An efficient and robust exfoliated bentonite/Ag3PO4/AgBr plasmonic photocatalyst for degradation of parabens.
Efficient visible-light-driven heterojunction photocatalysts have attracted broad interest owing to their promising adsorption and degradation performances in the removal of organic pollutants. In this study, a mesoporous exfoliated bentonite (EB)/Ag3PO4/AgBr (30%) photocatalyst was obtained by stripping and exfoliating bentonite as the support for loading Ag3PO4 and AgBr. The particle size ranges of Ag3PO4 and AgBr were about 10-30 nm and 5-10 nm, respectively. The exfoliated bentonite could greatly improve the dispersion and adsorption of Ag3PO4 and AgBr, and significantly enhance the stability of the material during paraben photodegradation. 0.2 g L-1 methylparaben (MPB) was completely decomposed over the EB/Ag3PO4/AgBr (30%) in 40 min under visible light irradiation. In addition, the photocatalytic activity of EB/Ag3PO4/AgBr (30%) remained at about 91% after five recycling runs manifesting that EB/Ag3PO4/AgBr (30%) possessed excellent stability. Radical quenching tests revealed that holes (h+) and hydroxyl radicals (·OH) were the major radicals. They attacked the side chain on the benzene ring of parabens, which were gradually oxidized to the intermediates, such as benzoic acid, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, azelaic acid, and eventually became CO2 and H2O. The enhancement of photocatalytic activity and photo-stability could be ascribed to the stable structural characteristics, enlarged surface area, high absorption ability, and improved light absorption ability from loading Ag3PO4 onto EB. Meanwhile, the matched energy levels of Ag3PO4 and AgBr made the photoelectron-hole pairs separate and transfer effectively at the interfaces. As a result, the photocatalytic properties of EB/Ag3PO4/AgBr (30%) composites were enhanced.


Unusual magnetic resonance imaging appearance of multiple cystic lesions in glioblastoma multiforme.
The differential diagnosis of multiple ring-enhancing intraaxial lesions includes neoplastic, infectious, inflammatory, demyelinating and vascular lesions. We report a case of a 41-year-old man who presented with a brief history of left lower extremity weakness and sensory loss. Magnetic resonance imaging demonstrated multiple ring-enhancing lesions in the right frontal and parietal lobes. Neuroradiology interpretation was felt to be unlikely for a neoplastic process. The patient underwent stereotactic brain biopsy, which was diagnostic for glioblastoma multiforme. This case demonstrates the importance of histological confirmation of intraaxial brain lesions whenever feasible. The course of his disease and treatment are discussed and the literature reviewed.


Obesity and cardiovascular risk in children and adolescents.
The global prevalence of overweight and obesity in children and adolescents has increased substantially over the past several decades. These trends are also visible in developing economies like India. Childhood obesity impacts all the major organ systems of the body and is well known to result in significant morbidity and mortality. Obesity in childhood and adolescence is associated with established risk factors for cardiovascular diseases and accelerated atherosclerotic processes, including elevated blood pressure (BP), atherogenic dyslipidemia, atherosclerosis, metabolic syndrome, type II diabetes mellitus, cardiac structural and functional changes and obstructive sleep apnea. Probable mechanisms of obesity-related hypertension include insulin resistance, sodium retention, increased sympathetic nervous system activity, activation of the renin-angiotensin-aldosterone system and altered vascular function. Adiposity promotes cardiovascular risk clustering during childhood and adolescence. Insulin resistance has a strong association with childhood obesity. A variety of proinflammatory mediators that are associated with cardiometabolic dysfunction are also known to be influenced by obesity levels. Obesity in early life promotes atherosclerotic disease in vascular structures such as the aorta and the coronary arteries. Childhood and adolescent adiposity has strong influences on the structure and function of the heart, predominantly of the left ventricle. Obesity compromises pulmonary function and increases the risk of sleep-disordered breathing and obstructive sleep apnea. Neglecting childhood and adolescent obesity will compromise the cardiovascular health of the pediatric population and is likely to result in a serious public health crisis in future.


We Need to Talk About Corruption in Health Systems.
The health sector consistently appears prominently in surveys of perceived corruption, with considerable evidence that this has serious adverse consequences for patients. Yet this issue is far from prominent in the international health policy discourse. We identify five reasons why the health policy community has been reluctant to talk about it. These are the problem of defining corruption, the fact that some corrupt practices are actually ways of making dysfunctional systems work, the serious challenges to researching corruption, concerns that a focus on corruption is a form of victim blaming that ignores larger issues, and a lack of evidence about what works to tackle it. We propose three things that can be done to address this situation. First, seek consensus on the scale and nature of corruption. Second, decide on priorities, taking account the importance of the particular problem and the feasibility of doing something about it. Third, take a holistic view, drawing on a wide range of disciplines.


Interleukin 6 mediates the therapeutic effects of adipose-derived stromal/stem cells in lipopolysaccharide-induced acute lung injury.
Adipose-derived stromal/stem cells (ASCs) have anti-inflammatory as well as immunosuppressive activities and are currently the focus of clinical trials for a number of inflammatory diseases. Acute lung injury (ALI) is an inflammatory condition of the lung for which standard treatment is mainly supportive due to lack of effective therapies. Our recent studies have demonstrated the ability of both human ASCs (hASCs) and mouse ASCs (mASCs) to attenuate lung damage and inflammation in a rodent model of lipopolysaccharide-induced ALI, suggesting that ASCs may also be beneficial in treating ALI. To better understand how ASCs may act in ALI and to elucidate the mechanism(s) involved in ASC modulation of lung inflammation, gene expression analysis was performed in ASC-treated (hASCs or mASCs) and control sham-treated lungs. The results revealed a dramatic difference between the expression of anti-inflammatory molecules by hASCs and mASCs. These data show that the beneficial effects of hASCs and mASCs in ALI may result from the production of different paracrine factors. Interleukin 6 (IL-6) expression in the mASC-treated lungs was significantly elevated as compared to sham-treated controls 20 hours after delivery of the cells by oropharyngeal aspiration. Knockdown of IL-6 expression in mASCs by RNA interference abrogated most of their therapeutic effects, suggesting that the anti-inflammatory properties of mASCs in ALI are explained, at least in part, by activation of IL-6 secretion.


Supercritical angle fluorescence correlation spectroscopy.
We explore the potential of a supercritical angle (SA) objective for fluorescence correlation spectroscopy (FCS). This novel microscope objective combines tight focusing by an aspheric lens with strong axial confinement of supercritical angle fluorescence collection by a parabolic mirror lens, resulting in a small detection volume. The tiny axial extent of the detection volume features an excellent surface sensitivity, as is demonstrated by diffusion measurements in model membranes with an excess of free dye in solution. All SA-FCS measurements are directly compared to standard confocal FCS, demonstrating a clear advantage of SA-FCS, especially for diffusion measurements in membranes. We present an extensive theoretical framework that allows for accurate and quantitative evaluation of the SA-FCS correlation curves.


Recurrent aphthous stomatitis. A study of the clinical characteristics of lesions in 93 cases.
We studied the clinical characteristics of 93 patients with recurrent aphthous stomatitis (RAS); 66 corresponded to minor aphthae (MiRAS), 20 to major aphthae (MaRAS), and 7 to herpes-like ulcerations (HU). MiRAS was seen to present the lowest rate of recurrences, as well as the shortest duration and the fewest lesions per episode. In turn, MaRAS presented the longest duration per recurrence, along with a number of lesions and recurrences that was lower than in HU but greater than in cases of MiRAS. Finally, HU developed the greatest number of lesions and recurrences. When we classified RAS according to the rate of episodes, no statistically significant differences were observed among the three types in terms of patient age, number and duration of lesions, or evolution time of the oral disorder.


New clues into the mechanisms of rice domestication.
Domestication of rice involved incorporation of specific yield-related changes in wild species of rice. This agricultural process has been of significant interest for plant biologists. The recent advance in genomics has provided new tools to investigate the genetic basis and consequences of domestication. Several genes involved in domestication and diversification process have been characterized, and as expected, this list is over-represented by transcription factors and their cofactors. Most often the modification orchestrated expression levels of genes such as those coding for transcription factors. It has been proposed that transcriptional regulators and their regulation is likely a major theme controlling morphological differences between crops and their progenitors. However, recent data indicate that single amino acid changes in genes coding for key proteins as well as epigenetic and small RNA-mediated pathways also contributed towards domesticationassociated phenotypes.


Health insurance coverage and take-up: lessons from behavioral economics.
Millions of uninsured Americans ostensibly have insurance available to them-many at very low cost-but do not take it up. Traditional economic analysis is based on the premise that these are rational decisions, but it is hard to reconcile observed enrollment patterns with this view. The policy prescriptions that the traditional model generates may thus fail to achieve their goals. Behavioral economics, which integrates insights from psychology into economic analysis, identifies important deviations from the traditional assumptions of rationality and can thus improve our understanding of what drives health insurance take-up and improved policy design. Rather than a systematic review of the coverage literature, this article is a primer for considering issues in health insurance coverage from a behavioral economics perspective, supplementing the standard model. We present relevant evidence on decision making and insurance take-up and use it to develop a behavioral approach to both the policy problem posed by the lack of health insurance coverage and possible policy solutions to that problem. We found that evidence from behavioral economics can shed light on both the sources of low take-up and the efficacy of different policy levers intended to expand coverage. We then applied these insights to policy design questions for public and private insurance coverage and to the implementation of the recently enacted health reform, focusing on the use of behavioral insights to maximize the value of spending on coverage. We concluded that the success of health insurance coverage reform depends crucially on understanding the behavioral barriers to take-up. The take-up process is likely governed by psychology as much as economics, and public resources can likely be used much more effectively with behaviorally informed policy design.


