Individual Susceptibility to Dental Caries: The Vipeholm Study.
The evidence for a genetic component to dental caries is in comparison much less explored in the literature than the other classically described components of the disease: microbiota and diet. Diet can be said to have been conclusively linked to the etiology of dental caries by the results of the Vipeholm study, which did not deal with any microbial aspect of the disease. What is much less emphasized is that these same results provided one of the most robust lines of evidence that exist in support of a genetic component to dental caries. The results of the study showed great variability, with some study participants showing a dramatic increase in the establishment of new carious lesions under conditions that did not affect the majority of the other subjects. Similarly, highly cariogenic conditions due to a diet rich in sugars did not cause an increase in new carious lesions in other participants. The best explanation for these variable results is the existence of individual biological factors (genetic variation) modulating the disease. This chapter also comments on the ethical controversy surrounding the study and the need for finally intervening on the effects of sugars in oral health.


Origin and mitigation of wind noise on balloon-borne infrasound microbarometers.
High-altitude monitoring of low-frequency acoustic waves (infrasound) on Earth has regained prominence in recent years, primarily driven by improvements in light-weight sensor technology and advances in scientific ballooning techniques. Balloon-borne infrasound monitoring is also being proposed as a remote sensing technique for planetary exploration. Contrary to ground-based infrasound monitoring, the infrasound noise background in the stratosphere as measured by a balloon remains uncharacterized and the efficacy of wind noise mitigation filters has not been investigated. In this study, an analysis of pressure data collected using infrasound microbarometers during the flight of a long-duration zero pressure balloon is presented. A dramatic reduction of background noise in the stratosphere is demonstrated and it is shown that wind noise mitigation filters are not effective at reducing wind noise under these conditions. Results from this study demonstrate stratospheric balloons as a low-noise platform for infrasound monitoring and motivate the development of improved noise mitigation tools.


Unified pharmacogenetics-based parent-metabolite pharmacokinetic model incorporating acetylation polymorphism for talampanel in humans.
The N-acetylation of the noncompetitive AMPA antagonist talampanel (TLP) represents a route of varying significance in various species. For a detailed analysis in humans, plasma concentrations of TLP and its N-acetyl metabolite (NAc-TLP) were measured for up to 48 h after administration of a single oral dose of 75 mg in 28 healthy volunteers following genotyping for the N-acetyltansferase NAT2 isozymes (alleles NAT2*4, *5, *6, and *7). Unified parent-metabolite pharmacokinetic (PK) models that allowed three different rates of acetylation were used to simultaneously fit plasma levels for both the parent drug and its metabolite following genotype-based classification as slow, intermediate, or fast acetylator. A perfect correspondence was found between the phenotype inferred from genotyping and the phenotype determined by using plasma metabolite-to-parent molar ratios indicating that this route of metabolism is indeed mediated by NAT2. Linear parent-metabolite PK models (first-order input, first-order elimination through two parallel routes one of which is through a metabolite with polymorphic rate of formation) gave adequate and sufficiently consistent fit. Parameters obtained suggest that for TLP in humans, N-acetylation represents only about 1/4th of the total elimination even in true (*4/*4 homozygous) fast acetylators, acetylation is about 8-12 times faster in fast and 3-6 times faster in intermediate acetylators than in slow acetylators, and the N-acetyl metabolite is eliminated faster than the parent drug. Such PK models can provide quantitative estimates of relative in vivo metabolism rates for routes catalyzed by functionally polymorphic enzymes.


[Concordance in the treatment of schizophrenia].
Rates of medication nonadherence among outpatients with schizophrenia have been found to approach 50% during the first year after hospital discharge. Poor adherence with antipsychotic medications increases the risk of relapse. Nonadherent patients have an average risk of relapse that is 3.7 times greater than that of adherent patients. Studies results have demonstrated a rate of rejection to one year of 40% to 50%. These percentages are increased to 75% when the time is more than a year of the beginning treatment. Outpatients with schizophrenia who form strong alliances with their therapists seem to be more likely to comply with prescribed medications than patients who form weaker alliances. The significant progresses in the treatments with drugs can be possible, through improving the profile of adverse effects, search of alternative routes of administration and global improvement of the effectiveness of the medication. The additional support services as those proportionate ones for programs of treatment of the community, the family therapy, community services and the general help with strategies of compliance, they have a clear paper and they improve the results.


Adrenocortical-pituitary hybrid tumor causing Cushing's syndrome.
We describe the first case of an adrenocortical-pituitary hybrid tumor causing Cushing's syndrome in a 17-yr-old boy. Adrenal vein sampling confirmed elevated secretion of both cortisol and ACTH precursors from a right adrenal mass, whereas pituitary ACTH levels, as determined by bilateral inferior petrosal sinus samples (IPSS), were unresponsive to CRH and equal to peripheral levels. There was no biochemical or histological evidence for a pheochromocytoma, but, rather, the tumor demonstrated lipid-rich clear cells characteristic of an adrenocortical adenoma. Immunohistochemical analysis revealed ACTH immunoreactivity and synaptophysin proteins in the tumor. Isolation of tumor cells by the novel technique of laser capture microdissection and subsequent RT-PCR showed expression of POMC messenger ribonucleic acid and cytochrome p450 enzyme messenger ribonucleic acid within the same cells. Finally, ultrastructural analysis provided ultimate proof for adrenocortical-pituitary hybrid cells exhibiting the characteristic vesicular mitochondria and abundant smooth endoplasmic reticulum of steroid cells and the typical secretory granules of corticotrophs within the cytoplasm of the same cells. The adrenocortical tumor expressed the pituitary transcription factor pituitary homeobox factor 1 and the steroidogenic factor 1. The intermingling of the centrally located ectodermally derived pituitary tissue with the mesodermally derived adrenocortical tissue in this adenoma suggests a hitherto unrecognized genetic and phenotypic plasticity within the hypothalamic-pituitary-adrenal axis.


Implantation of an EEG telemetric transmitter in the rat.
We describe a method of implanting a telemetric transmitter of EEG signals in the laboratory rat. The transmitter is available commercially and may be implanted in a subcutaneous pocket prepared in the hindermost dorsal region of the animal. The two stainless steel electrodes connected to the transmitter are led to the cranium through a subcutaneous tunnel, and are fixed to the cranium bones. EEG signals are collected by a receiver placed under the cage; reception of the signals is improved by suitably placed antennae. The method allows recording of EEG data from a free-moving rat during the expression of behavioral tasks in a limited space.


Transient divergent flow and transport in an infinite anisotropic porous formation.
When seeking to predict plume geometry resulting from fluid injection through partially penetrating wells, it is common to assume a steady-state spherically diverging flow field. In reality, the flow field is transient. The steady-flow assumption is likely to cause overestimation of injection plume radius since the accommodation of fluid by increases in porosity and fluid density is ignored. In this paper, a transient solution is developed, resulting in a nonlinear ordinary differential equation expressing plume radius as a function of time. It is shown that the problem can be fully described by one type curve. A critical time, t(c), is identified at which the percentage error of the steady-state flow solution compared to the fully dynamic problem is less than 1%. Only for large injection rates and low permeabilities, does t(c) become greater than 1 h. Nevertheless, an improved approximate solution is obtained by a simple linearization procedure. The critical time, t(c) for the new approximate solution is 0.3% of that required for the steady-state flow solution.


Outcomes of primary angle closure glaucoma management.
To investigate the results of primary angle closure glaucoma (PACG) management on intraocular pressure (IOP). This was a cross-sectional study conducted in the ophthalmology Department, Tabriz Medical Sciences University, Nikookary Eye Hospital, Tabriz, Iran. Subjects with angle closure were treated with YAG laser iridotomy at the time of diagnosis. These patients were re-examined in follow-up period for Patency of iridotomy, intraocular pressure (IOP), visual acuity, gonioscopic findings and automated threshold perimetry and peripapillary RNFL thickness for detecting progression. Iridotomy was classified unsuccessful in eyes where further surgical intervention was required or in which there was a loss of visual acuity to < 3/60 from glaucomatous optic neuropathy. All primary angle-closure glaucoma subjects (244 eyes) who had undergone Nd:YAG laser iridotomy between 2005 and 2008 were studied. A total of 244 patients were studied. The mean age of the study population was 64.60+9. 49 years with a median of 66 years (range: 45-80). The mean follow-up period was 21.59 +/- 12.37 months. Nd:YAG laser iridotomy for primary angle-closure glaucoma controlled the condition without any need for further medical or surgical therapy in 37 (15.2% ) cases, but the remainder who required added treatment included: 152 eyes (62.3%) medical treatment., 23 eyes (9.4%) trabeculectomy, 18 eyes (7.4%) phacoemulsification surgery, 8 eyes (3.3%) phacoemulsification with trabeculectomy and 6 eyes (2.5%) cyclophotocoagulation. In this study Nd:YAG laser iridotomy as a prophylactic procedure in the fellow eye of all patients was effective in preventing an acute angle-closure attack in the all the follow-up period. For most eyes with primary angle-closure glaucoma after Nd: YAG laser iridotomy, additional medicine and surgery was required in the follow-up period. Medication therapy was needed more than other therapy. Early phacoemulsification appeared to be more effective in preventing IOP rise in uncontrolled cases.


Characteristics and clinical value of 3D MR imaging in the diagnosis of pulmonary embolism.
The aim of the present study was to investigate the characteristics and value of 3D dynamic contrast-enhanced magnetic resonance pulmonary angiography (3D-DCE-MRPA) for the diagnosis of pulmonary embolism (PE). Among patients suspected with PE, 30 cases were scheduled for 3D-DCE-MRPA [magnetic resonance imaging (MRI) group], and 30 cases were examined using multislice computed tomographic pulmonary angiography (msCTPA) [computed tomography (CT) group]. Direct signs including location, number, morphology of emboli, and indirect signs such as pulmonary infarction, pneumonia and pleural effusion, were analyzed. Pulmonary artery enhancement was observed. Image quality was contrasted, branches of the pulmonary artery revealed, and differences in sensitivity, specificity and signal-to-noise ratio (SNR) were compared. The number and morphology of emboli in the two groups were compared, and there were no significant differences (P>0.05). In the MRI group, significantly more emboli were located in segmental and subsegmental bronchi (P<0.05). The indirect signs in the two groups were compared and the differences were not statistically significant (P>0.05). The difference in image quality between the two groups was not statistically significant (P>0.05). Levels 5 and 6 of the pulmonary artery branch were more evident in the MRI group compared to the CT group. The SNR and carrier-to-noise ratio in the MRI group were significantly higher than those in the CT group (P<0.05). Twenty-six cases of PE were diagnosed in the CT group, with a sensitivity of 90.5% and specificity of 86.7%. Twenty-five cases were diagnosed in the MRI group, with a sensitivity of 92.3% and specificity of 84.2%. In conclusion, 3D-DCE-MRPA surpassed msCTPA in revealing segmental and subsegmental pulmonary artery PE.


