Fluctuations of water quality time series in rivers follow superstatistics.
Superstatistics is a general method from nonequilibrium statistical physics which has been applied to a variety of complex systems, ranging from hydrodynamic turbulence to traffic delays and air pollution dynamics. Here, we investigate water quality time series (such as dissolved oxygen concentrations and electrical conductivity) as measured in rivers and provide evidence that they exhibit superstatistical behavior. Our main example is time series as recorded in the River Chess in South East England. Specifically, we use seasonal detrending and empirical mode decomposition to separate trends from fluctuations for the measured data. With either detrending method, we observe heavy-tailed fluctuation distributions, which are well described by log-normal superstatistics for dissolved oxygen. Contrarily, we find a double peaked non-standard superstatistics for the electrical conductivity data, which we model using two combined χ 2 -distributions.


Semantic processing of previews within compound words.
Previous studies have suggested that previews of words prior to fixation can be processed orthographically, but not semantically, during reading of sentences (K. Rayner, D. A. Balota, & A. Pollatsek, 1986). The present study tested whether semantic processing of previews can occur within words. The preview of the second constituent of 2-constituent Finnish compound nouns was manipulated. The previews were either identical to the 2nd constituent or they were incorrect in the form of a semantically related word, a semantically unrelated word, or a semantically meaningless nonword. The results indicate that previews of 2nd constituents within compound words can be semantically processed. The results have important implications for understanding the nature of preview and compound word processing. These issues are crucial to developing comprehensive models of eye-movement control and word recognition during reading.


Physical self-similarity enhances the gaze-cueing effect.
Important social information can be gathered from the direction of another person's gaze, such as their intentions and aspects of the environment that are relevant to those intentions. Previous work has examined the effect of gaze on attention through the gaze-cueing effect: an enhancement of performance in detecting targets that appear where another person is looking. The present study investigated whether the physical self-similarity of a face could increase its impact on attention. Self-similarity was manipulated by morphing participants' faces with those of strangers. The effect of gaze direction on target detection was strongest for faces morphed with the participant's face. The results support previous work suggesting that self-similar faces are processed differently from dissimilar faces. The data also demonstrate that a face's similarity to one's own face influences the degree to which that face guides our attention in the environment.


Sonographic assessment of the fetal palpebral fissure slant--an additional tool in the prenatal diagnosis of syndromes.
Several syndromes and aneuploidies are associated with ocular abnormalities including up- and down-slanting palpebral fissures. We describes a technique for the sonographic assessment of the fetal palpebral fissure slant which was used in 70 normal pregnancies from 14 to 36 weeks of gestation. In a frontal view of the fetal face, the inferior angle between the palpebral fissure and the midline of the skull was determined. The median angle was 89 degrees, with a range from 87 degrees to 90 degrees. In selected cases, sonographic assessment of the fetal palpebral fissure slant may be a helpful additional tool in the prenatal diagnosis of syndromes, as demonstrated in a fetus with Seckel syndrome associated with downslanting palpebral fissures and in a fetus with Down's syndrome associated with upslanting palpebral fissures.


Stickler syndrome: clinical characteristics and diagnostic criteria.
The purpose of this study was to establish diagnostic criteria for Stickler syndrome. Ninety patients from 38 families had complete evaluations for possible Stickler syndrome. Molecular confirmation of COL2A1 mutation status (type I Stickler syndrome) was available on 25 patients from six families. In the remaining 65 patients, 47 from 25 families were affected with Stickler syndrome and 18 from seven families were unaffected with Stickler syndrome. A diagnostic nosology based on type I Stickler patients with known COL2A1 mutations was applied to clinically affected and unaffected patients. A diagnostic scale of 9 points evaluated molecular data or family history data and characteristic ocular, orofacial, auditory, and musculoskeletal findings. A score of > or =5 was diagnostic of Stickler syndrome. These criteria demonstrate 100% sensitivity when applied to type I Stickler syndrome patients with known COL2A1 mutations, 98% sensitivity when applied to clinically affected Stickler patients, and 86% specificity when applied to patients unaffected based on clinical and/or molecular analysis. We conclude that diagnostic criteria based on type I Stickler patients with molecularly confirmed COL2A1 mutations appear to be sensitive and specific for the diagnosis of this syndrome and should be helpful to clinicians when making the diagnosis.


Osteonecrosis of the Femoral Head: Lipotoxicity Exacerbation in MSC and Modifications of the Bone Marrow Fluid.
Osteonecrosis of the femoral head (ON) is a multifactorial bone disease that can evolve to a progressive destruction of the hip joint. Different pathogenic processes have been proposed, among them, an increase of bone marrow (BM) fat resulting from adipocyte accumulation. Marrow adipocytes are active BM residents that influence the microenvironment by releasing cytokines, adipokines, and free fatty acids (FA). We explored the impact of palmitate (Palm) and oleate on function and survival of BM-derived mesenchymal stromal cells (MSC) of osteonecrotic patients (ONMSC) and healthy volunteers. Moreover, we analyzed the FA profile of the serum and the BM supernatant fluid (BMSF). We demonstrated that exposure to the saturated FA Palm favored MSC differentiation through the adipogenic lineage at the expense of the osteoblastic phenotype. Moreover, adipogenesis was intensified in ONMSC. The susceptibility to Palm toxicity was aggravated in ONMSC concomitantly with a greater activation of the proapoptotic extracellular signal-regulated kinase pathway. Moreover, cellular mechanisms implicated in the protection against lipotoxicity, such as stearoyl-coenzyme A desaturase 1 and carnitine palmitoyl transferase 1 expression, were dysregulated in ONMSC. Palm-induced interleukin (IL)-6 and IL-8 secretion was also exacerbated in ONMSC. Our results established that, in the serum, the FA profiles were comparable in ON and healthy subjects. However, both the concentrations and the FA composition were modified in the BMSF of ON patients, highlighting a drastic change of the BM microenvironment in ON patients. Altogether, our work suggests that marrow adipocyte enlargement could affect the process of bone remodeling and, therefore, play a role in the pathogenesis of ON.


A spiking network model of cerebellar Purkinje cells and molecular layer interneurons exhibiting irregular firing.
While the anatomy of the cerebellar microcircuit is well-studied, how it implements cerebellar function is not understood. A number of models have been proposed to describe this mechanism but few emphasize the role of the vast network Purkinje cells (PKJs) form with the molecular layer interneurons (MLIs)-the stellate and basket cells. We propose a model of the MLI-PKJ network composed of simple spiking neurons incorporating the major anatomical and physiological features. In computer simulations, the model reproduces the irregular firing patterns observed in PKJs and MLIs in vitro and a shift toward faster, more regular firing patterns when inhibitory synaptic currents are blocked. In the model, the time between PKJ spikes is shown to be proportional to the amount of feedforward inhibition from an MLI on average. The two key elements of the model are: (1) spontaneously active PKJs and MLIs due to an endogenous depolarizing current, and (2) adherence to known anatomical connectivity along a parasagittal strip of cerebellar cortex. We propose this model to extend previous spiking network models of the cerebellum and for further computational investigation into the role of irregular firing and MLIs in cerebellar learning and function.


Love hurts: the influence of social relations on exercise self-efficacy for older adults with osteoarthritis.
Exercise self-efficacy is a powerful predictor of physical activity behavior, which enhances health and well-being for older adults. Social relations have been proposed as influential precursors for exercise self-efficacy. In a longitudinal study of 160 older adults with osteoarthritis (76.9% women), the authors found that social support (but not social strain) significantly predicted exercise self-efficacy in a structural equation model examining cross-sectional data: chi(2) (178, N = 160) = 264.57, p < .01; RMSEA = .06; CFI = .92; TLI = .90. When data were examined longitudinally, however, social strain (but not social support) significantly predicted lower exercise self-efficacy 1 year later: Xi(2) (233, N = 160) = 288.64, p < .01; RMSEA = .04; CFI = .96; TLI = .95. Results support the negativity effect, suggesting that social strain might be the more potent aspect of social relations and should be the target of interventions.


Ion-ion correlations across and between electrified graphene layers.
When an ionic liquid adsorbs onto a porous electrode, its ionic arrangement is deeply modified due to a screening of the Coulombic interactions by the metallic surface and by the confinement imposed upon it by the electrode's morphology. In particular, ions of the same charge can approach at close contact, leading to the formation of a superionic state. The impact of an electrified surface placed between two liquid phases is much less understood. Here we simulate a full supercapacitor made of the 1-butyl-3-methylimidazolium hexafluorophosphate and nanoporous graphene electrodes, with varying distances between the graphene sheets. The electrodes are held at constant potential by allowing the carbon charges to fluctuate. Under strong confinement conditions, we show that ions of the same charge tend to adsorb in front of each other across the graphene plane. These correlations are allowed by the formation of a highly localized image charge on the carbon atoms between the ions. They are suppressed in larger pores, when the liquid adopts a bilayer structure between the graphene sheets. These effects are qualitatively similar to the recent templating effects which have been reported during the growth of nanocrystals on a graphene substrate.


Vaccine safety versus vaccine efficacy in mass immunisation programmes.
In community-wide immunisation programmes against childhood infections there is a conflict between the interests of the individual (vaccine safety and efficacy) and the interests of the community (vaccine uptake and level of herd immunity). Studies suggesting that the complication rate is greater with the high efficacy Urabe Am 9 mumps vaccine than with the lower efficacy Jeryl Lynn vaccine, have led to concern about whether the higher efficacy mumps vaccine should be introduced or retained in nationwide mass immunisation programmes. We describe the use of a mathematical model to assess benefits and risks to both individual and community, and illustrate this method by reference to immunisation programmes based on these vaccines. On the basis of current epidemiological data on viral transmission and vaccine coverage in England and Wales, data on vaccine-associated and infection-associated complication rates, and vaccine efficacies estimated from clinical trials, our analyses suggest there is little to choose between the two vaccines, but that overall performance depends on the level of vaccine coverage in a defined population. In community-based programmes, the greater apparent safety of the Jeryl Lynn vaccine (fewer vaccine-induced complications) is offset by the greater apparent efficacy of the Urabe Am 9 vaccine (fewer complications due to natural infection). The findings suggest that it may not always be in the interests of the community to use the vaccine with the lowest complication rate.


