Bacterial Biofilm Destruction: A Focused Review On The Recent Use of Phage-Based Strategies With Other Antibiofilm Agents.
Biofilms are bacterial communities that live in association with biotic or abiotic surfaces and enclosed in an extracellular polymeric substance. Their formation on both biotic and abiotic surfaces, including human tissue and medical device surfaces, pose a major threat causing chronic infections. In addition, current antibiotics and antiseptic agents have shown limited ability to completely remove biofilms. In this review, the authors provide an overview on the formation of bacterial biofilms and its characteristics, burden and evolution with phages. Moreover, the most recent possible use of phages and phage-derived enzymes to combat bacteria in biofilm structures is elucidated. From the emerging results, it can be concluded that despite successful use of phages and phage-derived products in destroying biofilms, they are mostly not adequate to eradicate all bacterial cells. Nevertheless, a combined therapy with the use of phages and/or phage-derived products with other antimicrobial agents including antibiotics, nanoparticles, and antimicrobial peptides may be effective approaches to remove biofilms from medical device surfaces and to treat their associated infections in humans.


Longitudinal analysis of 25 sequential sample-pairs using a custom multiple myeloma mutation sequencing panel (M(3)P).
Recent advances in genomic sequencing technologies now allow results from deep next-generation sequencing to be obtained within clinically meaningful timeframes, making this an attractive approach to better guide personalized treatment strategies. No multiple myeloma-specific gene panel has been established so far; we therefore designed a 47-gene-targeting gene panel, containing 39 genes known to be mutated in ≥3 % of multiple myeloma cases and eight genes in pathways therapeutically targeted in multiple myeloma (MM). We performed targeted sequencing on tumor/germline DNA of 25 MM patients in which we also had a sequential sample post treatment. Mutation analysis revealed KRAS as the most commonly mutated gene (36 % in each time point), followed by NRAS (20 and 16 %), TP53 (16 and 16 %), DIS3 (16 and 16 %), FAM46C (12 and 16 %), and SP140 (12 and 12 %). We successfully tracked clonal evolution and identified mutation acquisition and/or loss in FAM46C, FAT1, KRAS, NRAS, SPEN, PRDM1, NEB, and TP53 as well as two mutations in XBP1, a gene associated with bortezomib resistance. Thus, we present the first longitudinal analysis of a MM-specific targeted sequencing gene panel that can be used for individual tumor characterization and for tracking clonal evolution over time.


Efficient degradation of phenanthrene by biochar-supported nano zero-valent iron activated persulfate: performance evaluation and mechanism insights.
Biochar-supported nano zero-valent iron (BC@nZVI) is a novel and efficient non-homogeneous activator for persulfate (PS). This study aimed to identify the primary pathways, the degradation mechanism and the performance of phenanthrene (PHE) with PS activated by BC@nZVI (BC@nZVI/PS). BC@nZVI as an activator for PS was prepared by liquid phase reduction method. BC@nZVI was characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffractometer and Fourier transform infrared spectroscopy. The effects of the iron-carbon mass ratio and BC@nZVI dosage were investigated, and a pseudo-first-order kinetic model was used to evaluate the PHE degradation. The results showed that BC supported nZVI and inhibited the agglomeration of nZVI, improving PS's activation efficiency. The optimal iron-carbon mass ratio was determined to be 1:4, accompanied by a dosage of 0.6 g/L of BC@nZVI. During PS activation, nZVI was transformed to Fe2+ and Fe3+, with the majority being Fe3+. The reducibility of nZVI in BC@nZVI enabled the reduction of Fe3+ to Fe2+ to activate PS. Radical quenching and electron paramagnetic resonance (EPR) revealed that the oxidative radicals in the BC@nZVI/PS system were mainly SO4-· and ·OH, where SO4-· was the primary free radical under acidic and neutral conditions and ·OH in alkaline conditions. Additionally, BC@nZVI adsorption had a limited role in PHE removal. This study can provide mechanism insights of PHE degradation in water with BC@nZVI activation of the Na2S2O8 system.


A Novel Method for Training Mice in Visuo-Tactile 3-D Object Discrimination and Recognition.
Perceiving, recognizing and remembering 3-dimensional (3-D) objects encountered in the environment has a very high survival value; unsurprisingly, this ability is shared among many animal species, including humans. The psychological, psychophysical and neural basis for object perception, discrimination, recognition and memory has been extensively studied in humans, monkeys, pigeons and rodents, but is still far from understood. Nearly all 3-D object recognition studies in the rodent used the "novel object recognition" paradigm, which relies on innate rather than learned behavior; however, this procedure has several important limitations. Recently, investigators have begun to recognize the power of behavioral tasks learned through reinforcement training (operant conditioning) to reveal the sensorimotor and cognitive abilities of mice and to elucidate their underlying neural mechanisms. Here, we describe a novel method for training and testing mice in visual and tactile object discrimination, recognition and memory, and use it to begin to examine the underlying sensory basis for these cognitive capacities. A custom-designed Y maze was used to train mice to associate one of two 3-D objects with a food reward. Out of nine mice trained in two cohorts, seven reached performance criterion in about 20-35 daily sessions of 20 trials each. The learned association was retained, or rapidly re-acquired, after a 6 weeks hiatus in training. When tested under low light conditions, individual animals differed in the degree to which they used tactile or visual cues to identify the objects. Switching to total darkness resulted only in a transient dip in performance, as did subsequent trimming of all large whiskers (macrovibrissae). Additional removal of the small whiskers (microvibrissae) did not degrade performance, but transiently increased the time spent inspecting the object. This novel method can be combined in future studies with the large arsenal of genetic tools available in the mouse, to elucidate the neural basis of object perception, recognition and memory.


[Hygienic assessment of the radiation risk of radon emanation in the Altai Krai].
The unique climatic and geographical location of the Altai Krai determines the specific radiation dose load for the population, which is composed of the complex of radiological indices, the structure of which is largely dependent on the type of locality and, to a greater extent due to the action of radon, which is currently the main source of internal radiation of the population of upland districts and adjacent territories. There was performed a hygienic assessment of the radiation risk and the expected decline in life expectancy and population health due to radon exposure in the model areas of the Altai Krai. To calculate the additional risk there were used some models for radiation risk extrapolation: a risk constant model, model GSF (Jacobi's model), Lubin model (TSE/AGE/WL) and BEIR VI model for smoking and nonsmoking population, as well as the combined model. The lowest values of the radiation risk and the expected decline in life expectancy are typical for Charyshsko-Ust-Kalmanskaya zone, the maximum--for Kuryinsko--Pospelikhinskaya zone.


Acoustic communication and reproductive isolation in two species of wolf spiders.
Sound production by male wolf spiders during courtship is critical for behavioral reproductive isolation of two sibling species. Females only respond to and copulate with conspecific males, and acoustic signals through a substrate are necessary to induce receptivity. No reproductive barriers that could arise during mating (such as genital or mechanical incompatibility) or after mating (infertility) are in effect between the species, since forced interspecific matings produce viable offspring.


Xenopus Ran-binding protein 1: molecular interactions and effects on nuclear assembly in Xenopus egg extracts.
Ran is a nuclear GTPase implicated in nucleocytoplasmic transport, the maintenance of nuclear structure, mRNA processing, and cell cycle regulation. By two-hybrid interaction in yeast, we have identified a Xenopus homologue of Ran-binding protein 1 (RanBP1). Xenopus RanBP1 interacts specifically with the GTP-bound form of Ran and forms complexes in Xenopus egg extracts with Ran, importin-beta/karyopherin-beta and importin-alpha/karyopherin-alpha, but not p10, p120/RanBP7, RanBP2 or other nucleoporins. These complexes may play roles in the recycling of Ran and importins/karyopherins during nucleocytoplasmic transport. Increased concentrations of RanBP1 stabilise an interaction between Ran and RCC1 in egg extracts, inhibiting the exchange activity of RCC1 towards Ran. Under these conditions, the assembly of nuclei from chromatin is dramatically affected: the nuclei do not assemble a lamina and become very small with homogeneously condensed chromatin. They fail to actively import proteins and do not undergo DNA replication. By field emission in-lens scanning electron microscopy, we show that these nuclei have an intact nuclear envelope containing pore complexes, but the envelope is highly convoluted. However, RanBP1 does not directly inhibit nuclear protein import in assembled nuclei. These results suggest that RCC1 and/or Ran have a function early in nuclear assembly that is disrupted by RanBP1.


Unique Th1/Th2 phenotypes induced during priming and memory phases by use of interleukin-12 (IL-12) or IL-28B vaccine adjuvants in rhesus macaques.
Adjuvant compounds are usually included in vaccinations in order to bolster total vaccine-specific responses or to tailor an immune response toward a desired endpoint, such as the production of gamma interferon or an increase in antibody titers. While most adjuvants are studied in regard to their impact on vaccine-specific responses during and just after the vaccination period, a detailed analysis of how adjuvants skew the Th1/Th2 axis at more distant time points is not often undertaken. In the current study, we present data that suggests that adjuvants differ in their relative abilities to bolster and skew immune responses in the short term compared with more distant time points. To that end, we have employed interleukin-12 (IL-12) and IL-28B as adjuvants for DNA vaccination of rhesus macaques. While both adjuvants were able to bolster Th1-biased responses, our analysis shows that this skewing was achieved through different mechanisms. Moreover, analysis 3 months after the final immunization revealed the activity of the IL-12 adjuvant to be short lived, while the IL-28B adjuvant continued to exert its influence on the immune system. Taken together, these data suggest that the scientific and medical communities would benefit from a more detailed analysis of adjuvant function, including the determination of long-term influences of administered adjuvants.


