Pediatric In-Hospital Acute Respiratory Compromise: A Report From the American Heart Association's Get With the Guidelines-Resuscitation Registry.
The main objectives of this study were to describe in-hospital acute respiratory compromise among children (< 18 yr old), and its association with cardiac arrest and in-hospital mortality. Observational study using prospectively collected data. U.S. hospitals reporting data to the "Get With The Guidelines-Resuscitation" registry. Pediatric patients (< 18 yr old) with acute respiratory compromise. Acute respiratory compromise was defined as absent, agonal, or inadequate respiration that required emergency assisted ventilation and elicited a hospital-wide or unit-based emergency response. None. The primary outcome was in-hospital mortality. Cardiac arrest during the event was a secondary outcome. To assess the association between patient, event, and hospital characteristics and the outcomes, we created multivariable logistic regressions models accounting for within-hospital clustering. One thousand nine hundred fifty-two patients from 151 hospitals were included. Forty percent of the events occurred on the wards, 19% in the emergency department, 25% in the ICU, and 16% in other locations. Two hundred eighty patients (14.6%) died before hospital discharge. Preexisting hypotension (odds ratio, 3.26 [95% CI, 1.89-5.62]; p < 0.001) and septicemia (odds ratio, 2.46 [95% CI, 1.52-3.97]; p < 0.001) were associated with increased mortality. The acute respiratory compromise event was temporally associated with a cardiac arrest in 182 patients (9.3%), among whom 46.2% died. One thousand two hundred eight patients (62%) required tracheal intubation during the event. In-hospital mortality among patients requiring tracheal intubation during the event was 18.6%. In this large, multicenter study of acute respiratory compromise, 40% occurred in ward settings, 9.3% had an associated cardiac arrest, and overall in-hospital mortality was 14.6%. Preevent hypotension and septicemia were associated with increased mortality rate.


N tau-Methylhistidine excretion and myofibrillar protein breakdown in patients receiving intravenous or enteral nutrition.
1. N tau-Methylhistidine, nitrogen and creatinine were measured in the urine of 10 volunteers on normal and meat-free diets and in 10 vegetarians, and compared with the results from the urine of eight patients with intestine fistulae on intravenous or enteral nutrition containing no meat. The values obtained were used to calculate fractional breakdown rate of myofibrillar protein. 2. There was a significant fall in the excretion of N tau-methylhistidine and creatinine and in apparent fractional breakdown rates after 2 days on a meat-free diet. 3. One of the patients had lower, and two of the patients had higher, fractional breakdown rates compared with the vegetarians. 4. N tau-Methylhistidine and creatinine excretion may be a useful and non-invasive measurement of myofibrillar protein degradation in patients on meat-free diets. Firm conclusions cannot, however, be drawn without confirmatory, direct measurement of the breakdown rates of muscle protein in vivo.


Does the kyphotic change decrease the risk of fall?
Falls are a major problem in the elderly. Age-related degeneration of the human balance system increases the risk of falls. Kyphosis is a common condition of curvature of the upper spine in the elderly and its development occurs through degenerative change. However, relatively little is known about the effect of kyphotic changes on balance in the elderly. The aim of this study is to investigate the influence of kyphosis on the balance strategy through use of the motor control test (MCT) in computerized dynamic posturography. Fifty healthy subjects who were not affected by other medical disorders that could affect gait or balance were enrolled in the study. By simulation of kyphotic condition through change of the angles of the line connecting the shoulder to the hip and the ankle axis by approximately 30°, the latency and amplitude of the MCT were measured in upright and kyphotic condition. In the kyphotic condition, latency was shortened in backward movement. In forward movement, latency was shortened only in large stimulation. The amplitude in forward movement was decreased in kyphotic condition. However, the change of amplitude was not significant in large intensity backward movement in the same condition. Kyphotic condition decreases the latency of MCT, especially in backward movement. These findings imply that kyphotic condition may serve as a protective factor against falls.


Damage to actin filaments by glutaraldehyde: protection by tropomyosin.
Reaction of F-actin and the F-actin-tropomyosin complex with 20 mM glutaraldehyde for 19-22 h at 0 degrees C and 25 degrees C results in extensively cross-linked filaments, as judged by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. Electron micrographs show shorter, more irregular filaments for glutaraldehyde-treated F-actin in the absence of tropomyosin as compared to the presence of tropomyosin or untreated controls. There was a 40% drop in viscosity of glutaraldehyde-treated F-actin solutions but a 90% increase in viscosity for the glutaraldehyde-treated F-actin-tropomyosin complex in solution, as compared to the untreated controls, indicating different effects of cross-linking. SDS gels indicate that intrasubunit cross-links are introduced into F-actin and that when tropomyosin is present, intramolecular cross-link formation is inhibited. Inhibition of the salt-induced G leads to F polymerization results when intramolecular cross-links are introduced into G-actin under similar or milder reaction conditions. These data indicate that, under conditions for which extensive F-actin filament cross-linking (fixing) occurs, the filaments become damaged due to the concurrent formation of intrasubunit cross-links that cause local depolymerization and distortion and that tropomyosin protects against this damage.


Effect of intraluminal hydrocortisone on solute and water absorption in the human jejunum.
To compare the effects of intravenous and intraluminal hydrocortisone on jejunal transport, the proximal jejunum was perfused with glucose (28 mmol/l) in saline in two groups of normal subjects. In the first group of seven subjects, compared with the control period results there were no changes in sodium, water and glucose absorption during the intravenous administration of hydrocortisone. In contrast, intraluminal hydrocortisone (100 mg/l) increased sodium, water and glucose absorption by 169%, 223% and 81% respectively (P less than 0.001 in each case) above the control values, when peripheral plasma cortisol levels were similar to those achieved with intravenous hydrocortisone. In the second group of three subjects, intraluminal hydrocortisone (10 mg/l and 30 mg/l), followed by an intravenous infusion of hydrocortisone, had no effects on sodium, water and glucose absorption. In a third group of six normal subjects perfused with fructose (28 mmol/l) in saline and bicarbonate (28 mmol/l) in saline intraluminal hydrocortisone (100 mg/l) had no effect on solute and water absorption. These results suggest that intraluminal hydrocortisone stimulates glucose-coupled sodium transport by exerting a topical effect on the apical membrane of the jejunal mucosa.


Antimicrobial Activities of Marine Sponge-Associated Bacteria.
The misuse and overuse of antibiotics have led to the emergence of multidrug-resistant microorganisms, which decreases the chance of treating those infected with existing antibiotics. This resistance calls for the search of new antimicrobials from prolific producers of novel natural products including marine sponges. Many of the novel active compounds reported from sponges have originated from their microbial symbionts. Therefore, this study aims to screen for bioactive metabolites from bacteria isolated from sponges. Twelve sponge samples were collected from South Australian marine environments and grown on seven isolation media under four incubation conditions; a total of 1234 bacterial isolates were obtained. Of these, 169 bacteria were tested in media optimized for production of antimicrobial metabolites and screened against eleven human pathogens. Seventy bacteria were found to be active against at least one test bacterial or fungal pathogen, while 37% of the tested bacteria showed activity against Staphylococcus aureus including methicillin-resistant strains and antifungal activity was produced by 21% the isolates. A potential novel active compound was purified possessing inhibitory activity against S. aureus. Using 16S rRNA, the strain was identified as Streptomyces sp. Our study highlights that the marine sponges of South Australia are a rich source of abundant and diverse bacteria producing metabolites with antimicrobial activities against human pathogenic bacteria and fungi.


Nanodentistry: combining nanostructured materials and stem cells for dental tissue regeneration.
Regenerative dentistry represents an attractive multidisciplinary therapeutic approach that complements traditional restorative/surgery techniques and benefits from recent advances in stem cell biology, molecular biology, genomics and proteomics. Materials science is important in such advances to move regenerative dentistry from the laboratory to the clinic. The design of novel nanostructured materials, such as biomimetic matrices and scaffolds for controlling cell fate and differentiation, and nanoparticles for diagnostics, imaging and targeted treatment, is needed. The combination of nanotechnology, which allows the creation of sophisticated materials with exquisite fine structural detail, and stem cell biology turns out to be increasingly useful in regenerative medicine. The administration to patients of dynamic biological agents comprising stem cells, bioactive scaffolds and/or nanoparticles will certainly increase the regenerative impact of dental pathological tissues. This overview briefly describes some of the actual benefits and future possibilities of nanomaterials in the emerging field of stem cell-based regenerative dentistry.


Mechanism of the antimicrobial action of pyrithione: effects on membrane transport, ATP levels, and protein synthesis.
Pyrithione is a general inhibitor of membrane transport processes in fungi. A brief preincubation of Penicillium mycelia with pyrithione resulted in a marked decrease in the activities of a variety of independently regulated transport systems, including those for inorganic sulfate, inorganic phosphate, methylamine (actually, the NH(4) (+) permease), choline-O-sulfate, glucose, l-methionine (a specific system), and several hydrophobic l-alpha-amino acids (the general amino acid permease). The degree of inhibition at any fixed pyrithione concentration and exposure time increased as the pH of the incubation medium was decreased. This result strongly suggests that the active species is the un-ionized molecule and that pyrithione acts by collapsing a transmembrane DeltapH driving force. The degree of transport inhibition caused by a given concentration of pyrithione increased with increasing time of exposure to the inhibitor. However, exposure time and pyrithione concentration were not reciprocally related. At "low" pyrithione concentrations, transport inhibition plateaued at some finite value. This observation suggests that the fungi can detoxify low levels of the inhibitor. The concentration of pyrithione required for a given degree of growth inhibition increased as the experimental mycelial density increased. This phenomenon was consistent with the suggestion that the fungi are capable of inactivating pyrithione.


