Gauging the quality of qualitative research in adapted physical activity.
Qualitative inquiry is increasingly being used in adapted physical activity research, which raises questions about how to best evaluate its quality. This article aims to clarify the distinction between quality criteria (the what) and strategies (the how) in qualitative inquiry. An electronic keyword search was used to identify articles pertaining to quality evaluation published between 1995 and 2012 (n=204). A five phase systematic review resulted in the identification of 56 articles for detailed review. Data extraction tables were generated and analyzed for commonalities in terminology and meanings. Six flexible criteria for gauging quality were formulated: reflexivity, credibility, resonance, significant contribution, ethics, and coherence. Strategies for achieving the established criteria were also identified. It is suggested that researchers indicate the paradigm under which they are working and guidelines by which they would like readers to evaluate their work as well as what criteria can be absent without affecting the research value.


Being healthy in unhealthy places: health tactics in a homeless lifeworld.
Street life can compromise a person's health. In response, homeless people exert considerable agency in attempts to preserve their health. Drawing on ethnographic research in central Auckland, this article explores the ways in which a homeless man maintains his health. We consider the tactics Clinton develops to maintain his health and to gain respite while living on the streets, an unhealthy place. Of particular note are the ways in which he works to transform a 'landscape of despair' into a 'landscape of care'. The case of Clinton foregrounds the fundamentally emplaced and relational nature of homeless peoples' health.


[Current status of gene therapy for cancers].
Gene therapy with viral/unviral vectors is thought to be one of the most promising treatments for malignant diseases including cancers. The potential targeted genes researched are categorized into 2 groups: 1) those comprising oncogenes and oncosuppressor genes such as p 53 and E 1 A to directly kill tumors, and 2) others comprising immunoregulatory molecules such as TAA, cytokines, and T-cell costimulatory molecules to enhance anti-tumor immunity. These modalities have been intensively investigated for cancer treatment, and the anti-tumor efficacies are being shown in many preclinical studies using animal tumor models. To date, nevertheless, the clinical trials have not been successful overall. It is sometimes doubted whether this strategy with gene therapeutics is more beneficial than existing therapeutic modalities such as standard therapy with radiation and chemotherapeutics or immunotherapy with cytokines and immune cells to treat cancers. In fact,however,clinical responses of some targeted genes are now being revealed at higher levels of clinical trials, Phase II/III. Here, the genes targeted for cancer therapy and the current clinical trials are reviewed for a better understanding of cancer gene therapy.


Thyroid function during exchange transfusion.
The changes in plasma thyroid hormone concentration were studied during exchange transfusion performed for haemolytic disease. 24 transfusions were performed using blood preserved with acid-citrate and dextrose and in 11 cases 10 or 50 mug glucagon was added to the donor blood. Plasma tri-iodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroid hormone binding capacity, and free thyroxine index were measured in the donor blood and in the infant at the start and at intervals during the transfusion. Before transfusion the plasma TSH levels of the infants fell as postnatal age indreased and plasma T3 and T4 were correlated with one another. In 20 transfusions the mean infant/donor ratio of TSH was approximately 10, of T4 3, and of T3 2. During these transfusions there was a progressive fall in the infant's plasms TSH, T4, and T3 concentration. In 3 transfusions in which the donor plasma TSH was greater than that of the infant, plasma TSH levels rose during the transfusion and in 2 cases this was associated with a late rise in plasma T3 levels. The addition of glucagon to donor blood had no effect on thyroid hormone levels. It is concluded that erythroblastotic infants have normal thyroid function and that they became biochemically hypothyroid during transfusion. Acute changes in plasma thyroid hormone and glucagon concentration do not induce TSH responses by the neonatal pituitary during the period of the exchange transfusion.


Magnetic resonance imaging of the wrist in defining remission of rheumatoid arthritis.
To assess the efficacy of magnetic resonance imaging (MRI) in objectively defining a state of remission in rheumatoid arthritis (RA) after treatment. Ten patients with RA involving the wrist were evaluated before treatment with methotrexate and hydroxychloroquine, and then mean 14 mo later with a followup evaluation. Clinical variables, laboratory measurements, and MRI using various techniques (T1 weighted image, T2 weighted image, fat suppression T2 weighted image, postcontrast T1 weighted image, postcontrast dynamic image, postcontrast 3 dimensional image) were observed. Remission was defined by ACR criteria. MRI changes were observed using 3 variables: extent of synovial proliferation; extent of bone marrow edema; and development of new erosion. In 6 of 10 patients, synovial signal intensity time curve changes at 30 s (E30 ratio) were determined for quantitative assessment of synovitis. Four patients achieved remission and 6 did not. All patients in remission showed decrease in extent of synovial proliferation and bone marrow edema with no newly developed erosion after treatment, compared to baseline. Five of 6 patients in nonremission showed newly developed erosions with variable changes in extent of synovial proliferation and bone marrow edema. E30 ratio was determined in 3 patients in the remission group and 3 in the nonremission group, with 48% reduction in the former compared to 9% reduction in the latter. MRI is feasible for objectively defining remission and assessing the therapeutic effect of antirheumatic drugs; utility of MRI measures in clinical remission criteria remains to be verified.


The effect of external stimulation on functional networks in the aging healthy human brain.
Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310, <65 years) and older adults (N =310, $\geq $65) to characterize brain states in each group as a probabilistic metastable substate (PMS) space. We showed that the older group exhibited a reduced capability to access a metastable substate that overlaps with the rich club. Then, we fitted the PMS to a whole-brain model and applied in silico stimulations in each node to force transitions from the brain states of the older- to the middle-aged group. We found that the precuneus was the best stimulation target. Overall, these findings could have important implications for designing neurostimulation interventions for reversing the effects of aging on whole-brain dynamics.


Factors associated with poor physical performance in older adults of 11 Peruvian high Andean communities.
Background: Physical performance in the older adult has been extensively studied. However, only a few studies have evaluated physical performance among older adults of high Andean populations and none have studied the factors associated with it. The objective of this study was to evaluate factors associated with poor physical performance by using the Short Physical Performance Battery (SPPB) in older adults living in 11 Peruvian high Andean communities. Methods: An analytical cross-sectional study was carried out in inhabitants aged 60 or over from 11 high-altitude Andean communities of Peru during 2013-2017. Participants were categorized in two groups according to their SPPB score: poor physical performance (0-6 points) and medium/good physical performance (7-12 points). Additionally, we collected socio-demographic, medical, functional and cognitive assessment information. Poisson regression models were constructed to identify factors associated with poor physical performance. Prevalence ratio (PR) with 95% confidence intervals (95 CI%) are presented. Results: A total of 407 older adults were studied. The average age was 73.0 ± 6.9 years (range: 60-94 years) and 181 (44.5%) participants had poor physical performance (0-6 points). In the adjusted Poisson regression analysis, the factors associated with poor physical performance were: female gender (PR=1.29; 95%CI: 1.03-1.61), lack of social support (PR=2.10; 95%CI: 1.17-3.76), number of drugs used (PR=1.09; 95%CI: 1.01-1.17), urinary incontinence (PR=1.45; 95%CI: 1.16-1.82), exhaustion (PR=1.35; 95%CI: 1.03-1.75) and cognitive impairment (PR=1.89; 95%CI: 1.40-2.55). Conclusions: Almost half of the population evaluated had poor physical performance based on the SPPB. Factors that would increase the possibility of suffering from poor physical performance were: female gender, lack of social support, number of drugs used, urinary incontinence, exhaustion and cognitive impairment. Future studies with a larger sample and longitudinal follow-up are needed to design beneficial interventions for the high Andean population.


Neurotrophin 3/TrkC-regulated proteins in the human medulloblastoma cell line DAOY.
Medulloblastoma (MB) is the most common malignant childhood brain tumor and high neurotrophin (NP) receptor TrkC mRNA expression was identified as a powerful independent predictor of favorable survival outcome. In order to determine downstream effector proteins of TrkC signaling, the MB cell line DAOY was stably transfected with a vector containing the full-length TrkC cDNA sequence or an empty vector control. A proteomic approach was used to search for expressional changes by two mass spectrometric methods and immunoblotting for validation of significant results. Multiple time points for up to 48 h following NP-3-induced TrkC receptor activation were chosen. Thirteen proteins from several pathways (nucleoside diphosphate kinase A, stathmin, valosin-containing protein, annexin A1, dihydropyrimidinase-related protein-3, DJ-1 protein, glutathione S-transferase P, lamin A/C, fascin, cofilin, vimentin, vinculin, and moesin) were differentially expressed and most have been shown to play a role in differentiation, migration, invasion, proliferation, apoptosis, drug resistance, or oncogenesis. Knowledge on effectors of TrkC signaling may represent a first useful step for the identification of marker candidates or reflecting probable pharmacological targets for specific treatment of MB.


Vlasov simulations of thermal plasma waves with relativistic phase velocity in a Lorentz boosted frame.
For certain classes of relativistic plasma problems, performing numerical calculations in a Lorentz boosted frame can be even more advantageous for gridded momentum-space-time (e.g., Vlasov) problems than has been demonstrated for position space-time problems and result in a potential reduction in the number of calculations needed by a factor ∼γ_{b}^{6}. In this study, the Lorentz boosted frame technique was applied to the problem of warm wave-breaking limits of plasma waves with relativistic phase velocity. The numerical results are consistent with analytic conclusions. By appropriate normalization and for sufficiently warm plasma, the dynamics for the Vlasov equation in different Lorentz frames were found to be independent of γ_{p}.


