[Waist circumference reference values for screening cardiovascular risk factors in Chinese children and adolescents aged 7 - 18 years].
To explore the optimal threshold values of waist circumference (WC) in detecting the risk on cardiovascular (CV) among the Chinese children and adolescents. Association of WC and CV risk factors were studied among 65 898 children and adolescents aged 7 - 18 years whose data were pooled from nine studies carried out in China. Receive-operating characteristic analysis (ROC) and logistic regression were employed to derive optimal age- and sex-specific waist circumference references for predicting the CV risk factors. A slight increasing trend of CV risk factors was observed starting from the 75th percentile of waist circumference in the study population, while a remarkable increasing trend occurred from the 90th percentile. The optimal waist circumference thresholds for predicting high blood pressures were at the 75th percentile for both boys and girls, and at the 90th percentiles it could detect at least two of the above three CV risk factors. In comparison with children whose waist circumference was below the 75th percentile, the odds ratio of two CV risk factors doubled among children with waist circumference between 75th and 90th percentile, and increased by 6 times among children with waist circumference above the 90th percentile. The trend of high blood pressure increasing remained significant with waist circumference after having been stratified by BMI category. The 75th and the 90th percentile of WC appeared to be the optimal cut-off points for predicting an increased and a substantially increased risk of CV factors in Chinese children and adolescents.


Aesthetic Applications of Botulinum Toxin A in Asians: An International, Multidisciplinary, Pan-Asian Consensus.
Botulinum toxin type A remains the most popular nonsurgical aesthetic treatment worldwide. Previous consensus statements have focused on Caucasians and on Koreans as generally representative of Asians. However, indications and dosages vary among different ethnic groups. This publication reports the results of a multidisciplinary, pan-Asian consensus focusing on incobotulinumtoxinA. A consensus group of plastic surgeons and dermatologists from Asia, Europe, and the United States convened for a live meeting in Asia, followed by a questionnaire-based Delphi procedure. Treatment of Asians in both their native countries and countries of migration was discussed. For most items, the group achieved a majority consensus. A number of treatment indications, strategies, and dosages were identified in Asians, which are distinct to those previously described for Caucasians due to differences in facial morphotypes, anatomy, and cultural expectations. The group also formulated position statements for intradermal botulinum toxin type A ("mesotoxin"), body shaping with the calves as a paradigm, and reduction of parotid glands. While Asians have previously been considered a homogeneous group for the purposes of aesthetic treatment, this publication considers regional variations. A new classification of Asian facial morphotypes is proposed to aid treatment planning and implementation. This is the first pan-Asian consensus for aesthetic use of botulinum toxin type A. Its unique objective is to optimize treatment safety and efficacy for patients of complete or part-Asian ancestry in all regions. The recommendations for incobotulinumtoxinA may be extended with care to other botulinum toxin formulations.


Control of oculomotor reflexes: independent effects of strategic and automatic preparation.
The reduction in saccade latency when the fixation point is removed (fixation offset effect-FOE) reflects the degree to which fixation neurons are under influence by a stimulus at fixation. Strategic manipulations of oculomotor readiness that bring these neurons under endogenous control reduce the magnitude of the FOE. Using an aging foreperiod paradigm, and the FOE as a marker for cortical control of reflexive fixation, we showed that, for both prosaccades and antisaccades, increasing preparation across the foreperiod reduced both saccade latency and the FOE. Consistent with Los's trace conditioning account, these effects reflected greater preparation for trials when the current short foreperiod was preceded by a trial with a short foreperiod. The FOE was also smaller for antisaccades than for prosaccades demonstrating strategic modulation. However, the effects of trace conditioning were comparable in the two tasks, demonstrating that strategic and unconscious priming effects both independently modulate the control of ocular fixation.


Role of GTPases and GTPase regulatory proteins in oncogenesis.
The GTPases comprise a superfamily of GTP-binding proteins with intrinsic GTPase activity. Some members of this family representing either heterotrimeric or small G-proteins are involved in the transmission of mitogenic signals. Mutations that lead to constitutively activated G-proteins have been shown to contribute to malignant transformation. These genes represent, therefore, putative oncogenes. Examples are the gsp and gip2 oncogenes, encoding GTPase deficient alpha-subnits of Gs or Gi-2 proteins. Representatives from the family of small G-proteins are the products of the Harvey-, Kirsten- or N-ras oncogenes. These oncogenes, which are frequently expressed in human malignancies, code for proteins (p21ras) that are locked in the activated GTP-bound state because their GTPase is refractory to the ras-specific GTPase activating protein (GAP). In other cases p21ras-GTP levels have been found to be elevated as a result of an increase in GDP/GTP exchange rate. In neurofibromatosis v. Recklinghausen, a mutated gene (NF1) is detectable. The protein encoded by NF1 contains a GAP homology region, binds p21ras-GTP, and stimulates the hydrolysis of p21ras-bound GTP. Both ras-GAP (p120 GAP) and NF1-GAP are inhibited by acidic lipids. Elevated levels of these lipids may exert growth-stimulatory or perhaps tumor-promoting activity by increasing p21ras GTP. The function of transforming p21ras is under control of tumor suppressor genes. Putative suppressor genes isolated from revertants from ras-transformed cells include rsp-1 and the ras recision gene (rrg). Experimentally, an overexpression of Rap 1A/Krev-1 is able to antagonize transformation by p21ras. This mechanism also may be relevant under normal conditions. p53 also is capable of inhibiting transforming p21ras. It is postulated that p105-RB exerts a similar anti-ras effect. The mechanism by which retinoic acid suppresses transformation by ras is discussed. Current strategies for a pharmacological interference of p21ras function are described.


X-ray structure of a pokeweed antiviral protein, coded by a new genomic clone, at 0.23 nm resolution. A model structure provides a suitable electrostatic field for substrate binding.
We have determined the crystal structure of alpha-pokeweed antiviral protein, a member of ribosome-inactivating proteins, at 0.23 nm resolution, by the molecular-replacement method. The crystals belong to the space group P2(1)2(1)2 with unit-cell dimensions a = 4.71, b = 11.63 and c = 4.96 nm, and contain one protein molecule/asymmetric unit based on a crystal volume/unit protein molecular mass of 2.1 x 10(-3) nm3/Da. The crystallographic residual value was reduced to 17.2% (0.6-0.23 nm resolution) with root-mean-square deviations in bond lengths of 1.9 pm and bond angles of 2.2 degrees. The C alpha-C alpha distance map shows that alpha-pokeweed antiviral protein is composed of three modules, the N-terminal (Ala1-Leu76), the central (Tyr77-Lys185) and the C-terminal (Tyr186-Thr266) modules. The substrate-binding site is formed as a cleft between the central and C-terminal modules and all the active residues exist on the central module. The electrostatic potential around the substrate-binding site shows that the central and C-terminal module sides of this cleft have a negatively and a positively charged region, respectively. This charge distribution in the protein seems to provide a suitable interaction with the substrate rRNA.


The risk function for liver cirrhosis from lifetime alcohol consumption.
A hypothesis on the effects of level and duration of alcohol misuse on individual risks for liver cirrhosis is proposed. The hypothesized risk function is a generalized version of the exponential law of other researchers. Some predictions are derived and tested against two types of aggregate data--the age structure of cirrhosis mortality and time-series data for the general population. It is shown that both types of data are compatible with the proposed risk function. It is also shown that the fact that extensive alcohol misuse will result in death from cirrhosis only after a considerable number of years does not contradict the observation that changes in per capita consumption normally have an instantaneous effect on cirrhosis mortality.


Navigation for the Blind through Audio-Based Virtual Environments.
We present the design, development and an initial study changes and adaptations related to navigation that take place in the brain, by incorporating an Audio-Based Environments Simulator (AbES) within a neuroimaging environment. This virtual environment enables a blind user to navigate through a virtual representation of a real space in order to train his/her orientation and mobility skills. Our initial results suggest that this kind of virtual environment could be highly efficient as a testing, training and rehabilitation platform for learning and navigation.


[Malignant phyllodes tumor metastatic to the pancreas: a case report].
A woman in her 50s was admitted with obstructive jaundice due to a pancreatic mass. She had a history of a right breast phyllodes tumor treated with mastectomy 3 years previously. Diagnostic imaging (endoscopic ultrasonography (EUS), CT, and MRI) demonstrated a well-demarcated mass in the pancreatic head. EUS-FNA showed spindle shaped tumor cells. The pancreaticoduodenectomy specimen showed a malignant spindle cell tumor consistent with a metastatic malignant phyllodes tumor. In addition, immunohistochemical staining demonstrated that the staining pattern of pancreatic tumor was similar to that of the breast phyllodes tumor. Pancreatic metastases from breast phyllodes tumors have rarely been reported in the literature.


Extract from Arca granosa L. inhibits proliferation of human tumour cell lines with kidney and lung origin.
Marine organisms are being considered increasingly as sources of anti-tumour agents. The extract from Arca granosa L. has been shown to decrease the growth of tumours and this study was undertaken to determine its ability and mechanism of inhibition. The extract inhibited the proliferation of six human tumour cell lines from different origins with varying sensitivity. The cell lines Ketr-3, A549 and NCl-H460 with kidney or lung origins were more sensitive to the extract than those of the HepG-2, MCF-7 and MGC-803 cells from other origins. In the three sensitive cell lines (Ketr-3, A549 and NCI-H460) the extract was shown to block different phases of the cell cycle progression and inhibit DNA synthesis in a concentration-dependent manner. It was concluded that the extract from A. granosa is potentially a novel anti-tumour agent, especially on kidney and lung tumour cell lines.


