Skp2 regulates G2/M progression in a p53-dependent manner.
Targeted proteasomal degradation mediated by E3 ubiquitin ligases controls cell cycle progression, and alterations in their activities likely contribute to malignant cell proliferation. S phase kinase-associated protein 2 (Skp2) is the F-box component of an E3 ubiquitin ligase complex that targets p27(Kip1) and cyclin E1 to the proteasome. In human melanoma, Skp2 is highly expressed, regulated by mutant B-RAF, and required for cell growth. We show that Skp2 depletion in melanoma cells resulted in a tetraploid cell cycle arrest. Surprisingly, co-knockdown of p27(Kip1) or cyclin E1 failed to prevent the tetraploid arrest induced by Skp2 knockdown. Enhanced Aurora A phosphorylation and repression of G2/M regulators cyclin B1, cyclin-dependent kinase 1, and cyclin A indicated a G2/early M phase arrest in Skp2-depleted cells. Furthermore, expression of nuclear localized cyclin B1 prevented tetraploid accumulation after Skp2 knockdown. The p53 status is most frequently wild type in melanoma, and the tetraploid arrest and down-regulation of G2/M regulatory genes were strongly dependent on wild-type p53 expression. In mutant p53 melanoma lines, Skp2 depletion did not induce cell cycle arrest despite up-regulation of p27(Kip1). These data indicate that elevated Skp2 expression may overcome p53-dependent cell cycle checkpoints in melanoma cells and highlight Skp2 actions that are independent of p27(Kip1) degradation.


Light history and age-related changes in retinal light damage.
To determine the effects of age and long-term light- or dark-rearing environments on acute, intense-light-mediated retinal degeneration. Male albino rats were maintained in a dim cyclic light environment or in darkness for as long as 1 year. When aged 2, 4, 8, and 12 months, some rats were given the synthetic antioxidant dimethylthiourea (DMTU) by intraperitoneal injection and were exposed to intense visible light for as long as 24 hours. Uninjected control rats were exposed to light at the same time. Other rats were treated with light of lower intensity for various periods. Two weeks after intense-light treatment, photoreceptor cell degeneration was estimated by determining the level of rhodopsin and by measuring the content of photoreceptor cell DNA. Light-induced changes in retinal DNA were analyzed immediately after exposure by neutral gel electrophoresis and by 8-hydroxy-deoxyguanosine measurements. Expression of the antioxidative stress protein heme oxygenase-1 (HO-1) was determined by northern blot analysis of mRNA in retinal extracts. At all ages, rats reared in cyclic dim-light conditions had lower rhodopsin levels than did rats reared in darkness; photoreceptor cell DNA levels were unaffected by the rearing environment. Senescent losses in rhodopsin and retinal DNA were significant after rats were 12 months old. Dim-light-reared rats exhibited an age-related increase in retinal light damage susceptibility, whereas dark-reared rats were equally susceptible to damage at all ages. In both types of rats, the mechanism of light-induced cell death involved an apoptotic process, visualized by the pattern of DNA fragments on electrophoretic gels. The process also induced the expression of HO-1 mRNA. Photoreceptor cell loss determined by biochemical measurement, DNA fragmentation, and HO-1 induction were dramatically reduced by the administration of DMTU. The age-related increase in susceptibility to retinal light damage in rats is influenced by their long-term daily light history. Decreasing retinal irradiance by dark-rearing eliminates the age-related increase in light damage, suggesting a correlation between light environment and retinal gene expression associated with damage. In all rats, retinal light damage resulted in a pattern of DNA fragmentation consistent with apoptotic cell death and in an increased expression of HO-1 mRNA. Antioxidant treatment greatly reduced apoptosis and HO-1 expression. This indicates that light damage involves an oxidative process that may also trigger apoptosis in the retina. The rat aging model may provide useful insights into the role of light environment associated with retinal degeneration in an aging human population.


Nitrogen balance in postoperative patients receiving parenteral nutrition.
Fifteen patients were given parenteral nutrition with hyperosmolar glucose during the postoperative period (days 1 to 5): nine received an average of 10.5 gm of nitrogen and 2,340 kilocalories/day, six were given an average of 5.9 gm of nitrogen and 1,600 kilocalories/day. Eight patients (controls) received no nitrogen and 520 kilocalories/day. The results of this study confirm our early findings that total parenteral nutrition is capable of reversing the negative nitrogen balance of the immediate postoperative period; this reversal depends on administration of adequate nitrogen and calories. In patients with moderate surgical procedures, at least 8 gm of nitrogen and 1,800 kilocalories/day are required to correct the negative nitrogen balance. When total parenteral nutrition is instituted, adequate nitrogen and calories should be given even if insulin is required to control hyperglycemia.


Neurotransmitters and neurotrophins collaborate to influence brain development.
It is well recognized that the neurotrophin family of factors as well as neurotransmitters play critical roles in the ontogeny of the brain. Moreover, a growing literature suggests that these environmental signals do not operate individually, but interact in critical ways to enhance maturation. This review focuses on three brain systems where this collaboration is particularly evident: the cerebellum, the basal forebrain-hippocampus and locus coeruleus-hippocampus. The material presented indicates that cross-talk between neurotransmitters and neurotrophins may be a mechanism common to the development of multiple neuronal groups throughout the central nervous system. Moreover, this cross-talk appears to involve the interaction of both neuronal and glial cell populations.


Surface recrystallization of polyethylene extended-chain crystals.
Rough fracture surfaces of extended-chain polyethylene crystals become unstable at temperatures below the bulk melting point. There is no way for the extended chains, which are up to 20,000 methylene units long, to change position without collapse. As a result, the rough surfaces smooth out on heating by covering themselves with oriented folded-chain lamellae.


Quinary structure modulates protein stability in cells.
Protein quinary interactions organize the cellular interior and its metabolism. Although the interactions stabilizing secondary, tertiary, and quaternary protein structure are well defined, details about the protein-matrix contacts that comprise quinary structure remain elusive. This gap exists because proteins function in the crowded cellular environment, but are traditionally studied in simple buffered solutions. We use NMR-detected H/D exchange to quantify quinary interactions between the B1 domain of protein G and the cytosol of Escherichia coli. We demonstrate that a surface mutation in this protein is 10-fold more destabilizing in cells than in buffer, a surprising result that firmly establishes the significance of quinary interactions. Remarkably, the energy involved in these interactions can be as large as the energies that stabilize specific protein complexes. These results will drive the critical task of implementing quinary structure into models for understanding the proteome.


A psychometric evaluation of the Temperament in Middle Childhood Questionnaire (TMCQ) in a Swedish sample.
Personality is generally considered to be biologically founded in temperament, and temperamental qualities have proven to be relatively stable across childhood and into adulthood (Caspi, Roberts & Shiner, ). Temperament predicts important developmental outcomes such as academic performance (Muris, ), and social functioning (Eisenberg, Fabes, Guthrie & Reiser, ), and it has also been found to be strongly related to the etiology and maintenance of internalizing and externalizing psychopathology in children (Muris, Meesters & Blijlevens, ; Nigg, ). To allow for the possibility of making early interventions, identification of potential risk factors (such as temperamental dispositions) is of great importance (Rettew & McKee, ). As temperament is multidimensional and has many different manifestations, parents and teachers are valuable sources in providing information about children's temperament (Rothbart & Bates, ; Tackett, Slobodskaya, Mar et al., ), and caregiver questionnaires are frequently used in child personality research. However, such questionnaires are only useful if their reliability and validity have been established. The aim of the present study was to examine the psychometric properties of the Temperament in Middle Childhood Questionnaire (TMCQ; Simonds, Kieras, Rueda & Rothbart, ), which focuses specifically on the ages between 7 and 11 years. The TMCQ is the least validated of the Rothbart measures, and although reliability data have been presented, together with some validity data, for a computerized self-report version of the questionnaire (Simonds & Rothbart, ), information about the reliability and validity for the caregiver version is scant. In the present paper, we report such data for a Swedish sample.


Pre-treatment effect of different doses of soy isoflavones on spatial learning and memory in an ovariectomized animal model of Alzheimer's disease.
The aim of this study was to evaluate the effects of different doses of dietary soy meals (with or without isoflavone) on dementia in ovariectomized (OVX) animal model of Alzheimer's disease. Female Wistar's rats with the exception of intact group were ovariectomized at the first line of study. Animals were divided into 2 main groups: control (c) and pre-treatment groups. Animals in pre-treatment groups received one of five types of diet during four weeks prior Nucleus Basalis Magnocellularis (NBM) electrical lesion normal diet (0), 10 g soy with isoflavone (10), 20 g soy with isoflavone (20), 10 g soy without isoflavone (-10) and 20 g soy without isoflavone (-20) in 30 g daily diet. The spatial learning and memory were tested using Morris water maze after electrical lesion. Rats were trained in water maze to find a hidden escape Platform. Rats received 6 blocks that each block consisted of 3 trials. Following acquisition trials, one probe trial was conducted in which the platform was removed. Soy meal diet (with or without isoflavone) in ovariectomized rats with Alzheimer's disease caused improvement of performance across 18 trials of Acquisition. Our results suggest that soy meal is a potential alternative to estrogen in the prevention and treatment of Alzheimer's disease.


Association between traumatic bone marrow abnormalities of the knee, the trauma mechanism and associated soft-tissue knee injuries.
To determine the association between traumatic bone marrow abnormalities, the knee injury mechanism, and associated soft tissue injuries in a larger cohort than those in the published literature. Retrospective study including 220 patients with traumatic knee injuries. Knee MRIs were evaluated for trauma mechanism, soft tissue injury, and the location of bone marrow abnormalities. The locations of the abnormalities were correlated with trauma mechanisms and soft tissue injuries using the chi-square test with Bonferroni correction. One hundred and forty-four valgus injuries, 39 pivot shift injuries, 25 lateral patellar dislocations, 8 hyperextensions, and 4 dashboard injuries were included. Valgus and pivot shift injuries showed traumatic bone marrow abnormalities in the posterolateral regions of the tibia. Abnormalities after patellar dislocation were found in the anterolateral and centrolateral femur and patella. Hyperextension injuries were associated with abnormalities in almost all regions, and dashboard injuries were associated with changes in the anterior regions of the tibia and femur. Our study provides evidence of associations between traumatic bone marrow abnormality patterns and different trauma mechanisms in acute knee injury, and reveals some overlap, especially of the two most common trauma mechanisms (valgus and pivot shift), in a large patient cohort. • Specific bone marrow oedema patterns after knee trauma were confirmed. • New associations between bone marrow oedema patterns and knee trauma were shown. • Bone marrow oedema patterns help in identifying associated soft tissue injuries.