Beta-adrenoceptor-agonist and insulin actions on glucose metabolism in rat skeletal muscle in different thyroid states.
1. The actions of the beta-adrenoceptor agonist isoprenaline on glucose and glycogen metabolism, in the presence of various concentrations of insulin, were investigated in isolated soleus muscle preparations taken from eu-, hyper- and hypothyroid rats. 2. Hyperthyroidism, induced by 3,3',5-tri-iodo-D-thyronine (T3) administration for 5 days, increased the rate of lactate formation and suppressed the rate of glycogen synthesis in soleus muscle in response to isoprenaline, even in the presence of physiological or supraphysiological insulin concentrations. 3. Hypothyroidism, induced by administration of 6-n-propyl-2-thiouracil for 4 weeks, decreased the rate of isoprenaline-stimulated lactate formation at all insulin concentrations, but significantly decreased the responsiveness of lactate formation only at low insulin concentrations. In the presence of 100 or 10,000 mu-units of insulin/ml, the ability of isoprenaline to suppress the rate of glycogen synthesis was markedly impaired (inhibition at 100 mu-units of insulin/ml and 1 micro-M-isoprenaline: eu- 72.6 +/- 2.9%; hypo-41.0 +/- 2.1%; P less than 0.001). 4. Hyperthyroidism had no effect on the number or affinity of beta-adrenoceptors, defined by 125I-pindolol binding, or beta-adrenoceptor- or forskolin-stimulated adenylate cyclase activity in membrane preparations of gastrocnemius muscle, whereas hypothyroidism increased the beta-adrenoceptor density and decreased the beta-adrenoceptor-stimulated adenylate cyclase activity, without affecting the receptor affinity or forskolin-stimulated adenylate cyclase activity. 5. It is concluded that there is a complex interplay between insulin, catecholamines and thyroid hormones to regulate skeletal-muscle glucose metabolism. The changes observed in muscles in hypothyroidism may be explained, at least in part, by changes in beta-adrenoceptor-G-protein-adenylate cyclase coupling affecting the generation of cyclic AMP and the regulation of some of the key enzymes of glycogen metabolism; in contrast, the changes observed in muscles in hyperthyroidism do not appear to result from alterations at the level of the receptor-mediated second-messenger generation.


Arterial Topographic Anatomy Near the Femoral Head-Neck Perforation with Surgical Relevance.
Knowledge of the vascular supply of the femoral head is crucial for hip-preserving surgical procedures. The critical area for reshaping cam deformity is at the retinacular vessel penetration, an area with ill-defined topographic anatomy. We performed a cadaver study of the extension of the lateral retinaculum near the head-neck junction, distribution of the arterial vascular foramina, and initial intracapital course of these vessels. In 16 fresh proximal parts of the femur without head-neck deformities, the deep branch of the medial femoral circumflex artery was injected with gadolinium for magnetic resonance imaging (MRI) sequences to identify arterial structures. We found a mean number of 4.5 arterial foramina, showing a predominance from 10 to 12 o'clock. The retinaculum extended 20 mm from 1 to 10 o'clock. The surface distance from the cartilage border to the vascular foramina under the synovial fold was 6.5 mm, and the depth from the same cartilage border to the initial intraosseous vessel pathways was 5.3 mm. The data add further precision to the arterial topography at the retinacular foramina, an area that is crucial for the perfusion of the femoral head. It may overlap with the area of anterolateral cam deformity and plays a role in choosing the cuts for subcapital and intracapital osteotomies. The information is taken from normal hips and may not be directly applicable to the deformed hip. Nevertheless, it is a prerequisite for a surgeon to understand the normal anatomy and use those boundaries to prevent mistakes during intra-articular joint-preserving hip surgical procedures.


[Acute renal failure in critically ill patients].
Acute renal failure is common in critically ill patients and is associated with a high mortality rate. This paper reviews current management of patients with acute renal failure admitted to an intensive care unit. Literature search in databases (Medline, Cochrane database of systematic reviews, UpToDate). The prevalence of acute renal failure is 5-20 % in patients admitted to intensive care units; the associated hospital mortality is 30-60 %. The aetiology is usually multifactorial; inflammation (sepsis, surgery), hypovolaemia and drug toxicity commonly precipitate acute renal failure. There is no effective drug treatment, but early onset of renal replacement therapies with haemodialysis or haemofiltration is likely to prolong survival. Despite modern intensive care, mortality is high in acute renal failure and preventive measures should therefore be vigorously pursued. Haemodialysis and haemofiltration should be introduced early in acute renal failure, and should be available in all intensive care units.


Relationship of Imported Fire Ant (Hymenoptera: Formicidae) Integument Coloration to Cuticular Hydrocarbon and Venom Alkaloid Profiles.
Red imported fire ant (Solenopsis invicta Buren; RIFA) and black imported fire ant (Solenopsis richteri Forel (Hymenoptera: Formicidae); BIFA) are considered distinct species with introgression via a reproductively functional hybrid (HIFA). The RIFA and BIFA common names are based on relative coloration. Due to human color perception variation, using color to identify RIFA, BIFA or HIFA is challenging. Fire ant identification traditionally involves molecular or chemical techniques, but a colorimetric test could allow rapid and low-cost identification. In this study, ant integument coloration was measured by spectrophotometer, and color attributes were compared to a combined gas chromatography (GC) index derived from cuticular hydrocarbon and venom alkaloid indices. Significant Pearson Correlation coefficients were found for colony GC index versus color attributes red to green (a*), blue to yellow (b*), chroma (C*), and hue (h*), but not lightness (L*). The RIFA colonies were distinct from BIFA for four of five color attributes and plots of the a*b* and C*h* horizontal axis of the L*a*b* and L*C*h* color spaces. Color attributes for HIFA indices were not distinct from BIFA and RIFA parental species, but HIFA a*b* and C*h* plots were distinct from RIFA and a*b* plots from BIFA. Color attributes a*, b*, and C* increased and h* decreased with GC index in a sinusoidal pattern. In conclusion, most RIFA and BIFA color attributes were distinct and a*b* and C*h* color axes plots had potential to distinguish HIFA from parental species, but coloration of HIFA indices was variable and complicated identifications among HIFA phenotypes, RIFA and BIFA.


Association between PPARGC1A single nucleotide polymorphisms and increased risk of nonalcoholic fatty liver disease among Iranian patients with type 2 diabetes mellitus
Environmental and genetic factors may play a major role in the development of nonalcoholic fatty liver disease (NAFLD) among people with obesity and type 2 diabetes mellitus. Based on the fact that PGC-1α, as the protein encoded by the PPARGC1A gene, plays a key role in energy metabolism pathways, it has been hypothesized that polymorphisms within the PPARGC1Agene may be associated with increased risks of NAFLD. Thus, this study was designed to evaluate the Gly482Ser polymorphism (rs8192678) within the PPARGC1A gene and its association with the increased risk of NAFLD in Iranian patients with type 2 diabetes. A total of 145 NAFLD patients with a history of type 2 diabetes and 145 healthy control subjects were included in the study. Gly482Ser polymorphism genotyping was done using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique. The results showed a significant difference between the PPARGC1A Gly482Serpolymorphism in NAFLD patients and the healthy controls. Accordingly, the AA genotype and A allele were increased in the NAFLD patients when compared to the healthy controls. However, no significant correlation was observed between the Gly482Ser polymorphism and the physiological and biochemical parameters. Based on the results, the AA genotype, which is associated with the insertion of Ser, can be considered as a risk factor for the development of NAFLD in Iranian patients with diabetes type 2.


[Cyclic 3,5-adenosine monophosphate content and calcium transport in the aorta in hypertension due to experimental renal insufficiency].
The calcium, magnesium, and cyclic AMP content and 45Ca transport in the aorta and iliac artery and the mechanical properties of these vessels were studied in rats with experimental renal insufficiency. The development of hypertension was attended by an increase in the magnesium content in the vascular wall, a certain decrease in the cyclic AMP level, marked disturbance of 45Ca transport, and changes in the mechanical properties of the vascular wall. The use of dihydrotachysterol or a complex of sex steroids which correct calcium metabolism led to a decrease of arterial hypertension. It is suggested that disorder of calcium metabolism in chronic renal insufficiency plays an essential role in the inadequate regulation of the vascular tone and the development of hypertension.


The media-driven risk society, the anti-vaccination movement and risk of autismo.
Marked changes have been seen in the epidemiological profile of infectious diseases among middle-class families in industrialized countries due to beliefs related to the risks of vaccination. These beliefs are proliferating globally due to internet sites, blogs and the influence of celebrities in the mass communication media. Due to the complexity of a cultural phenomenon of this nature, contemporary concepts aligned to the idea of reflexivity in the risk society are analyzed. The concept of a receptive media-driven society in which the announcement of danger and protection in mutual reference and contradiction are also assessed. The frequent emergence of tensions derived from cycles of utterances and baseless comments construed as symbolic "biovalues" are discussed. The persistent effect of threatening biotechnological and fraudulent utterances has influenced virtual networks for almost three decades, supporting the debate about the connection between autism and vaccines. The conclusion reached is that the processes of production of significance interconnect at various levels in which representations circulate that support communication and group identity based on historical and cultural references.


Improved electroporation buffer enhances transient gene expression in Arachis hypogaea protoplasts.
An electroporation medium containing 50 mM glycine or 10 mM glycylglycine (glygly), 70 mM potassium glutamate, and 0.4 M mannitol was evaluated for its ability to improve transient β-glucuronidase (GUS) expression in immature cotyledonary protoplasts of Arachis hypogaea L. GUS activity in electroporated protoplasts was 8- to 430-fold greater than that obtained using any of other four commonly employed poration media. Analysis of viability and histochemical staining of protoplasts indicated that electroporation using the glycine- or glygly-based poration medium resulted in increased protoplast viability and GUS expression when compared with other poration media. Replacement of glygly with MES or HEPES buffers significantly reduced the level of GUS expression in electroporated protoplasts.


BACE is degraded via the lysosomal pathway.
Amyloid plaques are formed by aggregates of amyloid-beta-peptide, a 37-43-amino acid fragment (primarily Abeta(40) and Abeta(42)) generated by proteolytic processing of the amyloid precursor protein (APP) by beta- and gamma-secretases. A type I transmembrane aspartyl protease, BACE (beta-site APP cleaving enzyme), has been identified to be the beta-secretase. BACE is targeted through the secretory pathway to the plasma membrane where it can be internalized to endosomes. The carboxyl terminus of BACE contains a di-leucine-based signal for sorting of transmembrane proteins to endosomes and lysosomes. In this study, we set out to determine whether BACE is degraded by the lysosomal pathway and whether the di-leucine motif is necessary for targeting BACE to the lysosomes. Here we show that lysosomal inhibitors, chloroquine and NH(4)Cl, lead to accumulation of endogenous and ectopically expressed BACE in a variety of cell types, including primary neurons. Furthermore, the inhibition of lysosomal hydrolases results in the redistribution and accumulation of BACE in the late endosomal/lysosomal compartments (lysosome-associated membrane protein 2 (LAMP2)-positive). In contrast, the BACE-LL/AA mutant, in which Leu(499) and Leu(500) in the COOH-terminal sequence (DDISLLK) were replaced by alanines, only partially co-localized with LAMP2-positive compartments following inhibition of lysosomal hydrolases. Collectively, our data indicate that BACE is transported to the late endosomal/lysosomal compartments where it is degraded via the lysosomal pathway and that the di-leucine motif plays a role in sorting BACE to lysosomes.