Tracing syndrome-specific trajectories of attention across the lifespan.
This paper maintains that studies of atypical attention targeting one particular age group are unlikely to be informative of syndrome-specific deficits and their developmental changes. We propose a new approach to the study of attentional deficits in genetic disorders, arguing for tracing cross-syndrome developmental trajectories from infancy through childhood to adulthood. Few studies have incorporated a developmental approach to determine whether the pattern of deficits and proficiencies remains constant across developmental time. Fewer still have included a cross-syndrome perspective to address these issues. Focusing on the cognitive domain of attention and its component parts, and using a cross-syndrome developmental perspective, the present set of studies compared the trajectories of different aspects of attention in three developmental disorders: Fragile X syndrome (FXS), Down syndrome (DS) and Williams syndrome (WS). Hitherto, these syndromes have all been reported as displaying serious "attentional deficits" above those expected in the general population. We predicted that, when one considers in greater detail subcomponent processes of attention, then ostensibly common difficulties do not necessarily emerge from common developmental pathways. We addressed this question with two studies. The first focused on inhibitory control, orienting and selective attention in infants and toddlers, and the second concentrated on selective attention, sustained attention and inhibitory control in mid-late childhood. The current results and their integration with earlier findings in adults point both to commonalities and to important syndrome-specific differences in attentional component processes, questioning whether profiles remain constant across developmental time.


Transcription factor FOXC2 demarcates the jugular lymphangiogenic region in avian embryos.
In the human, mutations of the forkhead winged-helix transcription factor FOXC2 cause the lymphedema-distichiasis syndrome, which is characterized by a double row of eyelashes and pubertal onset lymphedema of the legs due to hyperplasia and malformation of lymphatic collectors. While a function of FOXC2 for the differentiation of lymphatic collectors is well documented, recent studies have indicated an early function for the sprouting of lymphatics from embryonic veins. We studied the expression of FoxC2 in early avian embryos and compared its expression pattern with that of the homeobox transcription factor Prox1, which is essential for lymphatic endothelial cell (LEC) development. We show that FoxC2 demarcates a segment of the somatopleura in the cervical region on embryonic day (ED) 3, before Prox1 is expressed. On ED 4, its expression domain coincides with that of Prox1 in the jugular region. This region is characterized by the confluence of Tie2-positive anterior and posterior cardinal veins. It has been shown that Prox1 expression in a subpopulation of venous endothelial cells induces transdifferentiation into LECs. Our data suggest that FoxC2, in addition to its late functions during lymph collector differentiation, has an early function during lymphendothelial commitment of venous ECs in the jugular region.


Metabolic syndrome among Puerto Ricans and other Hispanic populations.
Metabolic syndrome is a cluster of risk factors for cardiovascular disease that affects an estimated 50 million Americans. The present article reviews this syndrome with respect to its definition, epidemiology, pathophysiology, and management. A primary focus in research has been to elucidate the processes that have been determined to cause insulin resistance, the fundamental mechanism underlying metabolic syndrome; these processes are reviewed here along with the interplay of the syndrome with the renin-angiotensin system, circadian rhythm, and atherosclerosis. Lifestyle changes promoting exercise and a healthy diet can reduce the incidence and prevent the progression of metabolic syndrome; however, refractory cases may warrant drug therapy. Recent emphasis has been placed on targeting obesity and insulin resistance as new therapeutic modalities are developed. In this manuscript, the incidence, component characteristics, and complications of metabolic syndrome in island-living Puerto Ricans and other Hispanic populations are described. The fact that island patients suffering from the syndrome tend to have less aggressive coronary disease and relatively normal lipid profile compared to their stateside counterparts is also discussed.


Suppression of hypothalmic-pituitary-adrenal axis responses to stress in lactating women.
In the rat, lactation suppresses a variety of physiological responses to stress. We investigated whether stress-responsive neurohormonal systems are also restrained during breast feeding in humans. We chose treadmill exercise as a stressor because this stimulus produces an exercise intensity-dependent activation of the hypothalamic-pituitary-adrenal axis and the sympathomedullary system that is independent of differences in physical conditioning among subjects. Ten lactating and ten nonlactating women who were between 7 and 18 weeks postpartum performed 20 min of graded treadmill exercise. The final 5 min of exercise was set to elicit 90% of the maximal oxygen uptake of each subject. Plasma ACTH, cortisol, and glucose responses to exercise were significantly attenuated in lactating women (P < 0.001, P < 0.05, and P < 0.001, respectively). Basal norepinephrine levels were also reduced in lactating women (P < 0.05). These results indicate that stress-responsive neurohormonal systems are restrained in lactating women.


What Teachers Should Know About the Bootstrap: Resampling in the Undergraduate Statistics Curriculum.
Bootstrapping has enormous potential in statistics education and practice, but there are subtle issues and ways to go wrong. For example, the common combination of nonparametric bootstrapping and bootstrap percentile confidence intervals is less accurate than using t-intervals for small samples, though more accurate for larger samples. My goals in this article are to provide a deeper understanding of bootstrap methods-how they work, when they work or not, and which methods work better-and to highlight pedagogical issues. Supplementary materials for this article are available online. [Received December 2014. Revised August 2015].


Insurer Market Power Lowers Prices In Numerous Concentrated Provider Markets.
Using prices of hospital admissions and visits to five types of physicians, we analyzed how provider and insurer market concentration-as measured by the Herfindahl-Hirschman Index (HHI)-interact and are correlated with prices. We found evidence that in the range of the Department of Justice's and Federal Trade Commission's definition of a moderately concentrated market (HHI of 1,500-2,500), insurers have the bargaining power to reduce provider prices in highly concentrated provider markets. In particular, hospital admission prices were 5 percent lower and cardiologist, radiologist, and hematologist/oncologist visit prices were 4 percent, 7 percent, and 19 percent lower, respectively, in markets with high provider concentration and insurer HHI above 2,000, compared to such markets with insurer HHI below 2,000. We did not find evidence that high insurer concentration reduced visit prices for primary care physicians or orthopedists, however. The policy dilemma that arises from our findings is that there are no insurer market mechanisms that will pass a portion of these price reductions on to consumers in the form of lower premiums. Large purchasers of health insurance such as state and federal governments, as well as the use of regulatory approaches, could provide a solution.


In vivo study of trichoderma-pathogen-plant interactions, using constitutive and inducible green fluorescent protein reporter systems.
Plant tissue colonization by Trichoderma atroviride plays a critical role in the reduction of diseases caused by phytopathogenic fungi, but this process has not been thoroughly studied in situ. We monitored in situ interactions between gfp-tagged biocontrol strains of T. atroviride and soilborne plant pathogens that were grown in cocultures and on cucumber seeds by confocal scanning laser microscopy and fluorescence stereomicroscopy. Spores of T. atroviride adhered to Pythium ultimum mycelia in coculture experiments. In mycoparasitic interactions of T. atroviride with P. ultimum or Rhizoctonia solani, the mycoparasitic hyphae grew alongside the pathogen mycelia, and this was followed by coiling and formation of specialized structures similar to hooks, appressoria, and papillae. The morphological changes observed depended on the pathogen tested. Branching of T. atroviride mycelium appeared to be an active response to the presence of the pathogenic host. Mycoparasitism of P. ultimum by T. atroviride occurred on cucumber seed surfaces while the seeds were germinating. The interaction of these fungi on the cucumber seeds was similar to the interaction observed in coculture experiments. Green fluorescent protein expression under the control of host-inducible promoters was also studied. The induction of specific Trichoderma genes was monitored visually in cocultures, on plant surfaces, and in soil in the presence of colloidal chitin or Rhizoctonia by confocal microscopy and fluorescence stereomicroscopy. These tools allowed initiation of the mycoparasitic gene expression cascade to be monitored in vivo.


Whole genome sequencing.
Whole genome sequencing provides the most comprehensive collection of an individual's genetic variation. With the falling costs of sequencing technology, we envision paradigm shift from microarray-based genotyping studies to whole genome sequencing. We review methodologies for whole genome sequencing. There are two approaches for assembling short shotgun sequence reads into longer contiguous genomic sequences. In the de novo assembly approach, sequence reads are compared to each other, and then overlapped to build longer contiguous sequences. The reference-based assembly approach involves mapping each read to a reference genome sequence. We discuss methods for identifying genetic variation (single nucleotide polymorphisms, small indels, and copy number variants) and building haplotypes from genome assemblies, and discuss potential pitfalls. We expect methodologies to evolve rapidly as sequencing technologies improve and more human genomes are sequenced.


Melatonin improves memory acquisition under stress independent of stress hormone release.
Animal studies suggest that the pineal hormone melatonin influences basal stress hormone levels and dampens hormone reactivity to stress. We investigated whether melatonin also has a suppressive effect on stress-induced catecholamine and cortisol release in humans. As stress hormones affect memory processing, we further examined a possible accompanying modulation of memory function. Fifty healthy young men received a single oral dose of either 3 mg melatonin (n = 27) or placebo medication (n = 23). One hour later, they were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). During stress, subjects encoded objects distributed in the test room, for which memory was assessed a day later ("memory encoding under stress"). Fifteen minutes following stress, memory retrieval for words learnt the day before was tested ("memory retrieval after stress"). Plasma epinephrine and norepinephrine levels, salivary free cortisol levels and psychological responses (attention, wakefulness) were repeatedly measured before and after stress exposure. Melatonin specifically enhanced recognition memory accuracy of objects encoded under stress (p < 0.001). In contrast, 15 min after stress, when cortisol levels were highest, retrieval of memories acquired the day before was not influenced by melatonin. Moreover, melatonin did not influence stress-induced elevation of catecholamine and cortisol levels which in turn did not correlate with the effects of melatonin on memory. The findings point to a primary action of melatonin on central nervous stimulus processing under conditions of stress and possibly on memory consolidation and exclude any substantial suppressive action of the substance on hormonal stress responses.