Stemming the "ageism pandemic": A qualitative inquiry with older adults in residential care facilities during the Covid-19 outbreak.
The Covid-19 pandemic added to collective concerns, making health risks salient especially for the older population. The health emergency exacerbated an already widespread negative representation of aging, and phenomena such as ageism. With the present qualitative inquiry, 21 episodic interviews were collected with the aim of understanding the experience of older adults in residential care facilities, exploring their ideas of aging and the viewpoints that helped them to respond to the pandemic successfully. A thematic analysis was conducted using NudIst software. The results show that participants described multiple personal and relational resources they used to cope with the pandemic, and they were able to express counter-narratives to the ideas of aging as coinciding with decline, and of lockdown as a source of distress alone. The paper concludes with reflections on the relevance of research capable of challenging unhelpful dominant discourses and averting the risk of them turning into negative prophecies.


Somatic hypermutation of immunoglobulin genes in human neonates.
The antibody response in the young infant is limited in several ways; in particular, responses generally are of low affinity and restricted to IgM. This raises the question whether the affinity maturation process, consisting of somatic mutation of immunoglobulin genes coupled with selection of high-affinity variants, is operative in the neonate. Re-arranged V(H)6 genes were amplified by polymerase chain reaction (PCR) from cord blood and from peripheral blood of infants. Heteroduplex analysis detected mutation in only 2/18 cord blood samples, while mutations were seen from about 10 days of age onwards. Cloning and sequencing of mutated neonatal V(H)6 genes showed that mutated sequences contained relatively few mutations (one to three mutations per sequence) compared with published values of about 10 in adult IgM sequences. Selection was not evident in the majority of neonatal samples. Thus mutation can occur in the human neonate, but is minimal and generally not accompanied by selection. The age at which affinity maturation develops effectively is yet to be defined.


Chest radiographic findings and their correlation with disease progression in COVID-19 patients in northern India.
The present study was undertaken to describe and quantify the spectrum of radiographic findings on coronavirus disease 2019 (COVID-19) patients. The study also aimed to analyse the changes in chest X-ray (CXR) with disease progression. COVID-19 patients admitted between the period of 15 March 2020 and 1 July 2020 were retrospectively enrolled. CXR images were assessed and reported as 'Normal' or 'Abnormal'. A severity score was calculated using Warren et al.'s Radiographic Assessment of Lung Edema scoring. Correlations of the severity score thus calculated were sought with age, sex, clinical manifestations and presence of comorbidities. Five hundred patients (342 males, 158 females) were enrolled, median age being 35 years. Fever and cough were the most common symptoms but significant correlation of an abnormal CXR was found with dyspnoea. CXRs were normal in 67% and abnormal in 33% patients. The commonest comorbidities were diabetes mellitus and cardiovascular disease including hypertension, coronary artery disease and congestive heart failure. Predominant pattern was ground glass opacities, reticular alteration and consolidation peaking in the second week from symptom onset. The most frequent distribution was bilateral, peripheral with middle/lower predominance. Increasing age, male sex, presence of dyspnoea and comorbidities correlated with abnormal findings on CXR. Critical illness and mortality correlated strongly with increasing age, male sex and presence of dyspnoea, less so with presence of comorbidities. In the current scenario with clinicians and radiologists working in tandem, CXR seems to be a promising tool in providing relevant information in a simplified way.


Experimental evidence for supercontinuum generation by fission of higher-order solitons in photonic fibers.
We report on an experimental study of supercontinuum generation in photonic crystal fibers with low-intensity femtosecond pulses, which provides evidence for a novel spectral broadening mechanism. The observed results agree with our theoretical calculations carried out without making the slowly varying envelope approximation. Peculiarities of the measured spectra and their theoretical explanation demonstrate that the reason for the white-light generation in photonic crystal fibers is fission of higher-order solitons into redshifted fundamental solitons and blueshifted nonsolitonic radiation.


CO Adsorption on Reconstructed Ir(100) Surfaces from UHV to mbar Pressure: A LEED, TPD, and PM-IRAS Study.
Clean and stable surface modifications of an iridium (100) single crystal, i.e., the (1 × 1) phase, the (5 × 1) reconstruction, and the oxygen-terminated (2 × 1)-O surface, were prepared and characterized by low energy electron diffraction (LEED), temperature-programmed desorption (TPD), infrared reflection absorption spectroscopy (IRAS) and polarization modulation IRAS (PM-IRAS). The adsorption of CO in UHV and at elevated (mbar) pressure/temperature was followed both ex situ and in situ on all three surface modifications, with a focus on mbar pressures of CO. The Ir(1 × 1) surface exhibited c(4 × 2)/c(2 × 2) and c(6 × 2) CO structures under low pressure conditions, and remained stable up to 100 mbar and 700 K. For the (2 × 1)-O reconstruction CO adsorption induced a structural change from (2 × 1)-O to (1 × 1), as confirmed by LEED, TPD, and IR. For Ir (2 × 1)-O TPD indicated that CO reacted with surface oxygen forming CO2. The (5 × 1) reconstruction featured a reversible and dynamic behavior upon CO adsorption, with a local lifting of the reconstruction to (1 × 1). After CO desorption, the (5 × 1) structure was restored. All three reconstructions exhibited CO adsorption with on-top geometry, as evidenced by IR. With increasing CO exposure the resonances shifted to higher wavenumber, due to adsorbate-adsorbate and adsorbate-substrate interactions. The largest wavenumber shift (from 2057 to 2100 cm-1) was observed for Ir(5 × 1) upon CO dosing from 1 L to 100 mbar.


Contribution of the polymorphism rs1800469 of transforming growth factor β in the development of myocardial infarction: meta-analysis of 5460 cases and 8413 controls (MOOSE-compliant article).
Studies investigating the association between transforming growth factor (TGF-β-509C/T, rs1800469) promoter polymorphism and myocardial infarction (MI) risk reported inconsistent results. The aim of our study was to assess the association between the 509C/T polymorphism of the TGF-β gene (rs1800469) and MI risk.A total of 5460 cases and 8413 controls in 7 case-control studies were incorporated in our current meta-analysis. The original studies were selected through searching the databases of the PubMed and EMBASE. The odds ratio (OR) and 95% confidence interval (95% CI) of TGF-β 509C/T (rs1800469) for MI risk were applied to estimate the strength of the association.Our results showed that T allele carriers had a 13% increased risk of MI, when compared with the C allele carriers (OR = 1.13, 95% CI: 1.00-1.27). In the subset analysis by the type of MI, significantly elevated risk of MI was associated with the homozygote TT and heterozygote C/T in no-AMI subjects, when compared with the CC homozygote carriers (OR = 1.12, 95% CI:1.02-1.23).Our meta-analysis shows that the polymorphism with homozygote TT and heterozygote C/T of TGF-β 509C/T (rs1800469) is significantly associated with the increased risk of MI.


A technical review of canonical correlation analysis for neuroscience applications.
Collecting comprehensive data sets of the same subject has become a standard in neuroscience research and uncovering multivariate relationships among collected data sets have gained significant attentions in recent years. Canonical correlation analysis (CCA) is one of the powerful multivariate tools to jointly investigate relationships among multiple data sets, which can uncover disease or environmental effects in various modalities simultaneously and characterize changes during development, aging, and disease progressions comprehensively. In the past 10 years, despite an increasing number of studies have utilized CCA in multivariate analysis, simple conventional CCA dominates these applications. Multiple CCA-variant techniques have been proposed to improve the model performance; however, the complicated multivariate formulations and not well-known capabilities have delayed their wide applications. Therefore, in this study, a comprehensive review of CCA and its variant techniques is provided. Detailed technical formulation with analytical and numerical solutions, current applications in neuroscience research, and advantages and limitations of each CCA-related technique are discussed. Finally, a general guideline in how to select the most appropriate CCA-related technique based on the properties of available data sets and particularly targeted neuroscience questions is provided.


Soil humic-like organic compounds in prescribed fire emissions using nuclear magnetic resonance spectroscopy.
Here we present the chemical characterization of the water-soluble organic carbon fraction of atmospheric aerosol collected during a prescribed fire burn in relation to soil organic matter and biomass combustion. Using nuclear magnetic resonance spectroscopy, we observed that humic-like substances in fire emissions have been associated with soil organic matter rather than biomass. Using a chemical mass balance model, we estimated that soil organic matter may contribute up to 41% of organic hydrogen and up to 27% of water-soluble organic carbon in fire emissions. Dust particles, when mixed with fresh combustion emissions, substantially enhances the atmospheric oxidative capacity, particle formation and microphysical properties of clouds influencing the climatic responses of atmospheric aeroso. Owing to the large emissions of combustion aerosol during fires, the release of dust particles from soil surfaces that are subjected to intense heating and shear stress has, so far, been lacking.


Chemical and biomarker responses for site-specific quality assessment of the Lake Maggiore (Northern Italy).
Since the 1990s, the Lake Maggiore (Northern Italy) has been recognized as an aquatic environment contaminated by DDTs and other persistent organic pollutants, but to date just few studies were carried out to investigate the effects of pollution to aquatic organisms. The aim of this study was the application of a stepwise approach based on chemical data, a suite of biomarkers and the integration of their responses into a biomarker response index (BRI) to evaluate the site-specific quality assessment in different sampling stations of Lake Maggiore, one of the largest European lakes. We used as biological model the freshwater bivalve Zebra mussel (Dreissena polymorpha). Several hundred bivalve specimens were sampled on May 2011 from eight sampling sites located along the lake shoreline. We measured levels of DDTs, PCBs, HCHs, HCB, and PAHs accumulated in D. polymorpha soft tissues by GC/MSn, while the activities of catalase, superoxide dismutase, glutathione peroxidase, and glutathione S-transferase, as well as the lipid peroxidation and protein carbonyl content were evaluated in homogenates from native bivalves as oxidative stress indices. Moreover, DNA damage was investigated by the alkaline precipitation assay. Significant imbalances of enzymatic activity were found in mussels from most of the sampling sites, as well as notable increases of damage to macromolecules. Health status of mussels from Baveno was greatly affected by lake pollution, probably due to high levels of DDTs measured in this site, while a wide variability in biomarker responses was found in all the other stations. The application of a BRI allowed distinguishing impacts of pollution to bivalves, confirming mussels from Baveno as the most threatened and revealing that also the health status of bivalves from Suna, Brissago, Pallanza, and Laveno is affected. These evidences suggest the usefulness of a specific index to integrate all the biomarker endpoints in order to provide a correct environmental risk assessment.


