Prometastatic NEDD9 Regulates Individual Cell Migration via Caveolin-1-Dependent Trafficking of Integrins.
The dissemination of tumor cells relies on efficient cell adhesion and migration, which in turn depends upon endocytic trafficking of integrins. In the current work, it was found that depletion of the prometastatic protein, NEDD9, in breast cancer cells results in a significant decrease in individual cell migration due to impaired trafficking of ligand-bound integrins. NEDD9 deficiency does not affect the expression or internalization of integrins but heightens caveolae-dependent trafficking of ligand-bound integrins to early endosomes. Increase in mobility of ligand-bound integrins is concomitant with an increase in tyrosine phosphorylation of caveolin-1 (CAV1) and volume of CAV1-vesicles. NEDD9 directly binds to CAV1 and colocalizes within CAV1 vesicles. In the absence of NEDD9, the trafficking of ligand-bound integrins from early to late endosomes is impaired, resulting in a significant decrease in degradation of ligand-integrin complexes and an increase in recycling of ligand-bound integrins from early endosomes back to the plasma membrane without ligand disengagement, thus leading to low adhesion and migration. Reexpression of NEDD9 or decrease in the amount of active, tyrosine 14 phosphorylated (Tyr14) CAV1 in NEDD9-depleted cells rescues the integrin trafficking deficiency and restores cellular adhesion and migration capacity. Collectively, these findings indicate that NEDD9 orchestrates trafficking of ligand-bound integrins through the attenuation of CAV1 activity. This study provides valuable new insight into the potential therapeutic benefit of NEDD9 depletion to reduce dissemination of tumor cells and discovers a new regulatory role of NEDD9 in promoting migration through modulation of CAV1-dependent trafficking of integrins.


High genetic diversity and population differentiation in Clarias gariepinus of Yala Swamp: evidence from mitochondrial DNA sequences.
In order to improve the conservation and sustainable utilization of the African catfish Clarias gariepinus of the Yala Swamp in Kenya, genetic diversity and population structure of Lakes Kanyaboli and Namboyo populations of the species were studied using DNA sequences of the mitochondrial D-loop control region. Genetic diversity inferred as haplotype and nucleotide diversities and number of singletons and shared haplotypes was higher in the Lake Kanyaboli population (LKG) than the Lake Namboyo population (LNG) of C. gariepinus. Thirty-one haplotypes were inferred, of which 25 (80·6%) were private or singletons, while only six (19·4%) haplotypes were shared between LKG and LNG. Both populations were differentiated, with FST value that was significantly different from zero (P < 0·05). Two clusters were inferred both from the maximum likelihood tree and the spanning networks of phylogenetic relationships of haplotypes. Mismatch distribution for total sample was multi-modal but individually, distributions were uni-modal in LKG, but multimodal in LNG. The mean ± s.d. raggedness index for both populations was 0·085 ± 0·098 and not significantly different from zero (P > 0·05). Individual raggedness indices were 0·015 and 0·154 for LKG and LNG respectively. Fu's Fs was negative for both populations, with LKG recording -14·871, while LNG had -2·565, significantly different from zero for LKG (P < 0·05), but the value for LNG was not significant (P > 0·05). Tajima's D was negative for both populations, with LKG recording -1·734, while LNG had -1·136. Standardized square differences (SSD) were 0·001 for LKG and 0·048 for LNG and non-significant between them (P > 0·05). Values between all populations were also not significantly different (P > 0·05), mean ± s.d. SSD 0·025 ± 0·033.


Continuing-education needs of the currently employed public health education workforce.
This study examined the continuing-education needs of the currently employed public health education workforce. A national consensus panel of leading health educators from public health agencies, academic institutions, and professional organizations was convened to examine the forces creating the context for the work of public health educators and the competencies they need to practice effectively. Advocacy; business management and finance; communication; community health planning and development, coalition building, and leadership; computing and technology; cultural competency; evaluation; and strategic planning were identified as areas of critical competence. Continuing education must strengthen a broad range of critical competencies and skills if we are to ensure the further development and effectiveness of the public health education workforce.


Impact of titanium dioxide on androgen receptors, seminal vesicles and thyroid hormones of male rats: possible protective trial with aged garlic extract.
The aim of this study was to evaluate the effect of titanium dioxide (TiO2 ), a widely produced and consumed pigment in various food products, on the post-natal development of male albino rat seminal vesicle and thyroid hormones, as well as to evaluate the ameliorative effect of aged garlic extract (AGE) on TiO2 -induced alterations. Forty male rat pups (3 weeks old) were divided into four equal groups. The 1st group received distilled water orally (control group), 2nd group was given 2 ml kg-1 AGE, 3rd group was administered TiO2 (5 g kg-1 BW) day after day for 65 days, and the 4th group administered AGE 6 hr prior to TiO2 gavage. TiO2 -exposed rats showed nonsignificant changes in the serum testosterone, TSH, T3 and T4 , while serum glucose showed a significant decrease. Androgen receptor (AR) mRNA expression was significantly down-regulated and weak signal of AR immune labelling. Histopathologically, the epithelium cell lining of seminal vesicles showed focal areas of necrosis and fibrous tissue with the prominent fibrous stroma of the atrophied glands. Meanwhile, AGE supplementation ameliorated the deleterious effects of TiO2 intoxication through protecting the tissues from oxidative stress caused by TiO2 . In summary, oral administration of TiO2 resulted in abnormal developmental events in male rat seminal vesicle and AGE able to reduce TiO2 toxicity.


Synergy between antibiotics and natural agents results in increased antimicrobial activity against Staphylococcus epidermidis.
Staphylococcus epidermidis is one of the most frequent causes of biofilm-associated infections on indwelling medical devices. With the emergence of methicillin-resistant S. epidermidis (MRSE), there is an urgent need to discover novel active agents against a range of Gram-positive pathogens. We screened the clinical isolates of S. epidermidis for susceptibility/resistance against commonly prescribed antibiotics. Furthermore, we tested some natural agents alone and in combination with antibiotics to find possible synergistic antimicrobial effects. S. epidermidis clinical isolates were screened for susceptibility/resistance against vancomycin, erythromycin, tetracycline, chloramphenicol, ampicillin, ofloxacin, cephalexin, and gentamicin using the Kirby-Bauer disk diffusion method. The antimicrobial potential of Camellia sinensis, Juglans regia, and Hippophae rhamnoides alone and in combination with antibiotics were examined using the disk diffusion method, where the antimicrobial potential activity was measured in terms of formation of zones of inhibition. Most S. epidermidis isolates were found to be resistant to one or more antibiotics. Gentamycin and ofloxacin were found to be the most effective antibiotics against S. epidermidis isolates. Extracts of Hippophae rhamnoides, Juglans regia, and Camellia sinensis were found to be equally effective against S. epidermidis isolates. In combination with antibiotics, these extracts exhibited appreciable synergistic activity; the highest synergistic activity was observed with erythromycin and cephalexin. In the case of cephalexin, a reversion in resistance was observed. The plant extracts used in the study exhibited additive and synergistic antibacterial activity against S. epidermidis, hence providing an effective alternative to deal with the problem of multidrug resistance.


Laboratory technique for the measurement of thermal-emission spectra of greenhouse gases: CFC-12.
A new technique has been developed to make possible the laboratory study of the infrared-emission spectra of gases of atmospheric interest. The thermal-emission spectra are in local thermodynamic equilibrium, just as they are in the atmosphere, and are not chemiluminescent. Demonstration results obtained by the use of this new technique are presented for dichlorodifluoromethane (CFC-12) at a pressure of 0.5 Torr in a cell with a path length of 5 cm. The measured cell spectra have been compared with simulations with the FASCD3P radiation code. The measurements of the emission spectra of radiatively active gases may be important for the atmospheric greenhouse effect and global warming.


Temporal changes in incidence of dialysis-requiring AKI.
The population epidemiology of AKI is not well described. Here, we analyzed data from the Nationwide Inpatient Sample, a nationally representative dataset, to identify cases of dialysis-requiring AKI using validated International Classification of Diseases, Ninth Revision (ICD-9) codes. From 2000 to 2009, the incidence of dialysis-requiring AKI increased from 222 to 533 cases per million person-years, averaging a 10% increase per year (incidence rate ratio=1.10, 95% CI=1.10-1.11 per year). Older age, male sex, and black race associated with higher incidence of dialysis-requiring AKI. The rapid increase in incidence was evident in all age, sex, and race subgroups examined. Temporal changes in the population distribution of age, race, and sex as well as trends of sepsis, acute heart failure, and receipt of cardiac catheterization and mechanical ventilation accounted for about one third of the observed increase in dialysis-requiring AKI among hospitalized patients. The total number of deaths associated with dialysis-requiring AKI rose from 18,000 in 2000 to nearly 39,000 in 2009. In conclusion, the incidence of dialysis-requiring AKI increased rapidly in all patient subgroups in the past decade in the United States, and the number of deaths associated with dialysis-requiring AKI more than doubled.