[The measurement of patient safety culture: a literature review].
To determine if patient safety culture is measurable in healthcare organizations, if it has done, and in this case, how it is measured and which aspects have been taken into account. Literature review in the main database with a combination of DeCS and MeSH. 5 years, English and Spanish and this kind of documents: meta-analysis, clinical trials and systematic reviews. Critical reading was performed by CASPe lists. We selected 1 qualitative meta-analysis and 4 revisions. In them a thorough study of measurement tools is made. It is noticeable the great variability in content, size and focus. Although most takes into account the dimensions of leadership communication, procedures, personnel and reporting of incidents. Psychometric analysis is not always adequate and only one has established links with the results with certainty. The most qualified questionnaires are Safety Attitudes Questionnaire (SAQ) and the Hospital Survey on Patient Safety Culture (HSOPSC). Both widely used and with an appropriate psychometric analysis. Understanding the characteristics that define the patient safety culture is complex. Although the recommended questionnaires are the best at this time, it would be advisable to follow researching in the measuring tools. Patient safety requires an organizational and multidisciplinary approach, however, nursing plays a key role taking into account the rate of preventable adverse events, medication errors, pressure ulcers, lack of information, falls, nosocomial infections, ... are, in largely, within its competence.


Combined Percutaneous Procedure in Patient with Lutembacher Syndrome: A Case Report and Real-World Experience Review.
Even cardiac surgery has been accepted as the standard therapy for Lutembacher syndrome, a combination of congenital ostium secundum atrial septal defect (ASD) and acquired mitral valve stenosis (MVS), it also owns many limitations and disadvantages. Therefore, seeking for a less invasive therapy with the same efficacy may be worthwhile. Thanks to the development in technology and experience gaining in cardiovascular intervention, the combination of the two proved effective procedures, including percutaneous MVS treatment using balloon valvuloplasty and percutaneous ASD closure using atrial septal occluders, can be utilized as an attractive alternative therapy for these conditions. Here, we present a successful percutaneous intervention in Lutembacher syndrome using the combination of mitral balloon valvuloplasty and ASD device closure and thoroughly review the experience of using this combined procedure existing in the literature.


The morphological compensatory change of peritubular capillary network in chronic allograft rejection.
To clarify the compensatory hemodynamic alterations in the interstitium of renal allograft biopsies with chronic rejection, we evaluated the morphological changes in the peritubular capillary (PTC) network. Seven renal biopsy specimens from recipients with chronic rejection presenting with elevation of serum creatinine of 1.9 +/- 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart donors were used as normal controls. In each specimen, non-pathological interstitial areas without fibrosis, tubular atrophy or cell infiltration were compared with pathological areas (PA) showing fibrosis and/or tubular atrophy using a computer image analysis. Morphological measurements revealed that the mean cut surface area of the PTC in the non-pathological and pathological interstitial areas in the recipient biopsies were significantly larger than that of the normal controls (p < 0.001 and 0.001, respectively). In the recipient biopsies, both of the mean cut surface areas of the tubules and PTC in the non-pathological areas were significantly higher than those in the PA (p < 0.001). The mean glomerular diameter in the recipient biopsies was also significantly higher than that of the donors (p < 0.01). In this study, we provided pathological evidence for the compensatory interstitial and glomerular hemodynamic alterations in kidney graft with chronic rejection and the condition as single kidney.


Instant, Visual, and Instrument-Free Method for On-Site Screening of GTS 40-3-2 Soybean Based on Body-Heat Triggered Recombinase Polymerase Amplification.
On-site monitoring the plantation of genetically modified (GM) crops is of critical importance in agriculture industry throughout the world. In this paper, a simple, visual and instrument-free method for instant on-site detection of GTS 40-3-2 soybean has been developed. It is based on body-heat recombinase polymerase amplification (RPA) and followed with naked-eye detection via fluorescent DNA dye. Combining with extremely simplified sample preparation, the whole detection process can be accomplished within 10 min and the fluorescent results can be photographed by an accompanied smart phone. Results demonstrated a 100% detection rate for screening of practical GTS 40-3-2 soybean samples by 20 volunteers under different ambient temperatures. This method is not only suitable for on-site detection of GM crops but also demonstrates great potential to be applied in other fields.


Functional, c-myc-tagged Cf-9 resistance gene products are plasma-membrane localized and glycosylated.
The Cf-9 resistance gene from tomato confers resistance to races of the fungal pathogen Cladosporium fulvum that express the corresponding avirulence gene, Avr9. Avr9 encodes a secreted peptide. To investigate Cf-9 function, we tagged the Cf-9 protein with a triple myc epitope at either the amino- or carboxy-terminus of the mature protein. Tobacco plants carrying these constructs activate a defence response to Avr9 peptide. The Cf-9 sequence predicts a protein of 94 kDa, with 22 glycosylation sites. Using c-myc antibodies, c-myc : Cf-9 protein was detected as a unique band with a molecular size of 160 kDa. The band shifted to approximately 105 kDa after glucosidase treatment, indicating that Cf-9 protein is highly glycosylated. Plasma membranes were isolated using two-phase partitioning, and c-myc : Cf-9 was enriched in these fractions, indicating that Cf-9 is a plasma membrane protein. This was confirmed by silver-enhanced immunogold labelling of tobacco protoplasts carrying the amino-terminal c-myc tag; a higher labelling density was observed on the surface of protoplasts derived from c-myc : Cf-9 tobacco compared to untransformed control. The presence of Cf-9 in the plasma membrane is consistent with its role in conferring recognition of the extracellular Avr9 peptide.


Adhesion and sliding response of a biologically inspired fibrillar surface: experimental observations.
Inspired by the adhesion mechanisms of several animal species such as geckos, beetles and flies, several efforts in designing and fabricating surface engineering strategies have been made recently to mimic the adhesive and frictional behaviour of biological foot pads. An important feature of such biological adhesion systems is the ability to switch between strong attachment and easy detachment, which is crucial for animal locomotion. Recent investigations have suggested that such a 'switching' mechanism can be achieved by the elastic anisotropy of the attachment pad, which renders the magnitude of the detachment force to be direction dependent. This suggestion is supported by the observations that the fibres of the foot pads in geckos and insects are oriented at an angle to the base and that geckos curl their toes backwards (digital hyperextension) while detaching from a surface. One of the promising bio-inspired architectures developed recently is a film-terminated fibrillar PDMS surface; this structure was demonstrated to result in superior detachment force and energy dissipation compared with a bulk PDMS surface. In this investigation, the film-terminated fibrillar architecture is modified by tilting the fibres to make the surface vertically more compliant and elastically anisotropic. The directional detachment and the sliding resistance between the tilted fibrillar surfaces and a spherical glass lens are measured: both show significant directional anisotropy. It is argued that the anisotropy introduced by the tilted fibres and the deformation-induced change in the compliance of the fibre layer are responsible for the observed anisotropy in the detachment force.


Molecular Epidemiology of Salmonellosis in Florida, USA, 2017-2018.
The state of Florida reports a high burden of non-typhoidal Salmonella enterica with approximately two times higher than the national incidence. We retrospectively analyzed the population structure and molecular epidemiology of 1,709 clinical isolates from 2017 and 2018. We found 115 different serotypes. Rarefaction suggested that the serotype richness did not differ between children under 2 years of age and older children and adults and, there are ~22 well-characterized dominant serotypes. There were distinct differences in dominant serotypes between Florida and the USA as a whole, even though S. Enteritidis and S. Newport were the dominant serotypes in Florida and nationally. S. Javiana, S. Sandiego, and S. IV 50:z4, z23:- occurred more frequently in Florida than nationally. Legacy Multi Locus Sequence Typing (MLST) was of limited use for differentiating clinical Salmonella isolates beyond the serotype level. We utilized core genome MLST (cgMLST) hierarchical clusters (HC) to identify potential outbreaks and compared them to outbreaks detected by Pulse Field Gel Electrophoresis (PFGE) surveillance for five dominant serotypes (Enteritidis, Newport, Javiana, Typhimurium, and Bareilly). Single nucleotide polymorphism (SNP) phylogenetic-analysis of cgMLST HC at allelic distance 5 or less (HC5) corroborated PFGE detected outbreaks and generated well-segregated SNP distance-based clades for all studied serotypes. We propose "combination approach" comprising "HC5 clustering," as efficient tool to trigger Salmonella outbreak investigations, and "SNP-based analysis," for higher resolution phylogeny to confirm an outbreak. We also applied this approach to identify case clusters, more distant in time and place than traditional outbreaks but may have been infected from a common source, comparing 176 Florida clinical isolates and 1,341 non-clinical isolates across USA, of most prevalent serotype Enteritidis collected during 2017-2018. Several clusters of closely related isolates (0-4 SNP apart) within HC5 clusters were detected and some included isolates from poultry from different states in the US, spanning time periods over 1 year. Two SNP-clusters within the same HC5 cluster included isolates with the same multidrug-resistant profile from both humans and poultry, supporting the epidemiological link. These clusters likely reflect the vertical transmission of Salmonella clones from higher levels in the breeding pyramid to production flocks.