Behavioral Responses of Plum Curculio (Coleoptera: Curculionidae) to Different Enantiomer Concentrations and Blends of the Synthetic Aggregation Pheromone Grandisoic Acid.
The plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), is an important pest of fruit in North America. Males produce an aggregation pheromone (grandisoic acid) that attracts both sexes of the northern univoltine and the southern multivoltine strains. Grandisoic acid ((1R,2S)-1-methyl-2-(1-methylethenyl)-cyclobutaneacetic acid) is a chiral molecule containing one chiral center. A synthetic racemic mixture will contain two optical isomers that are mirror images of each other with equal amounts of (+)- and (-)-enantiomeric isomers. Male plum curculio only produce the (+) enantiomer. Some enantiomers can have antagonistic effects on the attraction of weevils to pheromones. An understanding of the effect of both enantiomers on the behaviour of plum curculio is needed to develop more efficient trap baits. Behavioural bioassays were conducted in a dual-choice still-air vertical olfactometer using a quantity of 1.5 ml of both (+) and (-) synthetic enantiomers and the racemic mixture of grandisoic acid with live female responders to determine which concentration and enantiomeric purity is the most attractive and if there is an antagonistic effect of the unnatural (-) enantiomer. Results indicated that plum curculio were attracted to low concentrations of the (+) enantiomer at 72% enantiomeric excess, but that strains were attracted to different concentrations of the (+) enantiomer (2×10(-7) mg/ml for univoltine, 2×10(-9) mg/ml for multivoltine).


Commentary on 'Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years'.
This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Furlong M, McGilloway S, Bywater T, Hutchings J, Smith SM, Donnelly M. Behavioural and cognitive-behavioural group-based parenting programmes for early-onset conduct problems in children aged 3 to 12 years. Cochrane Database of Systematic Reviews 2012, Issue 2. Art. No.: CD008225. DoI: 10.1002/14651858.CD008225.pub2.


Secure Data Aggregation Based on End-to-End Homomorphic Encryption in IoT-Based Wireless Sensor Networks.
By definition, the aggregating methodology ensures that transmitted data remain visible in clear text in the aggregated units or nodes. Data transmission without encryption is vulnerable to security issues such as data confidentiality, integrity, authentication and attacks by adversaries. On the other hand, encryption at each hop requires extra computation for decrypting, aggregating, and then re-encrypting the data, which results in increased complexity, not only in terms of computation but also due to the required sharing of keys. Sharing the same key across various nodes makes the security more vulnerable. An alternative solution to secure the aggregation process is to provide an end-to-end security protocol, wherein intermediary nodes combine the data without decoding the acquired data. As a consequence, the intermediary aggregating nodes do not have to maintain confidential key values, enabling end-to-end security across sensor devices and base stations. This research presents End-to-End Homomorphic Encryption (EEHE)-based safe and secure data gathering in IoT-based Wireless Sensor Networks (WSNs), whereby it protects end-to-end security and enables the use of aggregator functions such as COUNT, SUM and AVERAGE upon encrypted messages. Such an approach could also employ message authentication codes (MAC) to validate data integrity throughout data aggregation and transmission activities, allowing fraudulent content to also be identified as soon as feasible. Additionally, if data are communicated across a WSN, then there is a higher likelihood of a wormhole attack within the data aggregation process. The proposed solution also ensures the early detection of wormhole attacks during data aggregation.


Digital Filters for Molecular Interaction Field Descriptors.
Descriptor properties are often neglected when building 3D-QSAR models. The relevance of correlation and distribution profiles is tested in terms of the models' prediction power. A different approach to filter descriptors prior to variable selection is proposed. Additionally, a protocol for molecular interaction field descriptors selection and model validation is presented. The algorithms and protocols presented are quite simple and enable a different and powerful way to create parsimonious interaction field-based models.


Suitability of surgical tumor tissues, biopsy, or cytology samples for epidermal growth factor receptor mutation testing in non-small cell lung carcinoma based on chinese population.
Epidermal growth factor receptor (EGFR) mutation status is crucial in treatment selection for non-small cell lung cancer (NSCLC) patients; however, the detection materials' availability remains challenging in clinical practice. In this study, we collected surgical resection tissues, lymph node biopsy, and cytological samples for EGFR mutation testing and investigated the associations between gene mutation and clinical characteristics. Two hundred and seventy-six NSCLC adenocarcinoma specimens were collected, and highly sensitive amplification refractory mutation system method was implemented for EGFR mutation detection, with clinicopathologic characteristics involved in the final analysis. In the total of 276 samples, 96% (265/276) of tumors obtained evaluable EGFR mutation status, the frequency of mutation was 55.8% (148/265) in all specimens, and three different type samples shared a comparable successful testing rate: 97.4% (38/39) in surgical tumor tissues, 100% (108/108) in lymph node biopsy samples, and 92.2% (119/129) in cytological samples. EGFR mutation was significantly associated with sex, smoking history, lymph node metastasis status (N stage), primary tumor size, testing tissues origin, and sample type (P < .05). Multivariate analysis reconfirmed that smoking history and primary tumor size shared significant correlation with EGFR mutation after adjustment. Both lymph node biopsy and cytological samples were suitable surrogates for EGFR mutation detection in NSCLC compared with tumor tissues, gene status should be detected widely considering the high EGFR mutation rate, and nonsmoking history together with smaller primary tumor size was an independent indicator of EGFR mutation status.


Decline in verbal memory in non-demented older adults.
Decline in memory function was detected in 30% of healthy community-dwelling elderly over 6 years using a task assessing delayed word list recall. Individuals with memory decline over time also demonstrated relative deficits on additional tasks of memory and learning, a task of working memory and executive function, and on a verbal (category) fluency task at their most recent assessment. These relative deficits in the performance of individuals with memory decline cannot be explained by age-related changes, education, intelligence, mood, health-related factors, or the individuals' APOE epsilon 4 status. Decline in memory performance did not result in greater complaints of cognitive difficulties when compared with normal elderly, nor did it limit overall participation in life activities. Although the significance of memory decline in the current study was not determined quantitatively, memory decline is consistent with the early deterioration characteristic of mild cognitive impairment and preclinical Alzheimer's disease and confirms the need to monitor individuals with objective memory decline, even when these individuals fall within normal limits for a given neuropsychological task.


Myocardial contractility in the echo lab: molecular, cellular and pathophysiological basis.
In the standard accepted concept, contractility is the intrinsic ability of heart muscle to generate force and to shorten, independently of changes in the preload or afterload with fixed heart rates. At molecular level the crux of the contractile process lies in the changing concentrations of Ca2+ ions in the myocardial cytosol. Ca2+ ions enter through the calcium channel that opens in response to the wave of depolarization that travels along the sarcolemma. These Ca2+ ions "trigger" the release of more calcium from the sarcoplasmic reticulum (SR) and thereby initiate a contraction-relaxation cycle. In the past, several attempts were made to transfer the pure physiological concept of contractility, expressed in the isolated myocardial fiber by the maximal velocity of contraction of unloaded muscle fiber (Vmax), to the in vivo beating heart. Suga and Sagawa achieved this aim by measuring pressure/volume loops in the intact heart: during a positive inotropic intervention, the pressure volume loop reflects a smaller end-systolic volume and a higher end-systolic pressure, so that the slope of the pressure volume relationship moves upward and to the left. The pressure volume relationship is the most reliable index for assessing myocardial contractility in the intact circulation and is almost insensitive to changes in preload and after load. This is widely used in animal studies and occasionally clinically. The limit of the pressure volume relationship is that it fails to take into account the frequency-dependent regulation of contractility: the frequency-dependent control of transmembrane Ca2+ entry via voltage-gated Ca2+ channels provides cardiac cells with a highly sophisticated short-term system for the regulation of intracellular Ca2+ homeostasis. An increased stimulation rate increases the force of contraction: the explanation is repetitive Ca2+ entry with each depolarization and, hence, an accumulation of cytosolic calcium. As the heart fails, there is a change in the gene expression from the normal adult pattern to that of fetal life with an inversion of the normal positive slope of the force-frequency relation: systolic calcium release and diastolic calcium reuptake process is lowered at the basal state and, instead of accelerating for increasing heart rates, slows down. Since the force-frequency relation uncovers initial alteration of contractility, as an intermediate step between normal and abnormal contractility at rest, a practical index to measure it is mandatory. Measuring end-systolic elastance for increasing heart rates is impractical: increasing heart rates with atrial pacing has to be adjunct to the left ventricular conductance catheter, to the left ventricular pressure catheter, to the vena cava balloon, and to afterload changes. Furthermore, a noninvasive index is needed. Noninvasive measurement of the pressure/volume ratio for increasing heart rates during stress in the echo lab could be the practical answer to this new clinical demand in the current years of a dramatic increase in the number of heart failure patients.


SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer.
Checkpoint inhibitor (CPI) therapy revolutionized treatment for advanced non-small-cell lung cancer (NSCLC); however, most patients progress due to primary or acquired resistance. Sitravatinib is a receptor tyrosine kinase inhibitor that can shift the immunosuppressive tumor microenvironment toward an immunostimulatory state. Combining sitravatinib with nivolumab (sitra + nivo) may potentially overcome initial CPI resistance. In the phase III SAPPHIRE study, patients with advanced non-oncogenic driven, nonsquamous NSCLC who initially benefited from (≥4 months on CPI without progression) and subsequently experienced disease progression on or after CPI combined with or following platinum-based chemotherapy were randomized 1 : 1 to sitra (100 mg once daily administered orally) + nivo (240 mg every 2 weeks or 480 mg every 4 weeks administered intravenously) or docetaxel (75 mg/m2 every 3 weeks administered intravenously). The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR; all assessed by blinded independent central review), and safety. A total of 577 patients included randomized: sitra + nivo, n = 284; docetaxel, n = 293 (median follow-up, 17.1 months). Sitra + nivo did not significantly improve OS versus docetaxel [median, 12.2 versus 10.6 months; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.70-1.05; P = 0.144]. The median PFS was 4.4 versus 5.4 months, respectively (HR 1.08, 95% CI 0.89-1.32; P = 0.452). The ORR was 15.6% for sitra + nivo and 17.2% for docetaxel (P = 0.597); CBR was 75.5% and 64.5%, respectively (P = 0.004); median DOR was 7.4 versus 7.1 months, respectively (P = 0.924). Grade ≥3 treatment-related adverse events were observed in 53.0% versus 66.7% of patients receiving sitra + nivo versus docetaxel, respectively. Although median OS was numerically longer with sitra + nivo, the primary endpoint was not met in patients with previously treated advanced nonsquamous NSCLC. The safety profiles demonstrated were consistent with previous reports.