The potential of bacteriophages to control Xanthomonas campestris pv. campestris at different stages of disease development.
Xanthomonas campestris pv. campestris (Xcc) is a vascular pathogen that invades the xylem of Brassica crops. Current chemical and antibiotics-based control measures for this bacterium are unsustainable and inefficient. After establishing a representative collection of Xcc strains, we isolated and characterized bacteriophages from two clades of phages to assess their potential in phage-based biocontrol. The most promising phages, FoX2 and FoX6, specifically recognize (lipo) polysaccharides, associated with the wxc gene cluster, on the surface of the bacterial cell wall. Next, we determined and optimized the applicability of FoX2 and FoX6 in an array of complementary bioassays, ranging from seed decontamination to irrigation- and spray-based applications. Here, an irrigation-based application showed promising results. In a final proof-of-concept, a CaCl2 -formulated phage cocktail was shown to control the outbreak of Xcc in the open field. This comprehensive approach illustrates the potential of phage biocontrol of black rot disease in Brassica and serves as a reference for the broader implementation of phage biocontrol in integrated pest management strategies.


CO(2) Photoassimilation by the Spinach Chloroplast at Low Temperature.
Spinach chloroplasts were used to study the relationship between photosynthetic CO(2) fixation and temperature from 30 to -15 degrees C. In saturating light and high concentrations of CO(2), the temperature coefficients (Q(10)) above 20 degrees C were less than 2 in the intact chloroplast. Below 15 degrees C, the Q(10) values were greater than 2 and gradually increased with decreasing (down to 0 degrees C) temperature to approximately 4.4. Photosynthesis responded similarly to temperature in a reconstituted chloroplast preparation fortified with ribose 5-phosphate. In the intact chloroplast, temperature did not alter the Q(10) value in low light and high CO(2). Elevating the temperature to 25 degrees C after photosynthesizing at -15 degrees C (46 minutes) or 0 degrees C (17 minutes) restored the temperature-depressed photosynthetic rate without a lag in the intact chloroplast to the rate of a chloroplast continually at 25 degrees C. At 0 degrees C, the intact chloroplast photosynthetic rate responded slightly to the inorganic phosphate concentration (0.1-1.0 millimolar) and to pH (7.0-8.6). Relative to 25 degrees C, the levels of ribulose 1,5-bisphosphate and glycerate 3-phosphate were increased 1300 and 200%, respectively, whereas glycolate decreased 57% during intact chloroplast photosynthesis at 0 degrees C. Chilling temperature impeded the transport of photosynthetic intermediates from the stromal compartment to the external medium. Ethylene glycol was shown to be an appropriate additive to prevent freezing of the reaction mixture down to -15 degrees C for photosynthetic CO(2) assimilation.


Practice Patterns and Potential Barriers to Early Diagnosis of Autism in Bosnia and Herzegovina: A Preliminary Study.
The aim of this preliminary study was to identify the practice patterns and potential barriers to diagnosing autism in Bosnia & Herzegovina. 126 children aged 23 to 94 months with developmental concerns referred to treatment centers participated in the study. Although parents had reported developmental problems in their children usually around the age of 17 months, it took them 812 visits to professionals (> 6 visits per child) over several months (mean 16.8, range 2-52 months) to get diagnosed with any developmental disorder. Only 8 children (6.3%) received a diagnosis of autism. However, when we re-examined 110 of the 126 children, 90 of them (71%) were identified with autism. Implications of these findings are discussed.


Benefits of Sleep Extension on Sustained Attention and Sleep Pressure Before and During Total Sleep Deprivation and Recovery.
To investigate the effects of 6 nights of sleep extension on sustained attention and sleep pressure before and during total sleep deprivation and after a subsequent recovery sleep. Subjects participated in two experimental conditions (randomized cross-over design): extended sleep (EXT, 9.8 ± 0.1 h (mean ± SE) time in bed) and habitual sleep (HAB, 8.2 ± 0.1 h time in bed). In each condition, subjects performed two consecutive phases: (1) 6 nights of either EXT or HAB (2) three days in-laboratory: baseline, total sleep deprivation and after 10 h of recovery sleep. Residential sleep extension and sleep performance laboratory (continuous polysomnographic recording). 14 healthy men (age range: 26-37 years). EXT vs. HAB sleep durations prior to total sleep deprivation. Total sleep time and duration of all sleep stages during the 6 nights were significantly higher in EXT than HAB. EXT improved psychomotor vigilance task performance (PVT, both fewer lapses and faster speed) and reduced sleep pressure as evidenced by longer multiple sleep latencies (MSLT) at baseline compared to HAB. EXT limited PVT lapses and the number of involuntary microsleeps during total sleep deprivation. Differences in PVT lapses and speed and MSLT at baseline were maintained after one night of recovery sleep. Six nights of extended sleep improve sustained attention and reduce sleep pressure. Sleep extension also protects against psychomotor vigilance task lapses and microsleep degradation during total sleep deprivation. These beneficial effects persist after one night of recovery sleep.


Cloning and expression of Clostridium acetobutylicum phosphotransbutyrylase and butyrate kinase genes in Escherichia coli.
A 13.6-kilobase (kb) Sau3AI restriction endonuclease fragment of Clostridium acetobutylicum DNA cloned into pBR322 enabled Escherichia coli ato mutants to grow on butyrate as a sole carbon source (But+). Complementation of the ato defect by the recombinant plasmid pJC6 was due to expression of the genes for phosphotransbutyrylase (PTB) and butyrate kinase (BK). Both genes were efficiently expressed in E. coli, as their products were readily detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell extracts. PTB was found to have a polypeptide subunit molecular weight of approximately 31,000, while that of BK was approximately 39,000. Deletion analysis and Tn5 mutagenesis of plasmid pJC7 (a But+ subclone containing a 4.4-kb BamHI fragment from the insert of pJC6) localized the PTB and BK genes within a region spanning approximately 2.9 kb. Preliminary evidence suggests that the two genes may form an operon that is transcribed as a single unit from a promoter of clostridial origin within the 4.4-kb insert of pJC7.


Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch.
Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16 537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1636 genomes from 4 low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (eg, ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that 3 O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national, and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance.


In Situ Femtosecond-Laser-Induced Fluorophores on Surface of Polyvinyl Alcohol for H2O/Co2+ Sensing and Data Security.
In situ fluorophores were induced on polyvinyl alcohol (PVA) bulk materials by direct femtosecond laser writing. The generation of fluorophores was ascribed to localized laser-assisted carbonization. The carbonization of PVA polymers was confirmed through X-ray photoelectron spectroscopy analysis. The distinct fluorescence responses of fluorophores in various solutions were harnessed for implementing in situ reagent sensors, metal ion sensors, data encryption, and data security applications. The demonstrated water detection sensor in acetone exhibited a sensitivity of 3%. Meanwhile, a data encryption scheme and a "burn after reading" technique were demonstrated by taking advantage of the respective reversible and irreversible switching properties of the in situ laser-induced fluorophores. Taking a step further, a quantitative cobalt ion measurement was demonstrated based on the concentration-dependent fluorescence recovery. Combined with a laser-induced hydrophilic modification, our scheme could enable "lab-on-a-chip" microfluidics sensors with arbitrary shape, varied flow delay, designed reaction zones, and targeted functionalities in the future.


Pseudonocardia broussonetiae sp. nov., an endophytic actinomycete isolated from the roots of Broussonetia papyrifera.
A novel endophytic actinomycete, designated strain Gen 01T, was isolated from the roots of Broussonetia papyrifera and characterized by using a polyphasic approach. The predominant cellular fatty acids were iso-C16 : 0, summed feature 3, iso H-C16 : 1, C16 : 0 and iso-C14 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannosides, phospholipids of unknown structure containing glucosamine inositol, phosphatidylinositol and unidentified phospholipids. The major menaquinone was MK-8 (H4). The DNA G+C content of the genome sequence, consisting of 7 177 725 bp, was 74.5 mol%. Phylogenetic analysis of the full-length 16S rRNA gene sequences showed that strain Gen 01T belongs to the genus Pseudonocardia with the highest sequence similarity to Pseudonocardia petroleophila CGMCC 4.1532T (98.9 %) and lower than 98.7 % similarity to other species of the genus Pseudonocardia with validly published names. The average nucleotide identity and digital DNA-DNAhybridization values between strain Gen 01T and P. petroleophila CGMCC 4.1532T were 84.6 and 30.9 %, respectively. Furthermore, the morphological, physiological and biochemical characteristics were sufficient to categorize strain Gen 01T as being distinct from P. petroleophila CGMCC 4.1532T. Consequently, based on phenotypic and genotypic characteristics, strain Gen 01T represents a novel species of the genus Pseudonocardia, for which the name Pseudonocardia broussonetiae sp. nov. is proposed. The type strain is Gen 01T (=CICC 24820T=JCM 33840T).


HIRA: Heart Rate Interval based Rapid Alert score to characterize autonomic dysfunction among patients with sepsis-related acute respiratory failure (ARF).
Objective. To examine whether heart rate interval based rapid alert (HIRA) score derived from a combination model of heart rate variability (HRV) and modified early warning score (MEWS) is a surrogate for the detection of acute respiratory failure (ARF) in critically ill sepsis patients.Approach. Retrospective HRV analysis of sepsis patients admitted to Emory healthcare intensive care unit (ICU) was performed between sepsis-related ARF and sepsis controls without ARF. HRV measures such as time domain, frequency domain, and nonlinear measures were analyzed up to 24 h after patient admission, 1 h before the onset of ARF, and a random event time in the sepsis controls. Statistical significance was computed by the Wilcoxon Rank Sum test. Machine learning algorithms such as eXtreme Gradient Boosting and logistic regression were developed to validate the HIRA score model. The performance of HIRA and early warning score models were evaluated using the area under the receiver operating characteristic (AUROC).Main Results. A total of 89 (ICU) patients with sepsis were included in this retrospective cohort study, of whom 31 (34%) developed sepsis-related ARF and 58 (65%) were sepsis controls without ARF. Time-domain HRV for Electrocardiogram (ECG) Beat-to-Beat RR intervals strongly distinguished ARF patients from controls. HRV measures for nonlinear and frequency domains were significantly altered (p< 0.05) among ARF compared to controls. The HIRA score AUC: 0.93; 95% confidence interval (CI): 0.88-0.98) showed a higher predictive ability to detect ARF when compared to MEWS (AUC: 0.71; 95% CI: 0.50-0.90).Significance. HRV was significantly impaired across patients who developed ARF when compared to controls. The HIRA score uses non-invasively derived HRV and may be used to inform diagnostic and therapeutic decisions regarding the severity of sepsis and earlier identification of the need for mechanical ventilation.


