue mussels, a semi-sessile species. We hypothesize that seasonal variation in stresses and resources affects the strength of the interaction. We expected that, in benign conditions (here: high food availability, medium temperatures, low hydrodynamic stress), performance is dominated by growth and is better at low densities, while at adverse conditions (here: low food availability, low or high temperatures, high hydrodynamic stress), performance is dominated by survival and higher at high densities. Mussels were kept in shallow subtidal exclosures at 10 different densities for a one-month period. This exact procedure was repeated seven times at the same location within a one-year period. We measured development in mussel patch shape, performance, and environmental parameters. Environmental conditions for mussels were most benign in summer and most adverse in winter. Patches developed into less complex shapes at lower densities, but also after stronger hydrodynamic disturbances. Towards summer, mussels became more active, aggregation behavior increased, and interactions became more pronounced. Towards winter, mussels became less active: aggregation behavior and growth rates declined and at the lowest temperatures survival started to decrease with mussel density. Survival and growth (by proxy of mussel condition) were both density-dependent; however, contrary to our expectations we found positive interactions between density and survival at the most benign conditions in summer and negative interactions at the most adverse conditions in winter. In between the two seasons, the strength of the interactions increased towards summer and decreased towards winter following a bell-shaped pattern. This pattern might be explained by the environmental mediated aggregation behavior of the mussels. The obvious seasonal pattern in balance and strength of density-dependent interactions demonstrates that strength and direction of intra-specific interactions are both strongly affected by environmental context.


Morphological characteristics of malignant solitary pulmonary nodules.
The solitary pulmonary nodule is a common radiologic abnormality, which is often detected incidentally. It is defined as focal, round or oval areas of increased opacity in the lung which are caused by a variety of disorders, including neoplasm, infection, inflammations, and vascular and congenital abnormalities. Most of the solitary pulmonary nodules are benign, but up to 30%-40% of them are malignant. The main goal of the radiologic evaluation of suspected solitary pulmonary nodules is to differentiate benign from malignant lesions as accurately as possible. The aim of the study was the assessment of the morphological characteristics of the malignant solitary pulmonary nodules. Large nodule size, irregular, spiculated margins, inhomogeneous density of nodule thick walls in cavitary nodules suggest the presence of the malignant lesion. Smooth, well-defined margins, homogeneous density or the presence of diffuse, laminated, central or popcorn-like calcifications suggest the benign nodule. Diffuse, irregular amorphous calcifications suggest the malignant process. Unfortunately there is a kind of overlapping, and some benign nodules may show features typical of malignancy, and some malignant lesions may appear benign. Morphologic characteristics in computed tomography is however helpful in differentiation of benign from malignant nodules.


Ergonomic principles basic to hand tool design.
A survey of those features of hand tools relevant to the physical interaction between the implement and the human operator. Concepts basics to the optimization of forces are mentioned, followed by a description of some of the more common physiological problems and musculoskeletal complaints associated with improper hand tool and design and usage. An account of the distribution of contact pressures and possible consequences, if these are excessive, is followed by a description of the role of working gloves as related to ergonomic problems and their possible relationships to occupational diseases of the hand and wrist. Some aspects of anatomy and anthropometry pertinent to the optimization of posture, motion patterns and tool size precede a list of desirable features for power tools. A glossary is included as an aid to the reader. The concepts and situations described are applicable to the design and use of the vast majority of hand tools.


Development of the Experiences of Sex Work Stigma Scale Using Item Response Theory: Implications for Research on the Social Determinants of HIV.
While HIV stigma has received significant attention, limited work has been conducted on the measurement of intersecting stigmas. We developed the Experiences of Sex Work Stigma (ESWS) scale in the Dominican Republic (DR) and Tanzania. We conducted in-depth interviews with 20 female sex workers (FSW) per country to identify scale domains followed by cognitive debriefing interviews to assess content validity. Items were administered in a survey to FSW in DR (n = 211) and Tanzania (n = 205). Factor analysis established four sex work stigma domains including: shame (internalized), dignity (resisted), silence (anticipated) and treatment (enacted). Reliability across domains ranged from 0.81 to 0.93. Using item response theory (IRT) we created context-specific domain scores accounting for differential item functioning between countries. ESWS domains were associated with internalized HIV stigma, depression, anxiety, sexual partner violence and social cohesion across contexts. The ESWS is the first reliable and valid scale to assess multiple domains of sex work stigma and can be used to examine the effects of this form of intersectional stigma on HIV-related outcomes across settings.


Preliminary evaluation of a multiplex reverse transcription-PCR assay combined with a new DNA chip hybridization assay for detecting respiratory syncytial virus.
DNA chips represent a major advance in microbiology laboratories, enabling the detection of a wide range of possible pathogens using a single test. This study compared a multiplex reverse transcription-PCR combined with DNA chip hybridization (ProDect BCS RV chip; bcs Biotech) with the indirect immunofluorescence test commonly used to detect respiratory viruses. A total of 39 respiratory viruses (38 respiratory syncytial viruses [RSVs] and 1 influenza A virus) were detected in samples from 96 patients using the immunofluorescence test, while 36 viruses (34 RSV, 1 influenza A virus, and 1 influenza B virus) were detected by the DNA chip technique. Results showed a good level of agreement between the two tests for RSV detection; the incidence of other viruses was low, since samples were taken from patients with suspected bronchiolitis. DNA chips displayed high sensitivity (94.6%) and specificity (100%).