Does the local food environment around schools affect diet? Longitudinal associations in adolescents attending secondary schools in East London.
The local retail food environment around schools may act as a potential risk factor for adolescent diet. However, international research utilising cross-sectional designs to investigate associations between retail food outlet proximity to schools and diet provides equivocal support for an effect. In this study we employ longitudinal perspectives in order to answer the following two questions. First, how has the local retail food environment around secondary schools changed over time and second, is this change associated with change in diet of students at these schools? The locations of retail food outlets and schools in 2001 and 2005 were geo-coded in three London boroughs. Network analysis in a Geographic Information System (GIS) ascertained the number, minimum and median distances to food outlets within 400 m and 800 m of the school location. Outcome measures were 'healthy' and 'unhealthy' diet scores derived from adolescent self-reported data in the Research with East London Adolescents: Community Health Survey (RELACHS). Adjusted associations between distance from school to food retail outlets, counts of outlets near schools and diet scores were assessed using longitudinal (2001-2005 n=757) approaches. Between 2001 and 2005 the number of takeaways and grocers/convenience stores within 400 m of schools increased, with many more grocers reported within 800 m of schools in 2005 (p< 0.001). Longitudinal analyses showed a decrease of the mean healthy (-1.12, se 0.12) and unhealthy (-0.48, se 0.16) diet scores. There were significant positive relationships between the distances travelled to grocers and healthy diet scores though effects were very small (0.003, 95%CI 0.001 - 0.006). Significant negative relationships between proximity to takeaways and unhealthy diet scores also resulted in small parameter estimates. The results provide some evidence that the local food environment around secondary schools may influence adolescent diet, though effects were small. Further research on adolescents' food purchasing habits with larger samples in varied geographic regions is required to identify robust relationships between proximity and diet, as small numbers, because of confounding, may dilute effect food environment effects. Data on individual foods purchased in all shop formats may clarify the frequent, overly simple classification of grocers as 'healthy'.


Alveolar recruitment in pulmonary contusion: case report and literature review.
Treatment of pulmonary contusion when adequately established is very simple in most cases. Pathophysiological changes occur as a result of the effects produced by loss of chest wall integrity, accumulation of fluid in the pleural cavity, obstruction of the airways and lung dysfunction. The alveolar recruitment maneuver is the reopening of collapsed lung areas by increasing inspiratory pressure in the airway. The primary objective of this case report was to evaluate the effectiveness of the alveolar recruitment maneuver in a patient with pulmonary contusion. A 33 year old male patient, with a clinical condition of bilateral chest trauma and traumatic brain injury, evolved with reduction of the level of consciousness, acute respiratory failure, hypovolemic shock and hemoptysis. The patient underwent thoracentesis, bilateral thoracic drainage and was also submitted to invasive mechanical ventilation. After 48 hours of invasive mechanical ventilation, in accordance with protective strategy an alveolar recruitment maneuver mode, pressure-controlled ventilation, pressure controlled 10 cmH2O, respiratory rate 10 rpm, inspiratory time 3.0, positive end-expiratory pressure 30 cmH2O and FI0(2) 100%, for two minutes. After the alveolar recruitment maneuver, the patient presented clinical pulmonary improvement, but there was a variation of 185 to 322 of Pa0(2)/FiO2 (arterial partial pressure of oxygen/ fraction of inspired oxygen). He was discharged from the intensive care unit 22 days after admission. The alveolar recruitment maneuver in this patient showed significant results in the treatment of pulmonary contusion, improving blood oxygenation, preventing alveolar collapse and reversing atelectasis.


Paediatric antiretroviral overdose: A case report from a resource-poor area.
Toxic side effects from antiretroviral overdose in children have not been widely reported. Antiretroviral drugs are widely used as oral medications throughout sub-Saharan Africa. We describe the clinical presentation and management of a 3-year-old male in rural Kenya, who accidentally overdosed on abacavir/lamivudine combination pills. The number of pills taken was approximately 250 tablets, that is 15 g of abacavir and 7.5 g of lamivudine. He presented 24 hours later to Homabay County Referral Hospital, with unresponsiveness, inability to feed and absence of playfulness. Physical examination revealed a sick-looking, 'unconscious' child, responding only to voice, with tachycardia, hypertension and moderate dehydration. He was managed conservatively with rehydration, namely intravenous 1125 mL of 5% dextrose in 0.9% saline, and the monitoring of his neurologic status, urine output and all vital signs. He regained normal neurological function after 24 hours, and recovered uneventfully, but was lost to follow-up. In an area endemic for HIV and where antiretroviral drug use is commonplace, there is a need for health education to ensure that parents keep drugs out of the reach of children. In the case of a suspected overdose, parents need to be reminded to seek medical attention immediately. Physician awareness of the clinical presentation, management and challenges with an antiretroviral drug overdose is also important.


A novel allele of Alx4 results in reduced Fgf10 expression and failure of eyelid fusion in mice.
Normal fusion of developing eyelids requires coordination of inductive signals from the eyelid mesenchyme with migration of the periderm cell layer and constriction of the eyelids across the eye. Failure of this process results in an eyelids open at birth (EOB) phenotype in mice. We have identified a novel spontaneous allele of Alx4 that displays EOB, in addition to polydactyly and cranial malformations. Alx4 is expressed in the eyelid mesenchyme prior to and during eyelid fusion in a domain overlapping the expression of genes that also play a role in normal eyelid development. We show that Alx4 mutant mice have reduced expression of Fgf10, a key factor expressed in the mesenchyme that is required for initiation of eyelid fusion by the periderm. This is accompanied by a reduced number of periderm cells expressing phosphorylated c-Jun, consistent with the incomplete ablation of Fgf10 expression. Together, these data demonstrate that eyelid fusion in mice requires the expression of Alx4, accompanied by the loss of normal expression of essential components of the eyelid fusion pathway.


Molecular characterization and inhibition analysis of the acetylcholinesterase gene from the silkworm maggot, Exorista sorbillans.
Several organophosphorus (OP) insecticides can selectively kill the silkworm maggot, Exorista sorbillans (Es) (Diptera: Tachinidae), while not obviously affecting the host (Bombyx mori) larvae, but the mechanism is not yet clear. In this study, the cDNA encoding an acetylcholinesterase (AChE) from the field Es was isolated. One point mutation (Gly353Ala) was identified. The Es-353G AChE and Es-353A AChE were expressed in baculovirus- insect cell system, respectively. The inhibition results showed that for eserine and Chlorpyrifos, Es-353A AChE was significantly less sensitive than Es-353G AChE. Meanwhile, comparison of the I(50) values of eserine, dichlorvos, Chlorpyrifos and omethoate of recombinant Es AChEs with its host (Bombyx mori) AChEs indicated that, both Es AChEs are more sensitive than B. mori AChEs. The results give an insight of the mechanism that some OP insecticides can selectively kills Es while without distinct effect on its host, B. mori.


Shared liking and association valence for representational art but not abstract art.
We examined the finding that aesthetic evaluations are more similar across observers for representational images than for abstract images. It has been proposed that a difference in convergence of observers' tastes is due to differing levels of shared semantic associations (Vessel & Rubin, 2010). In Experiment 1, student participants rated 20 representational and 20 abstract artworks. We found that their judgments were more similar for representational than abstract artworks. In Experiment 2, we replicated this finding, and also found that valence ratings given to associations and meanings provided in response to the artworks converged more across observers for representational than for abstract art. Our empirical work provides insight into processes that may underlie the observation that taste for representational art is shared across individual observers, while taste for abstract art is more idiosyncratic.


Development of allele-specific therapeutic siRNA in Meesmann epithelial corneal dystrophy.
Meesmann epithelial corneal dystrophy (MECD) is an inherited eye disorder caused by dominant-negative mutations in either keratins K3 or K12, leading to mechanical fragility of the anterior corneal epithelium, the outermost covering of the eye. Typically, patients suffer from lifelong irritation of the eye and/or photophobia but rarely lose visual acuity; however, some individuals are severely affected, with corneal scarring requiring transplant surgery. At present no treatment exists which addresses the underlying pathology of corneal dystrophy. The aim of this study was to design and assess the efficacy and potency of an allele-specific siRNA approach as a future treatment for MECD. We studied a family with a consistently severe phenotype where all affected persons were shown to carry heterozygous missense mutation Leu132Pro in the KRT12 gene. Using a cell-culture assay of keratin filament formation, mutation Leu132Pro was shown to be significantly more disruptive than the most common mutation, Arg135Thr, which is associated with typical, mild MECD. A siRNA sequence walk identified a number of potent inhibitors for the mutant allele, which had no appreciable effect on wild-type K12. The most specific and potent inhibitors were shown to completely block mutant K12 protein expression with negligible effect on wild-type K12 or other closely related keratins. Cells transfected with wild-type K12-EGFP construct show a predominantly normal keratin filament formation with only 5% aggregate formation, while transfection with mutant K12-EGFP construct resulted in a significantly higher percentage of keratin aggregates (41.75%; p<0.001 with 95% confidence limits). The lead siRNA inhibitor significantly rescued the ability to form keratin filaments (74.75% of the cells contained normal keratin filaments; p<0.001 with 95% confidence limits). This study demonstrates that it is feasible to design highly potent siRNA against mutant alleles with single-nucleotide specificity for future treatment of MECD.