1800 MHz in vitro exposure device for experimental studies on the effects of mobile communication systems.
A wire patch cell (WPC) operating at the uplink frequency band of GSM 1800 MHz has been designed for in vitro experiments with the aim of investigating the possible biological effects of electromagnetic radiation associated with cellular phones. The 1800 MHz WPC design is a direct descendant of the original 900 MHz WPC introduced by Laval et al. This system provides a homogeneous specific absorption rate distribution, using four 3.5 cm petri dishes simultaneously. Numerical dosimetry has been performed using a commercial code (CST Microwave Studio), in order to evaluate accurately the efficiency of the structure (in terms of W kg(-1) per 1 W input power) and the distribution in the chosen biological target. The numerical results have been confirmed by experimental measurements performed by measuring thermal increase due to a high power impulse. The efficiency of the structure is 1.25 +/- 25% W kg(-1) per 1 W input power higher than the efficiency of the 900 MHz WPC. A few adjustments have been made in order to use the WPC in a standard incubator and to avoid thermal increases related to the radio frequency exposure. This exposure system has been adopted for the experiments scheduled in the RAMP and GUARD projects (VFPE).


Can an intracoronary Doppler wire accurately measure changes in coronary blood flow velocity?
The purpose of this study was to compare a newly developed Doppler guide wire in the measurement of coronary blood flow velocity (CBFV) and coronary flow reserve (CFR) when compared to a previously extensively validated Doppler catheter. Sequential measurements of Doppler signals from the Doppler catheter and wire were obtained in response to graded doses of intracoronary adenosine in the left circumflex of 10 anesthetized dogs. The Doppler catheter signal was recorded on a standard physiologic chart recorder; that from the Doppler wire was recorded both on the chart recorder and the commercially available spectral analysis recording system. High correlations were obtained between the change in coronary velocity and CFR which were independent of the recording system used. Peak flow reserve in response to maximum intracoronary adenosine (24 micrograms bolus) ranged from 3.7-5.6 x basal. These results are similar to those obtained in normal humans. In spite of major differences between engineering specifications of the Doppler wire and Doppler catheter, under optimal conditions these two techniques yield similar results. The Doppler wire may facilitate measurements of CFR during diagnostic angiography in small or diffusely diseased vessels.


Presence of synchrony-generating hubs in the human epileptic neocortex.
•Initiation of pathological synchronous events such as epileptic spikes and seizures is linked to the hyperexcitability of the neuronal network in both humans and animals. •In the present study, we show that epileptiform interictal-like spikes and seizures emerged in human neocortical slices by blocking GABAA receptors, following the disappearance of the spontaneously occurring synchronous population activity. •Large variability of temporally and spatially simple and complex spikes was generated by tissue from epileptic patients, whereas only simple events appeared in samples from non-epileptic patients. •Physiological population activity was associated with a moderate level of principal cell and interneuron firing, with a slight dominance of excitatory neuronal activity, whereas epileptiform events were mainly initiated by the synchronous and intense discharge of inhibitory cells. •These results help us to understand the role of excitatory and inhibitory neurons in synchrony-generating mechanisms, in both epileptic and non-epileptic conditions. Understanding the role of different neuron types in synchrony generation is crucial for developing new therapies aiming to prevent hypersynchronous events such as epileptic seizures. Paroxysmal activity was linked to hyperexcitability and to bursting behaviour of pyramidal cells in animals. Human data suggested a leading role of either principal cells or interneurons, depending on the seizure morphology. In the present study, we aimed to uncover the role of excitatory and inhibitory processes in synchrony generation by analysing the activity of clustered single neurons during physiological and epileptiform synchronies in human neocortical slices. Spontaneous population activity was detected with a 24-channel laminar microelectrode in tissue derived from patients with or without preoperative clinical manifestations of epilepsy. This population activity disappeared by blocking GABAA receptors, and several variations of spatially and temporally simple or complex interictal-like spikes emerged in epileptic tissue, whereas peritumoural slices generated only simple spikes. Around one-half of the clustered neurons participated with an elevated firing rate in physiological synchronies with a slight dominance of excitatory cells. By contrast, more than 90% of the neurons contributed to interictal-like spikes and seizures, and an intense and synchronous discharge of inhibitory neurons was associated with the start of these events. Intrinsically bursting principal cells fired later than other neurons. Our data suggest that a balanced excitation and inhibition characterized physiological synchronies, whereas disinhibition-induced epileptiform events were initiated mainly by non-synaptically synchronized inhibitory neurons. Our results further highlight the differences between humans and animal models, and between in vivo and (pharmacologically manipulated) in vitro conditions.


Prognostic significance of blood group antigen expression of tumor tissue in lung cancer patients.
Many prognostic factors have been evaluated both for SCLC and NSCLC. The prognostic significance of blood group antigen expression of tumor tissues has been studied particularly in NSCLC, yielding divergent results. The aim of the present study was to investigate the prognostic value of the tumoral expression of blood group antigens ABH in lung cancer. The presence of blood group antigens was assessed immunohistochemically in paraffin-embedded tumor samples from 92 patients diagnosed between 1996 and 1997. Monoclonal antibodies were used to detect blood group antigens. The median survival was longer in NSCLC patients whose tumors were positive for blood group antigen A (P = 0.009). Since the expression of blood group antigen A in tumor cells was limited to patients with type A or AB blood, survival analysis of these patients showed survival to be longer in non-small cell lung cancer patients with blood group antigen A-positive tumors (P= 0.0019). Expression of blood group antigen A in tumor cells is an important, favorable prognostic factor in patients with non-small cell lung cancer, which could be useful to stratify patients with blood group A or AB according to possible outcome, and to guide therapeutic decision-making. The expression of blood group antigens ABH should be evaluated in larger series of lung cancer patients (including small and non-small cell lung cancer) with all blood types.


Dough, tough, cough, rough: A "fast" fMRI localizer of component processes in reading.
In the current study, we present a novel fMRI protocol in which words, pseudowords, and other word-like stimuli are passively presented in a rapid, sequential fashion. In this "fast" localizer paradigm, items are presented in groups of four; within sets, words are related in orthographic, phonological, and/or semantic properties. We tested this protocol with a group of skilled adult readers (N=18). Analyses uncovered key regions of the reading network that were sensitive to different component processes at the group level; namely, left fusiform gyrus as well as the pars opercularis subregion of inferior frontal gyrus were sensitive to lexicality; several regions including left precentral gyrus and left supramarginal gyrus were sensitive to spelling-sound consistency; the pars triangularis subregion of inferior frontal gyrus was sensitive to semantic similarity. Additionally, in a number of key brain regions, activation in response to semantically similar words was related to individual differences in reading comprehension outside the scanner. Importantly, these findings are in line with previous investigations of the reading network, yet data were obtained using much less imaging time than comparable paradigms currently available, especially relative to the number of indices of component processes obtained. This feature, combined with the relatively simple nature of the task, renders it appropriate for groups of subjects with a wide range of reading abilities, including children with impairments.


Glass Fiber-Reinforced Phenol Formaldehyde Resin-Based Electrical Insulating Composites Fabricated by Selective Laser Sintering.
In this study, glass fiber (GF)/phenol formaldehyde resin (PF)/epoxy resin (EP) three-phase electrical insulating composites were fabricated by selective laser sintering (SLS) additive manufacturing technology and subsequent infiltration. In the three-phase composites, glass fibers modified by a silane coupling agent (KH-550) were used as reinforcements, phenol formaldehyde resin acted as the binder and matrix, and infiltrated epoxy resin was the filler. Mechanical and electrical properties such as tensile strength, bending strength, dielectric constant, electrical conductivity, and electric breakdown strength of the GF/PF/EP three-phase composite parts were investigated. The results indicated that after being infiltrated with EP, the bending strength and tensile strength of the GF/PF/EP composites increased by 30% and 42.8%, respectively. Moreover, the flexural strength and tensile strength of the GF/PF/EP composite increased with the increase of the glass fiber content. More importantly, the three-phase composites showed high electrical properties. Significant improvement in the dielectric constant, electric breakdown strength, and resistivity with the increase in the content of glass fiber was observed. This enables the prepared GF/PF/EP composites to form complex structural electrical insulation devices by SLS, which expands the materials and applications of additive manufacturing technology.


Application of nanosecond-UV laser ablation-inductively coupled plasma mass spectrometry for the isotopic analysis of single submicrometer-size uranium particles.
For the first time, laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) was used to carry out isotopic measurement on single submicrometer-size uranium particles. The analytical procedure was applied on two particle-containing samples already analyzed in the same laboratory by established techniques for particle analysis: combination of the fission track technique with thermo-ionization mass spectrometry (FT-TIMS) and secondary ion mass spectrometry (SIMS). Particles were extracted from their initial matrix with ethanol and deposited on a polycarbonate disk where they were fixed in a layer of an organic compound (collodion). Prior to the isotopic analysis, particles were precisely located on the disk's surface by scanning electron microscopy (SEM) for one sample and using the fission track technique for the other sample. Most of the particles were smaller than 1 μm, and their (235)U content was in the femtogram range. (235)U/(238)U ratios were successfully analyzed for all located particles using a nanosecond-UV laser (Cetac LSX 213 nm) coupled to a quadrupole-based ICPMS (Thermo "X-Series II"). LA-ICPMS results, although less precise and accurate (typically 10%) than the ones obtained by FT-TIMS and SIMS due to short (20-40 s), transient, and noisy signals, are in good agreement with the certified values or with the results obtained with other techniques. Thanks to good measurement efficiency (~6 × 10(-4)) and high signal/noise ratio during the analysis, LA-ICPMS can be considered a very promising technique for fast particle analysis, provided that uranium-bearing particles are fixed on the sample holder and located prior to isotope measurement.