Nuclear Translocation of fibroblast growth factor (FGF) receptors in response to FGF-2.
Members of the FGF family of growth factors localize to the nuclei in a variety of different cell types. To determine whether FGF receptors are also present within nuclei and if this localization is regulated by FGFs, nuclei were prepared from quiescent and FGF-2-treated Swiss 3T3 fibroblasts and examined for the presence of FGF receptors by immunoblotting with an antibody produced against the extracellular domain of FGF receptor-1 (FGFR-1). Little or no FGFR-1 is detected in nuclei prepared from quiescent cells. When cells are treated with FGF-2, however, there is a time- and dose-dependent increase in the association of FGFR-1 immunoreactivity with the nucleus. In contrast, treatment with either EGF or 10% serum does not increase the association of FGFR-1 with the nucleus. When cell surface proteins are labeled with biotin, a biotinylated FGFR-1 is detected in the nuclear fraction prepared from FGF-2-treated, but not untreated, cells indicating that the nuclear-associated FGFR-1 immunoreactivity derives from the cell surface. The presence of FGFR-1 in the nuclei of FGF-2-treated cells was confirmed by immunostaining with a panel of different FGFR-1 antibodies, including one directed against the COOH-terminal domain of the protein. Fractionation of nuclei from FGF-2-treated cells indicates that nuclear FGFR-1 is localized to the nuclear matrix, suggesting that the receptor may play a role in regulating gene activity.


Implementation contextual factors related to community-based active travel to school interventions: a mixed methods interview study.
Active travel to school contributes to multiple physical and psychosocial benefits for youth, yet population rates of active travel to school are alarmingly low in the USA and many other countries. Though walking school bus interventions are effective for increasing rates of active travel to school and children's overall physical activity, uptake of such interventions has been low. The objective of this study was to conduct a mixed methods implementation evaluation to identify contextual factors that serve as barriers and facilitators among existing walking school bus programs. Semi-structured interviews guided by the Consolidated Framework for Implementation Research (CFIR) were conducted with leaders of low-sustainability (n = 9) and high-sustainability (n = 11) programs across the USA. A combination of quantitative (CFIR-based) coding and inductive thematic analysis was used. The CFIR-based ratings were compared between the low- and high-sustainability programs and themes, subthemes, and exemplary quotes were provided to summarize the thematic analysis. In both the low- and high-sustainability programs, three of the 15 constructs assessed were commonly rated as positive (i.e., favorable for supporting implementation): student/family needs and resources, implementation climate, and planning. Three constructs were more often rated as positive in the high-sustainability programs: organizational incentives and rewards, engaging students and parents, and reflecting and evaluating. Three constructs were more often rated as positive in the low-sustainability programs: student/family needs and resources - built environment, available resources, and access to knowledge and information. Four themes emerged from the thematic analysis: planning considerations, ongoing coordination considerations, resources and supports, and benefits. Engagement of students, parents, and community members were among the factors that emerged across the quantitative and qualitative analyses as most critical for supporting walking school bus program implementation. The information provided by program leaders can help in the selection of implementation strategies that overcome known barriers for increasing the long-term success of community-based physical activity interventions such as the walking school bus.


Digitalis and digitalislike compounds down-regulate gene expression of the intracellular signaling protein 14-3-3 in rat lens.
Na+,K+-ATPase activity in the epithelial layer is fundamental to the maintenance of ionic concentration gradients and transparency of the lens. Recently we have identified endogenous digitalislike compounds (DLC), 19-norbufalin and its peptide derivatives, in human cataractous lenses (Lichtstein et al. Eur J Biochem 216: 261-268, 1993). Lenses were treated with 10 nM ouabain, bufalin or 19-norbufalin derivative for 24 h and were compared to control lenses. Differential display analysis revealed that one of the down-regulated genes was 14-3-3 theta. Down-regulation was confirmed by Northern blot and by RT-PCR analysis. RT-PCR of additional 14-3-3 isoforms revealed that the eta and gamma isoforms of 14-3-3 are also down-regulated by ouabain, bufalin and 19-norbufalin derivative, whereas the zeta isoform is down-regulated only by bufalin. These results demonstrate that one of the consequences of Na+,K+-ATPase inhibition by exogenous or endogenous inhibitors is the down-regulation of mRNA transcripts encoding several isoforms of 14-3-3. Since the 14-3-3 proteins are multifunctional regulatory proteins, the reduction in the abundance of various isoforms will have profound effects on cell function. Furthermore, These results, together with the demonstration of digitalislike compounds in the normal lens, and their increased level in human cataractous lenses, strongly suggests their involvement in the molecular mechanisms responsible for cataract formation.


Longitudinal evaluation of the occurrence of MRI-detectable bone marrow edema in osteoarthritis of the knee.
Bone marrow edema (BME) is a condition detectable with magnetic resonance imaging (MRI) and is present in different stages of osteoarthritis (OA). Its pathogenesis is still not completely known. To evaluate the longitudinal occurrence and persistence of BME in early OA of the knee. Twenty-three patients (eight females, 15 males; mean age 55.5+/-10.3 years) were scanned with a 1.5T MR imaging unit (sagittal fat-suppressed intermediate-weighted fast spin echo; 4-mm section thickness, 1-mm intersection gap, 256 x 192 matrix, 120-mm field of view). Images were obtained in all 23 patients at two time points (TPs) and in 12 patients at three TPs. Images were evaluated by two readers independently; discrepancies in image grading were reviewed and evaluated in consensus. A four-point image-grading scale was used (absence of BME to severe BME). Four main anatomical regions were evaluated (medial femur, lateral femur, medial tibia, lateral tibia), which were subcategorized into anterior, central, and posterior regions. One hundred five areas of BME in the 23 patients were found at all three TPs. In 16 areas, the BME was consistent at the same location over time, in seven locations the BME became larger, in six areas the BME became smaller, and in 16 locations it could not be detected in follow-up MRIs. In one case, the BME was smaller at TP2 but increased at TP3. In eight cases, only at the last time point could a BME be detected. BME is not a static phenomenon but changes over time. Correlation to physical activity and local inflammatory reaction should be evaluated.


[Non-A non-B hepatitis associated with cytomegalovirus infection].
A clinical case of a 58 year old male suffering from hepatitis non A, non B, and terminal chronic renal insufficiency under periodic dialysis, is presented. Following a 600 cc of packed red blood cells transfusion, there was an increase of antibodies IgG against cytomegalovirus (from 1/160 to 1/1560), detected by ELISA. At the same time, there were an increase of transaminases up to 404 UI/ml of GPT. Total bilirubin persisted normal. The possible etiology of the hepatitis non A, non B caused by cytomegalovirus is discussed and the results compared to those observed by other authors in immunosuppressed renal transplant patients.


Work-related ill health in doctors working in Great Britain: incidence rates and trends.
BackgroundDoctors have a higher prevalence of mental ill health compared with other professional occupations but incidence rates are poorly studied.AimsTo determine incidence rates and trends of work-related ill health (WRIH) and work-related mental ill health (WRMIH) in doctors compared with other professions in Great Britain.MethodIncidence rates were calculated using an occupational physician reporting scheme from 2005-2010. Multilevel regression was use to study incidence rates from 2001 to 2014.ResultsAnnual incidence rates for WRIH and WRIMH in doctors were 515 and 431 per 100 000 people employed, respectively. Higher incidence rates for WRIH and WRMIH were observed for ambulance staff and nurses, respectively. Doctors demonstrated an annual average incidence rates increase for WRIH and WRMIH, especially in women, whereas the other occupations demonstrated a decreasing or static trend. The difference in trends between the occupations was statistically significant.ConclusionsWRIH and WRMIH incidence rate are increasing in doctors, especially in women, warranting further research.


Capillary ion analysis of lithium concentrations in biological fluids and tissues of Poecilia (teleost).
Capillary ion analysis (CIA) is a form of capillary electrophoresis that uses the differential electrophoretic mobility of ions to perform a separation of an ionic mixture. Application of this technique for detection of lithium concentrations in plasma and tissues of Poecilia was the purpose of this investigation. CIA was performed using a 75 microm ID x 60 cm length fused-silica capillary and a run electrolyte of 67.7 mg hydroxyisobutyric acid (HIBA), 52.8 mg 18-crown-6-ether and 64 microL UV-CAT-1 reagent (4-methylbenzylamine) in a volume of 100 mL water (18 (M)omega) with a voltage of 20 kV using ultraviolet absorption detection at 214 nm. Migration times were: potassium, 2.98 min; calcium, 3.48 min; sodium, 3.60 min; barium (internal standard), 4.15 min and lithium, 4.26 min. Lithium and barium migration times were stable and reproducible. Correlation coefficients (r) between peak area ratios of lithium/barium for concentrations ranging from 0.1 to 2.0 mM were from 0.976 to 0.996. Coefficients of variation (CV) for lithium concentrations ranged from 4.07 to 15.71% between days and 4.38 to 7.76% within-day. Application of this methodology for determination of lithium concentrations in the plasma, brains and livers of fish dosed with lithium for 23 days are presented. CIA is applicable to analysis of lithium concentrations in biological fluids and tissues of fish.


[Cardiac imaging by nuclear magnetic resonance. II. Spectroscopy].
Nuclear magnetic resonance (NMR) spectroscopy is a new technique to study myocardial metabolism in living tissues by noninvasive means. The biochemical studies on intact hearts are performed in multinuclear NMR spectrometers using Fourier transform techniques for data acquisition. The biological NMR experiments preserve the tissues and can be repeated with a temporal resolution of seconds to several minutes in a reproducible fashion. As a marker of the intermediary metabolism P-31, C-13, H-1, F-19, N-14, Na-23, and K-39 isotopes are commonly used. NMR spectrum analysis permits the identification of several important substrates of the myocardial metabolism and their concentrational changes. In addition, the biophysical parameters of magnetic relaxation properties are measured. In some instances enzyme kinetics can be assessed. The disadvantage of NMR spectroscopy is the low sensitivity: only substrates with a intracellular concentration of greater than or equal to 0.5 mM can be detected. Improvements in sensitivity can be achieved, if the number of scans per spectrum and magnetic field strength are increased. The application of NMR spectroscopy in cardiovascular medicine is new and systematic studies on myocardial metabolism in vivo are not yet available. However, using P-31 MR spectroscopy several important results concerning the changes of the high energy phosphates and the intracellular pH changes during myocardial ischemia, as well as interesting insights into the regulatory principles of the cellular respiration were obtained. Similarly, C-13 NMR spectroscopy successfully described some aspects of glycogen metabolism and the kinetics of citric acid cycle in the myocardium. The clinical application of NMR spectroscopy appears feasible in a near future. The practical importance of this promising technique in clinical cardiology will depend on availability of the whole-body MR spectrometers, on the development of pertinent techniques for spatial MR signal resolution, and on our ability to uncover and to understand the biochemical principles of cardiac diseases. However, it is already today evident that MR spectroscopy successfully shifted the research interests towards biochemical processes at the cellular level as important causes and markers of cardiac diseases and extended our knowledge of the pathophysiology of the myocardium.