A computational method for assessing peptide- identification reliability in tandem mass spectrometry analysis with SEQUEST.
High-throughput protein identification in mass spectrometry is predominantly achieved by first identifying tryptic peptides by a database search and then by combining the peptide hits for protein identification. One of the popular tools used for the database search is SEQUEST. Peptide identification is carried out by selecting SEQUEST hits above a specified threshold, the value of which is typically chosen empirically in an attempt to separate true identifications from false ones. These SEQUEST scores are not normalized with respect to the composition, length and other parameters of the peptides. Furthermore, there is no rigorous reliability estimate assigned to the protein identifications derived from these scores. Hence, the interpretation of SEQUEST hits generally requires human involvement, making it difficult to scale up the identification process for genome-scale applications. To overcome these limitations, we have developed a method, which combines a neural network and a statistical model, for normalizing SEQUEST scores, and also for providing a reliability estimate for each SEQUEST hit. This method improves the sensitivity and specificity of peptide identification compared to the standard filtering procedure used in the SEQUEST package, and provides a basis for estimating the reliability of protein identifications.


The ambiguities of Indonesian Sustainable Palm Oil certification: internal incoherence, governance rescaling and state transformation.
There are persistent tensions of both a technical and political nature between Southeast Asia's two major palm oil producers, Indonesia and Malaysia, and the sustainability governance mechanisms shaping global environmental and trade standards emerging from Europe. The establishment of the national Indonesian Sustainable Palm Oil (ISPO) certification standard in 2011 is a sign of discontent with the transnational Roundtable on Sustainable Palm Oil (RSPO) regime, sparking debate about the legitimacy of private governance models initiated by non-governmental organizations and companies in Europe. This article questions whether the adoption of sustainability norms by Indonesia signals normative convergence or the emergence of rival governance structures that challenge the state. Evidence suggests that elements of norm adoption and rival governance coexist in Indonesia and that ISPO certification is an ambiguous policy with degrees of internal incoherence. The ambiguous nature of ISPO certification gives rise to unresolved disputes over power and authority between various actors. This article shows how these disputes came into being by framing these dynamics as part of a long historical process. Novel insights are gained by employing the state transformation framework and the concept of governance rescaling. Within this framework, we argue that the ambiguous nature of the ISPO results from complex interrelated processes of fragmentation, decentralization and the internationalization of the Indonesian state.


Prognostic factors of survival in head and neck cancer patients treated with surgery and postoperative radiation therapy.
Given that radiation therapy (RT) is currently initiated as soon as possible after surgery, our results indicate that the main prognostic factors of survival are pT and pN stages in patients treated with surgery and postoperative RT for locally advanced head and neck squamous cell carcinoma (HNSCC). To determine the prognostic factors for survival in patients treated with surgery and postoperative RT for locally advanced HNSCC. A retrospective study was performed on 308 consecutive patients treated from 1990 to 1998 with surgery and postoperative RT. In addition to histological factors, time-related factors were considered. The median age of the whole cohort was 56 years (range 35-83). Median follow-up was 98 months. Median interval from surgery to the start of RT was 44 days (range 18-157), while median RT duration was 52 days (range 22-115). From univariate analysis of overall survival, statistically significant prognostic factors were pT stage (p<0.0001), pN stage (p=0.008), RT duration (p=0.01) and total treatment time (p=0.02). Perineural invasion, perivascular invasion, extranodal spread and positive resection margins did not appear to be related to survival. From multivariate analysis, the only statistically independent prognostic factors appeared to be pT and pN stages.


Identification and characterisation of a hyper-variable apoplastic effector gene family of the potato cyst nematodes.
Sedentary endoparasitic nematodes are obligate biotrophs that modify host root tissues, using a suite of effector proteins to create and maintain a feeding site that is their sole source of nutrition. Using assumptions about the characteristics of genes involved in plant-nematode biotrophic interactions to inform the identification strategy, we provide a description and characterisation of a novel group of hyper-variable extracellular effectors termed HYP, from the potato cyst nematode Globodera pallida. HYP effectors comprise a large gene family, with a modular structure, and have unparalleled diversity between individuals of the same population: no two nematodes tested had the same genetic complement of HYP effectors. Individuals vary in the number, size, and type of effector subfamilies. HYP effectors are expressed throughout the biotrophic stages in large secretory cells associated with the amphids of parasitic stage nematodes as confirmed by in situ hybridisation. The encoded proteins are secreted into the host roots where they are detectable by immunochemistry in the apoplasm, between the anterior end of the nematode and the feeding site. We have identified HYP effectors in three genera of plant parasitic nematodes capable of infecting a broad range of mono- and dicotyledon crop species. In planta RNAi targeted to all members of the effector family causes a reduction in successful parasitism.


Exploring the cooccurrence patterns of multiple sets of genomic intervals.
Exploring the spatial relationship of different genomic features has been of great interest since the early days of genomic research. The relationship sometimes provides useful information for understanding certain biological processes. Recent advances in high-throughput technologies such as ChIP-seq produce large amount of data in the form of genomic intervals. Most of the existing methods for assessing spatial relationships among the intervals are designed for pairwise comparison and cannot be easily scaled up. We present a statistical method and software tool to characterize the cooccurrence patterns of multiple sets of genomic intervals. The occurrences of genomic intervals are described by a simple finite mixture model, where each component represents a distinct cooccurrence pattern. The model parameters are estimated via an EM algorithm and can be viewed as sufficient statistics of the cooccurrence patterns. Simulation and real data results show that the model can accurately capture the patterns and provide biologically meaningful results. The method is implemented in a freely available R package giClust. The method and the software provide a convenient way for biologists to explore the cooccurrence patterns among a relatively large number of sets of genomic intervals.


Multiresolution foveated laparoscope with high resolvability.
A key limitation of the state-of-the-art laparoscopes for minimally invasive surgery is the tradeoff between the field of view and spatial resolution in a single-view camera system. As such, surgical procedures are usually performed at a zoomed-in view, which limits the surgeon's ability to see much outside the immediate focus of interest and causes a situational awareness challenge. We proposed a multiresolution foveated laparoscope (MRFL) aiming to address this limitation. The MRFL is able to simultaneously capture wide-angle overview and high-resolution images in real time; it can scan and engage the high-resolution images to any subregion of the entire surgical field in analogy to the fovea of human eye. The MRFL is able to render equivalently 10 million pixel resolution with a low data bandwidth requirement. The system has a large working distance (WD) from 80 to 180 mm. The spatial resolvability is about 45 μm in the object space at an 80 mm WD, while the resolvability of a conventional laparoscope is about 250 μm at a typically 50 mm surgical distance.


Neurologic services in the nations of Africa.
To define the current state of neurologic health care services in the nations of Africa. A survey on neurologic services was prepared in English, French, and Portuguese and sent to representatives of 53 of 53 African nations. Representatives for each country were identified first through the Pan African Association of Neurologic Sciences, followed by the World Federation of Neurology and the World Health Organization (WHO). If these representatives did not return survey results, contacts were attempted through officials in the embassies in Washington, DC, or Addis Ababa, Ethiopia, or local ministries of health. Surveys were received from representatives of 38 (71.7%) of the 53 African nations. Data from the WHO were added for 12 nations, resulting in information on 50 (94.3%) of the 53 nations. The nations were divided into four categories according to the number of neurologists per nation. Group A (>10 neurologists/country) included 11 nations, averaging 711,856 population per neurologist. Group B (5 to 10 neurologists/country) included five nations, averaging 1,612,039 population per neurologist. Group C (1 to 4 neurologists/country) included 23 nations, averaging 5,099,908 population per neurologist. Group D included 12 nations with a total population of 25,939,273 that reported having no neurologists. The level of training, presence of local training programs, ancillary equipment, and practice setting options decreased progressively from Group A to Group D. The population/neurologist ratio in all African nations far exceeds that of the United States and other developed nations. Neurologic services in the African nations range from no formal care at all to established neurologic care with residency training and ancillary equipment.


NPM-ALK Is a Key Regulator of the Oncoprotein FOXM1 in ALK-Positive Anaplastic Large Cell Lymphoma.
Forkhead Box M1 (FOXM1) is an oncogenic transcription factor implicated in the pathogenesis of solid and hematologic cancers. In this study, we examined the significance of FOXM1 in NPM-ALK-positive anaplastic large cell lymphoma (NPM-ALK + ALCL), with a focus on how it interacts with NPM-ALK, which is a key oncogenic driver in these tumors. FOXM1 was expressed in NPM-ALK + ALCL cell lines (5/5), patient samples (21/21), and tumors arising in NPM-ALK transgenic mice (4/4). FOXM1 was localized in the nuclei and confirmed to be transcriptionally active. Inhibition of FOXM1 in two NPM-ALK + ALCL cells using shRNA and pharmalogic agent (thiostrepton) resulted in reductions in cell growth and soft-agar colony formation, which were associated with apoptosis and cell-cycle arrest. FOXM1 is functionally linked to NPM-ALK, as FOXM1 enhanced phosphorylation of the NPM-ALK/STAT3 axis. Conversely, DNA binding and transcriptional activity of FOXM1 was dependent on the expression of NPM-ALK. Further studies showed that this dependency hinges on the binding of FOXM1 to NPM1 that heterodimerizes with NPM-ALK, and the phosphorylation status of NPM-ALK. In conclusion, we identified FOXM1 as an important oncogenic protein in NPM-ALK+ ALCL. Our results exemplified that NPM-ALK exerts oncogenic effects in the nuclei and illustrated a novel role of NPM1 in NPM-ALK pathobiology.


Harmonization and Visualization of Data from a Transnational Multi-Sensor Personal Exposure Campaign.
Use of a multi-sensor approach can provide citizens with holistic insights into the air quality of their immediate surroundings and their personal exposure to urban stressors. Our work, as part of the ICARUS H2020 project, which included over 600 participants from seven European cities, discusses the data fusion and harmonization of a diverse set of multi-sensor data streams to provide a comprehensive and understandable report for participants. Harmonizing the data streams identified issues with the sensor devices and protocols, such as non-uniform timestamps, data gaps, difficult data retrieval from commercial devices, and coarse activity data logging. Our process of data fusion and harmonization allowed us to automate visualizations and reports, and consequently provide each participant with a detailed individualized report. Results showed that a key solution was to streamline the code and speed up the process, which necessitated certain compromises in visualizing the data. A thought-out process of data fusion and harmonization of a diverse set of multi-sensor data streams considerably improved the quality and quantity of distilled data that a research participant received. Though automation considerably accelerated the production of the reports, manual and structured double checks are strongly recommended.