Functional expression and mutational analysis of flavonol synthase from Citrus unshiu.
Flavonols are produced by the desaturation of flavanols catalyzed by flavonol synthase. The enzyme belongs to the class of intermolecular dioxygenases which depend on molecular oxygen and FeII/2-oxoglutarate for activity, and have been in focus of structural studies recently. Flavonol synthase cDNAs were cloned from six plant species, but none of the enzymes had been studied in detail. Therefore, a cDNA from Citrus unshiu (Satsuma mandarin) designated as flavonol synthase was expressed in Escherichia coli, and the purified recombinant enzyme was subjected to kinetic and mutational chacterizations. The integrity of the recombinant synthase was revealed by a molecular ion from MALDI-TOF mass spectrometry at m/z 37888 +/- 40 (as compared to 37899 Da calculated for the translated polypeptide), and by partial N-terminal sequencing. Maximal flavonol synthase activity was observed in the range of pH 5-6 with dihydroquercetin as substrate and a temperature optimum at about 37 degrees C. Km values of 272, 11 and 36 micro m were determined for dihydroquercetin, FeII and 2-oxoglutarate, respectively, with a sixfold higher affinity to dihydrokaempferol (Km 45 micro m). Flavonol synthase polypeptides share an overall sequence similarity of 85% (47% identity), whereas only 30-60% similarity were apparent with other dioxygenases. Like the other dioxygenases of this class, Citrus flavonol synthase cDNA encodes eight strictly conserved amino-acid residues which include two histidines (His221, His277) and one acidic amino acid (Asp223) residue for FeII-coordination, an arginine (Arg287) proposed to bind 2-oxoglutarate, and four amino acids (Gly68, His75, Gly261, Pro207) with no obvious functionality. Replacements of Gly68 and Gly261 by alanine reduced the catalytic activity by 95%, while the exchange of these Gly residues for proline completely abolished the enzyme activity. Alternatively, the substitution of Pro207 by glycine hardly affected the activity. The data suggest that Gly68 and Gly261, at least, are required for proper folding of the flavonol synthase polypeptide.


Magnetic resonance imaging of the neuroprotective effect of xaliproden in rats.
The neurotrophic effect of Xaliproden has been followed using sequential cerebral magnetic resonance imaging (MRI) in rats with vincristine-induced brain lesion as a model of Alzheimer disease. Nineteen rats received an intraseptal injection of vincristine on day 0, followed by a daily gavage with either the vehicle (Tween-20 1%) (n = 10) or Xaliproden (10 mg/kg) (n = 9). Eight sham-operated controls received a daily gavage with either the vehicle (n = 4) or Xaliproden (n = 4). Brain MR imaging was performed at 4.7 T on a Biospec 47/30 MR system before surgery then 3, 7, 10, and 14 days after surgery. At day 3 following vincristine injection, an increase in MR signal intensity in the septum was observed on T2-weighted images. This increase was maximal at day 10, and remained stable until day 14. Daily treatment with Xaliproden delayed the appearance of hypersignals until day 7 and reduced by Ca. 50% the magnitude of the increase in signal intensity from day 10. No changes were observed in the hippocampus. Quantitative MRI objectifies noninvasively the neuroprotective effect of Xaliproden on rat brain anatomy.


Promoting prenatal care: what do community leaders know and believe about it? (community leader beliefs about promotion).
Community leaders directly affect prenatal services in their local communities. Twenty-nine leaders in an urban community and 47 in a rural community in Wisconsin were interviewed to determine their knowledge and beliefs about and intent to promote prenatal care for low-income women in their communities. The findings showed that leaders generally assigned high importance to prenatal care for low-income women and intended to promote it during the next six months; and they demonstrated good general knowledge about prenatal care and perceived broad-based community support for their decision to promote it. Disturbingly, many community leaders did not know what percentage of local pregnant women entered prenatal care late or how many medical care providers were available to their constituents on Medicaid, cost was cited as a disadvantage to promoting prenatal care for low-income women, and several leaders in both communities believed that promoting prenatal care would result in low-income women wanting to have more babies or increasing their dependence on free programs. Public health nurses can use the findings of this study in their work with community leaders to ensure prenatal services for low-income populations.


Insulin therapy does not diminish beta-cell damage in the neonatal streptozotocin-injected rat.
In recent years it was suggested that in type 2 diabetes mellitus glucose exerts a direct toxic effect: the hyperglycaemic state itself could contribute to the defects in insulin secretion. We studied the effects of insulin treatment on pancreatic insulin content in neonatal Wistar rats made hyperglycaemic with streptozotocin (SZ, 90 mg/kg, injected intraperitoneally at two days of age). Our hypothesis was that normoglycaemia effected by insulin treatment could diminish the beta-cell damage in these animals. Insulin-treated animals received Lente MC insulin (8 mU/g body weight/day) during the first six days after SZ-injection. At four days of age, blood glucose levels (BG) in the fed state were 5.9 +/- 1.0 mmol/l in control animals (n = 14), whereas all untreated SZ-animals (n = 10) showed BG above 11 mmol/l (mean 15.9 +/- 3.4 mmol/l). In all 11 insulin-treated SZ-animals BG was below 10 mmol/l (mean 4.3 +/- 2.7 mmol/l). At 10 days of age plasma insulin levels did not differ between the three groups. However, pancreatic insulin content was 114 +/- 37 ng/mg tissue in the insulin-treated, and 93 +/- 34 ng/mg tissue (p = ns) in the untreated SZ-animals, compared to 516 +/- 257 ng/mg tissue in the controls (p less than 0.001). BG at four days and the pancreatic insulin contents at 10 days were not correlated. We conclude that intraperitoneal streptozotocin injection in neonatal rats produced marked hyperglycaemia and reduction of pancreatic insulin content. Insulin treatment did not result in improved recovery of the insulin stores in the pancreas. Thus, the additive toxic effect of hyperglycaemia on the beta-cells could not be demonstrated.