Knowledge, attitude, and practice of dental professionals regarding the effect and management of food impaction associated with fixed partial denture prostheses: A survey.
This survey was undertaken to assess dentist's opinion regarding the occurrence and pattern of food impaction in relation to fixed partial denture (FPD) prostheses, its commonly observed consequences, factors contributing to it, and its management. A descriptive survey was conducted on a sample size of 150 dental practitioners. The pro forma consisted of informed consent, demographic information, and questionnaire. The results were tallied and quantitative analysis was performed to obtain the descriptive statistics for the data using SPSS version 20. All the study respondents had come across patients who complained of food impaction in relation to FPD. The most common consequences of food impaction were proximal caries of the adjacent teeth and interdental bone loss. Majority of the dentists considered faulty FPD design with improper contact relation, improper crown contour, poor margin adaptation, and faulty pontic design as the most likely reason for food impaction. Repeating the FPD with emphasis on prescribing and reinforcing the use of proper interdental aids was considered as the ideal treatment option. It was also observed that about half of the dentists always communicated inadequate information of the FPD prostheses that needed replacement to the dental laboratory technician for the successive bridge. Most of the times, prosthodontists were consulted to rectify the problem of food impaction resulting from faulty FPD prostheses. However, it is obvious that it is easier and more prudent to prevent rather than treat food impaction. This study gives an overview of some of the common errors in designing the FPD prostheses which often lead to food impaction and measures to be taken to overcome them. It may be concluded as all the dentists participating in the survey agreed that food impaction is one of the common complaint among FPD Patients. Proximal caries and interdental bone loss were the prevalent outcomes of food impaction. Faulty FPD design was allegedly attributed as the reason for food impaction. Prosthodontists were routinely consulted to resolve the dilemma of food impaction. However, it is rational to prevent food impaction rather than to tackle the sequel later.


Optimization of large field tritan stimuli using concentric isoluminant annuli.
Large, nominally isoluminant chromatic gratings containing a short-wavelength component are prone to luminance contrast intrusions due to retinal inhomogeneity, especially as a result of the uneven distribution of macular pigment. Isoluminance is usually determined for a relatively small, central area, but a significantly larger stimulus cannot be isoluminant across the whole field, largely due to macular pigment absorption of short-wavelength light. This confounds attempts to maintain high selectivity, particularly in suprathreshold electrophysiological and brain-imaging studies that require large stimulus fields. Here we introduce the concept of a panisoluminant grating (PIG), which comprises a series of concentric annular regions, each adjusted to location-specific isoluminance for the observer. Gratings were modulated along subject-specific tritanopic confusion lines and the selectivity of responses to the PIG was tested according to both psychophysical and electrophysiological criteria. The psychophysically-determined temporal tuning function obtained using the PIG showed lower sensitivity and lower resolution than with a conventional tritan grating of equal diameter (18°). Chromatic onset visual evoked potentials (VEPs) to the PIG were dominated by a chromatic-specific negative wave and reduced achromatic response components that were prominent in VEPs to the conventional grating. These data demonstrate that a large tritan PIG is capable of eliciting selective responses of the S-cone-driven pathway at threshold and at suprathreshold levels. The PIG stimulus may prove beneficial in investigations that require large fields such as electrophysiological and brain imaging studies of chromatic processing.


CD40L is critical for protection from demyelinating disease and development of spontaneous remyelination in a mouse model of multiple sclerosis.
Theiler's murine encephalomyelitis virus (TMEV) induces acute neuronal disease followed by chronic demyelination in susceptible strains of mice. In this study we examined the role of a limited immune defect (deletion or blocking of CD40 ligand [CD40L]) on the extent of brain disease, susceptibility to demyelination, and the ability of demyelinated mice to spontaneously remyelinate following TMEV infection. We demonstrated that CD40L-dependent immune responses participate in pathogenesis in the cerebellum and the spinal cord white matter but protect the striatum of susceptible SJL/J mice. In mice on a background resistant to TMEV-induced demyelination (C57BL/6), the lack of CD40L resulted in increased striatal disease and meningeal inflammation. In addition, CD40L was required to maintain resistance to demyelination and clinical deficits in H-2b mice. CD40L-mediated interactions were also necessary for development of protective H-2b-restricted cytotoxic T cell responses directed against the VP2 region of TMEV as well as for spontaneous remyelination of the spinal cord white matter. The data presented here demonstrated the critical role of this molecule in both antibody- and cell-mediated protective immune responses in distinct phases of TMEV-mediated pathology.


Modification of leukocyte adhesion in spontaneously hypertensive rats by adrenal corticosteroids.
Leukocyte adhesion is a key factor in the pathogenesis of organ injury following a variety of stimuli. In this study we have addressed the role of leukocyte adhesion in hypertensives as a risk factor for organ injury. In the spontaneously hypertensive rat (SHR), the number of circulating leukocytes and their level of activation are significantly increased compared with its normotensive control, the Wistar-Kyoto rat (WKY). We have demonstrated that elevated levels of glucocorticoid in SHR suppress P-selectin-mediated leukocyte-endothelial interaction in the microcirculation. It is possible that the disturbance in leukocyte-endothelial interactions may result in an elevated number of leukocytes in the circulation. The aim of the present study was to investigate the contribution of the adrenal glands to the disturbance in leukocyte behavior in SHR by subjecting the animals to bilateral adrenalectomy and investigating the effect of hydrocortisone. In addition, we have studied by immunohistochemistry the expression of the endothelial adhesion molecule, P-selectin, in response to histamine in the mesenteric venules of normal and adrenalectomized SHR and WKY. The elevated blood pressure, above-normal leukocyte counts, and elevated number of activated neutrophils (nitroblue tetrazolium test) in SHR were blunted after adrenalectomy. The blunted histamine-induced leukocyte-endothelial interaction in the mesenteric venules of SHR was restored after adrenalectomy. Treatment with hydrocortisone significantly attenuated the elevated leukocyte adhesion in the adrenalectomized SHR as well as in WKY. The suppressed P-selectin expression in SHR mesentery was restored after adrenalectomy. In conclusion, the subnormal leukocyte-endothelial interaction in response to an inflammatory stimulation in SHR is abolished after adrenalectomy, suggesting a relationship between the altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensives.


Microbiological profile of early onset/aggressive periodontitis patients.
The objectives of this study were to characterize the bacterial profile and to seek possible bacterial associations in the subgingival microbiota of early onset periodontitis/aggressive periodontitis patients by using two different techniques, culture and immunofluorescence. The study group consisted of 66 systemically healthy individuals with evidence of early onset periodontitis - 41 females and 25 males aged 23-35 years (mean 31.1 +/- 3.1 years). Bacterial samples were collected from the deepest site in each quadrant, resulting in a total of 264 sites with a mean probing pocket depth of 6.6 +/- 1.5 mm. Samples were cultured anaerobically and in 10% CO(2) using selective and nonselective media, and isolates were characterized to species level. Indirect immunofluorescence using monoclonal antibodies was applied to detect Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia (Bacteroides forsythus, Tannerella forsythensis), Prevotella intermedia/Prevotella nigrescens, Campylobacter rectus, Peptostreptococcus micros and Actinomyces israelii. 93.6% of sampled sites showed bleeding on probing and 23.5% were positive for suppuration. P. intermedia/P. nigrescens, P. gingivalis, and C. rectus were detected in 77.3-85.9% of samples using culture methods and in 85.6-91.3% using immunofluorescence. P. micros and A. actinomycetemcomitans were found, respectively, in 63.3% and 25.0% of all sites using culturing and in 58.7% and 27.7% sites using immunofluorescence. Significantly strong positive associations were observed between T. forsythia and C. rectus (odds ratio 109.46), and T. forsythia and P. gingivalis (odd ratio 90.26), whereas a negative association was seen between P. intermedia/P. nigrescens and A. actinomycetemcomitans (odds ratio 0.42). Coinfection by P. gingivalis, T. forsythia, P. intermedia/P. nigrescens and C. rectus was observed in 62.1% of the test sites, and in 89.4% of the studied subjects. The sensitivity of immunofluorescence for T. forsythia, C. rectus, P. intermedia/P. nigrescens and P. gingivalis was found to be very high (0.99-0.94) using culture as the reference detection method. The agreement between culture and immunofluorescence in detecting the presence or absence of the investigated species was 85.2-88.1% for P. gingivalis, P. intermedia/P. nigrescens, C. rectus, and T. forsythia, 75.9% for A. actinomycetemcomitans and 70.4% for P. micros. The microbial profile of the early onset/aggressive periodontitis population was complex. The agreement between the two detection methods was very high.


Integrating sphere simulation: application to total flux scale realization.
A method is proposed for realizing the total flux scale of light sources by use of an integrating sphere with an opening to introduce a known amount of flux from a luminous intensity standard or a spectral irradiance standard lamp placed outside the sphere. Computer simulations were made on several models of an integrating sphere, designed to compare the total flux of a test lamp inside the sphere with the flux introduced from an external source. I describe the theory and algorithm of the simulation, present the results of the simulation for varying conditions of sphere geometry such as size and location of the baffles, internal source, and wall reflectance, and predict that one of the models has sufficient accuracy to calibrate lamps for total flux.


Surgeon volume compared to hospital volume as a predictor of outcome following primary colon cancer resection.
A strong association between high hospital procedure volume and survival following colon cancer resection has been demonstrated. However, the importance of surgeon case volume as a determinant of outcome has been less well studied, and it is unclear whether hospital or surgeon volume is the more powerful predictor of outcomes. A retrospective population-based cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database identified 24,166 colon cancer patients aged 65 years and older who had surgery for a primary tumor diagnosed in 1991-1996 in a SEER area. Hospital and surgeon-specific procedure volume was ascertained based on the number of claims submitted over the 6-year study period. Outcome measures were mortality at 30 days and 2 years, overall survival, and the frequency of operations requiring an intestinal stoma. Age, sex, race, comorbid illness, cancer stage, socioeconomic status, emergent hospitalization, and the presence of obstruction/perforation were used to adjust for differences in case-mix. After adjusting for surgeon procedure volume, high hospital procedure volume remained a strong predictor of low post-operative mortality rates (P < 0.001 for each outcome with and without adjustment for surgeon procedure volume). Surgeon-specific procedure volume was also an important predictor of surgical outcomes (P = 0.002 for 30-day mortality, P = 0.001 for 2-year mortality), although this effect was attenuated after adjusting for hospital volume (P = 0.03 for 30-day mortality, P = 0.02 for 2-year mortality). Hospital volume and surgeon volume were each an important predictor of the ostomy rate. Among high volume institutions and surgeons, individual providers with unusually high ostomy rates could be identified. Both hospital and surgeon-specific procedure volume predict outcomes following colon cancer resection; but hospital volume may exert a stronger effect. Therefore, efforts to optimize the quality of colon cancer surgery should focus on multidisciplinary aspects of hospital care rather than solely on intraoperative technique.