Experience-dependent changes in spatiotemporal properties of cutaneous inputs remodel somatosensory cortical maps following skin flap rotation.
Contiguous skin surfaces that tend to be synchronously stimulated are represented in neighbouring sectors of primary somatosensory maps. Moreover, neuronal receptive fields (RFs) are reshaped through ongoing competitive/cooperative interactions that segregate/desegregate inputs converging onto cortical neuronal targets. The present study was designed to evaluate the influence of spatio-temporal constraints on somatotopic map organization. A vascularized and innervated pedicle flap of the ventrum skin bearing nipples was rotated by 180 degrees . Electrophysiological maps of ventrum skin were elaborated in the same rats at 24 h after surgery and 2 weeks after parturition. Neurones with split RFs resulting from the surgical separation of formerly adjoining skin surfaces were more numerous in non-nursing than nursing rats. RFs that included newly adjacent skin surfaces on both sides of the scar line emerged in nursing rats, suggesting that the spatial contiguity of formerly separated skin surfaces induced a fusion of their cortical representations through nursing-induced stimulation. In addition, nursing-dependent inputs were found to reincorporate the rotated skin flap representation in an updated topographical organization of the cortical map. A skin territory including recipient and translocated skin areas was costimulated for 7 h, using a brushing device. Neural responses evoked by a piezoelectric-induced skin indentation before and after skin brushing confirmed the emergence of RFs crossing the scar line and contraction of non-brushed components of split RFs. Our findings provide further evidence that the spatiotemporal structure of sensory inputs changing rapidly or evolving in a natural context is critical for experience-dependent reorganization of cortical map topography.


Synthesis, characterization and catalytic performance of nanostructured dysprosium molybdate catalyst for selective biomolecule detection in biological and pharmaceutical samples.
The current study reports a new, simple and fast method using a flake-like dysprosium molybdate (Dy2MoO6; FL-DyM) nanostructured material to detect the antibiotic drug metronidazole (METZ). This nanocomposite material was employed on the surface of a glassy carbon electrode (GCE) to develop the electrode (FL-DyM/GCE). Further, the synthesized FL-DyM was systematically characterized by powder X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray diffraction (EDS), elemental mapping, X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) analyses. Cyclic (CV) and differential pulse voltammetry (DPV) techniques were used to study the electrochemical properties. The FL-DyM/GCE-based sensor demonstrated excellent selectivity and sensitivity for the detection of the drug METZ, which could be attributed to the strong affinity of FL-DyM towards the -NO2 group in METZ, and the good electrocatalytic activity and conductivity of FL-DyM. The fabrication and optimization of the working electrode were accomplished with CV and DPV obtained by scan rate and pH studies. Compared to the bare GCE and other rare-earth metal molybdates, the FL-DyM/GCE sensor displayed a superior electrocatalytic activity response for METZ detection. The sensor demonstrated a good linear relationship over the concentration range of 0.01-2363 μM. The quantification and detection limits were found to be 0.010 μM and 0.0030 μM, respectively. The FL-DyM/GCE sensor displayed excellent selectivity, repeatability, reproducibility, and stability for the detection of METZ in human urine and commercial METZ tablet samples, which validates the new technique for efficient drug sensing in practical applications.


Older men display elevated levels of senescence-associated exercise-responsive CD28null angiogenic T cells compared with younger men.
Aging is associated with elevated cardiovascular disease risk. As a result of aging, endothelial dysfunction develops, partly due to a reduction in vascular regenerative ability. CD31+ T cells (angiogenic T cells; TANG ) possess highly angiogenic capabilities; however, these cells are significantly reduced in older populations. In addition, older populations possess significantly higher senescent and highly differentiated T-cell levels in circulation, and these are reported to be highly exercise responsive. We investigated whether older adults display greater levels of circulating senescent (CD28null ) TANG cells and whether these cells were more exercise responsive than CD28+ TANG cells. Young (18-25 years; n = 9) and older (60-75 years; n = 10) healthy men undertook a 30-min cycling bout at 70% V˙O2 peak, with circulating TANG cells (CD3+ CD31+ CD28+/null ; including CD4+ and CD8+ subsets) measured preexercise, postexercise, and 1 h post exercise by flow cytometry. Older adults displayed reduced basal levels of TANG cells (mean ± SEM: 410 ± 81 vs. 784 ± 118 cells·μL, P = 0.017), despite a greater proportion of these cells being CD28null (26.26 ± 5.08 vs. 13.36 ± 2.62%, P = 0.044). Exercise significantly increased the circulating number of TANG cells in both young and older men. However, in older men alone, exercise preferentially mobilized CD28null CD8+ TANG cells compared with CD28+ TANG cells (time × phenotype interaction: P = 0.022; Δ74 ± 29 vs. Δ27 ± 15 cells·μL, P = 0.059), with no such difference observed between these phenotypes in the young population. In conclusion, this is the first study to demonstrate that despite observing lower circulating numbers of TANG cells, older adults display greater levels of senescent TANG cells in comparison with younger individuals, and these cells are more exercise responsive than CD28+ TANG cells. Lower number of circulating TANG and greater levels of senescent-associated CD28null TANG may contribute to greater CVD risk with advancing age.


No Structural Differences Are Revealed by VBM in 'De Novo' Parkinsonian Patients.
The identification of brain morphological alterations in newly diagnosed PD patients (i.e. 'de novo') could potentially serve as a biomarker and accelerate diagnosis. However, presently no consensus exists in the literature possibly due to several factors: small size cohorts, differences in segmentation techniques or bad control of false positive rates. In this study, we use the CAT12 pipeline, to seek for morphological brain differences in gray and white matter of 66 controls and 144 de novo PD patients from the PPMI database. Moreover, we search for subcortical structure differences using the VolBrain pipeline. We found no structural brain differences in this de novo Parkinsonian population, neither in tissues using a whole brain analysis nor in any of nine subcortical structures analyzed separately. We conclude that some results published in the literature may appear as false positives and we contest their reproductibility.


Toward Equity in Research on Intellectual and Developmental Disabilities.
Lack of diversity in IDD research is typically conceptualized only in terms of (1) recruitment of samples that do not appropriately represent the sociodemographics of the population, or (2) the limited number of researchers from historically marginalized backgrounds. Critically, the field also suffers from over-reliance on perspectives and social systems of dominant culture-both in how disability is regarded and in relation to other dimensions of identity and culture. These lenses lead to research findings that reinforce, rather than reduce, social inequities. We propose a framework that minimizes reliance on diagnostic categories, shifts from deficit- to person-centered models, acknowledges people's multiple identities, and includes self-advocates and diverse communities as partners in the research enterprise. The systems change necessary to support this framework is described.


[Pediatric asthma control and quality of life questionnaires].
The assessment of symptoms and quality of life are important aspects in the control of childhood asthma. Questionnaires regarding symptoms control and quality of life give valuable information about the disease from the perspective of the child and his family. The aim of this study is to discuss the most important characteristics of this type of questionnaire such as age range, language of validation, number of questions, administration mode, the evaluated period and fields, and the minimum clinically relevant difference. The ACT questionnaires, for children older than 11 years of age, and CAN questionnaires, for children between 2 and 14 years of age in their Spanish versions, are suitable for measuring asthma control in our country. Regarding quality of life, PAQLQ for children between 7 and 17 years of age and PACQLQ for their care givers are the most popular oversees; Spanish versions have been adapted for Chile.


How energy conservation limits our measurements.
Observations in quantum mechanics are subject to complex restrictions arising from the principle of energy conservation. Determining such restrictions, however, has been so far an elusive task, and only partial results are known. In this Letter, we discuss how constraints on the energy spectrum of a measurement device translate into limitations on the measurements which we can effect on a target system with a nonconstant energy operator. We provide efficient algorithms to characterize such limitations and, in case the target is a two-level quantum system, we quantify them exactly. Our Letter, thus, identifies the boundaries between what is possible or impossible to measure, i.e., between what we can see or not, when energy conservation is at stake.


Subtle genetic changes enhance virulence of methicillin resistant and sensitive Staphylococcus aureus.
Community acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) increasingly causes disease worldwide. USA300 has emerged as the predominant clone causing superficial and invasive infections in children and adults in the USA. Epidemiological studies suggest that USA300 is more virulent than other CA-MRSA. The genetic determinants that render virulence and dominance to USA300 remain unclear. We sequenced the genomes of two pediatric USA300 isolates: one CA-MRSA and one CA-methicillin susceptible (MSSA), isolated at Texas Children's Hospital in Houston. DNA sequencing was performed by Sanger dideoxy whole genome shotgun (WGS) and 454 Life Sciences pyrosequencing strategies. The sequence of the USA300 MRSA strain was rigorously annotated. In USA300-MRSA 2658 chromosomal open reading frames were predicted and 3.1 and 27 kilobase (kb) plasmids were identified. USA300-MSSA contained a 20 kb plasmid with some homology to the 27 kb plasmid found in USA300-MRSA. Two regions found in US300-MRSA were absent in USA300-MSSA. One of these carried the arginine deiminase operon that appears to have been acquired from S. epidermidis. The USA300 sequence was aligned with other sequenced S. aureus genomes and regions unique to USA300 MRSA were identified. USA300-MRSA is highly similar to other MRSA strains based on whole genome alignments and gene content, indicating that the differences in pathogenesis are due to subtle changes rather than to large-scale acquisition of virulence factor genes. The USA300 Houston isolate differs from another sequenced USA300 strain isolate, derived from a patient in San Francisco, in plasmid content and a number of sequence polymorphisms. Such differences will provide new insights into the evolution of pathogens.


Endoscopic sinus surgery in patients older than sixty.
Rhinosinusitis is the sixth most common chronic condition of the elderly. Functional endoscopic sinus surgery (FESS) has developed over the last 20 to 30 years into a widely accepted treatment modality for chronic rhinosinusitis in adults who have failed maximal medical management. The aim of this study was investigate the safety and efficacy of FESS in the geriatric population as compared to that of the adult population. Retrospective review of prospective measurement of outcomes in consecutive patients over 60 years of age who underwent FESS. Fifty-six patients over 60 years of age underwent FESS and were evaluated preoperatively and postoperatively at 3, 6, and 12 months with the Sino-Nasal Outcome Test-20 (SNOT-20) questionnaire, and a rigid nasal endoscopy scoring system. Data analysis was performed using the Student's t test to compare mean scores. Any complications were noted. Patients evaluated by the SNOT-20 scoring system experienced 64% improvement of symptom scores at 3 months, 73% improvement at 6 months, and 75% improvement at 12 months. Rigid nasal endoscopy scores improved by 76% at 3 months, 65% at 6 months, and 76% at 12 months. There were very few minor complications and no major complications of the surgery. These results are comparable to those of the literature that address outcomes in the adult population undergoing FESS. FESS in the geriatric population is a safe and effective treatment modality for rhinosinusitis that is refractory to medical therapy. C.