Ischaemic stroke management at Al-Shifa Hospital in the Gaza Strip: a clinical audit.
In the 2014 Palestinian annual health report, cerebrovascular accident was ranked as the third leading cause of death in the occupied Palestinian territory. Cerebrovascular accident is also one the most common causes of disability worldwide. Good management decreases mortality and morbidity. The aim of this study was to assess the current management of patients with ischaemic stroke at the Al-Shifa Hospital and to compare this with international guidelines. For this clinical audit, we used simple random sampling to select files of patients admitted with the diagnosis of ischaemic stroke to the Al-Shifa Hospital. Data collection sheets were completed, and clinical practice was compared with the 2013 American Stroke Association guidelines. Between January and June, 2016, 254 patients were admitted with ischaemic stroke, haemorrhagic stroke, or transient ischaemic attack. We selected 55 patient files. The International Classification of Diseases coding for cerebral infarction in patient files was relatively good, with 92% of files correctly coded. However, we found a substantial weakness in the documentation of duration, progression of symptoms (documented in 20% of files only), and physiotherapy assessment. Most essential acute investigations were done on time (for all [100%] patients needing blood count, renal function tests, and CT scan and for 42 [76%] patients needing ECG). However, thrombolytic drugs were not used because they were not available. Long-term antiplatelet therapy was provided properly to 51 (92%) patients discharged from hospital. However, the initial doses of antiplatelet therapy were generally lower than the international recommendations. Findings also showed a marked inconformity of blood pressure management, especially with respect to the treatment decision and the choice of antihypertensive drug. No local guidelines exist. Furthermore, the lack of availability of thrombolysis medication and the poor deviation in blood pressure management show a lack of evidence-based practice. These findings point to the urgent need for the development of local, evidence-based guidelines. None.


Peripheral arterial occlusive disease in general practice: the reproducibility of the ankle-arm systolic pressure ratio.
One of the non-invasive techniques used in the diagnosis of patients with peripheral arterial occlusive disease is the measurement of the Ankle-Arm Systolic Pressure Ratio ("AA-Ratio"). The magnitude of different sources of measurement variation, relevant to clinical practice as well as multi-observer studies, was estimated from a random effects analysis of variance model. Thirty-five GPs and 24 practice assistants performed 503 AA-Ratio measurements on nine patients over a period of nine weeks, using pocket Doppler devices. When the AA-Ratio is used for diagnostic purposes, a 95% prediction interval consisting of the measured value +/- 15-20% AA-Ratio has to be taken into account. Furthermore, when the AA-Ratio is used in the follow-up of a patient with vascular disease, the difference between two subsequent measurements has to be at least 15.6-19.0% AA-Ratio to have an 80% certainty that this difference is not due to (intra-observer) measurement error.


Association of End-stage Renal Disease with Radiographically and Clinically Diagnosed Apical Periodontitis: A Hospital-based Study.
The present study aimed to evaluate the prevalence of apical periodontitis (AP) and endodontic treatment in patients with end-stage renal disease (ESRD) as compared with patients with no history of ESRD. In this cross-sectional study, 40 patients diagnosed with nondiabetic ESRD were included. The control group consisted of 40 age-matched and sex-matched healthy individuals. Digital panoramic radiographs were exposed on patients in both the experimental and control groups. The number of remaining teeth and the prevalence of nonsurgical and/or surgical root canal treatment were evaluated. Also, the presence of AP in all teeth and endodontically treated teeth (ETT) was recorded using the periapical index. Logistic regression was used to determine the possible association between ESRD and AP. AP in at least 1 tooth was found in 29 of the patients with ESRD (73%) and in 16 of the control patients (40%) (odds ratio [OR] = 3.9, P < .05). In 21 (52%) patients with ESRD in the experimental group, at least 1 ETT was diagnosed with AP. In the control group, 11 (28%) individuals had AP affecting at least 1 of the ETT (OR = 2.9, P < .05). Adjusted for the number of teeth and endodontic treatment, ESRD was significantly associated with the presence of AP (P < .05; OR = 2.6; 95% confidence interval, 1.43-4.8). Also, the number of teeth with AP was significantly associated with the urea serum level in the experimental group (P < .05, β coefficient = 4.35). AP was significantly more prevalent in the experimental group. This may suggest that ESRD could possibly alter the pathogenesis of AP. However, these findings do not confirm the presence of any cause-and-effect relationship between these conditions. Also, considering the modifying effect of AP on urea serum level, the treatment of AP could be incorporated in the treatment planning of patients with ESRD.


Precursors to Molecular Slip on Smooth Hydrophobic Surfaces.
Experiments and simulations suggest that simple liquids may experience slip while flowing near a smooth, hydrophobic surface. Here we show how precursors to molecular slip can be observed in the complex response of a liquid to oscillatory shear. We measure both the change in frequency and bandwidth of a quartz crystal microbalance during the growth of a single drop of water immersed in an ambient liquid. By varying the hydrophobicity of the surface using self-assembled monolayers, our results show little or no slip for water on all surfaces. However, we observe excess transverse motion near hydrophobic surfaces due to weak binding in the corrugated surface potential, an essential precursor to slip. We also show how this effect can be easily missed in simulations utilizing finite-ranged interaction potentials.


How to analyze protein complexes by 2D blue native SDS-PAGE.
Natural compartmentalization makes proteome analysis of the cell, cell organelles and organelle subfractions possible. Protein complexes are the basis for the next level of compartmentalization that can be addressed well with proteomic technology. Protein complexes organize and maintain the cellular and organelle functions on all levels of complexity in time and space. Cell development and division, transcription and translation, respiration and photosynthesis, transport and metabolism can be defined by the activity of protein complexes. Since a large part of the protein complexes of the cell body are inserted in lipid membrane phases, isolation, separation and protein subunit identification were difficult to address. Blue native polyacrylamide gel electrophoresis (BN-PAGE) provides us with the technology for high resolution separation of membrane protein complexes. Here, we show that high resolution separation of protein complexes by BN-PAGE requires the establishment of a detailed solubilisation strategy. We show that BN/SDS-PAGE provides the scientist with a high resolution array of protein subunits which allows analysis of the specific subunit stoichiometry of a protein complex as well as the assembly of protein complexes by standard protein detection methodology like DIGE, gelblot analysis and mass spectrometry. We envision BN-PAGE to precede classical 2D IEF/SDS-analysis for detailed characterization of membrane proteomes.