Ocular burn from microwaved egg.
Ocular thermal injuries from improper use of a microwave oven are rare. Manufacturers recommend cooking eggs in the microwave only after the shell has been removed and the yolk sac has been pierced with a pin. Failure to follow these instructions is likely to result in ocular and facial burns. Only eight adult cases of such injuries have been documented so far. Ocular burn from the explosion of a microwaved egg in a pediatric patient is being reported for the first time in the English medical literature.


Endosomes, receptor tyrosine kinase internalization and signal transduction.
Upon the binding of insulin or epidermal growth factor to their cognate receptors on the liver parenchymal plasmalemma, signal transduction and receptor internalization are near co-incident. Indeed, the rapidity and extent of ligand mediated receptor internalization into endosomes in liver as well as other organs predicts that signal transduction is regulated at this intracellular locus. Although internalization has been thought as a mechanism to attenuate ligand mediated signal transduction responses, detailed studies of internalized receptors in isolated liver endosomes suggest an alternative scenario whereby selective signal transduction pathways can be accessed at this locus.


Tailoring elastic properties of silica aerogels cross-linked with polystyrene.
The effect of incorporating an organic linking group, 1,6-bis(trimethoxysilyl)hexane (BTMSH), into the underlying silica structure of a styrene cross-linked silica aerogel is examined. Vinyltrimethoxysilane (VTMS) is used to provide a reactive site on the silica backbone for styrene polymerization. Replacement of up to 88 mol % of the silicon from tetramethoxyorthosilicate with silicon derived from BTMSH and VTMS during the making of silica gels improves the elastic behavior in some formulations of the cross-linked aerogels, as evidenced by measurement of the recovered length after compression of samples to 25% strain. This is especially true for some higher density formulations, which recover nearly 100% of their length after compression to 25% strain twice. The compressive modulus of the more elastic monoliths ranged from 0.2 to 3 MPa. Although some of these monoliths had greatly reduced surface areas, changing the solvent used to produce the gels from methanol to ethanol increased the surface area in one instance from 6 to 220 m(2)/g with little affect on the modulus, elastic recovery, porosity, or density.


[Incorporation C14-glycine and H3-methionine into total and cytoplasmic proteins of rat skeletal muscles in insulin deficiency and glucocorticoid hormone excess].
It was shown that insulin stimulated and hydrocortisone inhibited 14C'glycine and 3H methionine incorporation into the skeletal muscle polysome, cytosol and total proteins of rats alloxan diabetes. Hydrocortisone inhibitory effect was slightly diminished after insulin administration when both hormones were used simultaneously. The blood glucose content of diabetic rats decreased under insulin action and rose after hydrocortisone use. It was concluded that the inhibition of skeletal muscle protein metabolism may be caused not only by insulin deficiency, but also by glucocorticoid hormone excess.


Muscarinic receptors and ligands in cancer.
Emerging evidence indicates that muscarinic receptors and ligands play key roles in regulating cellular proliferation and cancer progression. Both neuronal and nonneuronal acetylcholine production results in neurocrine, paracrine, and autocrine promotion of cell proliferation, apoptosis, migration, and other features critical for cancer cell survival and spread. The present review comprises a focused critical analysis of evidence supporting the role of muscarinic receptors and ligands in cancer. Criteria are proposed to validate the biological importance of muscarinic receptor expression, activation, and postreceptor signaling. Likewise, criteria are proposed to validate the role of nonneuronal acetylcholine production in cancer. Dissecting cellular mechanisms necessary for muscarinic receptor activation as well as those needed for acetylcholine production and release will identify multiple novel targets for cancer therapy.


Identification of neonatal white matter on DTI: influence of more inclusive thresholds for atlas segmentation.
Semi-automated diffusion tensor imaging (DTI) analysis of white matter (WM) microstructure offers a clinically feasible technique to assess neonatal brain development and provide early prognosis, but is limited by variable methods and insufficient evidence regarding optimal parameters. The purpose of this research was to investigate the influence of threshold values on semi-automated, atlas-based brain segmentation in very-low-birth-weight (VLBW) preterm infants at near-term age. DTI scans were analyzed from 45 VLBW preterm neonates at near-term-age with no brain abnormalities evident on MRI. Brain regions were selected with a neonatal brain atlas and threshold values: trace <0.006 mm2/s, fractional anisotropy (FA)>0.15, FA>0.20, and FA>0.25. Relative regional volumes, FA, axial diffusivity (AD), and radial diffusivity (RD) were compared for twelve WM regions. Near-term brain regions demonstrated differential effects from segmentation with the three FA thresholds. Regional DTI values and volumes selected in the PLIC, CereP, and RLC varied the least with the application of different FA thresholds. Overall, application of higher FA thresholds significantly reduced brain region volume selected, increased variability, and resulted in higher FA and lower RD values. The lower threshold FA>0.15 selected 78±21% of original volumes segmented by the atlas, compared to 38±12% using threshold FA>0.25. Results indicate substantial and differential effects of atlas-based DTI threshold parameters on regional volume and diffusion scalars. A lower, more inclusive FA threshold than typically applied for adults is suggested for consistent analysis of WM regions in neonates.


Effect of restricted daylength during the growing period on semen quality and fertility of turkey toms.
Two trials were conducted in which three daylength and light intensity treatments were applied to 144 growing turkey toms from 8 to 28 weeks of age. Treatments were (1) six hours of artificial light, (2) natural light and daylength, and (3) simulated natural daylength. At 28 weeks of age all toms were placed on 14 hours of daily light. Individual tom semen quality was evaluated every two weeks for six months, and on alternate weeks, eight hens were inseminated with semen pooled by treatment replicate to obtain fertility (May to December). Seasonal decline in semen production, sperm concentration, semen volume, and fertility was observed for toms on natural daylength after three months of production. Toms on six hours of light and those on simulated natural light maintained high levels of production and quality for the entire six month period. Semen production expressed as the average number of toms producing semen, sperm concentration, and fertily were significantly lower (P less than .01), and semen volume was significantly lower (P less than .05) for toms on natural light after six months. It was concluded that natural light was less desirable than controlled light for "off season" growing of toms.


Current status of medical oncology in Japan and changes over the most recent 7-year period: results of a questionnaire sent to designated cancer care hospitals.
According to a questionnaire sent to Designated Cancer Care Hospitals in Japan in 2013, only 39.4% of the institutes had medical oncology departments. Furthermore, most of these medical oncology departments were primarily responsible for the treatment of limited disease categories and the administration of newly developed therapeutic modalities, including molecular-targeted therapy. The aim of the present study was to update these previous findings and to clarify the changes over the intervening 7-year period. The questionnaire was sent to all 393 Designated Cancer Care Hospitals on 13 March 2020. Similar to the previous questionnaires, questions were asked regarding the presence of a medical oncology department, the number of physicians in the department and the degrees of responsibility for drug therapies provided by medical oncologists to adult patients with solid cancers. In total, 270 institutions (68.7%) responded. Overall, 145 of these 270 institutions (53.7%) had medical oncology departments, representing a significant increase compared with the results of the previous study (P < 0.01). Among the institutions with a medical oncology department, these departments were responsible for the administration of over 30% of all cytotoxic and molecular-targeted drug therapies for extragonadal germ cell tumors, cancers of unknown primary site, soft tissues, head and neck, esophagus, stomach, colon and rectum, and pancreas as well as the administration of immune checkpoint inhibitors (ICI) for microsatellite instability-high tumors, cancers of the stomach, esophagus and head and neck, and melanoma. The proportion of institutes with medical oncology departments in Japan has increased. In addition, the responsibility of medical oncology departments has expanded to include newly emerging drugs, such as ICIs.


Impact of Time to Surgery and Surgical Delay on Oncologic Outcomes for Renal Cell Carcinoma.
The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma. The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death. In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.


[Relevance and feasibility of reforms to create a universal health system in ChileRelevância e viabilidade de uma reforma para a criação de um sistema de saúde universal no Chile].
The health system in Chile is well developed, with broad national coverage. However, organizational limitations necessitate urgent structural reform due to a lack of resources and poor performance, with segmentation and inequity. The government's program for 2022-2026 proposes substantial reforms aimed at creating a universal health system. Other reform proposals formulated by various government programs and commissions, as well as think tanks, provide useful inputs to contextualize the government proposal.Different types of models coexist in the health system: public insurance is based on a social security model, the public system provides free care to the insured population, and private insurance and private care providers work on a market basis. The proposed system would function on the national health system model, combining a predominant national health service (Beveridge model) with a complementary social security system (Bismarck model), depending on the need for funding. With a focus on social project evaluation, the relevance (internal coherence and external alignment) and political and economic feasibility of the contents of the government program were reviewed. The proposal has internal coherence, but limited external alignment with the prevailing political and economic system, and little State capacity to increase the financing of public enterprises and their coverage. The contents of the proposal do not show sufficient facilitating conditions to reasonably suggest political and economic feasibility in terms of legal approval and effective implementation of the proposed reform.