Phytoestrogens for menopausal vasomotor symptoms.
Vasomotor symptoms, such as hot flushes and night sweats, are very common during the menopausal transition. Hormone therapy has traditionally been used as a highly effective treatment, but concerns about increased risk of some chronic diseases have markedly increased the interest of women in alternative treatments. Some of the most popular of these treatments are foods or supplements enriched with phytoestrogens-plant-derived chemicals that have estrogenic action. To assess the efficacy, safety and acceptability of food products, extracts and dietary supplements containing high levels of phytoestrogens when compared with no treatment, placebo or hormone therapy for the amelioration of vasomotor menopausal symptoms (such as hot flushes and night sweats) in perimenopausal and postmenopausal women. Searches targeted the following electronic databases: the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of randomised trials (29 July 2013), the Cochrane Register of Controlled Trials (CENTRAL; 29 July 2013), MEDLINE (inception to 29 July 2013), EMBASE (inception to 29 July 2013), AMED (1985 to 29 July 2013), PsycINFO (inception to 29 July 2013) and CINAHL (inception to 29 July 2013). Attempts were made to access grey literature by sending letters to pharmaceutical companies and performing searches of ongoing trial registers. Reference lists of included trials were also searched. Studies were included if they were randomised, included perimenopausal or postmenopausal participants with vasomotor symptoms (hot flushes or night sweats), lasted at least 12 weeks and provided interventions such as foods or supplements with high levels of phytoestrogens (not combined with other herbal treatments). Trials that included women who had breast cancer or a history of breast cancer were excluded. Selection of trials, extraction of data and assessment of quality were undertaken by at least two review authors. Most trials were too dissimilar for their results to be combined in a meta-analysis, so these findings are provided in narrative 'Summary of results' tables. Studies were grouped into broad categories: dietary soy, soy extracts, red clover extracts, genistein extracts and other types of phytoestrogens. Five trials used Promensil, a red clover extract; results of these trials were combined in a meta-analysis, and summary effect measures were calculated. A total of 43 randomised controlled trials (4,364 participants) were included in this review. Very few trials provided data suitable for inclusion in a meta-analysis. Among the five trials that yielded data assessing the daily frequency of hot flushes suitable for pooling, no significant difference overall was noted in the incidence of hot flushes between participants taking Promensil (a red clover extract) and those given placebo (mean difference (MD) -0.93, 95% confidence interval (CI) -1.95 to 0.10, I(2) = 31%). No evidence indicated a difference in percentage reduction in hot flushes in two trials between Promensil and placebo (MD 20.15, 95% CI -12.08 to 52.38, I(2) = 82%). Four trials that were not combined in meta-analyses suggested that extracts with high (> 30 mg/d) levels of genistein consistently reduced the frequency of hot flushes. Individual results from the remaining trials were compared in broad subgroups such as dietary soy, soy extracts and other types of phytoestrogens that could not be combined. Some of these trials found that phytoestrogen treatments alleviated the frequency and severity of hot flushes and night sweats when compared with placebo, but many trials were small and were determined to be at high risk of bias. A strong placebo effect was noted in most trials, with a reduction in frequency ranging from 1% to 59% with placebo. No indication suggested that discrepant results were due to the amount of isoflavone in the active treatment arm, the severity of vasomotor symptoms or trial quality factors. Also, no evidence indicated that these treatments caused oestrogenic stimulation of the endometrium or the vagina or other adverse effects when used for up to two years. No conclusive evidence shows that phytoestrogen supplements effectively reduce the frequency or severity of hot flushes and night sweats in perimenopausal or postmenopausal women, although benefits derived from concentrates of genistein should be further investigated.


How important is the duration of the brain death period for the outcome in kidney transplantation?
In kidney transplantation, graft survival using grafts from donation after brain death (DBD) donors is inferior to results after living donation. However, little is known about the effect of the duration of brain death (BDdur) on outcome after transplantation. This is a retrospective Organ Procurement and Transplant Network analysis using kidney donor and recipient data from 1994 to 2006. BDdur was calculated as the period between brain death declaration and aortic cross clamp. Effects of BDdur on delayed graft function (DGF), acute rejection and graft failure were calculated using binary logistic regression and Cox regression models. Median BDdur was 23.8 h. Longer BDdur decreased the risk for DGF and 1- and 3-year graft failure slightly, but not for acute rejection. In multivariate analysis, donor age and acute rejection were confounders. However, in a multivariate subgroup analysis of donors aged ≤ 55 years BDdur independently predicted DGF; each hour of BDdur decreasing the risk of DGF with 0.4% (P = 0.008). Longer BDdur is not detrimental and in fact slightly beneficial in DBD donors ≤ 55 years of age, reducing the chance of DGF in the recipient. This finding may have an impact on organ retrieval procedures, as no rush but rather an improved donor management prior to retrieval will benefit donor kidney viability.


Risk factors for infection with soil-transmitted helminths during an integrated community level water, sanitation, and hygiene and deworming intervention in Timor-Leste.
Water, sanitation and hygiene interventions have been advocated as important complements to deworming programs to improve soil-transmitted helminth control. Evidence for the impact of water, sanitation and hygiene on soil-transmitted helminth infections is mixed, and based mainly on cross-sectional studies. In this study, we assessed associations between individual- and household-level water, sanitation and hygiene variables and soil-transmitted helminth infections, using data collected during the 2 year follow-up study period of the WASH for WORMS randomised controlled trial in Timor-Leste. Data were collected across four surveys, conducted at 6 monthly intervals in 23 communities. We analysed water, sanitation and hygiene and sociodemographic variables as risk factors for infection with Necator americanus, Ascaris spp., and undifferentiated soil-transmitted helminth infection, using generalised linear mixed models to account for clustering at community, household and participant levels. Water, sanitation and hygiene risk factors were examined both concurrently and with a 6 month lag period that coincided with the most recent deworming. The analysis included 2333 participants. Factors associated with N. americanus infection included age group, male sex (adjusted odds ratio (aOR) 3.1, 95% confidence interval (CI) 2.4-4.2), working as a farmer (aOR 1.7, 95% CI 1.2-2.4), and completing secondary school or higher (aOR 0.29, 95% CI 0.16-0.53). Risk factors for Ascaris spp. infection included age group, living in a dwelling with more than six people (aOR 1.6, 95% CI 1.1-2.3), having a tube well or borehole as the household water source (aOR 3.7, 95% CI 1.3-10.8), and using a latrine shared between households 6 months previously (aOR 2.3, 95% CI 1.2-4.3). Handwashing before eating was protective against infection with any soil-transmitted helminth (aOR 0.79, 95% CI 0.65-0.95). In the context of regular deworming, few water, sanitation and hygiene-related factors were associated with soil-transmitted helminth infections. Future research examining the role of water, sanitation and hygiene in soil-transmitted helminth transmission is required, particularly in low transmission settings after cessation of deworming. Identifying improved indicators for measuring water, sanitation and hygiene behaviours is also a key priority.


Comparison of the web-based and paper [corrected] questionnaires of the Spanish and Catalan versionsof the KIDSCREEN-52.
The objectives of the study were to develop web-based Spanish and Catalan versions of the KIDSCREEN, and to compare scores and psychometric properties with the paper version. Internet and paper Spanish and Catalan versions of the KIDSCREEN-52 were included in a cross-sectional study in school-age children. Web-based and paper Spanish or Catalan versions of the KIDSCREEN-52 were administered to students aged 8 to 18 years from primary and secondary schools in Palafolls (Barcelona, Spain, n = 923). All students completed both web-based and paper versions during school time with an interval of at least 2 hours between administrations. The order of administration was randomized. The KIDSCREEN-52, the Strengths and Difficulties Questionnaire (SDQ), and sociodemographic variables were collected. Missing values, floor and ceiling effects, and internal consistency were compared between both versions, as well as mean score differences, level of agreement, and known groups and construct validity. Participation rate was 77% (n = 715). Web-based and paper versions showed low percentage of missing values and similar high ceiling effect (range 0 to 44%). Mean score differences showed an effect size (ES) lower than 0.2 in all dimensions. Internal consistency ranged from 0.7 to 0.88, and degree of agreement was excellent (Intraclass correlation coefficient [ICC] range 0.75 to 0.87). Expected differences were seen by sex, age, socioeconomic status and mental health status. The web-based KIDSCREEN-52 showed similar scale score and reliability and validity than the paper version. It will incorporate the child population in the assessment of quality of life providing a more attractive format.