The Synthesis and Photophysical Analysis of a Series of 4-Nitrobenzochalcogenadiazoles for Super-Resolution Microscopy.
A series of 4-nitrobenzodiazoles with atomic substitution through the chalcogen group were synthesised and their photophysical properties analysed with a view for use in single-molecule localisation microscopy. Sub-diffraction resolution imaging was achieved for silica nanoparticles coated with each dye. Those containing larger atoms were favoured for super-resolution microscopy due to a reduced blink rate (required for stochastic events to be localised). The sulfur-containing molecule was deemed most amenable for widespread use due to the ease of synthetic manipulation compared to the selenium-containing derivative.


Traits and climate are associated with first flowering day in herbaceous species along elevational gradients.
Phenological responses to changing temperatures are known as "fingerprints of climate change," yet these reactions are highly species specific. To assess whether different plant characteristics are related to these species-specific responses in flowering phenology, we observed the first flowering day (FFD) of ten herbaceous species along two elevational gradients, representing temperature gradients. On the same populations, we measured traits being associated with (1) plant performance (specific leaf area), (2) leaf biochemistry (leaf C, N, P, K, and Mg content), and (3) water-use efficiency (stomatal pore area index and stable carbon isotopes concentration). We found that as elevation increased, FFD was delayed for all species with a highly species-specific rate. Populations at higher elevations needed less temperature accumulation to start flowering than populations of the same species at lower elevations. Surprisingly, traits explained a higher proportion of variance in the phenological data than elevation. Earlier flowering was associated with higher water-use efficiency, higher leaf C, and lower leaf P content. In addition to that, the intensity of shifts in FFD was related to leaf N and K. These results propose that traits have a high potential in explaining phenological variations, which even surpassed the effect of temperature changes in our study. Therefore, they have a high potential to be included in future analyses studying the effects of climate change and will help to improve predictions of vegetation changes.


Kinetics of phase transformation on a Bethe lattice.
A kinetic Ising model is applied to the description of phase transformations on a Bethe lattice. A closed set of kinetic equations for a model with the coordination number q=3 is obtained using a procedure developed in a previous paper. For T close to Tc(T>Tc), where Tc is the phase transition temperature, and zero external field (absence of supersaturation), the rate of phase transformation (RPT) for small deviations from equilibrium is independent of time and tends to zero as (T-Tc). At T=Tc, the RPT depends on time and for large times behaves as t(-1). For T<Tc, we examine the transformation from the initial state with almost all spins "down" to the state with almost all spin "up" after the external field jumped from Bi<0 to Bf>0. The role of different mechanisms responsible for growth (decay), splitting (coagulation), and creation (annihilation) of clusters are examined separately. In all cases there is a critical value Bc of the external field, such that the phase transformation takes place only for Bf>Bc. This result is also obtained from a more simple consideration involving spherical-like clusters on a Bethe lattice. The characteristic time tR at which the polarization becomes larger than zero diverges as (Bf-Bc)(-b) for Bf-->Bc with b=0.47. The RPT has a rapid growth near tR and remains constant for t>tR. The average cluster size (number of spins in a cluster) exhibits a rapid unrestricted growth at a time td approximately tR which indicates the creation of infinite clusters. The only exception to the latter behavior occurs when the kinetics is dominated by cluster growth and decay processes. In this case, the average cluster size remains finite during the transformation process. In contrast to the classical theory, the present approach does not separate the processes of creation of clusters of critical size (nucleation) and of their growth, both being accounted for by the kinetic equations employed.


Comparative insights into the saccharification potentials of a relatively unexplored but robust Penicillium funiculosum glycoside hydrolase 7 cellobiohydrolase.
GH7 cellobiohydrolases (CBH1) are vital for the breakdown of cellulose. We had previously observed the enzyme as the most dominant protein in the active cellulose-hydrolyzing secretome of the hypercellulolytic ascomycete-Penicillium funiculosum (NCIM1228). To understand its contributions to cellulosic biomass saccharification in comparison with GH7 cellobiohydrolase from the industrial workhorse-Trichoderma reesei, we natively purified and functionally characterized the only GH7 cellobiohydrolase identified and present in the genome of the fungus. There were marginal differences observed in the stability of both enzymes, with P. funiculosum (PfCBH1) showing an optimal thermal midpoint (Tm) of 68 °C at pH 4.4 as against an optimal Tm of 65 °C at pH 4.7 for T. reesei (TrCBH1). Nevertheless, PfCBH1 had an approximate threefold lower binding affinity (Km), an 18-fold higher turnover rate (kcat), a sixfold higher catalytic efficiency as well as a 26-fold higher enzyme-inhibitor complex equilibrium dissociation constant (Ki) than TrCBH1 on p-nitrophenyl-β-d-lactopyranoside (pNPL). Although both enzymes hydrolyzed cellooligomers (G2-G6) and microcrystalline cellulose, releasing cellobiose and glucose as the major products, the propensity was more with PfCBH1. We equally observed this trend during the hydrolysis of pretreated wheat straws in tandem with other core cellulases under the same conditions. Molecular dynamic simulations conducted on a homology model built using the TrCBH1 structure (PDB ID: 8CEL) as a template enabled us to directly examine the effects of substrate and products on the protein dynamics. While the catalytic triads-EXDXXE motifs-were conserved between the two enzymes, subtle variations in regions enclosing the catalytic path were observed, and relations to functionality highlighted. To the best of our knowledge, this is the first report about a comprehensive and comparative description of CBH1 from hypercellulolytic ascomycete-P. funiculosum NCIM1228, against the backdrop of the same enzyme from the industrial workhorse-T. reesei. Our study reveals PfCBH1 as a viable alternative for CBH1 from T. reesei in industrial cellulase cocktails.