Electrochemical determination of metformin via a carbon paste electrode modified with an Ag NPs/Cu2O/CuO-decorated bacterial nanocellulose composite.
Metformin (MET) is widely used in the treatment of diabetes either alone or in combination with other drugs, in drug discovery to evaluate the anti-diabetic potential of other drugs, and usually as a comparison compound in pharmacokinetics/pharmacodynamics studies. Measuring the concentration of this substance is very important both pre-clinically in different species and clinically in the medical monitoring of diabetic patients to prevent toxicity and ensure adherence to described drugs. Therefore, it is very important to develop a sensitive and selective method to measure MET. In this work, a new electrochemical biosensor based on a carbon paste electrode, modified with bacterial nanocellulose, copper oxide, and silver nanoparticles (Ag NPs/Cu2O/CuO/BNC/CPE) was used for high-sensitivity MET determination. The morphology and structure of this bio-nanocomposite were characterized by ATR-IR, FE-SEM, EDS, mapping, XRD, and DRS techniques. Compared with the CPE electrode, the Ag NPs/Cu2O/CuO/BNC/CPE modified electrode showed much higher electrocatalytic activities toward the oxidation of MET. The measurements were carried out by the cyclic voltammetry technique. Surface conductance was evaluated using the impedance technique. The results showed an increase in surface conductivity. The detection limit was obtained at 42.3 nM and two linear ranges 0.1-76 and 76-1000.0 μM were observed. The developed sensor had good features such as high sensitivity, reproducibility and repeatability, low detection limit, and fast response time. The obtained results from the real sample (MET tablets) were completely satisfactory.


Sulforaphane induces cell cycle arrest and apoptosis in murine osteosarcoma cells in vitro and inhibits tumor growth in vivo.
Sulforaphane (SFN), a naturally occurring isothiocyanate, is an attractive agent due to its potent anticancer effects. SFN suppresses the proliferation of various cancer cells in vitro and in vivo. In this study, we report that SFN inhibited the proliferation of cultured murine osteosarcoma LM8 cells. Twenty micromolar SFN completely inhibited the growth of LM8 cells and caused G2/M-phase arrest. SFN induced the expression of p21(WAF1/CIP1) protein causing the cell cycle arrest in a dose-dependent manner. SFN induced apoptosis which was characterized by the appearance of cells with sub-G1 DNA content and the cleavage and activation of caspase-3. We showed that SFN induced the growth arrest and up-regulated the expression of p21(WAF1/CIP1) protein in a p53-independent manner in human osteosarcoma MG63 cells. We found that intraperitoneal administration of SFN (1 or 2 mg, 5 times/week) significantly inhibited the growth of LM8 xenografts to <30% of the controls in a preclinical animal model without causing any toxicity. In osteosarcoma cells, our findings provide in vivo evidence for the efficacy of SFN against the advanced growth of tumor. We showed that SFN induces cell cycle arrest and apoptosis in osteosarcoma cells and inhibits tumor xenograft growth. Furthermore, SFN is a potent inducer of p21(WAF1/CIP1) in osteosarcoma cells. These results raise the possibility that SFN may be a promising candidate for molecular-targeting chemotherapy against osteosarcoma.


Anatomical resection of hepatocellular carcinoma: A critical review of the procedure and its benefits on survival.
Hepatocellular carcinoma (HCC) is the sixth most common type of cancer and the third most frequent cause of cancer-related death. Advances in preoperative assessment of HCC (e.g., imaging studies and liver function tests), surgical techniques, and postoperative care have improved the surgical outcomes and survival of patients who undergo hepatic resection for HCC. However, in the last 20 years, the long-term survival after hepatectomy has remained unsatisfactory owing to the high rates of local recurrence and multicentric occurrence. Anatomical liver resection (AR) was introduced in the 1980s. Although several studies have revealed tangible benefits of AR for HCC, these benefits are still debated. Because most HCCs occur in patients with liver cirrhosis and poor hepatic function, there are many factors that affect survival, including the surgical method. Nevertheless, many studies have documented the perioperative and long-term benefits of AR in various conditions. In this article, we review the results of several recently published, well-designed comparative studies of AR, to investigate whether AR provides real benefits on survival outcomes. We also discuss the potential pitfalls associated with this approach.


Listen to your patient...
An 89-year-old patient was admitted to the emergency department (ED) because of sudden onset of chest pain. The chest radiograph appeared to show a detachment of the pleura on the right side. The diagnosis of a pneumothorax was made. Insertion of a chest tube was indicated, but the patient refused her consent. The next day, another chest radiograph was taken. It showed no more detachment of the pleura. The initial diagnosis of pneumothorax had to be abandoned as retrospectively the pneumothorax could be identified as an artefact. Different aspects of pseudopneumothorax are discussed.


Lithiation of tin oxide: a computational study.
We suggest that the lithiation of pristine SnO forms a layered LiXO structure, while the expelled tin atoms agglomerate into "surface" planes separating the LiXO layers. The proposed lithiation model widely differs from the common assumption that tin segregates into nanoclusters embedded in the lithia matrix. With this model, we are able to account for the various tin bonds that are seen experimentally and explain the three volume expansion phases that occur when SnO undergoes lithiation: (i) at low concentrations Li behaves as an intercalated species inducing small volume increases; (ii) for intermediate concentrations SnO transforms into lithia causing a large expansion; and (iii) finally, as the Li concentration further increases a saturation of the lithia takes place until a layered Li2O is formed. A moderate volume expansion results from this last process. We also report a "zipper" nucleation mechanism that could provide the seed for the transformation from tin oxide to lithium oxide.


Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links.
Type 2 diabetes mellitus (DM) is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD), which could lead to heart failure through a variety of mechanisms, including myocardial infarction and chronic pressure overload. Pathogenetic mechanisms, mainly linked to hyperglycemia and chronic sustained hyperinsulinemia, include changes in metabolic profiles, intracellular signaling pathways, energy production, redox status, increased susceptibility to ischemia, and extracellular matrix remodeling. The close relationship between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association. However, although the common risk factors of both CVD and type 2 DM, such as obesity, insulin resistance, dyslipidemia, inflammation, and thrombophilia, can be identified in the majority of affected patients, less is known about how these factors influence both conditions, so that efforts are still needed for a more comprehensive understanding of this relationship. The genetic, epigenetic, and environmental backgrounds of both type 2 DM and CVD have been more recently studied and updated. However, the underlying pathogenetic mechanisms have seldom been investigated within the broader shared background, but rather studied in the specific context of type 2 DM or CVD, separately. As the precise pathophysiological links between type 2 DM and CVD are not entirely understood and many aspects still require elucidation, an integrated description of the genetic, epigenetic, and environmental influences involved in the concomitant development of both diseases is of paramount importance to shed new light on the interlinks between type 2 DM and CVD. This review addresses the current knowledge of overlapping genetic and epigenetic aspects in type 2 DM and CVD, including microRNAs and long non-coding RNAs, whose abnormal regulation has been implicated in both disease conditions, either etiologically or as cause for their progression. Understanding the links between these disorders may help to drive future research toward an integrated pathophysiological approach and to provide future directions in the field.


Halobellus limi sp. nov. and Halobellus salinus sp. nov., isolated from two marine solar salterns.
Two halophilic archaea, strains TBN53(T) and CSW2.24.4(T), were characterized to elucidate their taxonomic status. Strain TBN53(T) was isolated from the Taibei marine solar saltern near Lianyungang city, Jiangsu province, China, whereas strain CSW2.24.4(T) was isolated from a saltern crystallizer in Victoria, Australia. Cells of the two strains were pleomorphic, stained Gram-negative and produced red-pigmented colonies. Strain TBN53(T) was able to grow at 25-55 °C (optimum 45 °C), with 1.4-5.1 M NaCl (optimum 2.6-3.9 M NaCl), with 0-1.0 M MgCl(2) (optimum 0-0.1 M MgCl(2)) and at pH 5.5-9.5 (optimum pH 7.0), whereas strain CSW2.24.4(T) was able to grow at 25-45 °C (optimum 37 °C), with 2.6-5.1 M NaCl (optimum 3.4 M NaCl), with 0.01-0.7 M MgCl(2) (optimum 0.05 M MgCl(2)) and at pH 5.5-9.5 (optimum pH 7.0-7.5). Cells of the two isolates lysed in distilled water. The minimum NaCl concentrations that prevented cell lysis were 8 % (w/v) for strain TBN53(T) and 12 % (w/v) for strain CSW2.24.4(T). The major polar lipids of the two strains were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and phosphatidylglycerol sulfate, with two glycolipids chromatographically identical to sulfated mannosyl glucosyl diether and mannosyl glucosyl diether, respectively. Trace amounts of other unidentified lipids were also detected. On the basis of 16S rRNA gene sequence analysis, strains TBN53(T) and CSW2.24.4(T) showed 94.1 % similarity to each other and were closely related to Halobellus clavatus TNN18(T) (95.0 and 94.7 % similarity, respectively). Levels of rpoB' gene sequence similarity between strains TBN53(T) and CSW2.24.4(T), and between these strains and Halobellus clavatus TNN18(T) were 88.5, 88.5 and 88.1 %, respectively. The DNA G+C contents of strains TBN53(T) and CSW2.24.4(T) were 69.2 and 67.0 mol%, respectively. The level of DNA-DNA relatedness between strain TBN53(T) and strain CSW2.24.4(T) was 25 %, and these two strains showed low levels of DNA-DNA relatedness with Halobellus clavatus TNN18(T) (30 and 29 % relatedness, respectively). Based on these phenotypic, chemotaxonomic and phylogenetic properties, two novel species of the genus Halobellus are proposed to accommodate these two strains, Halobellus limi sp. nov. (type strain TBN53(T) = CGMCC 1.10331(T) = JCM 16811(T)) and Halobellus salinus sp. nov. (type strain CSW2.24.4(T) = DSM 18730(T) = CGMCC 1.10710(T) = JCM 14359(T)).


Rodent malaria parasites: molecular karyotypes characterize species, subspecies and lines.
The molecular karyotypes of the African murine malaria parasites P. berghei (3 strains, 2 lines) P. yoeli (2 strains) P. chabaudi (3 strains, 1 line) and P. vinckei (4 strains) have been studied using orthogonal field alternation gel electrophoresis (OFAGE). The genome of each species was resolved into 9 to 11 distinct chromosomal DNA banas molecules of varying intensities which seem to represent 14 chromosomes ranging in size from 600 kb to 3500 kb. The position of certain chromosomes allowed the identification of a unique karyotype for each of the strains and lines under study. P. yoelii appears by criteria of chromosome size, chromosome numbers and localisation of DNA probes to differ considerably from the other three rodent malaria species. The chromosomal location of 5 DNA probes allowed the identification of corresponding chromosomes in rodent malaria parasites and the differentiation between species and strains. Assignment of the "PMMSA" gene of P. c. chabaudi IP-PC 1 enables the distinction of the four rodent malaria species. The molecular karyotype combined to chromosomal assignment of DNA probes provides a useful tool for a more precise characterization by a genetic definition of malaria parasites.