Family cancer history affecting risk of colorectal cancer in a prospective cohort of Chinese women.
An elevated risk of colorectal cancer has been associated with sporadic colorectal cancer in first-degree relatives, mostly in Western populations. Limited data exist from traditionally low-risk areas, such as Asia, where the prevalence of risk factors may differ. We examined the association of family history of cancer and subsequent colorectal cancer risk in a cohort of traditionally low-risk Chinese women. We followed 73,358 women in the Shanghai Women's Health Study for cancer incidence until December 2005. After an average of 7 years of follow-up, 391 women were diagnosed with colorectal cancer. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards models adjusted for age, smoking, family income, education, body mass index, physical activity, and history of diabetes. We observed a significant association between colorectal cancer risk and history of a parent being diagnosed with colorectal cancer (hazard ratio: 3.34; 95% confidence interval: 1.58, 7.06). No association was observed for colorectal cancer diagnosed among siblings. Colorectal cancer risk was not influenced by a positive family history of cancer generally or any of the other cancers investigated (lung, breast, prostate, gastric, esophageal, endometrial, ovarian, urinary tract, central nervous system, and small bowel). Our cohort results suggest that consistent with findings from Western populations, having a family history of colorectal cancer may influence colorectal cancer risk to a similar extent in a low-risk population.


Transgenerational and intergenerational epigenetic inheritance in allergic diseases.
It has become clear that early life (including in utero exposures) is a key window of vulnerability during which environmental exposures can alter developmental trajectories and initiate allergic disease development. However, recent evidence suggests that there might be additional windows of vulnerability to environmental exposures in the parental generation before conception or even in previous generations. There is evidence suggesting that information of prior exposures can be transferred across generations, and experimental animal models suggest that such transmission can be conveyed through epigenetic mechanisms. Although the molecular mechanisms of intergenerational and transgenerationational epigenetic transmission have yet to be determined, the realization that environment before conception can alter the risks of allergic diseases has profound implications for the development of public health interventions to prevent disease. Future research in both experimental models and in multigenerational human cohorts is needed to better understand the role of intergenerational and transgenerational effects in patients with asthma and allergic disease. This will provide the knowledge basis for a new approach to efficient intervention strategies aimed at reducing the major public health challenge of these conditions.


Calponin repeats regulate actin filament stability and formation of podosomes in smooth muscle cells.
Phorbol ester induces actin cytoskeleton rearrangements in cultured vascular smooth muscle cells. Calponin and SM22 alpha are major components of differentiated smooth muscle and potential regulators of actin cytoskeleton interactions. Here we show that actin fibers decorated with h1 CaP remain stable, whereas SM22 alpha-decorated actin bundles undergo rapid reorganization into podosomes within 30 min of PDBu exposure. Ectopic expression of GFP alpha-actinin had no effect on the stability of the actin cytoskeleton and alpha-actinin was transported rapidly into PDBu-induced podosomes. Our results demonstrate the involvement of CaP and SM22 alpha in coordinating the balance between stabilization and dynamics of the actin cytoskeleton in mammalian smooth muscle. We provide evidence for the existence of two functionally distinct actin filament populations and introduce a molecular mechanism for the stabilization of the actin cytoskeleton by the unique actin-binding interface formed by calponin family-specific CLIK23 repeats.


Blocking hypothalamic AT1 receptors lowers blood pressure in salt-sensitive rats.
Previous studies from our laboratory have shown that microinjection of DuP 753 (2-n-butyl-4-chloro-5-(hydroxymethyl)-1-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]imidazole, potassium salt), a highly selective nonpeptide antagonist of type 1 angiotensin II receptors, into the anterior hypothalamic area produces a dose-related depressor response in salt-sensitive spontaneously hypertensive rats fed a basal (1%) salt diet. The current study tested the hypothesis that the depressor response to anterior hypothalamic type 1 angiotensin II receptor blockade with DuP 753 or its metabolite EXP 3174 is enhanced by high (8%) salt feeding in this model. DuP 753 or EXP 3174 (40 micrograms in 100 nl artificial cerebrospinal fluid vehicle) or vehicle alone was microinjected into the anterior hypothalamic area of conscious salt-sensitive spontaneously hypertensive and Wistar-Kyoto rats that had been fed 1% or 8% salt diets for 3 weeks. Both DuP 753 and EXP 3174 caused significant decreases in mean arterial pressure in spontaneously hypertensive but not in Wistar-Kyoto rats fed either diet. The magnitude and duration of the depressor responses to DuP 753 and EXP 3174 were significantly greater in the 8% salt-fed spontaneously hypertensive rats than in 1% salt-fed rats. Vehicle injections had no effect on blood pressure in either strain-diet group. Microinjection of angiotensin II (2 micrograms in 100 nl artificial cerebrospinal fluid vehicle) into the anterior hypothalamic area caused significant pressor and bradycardiac responses in all strain-diet groups; dietary salt supplementation enhanced these effects in salt-sensitive spontaneously hypertensive rats but not in Wistar-Kyoto rats. These responses were blocked by pretreatment with EXP 3174.(ABSTRACT TRUNCATED AT 250 WORDS)


Racial/Ethnic Disparities in Dental Service Utilization for Foreign-Born and U.S.-Born Middle-Aged and Older Adults.
This study examines racial/ethnic disparities of dental service utilization for foreign-born and U.S.-born dentate residents aged 50 years and older. Generalized linear mixed-effects models (GLMM) were used to perform longitudinal analyses of five-wave data of dental service utilization from the Health and Retirement Study (HRS). We used stratified analyses for the foreign-born and U.S.-born and assessed the nonlinear trend in rates of dental service utilization for different racial/ethnic groups. Findings indicate that Whites had higher rates of service utilization than Blacks and Hispanics regardless of birthplace. For all groups, the rates of service utilization decreased around age 80, and the rates of decline for Whites were slower than others. The U.S.-born showed the trend of higher rates of service utilization than the foreign-born for all racial/ethnic groups. These findings suggest the importance of developing culturally competent programs to meet the dental needs of the increasingly diverse populations in the United States.


Pulmonary embolism after endovenous thermal ablation of the saphenous vein.
Pulmonary embolism (PE) after venous procedures is fortunately rare. Our goal was to analyze the data of patients who developed PE after endovenous thermal ablation and phlebectomy for varicose veins and to review the literature on this subject. We report on three patients who developed PE after radiofrequency ablation of the great saphenous vein and mini phlebectomy for symptomatic primary lower-extremity varicose veins. Early postoperative duplex scans confirmed successful closure of the great saphenous vein in all. One patient presented with chest pain and dyspnea, one with blood-tinged sputum, and the third with symptoms of saphenous thrombophlebitis. Two patients had PE from the saphenous vein thrombus and the third had gastrocnemius vein thrombosis extending into the popliteal vein. One had previous deep vein thrombosis. Computed tomography of the chest confirmed PE in all. Two patients were treated with anticoagulation, but the third patient with small PE declined such treatment. One patient underwent temporary inferior vena cava filter placement because of recurrent PE. In conclusion, PE is very rare but it can occur after endovenous thermal ablation of lower-extremity varicose veins. Selective thrombosis prophylaxis and preoperative counseling of the patients about signs and symptoms of deep vein thrombosis and PE are warranted for early recognition and rapid treatment.


Using a digital patient powered research network to identify outcomes of importance to patients with multiple myeloma.
Social media platforms give patients a voice by allowing them to discuss their health and connect with others. These unfiltered and genuine reports offer direct access to what matters most to patients. Exploring the patient-reported outcomes discussed in these platforms reveal clinical insights and behavioral patterns of the real-world patient journey. This research study reviewed health-related quality of life (HRQoL) concepts reported by patients with multiple myeloma (MM). Data were obtained using the Belong.life patient-powered research network (PPRN) using social media listening methods. The analysis cohort consisted of adults diagnosed with MM who signed into the Belong.life platform by June 2018. Natural language processing and medical neural networks were utilized to extract text data to mine and scan for concepts using programmed algorithms. The textual review of the data was conducted on two levels: the over-arching concept of interest (broad symptom and impact classification) and the more specific symptom and impacts report. Concepts were analyzed descriptively and summarized by age, gender, context of report, and stage of disease/treatment journey. Two hundred thirty patients with MM from the United States (52%), Israel (42%), Canada (3%), and 3% from Egypt, France, Greece, India, United Kingdom, and Australia were identified. A total of 57% were female and at account registration the median age was 57 years. A total of 126 patients had evaluable text data to search concepts being discussed. The PPRN platform identified 93% of the concepts from the conceptual model developed based on prior literature review. The most commonly reported symptoms were neuropathy, tiredness, nausea, back pain, fatigue, and bone pain. Back pain appeared as the most prominent symptom early in the disease and sometimes occurred prior to MM diagnosis. Tiredness, nausea, fatigue, and bone pain were frequently reported after MM diagnosis, with the start of treatment. Patient-oriented social media platforms, such as Belong.life, can capture and contribute to a holistic vision of concepts surrounding patients' HRQoL. The ability to understand when a certain debilitating symptom appeared and to which sub-population of patients may allow for a personalized approach to treatment, improving adherence and quality of care as well as increasing patient well-being.


Monitoring of wound healing process of human skin after fractional laser treatments with optical coherence tomography.
Fractional photothermolysis induced by non-ablative fractional lasers (NAFLs) or ablative fractional lasers (AFLs) can remodel the skin, regenerate collagen, and remove tumor tissue. However, fractional laser treatments may result in severe side effects, and multiple treatments are required to achieve the expected outcome. Thus, the treatment outcome and downtime after fractional laser treatments are key issues to determine the following treatment strategy. In this study, an optical coherence tomography (OCT) system was implemented for in vivo studies of wound healing after NAFL and AFL treatments. According to the OCT scanning results, the laser-induced photothermolysis including volatilization and coagulation could be morphologically identified. To continue monitoring the wound healing process, the treated regions were scanned with OCT at different time points, and the en-face images at various tissue depths were extracted from three-dimensional OCT images. Furthermore, to quantitatively evaluate the morphological changes at different tissue depths during wound healing, an algorithm was developed to distinguish the backscattering properties of untreated and treated tissues. The results showed that the coagulation damage induced by the NAFLs could be rapidly healed in 6 days. In contrast, the tissue volatilization induced by AFLs required a longer recovery time of 14 days. In conclusion, this study establishes the feasibility of this methodology as a means of clinically monitoring treatment outcomes and wound healing after fractional laser treatments.


