Effects of Repetitive Peripheral Sensory Stimulation in the Subacute and Chronic Phases After Stroke: Study Protocol for a Pilot Randomized Trial.
Repetitive peripheral nerve sensory stimulation (RPSS) is a potential add-on intervention to motor training for rehabilitation of upper limb paresis after stroke. Benefits of RPSS were reported in subjects in the chronic phase after stroke, but there is limited information about the effects of this intervention within the 1st weeks or months. The primary goal of this study is to compare, in a head-to-head proof-of-principle study, the impact of a single session of suprasensory vs. subsensory RPSS on the upper limb motor performance and learning in subjects at different phases after stroke subacute and chronic phases and mild upper limb motor impairments after stroke. In addition, we examine the effects of RPSS on brain perfusion, functional imaging activation, and γ-aminobutyric acid (GABA) levels. Subjects with mild upper limb motor impairments will be tested with MRI and clinical assessment either at an early (7 days to 3 months post-stroke) or at a chronic (>6 months) stage after stroke. In this multicenter, randomized, parallel-group, proof-of-principle clinical trial with blinded assessment of outcomes, we compare the effects of one session of suprasensory or subsensory RPSS in patients with ischemic or hemorrhagic stroke and upper limb paresis. Clinical assessment and MRI will be performed only once in each subject (either at an early or at a chronic stage). The primary outcome is the change in performance in the Jebsen-Taylor test. Secondary outcomes: hand strength, cerebral blood flow assessed with arterial spin labeling, changes in the blood oxygenation level-dependent (BOLD) effect in ipsilesional and contralesional primary motor cortex (M1) on the left and the right hemispheres assessed with functional MRI (fMRI) during a finger-tapping task performed with the paretic hand, and changes in GABA levels in ipsilesional and contralesional M1 evaluated with spectroscopy. The changes in outcomes will be compared in four groups: suprasensory, early; subsensory, early; suprasensory, chronic; and subsensory, chronic. The results of this study are relevant to inform future clinical trials to tailor RPSS to patients more likely to benefit from this intervention. NCT03956407.


Olfactory impairment predicts brain atrophy in Parkinson's disease.
Olfactory dysfunction is a frequent nonmotor symptom in idiopathic Parkinson's disease (PD) and may be considered as an early clinical feature of the disease preceding motor symptoms by years. According to recent neuropathological staging concepts, impaired olfaction is assumed to indicate an early pathological process and might be associated with structural changes in the brain. A morphometric analysis of magnetic resonance images [voxel-based morphometry (VBM)] was used to investigate gray matter atrophy related to psychophysically measured scores of olfactory function in early PD patients (n = 15, median Hoehn and Yahr stage 1.5), moderately advanced PD patients (n = 12, median Hoehn and Yahr stage 2.5), and age-matched healthy controls (n = 17). In PD patients, but not in controls, cortical atrophy in olfactory-related brain regions correlated specifically with olfactory dysfunction. Positive correlations between olfactory performance and gray matter volume were observed in the right piriform cortex in early PD patients and in the right amygdala in moderately advanced patients. The results provided first evidence that olfactory dysfunction in PD is related to atrophy in olfactory-eloquent regions of the limbic and paralimbic cortex. In addition, olfactory-correlated atrophy in these brain regions is consistent with the assumption that olfactory impairment as an early symptom of PD is likely to be associated with extranigral pathology.


Blockade by NIP-142, an antiarrhythmic agent, of carbachol-induced atrial action potential shortening and GIRK1/4 channel.
Mechanisms for the atria-specific action potential-prolonging action of NIP-142 ((3R*,4S*)-4-cyclopropylamino-3,4-dihydro-2,2-dimethyl-6-(4-methoxyphenylacetylamino)-7-nitro-2H-1-benzopyran-3-ol), a benzopyran compound that terminates experimental atrial arrhythmia, was examined. In isolated guinea-pig atrial tissue, NIP-142 reversed the shortening of action potential duration induced by either carbachol or adenosine. These effects were mimicked by tertiapin, but not by E-4031. NIP-142 concentration-dependently blocked the human G protein-coupled inwardly rectifying potassium channel current (GIRK1/4 channel current) expressed in HEK-293 cells with an EC50 value of 0.64 microM. At higher concentrations, NIP-142 blocked the human ether a go-go related gene (HERG) channel current with an EC50 value of 44 microM. In isolated guinea-pig papillary muscles, NIP-142 had no effect on the negative inotropic effect of carbachol under beta-adrenergic stimulation, indicating lack of effect on the muscarinic receptor and Gi protein. These results suggest that NIP-142 directly inhibits the acetylcholine-activated potassium current.


A point mutation and large deletion at the candidate avirulence locus AvrMlp7 in the poplar rust fungus correlate with poplar RMlp7 resistance breakdown.
The deployment of plant varieties carrying resistance genes (R) exerts strong selection pressure on pathogen populations. Rapidly evolving avirulence genes (Avr) allow pathogens to escape R-mediated plant immunity through a variety of mechanisms, leading to virulence. The poplar rust fungus Melampsora larici-populina is a damaging pathogen of poplars in Europe. It underwent a major adaptive event in 1994, with the breakdown of the poplar RMlp7 resistance gene. Population genomics studies identified a locus in the genome of M. larici-populina that probably corresponds to the candidate avirulence gene AvrMlp7. Here, to further characterize this effector, we used a population genetics approach on a comprehensive set of 281 individuals recovered throughout a 28-year period encompassing the resistance breakdown event. Using two dedicated molecular tools, genotyping at the candidate locus highlighted two different alterations of a predominant allele found mainly before the resistance breakdown: a nonsynonymous mutation and a complete deletion of this locus. This results in six diploid genotypes: three genotypes related to the avirulent phenotype and three related to the virulent phenotype. The temporal survey of the candidate locus revealed that both alterations were found in association during the resistance breakdown event. They pre-existed before the breakdown in a heterozygous state with the predominant allele cited above. Altogether, these results suggest that the association of both alterations at the candidate locus AvrMlp7 drove the poplar rust adaptation to RMlp7-mediated immunity. This study demonstrates for the first time a case of adaptation from standing genetic variation in rust fungi during a qualitative resistance breakdown.


Conditional Financing of Drugs in the Netherlands: Past, Present, and Future-Results From Stakeholder Interviews.
Conditional financing (CF) of hospital drugs was implemented in the Netherlands as a form of managed entry agreements between 2006 and 2012. CF was a 4-year process comprising 3 stages: initial health technology assessment of the drug (T = 0), conduct of outcomes research studies, and reassessment of the drug (T = 4). To analyze stakeholder experiences in implementing CF in practice. Public and private stakeholders were approached for participation in stakeholder interviews through standardized email invitations. An interview guide was developed to guide discussions that covered the following topics: perceived aims of CF, functioning of CF, impact of CF, and conclusions and future perspectives. Extensive summaries were generated for each interview and subsequently used for directed content analysis. Thirty stakeholders were interviewed. Differences emerged among the stakeholders on the perceived aims of CF. Conversely, there was some agreement among stakeholders on the shortcomings in the functioning of CF, the positive impact of CF on the Dutch healthcare setting, and improvement points for CF. Despite stakeholders' belief that CF either did not meet its aims or only partially did so, there was agreement on the need for new policy to address the same aims of CF in the future. Nevertheless, stakeholders diverged on whether CF should be improved on the basis of learnings identified and reintroduced into practice or replaced with new policy schemes.


Antecedents of positive and negative intergroup contact: Evidence from a diary study.
In our current globalised, multicultural world, understanding antecedents of reciprocal interactions between native people and people of immigrant background is a major issue, because intergroup contact plays a crucial role in building inclusive societies. In this vein, using daily diary data, we examined the relation between the number of daily positive and negative interactions of White British majority (N = 744) and Asian British minority people (N = 582) with members of the respective outgroup, with RWA, SDO, perceived ingroup norms, neighbourhood diversity and contextual deprivation. Results showed that for the majority group, ingroup norms in favour of intergroup contact were positively associated with positive intergroup encounters, whereas Right Wing Authoritarianism (RWA) was positively associated with negative intergroup contact. Neighbourhood diversity was positively associated with positive and negative intergroup encounters. Moreover, RWA moderated the relationship between neighbourhood diversity and both positive and negative contact of White British people. For the minority group, ingroup norms were positively associated with positive intergroup contact, and the relationship between ingroup norms and negative contact was moderated by SDO. Overall, different factors affect positive and negative intergroup contact of majority and minority groups. We discuss the implications of the findings for future research and interventions.


Effects of different origins and harvesting time on vitamin C, tocopherols, and tocotrienols in sea buckthorn (Hippophaë rhamnoides) berries.
Vitamin C, tocopherols, and tocotrienols in berries of wild and cultivated sea buckthorn (Hippophaë rhamnoides L.) of different origins and harvesting dates were determined with HPLC. Wild berries of subsp. sinensis, native to China, contained 5-10 times more vitamin C in the juice fraction than the berries of subsp. rhamnoides from Europe and subsp. mongolica from Russia (4-13 vs 0.02-2 g/L juice). Genetic background and berry-harvesting date were two primary factors determining the vitamin C content in the berries. Crossing different subspecies influenced the vitamin C content to some extent. For bushes cultivated in southwest Finland, the best berry-harvesting date for high vitamin C content was the end of August. The seeds of subsp. sinensis contained less tocopherols and tocotrienols (average 130 mg/kg) compared with seeds of subsp. rhamnoides (average 290 mg/kg) and mongolica (average 250 mg/kg). The fruit flesh of sinensis berries had contents of tocopherols and tocotrienols 2-3 times higher than those found in the other two subspecies (120 mg/kg vs 40 mg/kg in rhamnoides and 50 mg/kg in mongolica). The fresh whole berries of subsp. sinensis were clearly the best source of total tocopherols and tocotrienols. The total content of tocopherols and tocotrienols in the soft parts of the berries reached the maximum level around early- to mid-September, whereas the content in seeds continued to increase until the end of November. The excellent combination of the highest content of vitamin C and tocopherols and tocotrienols makes the berries of subsp. sinensis an optimal raw material for nutritional investigation as a candidate for functional foods with special antioxidative properties.