Targeting DNA-PKcs and telomerase in brain tumour cells.
Patients suffering from brain tumours such as glioblastoma and medulloblastoma have poor prognosis with a median survival of less than a year. Identifying alternative molecular targets would enable us to develop different therapeutic strategies for better management of these tumours. Glioblastoma (MO59K and KNS60) and medulloblastoma cells (ONS76) were used in this study. Telomerase inhibitory effects of MST-312, a chemically modified-derivative of epigallocatechin gallate, in the cells were assessed using telomere repeat amplification protocol. Gene expression analysis following MST-312 treatment was done by microarray. Telomere length was measured by telomere restriction fragments analysis. Effects of MST-312 on DNA integrity were evaluated by single cell gel electrophoresis, immunofluorescence assay and cytogenetic analysis. Phosphorylation status of DNA-PKcs was measured with immunoblotting and effects on cell proliferation were monitored with cell titre glow and trypan blue exclusion following dual inhibition. MST-312 showed strong binding affinity to DNA and displayed reversible telomerase inhibitory effects in brain tumour cells. In addition to the disruption of telomere length maintenance, MST-312 treatment decreased brain tumour cell viability, induced cell cycle arrest and double strand breaks (DSBs). DNA-PKcs activation was observed in telomerase-inhibited cells presumably as a response to DNA damage. Impaired DNA-PKcs in MO59J cells or in MO59K cells treated with DNA-PKcs inhibitor, NU7026, caused a delay in the repair of DSBs. In contrast, MST-312 did not induce DSBs in telomerase negative osteosarcoma cells (U2OS). Combined inhibition of DNA-PKcs and telomerase resulted in an increase in telomere signal-free chromosomal ends in brain tumour cells as well. Interestingly, continual exposure of brain tumour cells to telomerase inhibitor led to population of cells, which displayed resistance to telomerase inhibition-mediated cell arrest. DNA-PKcs ablation in these cells, however, confers higher cell sensitivity to telomerase inhibition, inducing cell death. Efficient telomerase inhibition was achieved with acute exposure to MST-312 and this resulted in subtle but significant increase in DSBs. Activation of DNA-PKcs might indicate the requirement of NHEJ pathway in the repair telomerase inhibitor induced DNA damage. Therefore, our results suggest a potential strategy in combating brain tumour cells with dual inhibition of telomerase and NHEJ pathway.


Epigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells.
Long interspersed nuclear element-1 (LINE-1 or L1) reactivation is linked to poor prognosis in non-small-cell lung carcinoma (NSCLC), but the molecular bases of this response remain largely unknown. In this report, we show that challenge of human bronchial epithelial cells (HBECs) with the lung carcinogen, benzo(a)pyrene (BaP), shifted the L1 promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (NuRD) complex. Carcinogen challenge was also associated with partial displacement of constituent proteins from the nuclear to the cytoplasmic compartment. Disruption of NuRD corepression by genetic ablation or carcinogen treatment correlated with accumulation of L1 mRNA and proteins. Mi2β bound directly to the L1 promoter to effect retroelement silencing, and this response required the DNA- and ATPase-binding domains of Mi2β. Sustained expression of L1 in HBECs was tumorigenic in a human-SCID mouse xenograft model, giving rise to tumors that regressed over time. Together, these results show that functional modulation of the NuRD constituent proteins is a critical molecular event in the activation of L1 retrotransposon. L1 expression creates a microenvironment in HBECs that is conducive to neoplasia and malignant transformation.


Anticoagulant fucoidan fractions from Fucus vesiculosus induce platelet activation in vitro.
Anticoagulant fucoidan fractions of different molecular weight and sulfate content were prepared and investigated for their effects on platelet function in vitro. The fucoidan fractions were incubated with human platelet rich plasma (PRP) at concentrations of 5, 10 and 50 micrograms/ml. Platelet activation was subsequently studied by a standard aggregation assay and flow cytometric determination of the activation dependent platelet-surface markers CD62p (P-selectin, GMP-140) and CD63 (GP53). All fucoidan fractions induced irreversible platelet aggregation in a dose-dependent manner. Comparing fractions of identical molecular weight (100 kDa) the low sulfate content fucoidan FF5 (S = 7.6%) exerted a significantly greater effect than the highly sulfated fucoidan FF7 (S = 10.2%) over the whole concentration range (n = 5, P < 0.05). Among fractions of identical sulfate content fucoidan-induced platelet aggregation was also found to depend on the molecular weight of the fucoidan. At concentrations of 10 and 50 micrograms/ml the high molecular weight fraction FF7/1 (150 kDa) showed a significantly greater effect than the 50 kDa fraction FF7/3 (24.8 +/- 6.7 vs. 7.0 +/- 3.5 and 54.6 +/- 13.5 vs. 15.0 +/- 9.0%, respectively; mean +/- SD, n = 5, P < 0.05). The molecular weight dependence of the fucoidan effect was also reflected by the flow cytometric data. Coincubation of FF7/1 and FF7/3 (10 micrograms/ml) with PRP increased the number of CD62p and CD63 positive platelets by 9.0 +/- 3.3 vs. 2 +/- 1.9 and 7.1 +/- 2.4 vs. 3.2 +/- 2.6% over control values, respectively (n = 5, P < 0.05). In conclusion, our results show that the low molecular weight fucoidan FF7/3 combines potent anticoagulant and fibrinolytic properties with only minor platelet activating effects and is therefore a suitable substance for further pharmacological studies.


Evaluation of the Safety and Effectiveness of Topical Intrapleural Application of Tranexamic Acid in Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Bleeding remains a common complication post-thoracic surgery. Although intravenous tranexamic acid (TXA) has been shown to decrease blood loss, its use has been associated with adverse effects. Accordingly, topical TXA has been proposed as an alternative to reduce bleeding with fewer systemic complications. We searched Medline, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing topical TXA versus control (i.e., placebo) in patients undergoing thoracic procedures. The primary outcome was total postoperative blood loss at 24 hours. Secondary outcomes included were the number of red blood cell (RBC) transfusions, and hospital length of stay (LOS). Meta-analyses were pooled using mean difference with inverse-variance weighting and random-effects. Out of the 575 unique studies that were screened, we identified three randomized controlled trials (RCTs) involving 399 patients. Out of the three RCTs analyzed, two studies, accounting for 67% of the total, were found to have a low risk of bias. The primary outcome of 24-h post-operative blood loss was significantly lower in patients who received TXA (mean difference [MD] -93.6 ml, 95% CI -121.8 to -65.4 ml, I2 = 45%). In addition, the need for RBC transfusion was significantly lower in the topical TXA group compared to control (MD -0.5 units, 95% CI -0.8 to -0.3 units, I2 = 60%). However, there was no significant difference in the hospital length of stay (LOS) (MD -0.3 days, 95% CI -0.9 to 0.4 days, I2 = 0%). These results remained consistent after several sensitivity analyses. The use of topical intrapleural tranexamic acid has also been found to be safe without any significant safety concerns. Topical intrapleural TXA reduces blood loss and the need for blood transfusions during thoracic surgery. In addition, there is no evidence of the increased safety concerns associated with its use. Larger trials are necessary to validate these findings and evaluate the safety and efficacy of different dosages.


Biomimetic and bioinspired silica: recent developments and applications.
In a previous review of biological and bioinspired silica formation (S. V. Patwardhan et al., Chem. Commun., 2005, 1113 [ref. 1]), we have identified and discussed the roles that organic molecules (additives) play in silica formation in vitro. Tremendous progress has been made in this field since and this review attempts to capture, with selected examples from the literature, the key advances in synthesising and controlling properties of silica-based materials using bioinspired approaches, i.e. conditions of near-neutral pH, all aqueous environments and room temperature. One important reason to investigate biosilicifying systems is to be able to develop novel materials and/or technologies suitable for a wide range of applications. Therefore, this review will also focus on applications arising from research on biological and bioinspired silica. A range of applications such as in the areas of sensors, coatings, hybrid materials, catalysis and biocatalysis and drug delivery have started appearing. Furthermore, scale-up of this technology suitable for large-scale manufacturing has proven the potential of biologically inspired synthesis.


Follow-up of the Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA 2) 1991-2003: methods and characterization of participants.
The Swiss Cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) was designed to investigate the health effects from long-term exposure to air pollution. The health assessment at recruitment (1991) and at the first reassessment (2001-3) consisted of an interview about respiratory health, occupational and other exposures, spirometry, a methacholine bronchial challenge test, end-expiratory carbon monoxide (CO) measurement and measurement for atopy. A bio bank for DNA and blood markers was established. Heart rate variability was measured using a 24-hour ECG (Holter) in a random sample of participants aged 50 years and older. Concentrations of nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulates in ambient air have been monitored in all study areas since 1991. Residential histories collected over the 11 year follow-up period coupled with GIS modelling will provide individual long-term air pollutant exposure estimates. Of 9651 participants examined in 1991, 8715 could be traced for the cohort study and 283 died. Basic information about health status was obtained for 8047 individuals (86% of alive persons), 6 528 individuals (70%) agreed to the health examination and 5 973 subjects (62%) completed the entire protocol. Non-participants in the reassessment were on average younger than participants and more likely to have been smokers and to have reported respiratory symptoms in the first assessment. Average weight had increased by 5.5 kg in 11 years and 28% of smokers in 1991 had quit by the time of the reassessment.


Establishment of two new myeloma cell lines from bilateral pleural effusions: evidence for sequential in vivo clonal change.
Two new human myeloma cell lines have been established from a 36-year-old woman with refractory IgG kappa multiple myeloma in whom bilateral malignant pleural effusions developed. The malignant plasma cells from each effusion were set up in a liquid culture using an L-15 medium containing catalase, glutathione, selenous acid, ascorbic acid, insulin, transferrin, additional glutamine hydrocortisone, and 2-mercaptoethanol and designated as M-3 medium. Two IgG kappa cell lines, LB -831 and LB-832, were established and proved to be Epstein-Barr virus negative using the internal repeat sequence DNA probe. Characteristic plasma cell morphology was evident by light and electron microscopy. Immunotyping revealed an IgG kappa , B1+, B2-, Ia (HLA-DR)+, CALLA+ phenotype for each cell line as well as for the original pleural fluid and bone marrow myeloma cells. The supernatants also contained IgG kappa, beta 2 microglobulin, and large amounts of osteoclast-activating factor (indicating bone-resorbing activity). Cytogenetic analysis of the LB-831 cell line revealed a nearly triploid highly abnormal karyotype with numerous clonal chromosomal abnormalities involving chromosomes 1, 3, 5, 7, 13, and 15; several structurally abnormal marker chromosomes; and a putative homogeneously staining region on chromosome 7p at band p22. Analysis of the LB-832 cell line revealed several additional clonal abnormalities. These additional cytogenetic changes suggest that in vivo sequential clonal evolution occurred in this patient. Therefore, two new but related cell lines have been established, which should prove useful for further biological studies.