The brain: integrated three-dimensional display of MR and PET images.
Three patients with intractable epilepsy, two with brain tumors, and one with encephalitis were imaged with magnetic resonance (MR) and positron emission tomography (PET). MR data were used to construct a three-dimensional (3D) computer model of the brain surface depicting the precentral (movement), postcentral (sensation), left inferior frontal (speech), and left superior temporal (hearing) gyri. PET-derived measurements of average surface metabolism were encoded as colors and mapped onto the 3D model by means of a retrospective technique for registering the two scans. The integrated 3D model depicted the location of PET-detected metabolic abnormalities with respect to the gyral anatomy visualized with MR. In each case, the predicted relationships were confirmed intraoperatively by means of inspection of the brain and electroencephalography. Multimodality 3D displays are likely to be particularly valuable for interpreting PET studies of epileptic patients and others with normal MR anatomy.


Fast Nonlinear Ultrasound Propagation Simulation Using a Slowly Varying Envelope Approximation.
Medical systems usually consider linear propagation of ultrasound, an approximation of reality. However, numerous studies have attempted to accurately simulate the nonlinear pressure wave distortion and to evaluate the contribution of harmonic frequencies. In such simulations, the computation time is very large, except for the method based on the angular spectrum scheme where the derivative order is reduced using the Fourier transform. However, the harmonic computation is usually limited to the second harmonic because of quasi-linear approximation. In this paper, a slowly varying envelope approximation (SVEA) is used in the Fourier domain to compute the entire nonlinear distortion induced, including high harmonics and nonlinear mixing frequencies. The simulation by SVEA is evaluated by comparison with other simulation tools. The obtained deviation and difference remain low enough to fully validate such an approximation. Moreover, the simulator is implemented on a GPU to obtain a very fast tool, where the full nonlinear distorted [Formula: see text] field is computed in less than 10 s.


Intraarterial thrombolysis of lower extremity occlusions: prospective, randomized comparison of forced periodic infusion and conventional slow continuous infusion.
A prospective randomized controlled trial compared forced infusion (FI) of urokinase (UK) with conventional slow continuous infusion (CI) in 25 patients with 25 acutely ischemic lower limbs. Demographics, ischemia categories, and infusion rates and doses were similar for both groups. A preliminary single-pass bolus of UK was injected into the thrombus in all patients with a pulsed-spray technique, and heparin was administered. UK was then infused with a CI pump (n = 13) or a prototype pulsed-spray pump (n = 12). The primary end point was patency, defined as at least 95% thrombolysis by volume, with brisk antegrade flow occurring within 4 hours. Eleven of the 12 patients (92%) who underwent FI and nine of the 13 (70%) who underwent CI had patency within 4 hours. However, 10 patients who underwent FI and nine who underwent CI had residual thrombi prolonging infusion. No significant differences between the two groups were apparent in speed of lysis, initial success rates, complication rates, or 30-day clinical outcome. Lytic therapy, however, was completed within 24 hours in 18 of 23 (78%) successfully treated patients (P = .01).


Schedule-induced behavior in hyperactive children.
A schedule-induced behavior paradigm was used to investigate the activity patterns of hyperactive children in a standardized situation. In Experiment I, 10 hyperactive and 10 normal control children matched for age, sex, and IQ were observed under conditions of baseline and schedule. Measures of a number of categorized activities were taken on a time-sampling basis. Hyperactive children were more active than controls in baseline and did not respond to the schedule, unlike the controls who became significantly more active in schedule conditions. In Experiment II, 12 hyperactive and 6 normal children were again subjected to the same experimental paradigm, but in two of the four experimental sessions the stimulant drug methylphenidate was administered in an attempt to reduce the amount of baseline activity. Results were substantially similar to those of Experiment I, with hyperactive children more active than controls in baseline and insensitive to the schedule. There was no overall effect of drug administration on the behavior of either group. There were some rate-dependent effects of both drug and schedule conditions.


[Epidemiology of decision on life-sustaining treatment in the general internal medicine division].
In the state of Israel there are no clear guidelines of decision-making for terminally ill patients. However, physicians do make decisions concerning life sustaining treatment. The rate of these decisions in medical wards in Israel is not known. The purpose of the study was to investigate prospectively, in a medical division, the rate of foregoing life-sustaining treatment. In addition, we wanted to find out whether or not senior physicians and families were involved in the decision-making process. The relationship of the decisions to the patients demographic and clinical characteristics was evaluated. Of 1039 patients hospitalized in 3/01, 12/01 and 1/02, the decision to forego life-sustaining treatment was taken in 8.8% of the cases. The highest rate was observed in the acute geriatric ward (23%) and the lowest in the Department of Cardiology (< 1%). Senior physicians were involved in 74% of the decision-making and the family was involved in only 29%. Age, marital status, dementia, functional state and the severity of sickness significantly affected the decision-making. However, on the basis of multi-regression analysis, only functional impairment prior to the hospitalization significantly affected the decision-making by the physician. The findings of this study support the essential need for accelerating legislation concerning decision-making for patients at the end of life. The adoption of the recommendations of the public committee on this subject, recently presented to the Minister of Health, provide legal validity to advance medical directives and may assist in ethical issues for end of life decision-making.


Intact endothelium-dependent dilation and conducted responses in resistance vessels of hypercholesterolemic mice in vivo.
Atherosclerosis and hyperlipidemia impair endothelium-dependent nitric oxide (NO)-mediated dilations in conducting arteries. In addition to NO, the endothelium releases an endothelium-derived hyperpolarizing factor (EDHF) in response to acetylcholine (ACh), which is particularly important in microvessels and initiates a dilation that conducts along the vessel through gap junctional communication. The expression of connexins is, however, altered by hypercholesterolemia. Therefore, we studied endothelium-dependent dilations and their conduction in murine hypercholesterolemic models. Dilations were assessed by intravital microscopy in arterioles with a diameter of approximately 35 microm in ApoE and LDL receptor (LDLR(-/-))-deficient mice after superfusion or locally confined application of ACh. ACh induced comparable concentration-dependent dilations in wild-type, LDLR(-/-), and ApoE(-/-) mice fed a normal or high-cholesterol diet, however EC(50) was slightly higher in ApoE(-/-) mice. Furthermore, the NO donor sodium-nitroprusside dilated arterioles to a similar extent (approximately 60%). Locally initiated ACh dilations (approximately 68%) conducted up to a distance of 1,100 microm without significant attenuation even under severe hypercholesterolemic conditions. Since ACh dilation in the arterioles of mice is mainly mediated via EDHF, we conclude that hypercholesterolemia does not alter EDHF release and efficacy. This conclusion is confirmed by an intact conducted response since EDHF is a prerequisite for this response. The intact conduction also suggests that gap-junctional communication is functionally preserved in these models.


Tubuloreticular reorganization of cytomembranes in cells treated with human alpha interferons--a review.
Human alpha interferons (IFN-a) cause a reorganization of internal cell membranes into tubuloreticular inclusions (TRI). Morphogenesis and cytochemistry indicate a pre-Golgi intracisternal origin from the endoplasmic reticulum. Clinically, TRI formation in human blood mononuclear cells correlates with systemic IFN-a treatment or with endogenous overproduction of IFN-a in viral or autoimmune diseases (e.g., rubella syndrome, AIDS, systemic lupus erythematosus). In vitro, TRI formation can be produced by treatment of Daudi lymphoblasts or vascular endothelial cells with IFN-a, and is blocked by actinomycin-D. In Daudi lymphoblasts or vascular endothelial cell cultures, TRI formation parallels induction of 2'-5' A synthetase, inhibition of thymidine kinase and growth inhibition; however, heavy water treatment of Daudi cells prevented TRI formation while induction of 2'-5' A synthetase and growth inhibition persisted. TRI formation was dissociated from IFN-a antiproliferative activity in a mutant clone of Daudi lymphoblasts. Decreased glycoprotein biosynthesis and increased phospholipid biosynthesis may accompany progressive TRI accumulation.


Suppression of spurious lateral modes in thickness-excited FBAR resonators.
Thin film bulk acoustic wave resonators (FBAR) utilize thickness-excited modes in which the resonant frequency is determined by the thickness of the structure and the wave velocity of the mode used. Unfortunately, other resonant modes also may be excited in the device. Some of these correspond to low-frequency, laterally-excited modes and, although a relatively small amount of the total energy is absorbed by these modes, their harmonics may produce an undesirable response around the fundamental resonance frequency of the desired thickness mode. This work explores various ways of suppressing the spurious effects caused by lateral-excited modes by studying their dependence of the electrode geometry. The origin of the lateral-excited modes is discussed in detail, and the results from a number of different electrode geometries are compared. A new elliptical electrode shape for suppression of spurious modes is developed and demonstrated.


Prognostic value of tumor architecture, tumor-associated vascular characteristics, and expression of angiogenic molecules in pancreatic endocrine tumors.
It is difficult to predict the biological behavior of pancreatic endocrine tumors (PETs). Our aim was to evaluate the prognostic significance of certain variables in PETs. The following variables were examined in 37 patients with PETs and then compared with other clinicopathologic characteristics: histologic tumor structure; microvessel density (MVD) measured by three different methods, including a unique method involving calculation of solid area MVD; endothelial proliferation; and the immunohistochemical expression of vascular endothelial growth factor-A and CXC chemokine CXCL-12. Intratumoral vascular structures were analyzed by double immunofluorescence using 30-microm-thick sections. The presence of focal and intensive solid growth of tumor cells (large solid nests; P = 0.003), low solid area MVD (P = 0.002), a high endothelial cell proliferation index (EPI; P = 0.005), and high expression of CXCL-12 in PET cells (P = 0.018) were significant unfavorable prognostic indicators. The predominant structure of the overall tumor histology and the expression of vascular endothelial growth factor-A did not separate aggressive PETs. In areas of focal solid growth, tumor-associated blood vessels had obviously low MVD and high EPI, and their structures were poorly formed with highly abnormal features, in comparison with other areas. High expression of CXCL-12 in tumor cells was significantly associated with variables representing tumor growth, hematogenous tumor spread, low MVD, high EPI, and the presence of large solid nests. This study has provided novel findings on the prognostic features of tumor architecture and tumor-associated angiogenesis in PETs. CXCL-12 is the first candidate molecule in association with neoangiogenesis in PETs.