WISH-PC2: a unique xenograft model of human prostatic small cell carcinoma.
Prostatic small cell carcinoma is an aggressive subtype of prostate cancer that usually appears as a progression of the original adenocarcinoma. We describe here the WISH-PC2, a novel neuroendocrine xenograft of small cell carcinoma of the prostate. This xenograft was established from a poorly differentiated prostate adenocarcinoma and is serially transplanted in immune-compromised mice where it grows within the prostate, liver, and bone, inducing osteolytic lesions with foci of osteoblastic activity. It secretes to the mouse Chromogranin A and expresses prostate plasma carcinoma tumor antigen-1, six-transmembrane epithelial antigen of the prostate, and members of the Erb-B receptor family. It does not express prostate-specific antigen, prostate stem cell antigen, prostate-specific membrane antigen, and androgen receptor, and it grows independently of androgen. Altogether, WISH-PC2 provides an unlimited source in which to study the involvement of neuroendocrine cells in the progression of prostatic adenocarcinoma and can serve as a novel model for the testing of new therapeutic strategies for prostatic small cell carcinoma.


Treatment of severe cold contact urticaria with omalizumab: case reports.
We report 2 patients with cold urticaria with different response to treatment with omalizumab (Xolair(®)). Cold contact urticaria (CCU) is a common subtype of physical urticaria. It is characterized by the development of wheal and/or angioedema within minutes after cold contact. Clinical manifestation of CCU can range from mild, localized whealing to life-threatening anaphylactic shock reactions. Omalizumab has been described to be useful in cases of chronic urticaria and may be an interesting option for treatment of CCU. We describe one patient with significant and long-lasting improvement of symptoms and one without any improvement after anti-immunoglobulin E therapy. In our case reports, we want to highlight that there is still a small group of patients without benefit from omalizumab treatment. It is necessary to identify this minor subgroup of patients where omalizumab does not represent an effective treatment possibility.


Morphometric evaluation of endometrial blood vessels.
Five hundred endometrial specimens were studied to document the changes in blood vessels in various phases of menstrual cycle, menstrual disturbances and in unexplained infertility. Sixty-three cases were taken as control and 437 cases as study group which included cases of dysfunctional uterine bleeding (DUB), endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium. Using light microscopy, the vascular morphology was studied. The blood vessels were concentrated more in basal layer in the proliferative phase and in functional layer in the secretory phase. Cases of complex hyperplasia and pill endometrium had significantly higher vessel concentration. Congestion and dilatation of blood vessels were significantly higher in cases of DUB. The present study showed a positive correlation between endometrial angiogenesis and menstrual disorders. The alteration in blood vessel morphology has significant role in prognosis and in various anti-angiogenic therapies.


Can we set a global threshold age to define mature forests?
Globally, mature forests appear to be increasing in biomass density (BD). There is disagreement whether these increases are the result of increases in atmospheric CO2 concentrations or a legacy effect of previous land-use. Recently, it was suggested that a threshold of 450 years should be used to define mature forests and that many forests increasing in BD may be younger than this. However, the study making these suggestions failed to account for the interactions between forest age and climate. Here we revisit the issue to identify: (1) how climate and forest age control global forest BD and (2) whether we can set a threshold age for mature forests. Using data from previously published studies we modelled the impacts of forest age and climate on BD using linear mixed effects models. We examined the potential biases in the dataset by comparing how representative it was of global mature forests in terms of its distribution, the climate space it occupied, and the ages of the forests used. BD increased with forest age, mean annual temperature and annual precipitation. Importantly, the effect of forest age increased with increasing temperature, but the effect of precipitation decreased with increasing temperatures. The dataset was biased towards northern hemisphere forests in relatively dry, cold climates. The dataset was also clearly biased towards forests <250 years of age. Our analysis suggests that there is not a single threshold age for forest maturity. Since climate interacts with forest age to determine BD, a threshold age at which they reach equilibrium can only be determined locally. We caution against using BD as the only determinant of forest maturity since this ignores forest biodiversity and tree size structure which may take longer to recover. Future research should address the utility and cost-effectiveness of different methods for determining whether forests should be classified as mature.


Continuous ES/Feeder Cell-Sorting Device Using Dielectrophoresis and Controlled Fluid Flow.
Pluripotent stem cells (PSCs) are considered as being an important cell source for regenerative medicine. The culture of PSCs usually requires a feeder cell layer or cell adhesive matrix coating such as Matrigel, laminin, and gelatin. Although a feeder-free culture using a matrix coating has been popular, the on-feeder culture is still an effective method for the fundamental study of regenerative medicine and stem cell biology. To culture PSCs on feeder cell layers, the elimination of feeder cells is required for biological or gene analysis and for cell passage. Therefore, a simple and cost-effective cell sorting technology is required. There are several commercialized cell-sorting methods, such as FACS or MACS. However, these methods require cell labeling by fluorescent dye or magnetic antibodies with complicated processes. To resolve these problems, we focused on dielectrophoresis (DEP) phenomena for cell separation because these do not require any fluorescent or magnetic dyes or antibodies. DEP imposes an electric force on living cells under a non-uniform AC electric field. The direction and magnitude of the DEP force depend on the electric property and size of the cell. Therefore, DEP is considered as a promising approach for sorting PSCs from feeder cells. In this study, we developed a simple continuous cell-sorting device using the DEP force and fluid-induced shear force. As a result, mouse embryonic stem cells (mESCs) were purified from a mixed-cell suspension containing mESCs and mouse embryonic fibroblasts (MEFs) using our DEP cell-sorting device.


Orotate phosphoribosyl transferase mRNA expression and the response of cholangiocarcinoma to 5-fluorouracil.
To determine whether expression of certain enzymes related to 5-fluorouracil (5-FU) metabolism predicts 5-FU chemosensitivity in cholangiocarcinoma (CCA). The histoculture drug response assay (HDRA) was performed using surgically resected CCA tissues. Tumor cell viability was determined morphologically with hematoxylin and eosin- and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling-stained tissues. The mRNA expression of thymidine phosphorylase (TP), orotate phosphoribosyl transferase (OPRT), thymidylate synthase (TS), and dihydropyrimidine dehydrogenase (DPD) was determined with real-time reverse transcriptase-polymerase chain reaction. The levels of gene expression and the sensitivity to 5-FU were evaluated. Twenty-three CCA tissues were obtained from patients who had been diagnosed with intrahepatic CCA and who underwent surgical resection at Srinagarind Hospital, Khon Kaen University from 2007 to 2009. HDRA was used to determine the response of these CCA tissues to 5-FU. Based on the dose-response curve, 200 μg/mL 5-FU was selected as the test concentration. The percentage of inhibition index at the median point was selected as the cut-off point to differentiate the responding and non-responding tumors to 5-FU. When the relationship between TP, OPRT, TS and DPD mRNA expression levels and the sensitivity of CCA tissues to 5-FU was examined, only OPRT mRNA expression was significantly correlated with the response to 5-FU. The mean expression level of OPRT was significantly higher in the responder group compared to the non-responder group (0.41 ± 0.25 vs 0.22 ± 0.12, P < 0.05). OPRT mRNA expression may be a useful predictor of 5-FU chemosensitivity of CCA. Whether OPRT mRNA could be used to predict the success of 5-FU chemotherapy in CCA patients requires confirmation in patients.


Tyrosine phosphorylation of myelin P(0) and its implication in signal transduction.
P(0), a major structural protein of peripheral myelin, belongs to the immunoglobulin superfamily. Sequence comparison of P(0) with PZR, a tyrosine phosphatase SHP-2 binding protein we recently cloned, revealed the presence of an immunoreceptor tyrosine-based inhibitory motif (ITIM) in the intracellular portion of the P(0) molecule. To study the role of this putative ITIM in signal transduction, we have expressed P(0) in HT-1080 and 293 cells. Stimulation of the transfected cells with pervanadate, a powerful inhibitor of tyrosine phosphatases, resulted in tyrosine phosphorylation of P(0) and its association with several tyrosine-phosphorylated proteins. Mutation of Y(220) embedded in the ITIM to phenylalanine abolished the tyrosine phosphorylation and the association. Tyrosine phosphorylation of P(0) and its association with other signaling proteins were also observed in pervanadate-treated RN22 Schwannoma cells, which express endogenous P(0). Furthermore, injection of pervanadate induced tyrosine phosphorylation of P(0) in peripheral nerves of newborn but not adult mice. The physiological importance of the ITIM in P(0) is implied by the fact that a naturally occurred P(0) mutant with a disrupted ITIM has a dominant role in causing Dejerine-Scotts syndrome. Taken together, P(0) is phosphorylated on Try(220). The presence of an ITIM in P(0) and its ability to mediate protein-protein interaction through tyrosine phosphorylation indicate that P(0) is not merely a structural protein but may also be a crucial player in cell signaling.


Suppression of cell-mediated immunity by street rabies virus.
Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.


Restless legs syndrome in patients on dialysis.
Restless legs syndrome (RLS) is an extremely distressing problem experienced by patients on dialysis; the prevalence appears to be greater than in the general population, with a wide variation from 6.6% to 80%. The diagnosis of RLS is a clinical one, and its definition has been clarified and standardized by internationally recognized diagnostic criteria, published in 1995 by the International Restless Legs Syndrome Study Group (IRLSSG). This study was designed to find out the prevalence of RLS in Saudi patients with end-stage renal disease (ESRD) on maintenance dialysis. This is a cross sectional study carried out between May and Sept 2007 at two centers, King Abdulaziz Medical City-King Fahad National Guard Hospital (KAMC-KFNGH), Riyadh and King Faisal Specialist Hospital and Research Centre (KFHRC), Jeddah, Saudi Arabia. Data were gathered on 227 Saudi patients on chronic maintenance hemodialysis or chronic peritoneal dialysis. The prevalence of RLS was measured using IRLSSG's RLS Questionnaire (RLSQ). Potential risk factors for RLS including other sleep disorders, underlying cause of chronic renal failure, duration on dialysis, dialysis shift, biochemical tests and demographic data were also evaluated. The overall prevalence of RLS was 50.22% including 53.7% males and 46.3% females. Their mean age was 55.7 +/- 17.2 years and mean duration on dialysis 40.4 +/- 37.8 months. Significant predictors of RLS were history of diabetes mellitus (DM), coffee intake, afternoon dialysis, gender and type of dialysis (P= 0.03, 0.01, < 0.001, 0.05 and 0.009 respectively). Patients with RLS were found to be at increased risk of having insomnia and excessive daytime sleepiness (EDS) (P= < 0.001 and 0.001, respectively). Our study suggests that RLS is a very common problem in dialysis population and was significantly associated with other sleep disorders, particularly insomnia, and EDS. Optimal care of dialysis patient should include particular attention to the diagnosis and management of sleep disorders.