Regulating the health professions: a tale of two jurisdictions.
Public policy is increasingly asking: What public policy objectives are achieved by a particular law regulating private acts or licensing a profession? These questions are particularly being asked of the health professions. There is a growing feeling that state legislatures are using licensing laws for purposes other than consumer protection and quality assurance, which are widely believed to be the only legitimate goals of occupational regulation. Are we protecting the profession or the public? These questions will not go away. Two jurisdictions, Ontario and Maine, illustrate this debate.


A simplified AFLP method for fingerprinting of common wheat (Triticum aestivum L.) cultivars.
The simplified AFLP method was developed and evaluated for identification and genetic diversity studies of wheat cultivars. Selective primers exploited in AFLP assay based on a single cutting enzyme PstI ((PstI)AFLP) generated total of 111 robust fragments, including 67 (60%) monomorphic and 12 (11%) cultivar-specific markers. Average similarity between 15 cultivars was 0.650, and varied from 0.293 ('Hope' vs. 'Aurora') to 0.865 ('Norman' vs. 'Hornet'). Mean similarities within groups of winter wheat cultivars with and without 1BL/1RS chromosome were 0.713 and 0.685, respectively. A higher variation was found in the group of spring wheats: 0.677. The obtained results confirm the usefulness of the proposed modification of the AFLP technique for diversity studies and identification of common wheat cultivars.


Blood pressure patterns in relation to age, weight and urinary electrolytes in three Kenyan communities.
The blood pressure patterns of three Kenyan communities have been studied: 861 members of the Luo tribe in a rural community, 281 members of the Kamba tribe in a rural community and 310 "urban" Luo living in Nairobi. The slope of linear regression of blood pressure with age was significantly different in each population: rural Luo had the smallest rise with age and urban Luo had the largest rise with age, while the Kamba tribe were in between. The differences could not be accounted for by weight. Urinary electrolyte data showed rural Luo had the lowest sodium ratios (sodium/creatinine, sodium/potassium) and the highest potassium/creatinine ratio: urban Luo had the highest sodium and lowest potassium ratios and rural Kamba had values in between. The differences in blood pressures between the two groups of the same tribe in different environments (rural and urban Luo) were far greater than those between different genetic groups (Kamba and Luo) underlining the importance of environmental factor(s) in the determination of arterial pressure. Furthermore, these data support the theory that the dietary intake of sodium and potassium are the major influential environmental factors affecting blood pressure.


An event-related source localization study of response monitoring and social impairments in autism spectrum disorder.
A number of studies suggest anterior cingulate cortex (ACC) abnormalities in autism spectrum disorder (ASD), which might underlie response monitoring and social impairments exhibited by children and adolescents with ASD. The goal of the present study was to extend this work by examining error and correct response monitoring using event-related potentials (ERN, Pe, CRN) and LORETA source localization in high functioning adults with ASD and controls. Adults with ASD showed reduced ERN and Pe amplitudes and reduced rostral ACC activation compared with controls. Adults with ASD also showed less differentiation between error and correct ERP components. Social impairments and higher overall autism symptoms were related to reduced rostral ACC activity at the time of the ERN, particularly in adults with ASD. These findings suggest that reduced ACC activity may reflect a putative brain mechanism involved in the origins and maintenance of social impairments and raise the possibility of the presence of stable brain-behavior relation impairment across development in some individuals with ASD.


Experience with oral tofacitinib in two adolescents and seven adults with alopecia areata.
Alopecia areata (AA) is a common disease that results in nonscarring hair loss. Recently, tofacitinib (TOFA) has been a novel promising therapy for AA. The aim of this study is to determine the efficacy of oral TOFA treatment for alopecia areata (AA), and alopecia universalis (AU). Data of nine patients treated with oral TOFA with either AA or AU were retrospectively evaluated. Treatment outcome, disease severity, and therapeutic response were evaluated by Severity of Alopecia Tool (SALT) scores along with regular photographic surveillance done at third and sixth months. Treatment response was established on four categories: complete response (90% change in latest SALT score), intermediate response (51-90% change), moderate response (6-50% change), and nonresponse (<5% change). Nine patients aged 13-33 years were reviewed. Four patients (44.4%) did not respond to oral TOFA therapy, three patients (33.3%) were moderate responders, 1 (11.1%) was intermediate responder, and 1 (11.1%) was complete responder at the end of 6 months. The clinical response rate (those who achieved ≥5-100% change in SALT score) was 41.4% for all patients. Most of the patients who responded to TOFA had AA instead of AU. Adverse effects were mild. The clinical response rate of TOFA seems reasonable and TOFA was well-tolerated in this cohort. However, to truly evaluate efficacy, future studies are needed to assess the efficacy, adverse effects, and durability of treatment with TOFA in randomized controlled trials.


Sulf-2: an extracellular modulator of cell signaling and a cancer target candidate.
Sulf-1 and Sulf-2 are sulfatases that edit the sulfation status of heparan sulfate proteoglycans (HSPGs) on the outside of cells and regulate a number of critical signaling pathways. The Sulfs are dysregulated in many cancers with Sulf-2 in particular implicated as a driver of carcinogenesis in NSCLC, pancreatic cancer and hepatocellular carcinoma. This review describes the novel activity of the Sulfs in altering the sulfation pattern of HSPG chains on the outside of cells. Thereby, the Sulfs can change the binding of growth factors to these chains and can either promote (e.g., Wnt) or inhibit (e.g., fibroblast growth factor-2) signaling. The review focuses on the widespread upregulation of both Sulfs in cancers and summarizes the evidence that Sulf-2 promotes the transformed behavior of several types of cancer cells in vitro as well as their tumorigenicity in vivo. Sulf-2 is a bonafide candidate as a cancer-causing agent in NSCLC and other cancers in which it is upregulated. Sulf-2 is an extracellular enzyme and as such would be an attractive therapeutic target for the treatment of NSCLC and other cancers.


Estrogen, insulin, and dietary signals cooperatively regulate longevity signals to enhance resistance to oxidative stress in mice.
To investigate the biological significance of a longevity mutation found in daf-2 of Caenorhabditis elegans, we generated a homologous murine model by replacing Pro-1195 of insulin receptors with Leu using a targeted knock-in strategy. Homozygous mice died in the neonatal stage from diabetic ketoacidosis, whereas heterozygous mice showed the suppressed kinase activity of the insulin receptor but grew normally without spontaneously developing diabetes during adulthood. We examined heterozygous insulin receptor mutant mice for longevity phenotypes. Under 80% oxygen, mutant female mice survived 33.3% longer than wild-type female mice, whereas mutant male mice survived 18.2% longer than wild-type male mice. These results suggested that mutant mice acquired more resistance to oxidative stress, but the benefit of the longevity mutation was more pronounced in females than males. Manganese superoxide dismutase activity in mutant mice was significantly upregulated, suggesting that the suppressed insulin signaling leads to an enhanced antioxidant defense. To analyze the molecular basis of the gender difference, we administered estrogen to mutant mice. It was found that the survival of mice under 80% oxygen was extended when they were administered estradiol. In contrast, mutant and wild-type female mice showed shortened survivals when their ovaries were removed. The influence of estrogen is remarkable in mutant mice compared with wild-type mice, suggesting that estrogen modulates insulin signaling in mutant mice. Furthermore, we showed additional extension of survival under oxidative conditions when their diet was restricted. Collectively, we show that three distinct signals; insulin, estrogen, and dietary signals work in independent and cooperative ways to enhance the resistance to oxidative stress in mice.


Cohesin regulates tissue-specific expression by stabilizing highly occupied cis-regulatory modules.
The cohesin protein complex contributes to transcriptional regulation in a CTCF-independent manner by colocalizing with master regulators at tissue-specific loci. The regulation of transcription involves the concerted action of multiple transcription factors (TFs) and cohesin's role in this context of combinatorial TF binding remains unexplored. To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver. We observe a positive correlation between the number of distinct TFs bound and the presence of CNC sites. In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes. We also show that cohesin presence partially explains the commonly observed discrepancy between TF motif score and ChIP signal. Evidence from these statistical analyses in wild-type cells, and comparisons to maps of TF binding in Rad21-cohesin haploinsufficient mouse liver, suggests that cohesin helps to stabilize large protein-DNA complexes. Finally, we observe that the presence of mirrored CTCF binding events at promoters and their nearby cohesin-bound enhancers is associated with elevated expression levels.


Fast and High Quality Highlight Removal From a Single Image.
Specular reflection exists widely in photography and causes the recorded color deviating from its true value, thus, fast and high quality highlight removal from a single nature image is of great importance. In spite of the progress in the past decades in highlight removal, achieving wide applicability to the large diversity of nature scenes is quite challenging. To handle this problem, we propose an analytic solution to highlight removal based on an L2 chromaticity definition and corresponding dichromatic model. Specifically, this paper derives a normalized dichromatic model for the pixels with identical diffuse color: a unit circle equation of projection coefficients in two subspaces that are orthogonal to and parallel with the illumination, respectively. In the former illumination orthogonal subspace, which is specular-free, we can conduct robust clustering with an explicit criterion to determine the cluster number adaptively. In the latter, illumination parallel subspace, a property called pure diffuse pixels distribution rule helps map each specular-influenced pixel to its diffuse component. In terms of efficiency, the proposed approach involves few complex calculation, and thus can remove highlight from high resolution images fast. Experiments show that this method is of superior performance in various challenging cases.