Glycoconjugate expression of sinus mucosa in chronic rhinosinusitis: a lectin histochemical study.
Glycoproteins are responsible for the rheological properties of the mucus. Changes in mucus viscosity may interfere with mucociliary clearance, leading to stasis and aggravation of chronic rhinosinusitis (CRS). The purpose of this study was to assess the composition and concentration of various sinus mucosa glycoproteins in normal and chronically inflamed sinuses. A semiquantitative scoring system was used to express the binding intensity of 10 lectins to 6 carbohydrates (galactose, sialic acid, N-acetylglucosamine, N-acetylgalactosamine [GalNac] [corrected], fucose, mannose) residing in the sinus mucosa of patients with CRS (N = 20) and normal controls (N = 10). The mean CT score, compatible with extensive sinus disease, was 13.9 +/- 6.7. All six carbohydrates were found in the epithelium and submucosal glands of patients and controls. Peanut agglutinin staining showed significantly higher concentration of disaccharide galactose beta 1,3 GalNac [corrected] in epithelial goblet cells and in submucosal mucous and mixed glands of patients compared with that of controls (p = 0.01, p = 0.03, and p = 0.018, respectively). The epithelial glycocalyx of patients was also significantly more abundant in fucose and in GalNac [corrected] (p = 0.015, and p < 0.001, respectively). Glycoconjugate expression of the sinus mucosa in CRS is markedly altered in extensive inflammatory conditions. The increased concentration of galactose beta 1,3 GalNac [corrected] in CRS probably contributes to the high viscosity of the nasal mucus and interferes with normal mucociliary clearance. Exposed peripheral galactose residues may serve as attachment receptor sites for pathogenic bacteria. Means interfering with the ability of bacteria to adhere to specific receptors on host tissues warrant additional research.


Child deaths in South Africa: Lessons from the child death review pilot.
South Africa (SA) has not met the child mortality target for the Millennium Development Goals, despite having invested substantially in programmes and policies to achieve these targets. The scale-up of the prevention of mother-to-child transmission programmes reduced HIV transmission from mother to child, but this has not been sustained owing to limitations in community-based child health services. Child mortality has declined, but has now plateaued. Children continue to die from preventable and treatable causes of death. Current data sources are incomplete, and do not provide information on deaths occurring out of health facilities. The child death review (CDR) pilot explores the pattern of child deaths and informs prevention strategies to improve child survival in SA. In this editorial we draw on the conclusions of the CDR pilot, where multiagency teams were established to investigate non-natural and unexpected deaths referred to two mortuary sites in order to strengthen child health and protection response systems and to prevent child deaths.


Cloning and characterization of a Caenorhabditis elegans cDNA encoding a new insulin/IGF-like peptide.
A Caenorhabditis elegans cDNA encoding a new insulin/IGF-like peptide was cloned and examined. The predicted peptide shows significant sequence similarity with the peptide Ceinsulin-1 reported previously and contains a characteristic insertion consisting of three residues in the putative B domain as with the Ceinsulin-1. The gene expression pattern during development is almost identical to that of Ceinsulin-1. The predicted tertiary structure of the peptide is quite similar to that of Ceinsulin-1, and their predicted receptor-recognition surfaces also closely match. These facts suggest that both peptides could recognize the same receptor.


Perceived Academic Stress and Depression: The Mediation Role of Mobile Phone Addiction and Sleep Quality.
Although academic stress is a well-known risk factor for students' depression, little is known about the possible psychological mechanisms underlying this association. In this study, we investigated the prevalence of depression and sleep disturbance among Chinese students, examined the relationship between perceived academic stress and depression, considered if mobile phone addiction and sleep quality is a mediator of this relationship, and tested if mobile phone addiction and sleep quality together play a serial mediating role in the influence of perceived academic stress on depression. A cross-sectional survey was conducted among students from September to December 2018 in Heilongjiang Province, China. The final analysis included 5,109 students. Mobile phone addiction, sleep quality, and depressive symptoms were assessed using the Mobile Phone Addiction Index, Pittsburgh Sleep Quality Index, and Center for Epidemiologic Studies-Depression scales, respectively. The serial mediation model was used to analyse the relationship between perceived academic stress, mobile phone addiction, sleep quality, and depression. Among all participants, the prevalence of depressive symptoms and sleep disturbance was 28.69 and 27.95%, respectively. High school students showed the highest scores of perceived academic stress (2.68 ± 1.06), and the highest prevalence of depressive symptoms (33.14%) and sleep disturbance (36.47%). The serial mediation model indicated that perceived academic stress was a significant predictor of depression (B = 0.10, SE = 0.02, 95% CI = 0.06 - 0.13). Additionally, mobile phone addiction (B = 0.08, 95% boot CI = 0.06-0.11) and sleep quality (B = 0.27, 95% boot CI = 0.22-0.33) played a mediating role between perceived academic stress and depression. Mobile phone addiction and sleep quality together played a serial mediating role in the influence of perceived academic stress on depression (B = 0.11, 95% boot CI = 0.08-0.14). Furthermore, the indirect effect (i.e., the mediating effect of mobile phone addiction and sleep quality) was significant and accounted for 64.01% of the total effect. Our research results underscore the need for stakeholders-including family members, educators, and policy makers-to take preventative intervention measures to address depression among Chinese students, especially high school students.


Effects of the ergot alkaloids dihydroergotamine, ergonovine, and ergotamine on growth of Escherichia coli O157:H7 in vitro.
A series of experiments were conducted to evaluate the effects of ergot alkaloids (dihydroergotamine, ergonovine, and ergotamine) on E. coli O157:H7 in both pure and mixed ruminal fluid culture. Alkaloids were added to solutions of E. coli O157:H7 strains 933 (pure and ruminal cultures) and 6058 (ruminal culture only), and growth rates and colony-forming units (CFU) of E. coli O157:H7 were measured. Two mixtures of all three alkaloids at either 2 or 500 microM for each alkaloid decreased (p < 0.001) the growth rate of E. coli O157:H7 in pure culture compared to the individual alkaloids. Dihydroergotamine tended (p = 0.07) to reduce growth rate of E. coli O157:H7 in pure culture compared with ergonovine or ergotamine alone. Increased concentrations of dihydroergotamine and ergotamine decreased (p < 0.003) growth rate of E. coli O157:H7 but increasing concentrations of ergonovine did not influence (p > 0.10) E. coli O157:H7 growth rate. Similar to results in pure culture, a mixture of all three alkaloids at various concentrations for each alkaloid decreased (p < 0.001) the CFU of E. coli O157:H7 strain 6058 in mixed ruminal culture compared to the individual ergot alkaloids. Dihydroergotamine decreased (p = 0.04) CFU of E. coli O157:H7 strain 6058 when compared to ergonovine but CFU were similar (p > 0.10) between dihydroergotamine and ergotamine. Ruminal and (or) intestinal populations of E. coli O157:H7 may be influenced in livestock consuming endophyte-infected tall fescue, and these alterations could be due to the presence of ergot alkaloids in fescue plants.


Influence of gait manipulation on running economy in female distance runners.
The aim of this investigation was to determine if gait manipulation influences running economy. Following 30 minutes of accommodation to level treadmill running at 3.35 m·s(-1) and determination of VO2peak, nine female distance runners (age = 23.3 ± 4.2 years; body mass = 57.5 ± 5.2 kg; height = 1.64 ± 0.10 m; body fat = 11.4 ± 2.4 %; VO2peak = 54.9 ± 4.1 ml·kg(-1)·min(-1)) completed two treadmill running sessions. In each session, standing VO2 was measured and subjects ran for 6 minutes at 3.35 m·s(-1) under 4 randomly-selected conditions: a) normal running (NL), b) hands behind back (BK), c) hands on head (HD), and d) running with exaggerated vertical oscillation (VOSC). During the last 2 minutes of each running bout, samples of expired air were analyzed to determine oxygen uptake (VO2). Data obtained by averaging gross VO2 values across sessions indicated that VOSC (51.0 ± 2.5 ml·kg(-1)·min(-1)) and HD (46.1 ± 2.0 ml·kg(-1)·min(-1)) resulted in significantly (p < 0.05) elevated VO2 values compared to BK (43.9 ± 2.4 ml·kg(-1)·min(-1)) and NL (43.4 2.6 ml·kg(-1)·min(-1)). VO2 measured during VOSC was also higher compared to HD. Viewed in concert, these results suggest that specific gait manipulations can produce marked decrements in running economy among trained female distance runners. Key pointsThis investigation demonstrates that specific biomechanical manipulations can produce substantive increases in the oxygen cost (VO2) of submaximal running in female distance runners.The magnitude of increases in VO2 reported in this study raises the intriguing possibility that meaningful improvements in running economy might be achieved by manipulating the gait of distance runners who exhibit specific aspects of running style that deviate markedly from the optimum.


Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest (DHCA)? Altogether, more than 62 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the seven papers used thiopental alongside other neuroprotective methods and agents. The methods included the use of ice packs to the head and core systemic hypothermia. Agents used alongside thiopental included nicardipine and mannitol. Thiopental was found to have the ability to lower oxygen consumption, where oxygen consumption was measured using the phosphocreatinine and adenosine triphosphate ratio. The neuroprotective effect of thiopental was evaluated by assessing the electrical activity of the brain during circulatory arrest, by which it was shown to be advantageous. However, other trials suggested that adding thiopental during circulatory arrest did not provide any extra protection to the brain. The timing of thiopental administration is of importance in order to gain positive outcomes, as it's ability to lower the cerebral energy state may result in unfavourable results if added before hypothermic circulatory arrest, where this may lead to an ischaemic event. We conclude that the use of thiopental during deep hypothermic circulatory arrest is beneficial, but if administered too early, it may replete the cerebral energy state before arrest and prove to be detrimental.