The organizational domain in HTA reports: towards a technology-oriented assessment.
Organizational aspects in Health Technology Assessment (HTA) reports play a significant role in managing policies and strategies to implement new health technologies. The organizational domain, however, is often under-represented in HTA reports. This study explored how organizational assessment is carried out in HTA reports and designed a new perspective through an empirical approach after the comparison with EUnetHTA's Core Model 3.0. Full HTA reports were extracted from the websites of members of International Network of Agencies for HTA and the aspects relating to the organizational assessment were analysed. HTA reports were classified into 4 typologies of technologies (device, diagnosis/screening, intervention and organizational procedures) and organizational aspects described were explored through a framework of 5 domains and 15 subdomains from Core Model. Specific Multiple Correspondence Analyses were carried out to identify technology-related domains for organizational assessment in reports. The analysis showed that domains and subdomains of Core Model were not covered homogeneously by the organizational assessments in the HTA reports. Through Multiple Correspondence Analyses, four new technology-related dimensions were identified and named according to the Core Model's subdomains in the four new clusters. This study analyzed the significance of organizational assessments in current literature and the challenges of improving this domain in HTA reports. Through an empirical analysis, we proposed a new methodology to cover the most relevant aspects of organizational appraisal according to new domains to promote support to the assessment of organizational issues in reports and fulfil the needs of future HTA research.


Mutations in Arabidopsis yellow stripe-like1 and yellow stripe-like3 reveal their roles in metal ion homeostasis and loading of metal ions in seeds.
Here, we describe two members of the Arabidopsis (Arabidopsis thaliana) Yellow Stripe-Like (YSL) family, AtYSL1 and AtYSL3. The YSL1 and YSL3 proteins are members of the oligopeptide transporter family and are predicted to be integral membrane proteins. YSL1 and YSL3 are similar to the maize (Zea mays) YS1 phytosiderophore transporter (ZmYS1) and the AtYSL2 iron (Fe)-nicotianamine transporter, and are predicted to transport metal-nicotianamine complexes into cells. YSL1 and YSL3 mRNAs are expressed in both root and shoot tissues, and both are regulated in response to the Fe status of the plant. Beta-glucuronidase reporter expression, driven by YSL1 and YSL3 promoters, reveals expression patterns of the genes in roots, leaves, and flowers. Expression was highest in senescing rosette leaves and cauline leaves. Whereas the single mutants ysl1 and ysl3 had no visible phenotypes, the ysl1ysl3 double mutant exhibited Fe deficiency symptoms, such as interveinal chlorosis. Leaf Fe concentrations are decreased in the double mutant, whereas manganese, zinc, and especially copper concentrations are elevated. In seeds of double-mutant plants, the concentrations of Fe, zinc, and copper are low. Mobilization of metals from leaves during senescence is impaired in the double mutant. In addition, the double mutant has reduced fertility due to defective anther and embryo development. The proposed physiological roles for YSL1 and YSL3 are in delivery of metal micronutrients to and from vascular tissues.


Macroscale fluorescence imaging against autofluorescence under ambient light.
Macroscale fluorescence imaging is increasingly used to observe biological samples. However, it may suffer from spectral interferences that originate from ambient light or autofluorescence of the sample or its support. In this manuscript, we built a simple and inexpensive fluorescence macroscope, which has been used to evaluate the performance of Speed OPIOM (Out of Phase Imaging after Optical Modulation), which is a reference-free dynamic contrast protocol, to selectively image reversibly photoswitchable fluorophores as labels against detrimental autofluorescence and ambient light. By tuning the intensity and radial frequency of the modulated illumination to the Speed OPIOM resonance and adopting a phase-sensitive detection scheme that ensures noise rejection, we enhanced the sensitivity and the signal-to-noise ratio for fluorescence detection in blot assays by factors of 50 and 10, respectively, over direct fluorescence observation under constant illumination. Then, we overcame the strong autofluorescence of growth media that are currently used in microbiology and realized multiplexed fluorescence observation of colonies of spectrally similar fluorescent bacteria with a unique configuration of excitation and emission wavelengths. Finally, we easily discriminated fluorescent labels from the autofluorescent and reflective background in labeled leaves, even under the interference of incident light at intensities that are comparable to sunlight. The proposed approach is expected to find multiple applications, from biological assays to outdoor observations, in fluorescence macroimaging.


Generalized analysis of shearing interferometers as applied for gas dynamic studies.
Shearing interferometers are classified as instruments in which interference is produced between rays that are sheared in the test object by a small lateral distance. When applied to gas dynamic investigations these interferometers respond to changes of the gradient of the gas density in the test field. A generalized first-order analysis is described that applies to all arrangements of such shearing interferometers and emphasizes the application for the study of compressible gas flows.


Self-Assembly of Telechelic Tyrosine End-Capped PEO and Poly(alanine) Polymers in Aqueous Solution.
The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(L-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into β-sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers--in particular the Tyr5-PEO6k-Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide-polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k-Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5-PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped "associative polymers". Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-groups.


Adverse effects of cannabinoids.
Cannabidiol is a cannabinoid-derived product that has recently been approved for the treatment of pharmacoresistant seizures in patients with epileptic encephalopathies such as Dravet Syndrome and Lennox-Gastaut Syndrome. Short-term side effects of cannabidiol are well know and well-documented in the clinical trials that lead to its approval. Generally, is a well tolerated drug with transitory, dose-dependent mild to moderate effects like somnolence, decreased appetite or diarrhoea. However severe life-threatening reactions can also occur, and are often related to the non-controlled toxic combination with other antiseizure drugs that are widely used in this type of patients like sodium valproate or clobazam. In this brief review we summarize the available data about the short-term adverse events of cannabidiol. Further studies are required to assess the long-term outcome and final resolution of these conditions regarding safety of these patients.


Whole body MRI of the non-human primate using a clinical 3T scanner: initial experiences.
With the advent of parallel imaging MRI techniques, whole-body MRI is being increasingly used in clinical diagnosis. However, its application in preclinical research using large animals remains very limited. In the present study, the whole-body MRI techniques for adult macaque monkeys were explored using a conventional clinic 3T scanner. The T1, T2 anatomical images, and MR angiography of adult macaque whole bodies were illustrated. The preliminary results suggest whole-body MRI can be a robust tool to examine multiple organs of non-human primate (NHP) models from head to toe non-invasively and simultaneously using a conventional clinical setting. As NHPs are intensely used in biomedical research such as HIV/AIDS and vaccine discovery, whole body MRI techniques can have a wide range of applications in translational research using NHPs.


Is it Beneficial to Treat Patients Presenting Three Weeks or Longer after the Onset of Sudden Sensorineural Hearing Loss?
The accepted treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) consists of oral or intratympanic steroids. The time from onset to treatment is considered as an important prognostic factor, although there is no clear cutoff point when treatment is no longer beneficial. This study aimed to assess the efficacy of treatment with oral or intratympanic steroids and carbogen, in patients presenting 21 days or later after the onset of hearing loss. A total of 895 patients with ISSNHL was seen in our center between 2010 and 2018. The study cohort included 103 patients treated with oral or intratympanic steroids or both with carbogen 21 days or longer after experiencing hearing loss. Retrospective analysis of files and audiometry was conducted, and pre- and post-treatment audiograms were compared. Improvement was defined by SRT (≥15 dB improvement), discrimination (≥15% improvement), or 15 dB improvement at specific frequencies (250-500, 4000-6000 Hz). Hearing improvement, according to the study definition, was seen in 22.3% (23/103) of patients within the time period of the treatment. All the 23 patients had functional hearing after treatment and 16 of them returned to their baseline or normal hearing. While the time from onset of ISSNHL to treatment varied, most patients demonstrating improvement were treated 21-30 days after onset. In this patient cohort treated late for sudden sensorineural hearing loss (SSNHL), a small but significant number of patients improved during the time of treatment. Although the lack of a control group makes it difficult to prove that the improvement resulted from the treatment, we recommend not to rule out treatment systematically in patients presenting late after ISSNHL. Additional prospective studies are warranted.


Sport and ageing: a systematic review of the determinants and trends of participation in sport for older adults.
The global population is ageing. As ageing is often associated with a decline in health, there is a need to further develop preventative health measures. Physical activity can positively influence older adults' (aged 50 years and older) health. Previous research on the relationship between physical activity and health for older adults has mainly focused on physical activity in general, and not specific types of exercise. Due to the social nature of sport, it may assist in improving physical, mental and social health for older adults. Sport, as a form of physical activity, has not been widely explored as a physical activity opportunity for older adults. This review concurrently explored two research questions: the determinants and the trends of sport participation for community dwelling older adults. Two parallel systematic searches of nine electronic databases were conducted in December 2015 for the two research questions. English language quantitative and qualitative studies that provided specific results for community dwelling older adults' sport participation were included and a quality ratings assessment was undertaken. There were 10,171 studies initially identified for the first research question and 1992 studies for the second research question. This culminated in 18 and 8 studies respectively that met the inclusion criteria. The most frequently mentioned determinants of participation were health and using sport to negotiate the ageing process. The most frequently mentioned trends of sport participation were the effect of historical sport participation on current participation, and sport participation across the lifespan. The main themes for both research questions had contrasting results, for example, participation in sport could improve health, but poor health was also a limitation of sport participation. This review demonstrates that older adults are a heterogeneous age group, and therefore require different strategies than other age groups to successfully participate in sport. It is recommended that the main findings from this review are incorporated into specific strategies to develop age appropriate sporting opportunities for older adults, so that sport can be presented as a viable physical activity option for this age group.