Sequencing of Australian wild rice genomes reveals ancestral relationships with domesticated rice.
The related A genome species of the Oryza genus are the effective gene pool for rice. Here, we report draft genomes for two Australian wild A genome taxa: O. rufipogon-like population, referred to as Taxon A, and O. meridionalis-like population, referred to as Taxon B. These two taxa were sequenced and assembled by integration of short- and long-read next-generation sequencing (NGS) data to create a genomic platform for a wider rice gene pool. Here, we report that, despite the distinct chloroplast genome, the nuclear genome of the Australian Taxon A has a sequence that is much closer to that of domesticated rice (O. sativa) than to the other Australian wild populations. Analysis of 4643 genes in the A genome clade showed that the Australian annual, O. meridionalis, and related perennial taxa have the most divergent (around 3 million years) genome sequences relative to domesticated rice. A test for admixture showed possible introgression into the Australian Taxon A (diverged around 1.6 million years ago) especially from the wild indica/O. nivara clade in Asia. These results demonstrate that northern Australia may be the centre of diversity of the A genome Oryza and suggest the possibility that this might also be the centre of origin of this group and represent an important resource for rice improvement.


Internet Addiction, Smartphone Addiction, and Hikikomori Trait in Japanese Young Adult: Social Isolation and Social Network.
Background: As the number of internet users increases, problems related to internet overuse are becoming more and more serious. Adolescents and youth may be particularly attracted to and preoccupied with various online activities. In this study, we investigated the relationship of internet addiction, smartphone addiction, and the risk of hikikomori, severe social withdrawal, in Japanese young adult. Methods: The subjects were 478 college/university students in Japan. They were requested to complete the study questionnaire, which consisted of questions about demographics, internet use, the Internet Addiction Test (IAT), the Smartphone Addiction Scale (SAS)-Short Version (SV), the 25-item Hikikomori Questionnaire (HQ-25), etc. We investigated the difference and correlation of the results between two groups based on the purpose of internet use or the total score of each self-rating scale, such as screened positive or negative for the risk of internet addiction, smartphone addiction, or hikikomori. Results: There was a trend that males favored gaming in their internet use while females used the internet mainly for social networking via smartphone, and the mean SAS-SV score was higher in females. Two-group comparisons between gamers and social media users, according to the main purpose of internet use, showed that gamers used the internet longer and had significantly higher mean IAT and HQ-25 scores. Regarding hikikomori trait, the subjects at high risk for hikikomori on HQ-25 had longer internet usage time and higher scores on both IAT and SAS-SV. Correlation analyses revealed that HQ-25 and IAT scores had a relatively strong relationship, although HQ-25 and SAS-SV had a moderately weak one. Discussion: Internet technology has changed our daily lives dramatically and altered the way we communicate as well. As social media applications are becoming more popular, users are connected more tightly to the internet and their time spent with others in the real world continues to decrease. Males often isolate themselves from the social community in order to engage in online gaming while females use the internet as to not be excluded from their communications online. Mental health providers should be aware of the seriousness of internet addictions and hikikomori.


Women's conceptions of coping with major depression in daily life: a qualitative, salutogenic approach.
The experience of having a severe disease such as major depression affects all aspects of the individual's life, including family, work, and social functioning. Therefore, the aim of this study was to describe, from a salutogenic approach, women's conceptions of coping with major depression in daily life with the help of professional and lay support. Thirteen women, previously hospitalized for major depression, were included in the study. The women were selected by strategic sampling, and data were analyzed by application of a phenomenographic approach. Four descriptive categories emerged: Self-Healing, Managing, Receiving Social Support, and Finding Meaning. While working their way out of the depression, the women needed to undergo a process of transition, involving both a cognitive and an emotional understanding, which they subsequently translated into health-related actions. The task of psychiatric mental health nurses is to provide care that empowers patients. Future nursing research should explore the circumstances that empower these women to start the transition process, as this process appears to be vital for recovery from major depression.


Balance Dysfunction in Parkinson's Disease: The Role of Posturography in Developing a Rehabilitation Program.
Balance dysfunction (BD) in Parkinson's disease (PD) is a disabling symptom, difficult to treat and predisposing to falls. The dopaminergic drugs or deep brain stimulation does not always provide significant improvements of BD and rehabilitative approaches have also failed to restore this condition. In this study, we investigated the suitability of quantitative posturographic indicators to early identify patients that could develop disabling BD. Parkinsonian patients not complaining of a subjective BD and controls were tested using a posturographic platform (PP) with open eyes (OE) and performing a simple cognitive task [counting (OEC)]. We found that patients show higher values of total standard deviation (SD) of body sway and along the medio-lateral (ML) axis during OE condition. Furthermore, total and ML SD of body sway during OE condition and total SD of body sway with OEC were higher than controls also in a subgroup of patients with normal Berg Balance Scale. We conclude that BD in Parkinsonian patients can be discovered before its appearance using a PP and that these data may allow developing specific rehabilitative treatment to prevent or delay their onset.


Crystal structure of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase: insight into the active site and catalytic mechanism of a novel decarboxylation reaction.
Alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) is a widespread enzyme found in many bacterial species and all currently sequenced eukaryotic organisms. It occupies a key position at the branching point of two metabolic pathways: the tryptophan to quinolinate pathway and the bacterial 2-nitrobenzoic acid degradation pathway. The activity of ACMSD determines whether the metabolites in both pathways are converted to quinolinic acid for NAD biosynthesis or to acetyl-CoA for the citric acid cycle. Here we report the first high-resolution crystal structure of ACMSD from Pseudomonas fluorescens which validates our previous predictions that this enzyme is a member of the metal-dependent amidohydrolase superfamily of the (beta/alpha)(8) TIM barrel fold. The structure of the enzyme in its native form, determined at 1.65 A resolution, reveals the precise spatial arrangement of the active site metal center and identifies a potential substrate-binding pocket. The identity of the native active site metal was determined to be Zn. Also determined was the structure of the enzyme complexed with cobalt at 2.50 A resolution. The hydrogen bonding network around the metal center suggests that Arg51 and His228 may play important roles in catalysis. The metal center configuration of PfACMSD is very similar to that of Zn-dependent adenosine deaminase and Fe-dependent cytosine deaminase, suggesting that ACMSD may share certain similarities in its catalytic mechanism with these enzymes. These data enable us to propose possible catalytic mechanisms for ACMSD which appear to be unprecedented among all currently characterized decarboxylases.


Ribokinase family evolution and the role of conserved residues at the active site of the PfkB subfamily representative, Pfk-2 from Escherichia coli.
Phosphofructokinase-2 (Pfk-2) belongs to the ribokinase family and catalyzes the ATP-dependent phosphorylation of fructose-6-phosphate, showing allosteric inhibition by a second ATP molecule. Several structures have been deposited on the PDB for this family of enzymes. A structure-based multiple sequence alignment of a non-redundant set of these proteins was used to infer phylogenetic relationships between family members with different specificities and to dissect between globally conserved positions and those common to phosphosugar kinases. We propose that phosphosugar kinases appeared early in the evolution of the ribokinase family. Also, we identified two conserved sequence motifs: the TR motif, not described previously, present in phosphosugar kinases but not in other members of the ribokinase family, and the globally conserved GXGD motif. Site-directed mutagenesis of R90 and D256 present in these motifs, indicate that R90 participates in the binding of the phosphorylated substrate and that D256 is involved in the phosphoryl transfer mechanism.


Pitx1 broadly associates with limb enhancers and is enriched on hindlimb cis-regulatory elements.
Extensive functional analyses have demonstrated that the pituitary homeodomain transcription factor Pitx1 plays a critical role in specifying hindlimb morphology in vertebrates. However, much less is known regarding the target genes and cis-regulatory elements through which Pitx1 acts. Earlier studies suggested that the hindlimb transcription factors Tbx4, HoxC10, and HoxC11 might be transcriptional targets of Pitx1, but definitive evidence for direct regulatory interactions has been lacking. Using ChIP-Seq on embryonic mouse hindlimbs, we have pinpointed the genome-wide location of Pitx1 binding sites during mouse hindlimb development and identified potential gene targets for Pitx1. We determined that Pitx1 binding is significantly enriched near genes involved in limb morphogenesis, including Tbx4, HoxC10, and HoxC11. Notably, Pitx1 is bound to the previously identified HLEA and HLEB hindlimb enhancers of the Tbx4 gene and to a newly identified Tbx2 hindlimb enhancer. Moreover, Pitx1 binding is significantly enriched on hindlimb relative to forelimb-specific cis-regulatory features that are differentially marked by H3K27ac. However, our analysis revealed that Pitx1 also strongly associates with many functionally verified limb enhancers that exhibit similar levels of activity in the embryonic mesenchyme of forelimbs and hindlimbs. We speculate that Pitx1 influences hindlimb morphology both through the activation of hindlimb-specific enhancers as well as through the hindlimb-specific modulation of enhancers that are active in both sets of limbs.


Electric-Potential Reconstructions of Single Particles Using L-Gradient Flows.
In this paper, we present a stable, reliable and robust method for reconstructing a three dimensional density function from a set of two dimensional electron microscopy images. By minimizing an energy functional consisting of a fidelity term and a regularization term, a L(2)-gradient flow is derived. The flow is integrated by a finite element method in the spatial direction and an explicit Euler scheme in temporal direction. The experimental results show that the proposed method is efficient and effective.


Diagnostic pitfall: pigmented lesion of the nipple--correlation between dermoscopy, reflectance confocal microscopy and histopathology.
We present an unusual case of a nevus of the nipple changing during pregnancy which caused a diagnostic pitfall. Nevi on the nipple and areola are infrequent, and diagnostic criteria for clinical, dermoscopy or reflectance confocal microscopy examination for nevi in this 'special location' are still missing. We comment on the literature on dermoscopic findings in mammary lesions and their management during pregnancy, as well as the challenging histopathology of nevi along the milk line. Finally, we focus on two main limitations of reflectance confocal microscopy: the misinterpretation of dendritic cells and the limitation of the imaging depth.