Chronic hypoglycemia and diabetes impair counterregulation induced by localized 2-deoxy-glucose perfusion of the ventromedial hypothalamus in rats.
Previous studies have demonstrated that the ventromedial hypothalamus (VMH) plays a critical role in sensing and responding to systemic hypoglycemia. To evaluate the mechanisms of defective counterregulation caused by iatrogenic hypoglycemia and diabetes per se, we delivered 2-deoxy-glucose (2-DG) via microdialysis into the VMH to produce localized cellular glucopenia in the absence of systemic hypoglycemia. Three groups of awake chronically catheterized rats were studied: 1) nondiabetic (with a mean daily glucose [MDG] of 6.9 mmol/l) BB control rats (n = 5); 2) chronically hypoglycemic nondiabetic (3-4 weeks, with an MDG of 2.7 mmol/l) BB rats (n = 5); and 3) moderately hyperglycemic insulin-treated diabetic (with an MDG of 12.4 mmol/l) BB rats (n = 8). In hypoglycemic rats, both glucagon and catecholamine responses to VMH glucopenia were markedly (77-93%) suppressed. In diabetic rats, VMH 2-DG perfusion was totally ineffective in stimulating glucagon release. The epinephrine response, but not the norepinephrine response, was also diminished by 38% in the diabetic group. We conclude that impaired counterregulation after chronic hypoglycemia may result from alterations of the VMH or its efferent pathways. In diabetes, the capacity of VMH glucopenia to activate the sympathoadrenal system is only modestly diminished; however, the communication between the VMH and the alpha-cell is totally interrupted.


The KIN28 gene is required both for RNA polymerase II mediated transcription and phosphorylation of the Rpb1p CTD.
Kin28p, associated with cyclin Ccl1p, is a putative cyclin-dependent kinase (CDK) of the p34cdc2 family in Saccharomyces cerevisiae. Search for mutations co-lethal (syn mutations) with a kin28 thermosensitive mutation (kin28-ts3) has uncovered genetic interactions between gene KIN28 and genes RAD3, SIN4, STI1 and CDC37. The genetic interaction between KIN28 and the CDC37 cell division cycle gene suggests that a connection exists between the activity of CDK-Kin28p and cell-cycle progression. Both RAD3 and SIN4 gene products are implicated in the RNA polymerase II transcription process. Here we show that RNA polymerase II transcription is drastically reduced in a kin28-ts mutant, at restrictive temperature. This impairment correlates with a markedly decreased phosphorylation of the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (Rpb1p). Thus, the Kin28 gene product is required in vivo for RNA polymerase II phosphorylation and transcriptional activity as recently suggested by experiments using an in vitro reconstituted system.


IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis.
IL-15, a T cell growth factor, has been linked to exacerbating autoimmune diseases and allograft rejection. To test the hypothesis that IL-15-deficient (IL-15-/-) mice would be protected from T cell-dependent nephritis, we induced nephrotoxic serum nephritis (NSN) in IL-15-/- and wild-type (IL-15+/+) C57BL/6 mice. Contrary to our expectations, IL-15 protects the kidney during this T cell-dependent immunologic insult. Tubular, interstitial, and glomerular pathology and renal function are worse in IL-15-/- mice during NSN. We detected a substantial increase in tubular apoptosis in IL-15-/- kidneys. Moreover, macrophages and CD4 T cells are more abundant in the interstitia and glomeruli in IL-15-/- mice. This led us to identify several mechanisms responsible for heightened renal injury in the absence of IL-15. We now report that IL-15 and the IL-15 receptor (alpha, beta, gamma chains) are constitutively expressed in normal tubular epithelial cells (TECs). IL-15 is an autocrine survival factor for TECs. TEC apoptosis induced with anti-Fas or actinomycin D is substantially greater in IL-15-/- than in wild-type TECs. Moreover, IL-15 decreases the induction of a nephritogenic chemokine, MCP-1, that attracts leukocytes into the kidney during NSN. Taken together, we suggest that IL-15 is a therapeutic for tubulointerstitial and glomerular kidney diseases.


Methodologic recommendations and possible interpretations of video-EEG recordings in immature rodents used as experimental controls: A TASK1-WG2 report of the ILAE/AES Joint Translational Task Force.
The use of immature rodents to study physiologic aspects of cortical development requires high-quality recordings electroencephalography (EEG) with simultaneous video recording (vEEG) of behavior. Normative developmental vEEG data in control animals are fundamental for the study of abnormal background activity in animal models of seizures or other neurologic disorders. Electrical recordings from immature, freely behaving rodents can be particularly difficult because of the small size of immature rodents, their thin and soft skull, interference with the recording apparatus by the dam, and other technical challenges. In this report of the TASK1 Working Group 2 (WG2) of the International League Against Epilepsy/American Epilepsy Society (ILAE/AES) Joint Translational Task Force, we provide suggestions that aim to optimize future vEEG recordings from immature rodents, as well as their interpretation. We focus on recordings from immature rodents younger than 30 days old used as experimental controls, because the quality and correct interpretation of such recordings is important when interpreting the vEEG results of animals serving as models of neurologic disorders. We discuss the technical aspects of such recordings and compare tethered versus wireless approaches. We also summarize the appearance of common artifacts and various patterns of electrical activity seen in young rodents used as controls as a function of behavioral state, age, and (where known) sex and strain. The information herein will hopefully help improve the methodology of vEEG recordings from immature rodents and may lead to results and interpretations that are more consistent across studies from different laboratories.


Knowns and unknowns of plastic waste flows in the Netherlands.
Plastic entering the environment is a growing threat for ecosystems. We estimate the annual mass of known Dutch plastic waste generated and littered and where it ends up. We use two methods: (1) a material flow analysis of plastic waste separately collected from 13 economic sectors (including households, industry and imports) and estimate the amount sent to processing plants or exported and (2) a mismanagement model from observations of litter (on Dutch beaches and riverbanks) plus estimates of inadequately managed exported plastic scraps entering the environment abroad. In 2017 (the most recent complete data set available), an estimate of 1990 (±111) kilotonnes [kt] of plastic waste was separately collected. The top three plastic waste generating sectors (74% of the total) were households, clothing and textiles, and importation. Our mismanagement model estimates that 4.3-21.2 kt enters the environment annually; almost all of which occurs in foreign countries after inadequate management of imported Dutch waste. We highlight unknowns, including the source and/or destination of imported (623 kt) and exported (514 kt) plastics, plastics in non-household mixed waste streams and the plastic fraction of some separately collected waste, for example, e-waste. Our results stress the need for improved monitoring and reporting of plastic waste. Beyond the Netherlands, our recommendations could also help other high-income countries' decision-makers reach their circular economy goals.


Distributions of vimentin and desmin in developing chick myotubes in vivo. II. Immunoelectron microscopic study.
The distribution of the intermediate filament proteins vimentin and desmin in developing and mature myotubes in vivo was studied by single and double immunoelectron microscopic labeling of ultrathin frozen sections of iliotibialis muscle in 7-21-d-old chick embryos, and neonatal and 1-d-old postnatal chicks. This work is an extension of our previous immunofluorescence studies of the same system (Tokuyasu, K. T., P. A. Maher and S. J. Singer, 1984, J. Cell Biol., 98:1961-1972). In immature myotubes of 7-11-d embryos, significant labeling for desmin and vimentin was found only in intermediate filaments, and these proteins coexisted in the same individual filaments. Each of the two proteins was present in irregular clusters along the entire length of a filament. No exclusively vimentin- or desmin-containing filaments were observed at this stage. In the early myotubes, the intermediate filaments were essentially all longitudinally oriented, even when they contained three times as much desmin as vimentin. No special relationship was recognized between the dispositions of the filaments and the organization of the myofibrils. Occasionally, several myofibrils were already aligned in lateral registry at this early stage, but labeling for desmin and vimentin was largely absent at the level of the Z bands. Instead, the Z bands appeared to be covered by elements of the sarcoplasmic reticulum. The confinement of intermediate filaments to the level of the Z bands occurred in the myotubes of later embryos after the extensive lateral registry of the Z bands. Thus, intermediate filaments are unlikely to play a primary role in producing the lateral registration of myofibrils during myogenesis, but may be important in determining the polarization of the early myotube and the alignment of its organelles. Throughout the development of myotubes, desmin and vimentin remained in the form of intermediate filaments, although the number of filaments per unit volume of myotube appeared to be reduced as myofibrils increased in number in maturing myotubes. This observation indicated that the transverse orientation of intermediate filaments in mature myotubes does not result from the de novo polymerization of subunits from Z band to Z band, but a continuous shifting of the positions and directions of intact filaments.