Continuing follow-up of malignant hypertension.
The history of accelerated (malignant) hypertension is reviewed, and unsolved problems related to the disease are illustrated, including its relationship to malignant nephrosclerosis, as well as terminology, current frequency and treatment. Over the past 25 years, out of a series of 131 patients, 53 were classified as suffering from essential malignant hypertension, the only suitable model on which the effects of pharmacological treatment on the disease can correctly be evaluated. In 2000, there were 24 survivors in our series and the maximum follow-up was 290 months. Multiple daily B.P. self-measurements allowed us to establish that pharmacological treatment was only able to approximate, to a varying degree, the conventional threshold of 140/90. Yet, despite this incomplete control over blood pressure levels, renal function was maintained in those patients whose initial creatininemia levels had not been higher than 2 mg/L. The renal protection effect of treatment was preserved even in patients who relapsed intoaccelerated disease phase one or more times over the study period.


Novel lipoxygenase inhibitor, 1-ethenoxy-2-methylbenzene, from marine cyanobacteria Microcoleus chthonoplastes.
Lipoxygenase (LOX) inhibitors are considered to be important anti-inflammatory agents as it can control many inflammatory responses to some extent. Even though the marine bio-systems are not well explored, they are considered to be one of the promising repositories for drug lead molecules against variety of diseases. In the present study a new LOX inhibitor compound, 1-ethenoxy-2-methylbenzene, reported first time from a living system, Microcoleus chthonoplastes, has been isolated by activity guided fractionation and further structurally characterised by techniques such as FTIR, NMR and LC MS/MS. Further enzyme kinetics, isothermal titration calorimetry and molecular docking methods were used in order to get a better understanding of enzyme-ligand interactions. This exploration suggests its worthiness as a lead molecule for the development of a better anti-inflammatory drug. Its high structure-activity resemblance to cuminaldehyde from cumin seeds, which is earlier reported as a LOX inhibitor, is also established.


Peptide-modified p(AAm-co-EG/AAc) IPNs grafted to bulk titanium modulate osteoblast behavior in vitro.
Interpenetrating polymer networks (IPNs) of poly(acrylamide-co-ethylene glycol/acrylic acid) (p(AAm-co-EG/AAc) applied to model surfaces prevent protein adsorption and cell adhesion. Subsequently, IPN surfaces functionalized with the RGD cell-binding domain from rat bone sialoprotein (BSP) modulated bone cell adhesion, proliferation, and matrix mineralization. The objective of this study was to utilize the same biomimetic modification strategy to produce functionally similar p(AAm-co-EG/AAc) IPNs on clinically relevant titanium surfaces. Contact angle goniometry and X-ray photoelectron spectroscopy (XPS) data were consistent with the presence of the intended surface modifications. Cellular response was gauged by challenging the surfaces with primary rat calvarial osteoblast (RCO) surfaces in serum-containing media. IPN modified titanium and negative control (RGE-IPN) surfaces inhibit cell adhesion and proliferation, while RGD-modified IPNs on titanium supported osteoblast attachment and spreading. Furthermore, the latter surfaces supported significant mineralization despite exhibiting lower levels of proliferation than positive control surfaces. These results suggest that with the appropriate optimization, this approach may be practical for surface engineering of osseous implants.


The effect of a self-monitored relaxation breathing exercise on male adolescent aggressive behavior.
This study sought to contribute to the identification of effective interventions in the area of male adolescent aggressive behavior. Existing research includes both group- and single-case studies implementing treatments which typically include an anger-management component and its attendant relaxation and stress-reduction techniques. The design of this study was single-subject with multiple baselines across 6 subjects on 2 behavioral measures. The setting was a residential juvenile justice program for male adolescents, and the treatment was a relaxation breathing exercise. The results of the study were mixed, with improvement on both behavioral measures in 2 of the 6 participants.


An overview of the past, present, and future of nongonadal LH/hCG actions in reproductive biology and medicine.
Even though there were hints, it was not until 1986 that a number of laboratories worldwide began to demonstrate unequivocally the presence and functions of luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors in various female and male nongonadal tissues. There was no species specificity but there was tissue specificity in the nongonadal LH/hCG receptor distribution. Nongonadal receptor levels were lower but they were regulated and processed and used signaling mechanisms similarly to gonadal receptors. Although still greater understanding is needed, gains made in the last decade demonstrate that nongonadal actions of LH/hCG are physiologically important and may have relevance to better understanding several diseases and their treatment. A recently developed LH receptor knockout model has begun to reaffirm and extend the importance of nongonadal LH signaling in the body.


Medical management of the comatose, vegetative, or minimally responsive patient.
This review outlines the range of medical problems occurring in brain injured patients in coma or emerging from coma, including the population of vegetative and minimally responsive patients. This range of medical problems includes those associated with the original brain injury or associated injuries, those representing complications of bedrest, and those caused by the use of medications that may retard recovery or contribute to an obtunded or comatose state. The review is organized by organ systems, each section including a brief discussion with reference to more indepth discussions in other sources. A number of algorithms are included to define approaches to evaluation of common clinical presentations which may be helpful to clinicians treating this population in acute or subacute settings.


Brain monoamine systems in multiple system atrophy: a positron emission tomography study.
Post-mortem studies of multiple system atrophy (MSA) patients have shown widespread subcortical neurodegeneration. In this study, we have used 18F-dopa PET, a marker of monoaminergic nerve terminal function, to explore in vivo changes in striatal and extrastriatal dopamine, noradrenaline, and serotonin transmission for a cohort of patients with MSA with predominant parkinsonism. Fourteen patients with MSA, ten patients with idiopathic Parkinson's disease (PD) matched for disease duration, and ten healthy controls were studied with 18F-dopa PET. Regions of interest (ROIs) were placed to sample 18F-dopa uptake in thirteen structures and mean activity was compared between groups. The MSA patients showed significantly decreased 18F-dopa uptake in putamen, caudate nucleus, ventral striatum, globus pallidus externa and red nucleus compared to controls, whereas PD patients only had decreased 18F-dopa uptake in putamen, caudate nucleus, and ventral striatum. MSA cases with orthostatic hypotension had lower 18F-dopa uptake in the locus coeruleus than patients without this symptom. In conclusion, 18F-dopa PET showed more widespread basal ganglia dysfunction in MSA than in PD with similar disease duration, and extrastriatal loss of monoaminergic innervation could be detected in the red nucleus and locus coeruleus. In contrast to PD, there was no evidence of early compensatory increases in regional 18F-dopa uptake.


Bronchoscopic findings of endobronchial vascular lesions in patients with haemoptysis.
Cases of endobronchial vascular lesions observed with bronchoscope are presented. These lesions tend to be diagnosed erroneously as true endobronchial tumours so that biopsies are tried frequently. Consequently, a catastrophic accident of massive bleeding can complicate the condition if endobronchial vascular lesions are injured during bronchoscopic biopsy or brushing. We present three types of endobronchial vascular lesion: tubular bulging type, mass-like type and haemangioma type. Because bronchoscopic findings of submucosal tubular structure and visible pulsation are highly suggestive of endobronchial vascular lesion, there must be extreme caution to prevent fatal bleeding.


[Primary hyperparathyroidism is common among postmenopausal women. Identification of genetic risk factors can contribute to individualized treatment].
Primary hyperparathyroidism (pHPT) is commonly seen in postmenopausal women. Along with the clinical characterisation of the disease, studies of molecular genetics have contributed to increased understanding of the etiology of pHPT. Genetic association studies have revealed that certain vitamin D receptor polymorphisms relate to the development of sporadic pHPT. A new type of familial pHPT was recently discovered. Studies of parathyroid adenomas have demonstrated that the tumor suppressor gene MEN1 and the oncogene cyclinD1 are of importance for the tumorigenesis.


Nanofunctionalisation for the treatment of peripheral nervous system injuries.
A construct based on the electrostatic layer-by-layer self assembly technique has been fabricated, to be used as a tailored device to encourage nerve regeneration. A multilayered nanocoating composed of three precursor bilayers of cationic poly(dimethyldiallylammonium) chloride (PDDA) and anionic poly(styrenesulfonate) (PSS), followed by bilayers of poly-D-lysine (PDL) and antibody specific to transforming growth factor 1 (anti-TGF-1), has been deposited on HYAFF 11. The assembly process has been monitored by quartz crystal microbalance (QCM) for its characterisation and then it has been used on HYAFF 11. Structural studies of the resulting multilayers confirmed stepwise deposition of anti-TGF-1, with an average layer thickness of 2.2+/-0.2 nm and an average surface density of 0.36+/-0.03 mug cm(-2). Scanning electron microscopy has been used to characterise multilayer uniformity. Finally, the immunological activity of the multilayered structure has been assessed. The results show that anti-TGF-1 can be included in its active form in a predetermined multilayered structure onto HYAFF 11 with quantitative control of layer thickness and weight, providing a high tool with great potential in tissue engineering.


Microbial Diagnostic Microarrays for the Detection and Typing of Food- and Water-Borne (Bacterial) Pathogens.
Reliable and sensitive pathogen detection in clinical and environmental (including food and water) samples is of greatest importance for public health. Standard microbiological methods have several limitations and improved alternatives are needed. Most important requirements for reliable analysis include: (i) specificity; (ii) sensitivity; (iii) multiplexing potential; (iv) robustness; (v) speed; (vi) automation potential; and (vii) low cost. Microarray technology can, through its very nature, fulfill many of these requirements directly and the remaining challenges have been tackled. In this review, we attempt to compare performance characteristics of the microbial diagnostic microarrays developed for the detection and typing of food and water pathogens, and discuss limitations, points still to be addressed and issues specific for the analysis of food, water and environmental samples.


Mechanisms prevalent during bioremediation of wastewaters from the pulp and paper industry.
Bioremediation of wastewaters represents an important treatment methodology, especially when examined against the backdrop of ever-stricter legislation that is evolving in order to regulate effluent release into the environment. It has been reported that bioremediation specifically holds promise in solving environmental problems. Crucial questions surrounding the treatment of effluents include: efficiency of the process, economic feasibility, legal requirements, and the mechanisms involved in the remediation process. Of all these issues mentioned, the last requires special attention. This paper investigates these matters and focuses on techniques that are currently employed to determine the efficiency of bioremediation and mechanisms involved therein. The physiological significance of biosorption is also examined, as this subject has not been fully addressed in previous publications.


A low-cost DAC BIST structure using a resistor loop.
This paper proposes a new DAC BIST (digital-to-analog converter built-in self-test) structure using a resistor loop known as a DDEM ADC (deterministic dynamic element matching analog-to-digital converter). Methods for both switch reduction and switch effect reduction are proposed for solving problems related to area overhead and accuracy of the conventional DAC BIST. The proposed BIST modifies the length of each resistor in the resistor loop via a merging operation and reduces the number of switches and resistors. In addition, the effect of switches is mitigated using the proposed switch effect reduction method. The accuracy of the proposed BIST is demonstrated by the reduction in the switch effect. The experimental results show that the proposed BIST reduces resource usages and the mismatch error caused by the switches.