Use of BODIPY-Labeled ATP Analogues in the Development and Validation of a Fluorescence Polarization-Based Assay for Screening of Kinase Inhibitors.
The screening of compound libraries to identify small-molecule modulators of specific biological targets is crucial in the process for the discovery of novel therapeutics and molecular probes. Considering the need for simple single-tool assay technologies with which one could monitor "all" kinases, we developed a fluorescence polarization (FP)-based assay to monitor the binding capabilities of protein kinases to ATP. We used BODIPY ATP-y-S as a probe to measure the shift in the polarization of a light beam when passed through the sample. We were able to optimize the assay using commercial Protein Kinase A (PKA) and H7 efficiently inhibited the binding of the probe when added to the reaction. Furthermore, we were able to employ the assay in a high-throughput fashion and validate the screening of a set of small molecules predicted to dock into the ATP-binding site of PKA. This will be useful to screen larger libraries of compounds that may target protein kinases by blocking ATP binding.


Influence of therapeutic concentrations of phenylbutazone on granulocyte function.
The influence of therapeutic concentrations of phenylbutazone on human granulocyte function has been examined using a method which facilitates a precise in vitro evaluation of the phagocytic and bactericidal activities of polymorphonuclear leucocytes. Phenylbutazone caused a marked reduction in intracellular killing of bacteria by the granulocytes. Whether this inhibition of granulocyte function also takes place in vivo resulting in enhanced susceptibility to infection, remains unknown.


HSP110-HER2/neu chaperone complex vaccine induces protective immunity against spontaneous mammary tumors in HER-2/neu transgenic mice.
Heat shock proteins (HSPs) are shown to be strong immunoadjuvants, eliciting both innate and adaptive immune responses against cancers. HSP110 is related in sequence to HSP70 and is approximately 4-fold more efficient in binding to and stabilizing denatured protein substrates compared with HSP70. In the present study we evaluated the ability of a heat shock complex of HSP110 with the intracellular domain (ICD) of human HER-2/neu to elicit effective antitumor immune responses and to inhibit spontaneous mammary tumors in FVB-neu (FVBN202) transgenic mice. The HSP110-ICD complex was capable of breaking tolerance against the rat neu protein and inhibiting spontaneous mammary tumor development. This vaccine induced ICD-specific IFN-gamma and IL-4 production. Depletion studies revealed that CD8(+) T cells were involved in protection against challenge with mouse mammary tumors, whereas CD4(+) T cells revealed partial protection. Increased IgG2a Ab titer in the sera of tumor-free animals after vaccination and elevated CD4(+) CD25(+) regulatory T cells in the PBL of tumor-bearing animals suggested that IFN-gamma-producing Th1 cells may be responsible for partial protection of CD4(+) T cells against the mammary tumor challenge, whereas CD4(+)CD25(+) regulatory T cells (Th2 cells) may suppress the antitumor immune responses. Together, these results suggest that HSP110-ICD complex can elicit effective IFN-gamma-producing T cells against spontaneous mammary tumors and that up-regulation of CD4(+) CD25(+) regulatory T cells may prevent complete eradication of the tumor following immunotherapy.


Discovering long-term potentiation (LTP) - recollections and reflections on what came after.
Chance events led me to a lifelong career in scientific research. They paved the way for being the first to see long-term potentiation of synaptic efficiency (LTP) in Per Andersen's laboratory in Oslo in 1966. Here I describe my way to this discovery and the experiments with Tim Bliss in 1968-1969 that led to Bliss and Lømo, 1973. Surprisingly, we later failed to reproduce these results. I discuss possible reasons for this failure, which made us both leave LTP research, in my case for good, in Tim's case for several years. After 30 years of work in a different field, I renewed my interest in the hippocampus and LTP in the early 2000s and published, for the first time, results that I had obtained 40 years earlier. Here I present my take on how interest in and research on LTP evolved after the early years. This includes a discussion of the functions of hippocampus as seen in those early days, the case of patient H.M., Donald Hebb's place in the story, the search for 'memory molecules' such as PKMζ, and the primary site for LTP expression (pre- and/or post-synaptic?). Throughout, I reflect on my life in science, how science is done and what drives it. The reflections are quite personal and I admit to mixed feelings about broadcasting them.


Dietary oxidized fat prevents ethanol-induced triacylglycerol accumulation and increases expression of PPARalpha target genes in rat liver.
Alcoholic fatty liver results from an impaired fatty acid catabolism due to blockade of PPARalpha and increased lipogenesis due to activation of sterol regulatory element-binding protein (SREBP)-1c. Because both oxidized fats (OF) and conjugated linoleic acids (CLA) have been demonstrated in rats to activate hepatic PPARalpha, we tested the hypothesis that these fats are able to prevent ethanol-induced triacylglycerol accumulation in the liver by upregulation of PPARalpha-responsive genes. Forty-eight male rats were assigned to 6 groups and fed isocaloric liquid diets containing either sunflower oil (SFO) as a control fat, OF prepared by heating of SFO, or CLA, in the presence and absence of ethanol, for 4 wk. Administration of ethanol lowered mRNA concentrations of PPARalpha and the PPARalpha-responsive genes medium chain acyl-CoA dehydrogenase, long chain acyl-CoA dehydrogenase, acyl-CoA oxidase, carnitine palmitoyl-CoA transferase I, and cytochrome P450 4A1 and increased triacylglycerol concentrations in the liver (P < 0.05). OF increased hepatic mRNA concentrations of PPARalpha-responsive genes and lowered hepatic triacylglycerol concentrations compared with SFO (P < 0.05) whereas CLA did not. Rats fed OF with ethanol had similar mRNA concentrations of PPARalpha-responsive genes and similar triacylglycerol concentrations in the liver as rats fed SFO or CLA without ethanol. In contrast, hepatic mRNA concentrations of SREBP-1c and fatty acid synthase were not altered by OF or CLA compared with SFO. This study shows that OF prevents an alcohol-induced triacylglycerol accumulation in rats possibly by upregulation of hepatic PPARalpha-responsive genes involved in oxidation of fatty acids, whereas CLA does not exert such an effect.


Thrombolysis with a novel modified tissue-type plasminogen activator, monteplase, combined with catheter-based treatment for major pulmonary embolism.
A novel modified tissue-type plasminogen activator, monteplase, has been approved for acute major pulmonary embolism (PE) in Japan. Monteplase has rapid and sustained lytic effects because of a steep rise in concentration after bolus infusion and a longer half-life. To assess the efficacy and safety of thrombolysis with monteplase in combination with catheter-based treatment, acute hemodynamic changes and clinical outcomes were assessed in 50 patients with angiographically confirmed major PE. Thrombolysis with monteplase in combination with embolus fragmentation and thrombectomy was the acute phase treatment. The study population comprised 31 females and 19 males (mean age 62 years). All patients had right ventricular (RV) overload; 12 patients presented in shock. The mean pulmonary artery pressure decreased significantly from 32+/-9 mmHg to 25+/-6 mmHg after acute phase treatment (P<0.0001). The mean dosage of monteplase was 12,265 IU/kg. Death at 30 days occurred in 3 patients (6%). Major bleeding occurred in 12 patients (24%). RV overload at discharge remained in only 3% of the patients with typically acute onset. Thrombolysis with monteplase, in combination with catheter-based treatment, is an effective and safe therapy for major PE.


Cerebriform sebaceous nevus.
A 20-year-old man presented with a well-defined, soft to firm, freely mobile pinkish-yellow plaque of 9.5 cm over the right parieto-occipital region with a typical cerebriform appearance. In total, nine folds were present with short black terminal hair in the sulci area. There was no follicular plugging. Skeletal survey and neurologic and ophthalmologic assessments were normal. Skin biopsy was compatible with sebaceous nevus showing mature sebaceous glands in the upper dermis and mature apocrine glands in the lower dermis with malformed hair germ.


One-Pot Mechanochemical Synthesis of Mono- and Bis-Indolylquinones via Solvent-Free Multiple Bond-Forming Processes.
Bis-indolylquinones are fungal natural products endowed with interesting pharmacological properties. Most of the previously described methodologies in solution for the construction of the bis-indolylquinone framework show disadvantages associated with long reaction times and difficult, waste-generating purifications. A one-pot mechanochemical methodology for the synthesis of indolylquinones was developed, starting from indoles and dihaloquinones in the presence of FeCl3 or p-TsOH as catalysts and Fetizon's reagent as an oxidant. In contrast to solution chemistry, mechanochemical activation allowed the double addition of indole to a quinone substrate in one pot, leading to symmetrical or non-symmetrical bis-indolylquinones via a domino processes comprising up to six steps. In terms of sustainability, the method has several advantages over the solution protocol, including much shorter reaction times, no external heating, one-pot operation, and the absence of chromatography, leading to a drastically better performance in green metrics and demonstrating the application of several principles of green chemistry, in particular principles 2, 3, and 5.


Immunohistochemical analysis of the infiltrated cells in tinea capitis patients.
Tinea capitis is a fungal infection of the skin and the hair with involvement of the hair shaft and the pilosebaceous unit. It may be the most common of all cutaneous mycoses in children. Tinea capitis can be inflammatory or noninflammatory. It is thought that humoral and cell-mediated immunities play a role in the formation of the clinical types of the disease. We studied twelve patients with acute inflammatory disease, four patients with chronic non-inflammatory disease, and one patient with a black-dot variant of tinea capitis. The composition of inflammatory infiltrates present in lesional skin was analyzed by antibodies to T cells (CD3) and B cells (CD20). Anti-CD3 revealed large numbers of T cells in twelve patients with acute, inflammatory dermatophytosis, whereas anti-CD20 revealed marked infiltrates of both B and T cells in all patients with chronic, non-inflammatory dermatophytosis. As a result, we thought that cell-mediated immunity might play a role in the acute, inflammatory type of tinea capitis and that humoral immunity might do so in the chronic, non-inflammatory type of tinea capitis.