Maltodextrin-binding protein hybrids carrying epitopes from the preS2 region of hepatitis B virus: expression, antibody-binding and preliminary crystallographic studies.
Five hybrid constructions of maltodextrin-binding protein (MBP), each containing an inserted epitope(s) from the preS2 region of the envelope proteins of hepatitis B virus (HBV), have been expressed. The anti-preS2 monoclonal antibody S2.3 was shown to cross-react with the MBP hybrid constructions, demonstrating that the epitopes presented by these recombinant proteins mimic the antigenic behaviour of the native viral antigen. In addition, all five hybrid proteins have been crystallized. Preliminary structural solutions obtained by molecular replacement indicate that the native conformation of MBP is preserved in the hybrid constructions despite the significant length of the epitope insertions.


N-terminal pro-C-type natriuretic peptide in serum associated with bone destruction in patients with multiple myeloma.
To examine whether N-terminal proCNP concentrations in serum is associated with bone destruction in patients with multiple myeloma. N-terminal proCNP and biochemical bone markers were measured in 153 patients. Radiographic bone disease and skeletal-related events were evaluated at specific time-points. N-terminal proCNP concentrations increased with age. High N-terminal proCNP concentrations were associated with high-risk disease and renal impairment. Renal function explained 22% of the variation. N-terminal proCNP concentrations correlated with serum bone ALP and serum PINP, but lacked association with bone resorption markers, radiographic bone disease and skeletal-related events. Serum N-terminal proCNP are associated with bone formation activity in patients with multiple myeloma, but should be interpreted with caution in patients with renal impairment.


Simple procedure for the analysis of coherent imaging systems.
A simple procedure is presented for determining the Fourier-optics-regime object-image relationship for spatially coherent wave fields in a general imaging system. The procedure links straightforward ray-optics methods for imaging system analysis with parameters of a wave-optics-based superposition kernel that represents the Fourier-optics aspects of the system. Standard formulas are presented, and several confirming examples are treated.


Ultrasonic Vocalizations of Male Mice Differ among Species and Females Show Assortative Preferences for Male Calls.
Male house mice (Mus musculus) emit ultrasonic vocalizations (USVs) during courtship, which attract females, and we aimed to test whether females use these vocalizations for species or subspecies recognition of potential mates. We recorded courtship USVs of males from different Mus species, Mus musculus subspecies, and populations (F1 offspring of wild-caught Mus musculus musculus, Mus musculus domesticus (and F1 hybrid crosses), and Mus spicilegus), and we conducted playback experiments to measure female preferences for male USVs. Male vocalizations contained at least seven distinct syllable types, whose frequency of occurrence varied among species, subspecies, and populations. Detailed analyses of multiple common syllable types indicated that Mus musculus and Mus spicilegus could be discriminated based on spectral and temporal characteristics of their vocalizations, and populations of Mus musculus were also distinctive regardless of the classification model used. Females were able to discriminate USVs from different species, and showed assortative preferences for conspecific males. We found no evidence that females discriminate USVs of males from a different subspecies or separate populations of the same species, even though our spectral analyses identified acoustic features that differ between species, subspecies, and populations of the same species. Our results provide the first comparison of USVs between Mus species or between Mus musculus subspecies, and the first evidence that male USVs potentially facilitate species recognition.


Should tumor depth be included in prognostication of soft tissue sarcoma?
Most staging systems for soft tissue sarcoma are based on histologic malignancy-grade, tumor size and tumor depth. These factors are generally dichotomized, size at 5 cm. We believe it is unlikely that tumor depth per se should influence a tumor's metastatic capability. Therefore we hypothesized that the unfavourable prognostic importance of depth could be explained by the close association between size and depth, deep-seated tumors on average being larger than the superficial ones. When tumor size is dichotomized, this effect should be most pronounced in the large size (>5 cm) group in which the size span is larger. We analyzed the associations between tumor size and depth and the prognostic importance of grade, size and depth in a population-based series of 490 adult patients with soft tissue sarcoma of the extremity or trunk wall with complete, 4.5 years minimum, follow-up. Multivariate analysis showed no major prognostic effect of tumor depth when grade and size were taken into account. The mean size of small tumors was the same whether superficial or deep but the mean size of large and deep-seated tumors were one third larger than that of large but superficial tumors. Tumor depth influenced the prognosis in the subset of high-grade and large tumors. In this subset deep-seated tumors had poorer survival rate than superficial tumors, which could be explained by the larger mean size of the deep-seated tumors. Most of the prognostic value of tumor depth in soft tissue sarcomas of the extremity or trunk wall can be explained by the association between tumor size and depth.


Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide.
It has been shown that peripheral chemoreceptor sensitivity is enhanced in both clinical and experimental heart failure (HF) and that impairment of nitric oxide (NO) production contributes to this enhancement. In order to understand the cellular mechanisms associated with the alterations of chemoreceptor function and the actions of NO in the carotid body (CB), we compared the outward K+ currents (IK) of glomus cells in sham rabbits with that in HF rabbits and monitored the effects of NO on these currents. Ik was measured in glomus cells using conventional and perforated whole-cell configurations. IK was attenuated in glomus cells of HF rabbits, and their resting membrane potentials (-34.7 +/- 1.0 mV) were depolarized as compared with those in sham rabbits (-47.2 +/- 1.9 mV). The selective Ca(2+)-dependent K+ channel (KCa) blocker iberiotoxin (IbTx, 100 nm) reduced IK in glomus cells from sham rabbits, but had no effect on IK from HF rabbits. In perforated whole-cell mode, the NO donor SNAP (100 microm) increased IK in glomus cells from HF rabbits to a greater extent than that in sham rabbits (P < 0.01), and IbTx inhibited the effects of SNAP. However, in conventional whole-cell mode, SNAP had no effect. N omega-nitro-L-arginine (L-NNA, NO synthase inhibitor) decreased Ik in sham rabbits but not in HF rabbits. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) inhibited the effect of SNAP on Ik. These results demonstrate that IK is reduced in CB glomus cells from HF rabbits. This effect is due mainly to the suppression of KCa channel activity caused by decreased availability of NO. In addition, intracellular cGMP is necessary for the KCa channel modulation by NO.


Segmented motion compensation for complementary coded ultrasonic imaging.
Ultrasonic imaging using complementary coded pulses offers the SNR improvements of signal coding without the filter side-lobes introduced by single-transmit codes. Tissue motion between coded pulse emissions, however, can introduce high side-lobes caused by misalignment of complementary filter outputs. This paper presents a method for filtering and motion compensation of complementary coded signals appropriate for use in medical imaging. The method is robust to the effects of non-ideal transducers on the imaging signals, includes mirrored compensation stages to reduce the impact of motion estimation error, and has been shown to reduce side-lobes to levels that compare favorably to systems using FM-coded signals of similar length and bandwidth while providing increased coding gain and range resolution. In addition, motion compensation allows the received data to be used without the frame-rate penalty usually incurred by complementary-coded imaging. The method has been verified using simulated point and speckle targets with both homogeneous and inhomogeneous motion profiles. Selected results have been verified experimentally.


Analytical nuclear gradients for the range-separated many-body dispersion model of noncovalent interactions.
An accurate treatment of the long-range electron correlation energy, including van der Waals (vdW) or dispersion interactions, is essential for describing the structure, dynamics, and function of a wide variety of systems. Among the most accurate models for including dispersion into density functional theory (DFT) is the range-separated many-body dispersion (MBD) method [A. Ambrosetti et al., J. Chem. Phys., 2014, 140, 18A508], in which the correlation energy is modeled at short-range by a semi-local density functional and at long-range by a model system of coupled quantum harmonic oscillators. In this work, we develop analytical gradients of the MBD energy with respect to nuclear coordinates, including all implicit coordinate dependencies arising from the partitioning of the charge density into Hirshfeld effective volumes. To demonstrate the efficiency and accuracy of these MBD gradients for geometry optimizations of systems with intermolecular and intramolecular interactions, we optimized conformers of the benzene dimer and isolated small peptides with aromatic side-chains. We find excellent agreement with the wavefunction theory reference geometries of these systems (at a fraction of the computational cost) and find that MBD consistently outperforms the popular TS and D3(BJ) dispersion corrections. To demonstrate the performance of the MBD model on a larger system with supramolecular interactions, we optimized the C60@C60H28 buckyball catcher host-guest complex. In our analysis, we also find that neglecting the implicit nuclear coordinate dependence arising from the charge density partitioning, as has been done in prior numerical treatments, leads to an unacceptable error in the MBD forces, with relative errors of ∼20% (on average) that can extend well beyond 100%.