Electrostatic frequency reduction: A negative stiffness mechanism for measuring dissipation in a mechanical oscillator at low frequency.
Broadband seismometers and gravitational wave detectors make use of mechanical resonators with a high quality factor to reduce Brownian noise. At low frequency, Brownian noise is ultimately dominated by internal friction in the suspension, which has a 1/f noise compared with the white noise arising from viscous dissipation. Internal friction is typically modeled as a frequency-dependent loss and can be challenging to measure reliably through experiment. In this work, we present the physics and experimental implementation of electrostatic frequency reduction (EFR) in a mechanical oscillator-a method to measure dissipation as a function of frequency. By applying a high voltage to two parallel capacitor plates, with the center plate being a suspended mass, an electrostatic force is created that acts as a negative stiffness mechanism to reduce the system's resonance frequency. Through EFR, the loss angle can be measured as a function of frequency by measuring amplitude decay response curves for a range of applied voltages. We present experimental measurements of the loss angle for three metal helical extension springs in the nominal frequency range 0.7-2.9 Hz at 0.2 Hz intervals, demonstrating the possibility for fine adjustment of the resonance frequency for loss angle measurements. A quality factor proportional to the resonance frequency squared was measured, an indication that internal friction and other non-viscous dissipation elements, such as electrostatic damping, were the prominent loss mechanisms in our experiments. Finally, we consider the implications of Brownian noise arising from internal friction on a low 1/f noise seismometer.


Soft contact lens wearers' compliance during the COVID-19 pandemic.
Contact lens wearers need to maintain optimal hygiene practices during the COVID-19 pandemic to minimise contact-lens complications including microbial keratitis and corneal infiltrative events. This online survey (UK and Ireland) explored contact lens wearers' compliance behaviours, attitudes and concerns during the pandemic. The 60-item anonymous online survey was distributed during a 1-month period via Qualtrics (starting on 14/04/20). The survey captured: a) demographic information, b) type of lenses worn and compliance with lens wear and care procedures, c) adherence to recommendations and d) concerns associated with contact lens wear during the pandemic. Two hundred and forty seven responses were received (34.3 ± 11.7 years old, 79% female). Seventy nine percent of participants reported that they were self-isolating or rigorously following social distance advice. Fifty-six percent of participants reported using their lenses less during the pandemic. Eighty-seven percent of respondents reported following the recommended 20-second rule most times/every time and 96% used soap and water during handwashing. Eleven percent of respondents admitted not following recommendations regarding disposal of lenses and 18% would not consider ceasing lens wear if unwell (with flu/cold) during the pandemic. Respondents reported wearing their contact lenses less than usual. Good compliance with handwashing was observed but soft reusable lens wearers showed a statistically significant lower compliance with lens wear and care compared to daily disposable lens wearers (p=<0.001).


Cyclin I: a new cyclin encoded by a gene isolated from human brain.
A new member of the cyclin family has been isolated from an equalized cDNA library derived from human forebrain cortex. This putative cyclin, designated cyclin I, contains a typical cyclin box near the N-terminus and a PEST sequence near the C-terminus. Cyclin I shows the highest sequence similarity in the cyclin box to cyclins G and E, while the similarity between cyclins I and G also extends toward the C-terminus from the cyclin box. Cyclin I mRNA was expressed at high levels in postmitotic tissues, including skeletal muscle, heart, and brain, and was expressed constantly during cell cycle progression. The expression of cyclin I mRNA does not correlate directly to the cell cycle, and therefore cyclin I may be a novel cyclin member that functions independently of the cell cycle control.


The fragile-to-strong dynamic crossover transition in confined water: nuclear magnetic resonance results.
By means of a nuclear magnetic resonance experiment, we give evidence of the existence of a fragile-to-strong dynamic crossover transition (FST) in confined water at a temperature T(L)=223+/-2 K. We have studied the dynamics of water contained in 1D cylindrical nanoporous matrices (MCM-41-S) in the temperature range 190-280 K, where experiments on bulk water were so far hampered by crystallization. The FST is clearly inferred from the T dependence of the inverse of the self-diffusion coefficient of water (1D) as a crossover point from a non-Arrhenius to an Arrhenius behavior. The combination of the measured self-diffusion coefficient D and the average translational relaxation time tau(T), as measured by neutron scattering, shows the predicted breakdown of Stokes-Einstein relation in deeply supercooled water.


Cancer chromosome breakpoints cluster in gene-rich genomic regions.
Cancer cells are characterized by chromosome abnormalities, of which some, in particular balanced rearrangements, are associated with distinct tumor entities and/or with specific gene rearrangements that represent important steps in the carcinogenic process. However, the vast majority of cytogenetically detectable structural aberrations in cancer cells have not been characterized at the nucleotide level; hence, their importance and functional consequences are unknown. By ascertaining the chromosomal breakpoints in 22 344 different clonal structural chromosome abnormalities identified in the karyotypes of 49 626 cases of neoplastic disorders we here show that the distribution of breakpoints is strongly associated (P < 0.0001) with gene content within the affected chromosomal bands. This association also remains highly significant in separate analyses of recurrent and nonrecurrent chromosome abnormalities as well as of specific subtypes of cancer (P < 0.0001 for all comparisons). In contrast, the impact of band length was negligible. The breakpoint distribution is thus not stochastic-gene-rich regions are preferentially affected. Several genomic features relating to transcription, replication, and chromatin organization have been found to enhance chromosome breakage frequencies; this indicates that gene-rich regions may be more break-prone. The salient finding in the present study is that a substantial fraction of all structural chromosome abnormalities, not only those specifically associated with certain tumor types, may affect genes that are pathogenetically important. If this interpretation is correct, then the prevailing view that the great majority of cancer chromosome aberrations is cytogenetic noise can be seriously questioned.


Characterisation of the sarcoidosis-associated variant of annexin A11.
Recent studies on the genetic background of sarcoidosis have resulted in the discovery of a strongly associated single nucleotide polymorphism (SNP) that switches a highly conserved arginine to a cysteine at position 230 in annexin A11. The effect of the R230C SNP on the cellular distribution and Ca(2+)-sensitivity of annexin A11 was investigated through over-expression of GFP tagged annexin A11 in A431 cells. Cells were stimulated with calcium mobilizing agonists and changes in the cellular localisation of GFP tagged annexin A11 were recorded. Neither variant of annexin 11, nor any truncation mutants, exhibited any response to EGF. In addition, there was no relocalisation of the GFP tagged C-terminal annexin A11 variants in response to ionomycin. However, both the wild type and sarcoidosis associated variants of annexin A11-GFP relocalised to the plasma membrane and then the nuclear envelope in response to ionomycin. These observations show that the sensitivity of annexin A11 to a robust, sustained rise in intracellular calcium, is not significantly affected by the sarcoidosis associated SNP. This does not rule out functional affects in the extracellular milieu, in cytokinesis, nuclear envelope breakdown or in response to other intracellular signals.


Developmental motor function plays a key role in visual search.
Adults often miss a disturbingly high percentage of rare targets in visual arrays. The mechanisms underlying this effect remain hotly debated. This study examines the effects of developing motor control on the speed and accuracy of visual search. Children detected targets that appeared rarely or frequently. Participants reported a target's presence or absence by either pressing a key or marking on recording sheets. The results replicated past reports of increased errors with reduced target prevalence in adults. A potential developmental trend in performance is linked to a measure of motor function. When the pressure to respond quickly was removed, search accuracy greatly improved for rare targets. A developmental account for the perceptual-motor mechanisms of prevalence effect is discussed.


Expression of VEGF splice variants 144/145 and 205/206 in adult male tissues.
Currently, at least five different mRNA species encoding vascular endothelial growth factor-A (VEGF-A) have been characterized. These variants result from alternative splicing of the VEGF-A transcript and encode human isoforms of VEGF protein of 121, 145, 165, 189, and 206 amino acids. In the rat, a similar profile of VEGF-A splice variants has been described, each encoding one fewer amino acid than the human species. Studies of mammalian tissues have shown that these mRNA isoforms vary in abundance. Whereas VEGF 188/189, 164/165, and 120/121 (rat/human, respectively) are the predominant forms expressed in most tissues and cells examined, VEGF 144/145 and 205/206 are rare variants. Previously, VEGF 144/145 had been detected only in placental and uterine tissues and endometrial carcinoma cell lines, whereas VEGF 205/206 was detected only in fetal liver and placenta. Using an RT-PCR technique, cDNA cloning, and sequencing, we have detected and confirmed the presence of mRNA encoding VEGF 144/145 and 205/206 in both adult rat lung and penis. Therefore, these low-abundance VEGF splice variants have a more diverse expression pattern than originally predicted.


Muscle wasting is associated with mortality in patients with cirrhosis.
Sarcopenia, defined as a low level of muscle mass, occurs in patients with cirrhosis. We assessed its incidence among cirrhotic patients undergoing evaluation for liver transplantation to investigate associations between sarcopenia and mortality and prognosis. We studied 112 patients with cirrhosis (78 men; mean age, 54 ± 1 years) who were consecutively evaluated for liver transplantation and had a computed tomography scan at the level of the third lumbar (L3) vertebrae to determine the L3 skeletal muscle index; sarcopenia was defined by using previously published, sex-specific cutoffs. Of the patients studied, 45 (40%) had sarcopenia. Univariate Cox analysis associated mortality with ascites (hazard ratio [HR], 2.12; P = .04), encephalopathy (HR, 1.99; P = .04), level of bilirubin (HR, 1.007; P < .01), international normalized ratio (HR, 7.69; P < .001), level of creatinine (HR, 1.01; P = .005), level of albumin (HR, 94; P = .008), serum level of sodium (HR, 89; P < .001), Model for End-Stage Liver Disease (MELD) score (HR, 1.14; P < .01), Child-Pugh score (HR, 2.84; P < .001), and sarcopenia (HR, 2.18; P = .006). By multivariate Cox analysis, only Child-Pugh (HR, 1.85; P = .04) and MELD scores (HR, 1.08; P = .001) and sarcopenia (HR, 2.21; P = .008) were independently associated with mortality. The median survival time for patients with sarcopenia was 19 ± 6 months, compared with 34 ± 11 months among nonsarcopenia patients (P = .005). There was a low level of correlation between L3 skeletal muscle index and MELD (r = -0.07; P = .5) and Child-Pugh scores (r = -0.14; P = .1). Sarcopenia is associated with mortality in patients with cirrhosis. It does not correlate with the degree of liver dysfunction evaluated by using conventional scoring systems. Scoring systems should include evaluation of sarcopenia to better assess mortality among patients with cirrhosis.