Relaxing effect of ylang ylang oil on humans after transdermal absorption.
The aim of this study was to investigate the effects of ylang ylang oil (Cananga odorata, Annonaceae) on human physiological parameters and self-evaluation after transdermal absorption. Forty healthy volunteers participated in the experiments. Physiological parameters recorded were skin temperature, pulse rate, breathing rate and blood pressure. Self-evaluation was assessed by means of visual analog scales (VAS). The ylang ylang oil caused a significant decrease of blood pressure and a significant increase of skin temperature. At the behavioral level, subjects in the ylang ylang oil group rated themselves more calm and more relaxed than subjects in the control group. These findings are likely to represent a relaxing effect of the ylang ylang oil and provide some evidence for the usage of the ylang ylang oil in aromatherapy such as causing a relief of depression and stress in humans.


Evaluation of a minimally invasive glucose biosensor for continuous tissue monitoring.
We describe here a minimally invasive glucose biosensor based on a microneedle array electrode fabricated from an epoxy-based negative photoresist (SU8 50) and designed for continuous measurement in the dermal compartment with minimal pain. These minimally invasive, continuous monitoring sensor devices (MICoMS) were produced by casting the structures in SU8 50, crosslinking and then metallising them with platinum or silver to obtain the working and reference electrodes, respectively. The metallised microneedle array electrodes were subsequently functionalised by entrapping glucose oxidase in electropolymerised polyphenol (PP) film. Sensor performance in vitro showed that glucose concentrations down to 0.5 mM could be measured with a response times (T90) of 15 s. The effect of sterilisation by Co60 irradiation was evaluated. In preparation for further clinical studies, these sensors were tested in vivo in a healthy volunteer for a period of 3-6 h. The sensor currents were compared against point measurements obtained with a commercial capillary blood glucometer. The epoxy MICoMS devices showed currents values that could be correlated with these. Graphical Abstract Microneedle arrays for continuous glucose monitoring in dermal interstitial fluid.


The effectiveness of Chair Massage on Stress and Pain in Oncology.
There is a high prevalence of moderate-to-high levels of chronic stress among nurses, as well as an occurrence of musculoskeletal disorders. To evaluate the effectiveness of chair massage to reduce chronic stress and musculoskeletal pain in the Oncology Nursing team. Two teaching cancer hospitals, one public and the other private, in São Paulo city, Brazil. A total of 60 women from the Oncology Nursing team. A randomized controlled trial divided into two groups: chair massage and control without intervention. The massage group received two chair massage sessions lasting 15 minutes, twice a week, for three weeks. Reduction of stress and pain measured by the List of Signs and Symptoms (LSS) and the Brief Pain Inventory (BPI), respectively. The average age was 32 (± 5.3) years. There was a reduction of stress measured by the LSS with a statistical difference in the group-time interaction (p < .001), with a Cohen's d value of 1.21 between groups. The BPI analysis showed a statistically significant difference in the group-time interaction for general activity (p < .008), mood (p < .03), work (p < .000), and sleep (p = .03), with reduced pain interference in these components. Chair massage reduced stress and pain interference in the team's daily life activities, bringing a positive impact in the context of work stress and pain in Oncology nursing professionals.


A constitutively active NFATc1 mutant induces a transformed phenotype in 3T3-L1 fibroblasts.
The calcineurin/nuclear factor of activated T cells (NFAT) signaling pathway is best known for its role in T lymphocyte activation. However, it has become increasingly apparent that this signaling pathway is also involved in the regulation of cell growth and development in a wide variety of different tissues and cell types. Here we have investigated the effects of sustained NFATc1 signaling on the growth and differentiation of the murine 3T3-L1 preadipocyte cell line. Remarkably, we find that expression of a constitutively active NFATc1 mutant (caNFATc1) in these immortalized cells inhibits their differentiation into mature adipocytes and causes them to adopt a transformed cell phenotype, including loss of contact-mediated growth inhibition, reduced serum growth requirements, protection from growth factor withdrawal-induced apoptosis, and formation of colonies in semisolid media. Furthermore, we find that caNFATc1-expressing cells acquire growth factor autonomy and are able to proliferate even in the complete absence of serum. We provide evidence that this growth factor independence is caused by the NFATc1-dependent production of a soluble heat-labile autocrine factor that is capable of promoting the growth and survival of wild type 3T3-L1 cells as well as potently inhibiting their differentiation into mature adipocytes. Finally, we demonstrate that cells expressing caNFATc1 form tumors in nude mice. Taken together, these results indicate that deregulated NFATc1 activity is able to induce the immortalized 3T3-L1 preadipocyte cell line to acquire the well established hallmarks of cellular transformation and thereby provide direct evidence for the oncogenic potential of the NFATc1 transcription factor.


Quality of health information for cervical cancer treatment on the internet.
The internet has become a frequently used and powerful tool for patients seeking medical information. This information may not undergo the same quality consideration as the peer-review criteria for publication of information in a journal. The aim of this study is to assess the quality of internet sites providing information on the treatment of cervical cancer, with comparisons between the quality assessments made by an educated lay person and an expert in the field. A search of the World Wide Web was made by a lay person to identify sites containing information on the treatment of cervical cancer. The credibility and accuracy of these sites was assessed using predefined criteria based on 'Criteria for Assessing the Quality of Health Information on the Internet' and accepted guidelines for the treatment of cervical cancer. The assessment was made independently and in duplicate by the lay reviewer and medical expert in order to allow comparison. 46 relevant websites were assessed. Only one site contained all the credibility and accuracy criteria, with a further website containing all the credibility criteria. The majority of sites, 38/46, were deemed easy to navigate. The agreement between lay person and expert was good with only 6 items in total changed by the expert. This study clearly shows there is wide variation in quality of websites available to patients on the treatment of cervical cancer. Further research and consideration is needed on the effects of website information on gynaecological cancer patients and how steps can be made to insure the posting of good quality information.


Community participation in formulating the post-2015 health and development goal agenda: reflections of a multi-country research collaboration.
Global discussion on the post-2015 development goals, to replace the Millennium Development Goals when they expire on 31 December 2015, is well underway. While the Millennium Development Goals focused on redressing extreme poverty and its antecedents for people living in developing countries, the post-2015 agenda seeks to redress inequity worldwide, regardless of a country's development status. Furthermore, to rectify the UN's top-down approach toward the Millennium Development Goals' formulation, widespread negotiations are underway that seek to include the voices of people and communities from around the globe to ground each post-2015 development goal. This reflexive commentary, therefore, reports on the early methodological challenges the Go4Health research project experienced in its engagement with communities in nine countries in 2013. Led by four research hubs in Uganda, Bangladesh, Australia and Guatemala, the purpose of this engagement has been to ascertain a 'snapshot' of the health needs and priorities of socially excluded populations particularly from the Global South. This is to inform Go4Health's advice to the European Commission on the post-2015 global goals for health and new governance frameworks. Five methodological challenges were subsequently identified from reflecting on the multidisciplinary, multiregional team's research practices so far: meanings and parameters around qualitative participatory research; representation of marginalization; generalizability of research findings; ethical research in project time frames; and issues related to informed consent. Strategies to overcome these methodological hurdles are also examined. The findings from the consultations represent the extraordinary diversity of marginal human experience requiring contextual analysis for universal framing of the post-2015 agenda. Unsurprisingly, methodological challenges will, and did, arise. We conclude by advocating for a discourse to emerge not only critically examining how and whose voices are being obtained at the community-level to inform the post-2015 health and development goal agenda, but also how these voices are being translated and integrated into post-2015 decision-making at national and global levels.


Protein stability and transcription factor complex assembly determined by the SCL-LMO2 interaction.
Gene expression programs are established by networks of interacting transcription factors. The basic helix-loop-helix factor SCL and the LIM-only protein LMO2 are components of transcription factor complexes that are essential for hematopoiesis. Here we show that LMO2 and SCL are predominant interaction partners in hematopoietic cells and that this interaction occurs through a conserved interface residing in the loop and helix 2 of SCL. This interaction nucleates the assembly of SCL complexes on DNA and is required for target gene induction and for the stimulation of erythroid and megakaryocytic differentiation. We also demonstrate that SCL determines LMO2 protein levels in hematopoietic cells and reveal that interaction with SCL prevents LMO2 degradation by the proteasome. We propose that the SCL-LMO2 interaction couples protein stabilization with higher order protein complex assembly, thus providing a powerful means of modulating the stoichiometry and spatiotemporal activity of SCL complexes. This interaction likely provides a rate-limiting step in the transcriptional control of hematopoiesis and leukemia, and similar mechanisms may operate to control the assembly of diverse protein modules.


How can physicians' learning styles drive educational planning?
As changes in health care delivery systems and in the global burden of disease call for a reassessment of how tomorrow's physicians should be educated--indeed, for a reconsideration of the diversity of roles the physician should play--there is an immediate need to produce continuing medical education (CME) programs with real impact. Curriculum planners are questioning both the content of medical education and the methods of instruction and training. The product, or content, and the mechanism for its delivery have been defined and discussed, but a significant body of literature has shown that new knowledge does not necessarily lead to new behavior. Ample evidence exists in the CME literature to support the implementation of more active and self-directed learning strategies to promote the desired change in behaviors. The question, then, that is the focus of this article is how educational planning might be better guided by an understanding of how physicians learn within the continuing medical education domain. Revisiting the principles of David Kolb's Learning Styles Inventory, the authors propose applying his experiential learning model to overall curriculum design work. The authors argue that promoting the application of all learning styles in sequence in an educational encounter is a most desirable approach, and that this approach to learning could extend far beyond individual learners to influence how every component of medical education is designed, from the individual lecture or class activity to entire courses or programs.