Influence of chronic moderate sleep restriction and exercise on inflammation and carcinogenesis in mice.
The effects of chronic moderate sleep restriction and exercise training on carcinogenesis were examined in adenomatous polyposis coli multiple intestinal neoplasma (APC Min(+/-)) mice, a genetic strain which is predisposed to developing adenomatous polyposis. The mice were randomized to one of four 11 week treatments in a 2×2 design involving sleep restriction (by 4 h/day) vs. normal sleep and exercise training (1h/day) vs. sedentary control. Wild-type control mice underwent identical experimental treatments. Compared with the wild-type mice, APC Min(+/-) mice had disrupted hematology and enhanced pro-inflammatory cytokine production from peritoneal exudate cells. Among the APC Min(+/-) mice, consistent interactions of sleep loss and exercise were found for measures of polyp formation, inflammation, and hematology. Sleep loss had little effect on these variables under sedentary conditions, but sleep loss had clear detrimental effects under exercise conditions. Exercise training resulted in improvements in these measures under normal sleep conditions, but exercise tended to elicit no effect or to exacerbate the effects of sleep restriction. Significant correlations of inflammation with polyp burden were observed. Among wild-type mice, similar, but less consistent interactions of sleep restriction and exercise were found. These data suggest that the benefits of exercise on carcinogenesis and immune function were impaired by chronic moderate sleep restriction, and that harmful effects of sleep restriction were generally realized only in the presence of exercise.


D-tagatose, a novel hexose: acute effects on carbohydrate tolerance in subjects with and without type 2 diabetes.
D-Tagatose (D-tag), a hexose bulk sweetener, does not affect plasma glucose levels when orally administered to rodents. Additionally, D-tag attenuates the rise in plasma glucose after mice are administered oral sucrose. The current study was undertaken to investigate the acute glycaemic effects of oral D-tag alone or in combination with oral glucose in human subjects with and without type 2 diabetes mellitus. Glycaemic responses to D-tag also were investigated in subjects after oral sucrose to examine whether the glucose-lowering effects of D-tag in rodents may result from a direct inhibition of intestinal disaccharidases. Eight normal and eight subjects with diabetes mellitus were administered 75 g of glucose, 75 g of D-tag, or 75 g of D-tag 30 min prior to a 75 g oral glucose tolerance test (OGTT). Five patients with diabetes mellitus were challenged with a 75 g oral sucrose tolerance test (OSTT) with and without oral pre-treatment with 75 g of D-tag. Patients with diabetes mellitus also received separate 0, 10, 15, 20 and 30 g of D-tag 30 min prior to a 75 g OGTT. Oral loading with D-tag alone led to no changes in glucose or insulin levels in either normal patients or those with diabetes mellitus. Pre-OGTT treatment with 75 g D-tag, however, attenuated the rise in glucose levels in patients with diabetes mellitus (p < 0.02 at 60 and 180 min, and p < 0.01 at 120 min). The glucose area under the curve (AUC) was reduced significantly also by pre-treatment with D-tag in a dose-dependent manner in patients with diabetes mellitus (p < 0.05 for 10 g D-tag, p < 0.001 for 20 g D-tag, and p = 0.0001 for 30 g D-tag). In patients with diabetes mellitus 75 g D-tag similarly attenuated the rise in glucose following an OSTT (p < 0.01 at 30 min, and p < 0.02 at 60 min). Pre-treatment with 75 g D-tag also tended to blunt the rise in insulin following an OGTT in normal patients (p = 0.07 for insulin AUC) but not patients with diabetes mellitus (p = 0.66). Following 75 g of oral D-tag in four normal patients, plasma D-tag levels rose to a mean peak level of 3.6 mg/dl at 90 min. The administration of 75 g D-tag led to diarrhoea, nausea and/or flatulence in 100% of subjects. When D-tag was administered at lower doses ranging from 10 g to 30 g, only three of 10 patients with diabetes mellitus had gastrointestinal symptoms which were much more mild than those evoked by 75 g D-tag. These results show that oral D-tag significantly blunts the rise in plasma glucose seen after oral glucose in patients with diabetes mellitus in a dose-dependent manner without significantly affecting insulin levels. The minimal elevation of plasma D-tag levels in normal patients and the adverse gastrointestinal effects seen following larger doses of D-tag support poor absorption of this hexose and suggest that D-tag may act by attenuating glucose absorption in the intestine. D-tag may be a useful therapeutic adjunct in the management of type 2 diabetes mellitus.


Alpers' syndrome presenting with seizures and multiple stroke-like episodes in a 17-year-old male.
Alpers' syndrome is a progressive neurodegenerative disorder with liver disease that usually presents in the first few years of life. Only rarely have patients presented later in life with delayed onset of Alpers' syndrome. Herein we present a case of a 17-year-old male with a progressive 8-month course of severe headaches, multiple stroke-like episodes with visual deficits, and seizures that concluded with acute hemorrhagic pancreatitis. Neuropathological findings were characteristic for Alpers' syndrome: neurodegeneration and astrogliosis of the occipital cortices including the striate cortices, similar but less advanced changes in the parietal cortices, right Ammons horn sclerosis, degeneration of the posterior columns, and mild cerebellar Purkinje cell loss. Examination of the liver revealed extensive centrilobular hepatocyte necrosis. Skeletal muscle did not contain ragged red fibers, nor were there mitochondrial DNA point mutations characteristic for mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS).


Tuning the resonance frequencies and mode shapes in a large range multi-degree of freedom micromirror.
The ability to actively shift the primary resonance of a 2D scanning micromirror allows the user to set the scanning direction, set the scanning frequency, and lift otherwise degenerate modes in a symmetrically designed system. In most cases, resonant scanning micromirrors require frequency stability in order to perform imaging and projection functions properly. This paper suggests a method to tune the tip and tilt resonant frequencies in real time while actively suppressing or allowing degeneracy of the two modes in a symmetric electrothermal micromirror. We show resonant frequency tuning with a range of degeneracy separation of 470 Hz or by approximately ±15% and controllable coupling.


Increased serum uric acid--a marker of non-gouty widespread pain? A study of female patients with inflammatory and non-inflammatory pain.
To study the relationship between reported chronic pain and the level of serum urate (SU) among women with various diagnoses of the musculoskeletal system. Consecutive female patients (aged 20-70 years, n = 124), at rheumatology and rehabilitation practices, with chronic musculoskeletal pain of different origins were followed for 1 year after an initial survey of pain, lifestyle, quality of life, and disability. Repeated blood samples (including urate, creatinine, cholesterol, and glucose) were analysed. Multiple regression analysis was performed to explain initial variations in SU level in relation to pain and confounding factors. The level of SU was increased among individuals with widespread pain (>5 locations) independent of underlying diagnoses compared to those with fewer pain sites (270.5 vs. 241.2 micromol/L). Serum creatinine, body mass index (BMI), the number of pain locations, and sleep disturbances independently contributed to the SU level and explained 43% of the variation in SU. Individual variation in SU during 4 months was low. Epidemiological data on the relationship between the extent of body pain and SU were confirmed in a clinical setting. Besides known factors such as impaired renal function and obesity, widespread pain and sleep disturbances were related to an increase in SU. Medication and alcohol intake could not explain the findings. Longitudinal studies are necessary to elucidate whether the level of SU has any implications for the prognosis of chronic pain.


Exploring the Potential of Data-Independent Acquisition Proteomics Using Untargeted All-Ion Quantitation: Application to Tumor Subtype Diagnosis.
Maximizing the recovery of meaningful biological information can facilitate proteomics-guided early detection and precise treatment of diseases. However, the conventional protein and peptide level targeted quantification of untargeted data independent acquisition (DIA) such as sequential window acquisition of all theoretical spectra (SWATH) is not necessarily descriptive of all information. Untargeted all-ion quantification theoretically could retrieve more features in SWATH digital maps by circumventing the initial identification process but is intrinsically susceptible to errors because of the extreme complexity of proteome samples and the poor selectivity of a single ion. In this study, we optimized and applied the untargeted all-ion quantification of SWATH data to differentiate tumor subtypes. Large peptides and low abundant peptides benefited more from untargeted all-ion quantification. Top-ranked significant ions were linked to their corresponding ion envelops, where multiple correlated ions were used for measurement and only ion envelopes containing at least three ions with consistent intensity ratio were kept as refined differentiating features. Multivariate statistical analysis revealed that for the tested data set, the refined markers discovered by untargeted SWATH analysis showed comparable diagnostic power to protein and peptide markers. Limitations and benefits of the approach are further discussed.


Passive IgA monoclonal antibody is no more effective than IgG at protecting mice from mucosal challenge with respiratory syncytial virus.
Respiratory syncytial virus (RSV) is a mucosally restricted pathogen that can cause severe respiratory disease. Although parenteral administration of sufficient RSV-specific IgG can reduce severity of lower respiratory tract infection in high-risk infants, delivery of antibody by direct airway administration is an attractive alternative. Topical and parenteral administration of an IgA monoclonal antibody (MAb) specific for the RSV F glycoprotein was compared with an IgG MAb, specific for the same antigenic site, for ability to protect mice against RSV infection. Administration of RSV-specific IgG was more effective in reducing RSV titers in lung (4.6 log10 pfu/g) than IgA MAb (3.6 log10 pfu/g) when given intranasally immediately prior to infection (P=.005). RSV titers in the nose were reduced only by prophylactic administration of IgG parenterally. Therefore, topical administration of IgA is no more effective than topically administered IgG and is less effective than systemically administered IgG for protecting against RSV infection.