General health, health conditions, and current pregnancy among U.S. women with and without chronic physical disabilities.
Although increasing numbers of reproductive-age U.S. women with chronic physical disabilities (CPD) are becoming pregnant, little is known about their general health or comorbid health conditions. To explore general health and comorbid health conditions among women with and without CPD by current pregnancy status. We analyzed responses of 47,629 civilian, noninstitutionalized women ages 18-49 from the 2006-2011 National Health Interview Surveys. The survey asks about: various movement difficulties; selected adult health conditions; self-reported general health; and current pregnancy. We identified women with CPD using responses from 8 movement difficulty questions. 6043 (12.7%) women report CPD. Among nondisabled women, 3.8% report current pregnancy, as do 2.0% of women with CPD. Among currently pregnant women with CPD, 29.1% report fair or poor health, compared with only 3.2% of nondisabled pregnant women. Currently pregnant women both with and without CPD are significantly less likely to report coexisting health conditions than nonpregnant women. Nonetheless, among currently pregnant women with CPD, only 24.5% report no coexisting conditions, while 28.7% report 1, 22.8% report 2, 13.2% report 3, and 10.8% report 4-6 health conditions. In a multivariable regression controlling for age category, health status, and health conditions, CPD is not statistically significantly associated with current pregnancy. According to national survey data, it appears that pregnant women with CPD may have a complex mix of health problems and often experience fair or poor health. Better understanding the obstetrical and subspecialty needs of these women with multimorbidities requires additional investigation.


Harmonizing Pain Outcome Measures: Results of the Pre-OMERACT Meeting on Partnerships for Consensus on Patient-important Pain Outcome Domains Between the Cochrane Musculoskeletal Group and OMERACT.
A variety of authorities in pain measurement and outcome methodology met prior to the Outcome Measures in Rheumatology (OMERACT) 12 meeting in May 2014 to develop partnerships for consensus on pain outcomes. Following overview presentations, discussion centered on pain-specific and global constructs in the domain of chronic pain. Practical issues for clinical trial implementation were also discussed. Breakout sessions were completed regarding additional details of domain constructs. A nominal group process involving all workshop participants confirmed that chronic pain outcome measures encompass a broad range of constructs and that existing scales may be inadequate for assessment in clinical trials. Participants endorsed that both pain intensity and pain interference are important constructs to be measured in clinical trials of chronic pain as it pertains to rheumatologic diagnoses. Further work is needed on inclusion of the patient perspective in the development of pain domains as well as Cochrane Collaboration summary of findings tables.


Vesicular exocytosis contributes to volume-sensitive ATP release in biliary cells.
Extracellular ATP is a potent autocrine/paracrine signal that regulates a broad range of liver functions through activation of purinergic receptors. In biliary epithelium, increases in cell volume stimulate ATP release through a phosphoinositide 3-kinase (PI3-kinase)-dependent mechanism. Because PI3-kinase also regulates vesicular exocytosis, the purpose of these studies was to determine whether volume-stimulated vesicular exocytosis contributes to cellular ATP release. In a human cholangiocarcinoma cell line, exocytosis was measured by using the plasma membrane marker FM1-43, whereas ATP release was assessed by using a luciferase-luciferin assay. Under basal conditions, cholangiocytes exhibited constitutive exocytosis at a rate of 1.6%/min, and low levels of extracellular ATP were detected at 48.2 arbitrary light units. Increases in cholangiocyte cell volume induced by hypotonic exposure resulted in a 10-fold increase in the rate of exocytosis and a robust 35-fold increase in ATP release. Both vesicular exocytosis and ATP release were proportional to cell volume, and both exhibited similar regulatory properties including: 1) dependence on intact PI3-kinase, 2) attenuation by inhibition of PKC, and 3) potentiation by activation of PKC before hypotonic exposure. These findings demonstrate that increases in cholangiocyte cell volume stimulate ATP release and vesicular exocytosis through similar regulatory paradigms. Functional interactions among cell volume, PKC, and PI3-kinase modulate exocytosis, thereby regulating ATP release and purinergic signaling in cholangiocytes. It is hypothesized that PKC is involved in the recruitment of a volume-sensitive vesicular pool to a readily releasable state.


Association between lung function and exacerbation frequency in patients with COPD.
To quantify the relationship between severity of chronic obstructive pulmonary disease (COPD) as expressed by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and the annual exacerbation frequency in patients with COPD. We performed a systematic literature review to identify randomized controlled trials and cohort studies reporting the exacerbation frequency in COPD patients receiving usual care or placebo. Annual frequencies were determined for total exacerbations defined by an increased use of health care (event-based), total exacerbations defined by an increase of symptoms, and severe exacerbations defined by a hospitalization. The association between the mean forced expiratory volume in one second (FEV(1))% predicted of study populations and the exacerbation frequencies was estimated using weighted log linear regression with random effects. The regression equations were applied to the mean FEV(1)% predicted for each GOLD stage to estimate the frequency per stage. Thirty-seven relevant studies were found, with 43 reports of total exacerbation frequency (event-based, n = 19; symptom-based, n = 24) and 14 reports of frequency of severe exacerbations. Annual event-based exacerbation frequencies per GOLD stage were estimated at 0.82 (95% confidence interval 0.46-1.49) for mild, 1.17 (0.93-1.50) for moderate, 1.61 (1.51-1.74) for severe, and 2.10 (1.51-2.94) for very severe COPD. Annual symptom-based frequencies were 1.15 (95% confidence interval 0.67-2.07), 1.44 (1.14-1.87), 1.76 (1.70-1.88), and 2.09 (1.57-2.82), respectively. For severe exacerbations, annual frequencies were 0.11 (95% confidence interval 0.02-0.56), 0.16 (0.07-0.33), 0.22 (0.20-0.23), and 0.28 (0.14-0.63), respectively. Study duration or type of study (cohort versus trial) did not significantly affect the outcomes. This study provides an estimate of the exacerbation frequency per GOLD stage, which can be used for health economic and modeling purposes.


Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis.
Routinely used therapies are not adequate to treat the heterogeneity of breast cancer, and consequently, more therapeutic targets are desperately needed. To identify novel targets, we generated a breast cancer cDNA library enriched for genes that encode membrane and secreted proteins. From this library we identified SUSD2 (Sushi Domain Containing 2), which encodes an 822-amino acid protein containing a transmembrane domain and functional domains inherent to adhesion molecules. Previous studies describe the mouse homolog, Susd2, but there are no studies on the human gene associated with breast cancer. Immunohistochemical analysis of human breast tissues showed weak or no expression of SUSD2 in normal epithelial cells, with the endothelial lining of vessels staining positive for SUSD2. However, staining was observed in pathologic breast lesions and in lobular and ductal carcinomas. SUSD2 interacts with galectin-1 (Gal-1), a 14-kDa secreted protein that is synthesized by carcinoma cells and promotes tumor immune evasion, angiogenesis, and metastasis. Interestingly, we found that localization of Gal-1 on the surface of cells is dependent on the presence of SUSD2. Various phenotype assays indicate that SUSD2 increases the invasion of breast cancer cells and contributes to a potential immune evasion mechanism through induction of apoptosis of Jurkat T cells. Using a syngeneic mouse model, we observed accelerated tumor formation and decreased survival in mice with tumors expressing Susd2. We found significantly fewer CD4 tumor infiltrating lymphocytes in mice with tumors expressing Susd2. Together, our findings provide evidence that SUSD2 may represent a promising therapeutic target for breast cancer.


Impact of the great recession on self-perceived health in Spain: a longitudinal study with individual data.
Our objective in this study is to evaluate the impact the Great Recession (2008-2014) had on self-perceived health in Spain. We use a longitudinal database (four waves of the Bank of Spain's Survey of Household Finances (2005, 2008, 2011 and 2014)) with repeated observations of the same individuals before and after the Great Recession. We consider the Great Recession in a natural experiment and we introduce it as an explanatory variable in a mixed logistic regression model in which we explain the probability of a subject declaring poor health (fair, bad and very bad). In the model we control for both observed and unobserved confounders at both individual and family level. We find an average downward trend in self-perceived health during the most severe period of the Great Recession (2009-2011). However, the fact that the adjusted measures are less volatile than the crude ones shows that variation in health status can be captured by either demographic or socioeconomic controls. In fact, there are significant differences in the impact the economic crisis had on health in terms of gender and age group. In particular, the (adjusted) risk of declaring poor health increases after the crisis began but only in those families in which the reference person is a woman younger than 45 years of age or a man aged 75 years or older. Given our results, we discuss the link between financial wealth and self-rated health and how policy-makers could address the health inequalities that arise from adverse economic and financial shocks.