Chronic disease self-management program in the workplace: opportunities for health improvement.
Disease management is becoming increasingly important in workplace health promotion given the aging workforce, rising chronic disease prevalence, and needs to maintain a productive and competitive American workforce. Despite the widespread availability of the Chronic Disease Self-Management Program (CDSMP), and its known health-related benefits, program adoption remains low in workplace settings. The primary purpose of this study is to compare personal and delivery characteristics of adults who attended CDSMP in the workplace relative to other settings (e.g., senior centers, healthcare organizations, residential facilities). This study also contrasts characteristics of CDSMP workplace participants to those of the greater United States workforce and provides recommendations for translating CDSMP for use in workplace settings. Data were analyzed from 25,664 adults collected during a national dissemination of CDSMP. Only states and territories that conducted workshops in workplace settings were included in analyses (n = 13 states and Puerto Rico). Chi-squared tests and t-tests were used to compare CDSMP participant characteristics by delivery site type. CDSMP workplace participant characteristics were then compared to reports from the United States Bureau of Labor Statistics. Of the 25,664 CDSMP participants in this study, 1.7% (n = 435) participated in workshops hosted in worksite settings. Compared to CDSMP participants in non-workplace settings, workplace setting participants were significantly younger and had fewer chronic conditions. Differences were also observed based on chronic disease types. On average, CDSMP workshops in workplace settings had smaller class sizes and workplace setting participants attended more workshop sessions. CDSMP participants in workplace settings were substantially older and a larger proportion were female than the general United States workforce. Findings indicate opportunities to translate CDSMP for use in the workplace to reach new target audiences.


Altered Actin Filament Dynamics in the Drosophila Mushroom Bodies Lead to Fast Acquisition of Alcohol Consumption Preference.
Alcohol use is highly prevalent in the United States and across the world, and every year millions of people suffer from alcohol use disorders (AUDs). Although the genetic contribution to developing AUDs is estimated to be 50-60%, many of the underlying molecular mechanisms remain unclear. Previous studies from our laboratory revealed that Drosophila melanogaster lacking RhoGAP18B and Ras Suppressor 1 (Rsu1) display reduced sensitivity to ethanol-induced sedation. Both Rsu1 and RhoGAP18B are negative regulators of the small Rho-family GTPase, Rac1, a modulator of actin dynamics. Here we investigate the role of Rac1 and its downstream target, the actin-severing protein cofilin, in alcohol consumption preference. We show that these two regulators of actin dynamics can alter male experience-dependent alcohol preference in a bidirectional manner: expressing either activated Rac1 or dominant-negative cofilin in the mushroom bodies (MBs) abolishes experience-dependent alcohol preference. Conversely, dominant-negative Rac1 or activated cofilin MB expression lead to faster acquisition of alcohol preference. Our data show that Rac1 and cofilin activity are key to determining the rate of acquisition of alcohol preference, revealing a critical role of actin dynamics regulation in the development of voluntary self-administration in DrosophilaSIGNIFICANCE STATEMENT The risks for developing an alcohol use disorder (AUD) are strongly determined by genetic factors. Understanding the genes and molecular mechanisms that contribute to that risk is therefore a necessary first step for the development of targeted therapeutic intervention. Here we show that regulators of actin cytoskeleton dynamics can bidirectionally determine the acquisition rate of alcohol self-administration, highlighting this process as a key mechanism contributing to the risk of AUD development.


A microscopic view of graphene-oxide/poly(acrylic acid) physical hydrogels: effects of polymer charge and graphene oxide loading.
In this work we have examined in detail by means of fully atomistic molecular dynamics simulations, physical hydrogels formed by a polymer electrolyte, poly(acrylic acid), and graphene oxide, at two different charging states of the polymer and two different graphene oxide concentrations. It was found that variations of these parameters incurred drastic changes in general morphological characteristics of the composite materials, the degree of physical adsorption of polyelectrolyte chains onto the graphene oxide surface, the polymer dynamic response at local and global length scales, in the charge distributions around the components, and in the mobility of the counterions. All these microscopic features are expected to significantly affect macroscopic physical properties of the hydrogels, such as their mechanical responses and their electrical behaviors.


Molecular hydrogen attenuates methamphetamine-induced behavioral sensitization and activation of ERK-ΔFosB signaling in the mouse nucleus accumbens.
Methamphetamine (METH) is one of the most prevalently used illegal psychostimulants in many countries. Continuous exposure to METH leads to behavioral sensitization in animals, which can be used as a behavioral model with many mechanisms in common with relapse in humans. Molecular hydrogen has recently gained attention for its potential as a novel healthcare product with preventive and therapeutic applicability to a wide range of pathological conditions. However, it remains unclear whether and, if so, how hydrogen regulates METH-induced behavioral abnormalities. In the present study, we investigated the roles of molecular hydrogen on the acquisition and transfer of METH-induced behavioral sensitization and the accompanying changes in ERK phosphorylation and ΔFosB activation in the nucleus accumbens (NAc) of mice. To this end, male C57BL/6 mice received METH (0.1, 0.5 and 1.0 mg/kg, i.p.) injections for 7 days followed by a METH challenge (0.1, 0.5 and 1.0 mg/kg, i.p.) after a 7-day transfer period. Molecular hydrogen, delivered through a hydrogen-rich saline (HRS) injection (10 mL/kg, i.p., 3-h interval), was administered during the acquisition and transfer periods. We found that HRS administration was able to inhibit the acquisition and transfer of 0.1 and 0.5 mg/kg METH-induced behavioral sensitization to a certain extent, thereby attenuating the expression of behavioral sensitization. The HRS injections alone did not induce any obvious changes in locomotor activity in mice. Intriguingly, the increases in pERK and ΔFosB in the NAc, which accompanied the METH-induced behavioral sensitization, were also attenuated by the HRS treatments. Due to the anti-oxidative function of molecular hydrogen, the HRS injections reduced METH-induced reactive oxygen species and malondialdehyde generation in the NAc. These results suggest that molecular hydrogen serves as an anti-oxidative agent with potentially therapeutic applicability to the treatment of METH addicts.


Distal femur rotation relates to joint obliquity in ACL-deficient Chinese.
The lower limb osteometry of Chinese differs from that of whites. The joint line of the knee in the coronal plane in Chinese is more medially inclined and the posterior condylar angle of the distal femur in the axial plane is larger. However, it is unclear whether there is any direct association between the coronal plane and axial plane osteometry. We asked whether the joint line obliquity of the knee is related to the posterior condylar angle of the distal femur in young Chinese subjects. Ninety-nine young Chinese patients with anterior cruciate ligament injuries were recruited. The lower limb alignment and joint line obliquity were measured using standing long radiographs of the whole lower limb. The rotational alignment of the distal femur was assessed in the axial cuts of the MRI. The distal femur rotational alignment was associated with the obliquity of the knee in Chinese. The posterior condylar angle was 5° ± 2°. The knee was 5° ± 3° medially inclined. The joint line of the knee in a group of young Chinese patients was more medially inclined than that of whites. The posterior condylar angle of the distal femur was larger. The presence of an association between distal femur rotational alignment and joint line obliquity in this group of young Chinese patients suggests a possible developmental cause explaining the difference in osteometry between races.


Archaeal nitrification in the ocean.
Marine Crenarchaeota are the most abundant single group of prokaryotes in the ocean, but their physiology and role in marine biogeochemical cycles are unknown. Recently, a member of this clade was isolated from a sea aquarium and shown to be capable of nitrification, tentatively suggesting that Crenarchaeota may play a role in the oceanic nitrogen cycle. We enriched a crenarchaeote from North Sea water and showed that its abundance, and not that of bacteria, correlates with ammonium oxidation to nitrite. A time series study in the North Sea revealed that the abundance of the gene encoding for the archaeal ammonia monooxygenase alfa subunit (amoA) is correlated with a decline in ammonium concentrations and with the abundance of Crenarchaeota. Remarkably, the archaeal amoA abundance was 1-2 orders of magnitude higher than those of bacterial nitrifiers, which are commonly thought to mediate the oxidation of ammonium to nitrite in marine environments. Analysis of Atlantic waters of the upper 1,000 m, where most of the ammonium regeneration and oxidation takes place, showed that crenarchaeotal amoA copy numbers are also 1-3 orders of magnitude higher than those of bacterial amoA. Our data thus suggest a major role for Archaea in oceanic nitrification.


Initial effects of the tongue crib on tongue movements during deglutition: a Cine-Magnetic resonance imaging study.
The objective of this study was to investigate the initial effects of a tongue crib on tongue movements during deglutition by using real time balanced turbo field echo (B-TFE) Cine-MR imaging. A total of 21 patients were evaluated in this study. The open-bite group (OBG) consisted of 11 patients (seven girls, four boys) who had a mean age of 11.09 +/- 2.02 years and a mean overbite of -5.14 +/- 1.83 mm. These patients were evaluated initially (T1) and while wearing a tongue crib (T2). A total of 10 patients (five girls, five boys) with a mean age of 14.5 +/- 2.6 years and with a mean overbite of 1.6 +/- 0.5 mm served as controls (CG), and only initial records were obtained from these patients. T2 was compared with T1 and CG. T1 was also compared with CG. We evaluated deglutition during three stages matching oral (1), pharyngeal (2), and esophageal (3) stages. Our results indicated that the tongue's tip positioned more posteriorly when the crib was in place (T2) compared with both T1 and CG; the anterior portion of the tongue's dorsum was at a lower position in T2 compared with both T1 and CG at stage 3; the midportion of the tongue's dorsum was at a lower position in T2 than in T1 and CG at stages 1 and 2. To compensate for the posterior position of the tongue's tip (caused by the tongue crib), adaptive changes occurred in the anterior and midportions of the dorsum of the tongue.