[Surgical and botulinum toxin treatment in two cases of abnormal retinal correspondence-exotropia with congenital homonymous hemianopsia].
We report 2 unusual cases of congenital occipital hemianopsia associated with abnormal retinal correspondence (ARC)-exotropia. Two Japanese males, 25 and 28 years of age, visited our hospital for surgical correction of manifest exotropia with dissociated vertical deviation and overaction of the superior oblique muscle. Visual field examination demonstrated homonymous hemianopsia with approximately 5 to 10 degrees of macular sparing. Visually evoked potential examination showed small amplitude similar to dissociated vertical deviation patients in all half-field stimulation. Electrooculogram examination demonstrated defective pursuit to the ipsilateral side. Some investigators have speculated that progressive exotropia compensates for homonymous hemianopsia and is a rare contraindication for strabismus surgery. To confirm the deterioration of motor and visual functions before surgery in these patients, we tried injections of botulinum A type toxin into the lateral rectus muscle ipsilateral to the hemianopsia. Contrary to the hypothesis, our patients had no change in their binocular visual fields and visual function. Finally, we performed recession of the lateral rectus muscle, so that both patients were satisfied with their ocular alignment, with no marked change of visual behavior.


Operando XRD studies on Bi2MoO6as anode material for Na-ion batteries.
Based on the same rocking-chair principle as rechargeable Li-ion batteries, Na-ion batteries are promising solutions for energy storage benefiting from low-cost materials comprised of abundant elements. However, despite the mechanistic similarities, Na-ion batteries require a different set of active materials than Li-ion batteries. Bismuth molybdate (Bi2MoO6) is a promising NIB anode material operating through a combined conversion/alloying mechanism. We report anoperandox-ray diffraction (XRD) investigation of Bi2MoO6-based anodes over 34 (de)sodiation cycles revealing both basic operating mechanisms and potential pathways for capacity degradation. Irreversible conversion of Bi2MoO6to Bi nanoparticles occurs through the first sodiation, allowing Bi to reversibly alloy with Na forming the cubic Na3Bi phase. Preliminary electrochemical evaluation in half-cellsversusNa metal demonstrated specific capacities for Bi2MoO6to be close to 300 mAh g-1during the initial 10 cycles, followed by a rapid capacity decay.OperandoXRD characterisation revealed that the increased irreversibility of the sodiation reactions and the formation of hexagonal Na3Bi are the main causes of the capacity loss. This is initiated by an increase in crystallite sizes of the Bi particles accompanied by structural changes in the electronically insulating Na-Mo-O matrix leading to poor conductivity in the electrode. The poor electronic conductivity of the matrix deactivates the NaxBi particles and prevents the formation of the solid electrolyte interface layer as shown by post-mortem scanning electron microscopy studies.


Helicobacter pylori gastritis mimicking gastric carcinoma at CT evaluation.
The abdominal computed tomographic (CT) scans from 61 patients with biopsy-proved Helicobacter (formerly Campylobacter) pylori gastritis were retrospectively reviewed. The CT scans were interpreted on the basis of the original report of the findings at CT examination and without knowledge of the results of biopsy. Of 19 patients (31%) with gastric abnormalities at CT, 14 (74%) had inflammatory changes initially reported as suspicious for gastric malignancy; malignancy was entertained as the primary diagnosis in four of those patients. In five of the 19 abnormal cases (26%), the diagnosis with CT was gastritis. The two major patterns of severe H pylori infection identified were (a) circumferential antral wall thickening and (b) thickening of the posterior gastric wall along the greater curvature, with or without evidence of ulceration. Thickening averaged 1.5-2.0 cm in cases suspicious for malignancy. The majority of abnormalities involved the gastric antrum (68%). No cases demonstrated significant adenopathy, obliteration of fat planes, or invasion of adjacent organs.


Grateful Med Version 2.0: an overview for searchers.
Grateful Med is a software interface developed by the National Library of Medicine (NLM) for searching several of NLM's databases: MEDLINE, its backfiles to 1966, and CATLINE. It is designed to facilitate access to medical information by health professionals and other end users with limited or no searching experience. This article describes the basic approach and specific searching features of Version 2.0 of the system.


The Use of the Cavity-Rim Cervical Cap in a Family Physician's Office.
This paper describes a retrospective study which looked at the effectiveness of the Prentif cavity-rim cervical cap, cap usage, cap-associated problems and acceptability for 95 women fitted with a cervical cap at a family physician's office. The pregnancy rate of this group was 12.28/100 years of exposure. Data on cap usage, cap-associated problems and acceptability are presented and briefly discussed. The authors believe that although cap fitting and teaching are time consuming, and that the reported pregnancy rate is relatively high, the cervical cap does remain a valuable alternative method of contraception for some women.


von Hippel-Lindau partner Jade-1 is a transcriptional co-activator associated with histone acetyltransferase activity.
Jade-1 was identified as a protein partner of the von Hippel-Lindau tumor suppressor pVHL. The interaction of Jade-1 and pVHL correlates with renal cancer risk. We have investigated the molecular function of Jade-1. Jade-1 has two zinc finger motifs called plant homeodomains (PHD). A line of evidence suggests that the PHD finger functions in chromatin remodeling and protein-protein interactions. We determined the cellular localization of Jade-1 and examined whether Jade-1 might have transcriptional and histone acetyltransferase (HAT) functions. Biochemical cell fractionation studies as well as confocal images of cells immunostained with a specific Jade-1 antibody revealed that endogenous Jade-1 is localized predominantly in the cell nucleus. Tethering of Gal4-Jade-1 fusion protein to Gal4-responsive promoters in co-transfection experiments activated transcription 5-6-fold, indicating that Jade-1 is a possible transcriptional activator. It was remarkable that overexpression of Jade-1 in cultured cells specifically increased levels of endogenous acetylated histone H4, but not histone H3, strongly suggesting that Jade-1 associates with HAT activity specific for histone H4. Deletion of the two PHD fingers completely abolished Jade-1 transcriptional and HAT activities, indicating that these domains are indispensable for Jade-1 nuclear functions. In addition, we demonstrated that TIP60, a known HAT with histone H4/H2A specificity, physically associates with Jade-1 and is able to augment Jade-1 HAT function in live cells, strongly suggesting that TIP60 might mediate Jade-1 HAT activity. Thus, Jade-1 is a novel candidate transcriptional co-activator associated with HAT activity and may play a key role in the pathogenesis of renal cancer and von Hippel-Lindau disease.


Postmortem examination of the blood supply and vascular pattern of small liver metastases in man.
Thirteen human cadavers with liver metastases were examined. Microfil was injected into the portal vein and hepatic artery. The liver metastases were examined under dissecting microscope, and their vascular supply and patterns were registered. It was found that most metastases had both arterial and portal supply even if the arterial supply dominated. Extensive filling of tumor vessels was observed in both lobes in one liver in which the portal vein of one lobe and the hepatic artery of the other was injected (i.e., the same kind of metastases could be filled from either the hepatic artery or the portal vein). It is suggested that the findings could be of great importance in planning treatment of patients with liver metastases.


Papaya epicarp extract protects against hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuronal cells.
Recent studies indicated that regular consumption of antioxidant-rich foods reduces cellular oxidative stress and protects against health-related problems. This study aimed to assess the in vitro antioxidant properties of the papaya epicarp extract against hydrogen peroxide (H(2)O(2))-induced oxidative stress in human SH-SY5Y neuronal cells. Our study revealed that papaya epicarp extract acted as a potent free radical scavenger and provided neuroprotection against H(2)O(2)-induced oxidative stress. Papaya epicarp extract ameliorated glutathione depletion, restored total antioxidant capacity and augmented the inhibition of antioxidant enzymes (catalase, glutathione peroxidases and superoxide dismutase). In conclusion, papaya epicarp extract can be used as a functional dietary ingredient that might help in reducing the neurological health problems associated with various oxidative stress insults.


The suppressive role and aberrent promoter methylation of BTG3 in the progression of hepatocellular carcinoma.
BTG3 (B-cell translocation gene 3) has been identified as a tumor suppressor and hypermethylation contributes to its down-regulation in some tumors, but its role in hepatocellular carcinoma (HCC) remain unknown. This study aimed to detect the expression and methylation status of BTG3 in HCC cell lines or tissues, and determine its function in HCC progression. The expression of BTG3 was detected in HCC cell lines and HCC tissue by real-time RT-PCR, Western blot or immunohistochemistry. The promoter methylation status of BTG3 was measured by using methylation-specific PCR in HCC cell lines. A series of assays were performed to evaluate the effect of BTG3 on proliferation, invasion and cell cycle transition in vitro. BTG3 expression was lower in HCC cell lines than in hepatocyte cell line LO2 (P<0.05). BTG3 was also down-regulated in HCC tissues. Its expression was positively correlated with differentiation and distant metastasis (P<0.05). Patients with lower BTG3 expression had shorter overall survival time (P=0.029). DNA methylation directed repression of BTG3 mRNA expression in HCC cell lines. BTG3 suppressed proliferation, invasion and induces G1/S cycle arrest of HCC cells in vitro. Down-regulation of BTG3 due to the promoter hypermethylation is closely associated with proliferation, invasion and cell cycle arrest of HCC cells. It may be a novel prognostic biomarker for HCC patients.


Details of the nucleic acid binding site of T4 gene 32 protein revealed by proteolysis and DNA Tm depression methods.
The affinities and location of oligonucleotides bound to intact and truncated bacteriophage T4 gene 32 protein have been elucidated by two independent and sensitive methods. The nucleic acid binding site is located within the core domain of 32 protein, residues 22-253. Oligonucleotides protect the core domain against proteolysis catalyzed by mammalian endoproteinase Arg-C. Of the three cleavage sites, Arg111, within the internal "LAST" ((Lys/Arg)3(Ser/Thr)2) motif, is selectively protected. We have previously suggested that these LAST residues, Lys-Arg-Lys-Thr-Ser, residues 110-114, are involved in nucleic acid binding, and our results are also consistent with crystallographic studies. The inhibitory effects of oligonucleotides on the kinetics of core domain proteolysis were used to quantify binding affinities. In addition, affinities of oligonucleotides for both core domain and intact protein were obtained from their effect on the Tm-depressing activities of these proteins. For both core and intact protein, the degree of affinity increases with oligonucleotide length. The presence of a 5' terminal phosphate increases the affinity two- to fourfold. Placement of methylphosphonodiester (uncharged) linkages at alternating linkages vastly lowers binding affinity for the intact protein and core domain. We conclude that at least two and likely three adjacent phosphodiester linkages are a minimal requirement for binding, further defining the electrostatic component of the interaction. The length-dependence of binding affinity suggests that additional interactions, both ionic and non-ionic, likely occur with longer oligonucleotides.