[Long course metastasis in renal adenocarcinoma. Adrenal gland involvement].
To report two cases of metachronic adrenal metastasis (one contralateral and the other bilateral) from renal cell carcinoma with long survival. Two patients with clear cell renal carcinoma that developed metastasis to the adrenals are described. Each patient had undergone three operations for solitary metastasis during the 8-years follow-up. The indications for the surgical management of solitary metastasis, morbidity, prognosis and recent investigational treatment possibilities reported in the literature are analyzed. Resection of the renal cell carcinoma achieved a survival of more than 8 years with a good quality of life and no significant surgical complications. The outcome, however, is poor. Although there was no lymph node involvement and the tumor was localized to the renal parenchyma, one patient developed solitary lung metastasis and contralateral adrenal metastasis 4 and 8 years after the initial diagnosis, respectively. In the other case, contralateral adrenal metastasis appeared three years later. The possibility of long-term metastasis to the adrenal gland should be taken into account due to renal vein involvement. Preservation of the adrenal gland at the initial surgery (lower pole tumor) led to adrenal metastasis 8 years after the initial diagnosis. The prognosis is poor in both cases and the situation is discouraging for the urologist.


Elucidating T Cell and B Cell Responses to SARS-CoV-2 in Humans: Gaining Insights into Protective Immunity and Immunopathology.
The SARS-CoV-2 pandemic is an unprecedented epochal event on at least two fronts. Firstly, in terms of the rapid spread and the magnitude of the outbreak, and secondly, on account of the equally swift response of the scientific community that has galvanized itself into action and has successfully developed, tested and deployed highly effective and novel vaccines in record time to combat the virus. The sophistication and diversification of the scientific toolbox we now have at our disposal has enabled us to interrogate both the breadth and the depth of the immune response to a degree that is unparalleled in recent memory. In terms of our understanding of what is critical to contain the virus and mitigate the effects the pandemic, neutralizing antibodies to SARS-CoV-2 garner most of the attention, however, it is essential to recognize that it is the quality and the fitness of the virus-specific T cell and B cell response that lays the foundation and the backdrop for an effective neutralizing antibody response. In this report, we will review some of the key findings that have helped define and delineate some of the essential attributes of T and B cell responses in the setting of SARS-CoV-2 infection.


Leprous polyneuritis cranialis mimicking orbital apex syndrome.
Leprosy is one of the most prevalent infections in India, with our country accounting for almost 60 percent of the world's patients. Hence unusual presentations of leprosy should be sought for and treated at the earliest. We report this rare case of polyneuritis cranialis secondary to leprosy. Affection ofa single cranial nerve has been described previously but there is only one report of leprosy presenting like orbital apex syndrome.


Circulating tumor DNA is readily detectable among Ghanaian breast cancer patients supporting non-invasive cancer genomic studies in Africa.
Circulating tumor DNA (ctDNA) sequencing studies could provide novel insights into the molecular pathology of cancer in sub-Saharan Africa. In 15 patient plasma samples collected at the time of diagnosis as part of the Ghana Breast Health Study and unselected for tumor grade and subtype, ctDNA was detected in a majority of patients based on whole- genome sequencing at high (30×) and low (0.1×) depths. Breast cancer driver copy number alterations were observed in the majority of patients.


AirWay Scope™ for Difficult Ventilation in a Patient With Epiglottic Cyst.
Epiglottic cysts often cause difficulty in airway management, with potential serious life-threatening complications. 1 This case report describes a patient with an epiglottic cyst in whom mask ventilation became difficult after induction of anesthesia. Immediately, an AirWay Scope™ (TMAWS-S100; Pentax, Japan) was inserted orally, and the location of the epiglottis was clarified to assess the reason for difficulty with ventilation. This case demonstrates usefulness of the AirWay Scope in patients with epiglottic cyst.


Model-Agnostic Structural Transfer Learning for Cross-Domain Autonomous Activity Recognition.
Activity recognition using data collected with smart devices such as mobile and wearable sensors has become a critical component of many emerging applications ranging from behavioral medicine to gaming. However, an unprecedented increase in the diversity of smart devices in the internet-of-things era has limited the adoption of activity recognition models for use across different devices. This lack of cross-domain adaptation is particularly notable across sensors of different modalities where the mapping of the sensor data in the traditional feature level is highly challenging. To address this challenge, we propose ActiLabel, a combinatorial framework that learns structural similarities among the events that occur in a target domain and those of a source domain and identifies an optimal mapping between the two domains at their structural level. The structural similarities are captured through a graph model, referred to as the dependency graph, which abstracts details of activity patterns in low-level signal and feature space. The activity labels are then autonomously learned in the target domain by finding an optimal tiered mapping between the dependency graphs. We carry out an extensive set of experiments on three large datasets collected with wearable sensors involving human subjects. The results demonstrate the superiority of ActiLabel over state-of-the-art transfer learning and deep learning methods. In particular, ActiLabel outperforms such algorithms by average F1-scores of 36.3%, 32.7%, and 9.1% for cross-modality, cross-location, and cross-subject activity recognition, respectively.


[Association between body mass index and aggressiveness of papillary thyroid carcinoma].
The aim of the study was to evaluate the association of the body mass index (BMI) with the clinical-pathological characteristics and the recurrence of papillary thyroid carcinoma. The cohort consisted of 208 patients with papillary thyroid carcinoma diagnosed in 2003-2014, in Buenos Aires, Argentina. The patients were grouped according to the BMI as follows: BMI <18.5 kg/m2 (low weight); BMI ≥ 18.5 and < 25 kg/m2 (normal weight); BMI ≥ 25 and < 30 kg/m2 (overweight); BMI ≥ 30 kg/m2 (obesity). Two experienced pathologists reviewed and cross-checked all pathology specimens to confirm diagnosis, tumor characteristics and extent of the disease. All patients were followed every 6 months for 2 years, and annually thereafter. Recurrences were searched by using diagnostic imaging and histological confi rmation when necessary. Regression analysis was applied to defi ne associations of BMI with clinical, pathological, and prognosis features of the disease. A 5-point increase in BMI was significantly associated with tumor size (OR 1.21; 95% CI 1.1-1.5; p = 0.01) and greater extranodal extension in cervical metastases (OR 1.11; 95% CI 1.06-1.21; p = 0.03). The analysis of prognostic variables showed no association between increase in BMI and risk of recurrence (HR 1.11; 95% CI 0.91-1.22). In conclusion, we found that BMI relates directly with tumor size and extranodal extension, but not with recurrence.


Integration of a nanostructured dielectrophoretic device and a surface-enhanced Raman probe for highly sensitive rapid bacteria detection.
This work reports a synergistic approach to the concentration, detection and kinetic monitoring of pathogens through the integration of nanostructured dielectrophoresis (DEP) with nanotag-labelled Surface Enhanced Raman Spectroscopy (SERS). A nanoelectrode array made of embedded Vertically Aligned Carbon Nanofibers (VACNFs) at the bottom of a microfluidic chip was used to effectively capture and concentrate nanotag-labelled E. coli DHα5 cells into a 200 μm × 200 μm area on which a Raman laser probe was focused. The SERS nanotags were based on iron oxide-gold (IO-Au) core-shell nanoovals (NOVs) of ∼50 nm size, which were coated with a QSY21 Raman reporter and attached to E. coli through specific immunochemistry. The combination of the greatly enhanced Raman signal by the SERS nanotags and the effective DEP concentration significantly improved the detection limit and speed. The SERS signal was measured with both a confocal Raman microscope and a portable Raman probe during DEP capture, and was fully validated with fluorescence microscopy measurements under all DEP conditions. The SERS measurements were sensitive enough to detect a single bacterium. A concentration detection limit as low as 210 cfu ml(-1) using a portable Raman system was obtained with a DEP capture time of only ∼50 s. These results demonstrate the potential to develop a compact portable system for rapid and highly sensitive detection of specific pathogens. This system is reusable, requires minimum sample preparation, and is amenable to field applications.


Exposure of black-legged kittiwakes to Lyme disease spirochetes: dynamics of the immune status of adult hosts and effects on their survival.
1. Despite a growing interest in wildlife disease ecology, there is a surprising lack of knowledge about the exposure dynamics of individual animals to naturally circulating infectious agents and the impact of such agents on host life-history traits. 2. The exploration of these questions requires detailed longitudinal data on individual animals that can be captured multiple times during their life but also requires being able to account for several sources of uncertainty, notably the partial observation or recapture of individuals at each sampling occasion. 3. We use a multi-year dataset to (i) assess the potential effect of exposure to the tick-borne agent of Lyme disease, Borrelia burgdorferi sensu lato (Bbsl), on adult apparent survival for one of its natural long-lived hosts, the Black-legged kittiwake (Rissa tridactyla), and (ii) investigate the temporal dynamics of individual immunological status in kittiwakes to infer the rate of new exposure and the persistence of the immune response. Using a multi-event modelling approach, potential uncertainties arising from partial observations were explicitly taken into account. 4. The potential impact of Bbsl on kittiwake survival was also evaluated via an experimental approach: the apparent survival of a group of breeding birds treated with an antibiotic was compared with that of a control group. 5. No impact of exposure to Bbsl was detected on adult survival in kittiwakes, in either observational or experimental data. 6. An annual seroconversion rate (from negative to positive) of 1·5% was estimated, but once an individual became seropositive, it remained so with a probability of 1, suggesting that detectable levels of anti-Bbsl antibodies persist for multiple years. 7. These results, in combination with knowledge on patterns of exposure to the tick vector of Bbsl, provide important information for understanding the spatio-temporal nature of the interaction between this host and several of its parasites. Furthermore, our analyses highlight the utility of capture-mark-recapture approaches handling state uncertainty for disease ecology studies.


The development of a disposable gas chromatography microcolumn.
The first molded gas chromatography (GC) microcolumn is described. This microcolumn consists of a single microtextured thermoset polymer composite which acts as both the structural material and the stationary phase. The resultant microcolumn is inexpensive and has been coupled to a disposable colorimetric sensor array, creating a disposable column-detector unit and demonstrating a proof of concept for a disposable GC microcolumn.