Manual therapy in the treatment of ankle hemophilic arthropathy. A randomized pilot study.
Although physiotherapy has demonstrated effectiveness in preventing ankle arthropathy compared to prophylaxis treatment from early ages, there have been no conclusive studies examining physiotherapy intervention once hemophilic arthropathy of the ankle has been established. The aim of this study was to evaluate the effectiveness of two physiotherapy interventions, in patients with hemophilic arthropathy of the ankle that had not been operated on previously. Nine patients with hemophilia (mean age of 35.7 SD 11.9 years) were randomized to a mobilization group (n = 5) and manual therapy group (n = 4). The two physiotherapy interventions were: (1) passive mobilization and stretching; and (2) manual orthopaedic therapy, both with proprioception training. The study lasted for six weeks, with two sessions a week. Ankle mobility and pain perception, lower limb proprioception and quality of life were the outcome measures. Both treatments improved all ankle movements (p < 0.05). The treatment with passive mobilizations also improved the perception of pain and quality of life. Six months later, both groups still had improved articular movement with the exception of plantar flexion and continued to perceive less pain. Both physiotherapy interventions improved the range of movement and lessened pain in patients with ankle arthropathy. No haemarthrosis was recorded during treatment or during the follow-up period.


Use of antihypertensive medications and breast cancer risk among women aged 55 to 74 years.
Antihypertensive agents are the most commonly prescribed class of medications in the United States. Evidence regarding the relationship between different types of antihypertensives and breast cancer risk is sparse and inconsistent, and prior studies have lacked the capacity to assess impacts of long-term use. To evaluate associations between use of various classes of antihypertensive medications and risks of invasive ductal and invasive lobular breast cancers among postmenopausal women. Population-based case-control study in the 3-county Seattle-Puget Sound metropolitan area. Participants were women aged 55 to 74 years, 880 of them with invasive ductal breast cancer, 1027 with invasive lobular breast cancer, and 856 with no cancer serving as controls. Recency and duration of use of antihypertensive medications. Risks of invasive ductal and invasive lobular breast cancers. Current use of calcium-channel blockers for 10 or more years was associated with higher risks of ductal breast cancer (odds ratio [OR], 2.4; 95% CI, 1.2-4.9) (P= .04 for trend) and lobular breast cancer (OR, 2.6; 95% CI, 1.3-5.3) (P= .01 for trend). This relationship did not vary appreciably by type of calcium-channel blocker used (short-acting vs long-acting, dihydropyridines vs non-dihydropyridines). In contrast, use of diuretics, β-blockers, and angiotensin II antagonists were not associated with risk. While some studies have suggested a positive association between calcium-channel blocker use and breast cancer risk, this is the first study to observe that long-term current use of calcium-channel blockers in particular are associated with breast cancer risk. Additional research is needed to confirm this finding and to evaluate potential underlying biological mechanisms.


A critical analysis of the current state of neurosurgery training in Pakistan.
To observe interdepartmental variation in the availability of resources and academic activities within the various neurosurgery programs of Pakistan. This was a proforma-based survey of neurosurgery trainees and young neurosurgeons of Pakistan, looking at the academic infrastructure and output of their programs. The proforma was filled by 36 respondents from 11 neurosurgery centers of the country. All these centers were accredited for neurosurgery training in Pakistan. Out of the 36 respondents, 30 were completing a Fellowship training (FCPS) and six were enrolled for a Master in Surgery (MS) program. About 80% of the participants used the Youman's Textbook of Neurosurgery as a reference book. Only 40% of the candidates had access to more than one indexed neurosurgery journal. Structured academic sessions (e.g., journal clubs and neuropathology meetings) were lacking in a majority of the training institutes, 95% of the trainees had no microsurgical laboratory experience, and modern neurosurgical tools (frameless neuronavigation system, neuroendoscopy) were in use at a few centers only. Neurosurgery training in Pakistan is not uniform and wide variations exist between the programs at the centers evaluated. We recommend exchange programs between centers at national and international levels, to allow trainees to gain first-hand exposure to training components not available in their own center.


The effects of asking a fertility intention question in primary care settings: a systematic review protocol.
Planning for pregnancy has been associated with reduced unwanted pregnancies and improved pregnancy outcomes. Despite the benefits of planned pregnancy, there are no guideline recommendations on routine counseling regarding pregnancy intention in primary care settings. The objective of the systematic review is to determine the effectiveness of incorporating questions of pregnancy intention into primary care. A systematic search of the literature will be conducted for any studies comparing questions of pregnancy intention in primary care settings with no intervention or a control intervention. Types of studies will include randomized controlled trials, non-randomized trials, and observation studies. Participants will include patients of reproductive age presenting to primary health care settings. Interventions will include any assessment of fertility intention and follow-up care compared with a control group or no intervention. Outcomes will include quantitative data with rates for contraceptive uptake, and any pregnancy related outcome. Databases (Ovid MEDLINE; Pubmed; CINAHL; EMBASE; CDR/DARE databases; Web of Science; ISRCTN registry; Clinicaltrials.gov; Cochrane Library) will be searched from the year 2000 to current. Screening of identified articles and data extraction will be conducted in duplicate by two independent reviewers. Methodological quality will be assessed using the Jadad scale. Methodological quality of observational and non-randomized trials will be assessed using the Newcastle-Ottawa scale. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analyses will be performed if appropriate. Determining the effect of including questions of pregnancy intention into primary care can provide evidence for the development of clinical practice guidelines and inform primary care providers if this simple and low-cost intervention should be routinely employed. This review will also identify any gaps in the current literature on this topic and provide direction for future research in this area of study. Systematic Review Registration: PROSPERO CRD42015019726.


Outcome of the acute glomerular injury in proliferative lupus nephritis.
Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.


The blood-brain barrier in multiple sclerosis: microRNAs as key regulators.
Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous system (CNS) leading to severe neurological deficits. To date, no treatment is available that halts disease progression, but clinical symptoms can be generally improved by therapies involving anti-inflammatory and/or immune modulatory reagents, which may cause off-target effects. Therefore, there remains a high and unmet need for more selective treatment strategies in MS. An early event in MS is a diminished function of the blood-brain barrier (BBB) which consists of specialized brain endothelial cells (BECs) that are supported in their barrier function by surrounding glial cells. Leakage and inflammation of the BECs in MS patients facilitate the massive influx of leukocytes into the brain parenchyma, which in turn induces irreversible demyelination, tissue damage and axonal dysfunction. Identification of ways to restore BBB function and promote its immune quiescence may therefore lead to the development of novel therapeutic regimes that not only specifically reduce leukocyte entry into the central nervous system but also restore the disturbed brain homeostasis. However, the complex network of molecular players that leads to BBB dysfunction in MS is yet to be fully elucidated. Recent discoveries unravelled a critical role for microRNAs (miRNAs) in controlling the function of the barrier endothelium in the brain. Here we will review the current knowledge on the involvement of BBB dysfunction in MS and the central role that miRNAs play in maintaining BBB integrity under inflammatory conditions.


Current approaches to cyanotoxin risk assessment and risk management around the globe.
Toxic cyanobacteria became more widely recognized as a potential health hazard in the 1990s, and in 1998 the World Health Organization (WHO) first published a provisional Guideline Value of 1 μg L-1 for microcystin-LR in drinking-water. In this publication we compare risk assessment and risk management of toxic cyanobacteria in 17 countries across all five continents. We focus on the three main (oral) exposure vehicles to cyanotoxins: drinking-water, water related recreational and freshwater seafood. Most countries have implemented the provisional WHO Guideline Value, some as legally binding standard, to ensure the distribution of safe drinking-water with respect to microcystins. Regulation, however, also needs to address the possible presence of a wide range of other cyanotoxins and bioactive compounds, for which no guideline values can be derived due to insufficient toxicological data. The presence of microcystins (commonly expressed as microcystin-LR equivalents) may be used as proxy for overall guidance on risk management, but this simplification may miss certain risks, for instance from dissolved fractions of cylindrospermopsin and cyanobacterial neurotoxins. An alternative approach, often taken for risk assessment and management in recreational waters, is to regulate cyanobacterial presence - as cell numbers or biomass - rather than individual toxins. Here, many countries have implemented a two or three tier alert level system with incremental severity. These systems define the levels where responses are switched from Surveillance to Alert and finally to Action Mode and they specify the short-term actions that follow. Surface bloom formation is commonly judged to be a significant risk because of the elevated concentration of microcystins in a scum. Countries have based their derivations of legally binding standards, guideline values, maximally allowed concentrations (or limits named otherwise) on very similar scientific methodology, but underlying assumptions such as bloom duration, average body size and the amount of water consumed while swimming vary according to local circumstances. Furthermore, for toxins with incomplete toxicological data elements of expert judgment become more relevant and this also leads to a larger degree of variation between countries' thresholds triggering certain actions. Cyanobacterial blooms and their cyanotoxin content are a highly variable phenomenon, largely depending on local conditions, and likely concentrations can be assessed and managed best if the specific conditions of the locality are known and their impact on bloom occurrence are understood. Risk Management Frameworks, such as for example the Water Safety Plan concept of the WHO and the 'bathing water profile' of the European Union are suggested to be effective approaches for preventing human exposure by managing toxic cyanobacteria from catchment to consumer for drinking water and at recreational sites.