Neuronal developmental marker FORSE-1 identifies a putative progenitor of the pulmonary neuroendocrine cell lineage during lung development.
The FORSE-1 (forebrain-surface-embryonic) monoclonal antibody (MAb) recognizes a carbohydrate cell surface epitope related to the Lewis-X (LeX) and stage-specific embryonic antigens (SSEAs). In the developing CNS, the FORSE-1 epitope is believed to serve as a marker of progenitor cells. We studied the expression of the FORSE-1 epitope in pulmonary neuroendocrine cells (PNECs) and related neuroepithelial bodies (NEBs), cell types implicated in paracrine regulation of lung development. We used dual immunolabeling to identify PNECs/NEBs in tissue sections from developing rabbit fetal lungs and corresponding primary lung cell cultures. During the early stage (E16), the FORSE-1 MAb labeled primitive airway epithelium, whereas serotonin (5HT) immunoreactivity, a marker of PNEC/NEB differentiation, was negative. After E18, FORSE-1 labeling became restricted to PNECs and NEBs, identified by co-expression with 5HT, then decreased coincident with an increase in 5HT. Expression of the FORSE-1 epitope correlated inversely with 5HT expression in PNEC/NEB cells. FORSE-1 immunoreactivity correlated with cell proliferation assessed by BrdU labeling. Downregulation of the FORSE-1 epitope correlated with maturation of PNECs/NEBs. The presence of few FORSE-1/5HT-positive cells in postnatal lung suggests retention of progenitors. The FORSE-1 epitope was associated with a high molecular weight (286 kD) glycoprotein that decreased with increasing gestational age, as demonstrated by immunoblotting. Overall expression of SSEA-1, -3, and -4 antigens was similar to FORSE-1/5HT, although the former was preferentially localized to neurite-like processes. Because the role of the FORSE-1 epitope in the CNS probably involves cell adhesion and differentiation, we propose a similar function in developing lung. The demonstration of LeX/SSEA antigen expression in the PNEC/NEB cell lineage underscores the importance of these cells in developing lung. Furthermore, the FORSE-1 antigen may identify committed progenitors of the PNEC/NEB cell system.


Laparoscopic spleen-preserving distal pancreatectomy for pancreatic neoplasms: a retrospective study.
To describe the clinical characteristics, technical procedures, and outcomes of patients undergoing laparoscopic spleen-preserving distal pancreatectomy (LSPDP) for benign and malignant pancreatic neoplasms. The clinical data of 38 patients who underwent LSPDP in the Sir Run Run Shaw Hospital between January 2003 and August 2013 were analyzed retrospectively. Surgical techniques for LSPDP included preservation of the splenic artery and vein (Kimura's technique) and ligation of the splenic pedicle with preservation of the short gastric vessels (Warshaw's technique). There were no conversions to open surgery in the 38 patients. Splenic vessels were conserved during spleen-preserving pancreatectomy, except in two patients who underwent resection of the splenic vessels and preservation only of the short gastric vessels. The mean operation time was 123.2 ± 52.4 min, the mean intraoperative blood loss was 78.2 ± 39.5 mL, and the mean postoperative hospital stay was 7.6 ± 2.9 d. The overall rate of postoperative complications was 18.4% (7/38), and the rate of clinical pancreatic fistula was 13.2% (5/38). All postoperative complications were treated conservatively. The postoperative pathological diagnoses were 22 cases of benign pancreatic disease and 16 cases of borderline or low-grade malignant lesions. During a median follow-up of 38 mo (range: 5-133 mo), no recurrence was observed. LSPDP is a safe, feasible and effective procedure for the treatment of benign and low-grade malignant tumors of the distal pancreas.


Laboratory-scale production of 13C-labeled lycopene and phytoene by bioengineered Escherichia coli.
Consumption of tomato products has been associated with decreased risks of chronic diseases such as cardiovascular disease and cancer, and therefore the biological functions of tomato carotenoids such as lycopene, phytoene, and phytofluene are being investigated. To study the absorption, distribution, metabolism, and excretion of these carotenoids, a bioengineered Escherichia coli model was evaluated for laboratory-scale production of stable isotope-labeled carotenoids. Carotenoid biosynthetic genes from Enterobacter agglomerans were introduced into the BL21Star(DE3) strain to yield lycopene. Over 96% of accumulated lycopene was in the all-trans form, and the molecules were highly enriched with 13C by 13C-glucose dosing. In addition, error-prone PCR was used to disrupt phytoene desaturase (crtI) function and create a phytoene-accumulating strain, which was also found to maintain the transcription of phytoene synthase (crtB). Phytoene molecules were also highly enriched with 13C when the 13C-glucose was the only carbon source. The development of this production model will provide carotenoid researchers a source of labeled tracer materials to further investigate the metabolism and biological functions of these carotenoids.


Interactions between gut peptides and the central melanocortin system in the regulation of energy homeostasis.
Genetic and pharmacological studies have shown that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Animals and humans with defects in the central melanocortin system display a characteristic melanocortin obesity phenotype typified by increased adiposity, hyperphagia, metabolic defects and increased linear growth. In addition to interacting with long-term regulators of energy homeostasis such as leptin, more recent data suggest that the central melanocortin system also responds to gut-released peptides involved in mediating satiety. In this review, we discuss the interactions between these systems, with particular emphasis on cholecystokinin (CCK), ghrelin and PYY(3-36).


Genetic lineage tracing in skin reveals predominant expression of HEY2 in dermal papilla during telogen and that HEY2+ cells contribute to the regeneration of dermal cells during wound healing.
Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear what the source of progenitor cells is for dermal cell regeneration during wound healing, and whether DP cells are involved in this process. We analyzed the gene expression profile of various skin cell populations using existing datasets and found that the Hey2 gene was predominantly expressed in DP cells. We introduced Hey2-CreERT2 knockin mice and crossed them with Rosa26-ZsGreen reporter mice. After induction in the double transgenic mice by administration of tamoxifen, the reporter ZsGreen was found to be predominantly expressed in DP cells both at anagen and telogen phases, and broadly expressed in some other dermal cells at anagen. We also created a wound after tamoxifen induction, and found there were abundant ZsGreen+ cells in the regenerated dermis. We conclude that the HEY2+ DP cells and dermal cells exhibit some stemness properties and can contribute to the dermal cell regeneration during wound healing.


Evaluation of immune protection against Toxoplasma gondii infection in mice induced by a multi-antigenic DNA vaccine containing TgGRA24, TgGRA25 and TgMIC6.
Toxoplasma gondii infection is prevalent in humans and animals worldwide. In this study, recombinant eukaryotic expression plasmids (pVAX-GRA24, pVAX-GRA25 and pVAX-MIC6) were constructed, and then injected into Kunming mice intramuscularly, as cocktailed plasmids or as single-gene plasmids. We evaluated immune protective responses by detecting the titer of antibodies and cytokine production of IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-23, the percentages of the subclasses of T lymphocytes, as well as the records of the survival time and cyst decrement in the brain of the mouse model after challenge with the T. gondii RH and Pru strains, respectively. Compared with the control groups, antibody and cytokine production were significantly increased, while the survival times of mice in all immunized groups were also prolonged, and the number of T. gondii cysts in their brains were decreased significantly (29.03% for pVAX-GRA24; 40.88% for pVAX-GRA25; 37.70% for pVAX-MIC6; 48.06% for pVAX-GRA24 + pVAX-GRA25; and 55.37% for pVAX-GRA24 + pVAX-GRA25 + pVAX-MIC6). The mouse group immunized with the three-gene cocktail (TgGRA24 + TgGRA25 + TgMIC6) had better performance in each detection index than the mouse groups immunized with the two-gene cocktail of TgGRA24 + TgGRA25, which was better than that in the group immunized with the single gene vaccine of TgGRA24, TgMIC6 or TgGRA25. In conclusion, TgGRA24 or TgGRA25 may be good vaccine candidates against T. gondii infection, but the three-gene cocktail of TgGRA24, TgMIC6 and TgGRA25 may induce the strongest protective immunity. Further studies of multi-antigenic DNA vaccines or cocktailed vaccines against T. gondii infection are necessary.


Possibility of a New Indication for Amantadine in the Treatment of Bipolar Depression-Case Series Study.
Bipolar disorder is a chronic and remitting mental illness. Antidepressants are not effective in treating acute bipolar depression, and antipsychotic drugs used in the treatment of bipolar depression cause frequent side effects. This situation justifies the search for new drugs as well as the repurposing of drugs used in other indications. In an open and naturalistic serious case study, 4 patients diagnosed with bipolar I disorder, chronically treated with a mood stabilizer, in whom at least two antidepressants were ineffective in the depressive phase, were treated with amantadine. The woman received 100 mg/day and 3 men received the target dose of 200 mg/day. All patients treated with amantadine improved their depressive symptoms after 1 week of treatment. None of them experienced side effects or manic switch. To reduce the risk of a manic switch, the treatment with amantadine was discontinued 2 weeks after the improvement of depressive symptoms, and no recurrence of depressive symptoms was observed. Amantadine may be a further therapeutic option for the treatment of acute bipolar depression. The drug in this indication may act quickly and be well tolerated. Confirmation of the antidepressant efficacy of amantadine in this indication requires replication of the results and conducting clinical trials.


Pickstone v. Freemans plc, 25 March 1987.
The applicants, female warehouse operatives for the defendant, challenged the defendant's policy of paying warehouse checkers more than they were being paid. They claimed that both groups were engaged in work of equal value and should be given equal pay. The case was dismissed by a lower court because the defendant employed men in both positions at the same pay as women in those positions and the Equal Pay Act 1970 prohibited suits in such circumstances. The Court of Appeal reversed this decision, holding that Article 119 of the EEC Treaty authorized the suit and overrode conflicting national legislation. It remanded the case for determination whether the pay differential between the two jobs was due to reasons other than sex discrimination.