One year results of the Middlesbrough early revascularisation to limit infarction (MERLIN) trial.
To report one year results of the MERLIN (Middlesbrough early revascularisation to limit infarction) trial, a prospective randomised trial comparing the strategy of coronary angiography and urgent revascularisation with conservative treatment in patients with failed fibrinolysis complicating ST segment elevation myocardial infarction (STEMI). The 30 day results have recently been published. At the planning stage of the trial, it was determined that follow up of trial patients would continue annually to three years to determine whether late benefit occurred. 307 patients who received a fibrinolytic for STEMI but failed to reperfuse early according to previously described ECG criteria and did not develop cardiogenic shock. Patients were randomly assigned to receive either emergency coronary angiography with a view to proceeding to urgent revascularisation (rescue percutaneous coronary intervention (rPCI) arm) or continued medical treatment (conservative arm). The primary end point was all cause mortality at 30 days. The secondary end points included the composite end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure at 30 days. The same end points were evaluated at one year and these results are presented. All cause mortality at one year was similar in the conservative arm and the rPCI arm (13.0% v 14.4%, p = 0.7, risk difference (RD) -1.4%, 95% confidence interval (CI) -9.3 to 6.4). The incidence of the composite secondary end point of death, reinfarction, stroke, unplanned revascularisation, or heart failure was significantly higher in the conservative arm (57.8% v 43.1%, p = 0.01, RD 14.7%, 95% CI 3.5% to 25.5%). This was driven almost exclusively by a significantly higher incidence of subsequent unplanned revascularisation in the conservative arm (29.9% v 12.4%, p < 0.001, RD 17.5%, 95% CI 8.5% to 26.4%). Reinfarction and clinical heart failure were numerically, but not statistically, more common in the conservative arm (14.3% v 10.5%, p = 0.3, RD 3.8%, 95% CI -3.7 to 11.4, and 31.2% v 26.1%, p = 0.3, RD 5.0%, 95% CI -5.1 to 15.1). There was a strong trend towards fewer strokes in the conservative arm (1.3% v 5.2%, p = 0.06, RD -3.9%, 95% CI -8.9 to 0.06). At one year of follow up, there was no survival advantage in the rPCI arm compared with the conservative arm. The incidence of the composite secondary end point was significantly lower in the rPCI arm, but this was driven almost entirely by a highly significant reduction in the incidence of further revascularisation.


A deep convolutional neural network approach to single-particle recognition in cryo-electron microscopy.
Single-particle cryo-electron microscopy (cryo-EM) has become a mainstream tool for the structural determination of biological macromolecular complexes. However, high-resolution cryo-EM reconstruction often requires hundreds of thousands of single-particle images. Particle extraction from experimental micrographs thus can be laborious and presents a major practical bottleneck in cryo-EM structural determination. Existing computational methods for particle picking often use low-resolution templates for particle matching, making them susceptible to reference-dependent bias. It is critical to develop a highly efficient template-free method for the automatic recognition of particle images from cryo-EM micrographs. We developed a deep learning-based algorithmic framework, DeepEM, for single-particle recognition from noisy cryo-EM micrographs, enabling automated particle picking, selection and verification in an integrated fashion. The kernel of DeepEM is built upon a convolutional neural network (CNN) composed of eight layers, which can be recursively trained to be highly "knowledgeable". Our approach exhibits an improved performance and accuracy when tested on the standard KLH dataset. Application of DeepEM to several challenging experimental cryo-EM datasets demonstrated its ability to avoid the selection of un-wanted particles and non-particles even when true particles contain fewer features. The DeepEM methodology, derived from a deep CNN, allows automated particle extraction from raw cryo-EM micrographs in the absence of a template. It demonstrates an improved performance, objectivity and accuracy. Application of this novel method is expected to free the labor involved in single-particle verification, significantly improving the efficiency of cryo-EM data processing.


Multimodal Therapeutic Platforms Based on Self-Assembled Metallacycles/Metallacages for Cancer Radiochemotherapy.
Discrete organometallic complexes with defined structures are proceeding rapidly in combating malignant tumors due to their multipronged treatment modalities. Many innovative superiorities, such as high antitumor activity, extremely low systemic toxicity, active targeting ability, and enhanced cellular uptake, make them more competent for clinical applications than individual precursors. In particular, coordination-induced regulation of luminescence and photophysical properties of organic light-emitting ligands has demonstrated significant potential in the timely evaluation of therapeutic efficacy by bioimaging and enabled synergistic photodynamic therapy (PDT) or photothermal therapy (PTT). This review highlights instructive examples of multimodal radiochemotherapy platforms for cancer ablation based on self-assembled metallacycles/metallacages, which would be classified by functions in a progressive manner. Finally, the essential demands and some plausible prospects in this field for cancer therapy are also presented.


Parasagittal hemangioma associates with unilateral cheiro-oral-pedal syndrome.
Cortical lesion might elicit restricted acral sensory deficit but a disparity of topographies in cheiro-oral-pedal syndrome is very rare. We report the first case of cheiro-oral-pedal syndrome due to a contralateral parasagittal hemangioma involving the supplement sensory area in parietal lobe. This unusual link between neuroanatomy and neurological feature is discussed.


Induction of precocious puberty in newborn female guinea pigs by a positive feedback action of estrogens.
The existence of a positive feedback of estrogen on the gonadotrophin-releasing mechanism at birth, was tested in the female guinea pig. Estradiol benzoate (100 ng during the first 5 days of life) or HCG (100 RU during the first 5 days of life) induced a true precocious puberty, with similar characteristics to the control animals (60% of the animals ovulated at puberty age: corpora lutea present at the ovaries). The uterus was larger in ovulating than in nonovulating animals. Reserpine (2.5 mg/kg) on 15, 17 and 19 days of age did not modify the precocious puberty induced by estradiol at birth. It is concluded that exogenous or endogenous estrogen (induced by exogenous gonadotrophin administration) have a positive feedback action on the newborn female guinea pig to release gonadotrophin and develop puberty. These results are very different than those observed in the rat and differences can be related to the stage of somatic and nervous maturation attained by the animals at birth.


Radiolytic degradation mechanism of gallic acid and its end-products.
Gallic acid is one of the most representative biorecalcitrant phenolic compounds present in cork processing wastewater. In this communication, chemical oxidation of gallic acid was studied by gamma irradiation as an advanced oxidation process. This technology turns out to be an advantageous tool for the degradation of gallic acid. The results obtained by UV-Vis and electrospray ionization mass spectrometry (ESI-MS) techniques are in agreement concerning the suitability of this technique to degrade gallic acid. ESI-MS and ESI-MS(2) monitoring of the non-irradiated and irradiated gallic acid solutions leads to the identification of the main intermediate products. Based on the overall results obtained a consistent mechanism of radiolytic degradation of gallic acid is proposed. The application of radiation as a tool to increase the biodegradability of wastewaters is an important issue from the perspective of Green Chemistry.


Transverse tubular system in glycerol-treated skeletal muscle.
Horseradish peroxidase used as an extracellular marker fills 98.5 percent of the central triadic elements (tubules) in normal muscle and 97.2 percent in muscle soaked in Ringer solution to which 400-millimolar glycerol is added. A glycerol-soaked muscle rapidly returned to normal Ringer solution has a disrupted transverse tubular system and has only 3.2 percent of triads filled with peroxidase.


Induction and persistence of B-cell tolerance to the thymus-dependent component of the alpha(1 leads to 6) glucosyl determinant of dextran. Recovery induced by treatment with dextranase in vivo.
A direct comparison was made between thymus-dependent (TD) and thymus-independent (TI) responses in mice tolerized for (1 leads to 6) glycosyl determinants by the injection of dextran B512. Long-lasting B-cell tolerance by dextran was reversed when mice were treated with dextranase in vivo. Complete or partial reversion of tolerance with the enzyme was invariably obtained for the TI response but the TD component proved to be more resistant and dependent on the immunogen used to test the reversion. The uniformity of the spectrotype in BALB/c mice, even under conditions of partial tolerance, permitted the analysis by isoelectric focussing of serum from tolerant mice treated with dextranase and immunized with TD dextran-ovalbumin. Results showed that, with one single exception, mice thus treated produced spectrotypes no different from the pattern normally found in immune animals. The results presented suggest that at least some alpha(1 leads to 6) specific B cells, both TD and TI, persist in tolerized mice for at least 2 weeks after tolerance induction and they do not support the concept of clonal elimination for either TI or TD responses in adult mice.


NIHSS applied to cerebral neurological dive injuries as a tool for dive injury severity stratification.
Evaluation via National Institutes of Health Stroke Scale (NIHSS) upon presentation in hospital triage following ischemic stroke is predictive of recovery or progression to neurological deficits. Cerebral injuries sustained while diving have symptoms similar to stroke. Applying the NIHSS to dive injuries may successfully summarize neurological dive injuries, providing a standardized tool for study of dive injury data. We retrospectively determined NIHSS scores for a diverse population of 192 divers presenting to the University of Hawaii recompression chamber from 1983-2002, both prior to initial treatment and after all treatment. Spinal and vestibular decompression sickness cases were excluded. The performance of the NIHSS among this diving population was similar to its performance as an accepted tool in evaluation of ischemic stroke, although results are influenced by the abundance of mild injury cases in the data set. The estimated C-statistic with NIHSS predicting no observable deficit was 0.88, and predicting post NIHSS of 0-1 was 0.85 (vs. 0.86 when applied to stroke). Sensitivity for predicting recovery (NIHSS 0-1) at discharge was 0.99 (vs. 0.97 for stroke). The NIHSS applied to cerebral dive injuries has adequate predictive ability and correlates with other measures of dive injuries, while providing a standardized, more graduated scale. The NIHSS may be useful as a standardized measurement for evaluation of treatment regimens and adjunctive therapy for diving injuries.


[Glomerulosclerosis: pathogenetic mechanisms and possibility of regression].
Glomerular sclerosis means an increase in the extracellular matrix of the glomerulus. It is a complex, heterogeneous phenomenon with multiple cellular and biochemical mechanisms and different morphological patterns, depending on a variety of local and systemic factors. The term as such does not indicate the quantity nor the type of components of the deposited matrix. The amount of extracellular matrix increases in three types of events: - matrix deposition in areas that were destroyed by a necrotizing process (scars following glomerular necrosis); - matrix deposition in glomerular regions where matrix is normally found (mesangium, glomerular basement membranes) as seen in diabetic nephropathy; - matrix deposition inside or around collapsing capillaries involving the entire glomerulus or a segment of it (focal segmental glomerular sclerosis with nephrotic syndrome). Knowledge of the diverse morphological patterns producing glomerular sclerosis and the cellular and molecular mechanisms involved is essential for obvious reasons: they represent the rationale for any therapy aimed at preventing or reducing the progression of sclerosis and can provide a starting point to determine which forms are, at least potentially, reversible.