Breakdown of brain-body allometry and the encephalization of birds and mammals.
The allometric relationship between brain and body size among vertebrates is often considered a manifestation of evolutionary constraints. However, birds and mammals have undergone remarkable encephalization, in which brain size has increased without corresponding changes in body size. Here, we explore the hypothesis that a reduction of phenotypic integration between brain and body size has facilitated encephalization in birds and mammals. Using a large dataset comprising 20,213 specimens across 4,587 species of jawed vertebrates, we show that the among-species (evolutionary) brain-body allometries are remarkably constant, both across vertebrate classes and across taxonomic levels. Birds and mammals, however, are exceptional in that their within-species (static) allometries are shallower and more variable than in other vertebrates. These patterns are consistent with the idea that birds and mammals have reduced allometric constraints that are otherwise ubiquitous across jawed vertebrates. Further exploration of ontogenetic allometries in selected taxa of birds, fishes and mammals reveals that birds and mammals have extended the period of fetal brain growth compared to fishes. Based on these findings, we propose that avian and mammalian encephalization has been contingent on increased variability in brain growth patterns.


Antibacterial activity and mechanism of action of zinc oxide nanoparticles against Campylobacter jejuni.
The antibacterial effect of zinc oxide (ZnO) nanoparticles on Campylobacter jejuni was investigated for inhibition and inactivation of cell growth. The results showed that C. jejuni was extremely sensitive to treatment with ZnO nanoparticles. The MIC of ZnO nanoparticles for C. jejuni was determined to be 0.05 to 0.025 mg/ml, which is 8- to 16-fold lower than that for Salmonella enterica serovar Enteritidis and Escherichia coli O157:H7 (0.4 mg/ml). The action of ZnO nanoparticles against C. jejuni was determined to be bactericidal, not bacteriostatic. Scanning electron microscopy examination revealed that the majority of the cells transformed from spiral shapes into coccoid forms after exposure to 0.5 mg/ml of ZnO nanoparticles for 16 h, which is consistent with the morphological changes of C. jejuni under other stress conditions. These coccoid cells were found by ethidium monoazide-quantitative PCR (EMA-qPCR) to have a certain level of membrane leakage. To address the molecular basis of ZnO nanoparticle action, a large set of genes involved in cell stress response, motility, pathogenesis, and toxin production were selected for a gene expression study. Reverse transcription-quantitative PCR (RT-qPCR) showed that in response to treatment with ZnO nanoparticles, the expression levels of two oxidative stress genes (katA and ahpC) and a general stress response gene (dnaK) were increased 52-, 7-, and 17-fold, respectively. These results suggest that the antibacterial mechanism of ZnO nanoparticles is most likely due to disruption of the cell membrane and oxidative stress in Campylobacter.


Female sterilization is more common among women with physical and/or sensory disabilities than women without disabilities in the United States.
Female sterilization accounts for 50% of all contraceptive use in the U.S. The extent to which U.S. women with physical and/or sensory disabilities have undergone female sterilization is unknown. Our primary objective was to determine the prevalence of sterilization for women with physical/sensory disabilities, and compare this to the prevalence for women without disabilities. We also compared use of long-acting reversible contraceptive (LARC) methods between women with and without disabilities. We conducted a secondary analysis of data from the National Survey of Family Growth 2011-2013, a population-based survey of U.S. women aged 15-44. Bivariate comparisons between women with and without disabilities by female sterilization and LARC use were conducted using chi-square tests. Using logistic regression, we estimated the odds of female sterilization based upon disability status. Women with physical/sensory disabilities accounted for 9.3% of the total sample (N = 4966). Among women with disabilities only, 28.2% had undergone female sterilization, representing 1.2 million women nationally. LARC use was lower among women with disabilities than those without disabilities (5.4%, 9.3%, respectively, p < 0.01). After adjusting for age, race/ethnicity, education, insurance, marital status, parity, and self-reported health, women with disabilities had higher odds of sterilization (OR 1.36, 95% CI 1.03, 1.79). The odds of female sterilization is higher among women with physical/sensory disabilities than those without disabilities. Future research is necessary to understand factors contributing to this finding, including possible underutilization of LARC methods.


Morphological, Molecular, and Differential-Host Characterization of Meloidogyne floridensis n. sp. (Nematoda: Meloidogynidae), a Root-Knot Nematode Parasitizing Peach in Florida.
A root-knot nematode, Meloidogyne floridensis n. sp., is described and illustrated from peach originally collected from Gainesville, Florida. This new species resembles M. incognita, M. christiei, M. graminicola, and M. hispanica, but with LM and SEM observations it differs from these species either by the body length, shape of head, tail and tail terminus of second-stage juveniles, body length and shape of spicules in males, and its distinctive female perineal pattern. This pattern has a high to narrowly rounded arch with coarsely broken and network-like striae in and around anal area, faint lateral lines interrupting transverse striae, a sunken vulva and anus, and large distinct phasmids. Molecular data from ribosomal IGS illustrate that M. floridensis n. sp. is different from the mitotic species M. arenaria, M. incognita, and M. javanica. Data from RAPDs confirm it and suggest that this new species lies in an intermediate phylogenetic position between the previous species and the meiotic species M. hapla, M. fallax, and M. chitwoodi. Differential host tests based on annual crops and on Prunus accessions are reported.


Valsalva retinopathy in pregnancy: a case report.
Valsalva retinopathy is a unilateral or bilateral condition that occurs when increased intra-thoracic or intra-abdominal pressure transmitted to the eye causes a sharp rise in the intra-ocular venous pressure, and rupture of superficial retinal capillaries. The patient often gives a history of a recent strenuous physical act, which could have increased the intra-thoracic pressure. Pregnancy is known to be a risk factor for Valsalva retinopathy. A 23-year-old woman in her seventh month of pregnancy presented with a history of decreased vision in her left eye of one-week duration. Examination of the affected eye showed best corrected visual acuity of 20/50, and fundus examination revealed a pre-retinal hemorrhage located in the macula. Based on clinical findings, the diagnosis of Valsalva retinopathy was made. Retinal hemorrhages can be generated by Valsalva maneuvers. Pregnancy is a known risk factor for Valsalva retinopathy; however, the diagnosis should be made only after excluding other causes of retinal hemorrhages. It is a self-limited event. We report a case of Valsalva retinopathy complicating normal pregnancy and confirm that, to date, there is no evidence to indicate that there is a risk of recurrence following spontaneous vaginal delivery.


[Favorable effects of vitamin A in measles infection].
The recent measles epidemic that hit the Netherlands in 1999 resulted in numerous hospitalisations and several fatalities, and resembled the previous epidemic of 1987-1988 in numbers and severity. The triple (parotitis epidemica, measles, and rubella) vaccine used in the nationwide, free-of-charge immunization programme is highly effective, but is not accepted for ideological reasons by specific groups in the Dutch community. High oral doses of vitamin A have been shown to reduce mortality and pulmonary and gastrointestinal complications of measles in children in developing countries, but this treatment option is little known to physicians in the Netherlands. The appropriate dose regimens for safe administration of vitamin A in complicated measles are: age under 6 months 50,000 IU, age between 6 months and 2 years 100,000 IU, and age over 2 years 200,000 IU, administered by mouth upon admission. A repeated dose can be administered on the following day. In the Netherlands, and elsewhere, universal measles immunisation remains the first goal in the fight against this highly contagious disease.


Longitudinal Hierarchy Co3O4 Mesocrystals with High-dense Exposure Facets and Anisotropic Interfaces for Direct-Ethanol Fuel Cells.
Novel electrodes are needed for direct ethanol fuel cells with improved quality. Hierarchical engineering can produce catalysts composed of mesocrystals with many exposed active planes and multi-diffused voids. Here we report a simple, one-pot, hydrothermal method for fabricating Co3O4/carbon/substrate electrodes that provides control over the catalyst mesocrystal morphology (i.e., corn tubercle pellets or banana clusters oriented along nanotube domains, or layered lamina or multiple cantilevered sheets). These morphologies afforded catalysts with a high density of exposed active facets, a diverse range of mesopores in the cage interior, a window architecture, and vertical alignment to the substrate, which improved efficiency in an ethanol electrooxidation reaction compared with a conventional platinum/carbon electrode. On the atomic scale, the longitudinally aligned architecture of the Co3O4 mesocrystals resulted in exposed low- and high-index single and interface surfaces that had improved electron transport and diffusion compared with currently used electrodes.


Nocodazole-dependent transport, and brefeldin A--sensitive processing and sorting, of newly synthesized membrane proteins in cultured neurons.
The envelope glycoproteins of Semliki Forest virus (SFV), Vesicular Stomatitis virus (VSV), and Influenza Fowl Plague virus (FPV) are vectorially targeted in neurons to the plasma membrane of dendrites (SFV and VSV) and axons (FPV). To gain insight into the mechanisms responsible for such polarized delivery we have examined the effects on neurons of nocodazole and brefeldin A (BFA), which are known to cause microtubule depolymerization and disassembly of the Golgi apparatus, respectively. Nocodazole treatment blocked transport of all viral glycoproteins to both axons and dendrites. BFA treatment induced disruption of the Golgi complex, including the trans-Golgi network (TGN), and tubulation of endosomes. However, the delivery of the SFV and FPV glycoproteins to the cell surface was not affected significantly by BFA, although processing and sorting were altered, as revealed by surface biotinylation and immunofluorescence microscopy of fixed nonpermeabilized cells. These results demonstrate the involvement of microtubules in axonal and dendritic transport of integral membrane glycoproteins, and the existence of a BFA-sensitive component in the sorting but not in the transport machinery.