Pharmacology of lacidipine, a vascular-selective calcium antagonist.
Lacidipine is a new 1,4-dihydropyridine (DHP) that induces a potent calcium antagonistic activity on vascular preparations. It has a markedly slow rate of onset, but its effect is still apparent after 9 h of drug washout. Calcium antagonistic activity has been evaluated on nonvascular smooth muscle, and lacidipine has proved to be more vascular-selective than standard DHP derivatives. In cardiac preparations, the concentrations required to induce negative inotropic effects are approximately 100 times higher than concentrations needed to antagonize calcium-induced contractions in vascular smooth muscle. In addition, lacidipine exhibits antioxidant properties in tests based on the autoperoxidation of rat cerebral cortical membranes. In spontaneously hypertensive rats (SHRs), lacidipine induces a potent and long-acting blood pressure reduction (ED25 = 0.19 mg/kg orally and 0.006 mg/kg intravenously, with durations greater than 12 and 3 h, respectively). In saline-loaded SHRs and at antihypertensive dosages, lacidipine increases urine volume as well as urinary excretion of sodium. In one-clip, two-kidney renal hypertensive dogs, the antihypertensive properties of lacidipine after both oral and intravenous administration were confirmed. The marked vascular selectivity of lacidipine was clearly evident both in pithed rats infused with angiotensin II and in anesthetized dogs, in which preferential and long-lasting coronary and vertebral blood flow increases were also observed.


The Sinorhizobium meliloti Nitrogen Stress Response Changes Radically in the Face of Concurrent Phosphate Stress.
Expression of hundreds of S. meliloti genes changed more than two-fold in response to either nitrogen or phosphate limitation. When these two stresses were applied together, stress responsive gene expression shifted dramatically. In particular, the nitrogen stress response in the presence of phosphate stress had only 30 of about 350 genes in common with the 280 genes that responded to nitrogen stress with adequate phosphate. Expression of sRNAs was also altered in response to these stresses. 82% of genes that responded to nitrogen stress also responded to phosphate stress, including 20 sRNAs. A subset of these sRNAs is known to be chaperoned by the RNA binding protein, Hfq. Hfq had previously been shown to influence about a third of the genes that responded to both nitrogen and phosphate stresses. Phosphate limitation influenced changes in gene expression more than nitrogen limitation and, when both stresses were present, phosphate stress sometimes reversed the direction of some of the changes induced by nitrogen stress. These nutrient stress responses are therefore context dependent.


Blood O2 affinity and maximal O2 consumption in elite bicycle racers.
The PO2 at which hemoglobin is half-saturated with O2 (P50) at 37 degrees C, PCO2 = 42 Torr, measured pH and 2,3-diphosphoglycerate-to-hemoglobin concentration ratio ( [2,3-DPG]/[Hb]) values, Hill's coefficient (n) at rest, and maximal O2 consumption (VO2max) were determined in 11 world-class professional bicycle racers off-season (control, C), after 3 mo of 3 h daily training (preseason, PrS), and after additional 6 mo of competitions (competitive season, CoS). The results indicate that the P50 observed in trained athletes was the same as that of a comparable group of sedentary subjects (Sed) under the same conditions of pH, PCO2, and [2,3-DPG]/[Hb] and was similar to that obtained after "normalization" in respect to pH and the [2,3-DPG]/[Hb]; [2,3-DPG]/[Hb] increased as a function of training from 0.72 to 0.95 (P less than 0.001); the slope of the central portion of the O2 equilibrium curve (OEC) was nearly unaffected by endurance training as indicated by the n value (NCoS = 2.70 +/- 0.08; nSed = 2.65 +/- 0.08); and VO2max increased in the course of training 7 and 9% (P less than 0.001), respectively, when expressed in absolute units or per kilogram body weight. The VO2max predicted on the basis of a computer simulation does not increase significantly as a consequence of the measured rise in [2,3-DPG]. Therefore, the observed increase of VO2max cannot be explained with adaptive changes of the OEC. The present results differ from previous findings reported in other types of athletes.


Effects of NIP-502 on antigen-induced bronchial responses and allergic reactions in animal models.
We examined the effect of a newly synthesized pyridazinone derivative, NIP-502 [4-chloro-5-(3-ethoxy)-4-phenoxybenzamine)-3(2H)-pyridazinone], on antigen-induced bronchial responses and allergic reactions in several animal models. NIP-502 (10 mg/kg, p.o.) inhibited the antigen-induced immediate asthmatic response in passively sensitized guinea pigs. The inhibitory effect was also observed in metyrapone (an inhibitor of 11 beta-hydroxylase)-pretreated guinea pigs. NIP-502 improved ovalbumin (OA)-induced airway hyperresponsiveness to acetylcholine and inhibited the OA-induced increase in the number of inflammatory leukocytes in the bronchoalveolar lavage fluid. These inhibitory effects on OA-induced responses were similar to those of prednisolone. NIP-502 also showed an inhibitory effect on the passive cutaneous anaphylactic reaction in rats but did not inhibit the reversed cutaneous anaphylactic reaction, reversed Arthus reaction or delayed type hypersensitivity reaction. On the other hand, prednisolone showed broad inhibitory effects except for the reversed cutaneous anaphylactic reaction. In the in vitro study, NIP-502 (30 microM) significantly inhibited Formyl-Met-Leu-Phe-induced superoxide anion production by the guinea pig alveolar macrophages. These results indicate that the inhibitory effects of NIP-502 on bronchial responses are similar to those of prednisolone, but this compound seemed to act more selectively on the respiratory tract than prednisolone. Because of its effectiveness against a variety of bronchial responses, NIP-502 may be useful in the treatment of bronchial asthma.


Isoform Specificity of PKMs during Long-Term Facilitation in Aplysia Is Mediated through Stabilization by KIBRA.
Persistent activity of protein kinase M (PKM), the truncated form of protein kinase C (PKC), can maintain long-term changes in synaptic strength in many systems, including the hermaphrodite marine mollusk, Aplysia californica Moreover, different types of long-term facilitation (LTF) in cultured Aplysia sensorimotor synapses rely on the activities of different PKM isoforms in the presynaptic sensory neuron and postsynaptic motor neuron. When the atypical PKM isoform is required, the kidney and brain expressed adaptor protein (KIBRA) is also required. Here, we explore how this isoform specificity is established. We find that PKM overexpression in the motor neuron, but not the sensory neuron, is sufficient to increase synaptic strength and that this activity is not isoform-specific. KIBRA is not the rate-limiting step in facilitation since overexpression of KIBRA is neither sufficient to increase synaptic strength, nor to prolong a form of PKM-dependent intermediate synaptic facilitation. However, the isoform specificity of dominant-negative-PKMs to erase LTF is correlated with isoform-specific competition for stabilization by KIBRA. We identify a new conserved region of KIBRA. Different splice isoforms in this region stabilize different PKMs based on the isoform-specific sequence of an α-helix "handle" in the PKMs. Thus, specific stabilization of distinct PKMs by different isoforms of KIBRA can explain the isoform specificity of PKMs during LTF in AplysiaSIGNIFICANCE STATEMENT Long-lasting changes in synaptic plasticity associated with memory formation are maintained by persistent protein kinases. We have previously shown in the Aplysia sensorimotor model that distinct isoforms of persistently active protein kinase Cs (PKMs) maintain distinct forms of long-lasting synaptic changes, even when both forms are expressed in the same motor neuron. Here, we show that, while the effects of overexpression of PKMs are not isoform-specific, isoform specificity is defined by a "handle" helix in PKMs that confers stabilization by distinct splice forms in a previously undefined domain of the adaptor protein KIBRA. Thus, we define new regions in both KIBRA and PKMs that define the isoform specificity for maintaining synaptic strength in distinct facilitation paradigms.


Peripheral nerve tumors. Large neurofibroma of the foot.
A neurofibroma of the foot is an uncommon finding and may be associated with von Recklinghausen's disease. A case of a large, solitary neurofibroma is presented with no apparent systemic involvement on history and physical examination. The surgical approach and perioperative treatment for this lesion is presented, and a review of peripheral nerve tumors and neurofibromatosis. A tumor of this size poses many unforeseen problems: large dead space, wound dehiscence, and infection caused by hematoma formation. Preoperative magnetic resonance imaging to determine position, depth, and involvements of vital structures is invaluable. The lazy S incision allows for greater exposure with less skin tension from retraction, thus reducing the risk of wound dehiscence. Careful dissection prevents cutting or injuring of underlying atrophied tissue. Two years after surgery, the plantar muscle has returned to normal strength and size and only a slight amount of sensory deficit exists. His gait is normal, without limp, and with normal heel-to-toe ambulation. This patient's life-style has returned to normal with no alterations.


Applicational possibilities of linear and non-linear (polynomial) regressions and analysis of variance: kinetics of chloramphenicol.
The dependance of the content and microbiological activity of Chloramphenicol (active substance) at dissolution on time and on pH, as well as that of the content and microbiological activity of Chloramphenicol (250 mg capsules) at release, on time, in in-vitro conditions, was determined using linear and non-linear (polynomial and generalized dilution) regressions. Based on the square error value, the dependance of the content and microbiological activity of Chloramphenicol (active substance) at dissolution on time and different pH values, as well as the dependance of the content and microbiological activity of Chloramphenicol (capsules) at release on time were best described by polynomial function. The comparison of the content and microbiological activity of Chloramphenicol (active substance) at dissolution at different pH values, as well as of Chloramphenicol (capsules) at release showed the significant correlation between these parameters (r = 0.999, P << 0.001). The comparision of the content, on one hand, and microbiological activity of Chloramphenicol (active substance), on the other, at dissolution at different pH values, as a function of time, was done using a modified method of one-way analysis of variance for linear regression comparisons. Based on the value of Fischer's coefficient (F), there is a statistically very significant difference between the contents and between the microbiological activities of chloramphenicol (active substance) at dissolution and different pH as a function of time (P << 0.005).