Maximization of imaging resolution in optical wireless sensor/lab-on-chip/SoC networks with solar cells.
The availability of sophisticated and low-cost hardware on a single chip, for example, CMOS cameras, CPU, DSP, processors and communication transceivers, optics, microfluidics, and micromechanics, has fostered the development of system-on-chip (SoC) technology, such as lab-on-chip or wireless multimedia sensor networks (WMSNs). WMSNs are networks of wirelessly interconnected devices on a chip that are able to ubiquitously retrieve multimedia content such as video from the environment and transfer it to a central location for additional processing. In this paper, we study WMSNs that include an optical wireless communication transceiver that uses light to transmit the information. One of the primary challenges in SoC design is to attain adequate resources like energy harvesting using solar cells in addition to imaging and communication capabilities, all within stringent spatial limitations while maximizing system performances. There is an inevitable trade-off between enhancing the imaging resolution and the expense of reducing communication capacity and energy harvesting capabilities, on one hand, and increasing the communication or the solar cell size to the detriment of the imaging resolution, on the other hand. We study these trade-offs, derive a mathematical model to maximize the resolution of the imaging system, and present a numerical example that demonstrates maximum imaging resolution. Our results indicate that an eighth-order polynomial with only two constants provides the required area allocation between the different functionalities.


Overall HIV-1 prevalence in pregnant women over-estimates HIV-1 in the predominantly rural population of Afar Region.
The appropriateness of sentinel sero-surveillance based upon ante-natal clinic (ANC) attendees to estimate HIV-1 prevalence in the general population has been questioned. In Ethiopia, where the population is heterogeneous and where economic and practical barriers to ANC attendance exist, problems of extrapolation may be exacerbated. We planned an unlinked anonymous sero-survey which included data on basic population characteristics to investigate whether sero-surveillance data from ANCs in Afar Region might be taken to represent the situation among the general population of the Region. 371 pregnant women attending Dubti Hospital and Assayta Health Centre were tested for HIV-1 (using a single ELISA test) and active syphilis (RPR test). Socio-demographic characteristics were collected for each woman. Of the women tested, 278 (75%) were 28 years of age or younger. Two hundred eighty (76%) were urban residents and 237 (64%) described themselves as being of Amhara ethnicity. Overall, 73 (19.7%) were HIV-1 positive, but prevalence was three times higher among the 237 women of Amhara ethnicity compared to the 112 of Afar ethnicity (24.9% vs 8.0%, p < 0.001), and almost three times higher for urban compared to rural residents (23.2% vs 8.8%, p < 0.001). Positive RPR results were strongly associated with HIV-1 infection (OR 3.37, 95% CI 1.47-7.71). According to the Demographic and Health Survey (DHS) 2000, only 4.5% of the population of Afar Region is of Amhara ethnicity, and 7.8% urban residents. We have demonstrated that basing ANC sero-surveillance in urban areas of Afar Region over-samples urban residents of Amhara ethnicity and yields a major over-estimation of overall HIV-1 prevalence for the Region. Reliable estimation of HIV-1 prevalence in Afar Region will require more flexible strategies that permit sampling of rural Afar residents.


Preferences of Gay and Bisexual Men for Pharmacy-Based HIV Testing and Over-the-Counter HIV Tests.
A 2013 study among 169 Indiana men aged 18-45 who have sex with men assessed the acceptability of and preferences for pharmacy-based and over-the-counter (OTC) HIV testing. Rural men in general and men who did not know their HIV status were more likely to purchase an OTC HIV test. Men who did not know their HIV status also preferred an OTC HIV test to pharmacy-based testing. Pharmacies should enhance information around the sale of OTC HIV tests, particularly in rural areas. Information should include test results, opportunities for consultation, and linkage to care.


Biomechanical Analysis of Defensive Cutting Actions During Game Situations: Six Cases in Collegiate Soccer Competitions.
The strengths of interpersonal dyads formed by the attacker and defender in one-on-one situations are crucial for performance in team ball sports such as soccer. The purpose of this study was to analyze the kinematics of one-on-one defensive movements in soccer competitions, and determine the relationships between lower limb kinematics and the center of mass translation during cutting actions. Six defensive scenes in which a player was responding to an offender's dribble attack were selected for analysis. To reconstruct the three-dimensional kinematics of the players, we used a photogrammetric model-based image-matching technique. The hip and knee kinematics were calculated from the matched skeleton model. In addition, the center of mass height was expressed as a ratio of each participant's body height. The relationships between the center of mass height and the kinematics were determined by the Pearson's product-moment correlation coefficient. The normalized center of mass height at initial contact was correlated with the vertical center of mass displacement (r = 0.832, p = 0.040) and hip flexion angle at initial contact (r = -0.823, p = 0.044). This suggests that the lower center of mass at initial contact is an important factor to reduce the downwards vertical center of mass translation during defensive cutting actions, and that this is executed primarily through hip flexion. It is therefore recommended that players land with an adequately flexed hip at initial contact during one-on-one cutting actions to minimize the vertical center of mass excursion.


Evolution of forelimb musculoskeletal function across the fish-to-tetrapod transition.
One of the most intriguing questions in vertebrate evolution is how tetrapods gained the ability to walk on land. Although many hypotheses have been proposed, few have been rigorously tested using the fossil record. Here, we build three-dimensional musculoskeletal models of the pectoral appendage in Eusthenopteron, Acanthostega, and Pederpes and quantitatively examine changes in forelimb function across the fin-to-limb transition. Through comparison with extant fishes and tetrapods, we show that early tetrapods share a suite of characters including restricted mobility in humerus long-axis rotation, increased muscular leverage for humeral retraction, but not depression/adduction, and increased mobility in elbow flexion-extension. We infer that the earliest steps in tetrapod forelimb evolution were related to limb-substrate interactions, whereas specializations for weight support appeared later. Together, these results suggest that competing selective pressures for aquatic and terrestrial environments produced a unique, ancestral "early tetrapod" forelimb locomotor mode unlike that of any extant animal.


Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level.
Immune responsiveness to phosphorylcholine (PC) in BALB/c mice has been characterized by combining (a) usuage of highly sensitive radioimmunoassays for quantitation of antibody, heavy-chain class, and idiotype on a weight basis; (b) isolation of PC-specific B cells in fragment cultures; and (c) stimulation in a carrier-primed environment with the PC hapten coupled to carrier through a tripeptide spacer in order to maximize carrier recognition. The specificity and accuracy of the radioimmunoassays have veen verified by specific inhibition, lack of nonspecific binding, and excellent concordance of values for monoclonal antibody concentration obtained independently for Fab and idiotype content. The latter evidence also serves as strong confirmation of the monoclonality of in vitro monofocal responses as well as the preservation of the idiotype on antibodies of differing immunoglobulin classes. The results indicate that while B cells expressing the TEPC 15 idiotype predominate, other idiotypes may be represented by 2-50% of PC-specific precursors, and monoclonal antibodies even of the TEPC 15 idiotype are produced in both the IgM and IgG1 immunoglobulin classes. These findings are confirmed by the analysis of serum antibodies produced in carrier-primed mice immunized with hapten coupled through a tripeptide spacer, thus re-emphasizint the enhancement of primary responsiveness, particularly IgG1 production, by maximizing carrier recognition. The finding of idiotype diversity in the PC response, as well as diversity of expression in terms of quantity and immunoglobulin class of antibody synthesized by the clonal progeny of B cells within the TEPC 15 clonotype, emphasize the heterogeneity of the B-cell population both in terms of specificity repertoire and the physiological state of cells even within a single clonotype.


CSF levels of apolipoprotein C1 and autotaxin found to associate with neuropathic pain and fibromyalgia.
Neuropathic pain and fibromyalgia are two common and poorly understood chronic pain conditions that lack satisfactory treatments, cause substantial suffering and societal costs. Today, there are no biological markers on which to base chronic pain diagnoses, treatment choices or to understand the pathophysiology of pain for the individual patient. This study aimed to investigate cerebrospinal fluid (CSF) protein profiles potentially associated with fibromyalgia and neuropathic pain. CSF samples were collected from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery, and n=11 for verification), 40 patients with fibromyalgia and 134 controls without neurological disease from two different populations. CSF protein profiling of 55 proteins was performed using antibody suspension bead array technology. We found increased levels of apolipoprotein C1 (APOC1) in CSF of neuropathic pain patients compared to controls and there was a trend for increased levels also in fibromyalgia patients. In addition, levels of ectonucleotide pyrophosphatase family member 2 (ENPP2, also referred to as autotaxin) were increased in the CSF of fibromyalgia patients compared to all other groups including patients with neuropathic pain. The increased levels of APOC1 and ENPP2 found in neuropathic pain and fibromyalgia patients may shed light on the underlying mechanisms of these conditions. Further investigation is required to elucidate their role in maintaining pain and other main symptoms of these disorders.