A Theoretical Study of the Adsorption Process of B-aflatoxins Using Pyracanthakoidzumii (Hayata) Rehder Biomasses.
Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) functional and basis set, the interaction of the aflatoxin B1 (AFB1) molecule and the functional groups present in the Pyracantha koidzumii biosorbent was investigated. Dissociation free energy and acidity equilibrium constant values were obtained theoretically both in solution (water) and gas phases. Additionally, the molecular electrostatic potential for the protonated molecules was calculated to verify the reactivity. Thus, methanol (hydroxyl group), methylammonium ion (amino group), acetate ion (carboxyl group), and acetone (carbonyl group), were used as representatives of the substrates present in the biomass; these references were considered using the corresponding protonated or unprotonated forms at a pH value of 5. The experimental infrared spectrophotometric data suggested the participation of these functional groups in the AFB1 biosorption process, indicating that the mechanism was dominated by electrostatic interactions between the charged functional groups and the positively charged AFB1 molecule. The theoretical determination indicated that the carboxylate ion provided the highest interaction energy with the AFB1 molecule. Consequently, an enriched biosorbent with compounds containing carboxyl groups could improve the yield of the AFB1 adsorption when using in vitro and in vivo trials.


Growth rate-dependent regulation of transfer ribonucleic acid (5-methyluridine) methyltransferase in Escherichia coli B/r.
Enzymes catalyzing the transfer of methyl groups from S-adenosyl-l-methionine to a precursor transfer ribonucleic acid (tRNA) and forming 5-methyluridine (m(5)U), 1-methylguanine (m(1)G), or 5-methylaminomethyl-2-thio-uridine (mam(5)s(2)U) are denoted tRNA(m(5)U)-(EC 22.214.171.124), tRNA(m(1)G)-(EC 220.127.116.11), and tRNA(mam(5)s(2)U)methyltransferase. We have studied the regulation of these tRNA biosynthetic enzymes in Escherichia coli under various physiological conditions and in bacterial mutants known to affect the regulation of components of the translational apparatus. Such studies have revealed that tRNA(m(5)U)-methyltransferase increases with the growth rate in the same fashion as stable RNA, whereas the activity of two other tRNA methyltransferases remains constant in relation to the growth rate. Thus, these tRNA biosynthetic enzymes were not coordinately regulated. Regulation of both tRNA(m(5)U)methyltransferase and stable RNA was similar during shift-up and shift-down experiments. This enzyme showed a stringent regulation in relA(+) strain (T. Ny and G. R. Björk, J. Bacteriol. 130:635-641, 1977) but also in two temperature-sensitive mutants, fusA and fusB, known to influence the accumulation of guanosine 5'-diphosphate 3'-diphosphate and RNA synthesis at nonpermissive temperatures. The tRNA(m(5)U)methyltransferase showed a gene dose effect when its structural gene, trmA, was carried on a plasmid or on lambda transducing phages. Although the regulation of tRNA-(m(5)U)methyltransferase was surprisingly coupled to that of stable RNA, this enzyme was expressed at a much lower level.


Mixed lymphocyte reaction: an in vitro test for antilymphocytic serum activity.
When Lewis rats were exposed to antilymphocytic serum, produced in rabbits, to Lewis lymphoid cells, the transformation of their thoracic duct lymphocytes in response to foreign lymphoid cells was markedly reduced in comparison with that in response to similar cells from donors treated with saline or normal rabbit serum. It is suggested that the mixed lymphocyte reaction may be used as an in vitro test for the in vivo activity of antilymphocytic serum.


[Establishment and characteristics of orthotopically transplanted model of human primary malignant small intestinal lymphoma in nude mice].
To establish orthotopically transplanted model of human malignant small intestinal lymphoma in nude mice and analyze their biologic characteristics. Small intestinal lymphoma tissues from 5 patients were transplanted into intestinal mucosa of nude mice. Tumorgenecity, invasion and metastasis of the transplanted tumors were observed by morphological analyses (light microscopy, electron microscopy and immunohistochemistry), karyotyping and DNA quantitative assay. Tumor tissues from 3 lymphoma patients were successfully transplanted. According to the World Health Organization classification, the three models were classified into non-Hodgkin's lymphoma (B cell) of human small intestine (HSIL-1), high metastasis of non-Hodgkin's lymphoma (B cell) of human small intestine (HSIL-2) and non-Hodgkin's lymphoma (T cell) of human small intestine (HSIL-3), respectively. Immunohistochemistry showed that CD19, CD20, CD22, CD40, CD45 and CD72 were positive in HSIL-1 and HSIL-2, whereas CD3, CD7 and CD45RO were positive in HSIL-3. The karyotypes of the transplanted tumors were all hypotriploid with modal numbers from 55 to 69 and the DNA index (DI) was 1.46 approximately 1.71. The three models had been passaged for 32, 27 and 21 generations respectively in 433 nude mice. The growth rate, resuscitation rate of the liquid nitrogen preserved tumor cells and spontaneous metastasis rate upon transplantation were all 100%. We observed an invasive growth of the transplanted tumors in small intestine, which resulted in disrupting of the intestinal wall, hematogenous metastasis, lymph node metastasis and seeding metastasis. The features of the transplanted tumors were similar to the original tumors in histopathology, ultrastructure, DNA content and karyotype. Three strains of orthotopically transplanted model of human primary malignant small intestinal lymphoma in nude mice were successfully developed. The result of research will provide ideal animal models for further studies on mechanism of tumorigenesis, invasion and metastasis of malignant small intestinal lymphoma and experimental therapy.


Utility of daily catheter-drawn blood cultures to predict catheter-related bacteremia in hematopoietic stem cell transplanted patients.
There is no diagnostic tool to identify which bacterial catheter colonization may eventually result in bloodstream infection. We speculated that a faster growth or repeated positivity of serial blood cultures drawn from the catheter might herald catheter-related bacteremia (CRB) before the onset of fever. We designed a prospective observational pilot study. All patients who underwent hematopoietic stem cell transplantation (HSCT) were prospectively included in the study over 10 months. Daily catheter-drawn blood cultures (DBC) were performed. We recorded the growth time of each blood culture and bacterial isolation. A fast-growing blood culture (positive <12 hours) or at least 2 positive identical cultures within 4 consecutive days in the DBC were defined as a marker of risk for CRB. The value of this marker to predict CRB was investigated. A total of 82 patients (843 days of catheter) were included in the study. Fast- growing or repeated identical cultures were present in 20 patients; among them, 15 had clinical criteria of CRB. Among 62 patients without fast-growing or repeated identical cultures, 11 met the criteria of CRB. Consequently, for the defined marker of risk, the positive predictive value was 75%, negative predictive value 82%, sensitivity 70%, and specificity 91%. Sixty-two blood cultures were needed to detect one case of CRB prior to the onset of fever. The use of routinely drawn catheter-blood cultures does not seem to be a useful tool for predicting CRB in HSCT patients.


Contemporary best practice urolithiasis in pregnancy.
Urolithiasis is the most common nonobstetric complication in the gravid patient. The experience can provoke undue stress for the mother, fetus, and management team. The physiologic changes of pregnancy render the physical exam and imaging studies less reliable than in the typical patient. Diagnosis is further complicated by the need for careful selection of imaging modality in order to maximize diagnostic utility and minimize obstetric risk to the mother and ionizing radiation exposure to the fetus. Ultrasound remains the first-line diagnostic imaging modality in this group, but other options are available if results are inconclusive. A trial of conservative management is uniformly recommended. In patients who fail spontaneous stone passage, treatment may be temporizing or definitive. While temporizing treatments have classically been deemed the gold standard, ureteroscopic stone removal is now acknowledged as a safe and highly effective definitive treatment approach. Ultimately, a multidisciplinary, team-based approach involving the patient, her obstetrician, urologist, radiologist, and anesthesiologist is needed to devise a maximally beneficial management plan.


[Parvovirus enteritis in dogs based on autopsy statistics 1978-1985].
The occurrence of canine parvovirus enteritis was monitored in post mortem record from 1978-1985. In a total of 7,615 canine necropsies 654 cases of parvovirus enteritis were diagnosed. The number of cases rose considerably in 1980, accounting for about 10% of the total of canine necropsies since then. Seasonal distribution of cases shows a maximum in November, December, and January and a minimum in June, July and September. In German shepherds and Yorkshireterriers parvovirus enteritis is diagnosed with significantly higher frequency than in other breeds. 80% of all cases of parvovirus enteritis necropsied were diagnosed up to the age of 6 months.


A historical perspective on diversity in Clinical Laboratory Sciences Programs.
Diversity is integral for an effective learning environment and pedagogy. In this study, we aim to determine the student and faculty diversity in the Clinical Laboratory Sciences programs at Stony Brook University. We retrospectively analyzed data over 20 years for the traditional program and 8 years for the hybrid program. Over 20 years, 502 students graduated from the traditional program, and 96 students graduated from the hybrid program. In the traditional program, an average of 25 students enrolled with 75% female and 25% male and in the hybrid program, an average of 12 students with 8.5 female and 3.5 male enrolled. The traditional program had the highest proportion of Asian students (50%), with White students making up 24.5%, whereas the highest proportions in the hybrid program were 35% White students and 24% Hispanic students. Among the 5 boroughs of New York City, the highest proportion of student representation was from Queens and Manhattan in both traditional (24.1%) and hybrid programs (16.7%). There were 30% male and 70% female faculty served in the traditional program whereas the current representation of fulltime faculty is 100% female. Our data show the diversity of students and faculty in clinical laboratory sciences programs at Stony Brook University institution.


A dual color Southern blot to visualize two genomes or genic regions simultaneously.
This report describes the development of a novel dual color Southern protocol to visualize two distinct genomes or genic regions simultaneously on a single Southern blot. The blot is developed with IRDye-conjugated antibody (Ab) and streptavidin that recognize digoxigenin (Dig)- or biotin-labeled probes, respectively and visualized on an infrared imager. This protocol was validated by visualizing viral and host genomes of human cytomegalovirus (HCMV)-infected human fibroblasts. This technique utilizes extremely sensitive fluorescent imaging, allowing the detection of nanogram quantities of DNA, as opposed to microgram quantities needed in Southerns using radioactively labeled probes, and eliminates the inherent loss in signal after stripping and reprobing a Southern blot. The probes are labeled with non-radioactive Dig and biotin and can be stored for extended periods of time. This protocol will aid in studies of any system with two genomes, such as cells infected with numerous types of microorganisms (virus/parasites/bacteria), or studies of mitochondrial and nuclear DNA within the same cells.