Formaldehyde Induces Mesenteric Artery Relaxation via a Sensitive Transient Receptor Potential Ankyrin-1 (TRPA1) and Endothelium-Dependent Mechanism: Potential Role in Postprandial Hyperemia.
Formaldehyde (FA), the smallest aldehyde, is generated endogenously, and is widespread in the environment in foods, beverages and as a gas phase product of incomplete combustion. The main metabolite of FA, formate, was increased significantly in murine urine (∼3×) after overnight feeding. Because feeding increases mesenteric blood flow, we explored the direct effects of FA in isolated murine superior mesenteric artery (SMA). Over the concentration range of 30-1,200 μM, FA strongly and reversibly relaxed contractions of SMA induced by three different agonists: phenylephrine (PE), thromboxane A2 analog (U46,619) and high potassium (60K, 60 mM K+). Formate (to 1.5 mM) induced a modest relaxation. FA (>1,500 μM) irreversibly depressed vascular function in SMA indicating vasotoxicity. The sensitivity (EC50) but not the efficacy (% relaxation) of FA-induced relaxations was dependent on blood vessel type (SMA << aorta) and contractile agonist (PE, EC50= 52 ± 14 μM; U46,619, EC50= 514 ± 129 μM; 60K, EC50= 1,093 ± 87 μM). The most sensitive component of FA vasorelaxation was within physiological levels (30-150 μM) and was inhibited significantly by: (1) mechanically impaired endothelium; (2) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME); (3) transient receptor potential ankyrin-1 (TRPA1) antagonist (A967079); (4) guanylyl cyclase (GC) inhibitor (ODQ); and, (5) K+ channel inhibitor (BaCl2). A similar mechanism of SMA vasorelaxation was stimulated by the TRPA1 agonist cinnamaldehyde. Positive TRPA1 immunofluorescent staining and gene-specific sequence were present in SMA but not in aorta. These data indicate FA, but not formate, robustly relaxes SMA via a sensitive TRPA1- and endothelium-dependent mechanism that is absent in aorta. Thus, as FA levels increase with feeding, FA likely contributes to the physiological reflex of post-prandial hyperemia via SMA vasodilatation.


The effect of the 3',5' thiophosphoryl linkage on the exonuclease activities of T4 polymerase and the Klenow fragment.
The 3'----5' exonuclease activities of T4 DNA polymerase and the Klenow fragment of Polymerase I towards the phosphoryl and thiophosphoryl 3',5' linkage were examined under comparable conditions of idling-turnover, duplex hydrolysis and turnover during polymerization. With the T4 enzyme there is a negligible effect of thiosubstitution on these activities; with the Klenow fragment there is a greater than one hundred-fold reduction in rate with the thiolinkage for the exonuclease but not polymerization activities. This inability to hydrolyze rapidly the thiophosphoryl linkage extends to the hydrolytic activity of Exonuclease III. The quantitation of the exonuclease activities of these three proteins under various conditions should aid in the successful employment of thiophosphoryl nucleoside triphosphates for their incorporation into DNA.


Infection of human thymic epithelial cells by human cytomegalovirus and other viruses: effect on secretion of interleukin 1-like activity.
Cultures of human thymic epithelial (TE) cells are able to produce a interleukin 1 (IL-1) like activity. This IL-1 activity can be detected either using mouse thymocytes in a traditional IL-1 assay, or using thymic lymphocytes obtained from cases of pediatric cardio-vascular surgery. Production of IL-1 activity by TE cells was found to be maximal between 3 and 4 weeks after culture initiation. Human thymocytes worked best as targets in an IL-1 assay, when these cells were derived from donors younger than 1 year of age. Infection of human TE cells by any of human cytomegalovirus, herpes simplex virus type 2, adenovirus 7, Coxsackie B1, and respiratory syncytial virus led to marked reductions in the ability of these cells to secrete measurable IL-1 activity. In the case of TE cells infected by cytomegalovirus, respiratory syncytial virus, and Coxsackie B1, this abrogation of production of IL-1 activity occurred in the absence of any obvious virus-induced cytopathic effect.


Motion blur and motion sharpening in the human visual system.
The effect of motion sharpening upon blur discrimination thresholds was examined for a range of speeds and blur widths. Blur discrimination thresholds were measured for drifting edges whose blur was either physically or perceptually constant. Under conditions where edges were kept at a constant physical blur width, discrimination thresholds rose as a function of speed as previously reported. However, when the perceived blur of edges was held constant, discrimination performance was more-or-less constant for speeds up to at least 6.3 deg sec-1. The results indicate that the deterioration of blur discrimination performance with speed may be due to motion sharpening and not motion blur as has previously been suggested. The results are discussed in terms of a scheme whereby a non-linearity in motion processing serves to sharpen moving edges, whilst the finite integration time of the system tends to smear them.


Al2O3-Cu-Ni Composites Manufactured via Uniaxial Pressing: Microstructure, Magnetic, and Mechanical Properties.
This study's main goal was to obtain and characterize Al2O3-Cu-Ni composites with different metallic phase content. The study analyzed the three series of samples differing in the metallic phase 5, 10, 15 vol.% volume contents. An identical volume share of the metallic components in the metallic phase was used. Ceramic-metal composites were formed using uniaxial pressing and sintered at a temperature of 1400 °C. The microstructural investigation of the Al2O3-Cu-Ni composite and its properties involved scanning electron microscopes observations and X-ray diffraction. The size of the metallic phase in the ceramic matrix was performed using a stereological analysis. Microhardness analysis with fracture toughness measures was applied to estimate the mechanical properties of the prepared materials. Additionally, magnetic measurements were carried out, and the saturation magnetization was determined on the obtained magnetic hysteresis loops. The prepared samples, regardless of the content of the metallic phase in each series, were characterized by a density exceeding 95% of the theoretical density. The magnetic measurements exhibited that the fabricated composites had ferromagnetic properties due to nickel and nickel-rich phases. The hardness of the samples containing 5, 10, 15 vol.% metallic phases decreased with an increase in the metallic phase content, equal to 17.60 ± 0.96 GPa, 15.40 ± 0.81 GPa, 12.6 ± 0.36 GPa, respectively.


A platform for fast screening potential anti-breast cancer compounds in traditional Chinese medicines.
Several Chinese herbs, namely, Pu-Gong-Ying, Gan-Cao, Chai-Hu, Mu-Xiang, Gua-Lou and Huang-Yao-Zi, are frequently used in complex traditional Chinese medicing formulas for breast hyperplasia and breast tumor therapy. The pharmacological effects of these Chinese herbs are all described as 'clearing heat-toxin and resolving masses' in traditional use. However, the chemical profiles of anti-breast cancer constituents in these herbs has not been investigated so far. In this study, a bioactivity-oriented screening platform, which was based on a human breast cancer MCF-7 cellular model, semi-preparative high performance liquid chromatography coupled with ultraviolet spectrophotometry and ultraperformance liquid chromatography coupled to quadrupole-time-of-flight mass spectrometer, was developed to rapidly screen the six Chinese herbs. Two potential anti-breast cancer compounds, which were costunolide (Cos) and dehydrocostus lactone (Dehy), were identified in Mu-Xiang. Combination of the two compounds showed a synergism on inhibiting the proliferation of MCF-7 cells in vitro, which exhibits a potential application prospect for breast cancer therapy. This bioactivity-oriented screening strategy is rapid, economical, reliable and specific for screening potential anti-breast cancer compounds in traditional Chinese medicines.


Antibiotics for acute bronchitis.
Antibiotic treatment of acute bronchitis, which is one of the most common illnesses seen in primary care, is controversial. Most clinicians prescribe antibiotics in spite of expert recommendations against this practice. The objective of this review was to assess the effects of antibiotic treatment for patients with a clinical diagnosis of acute bronchitis. In this updated review, we searched the Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004); MEDLINE (January 1966 to March 2004); EMBASE (January 2000 to December 2003); SciSearch from 1989 to 2004; reference lists of articles and the authors' personal collections up to 1996, and also wrote to study authors and drug manufacturers. EMBASE has previously been searched from 1974 to 2000). Randomised controlled trials comparing any antibiotic therapy with placebo in acute bronchitis or acute productive cough without other obvious cause in patients without underlying pulmonary disease. At least two reviewers extracted data and assessed trial quality. Authors were contacted for missing data. Nine trials involving over 750 patients aged eight to over 65 and including smokers and non-smokers were included in the primary analysis. The quality of the trials was variable. A variety of outcome measures were assessed. Overall, patients receiving antibiotics had better outcomes than did those receiving placebo. At a follow-up visit, they were less likely to have a cough (relative risk (RR) 0.64, 95% confidence interval (CI) 0.49 to 0.85; number-needed-to-treat (NNT) 5; 95% CI 3 to 14), show no improvement on physician assessment (RR 0.52; 95% CI 0.31 to 0.87; NNT 14; 95% CI 8 to 50), or have abnormal lung findings (RR 0.48; 95% CI 0.26 to 0.89; NNT 11; 95% CI 6 to 50); and had shorter durations of cough (weighted mean difference 0.58 days; 95% CI 0.01 to 1.16 days), productive cough (weighted mean difference (WMD) 0.52 days; 95% CI 0.01 to 1.03 days), and feeling ill (WMD 0.58 days; 95% CI 0.00 to 1.16 days). There were no significant differences regarding the presence of night cough, productive cough, or activity limitations at follow up, or in the mean duration of activity limitations. The benefits of antibiotics were less apparent in a sensitivity analysis that included data from two other studies of patients with upper respiratory tract infections with productive cough. There was a non significant trend towards an increase in adverse effects in the antibiotic group, relative risk (RR) 1.22 (95% CI 0.94 to 1.58). Overall, antibiotics appear to have a modest beneficial effect in patients who are diagnosed with acute bronchitis. The magnitude of this benefit, however, is similar to that of the detriment from potential adverse effects.


Simultaneous determination of seven flavonoids in dog plasma by ultra-performance liquid chromatography-tandem mass spectrometry and its application to a bioequivalence study of bioactive components in Herba Epimedii and Er-Xian Decoction.
In this study, a sensitive and specific ultra-performance liquid chromatography-tandem mass method has been developed and validated for the identification and determination of 7 flavonoids in dog plasma for the first time: epimedin A, epimedin B, epimedin C, icariin, sagittatoside B, 2″-O-rhamnosyl icariside II, and baohuoside I. Chromatographic separation was accomplished on an Agilent Zorbax-SB C(18) column (50 mm × 2.1mm, 1.8 μm) with a gradient elution system composed of 0.3% acetic acid and 0.3% acetic acid in acetonitrile at a flow rate of 0.4 mL/min. Detection was based on a triple quadrupole mass spectrometer using a multiple reaction monitoring mode with an electrospray ionization source. All of the calibration curves showed good linearity (r>0.99) within the tested concentration ranges. The lower limits of quantification of the seven analytes were all lower than 0.0654 ng/mL. The relative standard deviations for intra- and inter-batches of the seven analytes were less than 13.7% and 14.9%, respectively, at four concentration levels of quality control samples, and the recoveries were between 92.8% and 114.5%, respectively. In addition, the seven flavonoids were found to be stable in dog plasma samples under short- and long-term storage and processing conditions. The validated method was successfully applied to a bioequivalence study in dog plasma after the oral administration of extracts of Herba Epimedii and Er-Xian Decoction.