Long-range gap junctional signaling controls oncogene-mediated tumorigenesis in Xenopus laevis embryos.
In addition to the immediate microenvironment, long-range signaling may be an important component of cancer. Molecular-genetic analyses have implicated gap junctions-key mediators of cell-cell communication-in carcinogenesis. We recently showed that the resting voltage potential of distant cell groups is a key determinant of metastatic transformation and tumor induction. Here, we show in the Xenopus laevis model that gap junctional communication (GJC) is a modulator of the long-range bioelectric signaling that regulates tumor formation. Genetic disruption of GJC taking place within tumors, within remote host tissues, or between the host and tumors significantly lowers the incidence of tumors induced by KRAS mutations. The most pronounced suppression of tumor incidence was observed upon GJC disruption taking place farther away from oncogene-expressing cells, revealing a role for GJC in distant cells in the control of tumor growth. In contrast, enhanced GJC communication through the overexpression of wild-type connexin Cx26 increased tumor incidence. Our data confirm a role for GJC in tumorigenesis, and reveal that this effect is non-local. Based on these results and on published data on movement of ions through GJs, we present a quantitative model linking the GJC coupling and bioelectrical state of cells to the ability of oncogenes to initiate tumorigenesis. When integrated with data on endogenous bioelectric signaling during left-right patterning, the model predicts differential tumor incidence outcomes depending on the spatial configurations of gap junction paths relative to tumor location and major anatomical body axes. Testing these predictions, we found that the strongest influence of GJ modulation on tumor suppression by hyperpolarization occurred along the embryonic left-right axis. Together, these data reveal new, long-range aspects of cancer control by the host's physiological parameters.


Iron Load Toxicity in Medicine: From Molecular and Cellular Aspects to Clinical Implications.
Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity.


Impaired conditional discrimination learning in social phobia.
Eyelid conditional discrimination learning (ECDL) is a test of discriminative aversive conditioning. It places minimal demands on motivation and was shown to selectively test temporal lobe function. Twenty-five unmedicated social phobia (SP) patients (mean age 29.5 +/- 7.0 years), diagnosed according to DSM-IV criteria, and 25 age- and gender-matched healthy controls (HC, mean age 34.0 +/- 8.6 years) were examined with an ECDL paradigm. In the experiment two differently colored stimuli are randomly presented. Only one of the stimuli (reinforced trial) is followed by an aversive airpuff to the cornea, as opposed to unreinforced trials not followed by an airpuff. Conditioned responses (CRs) consist of reflex eyelid closures already upon light presentation. HC as well as SP patients showed a significant difference between reinforced and unreinforced trials. In SP patients, CR frequency did not increase during the ECDL task, while HCs showed appropriate conditional discrimination ability. Thus the results indicate an impairment of adequate behavior modification in an aversive conditioning task in SP.


Brief Emotion Regulation Training Facilitates Arousal Control During Sexual Stimuli.
Disgust, a negative emotion which evokes strong behavioral avoidance tendencies, has been associated with sexual dysfunction. Recently, it was postulated that healthy sexual functioning requires a balance between excitatory (increased sexual arousal) and inhibitory processes (lowered disgust levels). This suggests that amplification of excitatory processes (like sexual arousal) could be a valuable addition to treatments for affect-based sexual dysfunctions. The major aim of the present study was to establish whether up-regulation could effectively enhance arousal levels during sexual stimuli, and whether such a training would simultaneously reduce disgust. Students (N = 163, mean age = 20.73 years, SD = 2.35) were trained in up-regulation of affect using either a sexual arousal film (i.e., female-friendly erotic movie) or a threat arousal film clip (i.e., horror movie), while control groups viewed the films without training instructions. Following this, participants viewed and rated state emotions during a series of pictures (sexual, disgusting, or neutral). Up-regulation of mood successfully enhanced general arousal in both groups, yet these arousal levels were not paralleled by reductions in disgust. Overall, the findings indicate that emotion regulation training by maximizing positive affect and general arousal could be an effective instrument to facilitate affect-related disturbances in sexual dysfunctions.


Blood vessel tortuosity selects against evolution of aggressive tumor cells in confined tissue environments: A modeling approach.
Cancer is a disease of cellular regulation, often initiated by genetic mutation within cells, and leading to a heterogeneous cell population within tissues. In the competition for nutrients and growth space within the tumors the phenotype of each cell determines its success. Selection in this process is imposed by both the microenvironment (neighboring cells, extracellular matrix, and diffusing substances), and the whole of the organism through for example the blood supply. In this view, the development of tumor cells is in close interaction with their increasingly changing environment: the more cells can change, the more their environment will change. Furthermore, instabilities are also introduced on the organism level: blood supply can be blocked by increased tissue pressure or the tortuosity of the tumor-neovascular vessels. This coupling between cell, microenvironment, and organism results in behavior that is hard to predict. Here we introduce a cell-based computational model to study the effect of blood flow obstruction on the micro-evolution of cells within a cancerous tissue. We demonstrate that stages of tumor development emerge naturally, without the need for sequential mutation of specific genes. Secondly, we show that instabilities in blood supply can impact the overall development of tumors and lead to the extinction of the dominant aggressive phenotype, showing a clear distinction between the fitness at the cell level and survival of the population. This provides new insights into potential side effects of recent tumor vasculature normalization approaches.


Approximations of the measurable quantity in diffuse optical problems: theoretical analysis of model deviations.
Photon density and photon flux are widely used to model the measurable quantity in diffuse optical tomography problems. However, it is not these two quantities that are actually measured, but rather the radiance accepted by the detection system. We provide a theoretical analysis of the model deviations related to the choice of the measurable quantity-either photon density or flux. By using the diffusion approximation to the radiative transfer equation and its solution with extrapolated boundary conditions, an exact analytical expression of the measurable quantity has been obtained. This expression has been employed as a reference to assess model deviation when considering the photon density or the photon flux as the measurable quantity. For the case of semi-infinite geometry and for both continuous wave and time domains, we show that the photon density approximates the measurable quantity better than the photon flux. We also demonstrate that the validity of this approximation strongly depends on the optical parameters.


Portal vein and its tributaries: evaluation with thin-section three-dimensional contrast-enhanced dynamic fat-suppressed MR imaging.
To evaluate the visibility of the main portal vein (MPV) and its tributaries in healthy subjects at thin-section three-dimensional (3D) contrast material-enhanced dynamic fat-suppressed magnetic resonance (MR) imaging and to determine whether this technique provides useful information in the evaluation of patients with cirrhosis. Seventy-two patients (37 control subjects, 35 patients with cirrhosis) underwent imaging with a high-performance-gradient (25 mT/m) system. In the 37 subjects in the control group, the MPV was visualized in 37; splenic vein (SV), in 37; superior mesenteric vein (SMV), in 37; inferior mesenteric vein (IMV), in 35; posterior superior pancreaticoduodenal vein (PSPDV), in 35; gastrocolic trunk (GT), in 34; right gastroepiploic vein (RGEV), in 31; right colic vein, in 30; anterior superior pancreaticoduodenal vein, in 22; middle colic vein (MCV), in 29; and first jejunal vein (FJV), in 36. Satisfactory visualization (mean ratings of 2 or higher) was achieved in the MPV, SV, SMV, IMV, PSPDV, GT, RGEV, and FJV in the control group. Mean diameters of the SV, SMV, MCV, and FJV were significantly larger in the cirrhosis group than in the control group (P <.001, P <.001, P =.048, and P =.002, respectively). Thin-section 3D contrast-enhanced dynamic fat-suppressed MR imaging can facilitate precise visualization of the MPV and its tributaries. Dilatation of the tributaries may be a nonspecific secondary finding that is suggestive of cirrhosis.


Occupational exposure risk during spraying of biocidal paint containing silver nanoparticles.
The study assessed potential to exceed occupational exposure limits while spraying paint with and without a silver nanoparticle biocidal additive. A tradesperson performed the tasks in a sealed chamber with filtered air supply. Integrated air sampling entailed transmission electron microscopy with energy dispersive X-ray analysis, direct-reading of particle number concentrations, and determination of silver mass concentration by NIOSH Method 7300. Silver nanoparticles were primarily embedded in paint spray droplets but also observed as isolated particles. Using an α-level of 0.05, median nanoparticle number concentrations did not differ significantly when spraying conventional vs. biocidal paint, although statistically significant differences were observed at specific particle size ranges <100 nm. The geometric mean concentration of total silver while spraying biocidal paint (n = 6) was 2.1 µg/m3 (95% CI: 1.5-2.8 µg/m3), and no respirable silver was detected (<0.50 µg/m3). The results address a lack of silver nanoparticle exposure data in construction and demonstrate the feasibility of a practical sampling approach. Given similar conditions, the measurements suggest a low probability of exceeding a proposed silver nanoparticle exposure limit of 0.9 µg/m3 as an airborne 8-hr time-weighted average respirable mass concentration. A full workday of exposure to respirable silver at the highest possible level in this study (<0.50 µg/m3) would not exceed the exposure limit, although limitations in comparing short task-based exposures to an 8-hr exposure limit must be noted. There was airflow in the study chamber, whereas exposure levels could increase over time in work environments lacking adequate ventilation. Potential to exceed the exposure limit hinged upon the respirable fraction of the paint mist, which could vary by material and application method. Additional research would improve understanding of silver nanoparticle exposure risks among construction trades, and biological responses to these exposures. Given the potential for exposure variability on construction jobsites, safety and health professionals should be cognizant of methods to assess and control silver nanoparticle exposures.


Behavioral motor evaluation for neurotoxicity screening.
Behavioral motor testing is an important aspect of neurotoxicity screening. Previous test batteries have focused on simple measures of motor performance such as tapping rate, movement times and reaction times. These measures, although valuable in certain instances, do not provide a comprehensive description of motor disorders. An alternate approach to evaluate behavioral motor deficits is to use simple behaviors as an initial guide for the study of coordinated movements in more natural and thus more complex situations. The advantages of such an approach may be insights into the central neural correlates of motor disorders caused by toxic agents.