Mindful Eating With Diabetes.
IN BRIEF This article provides a description of mindfulness and mindful eating and addresses the application of mindful eating as a component of diabetes self-management education. Mindful eating helps individuals cultivate awareness of both internal and external triggers to eating, interrupt automatic eating, and eat in response to the natural physiological cues of hunger and satiety. Mindful eating interventions have been effective in facilitating improvement in dysregulated eating and dietary patterns. Through practice over time, eating mindfully can interrupt habitual eating behaviors and provide greater regulation of food choice. More research is needed to determine the long-term impact of mindful eating programs.


Characteristics and Distribution of Phosphorus in Surface Sediments of Limnetic Ecosystem in Eastern China.
Phosphorus (P) is an essential nutrient for aquatic organisms; however, excessive P inflow to limnetic ecosystems can induce eutrophication. P concentrations in the rivers, wetlands and lakes of Eastern China have been amplified by fertilizer and sewage inputs associated with the development of industry and agriculture. Yet, knowledge of the distribution and speciation of P is lacking at the regional scale. We determined the distribution and speciation of P in limnetic ecosystems in Eastern China using Standards, Measurements and Testing (SMT) and phosphorus nuclear magnetic resonance (31P-NMR). The results indicate that P pollution in surface sediments was serious. Inorganic P (Pi) was the primary drive of variation in total P (TP) among different river systems, and Pi accounted for 71% to 90% of TP in surface sediment in Eastern China. Also, the concentrations of TP and Pi varied among watersheds and Pi primarily drove the variation in TP in different watersheds. Sediments less than 10-cm deep served as the main P reservoir. Environmental factors affect the speciation and origin of P. NaOH-Pi, HCl-Pi and organic P (Po) were related to pH accordingly at the regional scale. The physicochemical properties of sediments from different limnetic ecosystems affect the P speciation. HCl-Pi was higher in wetland sediments than in riverine and lake sediments in Eastern China. Conversely, NaOH-Pi was lowest in wetland sediments. Total Po concentration was lower in riverine sediments than in other sediments, but Mono-P was higher, with an average concentration of 48 mg kg-1. Diesters-P was highest in lake sediments. By revealing the regional distribution of TP, Pi and Po, this study will support eutrophication management in Eastern China.


Microbiological quality of water and dialysate in all haemodialysis centres of Greece.
Bacterial contamination of treated water and dialysate comprises an important problem for patients undergoing haemodialysis. Both the progressive reduction of the thickness of cellulose membranes and the expanding use of high-flux membranes probably enhance the risk of pyrogenic reactions, therefore increasing the need for atoxic water and non-pyrogenic dialysis fluid. Samples of tap water, treated water, and effluent dialysate in all 85 haemodialysis centres in Greece were examined for total heterotrophic bacteria counts employing the pour plate method, total and faecal coliforms, faecal streptococci and pseudomonas spp. using the membrane filter technique, and sulphite-reducing clostridia applying the most probable number method. Overall 255 paired samples were tested from January to March 1997. For total heterotrophic bacteria, the overall compliance of treated water and dialysate to the American Association of Medical Instrumentation standards (<200 c.f.u./ml for water and <2000 c.f.u./ml for dialysate) was 92.6 and 63.7% respectively, whereas the compliance of tap water samples to our national standards (total heterotrophic bacteria < 10 c.f.u./ml and absence of the other indicator bacteria) was 80.7%. The most commonly isolated bacteria were pseudomonas spp., found in 22.2% of treated water and 59.5% of dialysate samples, whereas the respective frequencies were 12.3 and 36.2% for total coliforms, 8.6 and 30.0% for faecal coliforms, 14.8 and 28.7% for faecal streptococci, and sulphite-reducing clostridia were isolated in 5.8% of dialysate samples only. Haemodialysis centres equipped with storage tanks for treated water experienced lower levels of total heterotrophic bacteria, but higher counts of total and faecal coliforms, faecal streptococci, and pseudomonas spp., although the difference was statistically significant only for faecal streptococci counts, (P<0.05). Sixty-seven haemodialysis centres were equipped with bacterial filters, but mean values of all the examined microorganisms were not statistically different from those of the other centres. Faecal streptococci counts in treated water samples were positively correlated with ageing of both haemodialysis centres (P<0.005) and purification system (P<0.05), whereas pseudomonas counts were significantly correlated with ageing of the purification system (P<0.05).


Transient neonatal diabetes as a presentation of Fanconi- Bickel Syndrome.
Fanconi- Bickel Syndrome (FBS) is a rare type of glycogen storage disease (GSD) Characterized by hepatomegaly, proximal renal tubular acidosis (RTA) and marked growth retardation. We report a case of FBS presenting with diabetic ketoacidosis and transient neonatal diabetes. A female infant, product of consanguineous marriage presented with diabetic ketoacidosis at age 33 days, and was treated as neonatal diabetes with insulin. At age 14 months, insulin was discontinued. She presented with short stature, hepatomegaly, RTA and hypophosphatemic rickets at age 4 and (FBS) was diagnosed. Diagnosis was confirmed by mutation analysis, showing mutation in SLC2 A2 gene. In conclusion,: neonatal diabetes or diabetic ketoacidosis may be the first presentation of infants with FBS.


Hypothalamic regulation of pituitary FSH secretion.
Temporal changes in plasma LH and FSH concentrations were monitored during the afternoon of proestrus in controls and in rats in which the spontaneous LH/FSH surges were blocked with Nembutal. These values were compared with those obtained following electrochemical stimulation (ECS) of either the medial preoptic area (MPOA) or the dorsal anterior hypothalamic area (DAHA) in similar Nembutal-blocked animals. Whereas MPOA-ECS (60 muA/60 sec) elicited a release of both FSH and LH, similar unilateral stimulation of the DAHA resulted in a pronounced increase in plasma FSH and only a slight elevation in plasma LH. Increasing the amount of DAHA tissue stimulated (100 muA/60 sec) caused a significantly greater release of FSH but not LH. Bilateral DAHA-ECS (60 muA/60 sec) failed to produce a greater release of FSH than that observed after unilateral 100 muA/60 sec ECS but resulted in increased concentrations of LH in plasma. Surgical separation of the MPOA from the DAHA, leaving the preopticotuberal fibers intact, did not alter the spontaneous temporal patterns of discharge of FSH or LH 19-21 days post-operatively, although peak LH concentrations were reduced. Further, unilateral ECS (60 muA/60 sec) of the MPOA in such preparations elicited a release of FSH and LH similar to that observed in intact MPOA-ECS rats. In contrast, unilateral DAHA ECS (60 muA/60 sec) in rats with transected hypothalami, caused no release of LH and an attenuated FSH discharge when compared with intact DAHA-ECS rats (peak valued 189 +/- 8 ng/ml vs 274 +/- 11 ng/ml). These studies suggest the existence of specific cell bodies in the DAHA which can cause selective release of FSH when activated. Coexisting with this system is that level of control which is believed to be responsible for the cyclic discharge of both FSH and LH of which the MPOA is a component part.


The absence of a future: the effect of past experience and current developmental conflicts on a midlife analysis.
The four-year analysis of Mr. T, a highly intelligent, successful professional who entered analysis primarily because of a depression is presented; he had had no previous therapeutic experience but was very curious about analysis. The analytic work led to the discovery of a deeply held unconscious conviction of premature death that was related to interaction among the effects of a traumatic parental divorce during childhood, estrangement from both parents prior to their deaths, and signs of aging and illness in midlife. Before this analytic work the patient was unable to conceptualize, let alone plan for, late-life developmental experiences such as retirement and grandparenthood. Transference-countertransference themes are discussed, as is the importance of an understanding of midlife developmental concepts to successful analytic work with patients in this age group.


Quassinoid support studies: fused carbocycle synthesis from benzoic acid derivatives via 5-hexynyl and 6-heptynyl radical cyclizations.
Eight bromoalkynes were prepared from substituted benzoic acids and treated with n-Bu3SnH to provide trans-fused perhydroindans or cis- and trans-fused perhydronaphthalenes. Atom-transfer reactions that accompany the free radical reactions resulted in several tandem radical cyclizations with formation of up to three carbon-carbon bonds in a single reaction. The relationship between these reactions and an approach to the quassinoid family of natural products is also described.


General aspects of cadmium: transport, uptake and metabolism by the kidney.
Cadmium taken up from lung and gastrointestinal tract is transported via blood to liver and kidney. On long-term exposure to cadmium, renal tubular dysfunction develops in humans and experimental animals. Data from animal experiments demonstrate that initially after exposure cadmium in blood is bound to albumin and proteins with higher molecular weight. Such cadmium is mainly taken up in liver. For a few days after exposure cadmium exists as metallothionein in plasma and blood cells. After both single and long-term administration of cadmium bound to metallothionein, cadmium is taken up by the kidney. The concentration of metallothionein-bound cadmium in plasma is quite low due to continuous renal clearance. Cadmium from metallothionein is taken up in renal tubules by pinocytosis and subsequently degraded in lysosomes, thereby releasing cadmium which stimulates de novo synthesis of metallothionein but also binds to reabsorbed metallothionein. Catabolizing and rebinding are continuous and prevent excretion of cadmium. Because of differences in transport, renal metabolic handling forms of cadmium are also different for different forms of cadmium administered and rate of administration. A single dose of metallothionein-bound cadmium given intravenously is almost immediately and completely taken up in the renal tubule. Under such conditions, resynthesis and rebinding processes are insufficient to sequester cadmium from sensitive tissue receptors, and renal damage occurs at total tissue concentrations much lower than when renal cadmium concentrations rise slowly. This explains the wide range (10-200 micrograms Cd/g wet weight) of cadmium in the renal cortex that associated with renal tubular dysfunction in experimental animals.


[Photography as evidence, between medicine and religion].
Are we right to establish a parallel between, on the one hand, Bernadette Soubirous, the pious visionary of Lourdes, and Thérèse Martin, the nun of Lisieux, and on the other hand, the hysterical women who were shown in public by Charcot at the "Salpêtrière Hospital"? If we compare the way all of them were photographed, we bring to light something similar between two facts: I. - the attempts to give a new medical significance to religious-ordinarily speaking-poses; 2 - the attempts to give a particular religious significance to common body positions. So we are led to suggest meaningful changes in the links between medicine and religion, expressed by the language of women's bodies.


Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions.
Exon 20 insertions are the third most common family of epidermal growth factor receptor (EGFR) mutations found in non-small-cell lung cancer (NSCLC). Little is known about cancers harboring these mutations aside from their lack of response to EGFR tyrosine kinase inhibitors, impairing the development of effective targeted therapies. NSCLC patients with EGFR genotyping were studied using a mechanism approved by the Institutional Review Board. Cancers with exon 20 insertions were indentified, sequences were characterized, and effectiveness of different treatment regimens was reviewed retrospectively. Clinical characteristics and survival were compared with cancers harboring common EGFR mutations and cancers with wild-type EGFR. One thousand eighty-six patients underwent EGFR genotyping from 2004 to 2012. Twenty seven (2.5%) harbored exon 20 insertions, making up 9.2% of all cancers with documented EGFR mutations. Compared with wild-type cancers, those with exon 20 insertions were more commonly found in never-smokers and Asian patients. Insertion sequences were highly variable, with the most common variant (V769_D770insASV) making up only 22% of cases. Median survival of patients with exon 20 insertions was 16 months, similar to the survival of wild-type cancers and shorter than the survival of cancers with common EGFR mutations. Patients with EGFR exon 20 insertions have similar clinical characteristics to those with common EGFR mutations but a poorer prognosis. The prevalence of this subset of NSCLC is similar to that of other genotype-defined subsets of lung adenocarcinoma (e.g. those with BRAF mutations, HER2 insertions, ROS1 rearrangements) and is a population of interest for trials of new targeted therapies.


An expression-driven approach to the prediction of carbohydrate transport and utilization regulons in the hyperthermophilic bacterium Thermotoga maritima.
Comprehensive analysis of genome-wide expression patterns during growth of the hyperthermophilic bacterium Thermotoga maritima on 14 monosaccharide and polysaccharide substrates was undertaken with the goal of proposing carbohydrate specificities for transport systems and putative transcriptional regulators. Saccharide-induced regulons were predicted through the complementary use of comparative genomics, mixed-model analysis of genome-wide microarray expression data, and examination of upstream sequence patterns. The results indicate that T. maritima relies extensively on ABC transporters for carbohydrate uptake, many of which are likely controlled by local regulators responsive to either the transport substrate or a key metabolic degradation product. Roles in uptake of specific carbohydrates were suggested for members of the expanded Opp/Dpp family of ABC transporters. In this family, phylogenetic relationships among transport systems revealed patterns of possible duplication and divergence as a strategy for the evolution of new uptake capabilities. The presence of GC-rich hairpin sequences between substrate-binding proteins and other components of Opp/Dpp family transporters offers a possible explanation for differential regulation of transporter subunit genes. Numerous improvements to T. maritima genome annotations were proposed, including the identification of ABC transport systems originally annotated as oligopeptide transporters as candidate transporters for rhamnose, xylose, beta-xylan, and beta-glucans and identification of genes likely to encode proteins missing from current annotations of the pentose phosphate pathway. Beyond the information obtained for T. maritima, the present study illustrates how expression-based strategies can be used for improving genome annotation in other microorganisms, especially those for which genetic systems are unavailable.


Hepatic differentiation of rat induced pluripotent stem cells in vitro.
To show the efficient generation of hepatocyte-like cells (HLCs) differentiated from the induced pluripotent stem cells (iPSCs) of rats. Hepatic differentiation was achieved using a three-step protocol with several growth factors. First, rat iPSCs were differentiated into definitive endoderm cells using Activin A and Wnt3a treatment. Then fibroblast growth factor 4 and bone morphogenetic protein 2 were added to the culture medium and used to induce hepatic differentiation. Finally, hepatocyte growth factor, Oncostatin M and dexamethasone were used for hepatic maturation. The liver-related markers and functions of HLCs were assessed at the gene and protein levels. After endodermal induction, the differentiated cells expressed endodermal markers forkhead box protein A2 and SRY-box containing gene 17 at the mRNA and protein levels. After 20 d of culture, the iPSCs were differentiated into HLCs. These differentiated cells expressed hepatic markers including α-fetoprotein, albumin CK8, CK18, CK19, and transcription factor HNF-4α. In addition, the cells expressed functional proteins such as α1-antitrypsin, cytochrome P450 1A2 and CYP 3A4. They acted like healthy hepatic cells, storing glycogen and taking up indocyanine green and low-density lipoproteins. Also, the rates of urea synthesis (20 d 1.202 ± 0.080 mg/dL vs 0 d 0.317 ± 0.021 mg/dL, P < 0.01) and albumin secretion (20 d 1.601 ± 0.102 mg/dL vs 0 d 0.313 ± 0.015 mg/dL, P < 0.01) increased significantly as differentiation progressed. Rat iPSCs can differentiate into HLCs rapidly and efficiently. These differentiated cells may be an attractive resource for treatment of end-stage liver disease.


Transcriptional profiles in liver from mice treated with hepatotumorigenic and nonhepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.
Conazoles are environmental and pharmaceutical fungicides. The present study relates the toxicological effects of conazoles to alterations of gene and pathway transcription and identifies potential modes of tumorigenic action. In a companion study employing conventional toxicological bioassays (Allen et al., 2006), male CD-1 mice were fed triadimefon, propiconazole, or myclobutanil in a continuous oral-dose regimen for 4, 30, or 90 days. These conazoles were found to induce hepatomegaly, to induce high levels of hepatic pentoxyresorufin-O-dealkylase activity, to increase hepatic cell proliferation, to decrease serum cholesterol, and to increase serum triglycerides. Differentially expressed genes and pathways were identified using Affymetrix GeneChips. Gene-pathway associations were obtained from the Kyoto Encyclopedia of Genes and Genomes, Biocarta, and MetaCore compendia. The pathway profiles of each conazole were different at each time point. In general, the number of altered metabolism, signaling, and growth pathways increased with time and dose and were greatest with propiconazole. All conazoles had effects on nuclear receptors as evidenced by increased expression and enzymatic activities of a series of related cytochrome P450s (CYP). A subset of altered genes and pathways distinguished the three conazoles from each other. Triadimefon and propiconazole both altered apoptosis, cell cycle, adherens junction, calcium signaling, and EGFR signaling pathways. Triadimefon produced greater changes in cholesterol biosynthesis and retinoic acid metabolism genes and in selected signaling pathways. Propiconazole had greater effects on genes responding to oxidative stress and on the IGF/P13K/AKt/PTEN/mTor and Wnt-beta-catenin pathways. In conclusion, while triadimefon, propiconazole, and myclobutanil had similar effects in mouse liver on hepatomegaly, histology, CYP activities, cell proliferation, and serum cholesterol, genomic analyses revealed major differences in their gene expression profiles.


Cognitive functioning and treatment outcomes in a randomized controlled trial of internet-delivered drug and alcohol treatment.
Substance use disorders are associated with lower cognitive functioning, and this impairment is associated with poorer outcomes. The Therapeutic Education System (TES) is an internet-based psychosocial intervention for substance use disorders that may provide enhanced treatment for individuals with cognitive deficits. This secondary analysis investigates the association between cognitive functioning and treatment outcomes in a large (N = 507) randomized controlled effectiveness trial of TES compared to treatment-as-usual conducted within outpatient programs in the National Drug Abuse Treatment Clinical Trials Network. All participants completed a computer-based cognitive assessment (Microcog™ short version) at baseline. Scores on subtests of attention, reasoning, and spatial perception were tested as moderators of the treatment effect on abstinence and retention at the end of the 12-week treatment phase using mixed effects logistic regression. Cognitive functioning was not found to be a moderator of treatment on abstinence or retention. Post-hoc analysis of the main effect of cognitive functioning on retention and abstinence found impaired reasoning and cognitive flexibility were associated with lower retention. There were no other main effects of cognitive functioning on retention or abstinence. The benefit of internet delivered treatment over standard care was unchanged across a range of cognitive functioning. Consistent with previous research, mild to moderate impairment in reasoning and cognitive flexibility were associated with lower retention across both treatment arms. An internet-delivered cognitive behavioral intervention for substance use disorders, TES, is equally effective across a spectrum of cognitive functioning among diverse patients. (Am J Addict 2018;27:509-515).


Development and evaluation of a novel training program to build study staff skills in equitable and inclusive engagement, recruitment, and retention of clinical research participants.
Adequate equitable recruitment of underrepresented groups in clinical research and trials is a national problem and remains a daunting challenge to translating research discoveries into effective healthcare practices. Engagement, recruitment, and retention (ER&R) training programs for Clinical Research Professionals (CRPs) often focus on policies and regulations. Although some training on the importance of diversity and inclusion in clinical research participation has recently been developed, there remains a need for training that couples critical equity, diversity, and inclusion (EDI) concepts with skill development in effective recruitment and retention strategies, regulations, and best practices. We developed the ER&R Certificate program as a holistic approach to provide Duke University CRPs the opportunity to build competency in gap areas and to increase comfort in championing equitable partnerships with clinical research participants. The thirteen core and elective courses include blended learning elements, such as e-learning and wiki journaling prompts, to facilitate meaningful discussions. Pre- and post-assessments administered to CRP program participants and their managers assessed program impact on CRP skills in ER&R tasks and comfort in equitable, diverse, and inclusive engagement of clinical research participants. Results from the first two cohorts indicate that CRPs perceived growth in their own comfort with program learning objectives, especially those centered on participant partnership and EDI principles, and most managers witnessed growth in competence and responsibility for ER&R-related tasks. Results suggest value in offering CRPs robust training programs that integrate EDI and ER&R training.


Thiocarbamate herbicide-inducible nonheme haloperoxidase of Rhodococcus erythropolis NI86/21.
During biodegradation of thiocarbamate herbicides by Rhodococcus erythropolis NI86/21, a protein with an M(r) of 30,000 is induced (I. Nagy, G. Schoofs, F. Compernolle, P. Proost, J. Vanderleyden, and R.De Mot, J. Bacteriol. 177:676-687, 1995). Based on N-terminal sequence data for the protein purified by two-dimensional electrophoresis, the corresponding structural gene, thcF, was cloned and sequenced. The deduced protein sequence of ThcF is homologous to those of nonheme haloperoxidases. A particularly high level of sequence identity (72.6%) was observed for the chloroperoxidase from Pseudomonas pyrrocinia. A polyclonal antibody against the latter enzyme cross-reacted with ThcF either produced by the original Rhodococcus cells or overexpressed heterologously in Escherichia coli. In both thiocarbamate-grown Rhodococcus cells and E. coli cells expressing thcF, the haloperoxidase activity of ThcF was demonstrated. The thiocarbamate-inducible R. erythropolis ThcF protein represents the first (nonheme) haloperoxidase to be identified in a nocardioform actinomycete.


Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma.
Reconstitution of T-cell immunity after bone marrow transplantation (BMT) is often delayed, resulting in a prolonged period of immunodeficiency. Donor lymphocyte infusion (DLI) has been used to enhance graft-versus-leukemia activity after BMT, but the effects of DLI on immune reconstitution have not been established. We studied 9 patients with multiple myeloma who received myeloablative therapy and T-cell-depleted allogeneic BMT followed 6 months later by infusion of lymphocytes from the same donor. DLI consisted of 3 x 10(7) CD4(+) donor T cells per kilogram obtained after in vitro depletion of CD8(+) cells. Cell surface phenotype of peripheral lymphocytes, T-cell receptor (TCR) V beta repertoire, TCR rearrangement excision circles (TRECs), and hematopoietic chimerism were studied in the first 6 months after BMT and for 1 year after DLI. These studies were also performed in 7 patients who received similar myeloablative therapy and BMT but without DLI. Phenotypic reconstitution of T and natural killer cells was similar in both groups, but patients who received CD4(+) DLI developed increased numbers of CD20(+) B cells. TCR V beta repertoire complexity was decreased at 3 and 6 months after BMT but improved more rapidly in patients who received DLI (P =.01). CD4(+) DLI was also associated with increased numbers of TRECs in CD3(+) T cells (P <.001) and with conversion to complete donor hematopoiesis (P =.05). These results provide evidence that prophylactic infusion of CD4(+) donor lymphocytes 6 months after BMT enhances reconstitution of donor T cells and conversion to donor hematopoiesis as well as promoting antitumor immunity.


AAV Gene Therapy for Alcoholism: Inhibition of Mitochondrial Aldehyde Dehydrogenase Enzyme Expression in Hepatoma Cells.
Most ethanol is broken down in the liver in two steps by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH2) enzymes, which metabolize down ethanol into acetaldehyde and then acetate. Some individuals from the Asian population who carry a mutation in the aldehyde dehydrogenase gene (ALDH2*2) cannot metabolize acetaldehyde as efficiently, producing strong effects, including facial flushing, dizziness, hypotension, and palpitations. This results in an aversion to alcohol intake and protection against alcoholism. The large prevalence of this mutation in the human population strongly suggests that modulation of ALDH2 expression by genetic technologies could result in a similar phenotype. scAAV2 vectors encoding ALDH2 small hairpin RNA (shRNA) were utilized to validate this hypothesis by silencing ALDH2 gene expression in human cell lines. Human cell lines HEK-293 and HepG2 were transduced with scAAV2/shRNA, showing a reduction in ALDH2 RNA and protein expression with the two viral concentration assayed (1 × 104 and 1 × 105 vg/cell) at two different time points. In both cell lines, ALDH2 RNA levels were reduced by 90% and protein expression was inhibited by 90% and 52%, respectively, 5 days post infection. Transduced HepG2 VL17A cells (ADH+) exposed to ethanol resulted in a 50% increase in acetaldehyde levels. These results suggest that gene therapy could be a useful tool for the treatment of alcoholism by knocking down ALDH2 expression using shRNA technology delivered by AAV vectors.


Development of high-throughput quantum dot biosensor against Polymyxa species.
The plasmodiophoromycete Polymyxa betae and P. graminis are eukaryotic biotrophic parasites residing in the roots of chenopodiacae and gramineae plants. They are natural transmitting agents of several important plant viruses such as are beet necrotic yellow vein virus (BNYW), beet soil borne mosaic virus (BSBMV), wheat soil-borne mosaic virus (WSBMV). Developing advanced high-throughput diagnostic methods capable of accurate detection of these pathogens could assist with the screening programs and consequently with the development of disease-resistant germplasms. In the present study, a previously developed quantum dots (QDs) FRET-based nano-biosensor was upgraded to a high-throughput version. QDs were functionalized with a specific antibody against the P. betae's specific glutathione-S-transferase (GST) protein. On the other hand, GST was conjugated to Rhodamine dye. Ninety six-well polystyrene plates were used as the detection platform. The mutual affinity of the antigen and the antibody brought the CdTe QDs and rhodamine together close enough to allow the resonance dipole-dipole coupling required for fluorescence resonance energy transfer (FRET) to occur. The immunosensor constructed showed a high sensitivity and specificity of 100%, and was successfully used for high-throughput screening of 96 real samples with consistent results within the course of less than 30 minutes.


Autophagy Dysregulation and Obesity-Associated Pathologies.
Autophagy is one of the major degradative mechanisms that can eliminate excessive nutrients, toxic protein aggregates, damaged organelles and invading microorganisms. In response to obesity and obesity-associated lipotoxic, proteotoxic and oxidative stresses, autophagy plays an essential role in maintaining physiological homeostasis. However, obesity and its associated stress insults can often interfere with the autophagic process through various mechanisms, which result in further aggravation of obesity-related metabolic pathologies in multiple metabolic organs. Paradoxically, inhibition of autophagy, within specific contexts, indirectly produces beneficial effects that can alleviate several detrimental consequences of obesity. In this minireview, we will provide a brief discussion about our current understanding of the impact of obesity on autophagy and the role of autophagy dysregulation in modulating obesity-associated pathological outcomes.


A novel and effective approach to generate germline-like monoclonal antibodies by integration of phage and mammalian cell display platforms.
Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.


Feeling sad makes us feel older: Effects of a sad-mood induction on subjective age.
A mood-induction paradigm was implemented in a sample of 144 adults covering midlife and old age (40-80 years) to investigate associations between mood and subjective age. Sad or neutral mood was induced by texts and music pieces. Subjective age was operationalized as felt age relative to chronological age. Participants receiving the sad-mood induction reported changes toward older felt ages from pre- to postinduction. Participants receiving the neutral-mood induction reported comparable levels of subjective age at pre- and postinduction. Effects were comparable across middle- and older aged participants. Results suggest that sad affective states might dampen subjective age. (PsycINFO Database Record


Bizarre leiomyoma of scrotum.
Genital leiomyomas of the scrotal skin are extremely rare benign tumors, originating from the tunica dartos of the scrotum. We report our experience with one patients with scrotal bizarre leiomyoma.


New perspectives on nursing lower limb amputees.
New perspectives on nursing lower limb amputees arise from the author's researches into amputee rehabilitation and a summary of other recent research findings. These are dealt with in the context of basic amputee treatment and the nursing process. There is new material on the psychological and neurological sequelae of amputation, the practical problems of loss of a limb and the prosthetic dimension of treatment. The patients' reactions to lower limb amputation were found to vary from intense grief to intense relief, many noting it to be of minor or moderate consequence. The model of sudden and shocking loss is largely incorrect. Attention is drawn to an unrecognized ordinariness which should become part of amputee nursing. Patients have many practical problems. These are social and economic, personal and domestic. The ward environment is unsuited to these needs but, working closely with therapists, nurses can do much to facilitate amputee rehabilitation. The modern purpose of amputation surgery is prosthetic replacement. Nurses should be working with some urgency towards uniting patient and prosthesis. Pain and discomfort are underestimated and research shows them to be a major characteristic of amputation continually and for many years after surgery. A variety of pain syndromes are involved.


Sex hormones and autoimmune rheumatic disorders.
It has now been recognized that there are complex interactions between the gonadal endocrine and the immune systems. The action of sex hormones on the immune system has important physiological and pathological consequences. The preponderance in women of autoimmune diseases in humans and in experimental animals has a basis in sex hormones. Hypoandrogenic/hyperestrogenic states are thought to contribute to the disease process. This article presents evidence for the action of sex hormones in various experimental animal models of autoimmune diseases and discusses several mechanisms of sex hormone action on the immune system. These mechanisms remain complex and it is to be hoped that the recent advances in immunology, endocrinology, pharmacology, and molecular biology will enable the description and clarification of these mechanisms of action.


Modifier genes for hypertrophic cardiomyopathy.
During the past decade, more than 100 mutations in 11 causal gene coding for sarcomeric proteins, the gamma subunit of AMP-activated protein kinase and triplet-repeat syndromes and in mitochondrial DNA, have been identified in patients with hypertrophic cardiomyopathy (HCM). Genotype-phenotype correlation studies show significant variability in the phenotype expression of HCM among affected individuals with identical causal mutations. Overall, causal mutations account for a fraction of the variability of phenotypes and genetic background, referred to as the modifier genes, play a significant role. The final phenotype is the result of interactions between the causal genes, genetic background (modifier genes), and probably the environmental factors. The individual modifier genes for HCM remain largely unknown, and a large-scale genome-wide approach and candidate gene analysis are needed. Current studies are limited to simple polymorphism association studies, which explore the association of functional single nucleotide polymorphisms in genes implicated in cardiac growth with the severity of the clinical phenotypes, primarily cardiac hypertrophy. Several potential modifier genes including genes encoding the components of the renin-angiotensin-aldosterone system have emerged. The most commonly implicated is an insertion/deletion polymorphism in the angiotensin-1 converting enzyme 1 gene, which is associated with the risk of sudden cardiac death and the severity of hypertrophy. Therapeutic interventions aimed at targeting the modifier genes have shown salutary effects in animal models of HCM. It has now recognized that modifier genes affect the expression of cardiac phenotype. Identification of the modifier genes will complement the results of studies of causative genes and could enhance genetic based diagnosis, risk stratification, and implementation of preventive and therapeutic measures in patients with HCM.


High response piezoelectric and piezoresistive materials for fast, low voltage switching: simulation and theory of transduction physics at the nanometer-scale.
Field effect transistors are reaching the limits imposed by the scaling of materials and the electrostatic gating physics underlying the device. In this Communication, a new type of switch based on different physics, which combines known piezoelectric and piezoresistive materials, is described and is shown by theory and simulation to achieve gigahertz digital switching at low voltage (0.1 V).