High-Frequency Airway Oscillating Device for Respiratory Muscle Training in Subjects With COPD.
COPD is characterized by expiratory flow limitation, which results in symptomatic dyspnea and reduced exercise capacity. Changes in breathing mechanics mean the respiratory muscles are unable to respond to the ventilatory demands, increasing the sensation of dyspnea. A high-frequency oscillating device has been developed to improve dyspnea in patients with COPD. We conducted a feasibility trial to gain insight into the potential for recruitment, retention, and study design for a future randomized controlled trial. Symptomatic subjects with COPD were included on the basis of a Medical Research Council (MRC) score ≥ 3 and FEV1/FVC < 0.70). Patients were excluded if they received pulmonary rehabilitation within the last 6 months. The intervention employed the device for 8 weeks, 3 times daily. Clinical outcomes included the MRC score, maximal expiratory and inspiratory pressures (PEmax/PImax), the incremental shuttle walk test (ISWT), and the endurance shuttle walk test (ESWT). We successfully recruited 23 subjects with established COPD (65.2% male, mean age 65 ± 5.03 y, mean % predicted FEV1 43.9 ± 16, mean FEV1/FVC ratio 0.46 ± 0.13, and median [interquartile range] MRC 4 [3-5]). There was a significant change in MRC from 4 to 3 pre to post intervention (P = .003). There was a statistically significant difference in PEmaxP < .008 and PImaxP = .044. There were no significant differences observed in the ISWT or ESWT. This study design appeared feasible to proceed to a clinical effectiveness trial. The use of the device for 8 weeks showed a significant improvement in PEmax, PImax, and reduced symptomatic dyspnea on the MRC dyspnea score. The results of this study should encourage a randomized controlled trial.


Lifestyle and the risk of rheumatoid arthritis: cigarette smoking and alcohol consumption.
In a search for aspects of behaviour related to oral contraceptive use which might explain the favourable effect of oral contraception on the onset of rheumatoid arthritis (RA), cigarette smoking and alcohol consumption were studied as possible risk factors. Information on cigarette smoking and alcohol consumption was obtained by interview at the first visit to the outpatient clinic of 135 young women with confirmed definite or classical RA of recent onset and 378 control patients with soft tissue rheumatism or osteoarthritis. The diagnosis in all patients was confirmed by at least two years of follow up. Of the patients with RA, 44/135 (33%) were current cigarette smokers compared with 181/378 (48%) of the controls. The percentage of smokers among the controls was similar to that of women smokers in the general population. The adjusted risk of RA in women who smoked at least one cigarette a day was 0.61 (95% confidence interval (CI) 0.42 to 0.89). Thirty one (23%) patients with RA and 137 (36%) controls were alcohol drinkers. The risk of RA in women who consumed alcohol at least once a day was 0.52 (95% CI 0.33 to 0.84). The low relative risk estimates for cigarette smoking and alcohol consumption were mutually independent and also independent of oral contraceptive use, the presence of the HLA-DR4 antigen, or a positive family history of RA. The low incidence of alcohol consumption in the patients with RA might be due to the discontinuation of alcohol consumption after disease onset. The low incidence of cigarette smoking in the patients might reflect a protective effect of cigarette smoking on RA onset, possibly induced by changes in the immune system.


Inbreeding tolerance as a pre-adapted trait for invasion success in the invasive ant Brachyponera chinensis.
Identifying traits that facilitate species introductions and successful invasions of ecosystems represents a key issue in ecology. Following their establishment into new environments, many non-native species exhibit phenotypic plasticity with post-introduction changes in behaviour, morphology or life history traits that allow them to overcome the presumed loss of genetic diversity resulting in inbreeding and reduced adaptive potential. Here, we present a unique strategy in the invasive ant Brachyponera chinensis (Emery), in which inbreeding tolerance is a pre-adapted trait for invasion success, allowing this ant to cope with genetic depletion following a genetic bottleneck. We report for the first time that inbreeding is not a consequence of the founder effect following introduction, but it is due to mating between sister queens and their brothers that pre-exists in native populations which may have helped it circumvent the cost of invasion. We show that a genetic bottleneck does not affect the genetic diversity or the level of heterozygosity within colonies and suggest that generations of sib-mating in native populations may have reduced inbreeding depression through purifying selection of deleterious alleles. This work highlights how a unique life history may pre-adapt some species for biological invasions.


VariantSpark: population scale clustering of genotype information.
Genomic information is increasingly used in medical practice giving rise to the need for efficient analysis methodology able to cope with thousands of individuals and millions of variants. The widely used Hadoop MapReduce architecture and associated machine learning library, Mahout, provide the means for tackling computationally challenging tasks. However, many genomic analyses do not fit the Map-Reduce paradigm. We therefore utilise the recently developed SPARK engine, along with its associated machine learning library, MLlib, which offers more flexibility in the parallelisation of population-scale bioinformatics tasks. The resulting tool, VARIANTSPARK provides an interface from MLlib to the standard variant format (VCF), offers seamless genome-wide sampling of variants and provides a pipeline for visualising results. To demonstrate the capabilities of VARIANTSPARK, we clustered more than 3,000 individuals with 80 Million variants each to determine the population structure in the dataset. VARIANTSPARK is 80 % faster than the SPARK-based genome clustering approach, ADAM, the comparable implementation using Hadoop/Mahout, as well as ADMIXTURE, a commonly used tool for determining individual ancestries. It is over 90 % faster than traditional implementations using R and Python. The benefits of speed, resource consumption and scalability enables VARIANTSPARK to open up the usage of advanced, efficient machine learning algorithms to genomic data.


Attenuation-corrected fluorescence spectra unmixing for spectroscopy and microscopy.
In fluorescence measurements, light is often absorbed and scattered by a sample both for excitation and emission, resulting in the measured spectra to be distorted. Conventional linear unmixing methods computationally separate overlapping spectra but do not account for these effects. We propose a new algorithm for fluorescence unmixing that accounts for the attenuation-related distortion effect on fluorescence spectra. Using a matrix representation, we derive forward measurement formation and a corresponding inverse method; the unmixing algorithm is based on nonnegative matrix factorization. We also demonstrate how this method can be extended to a higher-dimensional tensor form, which is useful for unmixing overlapping spectra observed under the attenuation effect in spectral imaging microscopy. We evaluate the proposed methods in simulation and experiments and show that it outperforms a conventional, linear unmixing method when absorption and scattering contributes to the measured signals, as in deep tissue imaging.


Discovery of N-hydroxy-4-(1H-indol-3-yl)butanamide as a histone deacetylase inhibitor.
The indoles plant growth hormones have exhibited potentially antitumor activities. However, the targets of these indoles have not been clearly elucidated. By introduction of hydroxamic acid group to the structure of indolebutyric acid, the derived molecule (IBHA) exhibited potent HDAC2 (IC50 value of 0.32 ± 0.02 µM) and HDAC3 (IC50 value of 0.14 ± 0.01 µM) inhibitory activities compared with SAHA (IC50 value of 1.25 ± 0.06 µM and 0.97 ± 0.04 µM against HDAC2 and HDAC3). In the antiproliferative assays, the tested hematologic cell lines (U937 and K562) are more sensitive to IBHA than the solid tumor cell lines (MDA-MB-231 and PC-3). In the docking studies, the derived molecule (IBHA) could bind to the active site of human HDAC2 and HDAC3 by strong H-bond interactions and hydrophobic interactions. Pharmacophore mapping results revealed that properties of IBHA matches the receptor (HDAC3) based pharmacophore model.


Pomegranate extract (POMx) decreases the atherogenicity of serum and of human monocyte-derived macrophages (HMDM) in simvastatin-treated hypercholesterolemic patients: a double-blinded, placebo-controlled, randomized, prospective pilot study.
To analyze pomegranate extract (POMx) effects on serum and on human HMDM atherogenicity in simvastatin - treated hypercholesterolemic patients. Patients were randomly assigned to receive either simvastatin (20 mg/day) + vegan placebo pill (n = 11), or simvastatin (20 mg/day) + POMx pill (1g/day, n = 12). Fasting blood samples were collected at baseline and after 1 and 2 months of therapy. HMDM were collected from 3 patients in each group at baseline and after 2 months of therapy, as well as from 3 healthy subjects. After 2 months of therapy, serum LDL-cholesterol levels significantly decreased, by 23%, in the simvastatin + placebo group, and by 26% in the simvastatin + POMx group. Simvastatin + POMx therapy increased serum thiols concentration by 6%. Patients' HMDM reactive oxygen species (ROS) levels were significantly increased, by 69%, vs. healthy subjects HMDM. After 2 months of therapy, HMDM ROS levels decreased by 18% in the simvastatin + placebo group, whereas in the simvastatin + POMx group it decreased by up to 30%. A novel finding was the triglycerides levels in the patients' HMDM at baseline which were significantly higher, by 71%, vs. healthy subjects HMDM. The simvastatin + POMx, but not the simvastatin + placebo therapy, significantly reduced macrophage triglycerides content by 48%, vs. baseline levels. In addition, whereas the simvastatin + placebo therapy significantly decreased the patients' HMDM cholesterol biosynthesis rate by 33%, the simvastatin + POMx therapy further decreased it, by 44%. The addition of POMx to simvastatin therapy in hypercholesterolemic patients improved oxidative stress and lipid status in the patient's serum and in their HMDM. These anti-atherogenic effects could reduce the risk for atherosclerosis development.


Understanding urban green space as a health resource: a qualitative comparison of visit motivation and derived effects among park users in Sheffield, UK.
With increasing interest in the use of urban green space to promote human health, there is a need to understand the extent to which park users conceptualize these places as a resource for health and well-being. This study sought to examine park users' own reasons for and benefits from green space usage and compare these with concepts and constructs in existing person-environment-health theories and models of health. Conducted in 13 public green spaces in Sheffield, UK, we undertook a qualitative content analysis of 312 park users' responses to open-ended interview questions and identified a breadth, depth and salience of visit motivators and derived effects. Findings highlight a discrepancy between reasons for visiting and derived effects from the use of urban green space. Motivations emphasized walking, green space qualities, and children. Derived effects highlighted relaxation, positive emotions within the self and towards the place, and spiritual well-being. We generate a taxonomy of motivations and derived effects that could facilitate operationalization within empirical research and articulate a conceptual framework linking motivators to outcomes for investigating green space as a resource for human health and well-being.