Multimodel precipitation responses to removal of U.S. sulfur dioxide emissions.
Emissions of aerosols and their precursors are declining due to policies enacted to protect human health, yet we currently lack a full understanding of the magnitude, spatiotemporal pattern, statistical significance, and physical mechanisms of precipitation responses to aerosol reductions. We quantify the global and regional precipitation responses to U.S. SO2 emission reductions using three fully coupled chemistry-climate models: Community Earth System Model version 1, Geophysical Fluid Dynamics Laboratory Coupled Model 3, and Goddard Institute for Space Studies ModelE2. We contrast 200 year (or longer) simulations in which anthropogenic U.S. sulfur dioxide (SO2) emissions are set to zero with present-day control simulations to assess the aerosol, cloud, and precipitation response to U.S. SO2 reductions. In all three models, reductions in aerosol optical depth up to 70% and cloud droplet number column concentration up to 60% occur over the eastern U.S. and extend over the Atlantic Ocean. Precipitation responses occur both locally and remotely, with the models consistently showing an increase in most regions considered. We find a northward shift of the tropical rain belt location of up to 0.35° latitude especially near the Sahel, where the rainy season length and intensity are significantly enhanced in two of the three models. This enhancement is the result of greater warming in the Northern versus Southern Hemispheres, which acts to shift the Intertropical Convergence Zone northward, delivering additional wet season rainfall to the Sahel. Two of our three models thus imply a previously unconsidered benefit of continued U.S. SO2 reductions for Sahel precipitation.


A reliable and effective method of DNA isolation from old human blood paper cards.
Blood paper cards provide an effective DNA storage method. In this study, we used three DNA dissolving reagents (Tris-EDTA [TE] buffer, Tris-HCl buffer, and water) and one common commercially available kit (DN131 from MRC Inc) to elute DNA from 105 human blood paper cards collected up to 10 years ago. These DNA samples were used as templates for amplification of a single nucleotide polymorphism (SNP, C125T) region of human caspase-12 by PCR and a specific Taqman genotyping assay using the same amount of DNA. We show that DNA isolated by Tris-HCl buffer has higher yield and quality in comparison to DN131 solution. PCR success rate to amplify caspase-12 C125T SNP using Tris-HCl is comparable to the method using DN131 (89.5% vs 87.6%). The Taqman genotyping success rate using Tris-HCl is higher than using DN131 (81.9% vs 70.5%). Using TE or water, PCR success rates are lower than using DN131 (73.3% [TE]; 72.4% [H2O]), but Taqman genotyping success rates are comparable to the method using DN131 (70.5% [TE]; 79.1% [H2O]). We concluded that using Tris-HCl is a reliable and effective method to elute DNA from old human blood paper cards. The crude DNA isolated by Tris-HCl can be used to study genetic polymorphisms in human populations.


Is expert opinion reliable when estimating transition probabilities? The case of HCV-related cirrhosis in Egypt.
Data on HCV-related cirrhosis progression are scarce in developing countries in general, and in Egypt in particular. The objective of this study was to estimate the probability of death and transition between different health stages of HCV (compensated cirrhosis, decompensated cirrhosis and hepatocellular carcinoma) for an Egyptian population of patients with HCV-related cirrhosis. We used the "elicitation of expert opinions" method to obtain collective knowledge from a panel of 23 Egyptian experts (among whom 17 were hepatologists or gastroenterologists and 2 were infectiologists). The questionnaire was based on virtual medical cases and asked the experts to assess probability of death or probability of various cirrhosis complications. The design was a Delphi study: we attempted to obtain a consensus between experts via a series of questionnaires interspersed with group response feedback. We found substantial disparity between experts' answers, and no consensus was reached at the end of the process. Moreover, we obtained high death probability and high risk of hepatocellular carcinoma. The annual transition probability to death was estimated at between 10.1% and 61.5% and the annual probability of occurrence of hepatocellular carcinoma was estimated at between 16.8% and 58.9% (depending on age, gender, time spent in cirrhosis and cirrhosis severity). Our results show that eliciting expert opinions is not suited for determining the natural history of diseases due to practitioners' difficulties in evaluating quantities. Cognitive bias occurring during this type of study might explain our results.


Endothelial Notch activity promotes angiogenesis and osteogenesis in bone.
Blood vessel growth in the skeletal system and osteogenesis seem to be coupled, suggesting the existence of molecular crosstalk between endothelial and osteoblastic cells. Understanding the nature of the mechanisms linking angiogenesis and bone formation should be of great relevance for improved fracture healing or prevention of bone mass loss. Here we show that vascular growth in bone involves a specialized, tissue-specific form of angiogenesis. Notch signalling promotes endothelial cell proliferation and vessel growth in postnatal long bone, which is the opposite of the well-established function of Notch and its ligand Dll4 in the endothelium of other organs and tumours. Endothelial-cell-specific and inducible genetic disruption of Notch signalling in mice not only impaired bone vessel morphology and growth, but also led to reduced osteogenesis, shortening of long bones, chondrocyte defects, loss of trabeculae and decreased bone mass. On the basis of a series of genetic experiments, we conclude that skeletal defects in these mutants involved defective angiocrine release of Noggin from endothelial cells, which is positively regulated by Notch. Administration of recombinant Noggin, a secreted antagonist of bone morphogenetic proteins, restored bone growth and mineralization, chondrocyte maturation, the formation of trabeculae and osteoprogenitor numbers in endothelial-cell-specific Notch pathway mutants. These findings establish a molecular framework coupling angiogenesis, angiocrine signals and osteogenesis, which may prove significant for the development of future therapeutic applications.


Effectiveness of Lactobacillus reuteri in infantile colic and colicky induced maternal depression: a prospective single blind randomized trial.
Infant colic, excessive crying of unknown cause, is a major burden to families and effects about 10-30 % of infants. Despite decades of research, the exact cause and treatment of infant colic has remained elusive. The use of Lactobacillus reuteri (DSM 17938) in infant colic is somewhat controversial and hence, we designed this study to evaluate its efficacy in infantile colic. We recruited predominantly or exclusively breastfed infants, aged less than 4 months in a placebo controlled observational randomized study. Participants' were assigned to receive L. reuteri at a dose 10(8) colony forming units (n = 21) and placebo (n = 21). Placebo was an identical formulation without live micro-organisms. Treatment was given to subjects for 21 days and they were followed for 4 weeks. Treatment success (primary outcome), daily reduction in crying time, parent satisfaction and reduction in maternal depression (secondary outcomes) were assessed at the end of study period. Treatment success was observed in all infants (100 %) of the probiotic group while it was seen in 15.7 % of the placebo group. Mean daily crying time was more significantly reduced to 32.1 ± 8.3 min/day (P < 0.01) from 200.9 ± 6.3 min/day in the probiotic group as compared to the placebo group (120.6 ± 20.0 min/day). Moreover, throughout the study period, parent's satisfaction and improvement in maternal depression (Edinburgh postnatal depression scale) was also significantly higher in the probiotic group. In our study population, reduction in crying time was significant (P < 0.01) even during first week of initiation of therapy. We conclude that L. reuteri (DSM 17938) reduces daily crying time and maternal depression during infantile colic. We suggest L. reuteri may be a safe and efficacious option for reducing infant colic.


Design and fabrication of birefringent nano-grating structure for circularly polarized light emission.
Three different nano-grating structures are designed as phase retarders that can transform linearly polarized light to circularly polarized emission for the wavelengths of 488 nm, 532 nm and 632.8 nm, respectively. Gold based nano-grating structures with various periods are fabricated by utilizing laser interference lithography. The ellipticity of all circularly polarized emission can reach around 90% such that the structure has great potential in the applications of three-dimensional (3D) display. The effects of the slit width and metal thickness modulations are simulated by rigorous coupled wave analysis (RCWA) method. Besides, the field intensity and phase of the transmitted TM and TE waves are also simulated to understand their polarization characteristics.


Eight-plex iTRAQ analysis of variant metastatic human prostate cancer cells identifies candidate biomarkers of progression: An exploratory study.
Due to the heterogeneity in the biological behavior of prostate cancer, biomarkers that can reliably distinguish indolent from aggressive disease are urgently needed to inform treatment choices. We employed 8-plex isobaric Tags for Relative and Absolute Quantitation (iTRAQ), to profile the proteomes of two distinct panels of isogenic prostate cancer cells with varying growth and metastatic potentials, in order to identify novel biomarkers associated with progression. The LNCaP, LNCaP-Pro5, and LNCaP-LN3 panel of cells represent a model of androgen-responsive prostate cancer, while the PC-3, PC-3M, and PC-3M-LN4 panel represent a model of androgen-insensitive disease. Of the 245 unique proteins identified and quantified (>or=95% confidence; >or=2 peptides/protein), 17 showed significant differential expression (>or=+/-1.5), in at least one of the variant LNCaP cells relative to parental cells. Similarly, comparisons within the PC-3 panel identified 45 proteins to show significant differential expression in at least one of the variant PC-3 cells compared with parental cells. Differential expression of selected candidates was verified by Western blotting or immunocytochemistry, and corresponding mRNA expression was determined by quantitative real-time PCR (qRT-PCR). Immunostaining of prostate tissue microarrays for ERp5, one of the candidates identified, showed a significant higher immunoexpression in pre-malignant lesions compared with non-malignant epithelium (P < 0.0001, Mann-Whitney U-test), and in high Gleason grade (4-5) versus low grade (2-3) cancers (P < 0.05). Our study provides proof of principle for the application of an 8-plex iTRAQ approach to uncover clinically relevant candidate biomarkers for prostate cancer progression.


An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas.
To determine efficacy and safety of bevacizumab, a recombinant humanized antibody against vascular endothelial growth factor (VEGF), in the treatment of metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. In this single-arm phase II trial, 32 patients were enrolled and they received bevacizumab 15 mg/kg IV infusion in 21-day cycles. Patients had disease that was deemed not surgically resectable, Eastern Cooperative Oncology Group (ECOG) performance status of ≤1, adequate organ function and had not received any radiation treatment in the last 28 days. Of the 30 patients evaluated for efficacy and toxic effect, four (two angiosarcoma and two epithelioid hemangioendothelioma; 17%) had a partial response. Fifteen patients (11 angiosarcoma and 4 epithelioid hemangioendothelioma; 50%) showed stable disease with a mean time to progression of 26 weeks. Bevacizumab was well tolerated with only one grade 4 adverse event. Expected known toxic effects of the drug were manageable. Bevacizumab is an effective and well-tolerated treatment for metastatic or locally advanced angiosarcoma and epithelioid hemangioendotheliomas. Further phase III studies of bevacizumab in combination with other chemotherapeutic agents and/or radiation treatment are warranted.