ER stress activating ATF4/CHOP-TNF-α signaling pathway contributes to alcohol-induced disruption of osteogenic lineage of multipotential mesenchymal stem cell.
Studies have provided substantial evidence that osteoblasts and adipocytes share common progenitor‒multipotential mesenchymal stem cells in bone marrow (BMSCs), and excessive alcohol consumption shifts away from osteogenic to adipogenic lineage. However, how exactly alcohol impairs osteogenesis is still incompletely understood. This study was designed to shed light on this issue. We treated primary BMSCs from human subjects with alcohol for 24 days. We measured changes of genes related to endoplasmic reticulum (ER) stress, adipogenic markers and osteogenic markers using quantitative real-time RT-PCR and Western blot analysis. We performed Oil red O staining and quantification of adipogenesis. We also conducted caspase 3 activity assay to assess BMSC apoptosis. We showed here that chronic exposure of BMSCs to alcohol induced adipogenesis and disrupted osteogenesis as indicated by upregulation of adipogenic markers (PPARγ2 and aP2), downregulation of osteogenic markers (Osf2/Cbfa1), and accumulation of lipid droplets. Alcohol induced ER stress, as reflected by increased expression of glucose-regulated proteins GRP78 and GRP94, and by increased expression of transcription factors activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and enhanced caspase 3 activity. Additionally, ER stress also upregulated tumor necrosis factor-alpha (TNF-α). Simultaneous silencing of ATF4 and CHOP prevented upregulation of TNF-α. Knockdown of either ATF4 and CHOP or TNF-α by their siRNAs was able to reverse the ethanol-induced adipogenesis. Our data therefore revealed a role of ER stress and ATF4/CHOP in the ethanol-induced inhibition of osteogenesis, and activation of TNF-α signaling by ATF4/CHOP linking ER stress to adipogenic lineage in response to alcohol stimulation. This work should establish a new signaling pathway linking alcohol, ER stress, and TNF-α to loss of bone formation: Ethanol → ER stress↑↑↑ → ATF4 & CHOP↑↑↑ → TNF-α↑↑↑ → Osteoblasts↓↓↓.


Right-nostril use during sniffing at arousing stimuli produces higher cardiac activity in jumper horses.
Lateralization in horses, Equus caballus, has been reported at both motor and sensory levels. Here we investigated left- and right-nostril use in 12 jumper horses freely sniffing different emotive stimuli. Results revealed that during sniffing at adrenaline and oestrus mare urine stimuli, horses showed a clear right-nostril bias while just a tendency in the use of the right nostril was observed during sniffing of other odours (food, cotton swab and repellent). Sniffing at adrenaline and urine odours was also accompanied by increasing cardiac activity and behavioural reactivity strengthening the role of the right hemisphere in the analysis of intense emotion and sexual behaviour.


A dynamic synchrotron X-ray imaging study of effective temperature in a vibrated granular medium.
We present a dynamic synchrotron X-ray imaging study of the effective temperature Teff in a vibrated granular medium. By tracking the directed motion and the fluctuation dynamics of the tracers inside, we obtained Teff of the system using the Einstein relationship. We found that as the system unjams with increasing vibration intensities Γ, the structural relaxation time τ increases substantially which can be fitted by an Arrhenius law using Teff. And the characteristic energy scale of structural relaxation yielded by the Arrhenius fitting is E = 0.20 ± 0.02pd(3), where p is the pressure and d is the background particle diameter, which is consistent with those from hard sphere simulations in which the structural relaxation happens via the opening up of free volume against pressure.


Low serum cortisol in combination with high adrenocorticotrophic hormone concentrations are associated with poor outcome in children with severe meningococcal disease.
To study the correlation between serum concentrations of adrenocorticotrophic hormone (ACTH) and cortisol in relation to severity of disease in children with meningococcal sepsis. Subjects were children with meningococcal sepsis, admitted to the pediatric intensive care unit. Clinical data, laboratory values and blood samples were selected. Arterial cortisol, ACTH, interleukin 6 and tumor necrosis factor alpha concentrations were measured on admission and studied for their relation to severity of disease (sepsis, septic shock/survivors, septic shock/nonsurvivors). Seventy-two patients fulfilled the criteria for meningococcal sepsis. Sixty-two of these children with positive blood cultures of Neisseria meningitidis, who were not treated with corticosteroids before admission, were included. Fifty of the 62 patients had septic shock. Twelve of those children (24%) died. The median age of the subjects was 2.6 years (range, 0.3 to 16.1 years). Cortisol values were significantly lower in non-survivors (median, 654 nmol/l) than in survivors (median, 2184 nmol/l) (P < 0.01). ACTH values were significantly higher in children who died (median, 1271 ng/l) than in survivors (85 ng/l) (P < 0.01). The median cortisol:ACTH ratio decreased significantly depending on the disease severity categories. Low serum cortisol concentrations in combination with high ACTH concentrations are associated with poor outcome in children with severe meningococcal disease.


Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl.
Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to eradicate Bcr-Abl(+) leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl(+) leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib mesylate in CML cells. This screen identified numerous components of a Wnt/Ca(2+)/NFAT signaling pathway. Antagonism of this pathway led to impaired NFAT activity, decreased cytokine production, and enhanced sensitivity to Bcr-Abl inhibition. Furthermore, NFAT inhibition with cyclosporin A facilitated leukemia cell elimination by the Bcr-Abl inhibitor dasatinib and markedly improved survival in a mouse model of Bcr-Abl(+) acute lymphoblastic leukemia (ALL). Targeting this pathway in combination with Bcr-Abl inhibition could improve treatment of Bcr-Abl(+) leukemias.


Associations of plasma phospholipid omega-6 and omega-3 polyunsaturated Fatty Acid levels and MRI measures of cardiovascular structure and function: the multiethnic study of atherosclerosis.
Background. The association between plasma omega-6 fatty acids and cardiovascular disease (CVD) is unclear, and discrepancy remains concerning the cardiovascular benefit of the omega-3 fatty acid alpha-linolenic acid. Methods. Associations of plasma phospholipid fatty acid levels (arachidonic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid (DHA), and alpha-linolenic acid) with cardiac magnetic resonance imaging measures of left ventricular (LV) mass, LV volume, ejection fraction, stroke volume, and aortic distensibility were investigated in 1,274 adults. Results. Results of multivariate analysis showed no statistically significant associations of plasma omega-6 or omega-3 levels with cardiac magnetic resonance imaging measures. Stratification by gender revealed a positive association between DHA and LV mass in women (β = 1.89, P = 0.02; P interaction = 0.003) and a trend for a positive association between DHA and ejection fraction in men (β = 0.009, P = 0.05; P interaction = 0.03). Conclusion. Additional research is warranted to clarify the effects of plasma DHA on cardiac structure and function in women versus men.


Natalizumab: alpha 4-integrin antagonist selective adhesion molecule inhibitors for MS.
Natalizumab (Antegren, Elan Corp. plc.; Biogen Idec.) is the first alpha4-integrin antagonist in the class of selective adhesion molecule inhibitors and is in Phase III clinical trials for the treatment of multiple sclerosis. After a 300 mg intravenous infusion, natalizumab has an elimination half-life of 6 to 9 days, but alpha4-integrin receptors expressed on the surface of peripheral blood leukocytes are more than 80% saturated approximately 1 month postinfusion. Therefore, natalizumab is given as a 300 mg dose administered monthly. Preliminary efficacy results showed a marked reduction (approximately 90%) in the formation of new gadolinium-enhancing lesions and reduced the number of patients with relapse by 50% in patients with relapsing-remitting or secondary progressive multiple sclerosis receiving natalizumab versus those receiving placebo over a 6-month period. In clinical studies, natalizumab has demonstrated a favorable safety profile. Pivotal Phase III studies of natalizumab as monotherapy and in combination with intramuscular interferon-beta-1a are underway in patients with relapsing-remitting multiple sclerosis. Natalizumab may be an important addition to the therapeutic armamentarium for multiple sclerosis.


Determining a transitional scoring link between PROMIS® pediatric and adult physical health measures.
Having independent versions of the PROMIS® scales (for Pediatric and Adults) is problematic as scores cannot be evaluated longitudinally as individuals move from childhood into adulthood. The primary aim of this research project is to use item response theory (IRT) to develop a transitional scoring link (or "crosswalk") between the PROMIS adult and pediatric physical health measures. Sample 1 was collected at 6 rehabilitation hospitals in the U.S., and participants in Sample 2 were recruited from public health insurance programs and an online research panel. PROMIS pediatric and adult physical function, mobility, upper extremity, fatigue, and pain measures were administered to a sample of 874 individuals aged 14-20 years old with special health needs and a sample of 641 individuals aged 14-25 years with a disability. IRT-based scores were linked using a linear approximation to calibrated projection. Estimated latent variable correlations ranged between 0.84 and 0.95 for the PROMIS pediatric and adult scores. Root Expected Mean Square Difference values were below the 0.08 threshold in all cases except when comparing genders on the Mobility (0.097) and Pain (0.10) scales in the special health care needs sample. Sum score conversion tables for the pediatric and adult PROMIS measures are presented. The linking coefficients can be used to calculate scale scores on PROMIS adult measures from pediatric measure scores and vice versa. This may lead to more accurate measurement in cross-sectional studies spanning multiple age groups or longitudinal studies that require comparable measurement across distinct developmental stages.


Migration of BEAS-2B cells enhanced by H1299 cell derived-exosomes.
Previous studies reported that exosomes (Exos) secreted by tumor cells could affect the tumor cells themselves and normal cells. However, the effects of exosomes derived from tumor cells on normal cells' migration and mechanical characteristics are rarely reported. This work explores the effects of H1299 cell-derived exosomes (H1299-Exos) on the migration of BEAS-2B cells, and analyzes possible mechanical mechanisms. In the experiments, exosomes were isolated from the culture supernatants of H1299 cells by ultracentrifugation. The H1299-Exos were confirmed by scanning electron microscope (SEM) and western blotting (WB). The BEAS-2B cell migration was assessed using scratch assays. Cytoskeletal structure changes were detected by immunofluorescence. Surface morphology and mechanical properties were measured by atomic force microscopy (AFM). After incubation with H1299-Exos for 48 h, BEAS-2B cells enhanced migration ability, with increased filopodia and cytoskeletal rearrangements. The changes in the morphology and mechanical properties of the cells caused by H1299-Exos were detected using AFM, including the increase in cell length and the decrease in cell height, Young's modulus and adhesion. In short, H1299-Exos promoted the BEAS-2B cell migrations. It indicates that the morphological and mechanical properties can be used as a means to assess normal cell alterations induced by tumor cell derived-exosomes. This provides a method for studying the effects of exosomes secreted by tumor cells on normal cells and the changes in their physical properties.