Anticoagulation management in patients with mechanical heart valves having pacemaker or defibrillator insertion.
In patients with a high risk for stroke and having invasive procedures with a high risk for bleeding it is unclear how anticoagulant therapy should be managed. We reviewed data from all patients with mechanical heart valves, who had elective insertion or replacement of pacemaker or implantable cardioverter defibrillator (ICD) during the past 8years at our hospital. Data on anticoagulant treatment, pocket hematoma and thromboembolic complications were captured. Of the 111 patients reviewed, 68 (61%) had a mechanical valve in the mitral position with or without other valves replaced and 43 (39%) had a mechanical valve only in the aortic position. Fifty-nine (53%) were undergoing replacement for their device. Six patients received a tapered warfarin regimen and 102 received preoperative bridging anticoagulation of whom 12 also received postoperative bridging. One stroke occurred 40days after pacemaker replacement in a patient with mitral mechanical valve and without postoperative bridging. Six patients (5.5%) developed pocket hematoma without a significant association to postoperative bridging, type of mechanical valve or to type of device. Predictors for pocket hematoma appeared to be replacement surgery (odds ratio 12.5; 95% confidence interval [CI], 0.69-228) and an international normalized ratio of 1.5 or higher on the day of surgery (odds ratio 8.4; 95% CI, 0.96-68.1). We found a low risk for stroke in the absence of postoperative bridging. For patients with device replacement surgery reversal of the anticoagulant effect at the time of procedure might reduce the risk for pocket hematoma, but this requires prospective evaluation including the risk of thromboembolism.


"Being prevented from providing good care: a conceptual analysis of moral stress among health care workers during the COVID-19 pandemic".
Health care workers (HCWs) are susceptible to moral stress and distress when they are faced with morally challenging situations where it is difficult to act in line with their moral standards. In times of crisis, such as disasters and pandemics, morally challenging situations are more frequent, due to the increased imbalance between patient needs and resources. However, the concepts of moral stress and distress vary and there is unclarity regarding the definitions used in the literature. This study aims to map and analyze the descriptions used by HCWs regarding morally challenging situations (moral stress) and refine a definition through conceptual analysis. Qualitative data were collected in a survey of 16,044 Swedish HCWs who attended a COVID-19 online course in autumn 2020. In total, 643 free-text answers with descriptions of moral stress were analyzed through content analysis. Three themes emerged from the content analysis (1) "Seeing, but being prevented to act; feeling insufficient/inadequate and constrained in the profession," (2) "Someone or something hindered me; organizational structures as an obstacle," and (3) "The pandemic hindered us; pandemic-related obstacles." The three themes correspond to the main theme, "Being prevented from providing good care." The main theme describes moral stress as various obstacles to providing good care to patients in need and acting upon empathic ability within the professional role. The themes are discussed in relation to established definitions of moral stress and are assessed through conceptual analysis. A definition of moral stress was refined, based on one of the established definitions. On the basis of the study results and conceptual analysis, it is argued that the presented definition fulfils certain conditions of adequacy. It is essential to frame the concept of moral stress, which has been defined in different ways in different disciplines, in order to know what we are talking about and move forward in developing prevention measures for the negative outcomes of this phenomenon.


Follicular Lymphoma Evaluation Index (FLEX): A new clinical prognostic model that is superior to existing risk scores for predicting progression-free survival and early treatment failure after frontline immunochemotherapy.
Patients with advanced-stage follicular lymphoma (FL) who progress early after receiving first-line therapy have poor overall survival (OS). Currently applied clinical prognostic models such as FL International Prognostic Index [FLIPI], FLIPI-2 and PRIMA-Prognostic Index [PRIMA-PI] have suboptimal sensitivity and specificity to predict this poor prognosis subgroup. The primary objective was to develop a novel prognostic model, the FL Evaluation Index (FLEX) score, to identify high-risk patients and compare its performance with FLIPI, FLIPI-2 and PRIMA-PI. Progression-free survival (PFS) after first-line immunochemotherapy was the key endpoint, while OS and progression of disease within 24 months (POD24) were also assessed. The model, which includes nine clinical variables, was developed using a cohort of patients with previously untreated advanced-stage FL from the phase 3 GALLIUM trial (NCT01332968). The performance of the model was validated using data from the SABRINA trial (NCT01200758). In GALLIUM (n = 1004; 127 with and 877 without POD24), FLEX increased the intergroup (low-risk/high-risk) difference in 2-year and 3-year PFS rates and demonstrated superior intergroup differences in 2-year and 3-year OS rates compared with FLIPI, FLIPI-2 and PRIMA-PI. Sensitivity for a high-risk score to predict POD24 was 60% using FLEX compared with 53% for FLIPI and FLIPI-2, and 69% for PRIMA-PI, while specificity was 68% for FLEX compared with 58% for FLIPI, 59% for FLIPI-2 and 48% for PRIMA-PI. The prognostic value of FLEX in SABRINA was similar to FLIPI. Therefore, FLEX appears to perform better than existing prognostic models in previously untreated FL, in particular for the newer treatment regimens.


Dynamics in charity donation decisions: Insights from a large longitudinal data set.
Despite the vast body of research on charitable giving and its drivers, no research has investigated the longitudinal dynamics of individual donation decisions. We analyzed unique data with nearly 300,000 real donation decisions made by more than 20,000 individuals for a period of 10 months. Each decision entailed a choice of what to do with money received for completing a survey (on average, €0.67 per survey): keep it or donate to charity. We found that most of the participants (89%) always chose to keep the money. Within the group of people who sometimes kept and sometimes donated the money (that is, Switchers), we find that people do not change their decision very often (cf. moral consistency). However, the likelihood of donating increases when people kept the money the previous time, and the amount at stake differs substantially (both positively and negatively). Finally, once Switchers donated, they are more likely to keep the money next time if they can earn more (for example, €2 now versus €0.50 last time), signaling moral compensation. These longitudinal data provide a first step to better understand charity donation decisions, not only in terms of a more nuanced description of decision-makers but also in terms of the dynamics of charity donations.


Preparing Chinese patients with comorbid heart disease and diabetes for home management: a mixed methods study.
To explore how health education received by patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (T2DM) influences patients' self-efficacy and self-management and changes in behaviour at, and following, hospital discharge. This study used a convergent mixed methods design. Twenty-one participants with completed surveys and interviews at discharge and home follow-up were included in the analysis. At a coronary care unit of a major hospital in Shanghai, China. Most participants (n=17) did not perceive they had sufficient education or ability to manage both conditions. More concerning was that most participants (n=16) reported low self-efficacy in the management of ACS symptoms. Three major themes were identified: self-management of ACS and T2DM represents a complex interplay between individual self-efficacy, knowledge and skills, as individuals navigate shifting self-management priorities due to perceived condition severity; the social environment is integral to lifestyle and behaviour change and managing multiple health conditions requires body and mind systems' harmony. The inpatient education received did not enhance participants' confidence to manage either condition on discharge. While an unhealthy lifestyle was embedded within social roles and norms, some social activities, such as square dancing, positively influenced health behaviour. Culturally appropriate education for Chinese people with diabetes and ACS should contain information on maintaining mind and body harmony. Family members should be involved in formal education.


Life-expectancy changes from 2019 to 22: A case study of Japan using provisional death count.
Many countries struggled with suppressing the incidence of COVID-19 caused by SARS-CoV-2 Omicron variant (B.1.1.529). As the epidemic size of COVID-19 in 2022 became bigger than earlier years in Japan, the present study aimed to estimate life expectancy at birth at the end of 2022, using provisional death datasets in Aichi and Fukui prefectures. We collected monthly death count from 2019 to the end of 2022, computing the period life table. While the life expectancy at birth in Aichi, 2019 was 84.6 years, it was very slightly extended to 84.7 years in 2020 and 2021, followed by a shortening for nearly 0.4 years in 2022. In Fukui, monotonous extension pattern was seen, i.e., 85.5 years in 2019, 85.6 in 2020, followed by 85.8 and 86.2 years in 2021 and 2022, respectively. Although decades-long trend of extending life expectancy at birth was partly discontinued from 2020 due to the pandemic at the national level, we have shown that the pandemic impact was still small in Japan by the end of 2022. First Omicron wave occurred shortly after primary series vaccination, and even real time booster program was underway during that wave. Different demographic consequences between Aichi and Fukui are explained by differential epidemic sizes prior to vaccination.


Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused?
Surrogate outcomes are not intrinsically beneficial to patients, but are designed to be easier and faster to measure than clinically meaningful outcomes. The use of surrogates as an endpoint in clinical trials and basis for regulatory approval is common, and frequently exceeds the guidance given by regulatory bodies. In this article, we demonstrate that the use of surrogates in oncology is widespread and increasing. At the same time, the strength of association between the surrogates used and clinically meaningful outcomes is often unknown or weak. Attempts to validate surrogates are rarely undertaken. When this is done, validation relies on only a fraction of available data, and often concludes that the surrogate is poor. Post-marketing studies, designed to ensure drugs have meaningful benefits, are often not performed. Alternatively, if a drug fails to improve quality of life or overall survival, market authorization is rarely revoked. We suggest this reliance on surrogates, and the imprecision surrounding their acceptable use, means that numerous drugs are now approved based on small yet statistically significant increases in surrogates of questionable reliability. In turn, this means the benefits of many approved drugs are uncertain. This is an unacceptable situation for patients and professionals, as prior experience has shown that such uncertainty can be associated with significant harm. The use of surrogate outcomes should be limited to situations where a surrogate has demonstrated robust ability to predict meaningful benefits, or where cases are dire, rare or with few treatment options. In both cases, surrogates must be used only when continuing studies examining hard endpoints have been fully recruited.


Serum levels of carcinoembryonic antigen and a tumor-extracted carcinoembryonic antigen-related antigen in cancer patients.
Levels of carcinoembryonic antigen (CEA) and a tumor-extracted CEA-related antigen (TEX) were determined in sera from patients with carcinomas of the breast, colon, lung, head and neck, and a number of miscellaneous categories. The purpose of this study was to compare the levels of each antigen at various stages of malignant disease. Competitive radioimmunoassays developed in our laboratory were shown to be sufficiently specific to detect either of these two antigens independent of each other. The results indicate that: (a) with our specific assays, CEA was not significantly elevated in smoker controls, but TEX was elevated in 29% of smoker controls; (b) TEX was equivalent to CEA as a tumor marker for colonic cancer. TEX was better than CEA as a marker for lung cancer and, based on limited data, there is a possibility that TEX is a significantly better tumor marker than is CEA in early lung cancer; (c) TEX was superior to CEA as a tumor marker for breast and head and neck cancers; (d) there is a strong indication that serial determinations of TEX can be used as effectively as CEA in the monitoring of disease progress. These preliminary results must be confirmed by increasing the number of cancer patients and including nonmalignant disease controls.