Health Benefits In 2015: Stable Trends In The Employer Market.
The annual Kaiser Family Foundation/Health Research and Educational Trust Employer Health Benefits Survey found that in 2015, average annual premiums (employer and worker contributions combined) were $6,251 for single coverage and $17,545 for family coverage. Both premiums rose 4 percent from 2014, continuing several years of modest growth. The percentage of firms offering health benefits and the percentage of workers covered by their employers' plans remained statistically unchanged from 2014. Eighty-one percent of covered workers were enrolled in a plan with a general annual deductible. Among those workers, the average deductible for single coverage was $1,318. Half of large employers either offered employees the opportunity or required them to complete biometric screening. Of firms that offer an incentive for completing the screening, 20 percent provide employees with incentives or penalties that are tied to meeting those biometric outcomes. The 2015 survey included new questions on financial incentives to complete wellness programs and meet specified biometric outcomes as well as questions about narrow networks and employers' strategies related to the high-cost plan tax and the employer shared-responsibility provisions of the Affordable Care Act.


Opportunities and methods for studying alternative splicing in cancer with RNA-Seq.
The biogenesis, development and metastases of cancer are associated with many variations in the transcriptome. Alternative splicing of genes is a major post-transcriptional regulation mechanism that is involved in many types of cancer. The next-generation sequencing applied on RNAs (RNA-Seq) provides a new technology for studying transcriptomes. It provides an unprecedented opportunity for quantitatively studying alternative splicing in a systematic way. This mini-review summarizes the current RNA-Seq studies on cancer transcriptomes especially studies on cancer-related alternative splicing, and discusses the strategy for quantitative study of alternative splicing in cancers with RNA-Seq, the bioinformatics methods available and existing questions.


Naphthalene, Phenanthrene, and Pyrene as DNA Base Analogues: Synthesis, Structure, and Fluorescence in DNA.
We describe the synthesis, structures, and DNA incorporation of deoxyribonucleosides carrying polycyclic aromatic hydrocarbons as the DNA "base" analogue. The new polycyclic compounds are 1-naphthyl, 2-naphthyl, 9-phenanthrenyl, and 1-pyrenyl deoxynucleosides. The compounds are synthesized using a recently developed C-glycosidic bond formation method involving organocadmium derivatives of the aromatic compounds coupling with a 1α-chlorodeoxyribose precursor. The principal products of this coupling are the α-anomers of the deoxyribosides. An efficient method has also been developed for epimerization of the α-anomers to β-anomers by acid-catalyzed equilibration; this isomerization is successfully carried out on the four polycyclic nucleosides as well as two substituted phenyl nucleosides. The geometry of the anomeric substitution is derived from (1)H NOE experiments and is also correlated with a single-crystal X-ray structure of one α-isomer. Three of the polycyclic C-nucleoside derivatives are incorporated into DNA oligonucleotides via their phosphoramidite derivatives; the pyrenyl and phenanthrenyl derivatives are shown to be fluorescent in a DNA sequence. The results (1) broaden the scope of our C-glycoside coupling reaction, (2) demonstrate that (using a new acid-catalyzed epimerization) both α- and β-anomers are easily synthesized, and (3) constitute a new class of deoxynucleoside derivatives. Such nucleoside analogues may be useful as biophysical probes for the study of noncovalent interactions such as aromatic π-stacking in DNA. In addition, the fluorescence of the phenanthrene and pyrene nucleosides may make them especially useful as structural probes.


The global roadmap for advancing development of vaccines against sexually transmitted infections: Update and next steps.
In 2014, the World Health Organization, the US National Institutes of Health, and global technical partners published a comprehensive roadmap for development of new vaccines against sexually transmitted infections (STIs). Since its publication, progress has been made in several roadmap activities: obtaining better epidemiologic data to establish the public health rationale for STI vaccines, modeling the theoretical impact of future vaccines, advancing basic science research, defining preferred product characteristics for first-generation vaccines, and encouraging investment in STI vaccine development. This article reviews these overarching roadmap activities, provides updates on research and development of individual vaccines against herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, and discusses important next steps to advance the global roadmap for STI vaccine development.


The precise solar shape and its variability.
The precise shape of the Sun has not been convincingly determined, despite half a century of modern photoelectric observations. The expected deviation of the solar-limb shape from a perfect circle is very small, but such asphericity is sensitive to the Sun's otherwise invisible interior conditions, as well as the solar atmosphere. We use evidence from a long-running experiment based in space to show that, when analyzed with sufficiently high spatial resolution, the Sun's oblate shape is distinctly constant and almost completely unaffected by the solar-cycle variability seen on its surface. The solar oblateness is significantly lower than theoretical expectations by an amount that could be explained by a slower differential rotation in the outer few percent of the Sun.


Attitudes and experiences of Oregon hospice nurses and social workers regarding assisted suicide.
When the Oregon Death with Dignity Act (ODDA) legalizing physician-assisted suicide was enacted into law in 1997, Oregon hospice clinicians were uncertain how involved they would be with patients who wanted this option. However, 86% of the 171 persons in Oregon who have died by lethal prescription were enrolled in hospice programmes. A mailed questionnaire was sent to all hospice nurses and social workers in Oregon in 2001 (n=573) to assess their attitudes about legalized assisted suicide and interactions with patients concerning this issue. Responses from 306 nurses and 85 social workers are included in this report. Almost two-thirds of respondents reported that at least one patient had discussed assisted suicide as a potential option in the past year. Social workers were generally more supportive of both the ODDA and of patients choosing assisted suicide compared to nurses. Twenty-two per cent of all respondents were not comfortable discussing assisted suicide with patients. Ninety-five per cent of both groups, however, favoured hospice policies that would allow a patient to choose assisted suicide while enrolled in hospice and allow hospice clinicians to continue to provide care. Nurses and social workers in hospices and other settings can expect to encounter patient questions about physician-assisted suicide, whether legalized or not, and must be prepared to have these discussions. Most hospice professionals in Oregon do not believe that assisted suicide and hospice enrollment are mutually exclusive alternatives.


Generating environmental sampling and testing data for micro- and nanoplastics for use in life cycle impact assessment.
Ongoing efforts focus on quantifying plastic pollution and describing and estimating the related magnitude of exposure and impacts on human and environmental health. Data gathered during such work usually follows a receptor perspective. However, Life Cycle Assessment (LCA) represents an emitter perspective. This study examines existing data gathering and reporting approaches for field and laboratory studies on micro- and nanoplastics (MNPs) exposure and effects relevant to LCA data inputs. The outcomes indicate that receptor perspective approaches do not typically provide suitable or sufficiently harmonised data. Improved design is needed in the sampling, testing and recording of results using harmonised, validated and comparable methods, with more comprehensive reporting of relevant data. We propose a three-level set of requirements for data recording and reporting to increase the potential for LCA studies and models to utilise data gathered in receptor-oriented studies. We show for which purpose such data can be used as inputs to LCA, particularly in life cycle impact assessment (LCIA) methods. Implementing these requirements will facilitate proper integration of the potential environmental impacts of plastic losses from human activity (e.g. litter) into LCA. Then, the impacts of plastic emissions can eventually be connected and compared with other environmental issues related to anthropogenic activities.


Bovine feces from animals with gastrointestinal infections are a source of serologically diverse atypical enteropathogenic Escherichia coli and Shiga toxin-producing E. coli strains that commonly possess intimin.
Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) cells were isolated from 191 fecal samples from cattle with gastrointestinal infections (diagnostic samples) collected in New South Wales, Australia. By using a multiplex PCR, E. coli cells possessing combinations of stx1, stx2, eae, and ehxA were detected by a combination of direct culture and enrichment in E. coli (EC) (modified) broth followed by plating on vancomycin-cefixime-cefsulodin blood (BVCC) agar for the presence of enterohemolytic colonies and on sorbitol MacConkey agar for the presence of non-sorbitol-fermenting colonies. The high prevalence of the intimin gene eae was a feature of the STEC (35 [29.2%] of 120 isolates) and contrasted with the low prevalence (9 [0.5%] of 1,692 fecal samples possessed STEC with eae) of this gene among STEC recovered during extensive sampling of feces from healthy slaughter-age cattle in Australia (M. Hornitzky, B. A. Vanselow, K. Walker, K. A. Bettelheim, B. Corney, P. Gill, G. Bailey, and S. P. Djordjevic, Appl. Environ. Microbiol. 68:6439-6445, 2002). Forty-seven STEC serotypes were identified, including O5:H-, O8:H19, O26:H-, O26:H11, O113:H21, O157:H7, O157:H- and Ont:H- which are known to cause severe disease in humans and 23 previously unreported STEC serotypes. Serotypes Ont:H- and O113:H21 represented the two most frequently isolated STEC isolates and were cultured from nine (4.7%) and seven (3.7%) animals, respectively. Fifteen eae-positive E. coli serotypes, considered to represent atypical EPEC, were identified, with O111:H- representing the most prevalent. Using both techniques, STEC cells were cultured from 69 (36.1%) samples and EPEC cells were cultured from 30 (15.7%) samples, including 9 (4.7%) samples which yielded both STEC and EPEC. Culture on BVCC agar following enrichment in EC (modified) broth was the most successful method for the isolation of STEC (24.1% of samples), and direct culture on BVCC agar was the most successful method for the isolation of EPEC (14.1% samples). These studies show that diarrheagenic calves and cattle represent important reservoirs of eae-positive E. coli.


Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF.
HP1 proteins are transcriptional regulators that, like histones, are targets for post-translational modifications defining an HP1-mediated subcode. HP1γ has multiple phosphorylation sites, including serine 83 (S83) that marks it to sites of active transcription. In a guinea pig model for Shigella enterocolitis, we observed that the defective type III secretion mxiD Shigella flexneri strain caused more HP1γ phosphorylation in the colon than the wild-type strain. Shigella interferes with HP1 phosphorylation by injecting the phospholyase OspF. This effector interacts with HP1γ and alters its phosphorylation at S83 by inactivating ERK and consequently MSK1, a downstream kinase. MSK1 that here arises as a novel HP1γ kinase, phosphorylates HP1γ at S83 in the context of an MSK1-HP1γ complex, and thereby favors its accumulation on its target genes. Genome-wide transcriptome analysis reveals that this mechanism is linked to up-regulation of proliferative gene and fine-tuning of immune gene expression. Thus, in addition to histones, bacteria control host transcription by modulating the activity of HP1 proteins, with potential implications in transcriptional reprogramming at the mucosal barrier.