Attention in Bilingual Children With Developmental Language Disorder.
Purpose Attention and language are hypothesized to interact in bilingual children and in children with developmental language disorder (DLD). In children who are bilingual, attentional control may be enhanced by repeated experience regulating 2 languages. In children with DLD, subtle weaknesses in sustained attention may relate to impaired language processing. This study measured attentional control and sustained attention in monolingual and bilingual children with and without DLD in order to examine the potential influences of bilingualism and DLD, as well as their intersection, on attention. Method Monolingual English-only and bilingual Spanish-English children aged 6-8 years were categorized into participant groups based on eligibility testing and parent interviews. Parent interviews included standardized assessment of language environment and parent concern regarding language. Participants completed 2 nonlinguistic computerized assessments: a flanker task to measure attentional control and a continuous performance task to measure sustained attention. Results One hundred nine children met all eligibility criteria for inclusion in a participant group. Regression models predicting performance on the attention tasks were similar for both sustained attention and attentional control. For both tasks, DLD was a significant predictor, and bilingualism was not. Measuring bilingualism continuously using parent-reported exposure did not alter results. Conclusions This study found no evidence of a "bilingual cognitive advantage" on 2 types of attention among sequential Spanish-English bilingual children but also found a negative effect of DLD that was consistent across both types of attention and both bilingual and monolingual children. Results are consistent with the broader literature on subtle nonlinguistic deficits in children with DLD and suggest these deficits are minimally affected by diverse linguistic experience.


Joint hypothesis testing of the area under the receiver operating characteristic curve and the Youden index.
In the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) serves as an overall measure of diagnostic accuracy. Another popular ROC index is the Youden index (J), which corresponds to the maximum sum of sensitivity and specificity minus one. Since the AUC and J describe different aspects of diagnostic performance, we propose to test if a biomarker beats the pre-specified targeting values of AUC0 and J0 simultaneously with H0 : AUC ≤ AUC0 or J ≤ J0 against Ha : AUC > AUC0 and J > J0 . This is a multivariate order restrictive hypothesis with a non-convex space in Ha , and traditional likelihood ratio-based tests cannot apply. The intersection-union test (IUT) and the joint test are proposed for such test. While the IUT test independently tests for the AUC and the Youden index, the joint test is constructed based on the joint confidence region. Findings from the simulation suggest both tests yield similar power estimates. We also illustrated the tests using a real data example and the results of both tests are consistent. In conclusion, testing jointly on AUC and J gives more reliable results than using a single index, and the IUT is easy to apply and have similar power as the joint test.


Serum Potassium and Mortality Risk in Hemodialysis Patients: A Cohort Study.
Both hypo- and hyperkalemia can cause fatal cardiac arrhythmias. Although predialysis serum potassium level is a known modifiable risk factor for death in patients receiving hemodialysis, especially for hypokalemia, this risk may be underestimated. Therefore, we investigated the relationship between predialysis serum potassium level and death in incident hemodialysis patients and whether there is an optimum level. Prospective multicenter cohort study. 1,117 incident hemodialysis patients (aged >18 years) from the Netherlands Cooperative Study on the Adequacy of Dialysis-2 study were included and followed from their first hemodialysis treatment until death, transplantation, switch to peritoneal dialysis, or a maximum of 10 years. Predialysis serum potassium levels were obtained every 6 months and divided into 6 categories: ≤4.0 mmol/L, >4.0 mmol/L to ≤4.5 mmol/L, >4.5 mmol/L to ≤5.0 mmol/L, >5.0 mmol/L to ≤5.5 mmol/L (reference), >5.5 mmol/L to ≤6.0 mmol/L, and >6.0 mmol/L. 6-month all-cause mortality. Cox proportional hazards and restricted cubic spline analyses with time-dependent predialysis serum potassium levels were used to calculate the adjusted HRs for death. At baseline, the mean age of the patients was 63 years (standard deviation, 14 years), 58% were men, 26% smoked, 24% had diabetes, 32% had cardiovascular disease, the mean serum potassium level was 5.0 mmol/L (standard deviation, 0.8 mmol/L), 7% had a low subjective global assessment score, and the median residual kidney function was 3.5 mL/min/1.73 m2 (IQR, 1.4-4.8 mL/min/1.73 m2). During the 10-year follow-up, 555 (50%) deaths were observed. Multivariable adjusted HRs for death according to the 6 potassium categories were as follows: 1.42 (95% CI, 1.01-1.99), 1.09 (95% CI, 0.82-1.45), 1.21 (95% CI, 0.94-1.56), 1 (reference), 0.95 (95% CI, 0.71-1.28), and 1.32 (95% CI, 0.97-1.81). Shorter intervals between potassium measurements would have allowed for more precise mortality risk estimations. We found a U-shaped relationship between serum potassium level and death in incident hemodialysis patients. A low predialysis serum potassium level was associated with a 1.4-fold stronger risk of death than the optimal level of approximately 5.1 mmol/L. These results may imply the cautious use of potassium-lowering therapy and a potassium-restricted diet in patients receiving hemodialysis.


The purification and development of a radioimmunoassay for beta-core fragment of human chorionic gonadotrophin in urine: application as a marker of gynaecological cancer in premenopausal and postmenopausal women.
The beta-core fragment of human chorionic gonadotrophin (hCG) is a major part of the immunoreactive hCG-like material found in the urine of normal pregnant women. Patients with non-trophoblastic gynaecological malignancies have been found to have raised levels of urinary beta-core. We describe the purification of beta-core, the preparation of a polyclonal sheep antiserum and the development of radioimmunoassay. The minimum detection limit of this assay was 0.025 micrograms beta-core/l. There was no significant cross-reaction with the free alpha-subunit, hLH, hFSH and hTSH (less than 0.7%), and only partial cross-reaction with intact hCG and free beta-subunit of hCG (6.9 and 18%). Within-assay variability ranged from 2.03 to 12.5% and between-assay variability from 2.25 to 13.4%. The assay was applied to urine samples from 92 normal non-pregnant premenopausal women, 54 normal postmenopausal women and 65 women with active gynaecological disease (47 postmenopausal and 18 premenopausal). In normal premenopausal women the values ranged from less than 0.025 to 0.62 micrograms beta-core/l (median 0.043 micrograms beta-core/l). The values for normal postmenopausal women ranged from less than 0.025 to 0.64 micrograms beta-core/l (median 0.26 micrograms beta-core/l). Postmenopausal women with gynaecological malignancy had values which ranged from less than 0.025 to 4.0 micrograms/beta-core/l (median 0.31 micrograms beta-core/l); premenopausal women in this group had values which ranged from less than 0.025 to 1.15 micrograms beta-core/l (median 0.12 micrograms beta-core/l). On molecular sieve chromatography, the material found in the urine of normal postmenopausal women showed the physicochemical characteristics of authentic beta-core.(ABSTRACT TRUNCATED AT 250 WORDS)


The DA1 receptor agonist fenoldopam (SK & F 82526) is also an alpha 2-adrenoceptor antagonist.
The alpha-adrenoceptor activity of fenoldopam was evaluated in three different in vitro tissue preparations. In rabbit isolated aortic rings fenoldopam displayed weak alpha 1-adrenoceptor antagonist activity (-log KB = 5.41) and displayed no alpha 1-adrenoceptor agonist activity. In contrast, fenoldopam demonstrated moderately potent antagonist properties at the alpha 2-adrenoceptor in two other tissue preparations. In in vitro model systems used for the characterization of alpha 2-adrenoceptors, fenoldopam competitively antagonized the effects of the alpha 2-adrenoceptor agonist B-HT 920. In the dog isolated saphenous vein and in the isolated field-stimulated guinea-pig ileum, fenoldopam antagonized the effects of B-HT 920 with -log KB values of 7.78 and 7.60, respectively. These data indicate that in addition to being an agonist at DA1 receptors, fenoldopam is also a relatively selective antagonist at alpha 2-adrenoceptors.


Successful surgical treatment of giant main coronary artery fistula connecting to right atrium.
Coronary artery fistulas are rare; they are defined as congenital or acquired coronary artery abnormalities in which blood is shunted into a cardiac chamber, great vessel, or other structure, bypassing the myocardial capillary network. We report here on a case of successful surgical treatment of a giant left main coronary artery fistula in a 29-year-old man who presented to our institution with exertional dyspnea. In this report, the different methods of management are also discussed and the indications for the surgical technique are briefly outlined.


Effects of aerobic exercise training on heart rate variability during wakefulness and sleep and cardiorespiratory responses of young and middle-aged healthy men.
The purpose of the present study was to evaluate the effects of aerobic physical training (APT) on heart rate variability (HRV) and cardiorespiratory responses at peak condition and ventilatory anaerobic threshold. Ten young (Y: median = 21 years) and seven middle-aged (MA = 53 years) healthy sedentary men were studied. Dynamic exercise tests were performed on a cycloergometer using a continuous ramp protocol (12 to 20 W/min) until exhaustion. A dynamic 24-h electrocardiogram was analyzed by time (TD) (standard deviation of mean R-R intervals) and frequency domain (FD) methods. The power spectral components were expressed as absolute (a) and normalized units (nu) at low (LF) and high (HF) frequencies and as the LF/HF ratio. Control (C) condition: HRV in TD (Y: 108, MA: 96 ms; P<0.05) and FD - LFa, HFa - was significantly higher in young (1030; 2589 ms2/Hz) than in middle-aged men (357; 342 ms2/Hz) only during sleep (P<0.05); post-training effects: resting bradycardia (P<0.05) in the awake condition in both groups; VO2 increased for both groups at anaerobic threshold (P<0.05), and at peak condition only in young men; HRV in TD and FD (a and nu) was not significantly changed by training in either groups. The vagal predominance during sleep is reduced with aging. The resting bradycardia induced by short-term APT in both age groups suggests that this adaptation is much more related to intrinsic alterations in sinus node than in efferent vagal-sympathetic modulation. Furthermore, the greater alterations in VO2 than in HRV may be related to short-term APT.