Locally existing endothelial cells and pericytes in ovarian stroma, but not bone marrow-derived vascular progenitor cells, play a central role in neovascularization during follicular development in mice.
Neovascularization is necessary for follicular growth. Vascularization is first observed in preantral follicles, and thereafter the vasculature markedly increases in follicles undergoing development. Neovascularization includes angiogenesis and vasculogenesis. Vasculogenesis is the formation of new blood vessels by bone marrow-derived endothelial progenitor cells. It is unclear whether vasculogenesis occurs during follicular growth. Blood vessels must be mature to be functional blood vessels. Mature blood vessels are characterized by the recruitment of pericytes. However, it is unclear where pericytes come from and whether they contribute to neovascularization in the follicle during follicular growth. In this study, we investigated whether bone marrow-derived progenitor cells that differentiate into vascular endothelial cells or pericytes contribute to neovascularization during follicular growth. A parabiosis model was used in this study. Six-week-old wild-type and transgenic female mice expressing green fluorescent protein (GFP) were conjoined between the lateral abdominal regions to create a shared circulatory system. After 6 weeks, the ovaries were obtained and immunostained for CD31/CD34 (a vascular endothelial cell marker), platelet-derived growth factor receptor-β (PDGFR-β) (a pericyte marker), and GFP (a bone marrow-derived cell marker). Cells that were positive for CD34 and PDGFR-β were observed in the stroma adjacent to the primary or early preantral follicles and in the theca cell layer of the follicles from the late preantral stage to the preovulatory stage. CD31/CD34 and GFP double-positive cells were observed in the theca cell layer of the follicle from the antral stage to the preovulatory stage while the number of double-positive cells in the preovulatory follicles did not increase. PDGFR-β and GFP double-positive cells were observed in the theca cell layer of the preovulatory follicle but not in the smaller follicle. Locally existing endothelial cells and pericytes in the stroma play a central role in the neovascularization during follicular growth, while bone marrow-derived endothelial cells and pericytes partially contribute to this process.


Visualizing the replication of respiratory syncytial virus in cells and in living mice.
Respiratory syncytial virus (RSV) is the most important cause of severe lower-respiratory tract disease in calves and young children, yet no human vaccine nor efficient curative treatments are available. Here we describe a recombinant human RSV reverse genetics system in which the red fluorescent protein (mCherry) or the firefly luciferase (Luc) genes are inserted into the RSV genome. Expression of mCherry and Luc are correlated with infection rate, allowing the monitoring of RSV multiplication in cell culture. Replication of the Luc-encoding virus in living mice can be visualized by bioluminescent imaging, bioluminescence being detected in the snout and lungs of infected mice after nasal inoculation. We propose that these recombinant viruses are convenient and valuable tools for screening of compounds active against RSV, and can be used as an extremely sensitive readout for studying effects of antiviral therapeutics in living mice.


In situ, real time monitoring of surface transformation: ellipsometric microscopy imaging of electrografting at microstructured gold surfaces.
Surface chemical reactivity is imaged by combining electrochemical activation of a surface transformation process with spatiotemporal ellipsometric microscopy. An imaging ellipsometric microscope is built, allowing ellipsometric images of surfaces with a lateral resolution of ∼1 μm and a thickness sensitivity of ∼0.1 nm in air and 0.4 nm in a liquid. These performances are particularly adapted for using such optical setup as an in situ, real time chemical microscope to observe a chemical surface transformation. This microscope is tested for the monitoring of the electrochemically actuated diazonium grafting of a gold surface. Such reaction is a model system of organic material deposition on a gold surface induced by an electrochemical actuation. Using either plain or physically or chemically structured electrodes, it allows for the characterization of local phenomena associated with the electrografting process. This illustrates its potential to reveal the local (electro)chemical reactivity of surfaces.


The impact of individual and organisational factors on engagement of individuals with intellectual disability living in community group homes: a multilevel model.
Being engaged in daily activities is a strong indicator of quality of life for individuals with intellectual disability (ID) who live in small community group homes. This study aimed to identify individual and organisational factors that predict high levels of engagement. Individuals with ID (n = 78), direct support professionals (DSPs; n = 174) and supervisors (n = 21) from 21 US group homes participated in the study. For each individual with ID, we conducted 80 min of observation at the person's residence. Information was also gathered regarding demographic characteristics, DSP competence, supervisor years of experience and management practices. Data were analysed using multilevel modelling. On average, individuals were engaged in social activities 12% of observed time and non-social activities 35% of the time. Individuals with greater adaptive skills who were supported by more competent staff showed significantly higher levels of social engagement. Individuals with less severe deficits in adaptive behaviours and less challenging behaviour showed higher levels of non-social engagement. Although none of the factors related to group homes were significant, 24% of the variance in non-social engagement existed among group homes. These results suggested that engagement is a dynamic construct. The extent to which an individual with ID is engaged in daily life is a result of interplay between the individual's characteristics and the group home environment. Future research is needed to investigate the influence of variables specific to the group home on the engagement level of individuals with disabilities.


The Stress-Induced Soybean NAC Transcription Factor GmNAC81 Plays a Positive Role in Developmentally Programmed Leaf Senescence.
The onset of leaf senescence is a highly regulated developmental change that is controlled by both genetics and the environment. Senescence is triggered by massive transcriptional reprogramming, but functional information about its underlying regulatory mechanisms is limited. In the current investigation, we performed a functional analysis of the soybean (Glycine max) osmotic stress- and endoplasmic reticulum (ER) stress-induced NAC transcription factor GmNAC81 during natural leaf senescence using overexpression studies and reverse genetics. GmNAC81-overexpressing lines displayed accelerated flowering and leaf senescence but otherwise developed normally. The precocious leaf senescence of GmNAC81-overexpressing lines was associated with greater Chl loss, faster photosynthetic decay and higher expression of hydrolytic enzyme-encoding GmNAC81 target genes, including the vacuolar processing enzyme (VPE), an executioner of vacuole-triggered programmed cell death (PCD). Conversely, virus-induced gene silencing-mediated silencing of GmNAC81 delayed leaf senescence and was associated with reductions in Chl loss, lipid peroxidation and the expression of GmNAC81 direct targets. Promoter-reporter studies revealed that the expression pattern of GmNAC81 was associated with senescence in soybean leaves. Our data indicate that GmNAC81 is a positive regulator of age-dependent senescence and may integrate osmotic stress- and ER stress-induced PCD responses with natural leaf senescence through the GmNAC81/VPE regulatory circuit.


Lower limit characterization of segregation degree for large-size low-alloy steel.
Based on the original position statistic distribution analysis technique, the characterization method of segregation for large-size metal materials gives significant guidance to the research of material properties and production. However, random errors are inevitably brought into the calculation of segregation degree for materials characterization by the Spark Mapping Analysis for Large Sample (SMALS) technique, resulting in a misguide of the segregation degree. In this paper, we present the lower limit of segregation degree (Ds(L)) method to distinguish the random error from metal material segregation for large-size samples over the SMALS method. The random error of standard material in the 95% confidence interval was utilized as Ds(L) and the method has been applied for macro-segregation quantitative analysis. The precision correlation between Spark Atomic Emission Spectrometry (Spark-AES) and SMALS was established. Furthermore, the functional relationship between the Ds(L) and element content C can be obtained in the SMALS method. The Ds(L) method as the criterion can be used to not only characterize the minimum limit of the segregation degree but also the segregation existence for large-size samples. Applying to low-alloy steel can illustrate the effective performance of the Ds(L) method. Results on both spark mapping analysis and Spark-AES verify the substantial consistency.


[Evaluation of wound healing process].
Mathematical modelling of wound healing process gave use to new nontraditional methods for treatment of festered wounds of various origin: volume-loaded activated water with pH from 2.4 to 11.3, being used for dressings and prepared in electrohydrolyzer with graphite anode (which possessed electric potential +1.200 mV, electric potential of furacillin solution 1:500 widely used for dressing, is equal to +300 mV). This approach to the treatment of festered wounds in complex with radical surgery allowed to substantially improve the results of treatment in 1979-to 1994 in comparison with the period 1971-1988: the rate of repeated hospitalizations lowered 3.9-todd, frequency of allergic complications--5 told, mortality rate--1.5 told and without oncological and vascular diseases--5 told. The duration of hospital stay and temporary unemployment diminished 2 times.


Monocyte localization of elevated cAMP phosphodiesterase activity in atopic dermatitis.
Patients with atopic dermatitis (AD) manifest a number of immune abnormalities which correlate with in vitro defects including lymphocyte transformation, chemotaxis, and cytotoxicity. Past studies have shown reduced leukocyte cyclic 3',5'-adenosine monophosphate (cAMP) levels after exposure to adenylate cyclase-active agonists, and we have demonstrated that this results from increased catabolism due to elevated cAMP-phosphodiesterase activity. These results were obtained in preparations containing mixtures of lymphocytes and monocytes. In order to determine more precisely the cellular site of the defect we have separated the leukocytes into lymphocyte- and monocyte-enriched preparations using either Percoll-gradient centrifugation or adherence isolation. Both techniques yielded over 93% pure lymphocytes, whereas the former yielded 64% monocytes compared with the latter method which generated 94% pure monocytes. Atopic monocytes, obtained by either technique, consistently showed elevated phosphodiesterase activity compared with those of the nonatopic monocytes. Such differences were not evident in lymphocyte preparations from normal and atopic subjects. In spite of the increased rate of cAMP degradation in atopic leukocytes, the resting cAMP levels do not differ from those of normal subjects. We questioned whether this is caused by increased cAMP synthesis and evaluated cellular adenylate cyclase activity. We found no evidence in AD cells for an increased rate of adenylate cyclase catalysis, either basal activity or after stimulation by forskolin. Therefore, the resting cAMP levels must have been compensated by other mechanisms. Impaired cyclic nucleotide metabolism in atopic monocytes may affect a number of immunologic and inflammatory reactions and could account for many of the clinical abnormalities in atopic diseases.