Epidemiology of Pediatric Traumatic Brain Injury and Hypothalamic-Pituitary Disorders in Arizona.
Traumatic brain injury (TBI) in children can result in long-lasting social, cognitive, and neurological impairments. In adults, TBI can lead to endocrinopathies (endocrine system disorders), but this is infrequently reported in children. Untreated endocrinopathies can elevate risks of subsequent health issues, such that early detection in pediatric TBI survivors can initiate clinical interventions. To understand the risk of endocrinopathies following pediatric TBI, we identified patients who had experienced a TBI and subsequently developed a new-onset hypothalamic regulated endocrinopathy (n = 498). We hypothesized that pediatric patients who were diagnosed with a TBI were at higher risk of being diagnosed with a central endocrinopathy than those without a prior diagnosis of TBI. In our epidemiological assessment, we identified pediatric patients enrolled in the Arizona Health Care Cost Containment System (AHCCCS) from 2008 to 2014 who were diagnosed with one of 330 TBI International Classification of Diseases (ICD)-9 codes and subsequently diagnosed with one of 14 central endocrinopathy ICD-9 codes. Additionally, the ICD-9 code data from over 600,000 Arizona pediatric patients afforded an estimate of the incidence, prevalence, relative risk, odds ratio, and number needed to harm, regarding the development of a central endocrinopathy after sustaining a TBI in Arizona Medicaid pediatric patients. Children with a TBI diagnosis had 3.22 times the risk of a subsequent central endocrine diagnosis compared with the general population (±0.28). Pediatric AHCCCS patients with a central endocrine diagnosis had 3.2-fold higher odds of a history of a TBI diagnosis than those without an endocrine diagnosis (±0.29). Furthermore, the number of patients with a TBI diagnosis for one patient to receive a diagnosis of a central endocrine diagnosis was 151.2 (±6.12). Female subjects were more likely to present with a central endocrine diagnosis after a TBI diagnosis compared to male subjects (64.1 vs. 35.9%). These results are the first state-wide epidemiological study conducted to determine the risk of developing a hypothalamic-pituitary disorder after a TBI in the pediatric population. Our results contribute to a body of knowledge demonstrating a TBI etiology for idiopathic endocrine disorders, and thus advise physicians with regard to TBI follow-up care that includes preventive screening for endocrine disorders.


Molecular heterogeneity of adherens junctions.
We describe here the subcellular distributions of three junctional proteins in different adherens-type contacts. The proteins examined include vinculin, talin, and a recently described 135-kD protein (Volk, T., and B. Geiger, 1984, EMBO (Eur. Mol. Biol. Organ.) J., 10:2249-2260). Immunofluorescent localization of the three proteins indicated that while vinculin was ubiquitously present in all adherens junctions, the other two showed selective and mutually exclusive association with either cell-substrate or cell-cell adhesions. Talin was abundant in focal contacts and in dense plaques of smooth muscle, but was essentially absent from intercellular junctions such as intercalated disks or adherens junctions of lens fibers. The 135-kD protein, on the other hand, was present in the latter two loci and was apparently absent from membrane-bound plaques of gizzard or from focal contacts. Radioimmunoassay of tissue extracts and immunolabeling of cultured chick lens cells indicated that the selective presence of talin and of the 135-kD protein in different cell contacts is spatially regulated within individual cells. On the basis of these findings it was concluded that adherens junctions are molecularly heterogeneous and consist of at least two major subgroups. Contacts with noncellular substrates contain talin and vinculin but not the 135-kD protein, whereas their intercellular counterparts contain the latter two proteins and are devoid of talin. The significance of these results and their possible relationships to contact-induced regulation of cell behavior are discussed.


Examining factors associated with self-management skills in teenage survivors of cancer.
Monitoring long-term health of teenage cancer survivors is dependent on successful transition from pediatric to adult long-term follow-up (LTFU) care. This study identified factors associated with self-management skills (SMSs), an important correlate of successful transition. Data were collected from a cross-sectional survey conducted at three Canadian hospitals between July 2011 and January 2012. The sample included 184 childhood cancer survivors aged between 15 and 19 years. Independent factors included demographic- and illness-related factors. The outcome of interest was SMSs, measured using the SMSs scale, with higher scores indicating more SMSs. More SMSs were associated positively with older age (β = 1.2, 95 % confidence interval (CI) = 0.1 to 2.4), being female (β = 4.6, 95 % CI = 1.9 to 7.4), and having a non-married parent (β = 5.2, 95 % CI = 0.04 to 10.4). There was a negative association between SMSs and having had a central nervous system tumor (CNS) compared to having leukemia (β = -7.9, 95 % CI = -13.5 to -2.2). Younger, male, and CNS tumor survivors lack SMSs. Future research is needed to explore the extent and nature of associations between SMSs and parents' marital status. Younger, male, and CNS tumor survivors should be targeted for interventions in order to ensure that adequate SMSs are attained before completion of transition.


Capillary adhesion at the nanometer scale.
Molecular dynamics simulations are used to study the capillary adhesion from a nonvolatile liquid meniscus between a spherical tip and a flat substrate. The atomic structure of the tip, the tip radius, the contact angles of the liquid on the two surfaces, and the volume of the liquid bridge are varied. The capillary force between the tip and substrate is calculated as a function of their separation h. The force agrees with continuum predictions based on macroscopic theory for h down to ∼5 to 10 nm. At smaller h, the force tends to be less attractive than predicted and has strong oscillations. This oscillatory component of the capillary force is completely missed in the macroscopic theory, which only includes contributions from the surface tension around the circumference of the meniscus and the pressure difference over the cross section of the meniscus. The oscillation is found to be due to molecular layering of the liquid confined in the narrow gap between the tip and substrate. This effect is most pronounced for large tip radii and/or smooth surfaces. The other two components considered by the macroscopic theory are also identified. The surface tension term, as well as the meniscus shape, is accurately described by the macroscopic theory for h down to ∼1 nm, but the capillary pressure term is always more positive than the corresponding continuum result. This shift in the capillary pressure reduces the average adhesion by a factor as large as 2 from its continuum value and is found to be due to an anisotropy in the pressure tensor. The component in the plane of the substrate is consistent with the capillary pressure predicted by the macroscopic theory (i.e., the Young-Laplace equation), but the normal pressure that determines the capillary force is always more positive than the continuum counterpart.


Predictors of 1-year mortality in patients discharged from hospital following acute exacerbation of chronic obstructive pulmonary disease.
acute exacerbation of COPD (AECOPD) is a major cause of hospital admission, and predicts subsequent medium-term mortality. We aimed to examine mortality predictors in patients discharged from hospital after AECOPD. we obtained baseline demographic and clinical data from 100 patients (mean age (range)=73 (60-98) years; 48 males) admitted with AECOPD. All completed the following validated questionnaires: a quality of life questionnaire (Breathing Problems Questionnaire; BPQ); a screening questionnaire for depression (Brief Assessment Schedule Depression Cards; BASDEC); a disability questionnaire (Manchester Respiratory Activities of Daily Living questionnaire; MRADL). Following discharge all were prospectively followed and survival/mortality at 12 months confirmed from hospital notes and by contacting general practitioners. the prevalence of depression at recruitment was 56%. One-year mortality in the whole group was 36%. Odds ratios (95% confidence intervals) for mortality predictors (univariate logistic regression analysis) were: use of long-term oxygen therapy=2.72 (1.06-6.97); subsequent readmission=2.57 (1.08-6.12); MRADL score=0.87 (0.80-0.94) (disability predicting death); BASDEC score=1.13 (1.02-1.26) (depression predicting death); BPQ score=1.08 (1.04-1.12) (low quality of life predicting death); length of original hospital stay=1.03 (1.00-1.07). On multivariate logistic regression analysis the only mortality predictor was BPQ with an odds ratio (95% confidence limits) of 1.13 (1.04-1.22). In terms of mortality prediction for individuals, a threshold MRADL score of <12 gave a sensitivity of 86%, specificity of 55%, positive predictive value of 88% and negative predictive value of 52%, with similar predictive values using BPQ as an independent variable. 1-year mortality after AECOPD admission is high. The presence of depressive illness (which is extremely common), and levels of both disability and impairment of quality of life are univariate predictors of 1-year mortality in this patient group. This model may be useful in predicting prognosis for individuals and thus in guiding treatment decisions.


Insulin stimulates the phosphorylation of the 66- and 52-kilodalton Shc isoforms by distinct pathways.
In contrast to the 52-kDa Shc isoform, insulin stimulation caused a quantitative, time-dependent decrease in the SDS-PAGE mobility of 66-kDa Shc in both Chinese hamster ovary/IR cells and 3T3L1 adipocytes. Alkaline phosphatase treatment and direct phosphoamino acid analysis demonstrated that insulin stimulated an increase in serine phosphorylation of the 66-kDa isoform but not 52-kDa Shc, although the latter displayed a marked increase in tyrosine phosphorylation. To identify the responsible kinase pathway, we compared the effects on 66-kDa Shc serine phosphorylation by insulin, anisomycin, and osmotic shock, agents that specifically activate the ERK, JNK, or both pathways, respectively. Insulin and osmotic shock both stimulated a decrease in 66-kDa Shc mobility, whereas anisomycin had no effect. Furthermore, expression of a dominant-interfering Ras mutant (N17Ras) prevented the insulin-stimulated, but not the osmotic shock-induced serine phosphorylation of 66-kDa Shc. Consistent with a MEK-dependent pathway mediating 66-kDa Shc serine phosphorylation, the specific MEK inhibitor (PD98059) and expression of a dominant-interfering MEK mutant partially inhibited both the insulin and osmotic shock-induced reduction in 66-kDa Shc mobility. In contrast, expression of the MAP kinase phosphatase (MKP-1) completely prevented ERK activation but did not inhibit the serine phosphorylation of 66-kDa Shc. These data demonstrate that insulin stimulates the serine phosphorylation of the 66-kDa Shc isoform through a MEK-dependent mechanism.