Genetic and phenotypic characterization of a hybrid zone between polyandrous Northern and Wattled Jacanas in Western Panama.
Hybridization provides a unique perspective into the ecological, genetic and behavioral context of speciation. Hybridization is common in birds, but has not yet been reported among bird species with a simultaneously polyandrous mating system; a mating system where a single female defends a harem of males who provide nearly all parental care. Unlike simple polyandry, polyandrous mating is extremely rare in birds, with only 1% of bird species employing this mating system. Although it is classically held that females are "choosy" in avian hybrid systems, nearly-exclusive male parental care raises the possibility that female selection against heterospecific matings might be reduced compared to birds with other mating systems. We describe a narrow hybrid zone in southwestern Panama between two polyandrous freshwater waders: Northern Jacana, Jacana spinosa and Wattled Jacana, J. jacana. We document coincident cline centers for three phenotypic traits, mtDNA, and one of two autosomal introns. Cline widths for these six markers varied from seven to 142 km, with mtDNA being the narrowest, and five of the six markers having widths less than 100 km. Cline tails were asymmetrical, with greater introgression of J. jacana traits extending westward into the range of J. spinosa. Likewise, within the hybrid zone, the average hybrid index of phenotypic hybrids was significantly biased towards J. spinosa. Species distribution models indicate that the hybrid zone is located at the edge of a roughly 100 km wide overlap where habitat is predicted to be suitable for both species, with more westerly areas suitable only for spinosa and eastward habitats suitable only for J. jacana. The two species of New World jacanas maintain a narrow, and persistent hybrid zone in western Panama. The hybrid zone may be maintained by the behavioral dominance of J. spinosa counterbalanced by unsuitable habitat for J. spinosa east of the contact zone. Although the two parental species are relatively young, mitochondrial cline width was extremely narrow. This result suggests strong selection against maternally-inherited markers, which may indicate either mitonuclear incompatibilities and/or female choice against heterospecific matings typical of avian hybrid systems, despite jacana sex role reversal.


Wrong side of the tracks: the neglected human costs of transporting oil and gas.
The connection between human rights and climate change is most evident when examining carbon dioxide emissions that result from burning fossil fuels (e.g., sea level rise and displaced coastal cultures). However, the transport of fossil fuels also has human rights implications for human rights and climate change. This research focuses on the health and safety risks inflicted on those residents who are adjacent to the railways that ship fossil fuels along the US-Canada transportation corridors. Applying sociological and jurisprudential perspectives, we review the environmental/climate justice literature as it pertains to industrial transport corridors, documenting the forms of heightened risk imposed on those living along these transportation paths. Next, we develop an illustrative case study of Canada's worst rail catastrophe. In so doing, we provide evidence of a decades-long failure of US and Canadian regulators to prevent such disasters. We interpret that disaster through a human rights case law suggesting that States have an affirmative duty to protect their citizens from foreseeable disasters. Based on this analysis, we propose specific rail safety regulatory reforms. We argue that if the US and Canadian governments implement these regulations as required under human rights law, they can more effectively honor their obligations to their citizens who are paying a high human cost for the material benefits associated with increased energy production.


Effect of high-pressure homogenization preparation on mean globule size and large-diameter tail of oil-in-water injectable emulsions.
The effect of different high pressure homogenization energy input parameters on mean diameter droplet size (MDS) and droplets with > 5 μm of lipid injectable emulsions were evaluated. All emulsions were prepared at different water bath temperatures or at different rotation speeds and rotor-stator system times, and using different homogenization pressures and numbers of high-pressure system recirculations. The MDS and polydispersity index (PI) value of the emulsions were determined using the dynamic light scattering (DLS) method, and large-diameter tail assessments were performed using the light-obscuration/single particle optical sensing (LO/SPOS) method. Using 1000 bar homogenization pressure and seven recirculations, the energy input parameters related to the rotor-stator system will not have an effect on the final particle size results. When rotor-stator system energy input parameters are fixed, homogenization pressure and recirculation will affect mean particle size and large diameter droplet. Particle size will decrease with increasing homogenization pressure from 400 bar to 1300 bar when homogenization recirculation is fixed; when the homogenization pressure is fixed at 1000 bar, the particle size of both MDS and percent of fat droplets exceeding 5 μm (PFAT5) will decrease with increasing homogenization recirculations, MDS dropped to 173 nm after five cycles and maintained this level, volume-weighted PFAT5 will drop to 0.038% after three cycles, so the "plateau" of MDS will come up later than that of PFAT5, and the optimal particle size is produced when both of them remained at plateau. Excess homogenization recirculation such as nine times under the 1000 bar may lead to PFAT5 increase to 0.060% rather than a decrease; therefore, the high-pressure homogenization procedure is the key factor affecting the particle size distribution of emulsions. Varying storage conditions (4-25°C) also influenced particle size, especially the PFAT5.


Detection of Bisphenol A in aqueous medium by screen printed carbon electrodes incorporating electrochemical molecularly imprinted polymers.
Electrochemical molecularly imprinted polymers (e-MIPs) were for the first time introduced in screen-printed carbon electrodes (SPCE) as the sensing element for the detection of an organic pollutant. To play this sensing role, a redox tracer was incorporated inside the binding cavities of a cross-linked MIP, as a functional monomer during the synthesis step. Ferrocenylmethyl methacrylate was used for this purpose. It was associated with 4-vinylpyridine as a co-functional monomer and ethylene glycol dimethacrylate as cross-linker for the recognition of the endocrine disruptor, Bisphenol A (BPA), as a target. Microbeads of e-MIP and e-NIP (corresponding non-imprinted polymer) were obtained via precipitation polymerization in acetonitrile. The presence of ferrocene inside the polymers was assessed via FTIR and elemental analysis and the polymers microstructure was characterized by SEM and nitrogen adsorption/desorption experiments. Binding isotherms and batch selectivity experiments evidenced the presence of binding cavities inside the e-MIP and its high affinity for BPA compared to carbamazepine and ketoprofen. e-MIP (and e-NIP) microbeads were then incorporated in a graphite-hydroxyethylcellulose composite paste to prepare SPCE. Electrochemical properties of e-MIP-SPCE revealed a high sensitivity in the presence of BPA in aqueous medium compared to e-NIP-SPCE with a limit of detection (LOD) of 0.06 nM. Selectivity towards carbamazepine and ketoprofen was also observed with the e-MIP-SPCE.


First Report of Sweet potato chlorotic stunt virus and Sweet potato feathery mottle virus Infecting Sweet Potato in Spain.
Sweet potato chlorotic stunt virus (SPCSV), family Closteroviridae and Sweet potato feathery mottle virus (SPFMV), family Potyviridae are whitefly and aphid transmitted, respectively, which in double infections cause sweet potato virus disease (SPVD) that is a serious sweet potato (Ipomoea batatas Lam.) disease in Africa (2). During the past decade, sweet potato plants showing symptoms similar to SPVD have been observed in most areas of Spain. Nevertheless, not much information is available about the identity of the viruses infecting this crop in Spain. During the summer of 2002, sweet potato plants with foliar mosaic, stunting, leaf malformation, chlorosis, and ringspot symptoms were observed in several farms in Málaga (southern Spain) and Tenerife and Lanzarote (Canary Islands, Spain). Vine cuttings were collected from 21 symptomatic plants in Málaga and from eight plants on Lanzarote and six on Tenerife. Scions were grafted to the indicator hosts, Brazilian morning glory (I. setosa) and I. nil cv. Scarlett O'Hara. Three weeks after graft inoculations, all plants showed various degrees of mosaic, chlorosis, leaf malformation, and stunting. Four field collections (two from Málaga, one from Tenerife, and one from Lanzarote) with severe symptoms on I. setosa were selected for whitefly (Bemisia tabaci biotype Q) transmission experiments. Acquisition and transmission periods were 48 h. I. setosa was the acquisition host, and I. nil was the transmission host. For each isolate, groups of 10 whiteflies per I. nil plant were used. All I. nil plants used as transmission hosts with the four, field collections showed chlorosis and leaf malformation. Reverse-transcription polymerase chain reaction (RT-PCR) was performed on I. setosa (grafted with the four selected field collections) and I. nil plants (from the whitefly transmission experiments) with primers for the HSP70h gene of SPCSV. A 450-bp DNA fragment was obtained with all I. setosa and I. nil samples. Sequencing of the 450-bp DNA from two samples from Málaga yielded a nucleotide sequence with 98 to 99% similarity to the HSP70h gene of West African SPCSV isolates. Foliar samples from I. setosa, originally grafted with the 21 vine cuttings, were used for nitrocellulose membrane enzyme-linked immunosorbent assay (NCM-ELISA) testing with antiserum specific to SPFMV-RC (provided by J. Moyer, North Carolina State University, Raleigh). Positive control was sap extract from I. setosa that was infected with the common strain of SPFMV. Procedures for NCM-ELISA were as described (4). NCM-ELISA testing suggested that SPFMV was present in all samples. RT-PCR was conducted with degenerate primers POT1/POT2 (1). The nucleotide sequence that was amplified by these two primers spans part of the NIb protein and part of the coat protein gene of potyviruses. All samples yielded the expected 1.3-kb DNA. Sequencing of the RT-PCR products of two isolates from Malaga and sequence comparisons yielded nucleotide sequences with 97% similarity to two East African isolates (Nam 1 and Nam 3) of SPFMV (3). These results confirm the presence of SPCSV and SPFMV in sweet potato in Spain. References: (1) D. Colinet and J. Kummert. J. Virol. Methods 45:149, 1993. (2) R. W. Gibson et al. Plant Pathol. 47:95, 1998. (3) J. F. Kreuze et al. Arch. Virol. 145:567, 2000. (4) E. R. Souto et al. Plant Dis. 87:1226, 2003.