Acute cardiac herniation following pneumonectomy.
Pneumonectomy with partial pericardiectomy may result in herniation of the heart through the pericardial defect, leading to cardiovascular collapse and death. Awareness of this grave potential complication and familarity with its clinical and roentgenographic features should permit prompt diagnosis and facilitate lifesaving repeat thoracotomy.


Effects of ceramic thickness and curing unit on light transmission through leucite-reinforced material and polymerization of dual-cured luting agent.
This study investigated the influence of ceramic thickness and curing unit on light transmission through leucite-reinforced material and polymerization of a dual-cured resin luting agent. Discs of Empress Esthetic (Ivoclar Vivadent) of 0.7-, 1.4- and 2-mm thickness were prepared. Variolink II (Ivoclar Vivadent) was placed in a 1-mm-thick cylindrical mold, and light-activated through ceramic for 40 s, using QTH or LED units. The samples were divided into dual, light, and chemically-polymerized control groups. Knoop hardness indentations were made on the top and bottom surfaces. Data were subjected to split-plot design three-way ANOVA and Tukey's test (P < 0.05). The light spectrum transmitted through ceramic was obtained using a spectrometer. Samples activated through 1.4-and 2-mm-thick discs showed lower hardness than all others groups, except for the chemical control group. Dual and light-polymerized control samples showed similar hardness to those activated through the 0.7-mm ceramic, whereas chemically polymerized control samples showed similar hardness to those activated through 1.4- and 2-mm ceramics. No significant differences in hardness were detected between the curing units or between the top and bottom layers. No significant alteration in the light spectrum profile was observed for both units, irrespective of the ceramic thickness.


Presentation of research in anesthesia: Culmination into publication?
To assess the quality of research presentations made in conferences, its success or failure to be published in a peer-reviewed journal is a well-accepted marker. However, there is no data regarding the publication of research presentations made in Indian conferences of anesthesiology. The primary objective was to determine publication rate of research presented at the largest and best attended national conference in anesthesiology, the Indian Society of Anaesthesiologists' Conference (ISACON), and also compare it with the rate from an international conference American Society of Anesthesiologists (ASA annual meeting) held in the same year. All 363 abstracts presented as poster or podium presentations at the ISACON, and an equal number of randomly selected abstracts presented at ASA annual meeting were searched on Pubmed and Google Scholar for their full-text publications in peer-reviewed journals using a standardized search strategy. As secondary observations, abstracts were assessed for completeness by noting certain components central to research methodology. Also, changes between abstract of the presentation and published paper were noted with respect to certain components. The publication rate of presentations at ISACON and ASA meetings was 5% and 22%, respectively. The abstracts from ISACON lacked central components of research such as methods and statistical tests. The commonest change in the full-text publications as compared with the original abstract from both conferences was a change in authorship. Steps are required to augment full-text publication of Indian research, including a more rigorous peer review of abstracts submitted to ISACON to ensure their completeness.


Domiciliary experience of the Target Inhalation Mode (TIM) breathing maneuver in patients with cystic fibrosis.
The time requirements for multiple daily nebulizer treatments are important impediments to the quality of life for most patients with cystic fibrosis (CF). The I-neb Adaptive Aerosol Delivery (AAD) System can be used with a new mode of breathing during inhalation of aerosol, the Target Inhalation Mode (TIM). As a function of the TIM algorithm, the patient is guided to a slow and deep inhalation, which can result in shorter treatment times. This study was conducted as a 3-month patient handling study of the I-neb AAD System in 42 patients with CF aged 12-57 years. The I-neb AAD System was supplied in both the standard Tidal Breathing Mode (TBM), and in TIM. Patients were trained to use the I-neb AAD System in TIM for the delivery of all their inhaled medications, but if they were not comfortable with the TIM maneuver they could change to the TBM maneuver. The primary variables were compliance with the correct use of the I-neb AAD System, and treatment times. The secondary variables were based on study questionnaires at the end of the study and covered ease of use, patient confidence, and patient satisfaction with the I-neb AAD System. There were a total of 10,240 complete treatments and of these, 8979 (88%) were in TIM. Compliance with the correct use of the I-neb AAD System was 97.6%. The mean treatment time for complete treatments in TIM was 4.20 min, compared with 6.83 min when using the I-neb AAD System in TBM. The responses to the questionnaires indicated that over 77% of the patients found the I-neb AAD System in TIM to be either: very easy, easy, or acceptable to use. The results demonstrated that by using the I-neb AAD System in TIM, a 40-50% reduction of nebulizer treatment times, and a high level of compliance could be achieved. The results also showed that the patients found the I-neb AAD System easy to use.