Circulating miRNAs miR-34a and miR-150 associated with colorectal cancer progression.
Screening for the early detection of colorectal cancer is important to improve patient survival. The aim of this study was to investigate the potential of circulating cell-free miRNAs as biomarkers of CRC, and their efficiency at delineating patients with polyps and benign adenomas from normal and cancer patient groups. The expression of 667 miRNAs was assessed in a discovery set of 48 plasma samples comprising normal, polyp, adenoma, and early and advanced cancer samples. Three miRNAs (miR-34a, miR-150, and miR-923) were further examined in a validation cohort of 97 subjects divided into the same five groups, and in an independent public dataset of 40 CRC samples and paired normal tissues. High levels of circulating miR-34a and low miR-150 levels distinguished groups of patients with polyps from those with advanced cancer (AUC = 0.904), and low circulating miR-150 levels separated patients with adenomas from those with advanced cancer (AUC = 0.875). In addition, the altered expression of miR-34a and miR-150 in an independent public dataset of forty CRC samples and paired normal tissues was confirmed. We identified two circulating miRNAs capable of distinguishing patient groups with different diseases of the colon from each other, and patients with advanced cancer from benign disease groups.


Tetrodotoxins Occurrence in Non-Traditional Vectors of the North Atlantic Waters (Portuguese Maritime Territory, and Morocco Coast).
Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decade its presence has been more pronounced in the temperate waters of the Atlantic. In its last scientific opinion, the European Food Safety Authority (EFSA) stressed the need for data regarding TTX prevalence in European waters. To address EFSA's concerns, benthic organisms such as mollusks, crustaceans, echinoderms and fish with different feeding habits were collected along the Portuguese continental coast, islands (São Miguel, Azores, and Madeira) and the northwestern Moroccan coast. A total of 165 samples were analyzed by ultra high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) and ultra high performance chromatography mass spectrometry (UHPLC-MS/MS). Geographical tendencies were detected as follows, by descending order: S. Miguel Island (Azores), Moroccan coast, Madeira Island and Portuguese continental coast. The toxin amounts detected were significant, above the Dutch limit value established in 2017, showing the importance and the need for continuity of these studies to gain more knowledge about the prevalence of these toxins, unraveling new vectors, in order to better assess human health risk. This work represents a general overview of new TTX bearers (7) most of them in gastropods (Patella depressa, Nucella lapillus, Onchidella celtica and Aplysia depilans), followed by echinoderms (Echinus esculentus and Ophidiaster ophidianus) and puffer fish Sphoeroides marmoratus.


Tardive dyskinesia.
Tardive dyskinesia (TD) is a syndrome of involuntary movements that develops in predisposed individuals during neuroleptic drug treatment, with an average prevalence of 15%. Neuroleptic (antidopaminergic) drugs are the predominant etiological factor. Although no simple correlation can be established, both dosage and treatment duration seem to be of importance for the development of dyskinesia. It is still uncertain whether some neuroleptics carry a higher risk than others, but it appears that the atypical neuroleptic clozapine, which causes no or minimal dystonia, parkinsonism, or akathisia, also carries no or minimal risk of TD. The pathophysiological mechanisms underlying TD are unclear. The traditional dopamine hypersensitivity theory is no longer viable, whereby new hypotheses have been advanced: TD can be due to the blockade of a subset of striatal dopamine receptors, while parkinsonism is due to the blockade of another such subset, and/or can be due to a reduced GABA turnover in a subgroup of neurons connecting striatum with globus pallidus and substantia nigra. TD is best prevented by a course of neuroleptic medication involving as little antidopamine effect as possible, including minimal doses and shortest possible length of treatment. The main TD treatment principle consists of a gradual dose reduction, possibly over years. It should be added, however, that more recent investigations indicate that traditional antidopaminergic treatment in moderate doses may be safely continued over a long period without an increased risk of TD progression.


Endothelial cell dysfunction and cardiac hypertrophy in the STOX1 model of preeclampsia.
Preeclampsia is a disease of pregnancy involving systemic endothelial dysfunction. However, cardiovascular consequences of preeclampsia are difficult to analyze in humans. The objective of the present study is to evaluate the cardiovascular dysfunction induced by preeclampsia by examining the endothelium of mice suffering of severe preeclampsia induced by STOX1 overexpression. Using Next Generation Sequencing on endothelial cells of mice carrying either transgenic or control embryos, we discovered significant alterations of gene networks involved in inflammation, cell cycle, and cardiac hypertrophy. In addition, the heart of the preeclamptic mice revealed cardiac hypertrophy associated with histological anomalies. Bioinformatics comparison of the networks of modified genes in the endothelial cells of the preeclamptic mice and HUVECs exposed to plasma from preeclamptic women identified striking similarities. The cardiovascular alterations in the pregnant mice are comparable to those endured by the cardiovascular system of preeclamptic women. The STOX1 mice could help to better understand the endothelial dysfunction in the context of preeclampsia, and guide the search for efficient therapies able to protect the maternal endothelium during the disease and its aftermath.


Nkx3.1 mutant mice recapitulate early stages of prostate carcinogenesis.
Recent studies of human cancers and mutant mouse models have implicated the Nkx3.1 homeobox gene as having a key role in prostate carcinogenesis. Consistent with such a role, here we show that Nkx3.1 displays growth-suppressing activities in cell culture, and that aged Nkx3.1 mutant mice display histopathological defects resembling prostatic intraepithelial neoplasia (PIN), the presumed precursor of human prostate cancer. Using a tissue recombination approach, we found that PIN-like lesions from Nkx3.1 mutants can undergo progressively severe histopathological alterations after serial transplantation in nude mice. Our findings indicate that Nkx3.1 loss-of-function is a critical event in prostate cancer initiation, and that Nkx3.1 mutant mice accurately model early stages of prostate carcinogenesis. More generally, our tissue recombination assay provides an empirical test to examine the relationship of PIN to prostate carcinoma.


The long term economic impact of severe obstetric complications for women and their children in Burkina Faso.
This study investigates the long term economic impact of severe obstetric complications for women and their children in Burkina Faso, focusing on measures of food security, expenditures and related quality of life measures. It uses a hospital based cohort, first visited in 2004/2005 and followed up four years later. This cohort of 1014 women consisted of two main groups of comparison: 677 women who had an uncomplicated delivery and 337 women who experienced a severe obstetric complication which would have almost certainly caused death had they not received hospital care (labelled a "near miss" event). To analyze the impact of such near miss events as well as the possible interaction with the pregnancy outcome, we compared household and individual level indicators between women without a near miss event and women with a near miss event who either had a live birth, a perinatal death or an early pregnancy loss. We used propensity score matching to remove initial selection bias. Although we found limited effects for the whole group of near miss women, the results indicated negative impacts: a) for near miss women with a live birth, on child development and education, on relatively expensive food consumption and on women's quality of life; b) for near miss women with perinatal death, on relatively expensive foods consumption and children's education and c) for near miss women who had an early pregnancy loss, on overall food security. Our results showed that severe obstetric complications have long lasting consequences for different groups of women and their children and highlighted the need for carefully targeted interventions.


Visual feedback of force platform displacements for balance control training: what postural ability do healthy subjects have to develop to decrease the difference between center of pressure and center of gravity movements?
Past studies have emphasized the beneficial effect of additional visual feedback (VFB) on the capacity of healthy adults to decrease the amplitudes of the center-of-pressure minus center-of-gravity (CP-CG(v)) movements. To better assess these capacities, 56 subjects were asked to stand still on a force platform and to use the visual information provided. Dependency coefficients, based on their capacity to lower their CP-CG(v) movements and therefore relax their lower limb muscles, as well as parameters aimed at characterizing their postural strategies were measured across VFB conditions including (1) CP displacements in real time (VFB(CP0)), (2) CP displacements with a 600-ms delay (VFB(CP600)), and (3) CP-CG(v) displacements with a 600-ms delay (VFB(CP-CG600)). A non-VFB condition (eyes open) was also included. Several linear correlations were used to specify the relation between subjects' capacity to relax, compared with the VFB(CP0) condition, across the three remaining conditions. The data highlight the complementary nature of the VFB conditions and establish the postural control behaviors necessary to use these VFB protocols efficiently.


The effects of carbamazepine on sperm morphology in wistar rats.
Carbamazepine (5 H-dibenz (b, f) azepine-5-carboxamide), is an antiepileptic drug which is expected to be administered regularly over a substantial part of patients lifetime. As the gender focus in epilepsy the later years has primarily been on women, there certainly is a lack of studies focused on the effects particular to men. The present study was aimed to investigate its effects on germ cell's by employing the sperm morphology assay. Twelve groups of male wistar rats were treated with sterile water 0.5 ml, cyclophosphamide (CP) 20 mg/kg, carbamazepine 9, 18, 36 mg/kg (i.p) and 2% gumacasia 0.25 ml/100 g respectively for 5 consecutive days at intervals of 24 hrs. Following the last exposure, on days 14 and 35 sperm morphology assay was conducted as per the standard procedure. Mann-Whitney 'U' test was used for statistical analysis and the level of significance was P<0.01. Neither carbamazepine nor cyclophosphamide induced formation of abnormally shaped sperms at 14 day time interval. Whereas on day 35, with 18 mg/kg dose level of carbamazepine there was an increase in the number of sperms with heads defects (P<0.01); Whereas in the other two dose levels the number of abnormally shaped sperms had decreased. 2% gumacasia increased the number of sperms with tail defects at day 35. (Mann-Whitney 'U' test). Carbamazepine and 2% gumacasia could be germ cell mutagens and could cause infertility on prolonged use therefore further studies with serum drug level estimations are needed.


Osteoblast-directed osteoclast metabolism from patients with premature coronal synostosis.
Osteoclasts were harvested from explants of five patients with premature unilateral coronal synostosis and plated on devitalized bovine bone wafers. The planar surface areas of resorption lacunae were quantitated by means of light microscopy and a digital imaging system. Osteoclasts isolated from involved regions of premature synostosis exhibited enhanced resorption when compared with osteoclasts isolated from noninvolved cranial bone in the same patients (p < 0.05). When the involved osteoclasts were exposed to conditioned media from non-involved osteoblasts, the in vitro metabolism was reduced consistent with noninvolved osteoclasts. The results suggest there may be a primary cellular defect and that there appears to be a complex coupling between osteoblast and osteoclast function that may lead to sutural synostosis.