Mitogen-induced tyrosine phosphorylation of 41 kDa and 43 kDa proteins. Potential role in integrating multiple mitogenic signalling pathways.
We have examined the possible involvement of pertussis toxin (PT)-sensitive GTP-binding protein and protein kinase C (PKC) in mitogen-induced tyrosine phosphorylation of the 41 kDa and 43 kDa cytosol proteins using PT-pretreated (inactivation of PT-sensitive GTP-binding protein) or phorbol 12-myristate 13-acetate (PMA)-pretreated (depletion of PKC) mouse fibroblasts. The effects of the inactivation of PT-sensitive GTP-binding protein and the depletion of PKC on mitogen-stimulated tyrosine phosphorylation of the proteins were similar and varied significantly and systematically in response to growth factors. The important finding was that such inhibitory effects of PT-sensitive GTP-binding protein inactivation and PKC depletion on protein tyrosine phosphorylation induced by each mitogen always correlated well with their inhibitory effects on each mitogen-stimulated DNA synthesis. Although the extent of platelet-derived-growth-factor-induced phosphorylation of the proteins was decreased to approx. 50% in PT- and PMA-pretreated cells compared with native cells, protein phosphorylation itself was not affected and occurred at identical sites on each protein in native, PT- and PMA-pretreated cells. These results suggest that: (1) 41 kDa and 43 kDa proteins are located downstream of PT-sensitive GTP-binding protein and PKC in the mitogenic signalling pathways of growth factors, (2) protein phosphorylation occurs via a cascade of events which includes the activation of the receptor tyrosine kinases, PKC and other unidentified kinase(s) which directly participate(s) in the phosphorylation of the 41 kDa and 43 kDa proteins, and (3) their phosphorylation may play an important role in integrating multiple mitogenic signalling pathways.


Transcriptional mechanisms of WNT5A based on NF-kappaB, Hedgehog, TGFbeta, and Notch signaling cascades.
WNT5A is a cancer-associated gene involved in invasion and metastasis of melanoma, breast cancer, pancreatic cancer, and gastric cancer. WNT5A transduces signals through Frizzled, ROR1, ROR2 or RYK receptors to beta-catenin-TCF/LEF, DVL-RhoA-ROCK, DVL-RhoB-Rab4, DVL-Rac-JNK, DVL-aPKC, Calcineurin-NFAT, MAP3K7-NLK, MAP3K7-NF-kappaB, and DAG-PKC signaling cascades in a context-dependent manner. SNAI1 (Snail), CD44, G3BP2, and YAP1 are WNT5A target genes. We and other groups previously reported that IL6- or LIF-induced signaling through JAK-STAT3 signaling cascade is involved in WNT5A upregulation (STAT3-WNT5A signaling loop). Here, refined integrative genomic analyses of WNT5A were carried out to elucidate other mechanisms of WNT5A transcription. The WNT5A gene was found to encode two isoforms by using alternative first exons 1A and 1B. Quadruple Smad-binding elements (SBEs), single Sp1-binding site (GC-box), PPARgamma-binding site, C/EBP-binding site and bHLH-binding site within the promoter A region, 5'-adjacent to exon 1A, were conserved in human WNT5A, chimpanzee WNT5A, mouse Wnt5a, and rat Wnt5a. NF-kappaB-binding site, CUX1-binding site, double SBEs and double GC-boxes within the promoter B region, 5'-adjacent to exon 1B, were conserved in mammalian WNT5A orthologs. Quadruple FOX-binding sites and double SBEs within ultra-conserved intron 1 were also conserved in mammalian WNT5A orthologs. Conserved NF-kappaB-binding site within the WNT5A promoter B region elucidated the mechanisms that TNFalpha and toll-like receptor (TLR) signals upregulate WNT5A via MAP3K7. Quadruple FOX-binding sites rather than GLI-binding site revealed that Hedgehog signals induce WNT5A upregulation indirectly via FOX family members, such as FOXA2, FOXC2, FOXE1, FOXF1 and FOXL1. TGFbeta signals were found to upregulate WNT5A expression directly through the Smad complex, and also indirectly through Smad-induced CUX1 and MAP3K7-mediated NF-kappaB. Together these facts indicate that WNT5A is transcribed based on multiple mechanisms, such as NF-kappaB, Hedgehog, TGFbeta, and Notch signaling cascades.


Competing ultrafast energy relaxation pathways in photoexcited graphene.
For most optoelectronic applications of graphene, a thorough understanding of the processes that govern energy relaxation of photoexcited carriers is essential. The ultrafast energy relaxation in graphene occurs through two competing pathways: carrier-carrier scattering, creating an elevated carrier temperature, and optical phonon emission. At present, it is not clear what determines the dominating relaxation pathway. Here we reach a unifying picture of the ultrafast energy relaxation by investigating the terahertz photoconductivity, while varying the Fermi energy, photon energy and fluence over a wide range. We find that sufficiently low fluence (≲4 μJ/cm(2)) in conjunction with sufficiently high Fermi energy (≳0.1 eV) gives rise to energy relaxation that is dominated by carrier-carrier scattering, which leads to efficient carrier heating. Upon increasing the fluence or decreasing the Fermi energy, the carrier heating efficiency decreases, presumably due to energy relaxation that becomes increasingly dominated by phonon emission. Carrier heating through carrier-carrier scattering accounts for the negative photoconductivity for doped graphene observed at terahertz frequencies. We present a simple model that reproduces the data for a wide range of Fermi levels and excitation energies and allows us to qualitatively assess how the branching ratio between the two distinct relaxation pathways depends on excitation fluence and Fermi energy.


Schistosomiasis mansoni in Yemeni in California: duration of infection, presence of disease, therapeutic management.
Investigations of schistosomiasis mansoni in 218 Yemeni agricultural workers in the San Joaquin Valley of California revealed a prevalence of 56%. In those infected, quantitative egg counts performed by the Kato thick smear method revealed that 57% had light infections (1-100 eggs/g), 27% moderate infections (101-400 eggs/g), and 16% heavy infections (greater than 400 eggs/g; mean--918 eggs/g). The Yemeni had been migrating to the USA for the past 20 years, a period in which the prevalence of schistosomiasis had remained constant in the Yemen. The prevalence of schistosomiasis in those who had been away from Yemen for less than 5 years was 59% with a mean egg output of 236 eggs/g, but in those away for more than 5 years (up to 20 years) it was 32% with a mean egg output of 75% eggs/g. This is in spite of the fact that 75% of the latter had returned to Yemen for short visits. Statistical analysis by the Fisher's exact probability test revealed a significantly lower egg output in those away from Yemen more than 5 years. On the basis of these findings the mean life span of the Yemen strain of Schistosoma mansoni in man was estimated to be between 5 and 10 years. The presence of disease was assessed in this population by traditional medical means without prior knowledge of the status of the infection in the individuals examined. Under these circumstances, there were no differences in symptoms such as weakness, diarrhea and abdominal pain among the uninfected proportion of the population, total infected group and a small subgroup of those most heavily infected. None of the patients had hepatomegaly and only two had splenomegaly--one lightly and the other heavily infected. Because of the toxicity of antischistosomal drugs and the lack of treatment facilities only the 22 most heavily infected (greater than 200 eggs/g) of the 122 individuals with schistosomiasis mansoni were treated with niridazole. In addition the two individuals with splenomegaly were treated with antimony dimercaptosuccinate. Side effects, though common, were not severe. Although follow-up in this migrant population was poor the nine patients examined 3 to 7 months after treatment showed a mean decrease in egg output of 97%.


Use of Curcumin Mouthrinse in Radio-Chemotherapy Induced Oral Mucositis Patients: A Pilot Study.
Oral Mucositis is a complex and distinct pathobiologic entity resulting in injuries in mucosa that is a common complication in cancer patients undergoing chemotherapy (CT) and radiation therapy (RT). Phytochemicals, such as Curcumin, turmeric extract, has attracted great attention for its therapeutic benefits in clinical oncology due to its chemopreventive, antitumoral, chemosensibilizing and radiosensibilizing activities against various types of cancers and the complications associated with their management. To evaluate the efficacy and safety of curcumin mouthwash in the management of Oral Mucositis in cancer patients undergoing radio-chemotherapy. The research group consisted of 20 adult cancer patients undergoing radio-chemotherapy at the Regional Oncology Centre, who were evaluated for signs and symptoms of oral mucositis and then randomly divided into two groups. Standard preventive oral care i.e. chlorhexidine mouthwash 0.2% was given to one group while the other group was provided with freshly prepared curcumin mouthwash; each to be used thrice daily. Oral mucositis was assessed at days 0, 10 and 20. The World Health Organization (WHO) scale, the Oral Mucositis Assessment Scale (OMAS), and a Numerical Rating Scale (NRS; patient reporting scale of 0-10) were used. Adverse events were tracked. Descriptive statistics, Independent sample t-test and repeated measure ANOVA test were performed. Statistically significant difference was found in the NRS (p=0.000), Erythema (p=0.050), ulceration (p=0.000) and WHO scores (p=0.003) between the two groups. Curcumin was found to be better than chlorhexidine mouth wash in terms of rapid wound healing and better patient compliance in management of radio-chemotherapy induced oral mucositis. No oral or systemic complications were reported.