Impact of missing participant data for dichotomous outcomes on pooled effect estimates in systematic reviews: a protocol for a methodological study.
There is no consensus on how authors conducting meta-analysis should deal with trial participants with missing outcome data. The objectives of this study are to assess in Cochrane and non-Cochrane systematic reviews: (1) which categories of trial participants the systematic review authors consider as having missing participant data (MPD), (2) how trialists reported on participants with missing outcome data in trials, (3) whether systematic reviewer authors actually dealt with MPD in their meta-analyses of dichotomous outcomes consistently with their reported methods, and (4) the impact of different methods of dealing with MPD on pooled effect estimates in meta-analyses of dichotomous outcomes. We will conduct a methodological study of Cochrane and non-Cochrane systematic reviews. Eligible systematic reviews will include a group-level meta-analysis of a patient-important dichotomous efficacy outcome, with a statistically significant effect estimate. Teams of two reviewers will determine eligibility and subsequently extract information from each eligible systematic review in duplicate and independently, using standardized, pre-piloted forms. The teams will then use a similar process to extract information from the trials included in the meta-analyses of interest. We will assess first which categories of trial participants the systematic reviewers consider as having MPD. Second, we will assess how trialists reported on participants with missing outcome data in trials. Third, we will compare what systematic reviewers report having done, and what they actually did, in dealing with MPD in their meta-analysis. Fourth, we will conduct imputation studies to assess the effects of different methods of dealing with MPD on the pooled effect estimates of meta-analyses. We will specifically calculate for each method (1) the percentage of systematic reviews that lose statistical significance and (2) the mean change of effect estimates across systematic reviews. The impact of different methods of dealing with MPD on pooled effect estimates will help judge the associated risk of bias in systematic reviews. Our findings will inform recommendations regarding what assumptions for MPD should be used to test the robustness of meta-analytical results.


Development of mutagenicity during degradation of N-nitrosamines by advanced oxidation processes.
Development of mutagenicity of five N-nitrosamines (N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosodi-n-propylamine (NDPA), N-nitrosopyrrolidine (NPYR) and N-nitrosodiphenylamine (NDPhA)) was investigated during oxidative processes involving UV-photolysis, ozone and OH radicals. The mutagenicity was detected by the Ames test with 3 different strains, TA98, TAMix and YG7108, a strain which is sensitive for N-nitrosamines, in presence and absence of metabolic activation (S9). UV photolysis of mutagenic N-nitrosamines (NDMA, NDEA, NDPA and NPYR) leads to the removal of their specific mutagenic activity as detected in YG7108 in the presence of S9. A formation of mutagens during UV photolysis was detected only in case of NDPhA in the strain TA98. Oxidation products of NDMA, NDEA and NDPhA did not show any significant mutagenicity in the strains used, whereas oxidation of NDPA and NPYR by hydroxyl radicals seems to lead to the formation of direct mutagens (mutagenic in the absence of S9) in YG7108 and TAMix. Oxidation by hydroxyl radicals of N-nitrosamines with chains longer than ethyl can mimic metabolic activation of N-nitrosamines in vivo.


Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia.
Bronchopulmonary dysplasia (BPD) is an important complication of mechanical ventilation in preterm infants, and no definite therapy can eliminate this complication. Pulmonary inflammation plays a crucial role in its pathogenesis, and glucocorticoid is one potential therapy to prevent BPD. To compare the effect of intratracheal administration of surfactant/budesonide with that of surfactant alone on the incidence of death or BPD. A clinical trial was conducted in three tertiary neonatal centers in the United States and Taiwan, in which 265 very-low-birth-weight infants with severe respiratory distress syndrome who required mechanical ventilation and inspired oxygen (fraction of inspired oxygen, ≥50%) within 4 hours of birth were randomly assigned to one of two groups (131 intervention and 134 control). The intervention infants received surfactant (100 mg/kg) and budesonide (0.25 mg/kg), and the control infants received surfactant only (100 mg/kg), until each infant required inspired O2 at less than 30% or was extubated. The intervention group had a significantly lower incidence of BPD or death (55 of 131 [42.0%] vs. 89 of 134 [66%]; risk ratio, 0.58; 95% confidence interval, 0.44-0.77; P < 0.001; number needed to treat, 4.1; 95% confidence interval, 2.8-7.8). The intervention group required significantly fewer doses of surfactant than did the control group. The intervention group had significantly lower interleukin levels (IL-1, IL-6, IL-8) in tracheal aspirates at 12 hours and lower IL-8 at 3-5 and 7-8 days. In very-low-birth-weight infants with severe respiratory distress syndrome, intratracheal administration of surfactant/budesonide compared with surfactant alone significantly decreased the incidence of BPD or death without immediate adverse effect. Clinical trial registered with www.clinicaltrials.gov (NCT-00883532).


Local intramural delivery of L-arginine enhances nitric oxide generation and inhibits lesion formation after balloon angioplasty.
Long-term oral administration of L-arginine has been shown to enhance production of nitric oxide (NO) and to reduce lesion formation. The goal of this study was to determine whether local intramural administration of L-arginine could enhance NO generation and reduce intimal thickening. New Zealand White rabbits (n = 27) received a 1% cholesterol diet. For the short-term study, after 1 week of diet, both iliac arteries were balloon injured. Four weeks later, vasoreactivity was assessed angiographically during infusion of acetylcholine (Ach) before and after delivery of L-arginine or saline into the right or left iliac artery (800 mg/5 mL; 0.2 mL/min, 15 minutes) by use of a local drug-delivery balloon. Vessels were then harvested for measurements of NO. For the long-term study, after balloon injury, drugs were delivered as above into the iliac arteries. Two and 4 weeks after L-arginine delivery, vasoreactivity was determined. Subsequently, the iliac arteries were harvested for histomorphometric analysis and measurements of NO. In the short-term study, local delivery of L-arginine restored endothelium-dependent vasodilatation (Ach 10(-5) mol/L; L-arginine +35 +/- 10%; saline -14 +/- 5%; P < .001) and enhanced local production of nitrogen oxides (L-arginine 152 +/- 28; saline 78 +/- 12 nmol/L per milligram of tissue per hour; P < .04). In the long-term study, local administration of L-arginine enhanced vascular NO production as long as 1 week after the injury (L-arginine 394.4 +/- 141.6; saline 86.3 +/- 34.3 nmol/L per milligram of tissue per hour; P < .01) and reduced intimal thickening 4 weeks later (intima/ media ratio: L-arginine 0.56 +/- 0.1; saline 1.40 +/- 0.2; P < .001), largely due to suppression of macrophage accumulation. A single intramural administration of L-arginine enhances vascular NO generation and inhibits lesion formation. Local augmentation of NO production at the site of balloon angioplasty may be a novel strategy to prevent restenosis.


Insect freeze tolerance: Roles of protein phosphatases and protein kinase A.
Freeze-tolerant larvae of the goldenrod gall fly, Eurosta solidaginis Fitch, show multiple metabolic adaptations for subzero survival including the autumn synthesis of high concentrations of polyols. The induction and regulation of cold hardiness adaptations requires the intermediary action of signal transduction enzymes. The present study evaluates changes in the activities of cAMP-dependent protein kinase (PKA), protein phosphatases 1 (PP1), 2A, 2C, and protein tyrosine phosphatases (PTPs) over the course of the winter season and also in insects exposed to -4, -20 degrees C, or anoxic conditions in the laboratory. The increased PKA and decreased PP1 over the winter season and/or at subzero temperature support a regulatory role for these enzymes in cryoprotectant polyol synthesis. PTP activities were also strongly increased under these conditions and may act to antagonize tyrosine kinase mediated cell growth and proliferation responses and, thereby, contribute to hypometabolism and diapause over the winter.


Impact of rising sea levels on Australian fur seals.
Global warming is leading to many unprecedented changes in the ocean-climate system. Sea levels are rising at an increasing rate and are amplifying the impact of storm surges along coastlines. As variability in the timing and strength of storm surges has been shown to affect pup mortality in the Australian fur seal (Arctocephalus pusillus doriferus), there is a need to identify the potential impacts of increased sea level and storm surges on the breeding areas of this important marine predator in Bass Strait, south-eastern Australia. Using high-resolution aerial photography and topographic data, the present study assessed the impacts of future inundation levels on both current and potential breeding habitats at each colony. Inundation from storm surges, based on a predicted rise in sea level, was modeled at each colony from 2012 to 2100. As sea level increases, progressively less severe storm surge conditions will be required to exceed current inundation levels and, thus, have the potential for greater impacts on pup mortality at Australian fur seal colonies. The results of the present study indicate that by 2100, a 1-in-10 year storm will inundate more habitat on average than a present-day 1-in-100 year storm. The study highlights the site-specific nature of storm surge impacts, and in particular the importance of local colony topography and surrounding bathymetry with small, low-lying colonies impacted the most. An increased severity of storm surges will result in either an increase in pup mortality rates associated with storm surges, or the dispersal of individuals to higher ground and/or new colonies.