Disifin (sodium tosylchloramide) and Toll-like receptors (TLRs): evolving importance in health and diseases.
Disifin has emerged as a unique and very effective agent used in disinfection of wounds, disinfection of surfaces, materials and water, and other substances contaminated with almost every type of pathogenic microorganism ranging from viruses, bacteria, fungi and yeast, and, very possibly, protozoan parasites, as well. The major active component of Disifin is tosylchloramide sodium (chloramine T). However, the mechanism by which Disifin suppresses the activities of pathogenic microbial agents remains enigmatic. The molecular mechanisms, and the receptors and the signal transducing pathways responsible for the biological effects of Disifin are largely unknown. Despite considerable advances, enormous investigative efforts and large resources invested in the research on infectious diseases, microbial infection still remains a public health problem in many parts of the world. The exact nature of the pathogenic agents responsible for many infectious diseases, and the nature of the receptors mediating the associated inflammatory events are incompletely understood. Recent advances in understanding the molecular basis for mammalian host immune responses to microbial invasion suggest that the first line of defense against microbes is the recognition of pathogen-associated molecular patterns (PAMPs) by a family of transmembrane pattern-recognizing and signal transducing receptor proteins called Toll-like receptors (TLRs). The TLR family plays an instructive role in innate immune responses against microbial pathogens, as well as the subsequent induction of adaptive immune responses. TLRs mediate recognition and inflammatory responses to a wide range of microbial products and are crucial for effective host defense by eradication of the invading pathogens. Now, recent updates demonstrated the ability of Disifin-derived products, Disifin-Animal and Disifin-Pressant to effectively suppress the progression and activities of Chikungunya fever and that of avian influenza A virus [A/cardialis/Germany/72, H7N1: the agent of a highly pathogenic avian influenza (HPAI)] infection, respectively. Overall, the above findings led me to suggest that Disifin and TLRs may mechanistically overlap in the processes of executing their functions against pathogenic microbial organisms. Thus, elucidating and better understanding of the molecular underpinnings responsible for the biochemical effects of Disifin-products, and the nature and mode of the interaction(s) of Disifin with TLRs in the process of exerting their biological effects may open a novel dimension in the research of infectious diseases, which may provide novel therapeutic targets for the prevention and treatment of a wide range of infectious diseases.


Separation of protein synthesis in meningopneumonitisgent from that in L cells by differential susceptibility to cycloheximide.
Cycloheximide had no effect on multiplication of the meningopneumonitis agent in L cells in concentrations which eliminated over 90% of the protein synthesis in the host cells. Infected L cells treated with cycloheximide, however, incorporated labeled amino acids into the trichloroacetic acid-insoluble fraction. This incorporation was attributed to the biosynthetic activity of the meningopneumonitis agent. Synthesis of meningopneumonitis protein was abolished by chloramphenicol and chlortetracycline, inhibitors of bacterial protein synthesis, at concentrations which did not inhibit protein synthesis in L cells. Protein synthesis in the meningopneumonitis agent was sustained at a high rate when the host cells remained viable and declined as the L cells died. Overall host protein synthesis was not inhibited by multiplication of the meningopneumonitis agent.


[On the effect of Chinese lacquer upon the cell division of root tip of Allium cepa].
Chinese Lacquer, as a fine coating, has been studied and applied for thousands years. The allergic reaction in Chinese Lacquer on the human skin has also been known early. The reaction of Chinese Lacquer on mitosis of cell in plant meristem have not been reported yet and was carefully studied in this paper. The result showed that Chinese Lacquer induced severe abnormality of mitotic division in Allium cepa root tips. This was more obvious in the anaphase and telophase, especially in the former phase laggard chromosomes, chromosome bridges, acentric fragments and polypolar distribution could be seen frequently. A lot of polynuclear bodies were observed in the telophase. Therefore, we think that the Chinese Lacquer can be used as a plant cell mutagen, and suggest geneticists and physiologists to do more researches on the effects of Chinese Lacquer at the genetic variation, metabolism etc.


Skeletal muscle capillary hemodynamics from rest to contractions: implications for oxygen transfer.
Muscle contractions evoke an immediate rise in blood flow. Distribution of this hyperemia within the capillary bed may be deterministic for muscle O(2) diffusing capacity and remains unresolved. We developed the exteriorized rat (n = 4) spinotrapezius muscle for evaluation of capillary hemodynamics before (rest), during, and immediately after (post) a bout of twitch contractions to resolve (second-by-second) alterations in red blood cell velocity (V(RBC)) and flux (f(RBC)). Contractions increased (all P < 0.05) capillary V(RBC) (rest: 270 +/- 62 microm/s; post: 428 +/- 47 microm/s), f(RBC) (rest: 22.4 +/- 5.5 cells/s; post: 44.3 +/- 5.5 cells/s), and hematocrit but not the percentage of capillaries supporting continuous RBC flow (rest: 84.0 +/- 0.7%; post: 89.5+/-1.4%; P > 0.05). V(RBC) peaked within the first one or two contractions, whereas f(RBC) increased to an initial short plateau (first 12-20 s) followed by a secondary rise to steady state. Hemodynamic temporal profiles were such that capillary hematocrit tended to decrease rather than increase over the first approximately 15 s of contractions. We conclude that contraction-induced alterations in capillary RBC flux and distribution augment both convective and diffusive mechanisms for blood-myocyte O(2) transfer. However, across the first 10-15 s of contractions, the immediate and precipitous rise in V(RBC) compared with the biphasic and prolonged increase of f(RBC) may act to lower O(2) diffusing capacity by not only reducing capillary transit time but by delaying the increase in the instantaneous RBC-to-capillary surface contact thought crucial for blood-myocyte O(2) flux.


Diversification of piRNAs expressed in PGCs and somatic cells during embryonic gonadal development.
piRNAs are small non-coding RNAs known to play a main role in defence against transposable elements in germ cells. However, other potential functions, such as biogenesis and differences in somatic and germline expression of these regulatory elements, are not yet fully unravelled. Here, we analysed a variety of piRNA sequences detected in mouse male and female primordial germ cells (PGCs) and gonadal somatic cells at crucial stages during embryonic differentiation of germ cells (11.5-13.5 days post-coitum). NGS of sncRNA and bioinformatic characterization of piRNAs from PGCs and somatic cells, in addition to piRNAs associated with TEs, indicated functional diversification in both cell types. Differences in the proportion of the diverse types of piRNAs are detected between somatic and germline during development. However, the global diversified patterns of piRNA expression are mainly shared between germ and somatic cells, we identified piRNAs related with molecules involved in ribosome components and translation pathway, including piRNAs derived from rRNA (34%), tRNA (10%) and snoRNA (8%). piRNAs from both tRNA and snoRNA are mainly derived from 3' and 5' end regions. These connections between piRNAs and rRNAs, tRNAs or snoRNAs suggest important functions of specialized piRNAs in translation regulation during this window of gonadal development.