Exploring Chronic Drug Effects on Microengineered Human Liver Cultures Using Global Gene Expression Profiling.
Global gene expression profiling is useful for elucidating a drug's mechanism of action on the liver; however, such profiling in rats is not very sensitive for predicting human drug-induced liver injury, while dedifferentiated monolayers of primary human hepatocytes (PHHs) do not permit chronic drug treatment. In contrast, micropatterned cocultures (MPCCs) containing PHH colonies and 3T3-J2 fibroblasts maintain a stable liver phenotype for 4-6 weeks. Here, we used MPCCs to test the hypothesis that global gene expression patterns in stable PHHs can be used to distinguish clinical hepatotoxic drugs from their non-liver-toxic analogs and understand the mechanism of action prior to the onset of overt hepatotoxicity. We found that MPCCs treated with the clinical hepatotoxic/non-liver-toxic pair, troglitazone/rosiglitazone, at each drug's reported and non-toxic Cmax (maximum concentration in human plasma) for 1, 7, and 14 days displayed a total of 12, 269, and 628 differentially expressed genes, respectively, relative to the vehicle-treated control. Troglitazone modulated >75% of transcripts across pathways such as fatty acid and drug metabolism, oxidative stress, inflammatory response, and complement/coagulation cascades. Escalating rosiglitazone's dose to that of troglitazone's Cmax increased modulated transcripts relative to the lower dose; however, over half the identified transcripts were still exclusively modulated by troglitazone. Last, other hepatotoxins (nefazodone, ibufenac, and tolcapone) also induced a greater number of differentially expressed genes in MPCCs than their non-liver-toxic analogs (buspirone, ibuprofen, and entacapone) following 7 days of treatment. In conclusion, MPCCs allow evaluation of time- and dose-dependent gene expression patterns in PHHs treated chronically with analog drugs.


Storage induced changes in coliform, heterotrophic groups of bacteria and nutrient levels of human urine for its safe use in biological production.
Human urine is a potential source of various nutrients, minerals and trace elements. Its use as a fertilizer is growing popular among farmers. Here, we examined the pattern of changes in the counts of coliform, heterotrophic bacteria as well as physico-chemical characteristics of human urine during different days of storage under closed conditions at ambient temperature. We observed that after 253 days of storage under closed condition, the coliform counts were reduced significantly and remained within the safe limit to be used as fertilizer. With increase in storage period, the concentration of phosphate showed decline coupled with rise in pH, alkalinity and electrical conductance. Our study revealed that human urine can be used as safe fertilizer after 8 months of storage under closed conditions at ambient temperature ranging 25-35ºC.


Quantum Hall exciton condensation at full spin polarization.
Using Coulomb drag as a probe, we explore the excitonic phase transition in quantum Hall bilayers at nu(T) = 1 as a function of Zeeman energy E(Z). The critical layer separation (d/l)(c) for exciton condensation initially increases rapidly with E(Z), but then reaches a maximum and begins a gentle decline. At high E(Z), where both the excitonic phase at small d/l and the compressible phase at large d/l are fully spin polarized, we find that the width of the transition, as a function of d/l, is much larger than at small E(Z) and persists in the limit of zero temperature. We discuss these results in the context of two models in which the system contains a mixture of the two fluids.


Impact of arteriovenous fistula cannulation on the quality of dialysis.
Adequate hemodialysis directly improves health. Puncturing an arteriovenous fistula (AVF) and the amount of blood recirculation greatly affect the quality of dialysis. Few studies have assessed the method to cannulate a fistula and its influence on efficiency of hemodialysis. This prospective pilot study included 14 patients with end-stage renal failure receiving regular intermittent hemodialysis. Patients received three consecutive treatments with both needles directed upstream then three consecutive treatments with the venous needle directed upstream and the arterial needle directed downstream. With both techniques, the distance between the needles was kept constant at 2.5 cm. Recirculation rate and Kt/V ratio were measured during each treatment using thermodilution and a diascan Fresenius generator. The 14 patients received 84 hemodialysis sessions: i.e., 8 (57.1%) males and 6 (42.8%) females, mean age 62.3 ± 15.57 years. Results showed that mean recirculation rates and Kt/V did not significantly differ between the two techniques. Because no significant difference was found between the two techniques, the direction of insertion of needles should be decided upon on a case-by-case basis depending on the anatomy of the AVF and the feasibility of the puncture.


Achieving safe sharps practice.
The use of sharps should be avoided where possible. However, when their use is essential, particular care is required in handling and disposal and, if possible, safer devices should be used.


Mechanistic study on lowering the sensitivity of positive atmospheric pressure photoionization mass spectrometric analyses: size-dependent reactivity of solvent clusters.
Understanding the mechanism of atmospheric pressure photoionization (APPI) is important for studies employing APPI liquid chromatography/mass spectrometry (LC/MS). In this study, the APPI mechanism for polyaromatic hydrocarbon (PAH) compounds dissolved in toluene and methanol or water mixture was investigated by use of MS analysis and quantum mechanical simulation. In particular, four different mechanisms that could contribute to the signal reduction were considered based on a combination of MS data and quantum mechanical calculations. The APPI mechanism is clarified by combining MS data and density functional theory (DFT) calculations. To obtain MS data, a positive-mode (+) APPI Q Exactive Orbitrap mass spectrometer was used to analyze each solution. DFT calculations were performed using the general atomic and molecular electronic structure system (GAMESS). The experimental results indicated that methanol significantly reduced the signal in (+) APPI, but no significative signal reduction was observed when water was used as a co-solvent with toluene. The signal reduction is more significant especially for molecular ions than for protonated ions. Therefore, important information about the mechanism of methanol-induced signal reduction in (+) APPI-MS can be gained due its negative impact on APPI efficiency. The size-dependent reactivity of methanol clusters ((CH3 OH)n , n = 1-8) is an important factor in determining the sensitivity of (+) APPI-MS analyses. Clusters can compete with toluene radical ions for electrons. The reactivity increases as the sizes of the methanol clusters increase and this effect can be caused by the size-dependent ionization energy of the solvent clusters. The resulting increase in cluster reactivity explains the flow rate and temperature-dependent signal reduction observed in the analytes. Based on the results presented here, minimizing the sizes of methanol clusters can improve the sensitivity of LC/(+)-APPI-MS.


Iron Carbide@Carbon Nanocomposites: A Tool Box of Functional Materials.
Iron carbide (Fe₃C) is a ceramic magnetic material with high potential for applications in different fields, including catalysis, medicine imaging, coatings, and sensors. Despite its interesting properties, it is still somehow largely unexplored, probably due to challenging synthetic conditions. In this contribution, we present a sol-gel-based method that allows preparing different Fe₃C@C nanocomposites with tailored properties for specific applications, in particular, we have focused on and discussed potential uses for adsorption of noxious gas and waste removal. Nanocomposites were prepared using readily available and "green" sources, such as urea, simple and complex sugars, and chitosan. The nanocomposite prepared from chitosan was found to be more efficient for CO₂ uptake, while the sample synthetized from cellulose had optimal capability for dye absorption and waste oil removal from water.


Steroid receptor coactivator-1 can regulate osteoblastogenesis independently of estrogen.
Steroid receptor coactivator-1 (SRC-1), a well-studied coactivator of estrogen receptor (ER), is known to play an important and functional role in the development and maintenance of bone tissue. Previous reports suggest SRC-1 maintains bone mineral density primarily through its interaction with ER. Here we demonstrate that SRC-1 can also affect bone development independent of estrogen signaling as ovariectomized SRC-1 knockout (SRC-1 KO) mouse had decreased bone mineral density. To identify estrogen-independent SRC-1 target genes in osteoblastogenesis, we undertook an integrated analysis utilizing ChIP-Seq and mRNA microarray in transformed osteoblast-like U2OS-ERα cells. We identified critical osteoblast differentiation genes regulated by SRC-1, but not by estrogen including alkaline phosphatase and osteocalcin. Ex vivo primary culture of osteoblasts from SRC-1 wild-type and KO mice confirmed the role of SRC-1 in osteoblastogenesis, associated with altered ALPL levels. Together, these data indicate that SRC-1 can impact osteoblast function in an ER-independent manner.


Glycosaminoglycan functionalization of electrospun scaffolds enhances Schwann cell activity.
Nerve fibers of the peripheral nervous system (PNS) have a remarkable ability to regenerate up to an almost complete recovery of normal function following a crush or a Sunderland Type II injury. This process is governed by glial cells, known as Schwann cells, through their unique capacity to dedifferentiate into cells that drive the healing process. Despite that many progresses have occurred in restorative medicine and microsurgery, the regenerative process after a severe lesion of a major nerve trunk (e.g., Sunderland Types III-V) is often incomplete and functional recovery is unsatisfactory. In this aspect, it is known that glycosaminoglycans (GAGs) of the extracellular matrix are involved in proliferation, synaptogenesis, neural plasticity, and regeneration of the PNS. Here, we developed poly(caprolactone) (PCL) fibrous scaffolds functionalized with GAGs, which allowed us to assess their influence on the adhesion, proliferation, and differentiation of Schwann cells. We found that both aligned and random fiber scaffolds functionalized with GAGs resulted in increased cell proliferation on day 1. In addition, aligned functionalized scaffolds also resulted in increased GAG presence on day 1, probably because of cell extracellular matrix (ECM) formation and an increased syndecan-4 expression on day 7. A different modification and activation of Schwann cells in the presence of GAG versus no-GAG scaffolds was underlined by proteomic comparative analysis, where a general downregulation of the expression of intracellular/structural and synthetic proteins was shown on day 7 for GAG-functionalized scaffolds with regard to the nonfunctionalized ones. In conclusion, we have shown that GAG-functionalized scaffolds are effective in modulating Schwann cell behavior in terms of adhesion, proliferation, and differentiation and should be considered in strategies to improve PNS repair. STATEMENT OF SIGNIFICANCE: Nerve fibers functional recovery following a severe trauma of the Peripheral Nervous System (PNS) still represents a huge challenge for neurosurgery nowadays. In this respect, tissue engineering is committed to develop new constructs able to guide Schwann cells by mimicking the natural extracellular matrix environment. To this purpose, we successfully fabricated polycaprolactone (PCL) scaffolds with two well-defined fiber deposition patterns, functionalized with glycosaminoglycans (GAGs) and assessed for their potential as support for Schwann cells adhesion, growth and differentiation, by both classical biochemistry and LC-MS-based proteomic profiling. By this way, we showed that PCL-GAGs scaffolds could represent a promising artificial substrate that closely mimics the recently established pattern of Schwann cells migration into the regenerating nerve and, therefore, it should be considered in strategies to improve PNS repair.