The switch from etanercept originator to SB4: data from a real-life experience on tolerability and persistence on treatment in joint inflammatory diseases.
Switching from originator to biosimilar is part of current practice in inflammatory rheumatic musculoskeletal diseases (iRMDs) such as rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA), with evidences derived from both etanercept (ETN) to SB4-switching randomized controlled trials and real-life registries. We investigated the safety and treatment persistence of ETN/SB4 in a multi-iRMD cohort derived from two rheumatology departments in our region. Adult patients with iRMDs, treated with ETN for at least 6 months and switched to SB4 in stable clinical condition, were eligible for this retrospective evaluation. Retrospective data on adverse events, loss of efficacy and persistence on treatment were collected until latest available follow-up. A total of 220 patients (85 RA, 81 PsA, 33 axSpA, 14 juvenile idiopathic arthritis and seven other conditions; 142 females, mean age 58 ± 7 years, disease duration 12 ± 4 years, ETN duration 7 ± 4 years) were enrolled, with median follow-up of 12.1 (9.7-15.8) months. A total of 50 patients (22.7%) presented with at least one adverse event, with 36 (16.4%) disease flares and 30 (13.6%: 11 for safety and 19 loss of efficacy) SB4 withdrawals. Cumulative SB4 treatment persistence was 99.1%, 88.6% and 64.6% at 6, 12 and 18 months respectively. Back-switch to ETN was performed in 17/30 cases, the remaining cases were managed with change of biologic disease modifying or conventional synthetic anti-rheumatic drug. Age was the only significant predictor of SB4 interruption at 6 months. Our real-life data confirm the safety profile of switching from ETN to SB4, with slightly higher treatment persistence rates compared with other real-life registries.


Association of Vitamin D Metabolites with Parathyroid Hormone, Fibroblast Growth Factor-23, Calcium, and Phosphorus in Dogs with Various Stages of Chronic Kidney Disease.
Hypovitaminosis D is associated with progression of renal disease, development of renal secondary hyperparathyroidism (RHPT), chronic kidney disease-mineral bone disorder (CKD-MBD), and increased mortality in people with CKD. Despite what is known regarding vitamin D dysregulation in humans with CKD, little is known about vitamin D metabolism in dogs with CKD. The purpose of our study was to further elucidate vitamin D status in dogs with different stages of CKD and to relate it to factors that affect the development of CKD-MBD, including parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), calcium, and phosphorus concentrations. Thirty-seven dogs with naturally occurring CKD were compared to 10 healthy dogs. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D], and PTH and FGF-23 concentrations were measured. Their association with serum calcium and phosphorus concentrations and IRIS stage was determined. Compared to healthy dogs, all vitamin D metabolite concentrations were significantly lower in dogs with International Renal Interest Society (IRIS) stages 3 and 4 CKD (r [creatinine]: -0.49 to -0.60; P < .05) but not different in dogs with stages 1 and 2 CKD. All vitamin D metabolites were negatively correlated with PTH, FGF-23, and phosphorus concentrations (r: -0.39 to -0.64; P < .01). CKD in dogs is associated with decreases in all vitamin D metabolites evaluated suggesting that multiple mechanisms, in addition to decreased renal mass, affect their metabolism. This information could have prognostic and therapeutic implications.


[Analysis of economic viability of a mobile eye clinic of a referral Ophthalmology Service].
To analyse the economic viability of a mobile eye clinic of a tertiary referral Ophthalmology Service. The amount of money spent with the purchase and construction of the unit in 2000, and the expenses with its maintenance and operation in 2001 were considered, comparing these expenses with the income obtained from appointments, supplementary tests and eye surgeries through the "Sistema Unico de Saúde" (a health care service provided by the government), in 2001. In order to make an economic analysis, an interest rate of 10% per year and a period of depreciation of 10 years were stipulated. The total amount spent to buy and set up a mobile unit of "Hospital Oftamológico de Sorocaba" was R$ 184,140,00. The amount spent with its maintenance and operation during 2001 was R$ 28,000.00. The unit was used on average during 2 days each week in 2001 and 6492 appointments were made in this period, generating an income of R$ 32,460.00. The appointments generated complementary tests and eye surgeries making up R$ 51,540.00. Therefore, the total amount received directly with the appointments, complementary tests and eye surgeries during 2001 was R$ 84,000.00 paid by the "Sistema Unico de Saúde", according to values established beforehand. Using these values it is possible to make an economic analysis of this enterprise and this was done with and without money savings for depreciation, taking into account the income and the expenses. Besides attending poor communities that are located in distant neighborhoods, a mobile eye clinic can be a source of income for ophthalmologic services.


Clinical Association of CD44 Expression with Proliferative Activity and Apoptotic State in Egyptian Patients Suffering from Ulcerative Colitis and Colorectal Carcinoma.
Cancer stem cell markers were thoroughly investigated as a promising strategy for the prediction of patient outcome and therapeutic response. The prospective role of CD44 cell adhesion molecule in tumorigenic potential and its association with the proliferative activity and apoptotic status of Egyptian patients with ulcerative colitis (UC) and colorectal cancer (CRC) were investigated in this study. Flow cytometric analyses of CD44, DNA cell cycle, and apoptosis identified by Annexin V/PI were performed on colonic tissue specimens obtained from 44 CRC patients, 36 UC patients, and 30 controls. The CRC patients showed overexpression of CD44 marker (p < 0.0001) in comparison with UC and control groups. Regression analysis identified CD44 marker as an independent predictor for tumor staging and grading (p < 0.0001) of CRC patients. The CD44 expression was positively correlated with tumor stage (r = 0.656), tumor grade (r = 0.645), and the proliferative activity of DNA cell cycle (S phase, r = 0.396). However, CD44 expression was negatively correlated with early apoptosis (r = - 0.525). According to our findings, there was a significant and positive association between CD44 dysregulated expression and S phase of DNA cell cycle but a negative association with early apoptosis in CRC patients, suggesting CD44 role in apoptosis suppression reducing the tumor growth reserve.


Kinetic studies of calcium binding to parvalbumins from bullfrog skeletal muscle.
In addition to steady-state properties of calcium binding to parvalbumins, kinetic studies are required for adequate evaluation of the physiological roles of parvalbumins. By using a dual-wavelength spectrophotometer equipped with a stopped-flow accessory, the transient kinetics of calcium binding to parvalbumins (PA-1 and 2) from bullfrog skeletal muscle was examined at 20 degrees C in medium containing 20 mM MOPS-KOH, pH 6.80, 0.13 mM tetramethylmurexide, 25 microM CaCl2, metal-deprived PA-1 or PA-2, various concentrations of Mg2+, and KCl to adjust the ionic strength of the medium to 0.106. The results can be explained in terms of the following rate constants under the conditions mentioned above when a second-order kinetic scheme is assumed. For PA-1, the association and apparent dissociation rate constants for Ca2+ are 1.5 X 10(7) M-1 X s-1 and 1.5 s-1, respectively, or more. The rate constants for Mg2+ are 7,500 M-1 X s-1 and 5-6 s-1, respectively. For PA-2, the rate constants for Ca2+ are 7 X 10(6) M-1 X s-1 and 1.16 s-1, respectively, and those for Mg2+ are 3,500 M-1 X s-1 and 3.5-4 s-1, respectively. Increased affinities for Ca2+ and Mg2+ at 10 degrees C are largely due to decreased apparent dissociation rate constants for these divalent cations, because no significant change in the association rate constants was found.


Cross-reactivity on western blots in HIV-1 and HIV-2 infections.
To examine cross-reactivity of antibodies to heterologous antigens, on HIV-1 and HIV-2 Western blots, we tested sera from 1362 consecutive tuberculosis (TB) patients and 2127 consecutive blood donors. Specimens positive on enzyme-linked immunosorbent assay (ELISA) for HIV-1 or HIV-2 were further characterized by synthetic peptide-based tests, and tested by HIV-1- and HIV-2-specific Western blots. Dual serologic reactivity on synthetic peptide tests was proportionately more frequent in HIV-positive TB patients than in blood donors, and HIV-2 reactivity less frequent. Positive HIV-1 Western blots were seen in 73-83% of specimens specifically characterized as positive for HIV-2 on synthetic peptide tests. Cross-reactivity to HIV-2 Western blots by HIV-1-positive specimens was significantly more frequent in TB patients (35%) than in asymptomatic donors (9%; P less than 0.001). Using recently recommended criteria for HIV-2 Western blot interpretation (presence of two env bands) reduced the overall proportion of HIV-1-positive specimens having a positive HIV-2 Western blot from 27.5 to 16.4%, with [corrected] minimal effect on sensitivity in the diagnosis of HIV-2 reactivity on specimens positive on synthetic peptide tests.


Efficacy of fibrinogen and prothrombin complex concentrate used to reverse dilutional coagulopathy--a porcine model.
This study was conducted to assess whether the combined administration of fibrinogen and prothrombin complex concentrate (PCC) enables the reversal of dilutional coagulopathy resulting from intended blood loss and fluid replacement, and whether this treatment reduces further blood loss and mortality. In 20 anaesthetized pigs, approximately 65% of the estimated blood volume was withdrawn and replaced with the same amount of hydroxyethyl starch (6% HES 130/0.4) to mimic blood loss and to develop a dilutional coagulopathy. Pigs (randomized) received either fibrinogen (200 mg kg(-1)) and PCC (35 IU kg(-1)) (n=10), or placebo (n=10). Thereafter, a standard liver laceration was performed to induce uncontrolled haemorrhage. The subsequent blood loss and survival time were determined as primary outcome variables. Throughout the experiment serial blood samples were obtained to assess the competence of the haemostatic system using standard coagulation tests, modified Thrombelastograph measurements (ROTEM) and electron microscopy clot imaging. As compared with baseline, after haemodilution both groups showed statistically significant impairment of haemostasis as measured with standard coagulation tests and thrombelastography. These parameters significantly improved after administration of the study drugs while aPPT measurements remained unchanged. Blood loss after liver injury was significantly less in the treatment group as compared with placebo: 240 ml (50-830) vs 1800 ml (1500-2500) (P<0.0001). All treated animals survived, whereas 80% of the placebo group died (P<0.0001). During haemodilution, substitution of fibrinogen and PCC causes an enhancement of coagulation and final clot strength. This reversal of dilutional coagulopathy may reduce blood loss and mortality when large amounts of colloids are needed to maintain normovolaemia during huge blood losses.


Seroepidemiological studies indicate frequent and repeated exposure to Campylobacter spp. during childhood.
The annual number of episodes of clinical gastroenteritis caused by Campylobacter spp. in The Netherlands is estimated to be 75 000, i.e. once per 200 person life-years. This number is based on extrapolation of culture results from population-based studies. The number of culture-confirmed cases of Campylobacter infection peaks in the first 3 years of life and again between the ages of 20 and 25 years. The seroepidemiology of Campylobacter describes the relationship between age and exposure to Campylobacter and reflects both symptomatic and asymptomatic infections. Using a validated ELISA system, antibodies to Campylobacter were measured in an age-stratified sample (n=456) of the PIENTER serum collection of the Dutch general population. The seroprevalence of Campylobacter IgG antibodies increased with age, reaching almost 100% at age 20 years. Antibody levels steadily increased with age until young adulthood, suggesting repeated exposure to Campylobacter. In conclusion, seroepidemiological data demonstrated repeated exposures to Campylobacter throughout life, most of which do not lead to clinical symptoms. From young adulthood, >95% of the population in The Netherlands had serological evidence for exposure to Campylobacter.