Maintenance of increased bone mass after recombinant human parathyroid hormone (1-84) with sequential zoledronate treatment in ovariectomized rats.
The concept of lose, restore, maintain (LRM) for reversing existing osteoporosis was tested in rats. The withdrawal of PTH results in the loss of the acquired bone mass, but sequential therapy with zoledronate quite effectively maintained the PTH(1-84)-acquired bone quantity and quality. Because antiresorptive agents against osteoporosis are presently quite limited, strong anabolic agents such as human parathyroid hormone (hPTH) are quite helpful. However, because hPTH(1-34) is available only through injection and has a critical side effect of causing bone tumors during life-long administration in the rat, it would be practical to use PTH for the shortest possible duration to obtain the maximal effect. To determine the effectiveness of the osteoporosis-reversing concept of lose, restore, and maintain (LRM), recombinant hPTH(1-84) [rhPTH(1-84)] and the respective antiresorptive agents were sequentially studied. Thirty-six, 20-week-old Sprague-Dawley rats were used. Treatment started at the 25th week after ovariectomy, which was performed at 20 weeks of age, with 5 weeks of rhPTH(1-84) 100 microg/kg/day, 5 days/week, followed by the respective sequential therapies for 5 weeks as follows: (1) ovariectomized rats (OVX; n = 6), (2) sham-operated rats (SHAM; n = 6), (3) OVX rats with PTH maintenance (PTH-M; n = 6), (4) OVX rats treated with PTH and then PTH was withdrawn (PTH-W; n = 6), (5) PTH-treated OVX rats treated with 17beta-estradiol (PTH-E; 10 microg/day SC, 5 days/week; n = 6), and (6) PTH-treated OVX rats treated with zoledronate (PTH-Z; 12.5 microg/kg SC weekly; n = 6). BMD of the right femora was measured by DXA. microCT was used to measure the structural parameters of the second lumbar vertebrae. Three-point bending test of the femora and compressive tests of vertebrae were also performed. Bone quantity data showed that the BMD and most of the microstructural parameters were significantly higher in the PTH-M and PTH-Z groups than in the OVX and PTH-W groups (p < 0.05). Measurement of the cortical thickness revealed that only the PTH-M group showed a significant increase (p = 0.001). The ultimate force (Fu) at the midshaft of the femora was similar in the treated groups and stronger than in the OVX group (p < 0.05). However, in the vertebrae, the Fu of the PTH-M and PTH-Z groups was significantly higher, by approximately 44-47%, than in the OVX and PTH-E groups and showed a higher tendency than in the PTH-W group. PTH withdrawal resulted in the loss of acquired BMD, and sequential therapy with antiresorptives prevented further loss (17beta-estradiol versus zoledronate). The zoledronate after rhPTH(1-84) as a sequential regimen was quite consistently effective.


Undersized mitral annuloplasty inhibits left ventricular basal wall thickening but does not affect equatorial wall cardiac strains.
Undersized mitral annuloplasty has been widely employed for patients with ischemic mitral regurgitation. Beyond correction of mitral regurgitation, ring annuloplasty is postulated to normalize global left ventricular (LV) shape, thereby decreasing LV wall stress and promoting reverse LV remodeling. The effect of undersized annuloplasty on regional transmural LV wall thickening and strain patterns, however, has not been examined. In nine sheep, transmural radiopaque beadsets were inserted into the anterobasal and equatorial lateral LV walls, with additional markers silhouetting the left ventricle and mitral annulus. Four-dimensional marker dynamics were studied with biplane videofluoroscopy (open-chest) before and after tightening a Paneth-type mitral annuloplasty suture. LV volumes, mitral dimensions, transmural circumferential, longitudinal, and radial systolic strains, and end-diastolic (ED) and end-systolic (ES) remodeling strains in the two LV regions were computed. In the anterobasal LV wall close to the mitral annulus, annuloplasty increased ED wall thickness and surprisingly reduced systolic radial strain (wall thickening) at all transmural depths. Radial subepicardial, midwall, and subendocardial wall-thickening strains at ES in the anterobasal LV site were 0.25 +/- 0.15, 0.33 +/- 0.16, and 0.47 +/- 0.29, respectively, before tightening the suture annuloplasty, compared to 0.13 +/- 0.12, 0.15 +/- 0.18, and 0.20 +/- 0.26 after tightening. In the equatorial lateral LV wall further away from the annulus, most LV transmural systolic and remodeling strains did not change. Simulated undersized annuloplasty acutely decreased transmural systolic LV wall thickening in the anterobasal region, without substantially affecting transmural deformations in the lateral LV wall. These acute effects of undersized annuloplasty require a better understanding as they may potentially be deleterious, and a direct ventricular approach may be needed as an adjunct to promote reverse LV remodeling.


Increased cell migration and plasticity in Nrf2-deficient cancer cell lines.
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression is deregulated in many cancers. Genetic and biochemical approaches coupled with functional assays in cultured cells were used to explore the consequences of Nrf2 repression. Nrf2 suppression by Keap1-directed ubiquitylation or the expression of independent short hairpin RNA (shRNA)/siRNA sequences enhanced cellular levels of reactive oxygen species, Smad-dependent tumor cell motility and growth in soft agar. Loss of Nrf2 was accompanied by concomitant Smad linker region/C-terminus phosphorylation, induction of the E-cadherin transcriptional repressor Slug and suppression of the cell-cell adhesion protein E-cadherin. Ectopic expression of the wildtype but not dominant-negative Nrf2 suppressed the activity of a synthetic transforming growth factor-beta1-responsive CAGA-directed luciferase reporter. shRNA knock-down of Nrf2 enhanced the activity of the synthetic CAGA reporter, as well as the expression of the endogenous Smad target gene plasminogen activator inhibitor-1. Finally, we found that Nrf2/Smad3/Smad4 formed an immunoprecipitable nuclear complex. Thus, loss of Nrf2 increased R-Smad phosphorylation and R-Smad signaling, supporting the hypothesis that loss of Nrf2 in an oncogenic context-dependent manner can enhance cellular plasticity and motility, in part by using transforming growth factor-beta/Smad signaling.


Acteoside protects endothelial cells against free radical-induced oxidative stress.
The protective effect of acteoside against membrane lipid oxidation and free radical-mediated impairment of endothelial function was investigated. Results showed that iron-mediated oxidative modification of the cell membrane in cultured bovine pulmonary endothelial cells (PAECs) was significantly attenuated by acteoside as measured by thiobarbituric acid-reactive substances (TBARS). Fenton's reagent (H2O2/Fe2+) was used to generate hydroxyl radicals (*OH) and induce oxidative stress. Acteoside not only effectively minimized the loss of cell viability induced by hydroxyl radicals in cultured endothelial cells but also countered the free radical-induced destruction of the endothelium-dependent relaxation to acetylcholine in rat aorta. Furthermore, acteoside showed a dose-dependent scavenging effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals and appeared to be the most efficient in comparison with the four reference compounds (alpha-tocopherol, vitamin C, probucol and resveratrol). These data suggested that acteoside protects the cell from oxidative stress and that scavenging of free radicals could be a key mechanism contributing to the cytoprotective effect of acteoside.


Method validation and simultaneous determination of retinol, retinyl palmitate, β-carotene, α-tocopherol and vitamin C in rat serum treated with 7,12 dimethylbenz[a]anthracene and Plantago major L. by high- performance liquid chromatography using diode-array detection.
A new and simple high-performance liquid chromatography method was developed and validated for the simultaneous determination of retinol, retinyl palmitate, β-carotene, α-tocopherol and vitamin C in rat serum treated with Plantago Major L. and 7,12 dimethylbenz[a]anthracene. High-performance liquid chromatography analysis was performed utilizing an Inertsil ODS3 reversed phase column with methanol-tetrahydrofuran-water as mobile phase under gradient conditions, at 1.5 mL min(-1) flow rate and 25 °C. Diode-array detection was at 325, 450, 290 and 270 nm (retinol and retinyl palmitate), β-carotene, α-tocopherol and vitamin C, respectively and runnig time 18 min. The high-performance liquid chromatography assay and extraction procedure proposed are simple, rapid, sensitive and accurate. The method was then applied for the determination of retinol, retinyl palmitate, β-carotene, α-tocopherol and vitamin C in rat serum. Results of this study demonstrated that; at 60th day DMBA-treated group, there was a significant decrease in vitamin levels compared to the levels of control group. A significant increase was observed in vitamin levels of 7,12 dimethylbenz[α]anthracene+Plantago Major L.-treated group compared to the DMBA-treated group. Additionally, the results obtained in the study are found to be in agreement with data reported in the literature.


Pharmacological management of delirium in hospitalized adults--a systematic evidence review.
Despite the significant burden of delirium among hospitalized adults, there is no approved pharmacologic intervention for delirium. This systematic review evaluates the efficacy and safety of pharmacologic interventions targeting either prevention or management of delirium. We searched Medline, PubMed, the Cochrane Register of Controlled Trials, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) information systems from January 1966 to October 2008. We included randomized, controlled trials comparing pharmacologic compounds either to each other or placebo. We excluded non-comparison trials, studies with patients aged < 18 years, a history of an Axis I psychiatric disorder, and patients with alcohol-related delirium. Three reviewers independently extracted the data for participants, interventions and outcome measures, and critically appraised each study using the JADAD scale. We identified 13 studies that met our inclusion criteria and evaluated 15 compounds: second-generation antipsychotics, first-generation antipsychotics, cholinergic enhancers, an antiepileptic agent, an inhaled anesthetic, injectable sedatives, and a benzodiazepine. Four trials evaluated delirium treatment and suggested no differences in efficacy or safety among the evaluated treatment methods (first and second generation antipsychotics). Neither cholinesterase inhibitors nor procholinergic drugs were effective in preventing delirium. Multiple studies, however, suggest either shorter severity and duration, or prevention of delirium with the use of haloperidol, risperidone, gabapentin, or a mixture of sedatives in patients undergoing elective or emergent surgical procedures. The existing limited data indicates no superiority for second-generation antipsychotics over haloperidol in managing delirium. Although preliminary results suggest delirium prevention may be accomplished through various mechanisms, further studies are necessary to prove effectiveness.


Arthritic hand-finger movement similarity measurements: tolerance near set approach.
The problem considered in this paper is how to measure the degree of resemblance between nonarthritic and arthritic hand movements during rehabilitation exercise. The solution to this problem stems from recent work on a tolerance space view of digital images and the introduction of image resemblance measures. The motivation for this work is both to quantify and to visualize differences between hand-finger movements in an effort to provide clinicians and physicians with indications of the efficacy of the prescribed rehabilitation exercise. The more recent introduction of tolerance near sets has led to a useful approach for measuring the similarity of sets of objects and their application to the problem of classifying image sequences extracted from videos showing finger-hand movement during rehabilitation exercise. The approach to measuring the resemblance between hand movement images introduced in this paper is based on an application of the well-known Hausdorff distance measure and a tolerance nearness measure. The contribution of this paper is an approach to measuring as well as visualizing the degree of separation between images in arthritic and nonarthritic hand-finger motion videos captured during rehabilitation exercise.