The 3' long terminal repeat of a transcribed yet defective endogenous retroviral sequence is a competent promoter of transcription.
Although actively transcribed and present as multiple genomic copies, a distinct class of endogenous murine leukemia virus-related sequence does not give rise to infectious virus. Since the long terminal repeat at the 3' terminus provides the transcriptional start site after reintegration, we determined the structure and potential promoter activity of that sequence obtained from cDNA of endogenous retroviral transcripts. These studies demonstrate that the distinctive 3' long terminal repeat sequence of these transcripts could serve as an effective promoter of transcription and, therefore, may not be the primary defect in the infectious cycle of retroviral replication but may result in the propagation of these endogenous retroviral sequences in the genome as retrotransposons.


Attentional bias training and cue reactivity in cigarette smokers.
Attentional bias for drug-related cues has been associated with drug maintenance and relapse. We investigated whether attentional bias for smoking-related stimuli could be altered using a modified visual probe task in cigarette smokers. We also sought to determine whether changes in attentional bias were associated with changes in subsequent craving and cue reactivity. Male and female (n=54) current smokers (>or=5 cigarettes per day), aged between 18 and 40 years, were recruited from staff and students of the University of Bristol, and from the general population. Participants attended a single test session and completed an attentional training procedure in which they were either trained to attend to smoking-related pictorial stimuli (attend group) or to neutral pictorial stimuli (avoid group). Group allocation was randomized. Following attentional training, participants underwent a smoking cue exposure procedure in which they were exposed to smoking-related stimuli. Subjective measures of mood and craving were taken at baseline and before and after cue exposure. Participants then smoked a cigarette and smoking topography was measured. Attentional training increased attentional bias among participants in the attend group, and decreased attentional bias among those in the avoid group. There were also differences between the attend and avoid groups in post-training changes in craving during exposure to in vivo smoking cues, reflecting greater increases in craving in the attend group, although these effects were observed in males only. These data are the first to show alterations in attentional bias for smoking-related stimuli following a modified visual probe training procedure. Furthermore, post-training group differences in subjective craving suggest potential clinical utility of training procedures, although these effects may operate only in males. Future research should investigate whether multiple training sessions enhance post-training reductions in craving and cue reactivity, and the longer-term persistence of training effects.


Statistical Approaches to Study Exposome-Health Associations in the Context of Repeated Exposure Data: A Simulation Study.
The exposome concept aims to consider all environmental stressors simultaneously. The dimension of the data and the correlation that may exist between exposures lead to various statistical challenges. Some methodological studies have provided insight regarding the efficiency of specific modeling approaches in the context of exposome data assessed once for each subject. However, few studies have considered the situation in which environmental exposures are assessed repeatedly. Here, we conduct a simulation study to compare the performance of statistical approaches to assess exposome-health associations in the context of multiple exposure variables. Different scenarios were tested, assuming different types and numbers of exposure-outcome causal relationships. An application study using real data collected within the INMA mother-child cohort (Spain) is also presented. In the simulation experiment, assessed methods showed varying performance across scenarios, making it challenging to recommend a one-size-fits-all strategy. Generally, methods such as sparse partial least-squares and the deletion-substitution-addition algorithm tended to outperform the other tested methods (ExWAS, Elastic-Net, DLNM, or sNPLS). Notably, as the number of true predictors increased, the performance of all methods declined. The absence of a clearly superior approach underscores the additional challenges posed by repeated exposome data, such as the presence of more complex correlation structures and interdependencies between variables, and highlights that careful consideration is essential when selecting the appropriate statistical method. In this regard, we provide recommendations based on the expected scenario. Given the heightened risk of reporting false positive or negative associations when applying these techniques to repeated exposome data, we advise interpreting the results with caution, particularly in compromised contexts such as those with a limited sample size.


Pharmacodynamics and toxicity of chlorine in drinking water in the rat.
Chlorine interacts with organic materials in surface water, leading to the formation of trihalomethanes, that may be carcinogenic. Studies were conducted to investigate the pharmacodynamics and toxicity of chlorine (0, 1, 10, 100 mg 1(-1] in drinking water in rats. Blood glutathione (GSH) was significantly decreased after 6 months of treatment and this effect persisted after 1 year treatment in the 10 and 100 mg 1(-1) groups. Treatment groups showed an increase in blood osmotic fragility. The acute study revealed that GSH was significantly decreased as early as 30 min after the administration of 30 and 120 micrograms chlorine. The effect was maintained up to 1 h. However, the GSH level returned to control value by 2 h. Blood osmotic fragility of the acute exposure was incresed after 15 min and was without change after 30 min. Of the hematological parameters only the red blood cell count and hematocrit were significantly decreased in the 100 mg 1(-1) group after 3 months of treatment. An examination of blood chloroform content in all the groups after 4, 6, 9 and 12 months showed no significant difference compared with the control. Chlorine administered chronically in drinking water for 3 months increased the incorporation of 3H-thymidine into nuclei of rat kidney and testes in the 100 mg 1(-1) group.