"Please keep an eye on your younger sister": sibling supervision and young children's risk of unintentional injury.
Parental supervision reduces young children's risk of unintentional injuries, but supervision by older siblings has been shown to increase risk. The current study explored how this differential risk of injury may arise. The supervision behaviours of mothers were compared to those of their older children when each was the designated supervisor of a young child in their family in a setting having 'contrived hazards'. Mothers engaged in more proactive safety behaviours by removing hazards, whereas older siblings more often modelled injury-risk behaviours by interacting with hazards, and supervisees were likely to interact with hazards the older sibling touched. Supervisees displayed more injury-risk behaviours when supervised by a sibling, yet sibling supervisors were less attentive to supervisee risk behaviours than mothers. Supervisees also were more non-compliant with older siblings than mothers when requested to stop risk taking. Both supervisor and supervisee behaviour patterns contribute to increase the risk of injury when older siblings supervise younger ones.


Sorption of Metal Ions on Alumina
Precipitation and adsorption of metal ions (Co(II), Ni(II), Cu(II), and Cr(III)) on gamma-alumina were investigated experimentally. A surface chemical reaction model to calculate concentrations of aluminum ions, metal ions, and pH as variables depending on amount of alumina, volume of liquid and gas phase, initial metal concentration, and amount of acid or base added is presented. In the case of Co(II) the pH dependence of rest concentrations with and without alumina is equal; adsorption may be disregarded. For the other ions adsorption is important. Considering the charge of the surface does not improve the fit. In the pH region, where adsorption leads to lower rest concentrations than precipitation, adsorption may be described by a Henry isotherm. Copyright 1997 Academic Press. Copyright 1997Academic Press


A case-control study of oxidized low density lipoproteins and preeclampsia risk.
Diffuse vascular endothelial dysfunction, secondary to oxidative stress, is an important pathological feature of preeclampsia. Oxidative conversion of low density lipoproteins (LDL) to oxidized-LDL (Ox-LDL) is considered an important step in transforming macrophages into lipid-laden foam cells destined to develop into early atherosclerotic-like lesions. In our study of 95 women with preeclampsia and 100 controls, we evaluated the association between maternal plasma Ox-LDL concentrations and preeclampsia risk. Ox-LDL concentrations were measured using a solid phase two-site enzyme immunoassay. Plasma lipids were measured using standard enzymatic procedures. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. Plasma Ox-LDL concentrations were positively correlated with cholesterol, triglyceride (TG), and LDL concentrations in cases and controls, (Spearman's r ranging from 0.39-0.48, p-values all <0.01). There was no evidence of an increased risk of preeclampsia across increasing quartiles of Ox-LDL. The ORs for successive quartiles, with the lowest as the reference group, were as follows: 1.0, 1.1, 0.6, and 1.2. Women with extremely high concentrations of Ox-LDL (> or =73 U/L, the upper decile), as compared with those with lower values (<73 U/L) had a 2.7-fold increased risk of preeclampsia (95% CI 1.0-6.8). Women with high Ox-LDL and high TG concentrations (> or =284 mg/dl), as compared with those without these two factors, had a 9.6-fold increased preeclampsia risk (95% CI 2.0-45.6). Elevated Ox-LDL, particularly in conjunction with elevated TG, appears to be a risk factor of preeclampsia.


Nutraceuticals for metabolic syndrome management: from laboratory to benchside.
Metabolic syndrome (MetS) is a world-wide epidemic disease associated with increased morbidity and mortality. Treatment strategies include pharmacologic and non-pharmacologic methods, with varying degrees of success rate all over the world. Pharmaceutical interest in this field is growing, together with patients' requests for supplementary (or "alternative") treatments. The knowledge of nutraceuticals beneficial effects in subjects with the MetS could help us to better define the appropriate treatment for these subjects, in particular those with contraindications for commonly used drugs, or to achieve guidelines suggested targets. On the other side, it could be not convenient to use a nutraceutical to treat each metabolic syndrome component (i.e. from 3 to 5) in each affected subjects. Thus, this review tries to focus on widely marketed nutraceuticals with clinically demonstrated effects on more than one component of the MetS, namely omega-3 fatty acids, berberine, psyllium and other soluble fibers, cinnamon, chromium picolinate, banaba, and bitter gourd.


The Effects of Different Classes of Antihypertensive Drugs on Patients with COVID-19 and Hypertension: A Mini-Review.
Hypertension is a major risk factor for cardiovascular disease. Previous studies showed that patients with hypertension are at an increased risk of developing severe COVID-19 infection. Therefore, proper blood pressure control in hypertensive patients with COVID-19 is of great importance. In this review, we discussed the effects of different classes of antihypertensive drugs on patients with hypertension and COVID-19.


Effects of salience are both short- and long-lived.
A salient object can attract attention irrespective of its relevance to current goals. However, this bottom up effect tends to be short-lived (e.g. <150 ms) and it is generally assumed that top down processes such as goals or task instructions operating in later time windows override the effect of salience operating in early time windows. While the majority of studies on visual search and scene viewing comply with the assumptions of top down and bottom up processes operating in different time windows and that the former overrides the latter, we point to some possible anomalies in decision research. To explore these anomalies and thereby test the two key assumptions, we manipulate the salience and valence of one information cue in a decision task. Our analyses reveal that in decision tasks top down and bottom up processes do not operate in different time windows as predicted, nor does the former process necessarily override the latter. Instead, we find that the maximum effect of salience on the likelihood of making a saccade to the target cue is delayed until about 20 saccades after stimulus onset and that the effects of salience and valence are additive rather than multiplicative. Further, we find that in the positive and neutral valence conditions, salience continues to exert pressure on saccadic latency, i.e. the interval between saccades to the target with high salience targets being fixated faster than low salience targets. Our findings challenge the assumption that top down and bottom up processes operate in different time windows and the assumption that top down processes necessarily override bottom up processes.


Magnetic resonance imaging of bilateral mesial temporal sclerosis in chronic kernicterus.
Kernicterus is an encephalopathy resulting from the cerebral deposition of unconjugated bilirubin in the neonatal period. We report a case of kernicterus where MRI demonstrated bilateral symmetric high signal intensity and volume loss in the hippocampus in addition to globus pallidus and subthalamic nucleus hyperintensity onT2-weighted images. The authors believe that hippocampal sclerosis, plays a role in adding specificity to the imaging diagnosis of kernicterus.


Estrogen inhibition of EAE involves effects on dendritic cell function.
Estrogen has been found to have suppressive effects on the induction of experimental autoimmune encephalomyelitis (EAE), an animal model for the human disease multiple sclerosis. We have investigated the effects of 17beta-estradiol (E2) treatment on dendritic cells (DCs) in two different mouse models of EAE. The frequency of CD11b(+)/CD11c(+) DCs was significantly decreased in the brain of mice protected from EAE induction by E2 treatment. In addition, the frequency of CD11c(+)/CD8alpha(+) DCs producing tumor necrosis factor (TNF)alpha and interferon (IFN)gamma in the spleen of E2-treated mice was dramatically decreased compared to that in control mice with EAE, demonstrating an effect of E2 on DC function. In order to examine E2 effects on DCs in more detail, splenic DCs were cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 to promote maturation. E2 pretreatment was found to suppress the ability of cultured DCs bearing a mature phenotype to present Ag to myelin basic protein (MBP)-specific T cells. Analysis of cytokine production demonstrated that E2 decreased TNFalpha, IFNgamma and IL-12 production in mature DCs. In addition, MBP-specific T cells cocultured with E2-pretreated mature DCs in the presence of antigen demonstrated a shift towards production of Th2 cytokines IL-4 and IL-10 and a concomitant decrease in the production of Th1 cytokines TNFalpha and IFNgamma. Thus, E2 treatment appears to have multiple effects on the DC population, which may contribute to a down-regulation or block in the activation of Th1 cells involved in the induction of EAE.


The search for new antimicrobials: why we need new options.
The increasing identification of antibiotic-resistant pathogens that cause serious infections cannot be ignored. Although the future cannot be predicted with certainty, it is surely possible that an extensive epidemic of resistant bacterial infections could potentially harm millions of people. Given that it takes more than 10 years to establish the efficacy and safety of new compounds, there is an urgent need to restock the antibiotic pipeline. Only a few new antibacterial agents have received approval by the US Food and Drug Administration in the last 5 years, including linezolid in 2001, cefditoren, pivoxil and ertapenem in 2002, gemifloxacin and daptomycin in 2003, and telithromycin in 2004. Many of these agents are improved derivatives from established classes of antibiotics, and several are directed primarily at resistant Gram-positive bacteria (e.g., linezolid and daptomycin). One promising new addition is the recent approval of tigecycline (Tigacyl, Wyeth) in June 2005.


24-hour profiles of blood pressure and heart rate in Cushing's syndrome. Evidence for differential control of cardiovascular variables by glucocorticoids.
We monitored the circadian profile of cortisol, systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) in 33 normotensive subjects aged 20-40 years, 20 normotensive subjects aged 40-60, 32 patients with essential hypertension and 13 patients with Cushing's syndrome (6 pituitary adenomas, 5 adrenal adenomas and 2 adrenal carcinomas). All controls and patients underwent serial blood drawings at 4-h intervals during the 24-h cycle. BP and HR were recorded every 30 min by an automatic, room-restricted instrument. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry) to quantify rhythm parameters such as the MESOR (rhythm-adjusted average), amplitude (difference between maximum and MESOR) and acrophase (timing of the crest of the rhythm). Both the control and essential hypertensive subjects showed a BP and HR circadian profile characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: p less than 0.001). The chronobiological analysis did not reveal any significant difference between healthy young and aged subjects. BP rhythmicity was disrupted in patients affected by Cushing's syndrome, whereas the 24-h oscillation of HR was preserved (p less than 0.001). Patients with pituitary-dependent Cushing's syndrome had higher BP levels than adrenal-dependent subjects (p less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control.