Prognostic significance of tenascin-C expression in clear cell renal cell carcinoma.
Tenascin-C is an extracellular matrix protein that plays an important role in cell proliferation, migration and tumor invasion in various types of cancer. However, few reports exist on tenascin-C expression in renal cell carcinoma (RCC). This study aimed to assess the prognostic significance of tenascin-C in clear cell RCC. Using immunohistochemistry, 137 formalin-fixed, paraffin-embedded tissue sections obtained from patients with clear cell RCC were examined for tenascin-C expression. Tenascin-C expression was observed in 55 (40.1%) of the 137 clear cell RCC sections. Tumor cells displayed membranous and/or cytoplasmic staining for tenascin-C. Tenascin-C expression was more prominent near the pseudocapsule of the tumor and around the tumor vessels. Tenascin-C expression was significantly associated with a higher stage (P=0.0065) and higher nuclear grade (P=0.0001). However, there was no correlation between the tenascin-C expression and venous involvement. The cancer-specific survival rate in patients with a tenascin-C-positive primary tumor was significantly lower than that in those with a tenascin-C-negative primary tumor in univariate analysis (P=0.0017). However, tenascin-C expression did not exhibit a significant value for cancer-related death in the Cox regression analysis. In patients with stage 1-3 disease, the 5-year metastasis-free rate in patients with the tenascin-C-positive primary tumor was significantly lower than that in those with the tenascin-C-negative primary tumor (67.8 vs. 88.5%, respectively; P=0.0038). The Cox regression analysis showed that tenascin-C expression is a significant predictor of metastasis (P=0.0345). The tenascin-C expression was strongly related to the stage, nuclear grade and 5-year metastasis-free rate. Therefore, tenascin-C expression may be a possible marker for the metastatic potential of clear cell RCC.


A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin.
Pregabalin and gabapentin share a similar mechanism of action, inhibiting calcium influx and subsequent release of excitatory neurotransmitters; however, the compounds differ in their pharmacokinetic and pharmacodynamic characteristics. Gabapentin is absorbed slowly after oral administration, with maximum plasma concentrations attained within 3-4 hours. Orally administered gabapentin exhibits saturable absorption--a nonlinear (zero-order) process--making its pharmacokinetics less predictable. Plasma concentrations of gabapentin do not increase proportionally with increasing dose. In contrast, orally administered pregabalin is absorbed more rapidly, with maximum plasma concentrations attained within 1 hour. Absorption is linear (first order), with plasma concentrations increasing proportionately with increasing dose. The absolute bioavailability of gabapentin drops from 60% to 33% as the dosage increases from 900 to 3600 mg/day, while the absolute bioavailability of pregabalin remains at > or = 90% irrespective of the dosage. Both drugs can be given without regard to meals. Neither drug binds to plasma proteins. Neither drug is metabolized by nor inhibits hepatic enzymes that are responsible for the metabolism of other drugs. Both drugs are excreted renally, with elimination half-lives of approximately 6 hours. Pregabalin and gabapentin both show dose-response relationships in the treatment of postherpetic neuralgia and partial seizures. For neuropathic pain, a pregabalin dosage of 450 mg/day appears to reduce pain comparably to the predicted maximum effect of gabapentin. As an antiepileptic, pregabalin may be more effective than gabapentin, on the basis of the magnitude of the reduction in the seizure frequency. In conclusion, pregabalin appears to have some distinct pharmacokinetic advantages over gabapentin that may translate into an improved pharmacodynamic effect.


Common and unique network dynamics in football games.
The sport of football is played between two teams of eleven players each using a spherical ball. Each team strives to score by driving the ball into the opposing goal as the result of skillful interactions among players. Football can be regarded from the network perspective as a competitive relationship between two cooperative networks with a dynamic network topology and dynamic network node. Many complex large-scale networks have been shown to have topological properties in common, based on a small-world network and scale-free network models. However, the human dynamic movement pattern of this network has never been investigated in a real-world setting. Here, we show that the power law in degree distribution emerged in the passing behavior in the 2006 FIFA World Cup Final and an international "A" match in Japan, by describing players as vertices connected by links representing passes. The exponent values γ ~ 3.1 are similar to the typical values that occur in many real-world networks, which are in the range of 2<γ<3, and are larger than that of a gene transcription network, γ ~ 1. Furthermore, we reveal the stochastically switched dynamics of the hub player throughout the game as a unique feature in football games. It suggests that this feature could result not only in securing vulnerability against intentional attack, but also in a power law for self-organization. Our results suggest common and unique network dynamics of two competitive networks, compared with the large-scale networks that have previously been investigated in numerous works. Our findings may lead to improved resilience and survivability not only in biological networks, but also in communication networks.


Extensive Bilateral Lemierre Syndrome due to Methicillin-Resistant Staphylococcus epidermidis in a Patient with Lung Adenocarcinoma.
Lemierre syndrome (LS) is a septic thrombophlebitis of the internal jugular vein (IJV) following an oropharyngeal infection. LS is commonly caused by normal anaerobic flora and treated with appropriate antibiotics and anticoagulation therapy. Although the incidence of disease is very rare, 15% cases of LS are fatal even in the antibiotic era because of disseminated septic thromboemboli. We reported a case of extensive bilateral LS due to methicillin-resistant Staphylococcus epidermidis in a 63-year-old female with lung adenocarcinoma. Initial examination revealed a retropharyngeal abscess; hence, intravenous ceftriaxone and steroid were initiated empirically. However, pulmonary thromboembolism developed and methicillin-resistant S. epidermidis was identified in the bacterial culture. Despite intensive antibiotic and anticoagulation therapies, extensive septic thrombophlebitis involving the bilateral IJV and superior vena cava developed. Adjunctive catheter-directed thrombolysis and superior vena cava stenting were performed and the patient received antibiotic therapy for an additional 4 weeks, resulting in complete recovery.


Neonatal sciatic nerve transection induces TUNEL labeling of neurons in the rat spinal cord and DRG.
Transection of a peripheral nerve in neonatal rats induces an extensive death of axotomized neurons. We demonstrate here that spinal motoneurons and sensory dorsal root ganglia neurons become TUNEL-labeled after sciatic nerve transection in neonatal rats, thus indicating that apoptotic mechanisms are involved in the death process. Interestingly, there is also a profound increase of TUNEL-labeled interneurons in the deep dorsal horn. This location suggests that an intact afferent input and/or contact with target cells is essential for interneuronal survival. Death of motoneurons and sensory neurons could be a result of the injury per se and/or the deprivation of neurotrophic substances, secondary to the loss of contact with target cells.


Medical Genetics and the First Studies of the Genetics of Populations in Mexico.
Following World War II (WWII), there was a new emphasis within genetics on studying the genetic composition of populations. This probably had a dual source in the growing strength of evolutionary biology and the new international interest in understanding the effects of radiation on human populations, following the atomic bombings in Japan. These global concerns were shared by Mexican physicians. Indeed, Mexico was one of the leading centers of this trend in human genetics. Three leading players in this story were Mario Salazar Mallén, Adolfo Karl, and Rubén Lisker. Their trajectories and the international networks in human genetics that were established after WWII, paved the way for the establishment of medical and population genetics in Mexico. Salazar Mallén's studies on the distribution and characterization of ABO blood groups in indigenous populations were the starting point while Karl's studies on the distribution of abnormal hemoglobin in Mexican indigenous populations showed the relationships observed in other laboratories at the time. It was Lisker's studies, however, that were instrumental in the development of population genetics in the context of national public policies for extending health care services to the Mexican population. In particular, he conducted studies on Mexican indigenous groups contributing to the knowledge of the biological diversity of human populations according to international trends that focused on the variability of human populations in terms of genetic frequencies. From the start, however, Lisker was as committed to the reconstruction of shared languages and practices as he was to building networks of collaboration in order to guarantee the necessary groundwork for establishing the study of the genetics of human populations in Mexico. This study also allows us to place Mexican science within a global context in which connected narratives describe the interplay between global trends and national contexts.


PSORTb v.2.0: expanded prediction of bacterial protein subcellular localization and insights gained from comparative proteome analysis.
PSORTb v.1.1 is the most precise bacterial localization prediction tool available. However, the program's predictive coverage and recall are low and the method is only applicable to Gram-negative bacteria. The goals of the present work are as follows: increase PSORTb's coverage while maintaining the existing precision level, expand it to include Gram-positive bacteria and then carry out a comparative analysis of localization. An expanded database of proteins of known localization and new modules using frequent subsequence-based support vector machines was introduced into PSORTb v.2.0. The program attains a precision of 96% for Gram-positive and Gram-negative bacteria and predictive coverage comparable to other tools for whole proteome analysis. We show that the proportion of proteins at each localization is remarkably consistent across species, even in species with varying proteome size. Web-based version: http://www.psort.org/psortb. Standalone version: Available through the website under GNU General Public License. firstname.lastname@example.com, email@example.com http://www.psort.org/psortb/supplementaryinfo.html.


Tumor Variant Identification That Accounts for the Unique Molecular Landscape of Pediatric Malignancies.
Precision oncology trials for pediatric cancers require rapid and accurate detection of genetic alterations. Tumor variant identification should interrogate the distinctive driver genes and more frequent copy number variants and gene fusions that are characteristics of pediatric tumors. Here, we evaluate tumor variant identification using whole genome sequencing (n = 12 samples) and two amplification-based next-generation sequencing assays (n = 28 samples), including one assay designed to rapidly assess common diagnostic, prognostic, and therapeutic biomarkers found in pediatric tumors. Variant identification by the three modalities was comparable when filtered for 151 pediatric driver genes. Across the 28 samples, the pediatric cancer-focused assay detected more tumor variants per sample (two-sided, P < .05), which improved the identification of potentially druggable events and matched pathway inhibitors. Overall, our data indicate that an assay designed to evaluate pediatric cancer-specific variants, including gene fusions, may improve the detection of target-agent pairs for precision oncology.