Assessing the effects of time and spatial averaging in 15N chemical shift/15N-1H dipolar correlation solid state NMR experiments.
The effect of time and spatial averaging on (15)N chemical shift/(1)H-(15)N dipolar correlation spectra, i.e., PISEMA spectra, of alpha-helical membrane peptides and proteins is investigated. Three types of motion are considered: (a) Librational motion of the peptide planes in the alpha-helix; (b) rotation of the helix about its long axis; and (c) wobble of the helix about a nominal tilt angle. A 2ns molecular dynamics simulation of helix D of bacteriorhodopsin is used to determine the effect of librational motion on the spectral parameters. For the time averaging, the rotation and wobble of this same helix are modelled by assuming either Gaussian motion about the respective angles or a uniform distribution of a given width. For the spatial averaging, regions of possible (15)N chemical shift/(1)H-(15)N dipolar splittings are computed for a distribution of rotations and/or tilt angles of the helix. The computed spectra show that under certain motional modes the (15)N chemical shift/(1)H-(15)N dipolar pairs for each of the residues do not form patterns which mimic helical wheel patterns. As a result, the unambiguous identification of helix tilt and helix rotation without any resonance assignments or on the basis of a single assignment may be difficult.


The self-importance of moral identity.
Recent theorizing in moral psychology extends rationalist models by calling attention to social and cultural influences (J. Haidt, 2001). Six studies using adolescents, university students, and adults measured the associations among the self-importance of moral identity, moral cognitions, and behavior. The psychometric properties of the measure were assessed through an examination of the underlying factor structure (Study 1) and convergent, nomological, and discriminant validity analyses (Studies 2 and 3). The predictive validity of the instrument was assessed by examinations of the relationships among the self-importance of moral identity, various psychological outcomes, and behavior (Studies 4, 5, and 6). The results are discussed in terms of models of moral behavior, social identity measurement, and the need to consider moral self-conceptions in explaining moral conduct.


Prevalence of psychiatric disorders in sick listed chronic low back pain patients.
Previous findings have shown a high degree of comorbid psychopathology in chronic low back pain (CLBP), but less is known about the broad range of comorbid psychiatric disorders. The prevalence is reported to be between 40% and 100% depending on methods being used, sample or setting. To assess the prevalence of psychiatric comorbidity in a population of CLBP patients, using a psychiatric diagnostic interview. 565 patients sick listed between 2 and 10months for unspecific LBP were included in the study. All were recruited as part of an ongoing trial in secondary care, and were assessed with the Mini-International Neuropsychiatric Interview (MINI), which is a short structured diagnostic interview for DSM-IV and ICD-10 psychiatric disorders. The prevalence of current psychiatric disorders was 31%. The diagnoses included 19 Axis I disorders, with the most common being somatoform disorders (18%) and anxiety disorders (12%). Major depressive disorders were reported in 4%. There were no gender differences in prevalence of psychiatric disorders. In a large population of CLBP patients, 31% fulfilled the criteria for at least one current psychiatric disorder when measured with a diagnostic interview. The diagnoses included a wide range of psychiatric disorders, with the most common being somatoform disorders (18%) and anxiety disorders (12%). The results imply that screening CLBP patients for psychiatric comorbidity in secondary care is important since psychopathology may have serious consequences for prognosis, outcome and health care utilization.


Reversal of tubal sterilization versus IVF in the era of assisted reproductive technology: a clinical dilemma.
Two treatment options are available to women who wish to become pregnant after having had tubal sterilization: microsurgical reversal or IVF. The first approach is designed to restore tubal function, whereas the second replaces it. The first, to be successful, requires the presence of sufficient tubal length and normal or treatable fertility parameters. Treatment should therefore be individualized, based upon the findings of the couple's investigation, their wishes and the costs involved. The age of the female is the most important factor that affects the outcome with both treatment options. The live birth rate per cycle with IVF is 28%, but only 65.8% are singletons; 31.0% are twins and 3.2% triplets or more. Microsurgical tubal anastomosis yields a birth rate that exceeds 55%, without increased risk of multiple pregnancy. It offers the couple multiple cycles in which to achieve conception naturally, and the opportunity to have more than one pregnancy from a single intervention. The real dilemma lies with the 'industrialization' of IVF, and its frequent use as primary treatment for infertility. The dilemma is heightened by the fact that reconstructive tubal microsurgery is being taught and practised less and less, thereby eliminating this credible surgical option in most centres.


Cortical thickness of primary visual cortex correlates with motion deficits in periventricular leukomalacia.
Impairments of visual motion perception and, in particular, of flow motion have been consistently observed in premature and very low birth weight subjects during infancy. Flow motion information is analyzed at various cortical levels along the dorsal pathways, with information mainly provided by primary and early visual cortex (V1, V2 and V3). We investigated the cortical stage of the visual processing that underlies these motion impairments, measuring Grey Matter Volume and Cortical Thickness in 13 children with Periventricular Leukomalacia (PVL). The cortical thickness, but not the grey matter volume of area V1, correlates negatively with motion coherence sensitivity, indicating that the thinner the cortex, the better the performance among the patients. However, we did not find any such association with either the thickness or volume of area MT, MST and areas of the IPS, suggesting damage at the level of primary visual cortex or along the optic radiation.


Comparison of prescribing and dispensing processes between veterinarians and pharmacists in New Zealand: Are there opportunities for cooperation?
Prescribing and dispensing of medicines are fundamental processes in providing healthcare for both human and animal patients. There has been recent discussion in the literature to advocate for increased co-operation between pharmacists and veterinarians, however there is little data available about veterinary prescribing and dispensing processes. The aims of this study were to gain information on veterinary prescribing and dispensing processes for companion animals in the Dunedin region of New Zealand. Open interviews were conducted with a selection of five veterinarians at practices in Dunedin. All interviews were transcribed verbatim. In New Zealand almost all dispensing of medicines for animals is carried out by veterinarians or their staff. There is a lack of standard treatment guidelines and a lack of regulation around the treatment period for which medicines can be dispensed at one time (i.e. period of supply). Medicines for animals are sometimes dispensed by community pharmacies, where clients are experiencing financial difficulties or when particular medicines are not held by veterinary practices. Record keeping requirements and practices for veterinarians are similar to those for community pharmacies. Processes undertaken by veterinarians in terms of prescribing and dispensing were similar to pharmacists' practices for human patients and so there is opportunity for collaboration between the two professions. Pharmacists also have complementary knowledge about dosing and formulating medicines that can assist in delivering optimal healthcare to animal patients.


Contributions of biofilm and suspended sludge to nitrogen transformation and nitrous oxide emission in hybrid sequencing batch system.
Hybrid system combines the nature of suspended growth and attached growth has been widely applied to wastewater treatment. In this research, the contributions to N transformation and N2O emission by biofilm and suspended sludge in the hybrid sequencing-batch reactor for a simultaneous nitrification, denitrification and phosphorus removal process were investigated. For the hybrid system, nitrification occurred mostly in the suspended sludge, while the biofilm played the major role in denitrification. The interaction of the biofilm and the suspended sludge in the same reactor resulted in a better overall nitrogen removal performance with simultaneous nitrification and denitrification. However, N2O emission was the main end product of nitrogen removal for the hybrid system; while it was N2 for the biofilm. The relative low N2O emissions from the pure biofilm and the pure suspended sludge corresponded to the relatively high nitrate at the end of the aeration period compared with the hybrid system.


Effectiveness, Feasibility, and Acceptability of Dynamic Elastomeric Fabric Orthoses (DEFO) for Managing Pain, Functional Capacity, and Quality of Life during Prenatal and Postnatal Care: A Systematic Review.
Conservative interventions for addressing prenatal and postnatal ailments have been described in the research literature. Research results indicated that maternity support belts assist with reducing pain and other symptoms in these phases; however, compliance in wearing maternity support belts is poor. To combat poor compliance, commercial manufacturers designed dynamic elastomeric fabric orthoses (DEFO)/compression garments that target prenatal and postnatal ailments. This systematic review aimed to identify, critically appraise, and synthesize key findings on the effectiveness, the feasibility, and the acceptability of using DEFO to manage ailments during pre-natal and postnatal phases of care. Electronic databases were systematically searched to identify relevant studies, resulting in 17 studies that met the eligibility criteria. There were variations in DEFO descriptors, including hosiery, support belts, abdominal binders and more, making it difficult to compare findings from the research articles regarding value of DEFO during prenatal and/or postnatal phases. A meta-synthesis of empirical research findings suggests wearing DEFOs during pregnancy has a significant desirable effect for managing pain and improving functional capacity. Further research is required to investigate the use of DEFOs for managing pain in the postnatal period and improving quality life during prenatal and postnatal care.