An update on trials of novel lipid-lowering drugs.
A number of novel trials have assessed the efficacy of new lipid-lowering therapies in cardiovascular disease (CVD). Proprotein convertase subtilisin kexin-9 inhibitors reduce low-density lipoprotein cholesterol (LDL-C) by 50-55%. A CVD outcome trial in patients with acute coronary syndromes with evolocumab achieved a LDL-C of 0.8 mmol/l (31 mg/dl) and a 20% relative risk reduction in CVD events in 2.2 years. Cholesterol ester transfer protein inhibitors raise high-density lipoprotein cholesterol and can lower LDL-C. Anacetrapib reduced coronary artery disease events by 7%, but not wider composite CVD outcomes, in a population with chronic CVD with pretreatment LDL-C of 1.6 mmol/l (62 mg/dl). The conflicting outcomes of cholesterol ester transfer protein inhibitor trials means these compounds are not being developed further. Trials using lipid drugs targeting inflammation have previously been generally unsuccessful, but recent data on the interleukin-1B receptor antagonist canakinumab has proven the concept of intervention on inflammation in atherosclerosis by showing a reduction in acute coronary interventions, but at the predictable cost of increased infections. Despite the success of proprotein convertase subtilisin kexin-9 inhibition, the ability to achieve low LDL-C with off-patent medications and the costs of novel therapies will limit their use even in high-risk patients and confine them to the highest-risk sub-groups of patients.


The cation-chloride cotransporter, masBSC, is widely expressed in Manduca sexta tissues.
Cation-chloride cotransporters, including the Na-K-Cl cotransporter, play an important role in epithelial ion transport in insects. We have determined the tissue distribution of Manduca sexta bumetanide sensitive cotransporter (masBSC), a putative Na-K-Cl cotransporter that was originally cloned from M. sexta Malpighian tubules. We developed a polyclonal antibody (M6) against a C-terminal fragment of masBSC. masBSC protein was detected by M6 at an apparent molecular mass of approximately 220kDa in M. sexta foregut, midgut, hindgut, Malpighian tubule, salivary gland, fat body, trachea, and nerve cord. Higher expression was observed in the foregut than in other tissues. M6 stained the apical membrane of midgut epithelial cells in cross-sections of third instar larvae. The transcript of masBSC was detected by RT-PCR in midgut, Malpighian tubule, hindgut, trachea, nerve cord, and fat bodies. Taken together, these findings demonstrate that masBSC is widely expressed in M. sexta. While the specific function of masBSC remains unknown, the wide distribution indicates a role of masBSC in a broad range of tissues.


Health care utilisation and attitudes towards health care in subjects reporting environmental annoyance from electricity and chemicals.
Environmentally intolerant persons report decreased self-rated health and daily functioning. However, it remains unclear whether this condition also results in increased health care costs. The aim of this study was to describe the health care consumption and attitudes towards health care in subjects presenting subjective environmental annoyance in relation to the general population, as well as to a group with a well-known disorder as treated hypertension (HT). Methods. Postal questionnaire (n = 13 604) and record linkage with population-based register on health care costs. Results. Despite significantly lower subjective well being and health than both the general population and HT group, the environmentally annoyed subjects had lower health care costs than the hypertension group. In contrast to the hypertension group, the environmentally annoyed subjects expressed more negative attitudes toward the health care than the general population. Conclusions. Despite their impaired subjective health and functional capacity, health care utilisation costs were not much increased for the environmentally annoyed group. This may partly depend on negative attitudes towards the health care in this group.


A double-blind, randomized, placebo-controlled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania.
The therapeutics for bipolar disorders are still far from adequate, and new options with improved effectiveness, safety, and tolerability in a wide range of patients are necessary. Preliminary data have suggested a role for dysfunctions targeting the purinergic system in mood disorders. This study aimed to evaluate the efficacy and tolerability of the purinergic agents allopurinol and dipyridamole combined with lithium in bipolar mania. A randomized, placebo-controlled, double-blind study was performed in adult inpatients (N = 180) with a DSM-IV-TR diagnosis of bipolar I disorder, current episode manic with or without psychotic features (rapid cyclers and mixed episodes were not included). No antipsychotic agent was used during the study. Subjects were given fixed oral doses of either allopurinol 600 mg/day (N = 60), dipyridamole 200 mg/day (N = 60), or placebo (N = 60) added to lithium for 4 weeks. Subjects were rated at baseline and days 7, 14, 21, and 28 using the Young Mania Rating Scale (YMRS) as the primary efficacy measure. The study was conducted between September 2003 and September 2006. Allopurinol resulted in greater mean reductions in YMRS scores from baseline to day 21 (p < .001) and day 28 (p = .003) compared with placebo using a linear model analysis (d = 0.32, 95% CI = 0.07 to 0.57). Remission rates were significantly higher for allopurinol compared with dipyridamole and placebo (p = .008). Lithium showed a significant antimanic efficacy even in the placebo group. Decrease in plasma uric acid levels showed a significant positive association with antimanic effects in the allopurinol group (p < .001). Allopurinol is clinically effective and well-tolerated adjunctively with lithium in manic episodes and may represent an alternative approach in the treatment of acute mania, especially for those presenting tolerability and safety issues with antipsychotics. The present results strongly support the involvement of the purinergic system in the pathophysiology and therapeutics of bipolar disorder. Further placebo-controlled studies with allo-purinol compared with standard mood stabilizers in mania and maintenance are warranted. clinicaltrials.gov Identifier: NCT00560079.


Evaluation of daily living tasks: the home care advantage.
Occupational therapists working in home care have an advantage over those working in other settings because they can observe the influence of the naturalistic context on task performance. However, to use this advantage, therapists working in home care must use an evaluation approach that enables them to capture the client-task-context transaction. In this article, we discuss the ability of four "evaluation approaches"--norm-referenced, criterion-referenced, dynamic, informal--to provide information about the client-task-context transaction that therapists need in order to plan effective intervention. The potential of each approach for identifying clients' performance problems, suggesting etiologies, determining rehabilitation potential, and guiding intervention is analyzed, and the appropriateness of each approach for application in the home is appraised. This analysis highlights the utility of combining the criterion-referenced and dynamic assessment approaches for use in home care. A sequential process for integrating these two approaches is provided, and the proposed outcomes to be obtained from this process are identified.


Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.


Stomatal responses to changes in vapor pressure deficit reflect tissue-specific differences in hydraulic conductance.
The vapor pressure deficit (D) of the atmosphere can negatively affect plant growth as plants reduce stomatal conductance to water vapor (g(wv)) in response to increasing D, limiting the ability of plants to assimilate carbon. The sensitivity of g(wv) to changes in D varies among species and has been correlated with the hydraulic conductance of leaves (K(leaf) ), but the hydraulic conductance of other tissues has also been implicated in plant responses to changing D. Among the 19 grass species, we found that K(leaf) was correlated with the hydraulic conductance of large longitudinal veins (K(lv), r(2) = 0.81), but was not related to K(root) (r(2) = 0.01). Stomatal sensitivity to D was correlated with K(leaf) relative to total leaf area (r(2) = 0.50), and did not differ between C3 and C4 species. Transpiration (E) increased in response to D, but 8 of the 19 plants showed a decline in E at high D, indicative of an 'apparent feedforward' response. For these individuals, E began to decline at lower values of D in plants with low K(root) (r(2) = 0.72). These results show the significance of both leaf and root hydraulic conductance as drivers of plant responses to evaporative demand.


Development and validation of a screen for specialized discharge planning services.
There is no rigorously developed and empirically validated screening tool to identify, early in the hospital stay, those adults who will use specialized hospital discharge planning services. To develop and validate a screen using hospital admission clinical data that discriminates between adults who use and do not use specialized discharge planning services. Subjects consisted of prospectively sampled adult patients admitted to two hospitals located in a Midwestern United States city in 1998 (tool development sample, n = 991) and 2002 (validation sample, n = 303). Variables suggestive of being predictive of use of specialized hospital discharge planning services were identified from the literature and were obtained from direct participant interviews, record review, and administrative databases. The outcome was a documented referral for involvement of specialized discharge planning personnel with the patient's plan of care and was identified from review of hospital records. Of 24 variables examined, only age, disability, living alone, and self-rated walking limitation were jointly predictive of use of specialized discharge planning services in the development sample. Standardized coefficients from the joint model were used to estimate a screening score. A cut-point was derived and had a sensitivity of 75% and specificity of 78% in the development sample. The screen performed equally well in the validation sample and the development sample. A screening tool consisting of a limited number of characteristics readily available early in the hospital stay that were shown to be highly predictive of the use of specialized discharge planning services was developed. The application of such a tool will hopefully assist providers to deploy services appropriately and in a timely fashion.


[Pulmonary hypertension in autoimmune rheumatic diseases].
Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a specific autoimmune rheumatic disease, is a risk factor for the development of pulmonary hypertension. One hundred and thirteen Italian patients with connective tissue diseases (105 females, 8 males), aged 19 to 83 yrs, entered the study. Fifty-one had systemic sclerosis (SSc): 49 were females, 2 males, aged 34 to 83 yrs; 41 had limited cutaneous SSc, 8 diffuse cutaneous SSc, and 2 SSc sine scleroderma. Thirty-three patients had systemic lupus erythematosus (SLE): all but one were females, their age ranged from 19 to 82 yrs. Twenty-five had rheumatoid arthritis (RA): 21 females, 4 males, aged 26 to 45 yrs. Three females and one male, 51-77 yrs, had mixed connective tissue disease (MCTD). Systolic pulmonary arterial pressure (SPAP) was assessed by Doppler echocardiography. Twenty three patients had pulmonary hypertension, which was more frequent in MCTD than in SLE (75% vs 6.1%, p=0.0002) or in AR (20%, p=0.0313). Pulmonary hypertension was more frequent in SSc than in SLE (25.5% vs 6.1%, p=0.0028) and in limited than in diffuse SSc (21.6% vs 3.9%). SPAP was significantly related to age (r=0.35, p=0.0275), with patients with pulmonary hypertension older than patients with normal SPAP (66+/-13 vs 52+/-16 yrs, p=0.0003). These data show a significant association between pulmonary hypertension and autoimmune rheumatic diseases. Therefore, pulmonary hypertension assessment seems mandatory, at least in MCTD and SSc. However, more studies are needed to clarify the relationship between age and pulmonary hypertension and to verify whether the low prevalence of pulmonary hypertension we found in our SLE patients is related or not to their lower age.