Selective massive amyloidosis of small intestine.
A patient with intestinal amyloidosis with perforation was successfully treated by resection of almost the whole involved small intestine and is recuperating on hyperalimentation therapy. Because there were no signs of amyloiditic deposition in other parts of the body and no other cause of the amyloidosis, the case was considered to be selective localized intestinal amyloidosis. This is the third reported case of perforated amyloiditic intestine and apparently the first case of selective small intestinal amyloidosis involving such a complication.


Anaphylaxis or so-called encephalopathy in mice sensitized to an antigen with the aid of pertussigen (pertussis toxin).
Sensitization of mice with 1 mg of bovine serum albumin (BSA) or chicken egg albumin (EA) given intraperitoneally and 300 to 400 ng of pertussigen (pertussis toxin [Ptx]) given intravenously (i.v.) induced a high degree of anaphylactic sensitivity when the mice were challenged i.v. with 1 mg of antigen 14 days later. Regardless of H-2 haplotype, all of the strains tested (CFW, BALB/cJ, DBA/2J, and C3H.SW/SnJ) were susceptible to anaphylaxis. Sensitization of mice by a multiple-dose procedure that has been reported to induce fatal encephalopathy in mice (L. Steinman, A. Weiss, N. Adelman, M. Lim, R. Zuniga, J. Oehlert, E. Hewlett, and S. Falkow, Proc. Natl. Acad. Sci. USA 82, 8733-8736, 1982) (1 mg of BSA on day -1, 100 to 400 ng of Ptx on day zero 1 mg of BSA on day +1, 100 to 400 ng of Ptx on day +2, and 1 mg of BSA on day +6) induced shock in BALB/cJ, DBA/2J, and C3H.SW/SnJ mice, but not in CFW mice. When EA was used instead of BSA, CFW, BALB/cJ, and C3H.SW/SnJ mice did not develop fatal shock, whereas DBA/2J mice did. When dose 3 of antigen (BSA or EA) was postponed to day +21, all mouse strains sensitized by the multiple-dose procedure were found to be susceptible to shock. The fatal shock induced by this procedure, as well as that induced by giving a single sensitizing dose of antigen and Ptx, could be prevented by one to three 1-ml doses of saline given i.v. at the time signs of severe shock appeared. Although only one dose of saline was often sufficient to save the mice, two or three doses were usually needed. Microscopic changes were not found in midsagittal sections of the brains of mice sensitized by either procedure. This was true of mice that died from shock or were saved from shock by injections of saline. From these results, we concluded that the proposed model for encephalopathy induced in mice by Ptx and BSA demonstrates only the well-known anaphylactogenic effect of Ptx or pertussis vaccine. Since there are many other more sensitive methods to detect Ptx, induction of anaphylaxis is not of much value for detection or quantitation of Ptx in pertussis vaccine.


Risk of Iodine Deficiency in Extremely Low Gestational Age Newborns on Parenteral Nutrition.
Iodine is an essential component of thyroid hormones, which play a critical role in neurodevelopment. The iodine status of pregnant women and their newborns is not checked routinely. Extremely Low Gestational Age Newborns do not receive Iodine supplementation while on parenteral nutrition (PN). We measured urine iodine levels and thyroid function tests in 50 mother-infant dyads at birth, at 1 week, 1, 2, 3 months and near discharge. We correlated maternal and neonatal urine iodine levels with thyroid functions and measured iodine levels in milk and PN. In our study, 64% of mothers were iodine deficient at the time of delivery, their free T4 levels were 0.48 (0.41-0.54) ng/dL with normal thyroid-stimulating hormone (TSH). Iodine levels were thirty-fold higher in extremely low gestational age newborns (ELGAN) exposed to iodine comparing to full terms (p < 0.001), but this effect lasted <1 week. At 1 month of age, ELGAN on PN developed iodine deficiency (p = 0.017) and had high thyroglobulin levels of 187 (156-271) ng/mL. Iodine levels improved with enteral feeds by 2 months of age (p = 0.01). Iodine deficiency is prevalent among pregnant women and ELGAN; in particular, those on PN are at risk of hypothyroidism. Iodine supplementation during pregnancy and postnatally should be considered to avoid iodine deficiency.


Systematic review of flexion/extension radiography of the cervical spine in trauma patients.
The aim of this review was to investigate whether Flexion/Extension (F/E) radiography adds diagnostic value to CT or MRI in the detection of cervical spine ligamentous injury and/or clinically significant cervical spine instability of blunt trauma patients. A systematic search of literature was done in Pubmed, Embase and Cochrane Library databases. Primary outcome was sensitivity and specificity of F/E radiography. Secondary outcomes were the positive predicting value (PPV) and negative predicting value (NPV) (with CT or MRI as reference tests due to the heterogeneity of the included studies) of each modality and the quality of F/E radiography. F/E radiography was overall regarded to be inferior to CT or MRI in the detection of ligamentous injury. This was reflected by the high specificity and NPV for CT with F/E as reference test (ranging from 97 to 100% and 99 to 100% respectively) and the ambiguous results for F/E radiography with MRI as its reference test (0-98% and 0-83% for specificity and NPV respectively). Image quality of F/E radiography was reported to have 31 to 70% adequacy, except in two studies which reported an adequacy of respectively 4 and 97%. This systematic review of the literature shows that F/E radiography adds little diagnostic value to the evaluation of blunt trauma patients compared to CT and MRI, especially in those cases where CT or MRI show no indication of ligamentous injury.


Ovarian reserve after laparoscopic treatment of unilateral ovarian endometrioma.
To evaluate the effect of laparoscopic treatment of unilateral ovarian endometrioma on ovarian reserve using ultrasonographic markers, ovarian volume and antral follicle count (AFC), and two biochemical markers, serum levels of Follicle-stimulating hormone (FSH) and Estradiol (E2). This prospective study included 40 patients in their reproductive age, between 18 and 40 years old. They were treated laparoscopically for unilateral ovarian endometrioma. Markers of ovarian reserve were investigated before and three months after surgery. Transvaginal ultrasound examination was used for measurement of ovarian volume and AFC. Biochemical markers (FSH and E2 levels) were determined by chemiluminescent tests. Ovarian volume was significantly reduced after surgery. There was significant increase of AFC and non-significant increase of E2 levels in treated patients after three months. Laparoscopic cystectomy of unilateral ovarian endometrioma decreased ovarian reserve immediately after surgery with decrease of ovarian volume. But ovarian reserve was increased after three months with increase of AFC and estradiol levels.


Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial.
To investigate the effect of a restricted intravenous fluid regimen versus a standard regimen on complications after colorectal resection. Current fluid administration in major surgery causes a weight increase of 3-6 kg. Complications after colorectal surgery are reported in up to 68% of patients. Associations between postoperative weight gain and poor survival as well as fluid overload and complications have been shown. We did a randomized observer-blinded multicenter trial. After informed consent was obtained, 172 patients were allocated to either a restricted or a standard intraoperative and postoperative intravenous fluid regimen. The restricted regimen aimed at maintaining preoperative body weight; the standard regimen resembled everyday practice. The primary outcome measures were complications; the secondary measures were death and adverse effects. The restricted intravenous fluid regimen significantly reduced postoperative complications both by intention-to-treat (33% versus 51%, P = 0.013) and per-protocol (30% versus 56%, P = 0.003) analyses. The numbers of both cardiopulmonary (7% versus 24%, P = 0.007) and tissue-healing complications (16% versus 31%, P = 0.04) were significantly reduced. No patients died in the restricted group compared with 4 deaths in the standard group (0% versus 4.7%, P = 0.12). No harmful adverse effects were observed. The restricted perioperative intravenous fluid regimen aiming at unchanged body weight reduces complications after elective colorectal resection.


Ultrabroadband red luminescence of Mn4+ in MgAl2O4 peaking at 651 nm.
Blue light pumped red luminescence with broadband and high photon-energy emission is highly desired for phosphor-converted white light-emitting diodes (pc-wLEDs), to achieve a high color rendering index and high luminous efficacy. Mn4+-doped red-emitting phosphors generally exhibit sharp vibronic emissions associated with the parity- and spin-forbidden 2Eg→4A2g transitions. In this paper, two abnormal luminescence behaviors were observed for Mn4+ in the MgAl2O4:Mn4+ spinel phosphor with a short wavelength emission band peaking at 651 nm. Firstly, the Mn4+ 2Eg→4A2g transition exhibits ultrabroadband luminescence in MgAl2O4 and the large full-width at half-maximum (FWHM) is dependent both on the calcination temperature and on the partial substitution of Al3+ with Ga3+. Secondly, the thermal quenching behavior of the Mn4+ 2Eg→4A2g luminescence in MgAl2O4 shows a dependence on its thermal treatment and preparation method. The Rietveld refinement and Raman results demonstrate that the variation in the FWHM of the luminescence spectra is a sum effect of structural ordering (i.e., isotropic displacement decrease of constituent atoms) and the Mg ↔ Al anti-site disorder. A model for the observed varying thermal quenching of luminescence was tentatively proposed. The intrinsic thermal quenching temperature of Mn4+ luminescence in MgAl2O4 was found to be 390-400 K using the samples prepared by the co-precipitation and molten salt methods. The present work gives a novel perspective to understand the luminescence spectra of Mn4+ 2Eg→4A2g transition.


The effect of music on parental participation during pediatric laceration repair.
The purpose of this quasi-experimental study was to test an intervention on the use of music during simple laceration repair to promote parent-led distraction in children aged 1 to 5. Children's songs were broadcast via speakers during laceration repair and parents were encouraged to participate in distracting their child. The proportion of parental participation was determined. Laceration procedures were videotaped and objectively scored using the Procedure Behavior Check List. A total of 57 children participated in the study. There was no difference in parental involvement between the control and intervention groups. When age, sex, and condition were controlled for, distress scores were significantly higher if the father was present in the procedure room than if only the mother was present (43.68 vs. 23.39, t(54) 4.296, p = < 0.001). It was concluded that distress varies with the age of the child and the parent who is present during the procedure. Providing music during simple laceration repair did not increase the proportion of parents who were involved in distraction.