Monoassociation of SCID mice with Helicobacter muridarum, but not four other enterics, provokes IBD upon receipt of T cells.
Recently, a number of animal models for different aspects of inflammatory bowel disease (IBD) have been developed. The aim of this study was to use one of these to determine whether particular, ostensibly innocuous, intestinal bacteria could provoke or exacerbate IBD. Conventionally reared C.B17 SCID mice were compared with germ-free and gnotobiotic mice, monoassociated with 1 of 5 intestinal bacteria, after transfer of CD45RB(high) CD4(+) T cells from conventionally reared congenic BALB/c mice. Recipient mice were monitored over 7-12 weeks for clinical signs of IBD, and tissues were analyzed by histology/flow cytometry for abnormal inflammation and CD4(+) T cell outgrowth. Neither germ-free mice nor mice monoassociated with segmented filamentous bacteria, Ochrobactrum anthropi, a nonpathogenic mutant of Listeria monocytogenes, or Morganella morganii developed any signs of IBD. In contrast, mice monoassociated with Helicobacter muridarum displayed an accelerated development of IBD in 5-6 weeks compared with 8-12 weeks observed in conventionally reared mice. The outgrowth of CD4(+) T cells in spleen and large intestine of H. muridarum monoassociated mice, as well as in conventionally reared mice was significantly higher than that in the other monoassociated mice. Among the intestinal bacteria tested, H. muridarum can serve as a provocateur of IBD in this model.


Molecular analysis of an extended family with type IA (tyrosinase-negative) oculocutaneous albinism.
We have analyzed the tyrosinase coding region of three individuals having Type IA OCA within an extended family using genomic DNA amplification and dideoxy sequencing. Two of the affected individuals are dizygotic twins. All three have a common missense mutation at codon 81 (Pro----Leu) within exon I. The twins have a second missense mutation at codon 371 (Asn----Thr) within exon III and the third individual has a second missense mutation at codon 47 (Gly----Asp) within exon I. For each of these three individuals, the loss of enzyme function is the result of two different mutations, showing that they are compound heterozygotes of two mutant tyrosinase alleles.


Overexpression of repressive cAMP response element modulators in high glucose and fatty acid-treated rat islets. A common mechanism for glucose toxicity and lipotoxicity?
The hyperlipidemia and hyperglycemia of the diabetic state accelerate beta-cell dysfunction, yet the mechanisms are not fully defined. We used rat islet-specific oligonucleotide arrays (Metabolex Rat Islet Genechips) to identify genes that are coordinately regulated by high glucose and free fatty acids (FFA). Exposure of rat islets to FFA (125 microM for 2 days) or glucose (27 mM for 4 days) reduced glucose-stimulated insulin secretion by 70 +/- 5 and 40 +/- 4%, respectively, relative to control-cultured islets. These treatments also substantially reduced the insulin content of the islets. Islet Genechips analysis revealed that the mRNA levels of cAMP response element modulator (CREM)-17X and inducible cAMP early repressor were significantly increased in both 27 mM glucose- and FFA-treated islets. Removing FFA or high glucose from the culture medium restored glucose-stimulated insulin secretion and the mRNA levels of the two CREM repressors to normal. Northern blot analysis revealed a 5-fold increase in the abundance of CREM-17X mRNA and a concomitant 50% reduction in the insulin mRNA in FFA-treated islets. Transient transfection of the insulin-secreting beta HC9 cells with CREM-17X suppressed rat insulin promoter activity by nearly 50%. Overexpression of CREM-17X in intact islets via adenovirus infection decreased islet insulin mRNA levels and insulin content and resulted in a significant decrease in glucose- or KCl-induced insulin secretion. Taken together, these data suggest that up-regulation of CREM repressors by either FFA or high glucose exacerbates beta-cell failure in type 2 diabetes by suppressing insulin gene transcription.


Novel multidisciplinary approach for treatment of langerhans cell histiocytosis of the skull base.
Langerhans cell histiocytosis frequently manifests as lesions of the skull. The disease can present with a wide spectrum of forms, from an isolated eosinophilic granuloma to multiple lesions with diffuse systemic involvement. The authors report the case of a 12-year-old boy with a 1-month history of left temporal and periorbital pain and headaches. Noncontrast computed tomography of the head was done at the time of initial presentation and was interpreted as normal. Over the next month, the patient continued to have headaches and periorbital swelling and began having bloody discharge from his nose. Magnetic resonance imaging of the brain ordered by his pediatrician showed a lesion in the left infratemporal fossa, left orbit, and sphenoid bone. The lesion was biopsied and confirmed to be Langerhans cell histiocytosis. We describe a novel multidisciplinary approach for treatment of this tumor.


PtNPs as Scaffolds to Regulate Interenzyme Distance for Construction of Efficient Enzyme Cascade Amplification for Ultrasensitive Electrochemical Detection of MMP-2.
The high catalytic efficiency of enzyme cascade reaction mainly depends on optimal interenzyme distance regulated by the special scaffolds. In this work, the rigid PtNPs with different sizes were employed as scaffolds to regulate interenzyme distance for efficient enzyme cascade amplification to construct electrochemical biosensor for sensitive detection of matrix metalloproteinases-2 (MMP-2), which overcame the drawbacks of instable construction and sophisticated preparation induced by conventional scaffolds such as metal-organic frameworks (MOFs), DNA nanostructures. Here, cucurbit[7]uril functionalized PtNPs (CB[7]@PtNPs) was utilized to load ferrocene (Fc)-labeled horseradish peroxidase (HRP) and glucose oxidase (GOx) via host-guest interaction between Fc and CB[7], respectively, resulting in the formation of a stable three-dimensional netlike structure containing amounts of enzymes. Interestingly, the enzyme cascade reaction regulated by 10 nm PtNPs as scaffold showed highly catalytic efficiency. Meanwhile, the PtNPs could also serve as catalyst to accelerate the enzyme cascade reaction with further enhanced catalytic efficiency. As a result, the proposed biosensor exhibited excellent sensitivity with a wide linear range of 0.1 pg·mL-1 to 20 ng·mL-1 and a detection limit of 0.03 pg·mL-1 for MMP-2. Such a strategy opened a new avenue for adopting metal nanoparticles to regulate interenzyme distance for efficient enzyme cascade amplification, thus providing a universal and easy operating method for sensitively detecting various targets such as DNA, metal ion, and protein.