Patterns of pesticide use in California and the implications for strategies for reduction of pesticides.
We used the California Pesticide Use Reports to study use of fungicides, bactericides, fumigants, and selected insecticides, primarily for vegetable, fruit, and nut production in California from 1993 to 2000. There were no obvious trends in decreased use of most compounds used to treat plant disease. However, growers have rapidly adopted recently introduced "conventional" compounds. There is very limited use of microbial biocontrol agents to control plant disease and no indication of an increase. We used case studies to explore the potential of different strategies to reduce pesticide use or risk. There have been reductions in use of organophosphate insecticides, largely by substitution with pyrethroids. Theoretically, replacement of "calendar spray" pesticide programs with "environmentally driven" programs could reduce pesticide use in years with lower disease pressure, but this assumes that the majority of growers currently use a "calendar spray" program and that growers who use less than recommended by an environmentally driven program would not increase their use.


Influence of cultivation conditions on mechanical and morphological properties of bacterial cellulose tubes.
Bacterial cellulose (BC) was deposited in tubular form by fermenting Acetobacter xylinum on top of silicone tubes as an oxygenated support and by blowing different concentrations of oxygen, that is, 21% (air), 35%, 50%, and 100%. Mechanical properties such as burst pressure and tensile properties were evaluated for all tubes. The burst pressure of the tubes increased with an increase in oxygen ratio and reached a top value of 880 mmHg at 100% oxygen. The Young's modulus was approximately 5 MPa for all tubes, irrespective of the oxygen ratio. The elongation to break decreased from 30% to 10-20% when the oxygen ratio was increased. The morphology of the tubes was characterized by Scanning Electron Microscopy (SEM). All tubes had an even inner side and a more porous outer side. The cross section indicated that the tubes are composed of layers and that the amount of layers and the yield of cellulose increased with an increase in oxygen ratio. We propose that an internal vessel wall with high density is required for the tube to sustain a certain pressure. An increase in wall thickness by an increase in oxygen ratio might explain the increasing burst pressure with increasing oxygen ratio. The fermentation method used renders it possible to produce branched tubes, tubes with unlimited length and inner diameters. Endothelial cells (ECs) were grown onto the lumen of the tubes. The cells formed a confluent layer after 7 days. The tubes potential as a vascular graft is currently under investigation in a large animal model at the Centre of Vascular Engineering, Sahlgrenska University


Rescue of hypoxia-inducible factor-1alpha-deficient tumor growth by wild-type cells is independent of vascular endothelial growth factor.
In tumors, rapid cell proliferation associated with deficient vascularization leads to areas of hypoxia. Tumor hypoxia has direct consequences on clinical and prognostic parameters and is a potential therapeutic target. The hypoxic response depends critically on hypoxia-inducible factor-1alpha (HIF-1alpha) in pathological (e.g., tumorigenesis) as well as physiological (e.g., development and wound healing) processes. By s.c. injection of HIF-1alpha(-/-) embryonic stem (ES) cells in nude mice, we were able to demonstrate the role of HIF-1alpha in cell differentiation of teratocarcinomas. HIF-1alpha(+/+) tumors grow fast and preferentially form neuronal tissue, whereas HIF-1alpha(-/-) tumors show delayed growth and favorably form mesenchyme-derived tissue. Mixing wild-type and HIF-1alpha(-/-) ES cells in the same tumor at a ratio as low as 1:100, we showed that HIF-1alpha(+/+) cells can rescue the growth of mixed tumors although these tumors are not significantly different phenotypically or genotypically from the original HIF-1alpha(-/-) tumors. Interestingly, these results are not restricted to teratocarcinomas: they were confirmed with mixtures of Hepa1/Hepa1C4 cells (where HIF-1beta is mutated), demonstrating that growth changes are not related to differences in differentiation observed within teratocarcinomas. We also showed that despite lower mRNA expression, vascular endothelial growth factor protein status in HIF-1alpha(-/-) and mixed tumors does not significantly differ from the HIF-1alpha(+/+) tumors. Moreover, we demonstrated that tumor vascularization remains proportional to vascular endothelial growth factor protein levels, but that hypoxic up-regulation of this growth factor is not the decisive factor influencing tumor growth. Differences in levels of apoptosis are not responsible for alteration in growth because poly(ADP-ribose) polymerase cleavage, a hallmark of the apoptotic process, was similar in HIF-1alpha(+/+), HIF-1alpha(-/-), and mixed tumors. Our data demonstrate that the HIF-1alpha-dependent response of a few cells is capable of sustaining the growth of the whole tumor, probably through the secretion of factors up-regulated under low oxygen conditions.


Cryosurgery after chemoembolization for hepatocellular carcinoma in patients with cirrhosis.
Most cirrhotic patients with hepatocellular carcinoma (HCC) are not candidates for resection. Transarterial chemoembolization (TACE) may ablate a significant portion of the tumor but has a high rate of recurrence. Cryosurgery may permit successful ablation of hepatic tumors but can be complicated by postoperative hemorrhage and is also associated with a significant risk of recurrence. The combination of the two techniques might be beneficial. We evaluated in a prospective study the safety and efficacy of this combination in cirrhotic patients with unresectable HCC. Fifteen patients were included in this study. All but one patient underwent one or several sessions of TACE before cryosurgery. Cryoablation was successfully performed in each patient. The patient who did not undergo preoperative TACE required reoperation for hemorrhage. Another patient with Child-Pugh class B cirrhosis died postoperatively of hepatic and multiorgan failure. At a mean follow-up of 2.5 years, three patients had recurrence of disease, and 13 of 15 patients were alive with the longest survival time being 5 years. The actuarial survival rate at 5 years was 79%. Cryosurgery after TACE is feasible in cirrhotic livers with HCC and can increase the cure rate in large tumors. TACE may reduce the risk of hemorrhage after cryosurgery but can increase the risk of hepatic failure in patients with poor hepatic function.


[An introduction to contextual family nursing therapy].
The author has extensive experience interacting with families in clinical settings, clinical competency, multidisciplinary collaboration experience, and experience exploring the development of the nursing role. I used four research steps to integrate several decades of research experience and findings in order to propose a theoretical framework and practical therapeutic competency. I hope this introduction offers insights to hardworking nurses and helps them address the many possible family situations that could arise in clinical settings.


Increase in Tac mRNA expression in natural killer-like cell line in response to interleukin-1 and interleukin-2 shown at the population and cellular level by in situ hybridization.
Our previous results have shown that the increased expression of the Tac component of the interleukin-2 (IL-2) receptor at the surface of a natural killer-like cell line (YTN10) in response to interleukin-1 (IL-1) is associated with an eightfold increase in Tac mRNA production. Tac expression was detected by flow cytometry and anti-Tac binding studies, and mRNA synthesis was assessed by Northern and dot blots. These findings have now been extended utilizing recombinant IL-1 and autoradiographic techniques in experiments using both the parent YT and YTN10 cells. In situ hybridization experiments have shown that the increase in mRNA expression is manifested both in the percentage of cells expressing it and in the level of expression per cell. Consistent results were obtained in both sublines. In addition, exposure of both sublines to recombinant IL-2 also induced increased Tac mRNA synthesis, while inducing only a marginal increase in Tac expression at the membrane level.


In vitro formation of DNA adducts with bile acids.
The in vitro experiment was carried out following 32P-postlabeling analysis to determine the DNA-reactive bile acids present in the human body. The unconjugated and conjugated forms of cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA) and lithocholic acid (LCA) were added to calf thymus DNA followed by 1 h of incubation at 37 degrees C. After the incubation the mixture was analyzed by the nuclease P1 modification of 32P-postlabeling. Among the 12 bile acids tested, our results showed that unconjugated CDCA and LCA and the glycine and taurine conjugates of LCA (g-LCA, t-LCA) were able to bind covalently with naked DNA in vitro without intervention of any catalyst. It was also shown that bile acid alone did not give any spot on TLC. These binding reactions depended on the bile acid concentration in a linear manner. The data on the extent of binding at a concentration of 0.1 mg/ml showed values of 28.5 (t-LCA), 23.7 (g-LCA), 3.47 (LCA) and 1.32 (CDCA) adducts per 10(8) nucleotides. These reactive bile acids were also incubated with COLO 205 human colon carcinoma cells and Hep G2 human hepatocellular carcinoma cells for 24 h, but no specific DNA adduct was formed. Further, when LCA or CDCA was administered into male Fischer 344 rats by gavage at a dose of 10 mg/rat every 8 h for 3 days, no specific DNA adduct was detected in their liver or colon. Covalent DNA adducts are believed to cause alteration of the primary structure of genes, which is potentially linked to carcinogenesis. Though our preliminary data failed to detect any bile acid-related DNA adducts in the cultured cells or in rats, the results may provide a basis for assuming some of these bile acids to be potential initiators of colon cancer.


Tendon-lengthening in squint surgery.
A procedure of tendon-lengthening to correct horizontal deviation of squinting eyes is repopularized. The principle is that the internus rectus muscle is exposed and divided into 3 portions which after suturing will form one elongated portion. Technique, dosage, suturing materials, instrumentation, disadvantages and advantages as well as postoperative care of this method are discussed.


Telehealth and the national health information technology strategic framework.
Telehealth has a role in the federally sponsored plan for health information technology (HIT) that encompasses electronic health records (EHRs) and the National Health Information Network (NHIN). The goals of telehealth and the national plan are complementary. One focuses on improving access to high quality health-care services and the other on the information systems to support those services. Telehealth needs the fully realized EHR to provide the best possible care when patients are geographically and chronologically separated from their providers. Some current telehealth projects are natural examples of how a distributed, accessible EHR such as that envisaged by the plan can be used to provide better care. The experiences of telehealth in organizing large networks of heterogeneous health-care entities can provide useful lessons as the process of implementing HIT moves forward.