The frequency-following response as an assessment of spatial processing.
Objective: It is important to detect children with difficulties distinguishing speech-in-noise early. Prompt identification may be assisted by an evoked potential. The aims of the present study were: 1) to evaluate the frequency-following response (FFR) as a measure of binaural processing and spatial listening and, 2) to investigate the relationship between the FFR and a behavioural measure of binaural processing and spatial listening. Design: A single group, repeated measures design. The FFR was recorded in two different spatial conditions and amplitudes compared to spatial listening ability. Study Sample: Thirty-two children (aged 6.0 to 13.1 years) with a range of spatial processing abilities as measured behaviourally using the Listening in Spatialised Noise Sentences test (LiSN-S). Results: FFR waveforms were elicited using speech-like stimuli in co-located and separated conditions. A significant (p≤0.005) spatial advantage effect was observed with larger amplitudes in the separated condition. No correlations were observed between FFR amplitude and LiSN-S results. Conclusions: The FFR shows promise as a measure of binaural processing and spatial listening, but could be measuring different processes to those measured by the LiSN-S.


Beta-1 syntrophin (SNTB1) regulates colorectal cancer progression and stemness via regulation of the Wnt/β-catenin signaling pathway.
Beta-1 syntrophin (SNTB1) is an intracellular scaffold protein that provides a platform for the formation of signal transduction complexes, thereby modulating and coordinating various intracellular signaling events and crucial cellular processes. However, the physiological role of SNTB1 is poorly understood. This study aims to explore the role of SNTB1 in colorectal cancer (CRC) tumorigenesis and progression, with particular focus on SNTB1's expression pattern, clinical relevance, and possible molecular mechanism in CRC development. SNTB1 expression was analyzed in both clinical tissues and The Cancer Genome Atlas (TCGA) database. Real-time polymerase chain reaction (PCR), Western blot, and immunohistochemical assays were used to detect the relative mRNA and protein levels of SNTB1. Statistical analysis was performed to examine the correlation between SNTB1 expression and the clinicopathological characteristics of patients with CRC. Bioinformatics gene set enrichment analysis (GSEA), Western blot, luciferase assay, and agonist recovery assays were conducted to evaluate the relevance of SNTB1 and the β-catenin signaling pathway in CRC. A flow cytometry-based Hoechst 33342 efflux assay was applied to assess the proportion of the side population (SP) within total CRC cells. Elevated levels of SNTB1 were identified in CRC tissues and cell lines. The elevation of SNTB1 was positively correlated with the degree of malignancy and poor prognosis in CRC. We further revealed that, by modulating the β-catenin signaling pathway, silencing SNTB1 expression suppressed tumor growth and cancer stemness in vitro, as well as tumorigenesis in vivo. These findings suggest that SNTB1 plays a crucial role in colorectal tumorigenesis and progression by modulating β-catenin signaling and the stemness maintenance of cancer cells.


Electronic Information Standards to Support Obesity Prevention and Bridge Services Across Systems, 2010-2015.
Electronic information technology standards facilitate high-quality, uniform collection of data for improved delivery and measurement of health care services. Electronic information standards also aid information exchange between secure systems that link health care and public health for better coordination of patient care and better-informed population health improvement activities. We developed international data standards for healthy weight that provide common definitions for electronic information technology. The standards capture healthy weight data on the "ABCDs" of a visit to a health care provider that addresses initial obesity prevention and care: assessment, behaviors, continuity, identify resources, and set goals. The process of creating healthy weight standards consisted of identifying needs and priorities, developing and harmonizing standards, testing the exchange of data messages, and demonstrating use-cases. Healthy weight products include 2 message standards, 5 use-cases, 31 LOINC (Logical Observation Identifiers Names and Codes) question codes, 7 healthy weight value sets, 15 public-private engagements with health information technology implementers, and 2 technical guides. A logic model and action steps outline activities toward better data capture, interoperable systems, and information use. Sharing experiences and leveraging this work in the context of broader priorities can inform the development of electronic information standards for similar core conditions and guide strategic activities in electronic systems.


Gastroprotective effects of Leejung-tang, an oriental traditional herbal formula, on ethanol-induced acute gastric injury in rats.
Leejung-tang (LJT, Rechu-to in Japanese and Lizhong-tang in Chinese) is an oriental traditional traditional herbal formula. LJT has been used for treatment of gastrointestinal disorders in Korea, Japan, and China for a long time. In present study, we investigated the protective effects of LJT against absolute ethanol induced gastric injuries. Rats in the control group were given PBS orally (5 mL/kg body weight) as the vehicle, and the absolute-ethanol group (EtOH group) received absolute ethanol (5 mL/kg body weight) by oral gavage. Rats in the positive control group were given omeprazole orally (50 mg/kg body weight) 2 h prior to the administration of absolute ethanol. The treatment groups received LJT (400 mg/kg body weight) 2 h prior to absolute ethanol administration. All rats were sacrificed 1 h after receiving the ethanol treatment. The stomach was excised for macroscopic examination and biochemical analysis. The administration of LJT protected gastric mucosa against ethanol-induced acute gastric injury, including hemorrhage and hyperemia. LJT reduced the increase in lipid peroxidation in ethanol-induced acute gastric lesions. LJT increased GSH content and activities of the antioxidant enzymes, catalase, glutathione-S-transferase, glutathione reductase, glutathione peroxidase, and superoxide dismutase. These results indicate that LJT protects gastric mucosa against ethanol-induced acute gastric injury by increasing their antioxidant content. We suggest that LJT can be developed as an effective drug for the treatment of acute gastric injury.


Cancer mortality and environmental exposure to DDE in the United States.
To explore the role of DDE, the major and most persistent DDT derivative, in cancer etiology, we examined the association of the 1968 adipose DDE levels of population samples from 22 U.S. states with age-adjusted mortality rates between 1975 and 1994 for multiple myeloma; non-Hodgkin lymphoma (NHL); and cancer of the breast, corpus uteri, liver, and pancreas. Separate analyses were conducted by gender and race. Covariates in the regression models included average per-capita income, percent metropolitan residents, and the population density. Liver cancer mortality increased significantly with adipose DDE levels in both sexes among whites, but not among African Americans. No association was observed for pancreatic cancer and multiple myeloma. Breast cancer mortality was inversely correlated with adipose DDE levels among both white and African American women. Significant inverse correlations were also observed for uterine cancer among white women, whereas no association was observed for African Americans and for NHL among whites (men and women) and African American women. The results for pancreatic cancer, multiple myeloma, NHL, breast cancer, and uterine cancer did not support the hypothesis of an association with past adipose levels of the DDT derivative DDE. The multivariate analysis confirmed most findings. The association between liver cancer and DDE observed among whites, particularly in view of the occurrence of hepatic neoplasms in laboratory animals exposed to DDT, warrants further investigation.


High-resolution velocimetry technique based on the decaying streaks of phosphor particles.
This Letter introduces a new, to the best of our knowledge, particle streak velocimetry technique based on decaying streaks formed by individual phosphor particles following pulsed excitation. Tin-doped phosphor particles are dispersed into flows and excited by a pulsed UV laser light sheet. Emission streaks are recorded as a result of particle motion during the persistence of luminescence (here ∼27µs). The two components of the flow velocity are derived from the streaks without directional ambiguity by applying to each streak a two-dimensional fit describing a linearly moving point source with a mono-exponential decaying emission. This technique can achieve high spatial resolution compared to particle image velocimetry (PIV), while also requiring much fewer computational resources than particle tracking velocimetry (PTV) at high seeding densities. The wavelength-shifted luminescence also allows rejection of reflected laser light. The approach was validated in a free jet against simultaneous PTV and PIV and then successfully applied to measure a canonical boundary layer flow.


Assessment of novel anti-p185HER-2 monoclonal antibodies for internalization-dependent therapies.
Novel therapies that require internalization of effector domains may be improved by assessing the efficacy of postbinding receptor-mediated endocytosis. To achieve targeted gene therapy of immunotoxin therapy, natural vector-host tropisms must be altered. Recent improvements in monoclonal antibody (MAb) engineering have expanded the potential range of host cells that can be targeted for therapeutic intervention. However, relatively little is known about cellular responses after binding of a vector construct. We have tested the utility of four novel MAbs recognizing the extracellular domain of p185HER-2, a membrane receptor protein, for use in internalization-dependent therapies. All four antibodies bound to p185HER-2 in a number of immunoassays. Two antibodies recognized accessible epitopes of p185HER-2 on viable cells. Radioimmunoassay demonstrated that antibody-membrane receptor complexes formed by two antibodies were internalized and trafficked through an endolysosomal degradative pathway. Two of the four antibodies evaluated were found to have favorable internalization characteristics suitable for incorporation in a targeting vector. This analytical approach could be applied to antibodies prior to and after fusion with various vectors or toxins to determine the potential utility of the antibodies for targeted therapy.


Semiblind spatial ICA of fMRI using spatial constraints.
Independent component analysis (ICA) utilizing prior information, also called semiblind ICA, has demonstrated considerable promise in the analysis of functional magnetic resonance imaging (fMRI). So far, temporal information about fMRI has been used in temporal ICA or spatial ICA as additional constraints to improve estimation of task-related components. Considering that prior information about spatial patterns is also available, a semiblind spatial ICA algorithm utilizing the spatial information was proposed within the framework of constrained ICA with fixed-point learning. The proposed approach was first tested with synthetic fMRI-like data, and then was applied to real fMRI data from 11 subjects performing a visuomotor task. Three components of interest including two task-related components and the "default mode" component were automatically extracted, and atlas-defined masks were used as the spatial constraints. The default mode network, a set of regions that appear correlated in particular in the absence of tasks or external stimuli and is of increasing interest in fMRI studies, was found to be greatly improved when incorporating spatial prior information. Results from simulation and real fMRI data demonstrate that the proposed algorithm can improve ICA performance compared to a different semiblind ICA algorithm and a standard blind ICA algorithm.


Aging, encoding fluency, and metacognitive monitoring.
Encoding fluency (how rapidly one generates a mediator for a new association) may be a cue used to judge one's own learning. To evaluate age differences in utilization of this cue, older and younger adults were instructed to use interactive imagery to study paired associates, pressing a button to indicate when an image had been formed for a given pair. A judgment of learning (JOL) was also made immediately after each pair had been studied. Hence, at least two cues pertaining to encoding fluency-whether an image had been formed (a diagnostic cue) and the latency of formation (a nondiagnostic one)-were available when making JOLs. Age equivalence was found in JOL accuracy, and JOLs for both age groups were positively related to imagery formation and were negatively related to the latency of image formation. Moreover, subjectively judged latency correlated higher with JOLs than actual (objective) latency, supporting the hypothesis that perceived fluency is a cue used in constructing JOLs.