Subsurface Defect Localization by Structured Heating Using Laser Projected Photothermal Thermography.
The presented method is used to locate subsurface defects oriented perpendicularly to the surface. To achieve this, we create destructively interfering thermal wave fields that are disturbed by the defect. This effect is measured and used to locate the defect. We form the destructively interfering wave fields by using a modified projector. The original light engine of the projector is replaced with a fiber-coupled high-power diode laser. Its beam is shaped and aligned to the projector's spatial light modulator and optimized for optimal optical throughput and homogeneous projection by first characterizing the beam profile, and, second, correcting it mechanically and numerically. A high-performance infrared (IR) camera is set up according to the tight geometrical situation (including corrections of the geometrical image distortions) and the requirement to detect weak temperature oscillations at the sample surface. Data acquisition can be performed once a synchronization between the individual thermal wave field sources, the scanning stage, and the IR camera is established by using a dedicated experimental setup which needs to be tuned to the specific material being investigated. During data post-processing, the relevant information on the presence of a defect below the surface of the sample is extracted. It is retrieved from the oscillating part of the acquired thermal radiation coming from the so-called depletion line of the sample surface. The exact location of the defect is deduced from the analysis of the spatial-temporal shape of these oscillations in a final step. The method is reference-free and very sensitive to changes within the thermal wave field. So far, the method has been tested with steel samples but is applicable to different materials as well, in particular to temperature sensitive materials.


Divergent Neuroinflammatory Regulation of Microglial TREM Expression and Involvement of NF-κB.
The triggering receptor expressed on myeloid cells (TREM) family of proteins are cell surface receptors with important roles in regulation of myeloid cell inflammatory activity. In the central nervous system, TREM2 is implicated in further roles in microglial homeostasis, neuroinflammation and neurodegeneration. Different TREM receptors appear to have contrasting roles in controlling myeloid immune activity therefore the relative and co-ordinated regulation of their expression is important to understand but is currently poorly understood. We sought to determine how microglial TREM expression is affected under neuroinflammatory conditions in vitro and in vivo. Our data show that microglial Trem1 and Trem2 gene expression are regulated in an opposing manner by lipopolysaccharide (LPS) in vitro in both adult murine and human microglia. LPS caused a significant induction of Trem1 and a contrasting suppression of Trem2 expression. We also observed similar divergent Trem1 and Trem2 responses in vivo in response to acute brain inflammation and acute cerebral ischaemia. Our data show that inhibition of NF-κB activation prevents the LPS-induced alterations in both Trem1 and Trem2 expression in vitro indicating NF-κB as a common signaling intermediate controlling these divergent responses. Distinct patterns of microglial Trem1 induction and Trem2 suppression to different Toll-like receptor (TLR) ligands were also evident, notably with Trem1 induction restricted to those ligands activating TLRs signaling via TRIF. Our data show co-ordinated but divergent regulation of microglial TREM receptor expression with a central role for NF-κB. Neuroinflammatory conditions that alter the balance in TREM expression could therefore be an important influence on microglial inflammatory and homeostatic activity with implications for neuroinflammatory and neurodegenerative disease.


Quantized Exciton Motion and Fine Energy-Level Structure of a Single Perovskite Nanowire.
The quantum-confinement effect profoundly influences the exciton energy-level structures and recombination dynamics of semiconductor nanostructures but remains largely unexplored in traditional one-dimensional nanowires mainly due to their poor optical qualities. Here, we show that in defect-tolerant perovskite material of highly luminescent CsPbBr3 nanowires, the exciton's center-of-mass motion perpendicular to the axial direction is severely confined. This is reflected in the two sets of photoluminescence spectra emitted from a single CsPbBr3 nanowire, each of which consists of doublet peaks with linear polarizations perpendicular and parallel to the axial direction. Moreover, different exciton states can be mixed by the Rashba spin-orbit coupling effect, resulting in two single photoluminescence peaks with linear polarizations both along the nanowire axis. The above findings mark the emergence of an ideal platform for the exploration of intrinsic one-dimensional exciton photophysics and optoelectronics, thus bridging the long-missing research gap between the well-studied two- and zero-dimensional semiconductor nanostructures.


Energy-Efficient Channel Coding Strategy for Underwater Acoustic Networks.
Underwater acoustic networks (UAN) allow for efficiently exploiting and monitoring the sub-aquatic environment. These networks are characterized by long propagation delays, error-prone channels and half-duplex communication. In this paper, we address the problem of energy-efficient communication through the use of optimized channel coding parameters. We consider a two-layer encoding scheme employing forward error correction (FEC) codes and fountain codes (FC) for UAN scenarios without feedback channels. We model and evaluate the energy consumption of different channel coding schemes for a K-distributed multipath channel. The parameters of the FEC encoding layer are optimized by selecting the optimal error correction capability and the code block size. The results show the best parameter choice as a function of the link distance and received signal-to-noise ratio.


Age-related macular degeneration: what do patients find on the internet?
To assess the quality of information and readability of the top internet sites for age-related macular degeneration (AMD). An examination of the technical information provision, quality and readability of websites found during an internet search for 'age-related macular degeneration'. Setting Six internet search engines were used to find 26 unique sites on AMD. Technical information and quality were assessed using a simple grading system. Readability was assessed using a Simple Measure Of Gobbledygook (SMOG) rating. Twelve organizational, seven academic and seven commercial sites were identified. The average technical scores were 82.3%, 67.9% and 65.2% for each type of site, respectively (P=0.097, one way ANOVA). The average quality scores were 62.2%, 62.6%, and 49.5% for each type of site, respectively (P=0.356, one-way ANOVA). The average SMOG ratings were 16.3, 16.1, and 16.2 for each type of site, respectively (P=0.983, one-way ANOVA). Fifteen of the sites provided details of new and emerging treatments, with seven providing a detailed discussion. Many websites are now meeting the challenge of providing comprehensive information about AMD and its new treatments. Quality scores were disappointing, with sites needing to provide more evidence of authorship and attribution of information. The majority of sites had SMOG scores above 10, making them difficult for the average person to understand. As physicians we need to help design and direct patients to sites that provide high quality, current information.


Learning and Inferring "Dark Matter" and Predicting Human Intents and Trajectories in Videos.
This paper presents a method for localizing functional objects and predicting human intents and trajectories in surveillance videos of public spaces, under no supervision in training. People in public spaces are expected to intentionally take shortest paths (subject to obstacles) toward certain objects (e.g., vending machine, picnic table, dumpster etc.) where they can satisfy certain needs (e.g., quench thirst). Since these objects are typically very small or heavily occluded, they cannot be inferred by their visual appearance but indirectly by their influence on people's trajectories. Therefore, we call them "dark matter", by analogy to cosmology, since their presence can only be observed as attractive or repulsive "fields" in the public space. A person in the scene is modeled as an intelligent agent engaged in one of the "fields" selected depending his/her intent. An agent's trajectory is derived from an Agent-based Lagrangian Mechanics. The agents can change their intents in the middle of motion and thus alter the trajectory. For evaluation, we compiled and annotated a new dataset. The results demonstrate our effectiveness in predicting human intent behaviors and trajectories, and localizing and discovering distinct types of "dark matter" in wide public spaces.


Immobilization of soluble fibrin on factor XIIIa-coated polystyrene beads mediated by N-terminal fibronectin fragments. II. Demonstration of covalent adducts of fibrin peptide chains and fibronectin fragments.
Previous experiments had shown that the free N-terminal fibronectin 30-kDa-domain mediates binding of soluble 125I-fibrin to transamidase-coated polystyrene beads (Hörmann et al., Biol. Chem. Hoppe-Seyler 368, 669-674, 1987). Now, the formation of covalent adducts of the N-terminal fragment with fibrin peptide chains is demonstrated. Binding of soluble 125I-fibrin was performed in presence of N-terminal fibronectin 30-kDa or 70-kDa fragments. The material adsorbed was removed from the beads under reducing conditions and analysed by dodecylsulfate gel electrophoresis followed by autoradiography. The 30-kDa fragment gave rise to bands of 80 kDa and 180-200 kDa which were lacking in the products of the 70-kDa compound. Instead, they showed bands at 120 kDa and ca. 280 kDa. Evidently, those bands represented covalent adducts of fibrin peptide chains or their dimers with the 30-kDa or the 70-kDa fragment, respectively. In addition, dimeric gamma-chains and alpha-chain polymers of fibrin were present indicating partial polymerization of bead-attached fibrin.


Defective neutrophil function in the autoimmune mouse strain MRL/lpr. Potential role of transforming growth factor-beta.
Patients with systemic autoimmune diseases such as SLE and rheumatoid arthritis have increased rates of morbidity and mortality caused by infection. Although this increased risk of infection has been primarily attributed to therapeutic immuno-suppression, some reports exist of defective polymorphonuclear leukocytes (PMN) function in these patients. The purpose of the present work is to investigate the recruitment of PMN phagocytic function in a murine model of autoimmunity, the MRL/lpr mouse. PMN from MRL/lpr, but not from congenic MRL/n mice, exhibit a marked defect in the amplification of FcR-mediated phagocytosis stimulated by various inflammatory mediators. This defect is acquired and correlates with the onset of the autoimmune disease observed in this strain. In addition, MRL/lpr but not MRL/n PMN exhibit a defect in extravasation into the thioglycollate-inflamed peritoneum. Incubation of MRL/n PMN in MRL/lpr serum induces a defect in the amplification of PMN phagocytic function identical to that observed with MRL/lpr PMN. The activity in the serum that induces this defect is neutralized by an antibody to TGF-beta but not by control antibodies. Incubation of murine and human PMN with purified TGF-beta induces an identical defect in stimulated FcR-mediated ingestion. In addition, TGF-beta-treated MRL/n PMN fail to extravasate into the thioglycollate-inflamed peritoneum after injection into normal MRL/n recipient mice. In addition, direct injection of TGF-beta into MRL/n mice also reduces the percentage and number of PMN in the thioglycollate-stimulated peritoneal exudates of these mice. The defect in PMN extravasation and phagocytic function was not caused by failure of the defective PMN to modulate the expression of the adhesion molecules, Mac-1 and Mel-14. These data indicate that defects in PMN function can be observed in a murine model of autoimmunity and that spontaneous production of TGF-beta possibly may play a crucial role in the pathogenesis of the defective PMN function in this animal model.