Decoding of Electroencephalogram Signals Shows No Evidence of a Neural Signature for Subitizing in Sequential Numerosity.
Numerosity perception is largely governed by two mechanisms. The first so-called subitizing system allows one to enumerate a small number of items (up to three or four) without error. The second system allows only an approximate estimation of larger numerosities. Here, we investigate the neural bases of the two systems using sequentially presented numerosity. Sequential numerosity (i.e., the number of events presented over time) starts as a subitizable set but may eventually transition into a larger numerosity in the approximate estimation range, thus offering a unique opportunity to investigate the neural signature of that transition point, or subitizing boundary. If sequential numerosity is encoded by two distinct perceptual mechanisms (i.e., for subitizing and approximate estimation), neural representations of the sequentially presented items crossing the subitizing boundary should be sharply distinguishable. In contrast, if sequential numerosity is encoded by a single perceptual mechanism for all numerosities and subitizing is achieved through an external postperceptual mechanism, no such differences in the neural representations should indicate the subitizing boundary. Using the high temporal resolution of the EEG technique incorporating a multivariate decoding analysis, we found results consistent with the latter hypothesis: No sharp representational distinctions were observed between items across the subitizing boundary, which is in contrast with the behavioral pattern of subitizing. The results support a single perceptual mechanism encoding sequential numerosities, whereas subitizing may be supported by a postperceptual attentional mechanism operating at a later processing stage.


Pseudomyxoma peritonei: inflammatory responses in the peritoneal microenvironment.
Pseudomyxoma peritonei (PMP), a peritoneal mucinous neoplasm of appendiceal origin, is associated with inflammation and fibrosis, which is central to its biology. The significance of the microenvironment in PMP has not been well characterized. Immunoassays were used to measure cytokines and C-reactive protein (CRP). Forty-two cytokines were initially measured in 23 PMP ascites and 10 PMP peritoneal washings. On the basis of these results, matching serum and ascites samples were analyzed for ten relevant cytokines (n = 32) and CRP (n = 28). Immunohistochemistry was performed on formalin-fixed tissue sections. Statistical analysis was by Wilcoxon signed rank test, Mann-Whitney U-test, and bivariate analysis. Serum CRP was elevated in PMP and correlated to CRP level in ascites. Interleukin (IL)-6, IL-8 (CXCL8), interferon gamma-induced protein 10 (IP-10), (CXCL10), monocyte chemotactic protein (MCP)-1 (CCL2), and macrophage inflammatory protein (MIP)-1α (CCL3) levels were grossly elevated in ascites but did not correlate with serum levels. Cytokines normally associated with infection or tissue injury (e.g., IL-1, IL-2, interferon gamma) were not elevated. Immunohistochemistry localized IL-6 to stroma, IP-10, and MCP-1 to tumor cells and IL-8 to adipose tissue. There were complex interactions among cytokines. IL-6, in particular, had many significant correlations in ascites. Serum IL-8, MIP-1β, and CRP were higher in PMP compared to controls. The pattern of cytokines in PMP is distinct from infection- or injury-associated inflammation. The results support peritoneal synthesis for cytokines. CRP, IL-8, and MIP-1β are potential serum markers for PMP. IL-6 appears to play a central role in PMP biology. This study provides new details about PMP tumor biology and identifies possible therapeutic targets.


Activity- and Occupation-Based Interventions to Support Mental Health, Positive Behavior, and Social Participation for Children and Youth: A Systematic Review.
Children and youth are often challenged to maintain well-being, positive behavior, and social participation. To identify evidence for occupational therapy interventions for children and youth with and at risk for mental health concerns. Articles published in English-language peer-reviewed journals between January 2010 and March 2017 identified through searches of MEDLINE, PsycINFO, CINAHL, ERIC, OTseeker, and Cochrane databases. : The methodology in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was used to complete the review. Of 5,310 articles screened by title and abstract, 357 were retrieved for full-text review, and 62 met inclusion criteria. Articles describing interventions that were activity or occupation based were included. Conference proceedings, non-peer reviewed publications, dissertations, theses, and presentations were excluded. Of the 62 studies included in the review, 20 (32%) were Level I studies, 22 (36%) were Level II studies, and 20 (32%) were Level III studies. Articles were categorized by type: outdoor camps, video and computer games, productive occupations and life skills, meditation, animal-assisted interventions, creative arts, play, sports, and yoga. Moderate to strong evidence supports the use of yoga and sports. Moderate-strength evidence supports the use of play and creative arts. Evidence for the use of animal-assisted interventions, meditation, video and computer games, and productive occupations was of low strength. Substantial evidence exists to support the use of activity- and occupation-based interventions to address the mental health, behavioral, and social participation concerns of children and youth. Occupational therapy practitioners should match the desired outcome of therapy with the appropriate intervention to provide the best and most effective services to their clients. This review provides additional support for the use of activity- and occupation-based interventions (i.e., those that involve active participation) to improve the behavior, social participation, and mental health of children and youth.


Extended lifespan of Drosophila parkin mutants through sequestration of redox-active metals and enhancement of anti-oxidative pathways.
The mechanisms underlying neuron death in Parkinson's disease are unknown, but both genetic defects and environmental factors are implicated in its pathogenesis. Mutations in the parkin gene lead to autosomal recessive juvenile Parkinsonism (AR-JP). Here we report that compared to control flies, Drosophila lacking parkin show significantly reduced lifespan but no difference in dopamine neuron numbers when raised on food supplemented with environmental pesticides or mitochondrial toxins. Moreover, chelation of redox-active metals, anti-oxidants and overexpression of superoxide dismutase 1 all significantly reversed the reduced longevity of parkin-deficient flies. Finally, parkin deficiency exacerbated the rough eye phenotype of Drosophila caused by overexpression of the copper importer B (Ctr1B). Taken together, our results demonstrate an important function of parkin in the protection against redox-active metals and pesticides implicated in the etiology of Parkinson's disease. They also corroborate that oxidative stress, perhaps as a consequence of mitochondrial dysfunction, is a major determinant of morbidity in parkin mutant flies.


The body social: an enactive approach to the self.
what is the human self? It offers a proposal for theorizing the self from an enactive perspective as an autonomous system that is constituted through interpersonal relations. It addresses a prevalent issue in the philosophy of cognitive science: the body-social problem. Embodied and social approaches to cognitive identity are in mutual tension. On the one hand, embodied cognitive science risks a new form of methodological individualism, implying a dichotomy not between the outside world of objects and the brain-bound individual but rather between body-bound individuals and the outside social world. On the other hand, approaches that emphasize the constitutive relevance of social interaction processes for cognitive identity run the risk of losing the individual in the interaction dynamics and of downplaying the role of embodiment. This paper adopts a middle way and outlines an enactive approach to individuation that is neither individualistic nor disembodied but integrates both approaches. Elaborating on Jonas' notion of needful freedom it outlines an enactive proposal to understanding the self as co-generated in interactions and relations with others. I argue that the human self is a social existence that is organized in terms of a back and forth between social distinction and participation processes. On this view, the body, rather than being identical with the social self, becomes its mediator.


SUPPORT Tools for evidence-informed health Policymaking (STP) 4: Using research evidence to clarify a problem.
This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers. Policymakers and those supporting them often find themselves in situations that spur them on to work out how best to define a problem. These situations may range from being asked an awkward or challenging question in the legislature, through to finding a problem highlighted on the front page of a newspaper. The motivations for policymakers wanting to clarify a problem are diverse. These may range from deciding whether to pay serious attention to a particular problem that others claim is important, through to wondering how to convince others to agree that a problem is important. Debates and struggles over how to define a problem are a critically important part of the policymaking process. The outcome of these debates and struggles will influence whether and, in part, how policymakers take action to address a problem. Efforts at problem clarification that are informed by an appreciation of concurrent developments are more likely to generate actions. These concurrent developments can relate to policy and programme options (e.g. the publication of a report demonstrating the effectiveness of a particular option) or to political events (e.g. the appointment of a new Minister of Health with a personal interest in a particular issue). In this article, we suggest questions that can be used to guide those involved in identifying a problem and characterising its features. These are: 1. What is the problem? 2. How did the problem come to attention and has this process influenced the prospect of it being addressed? 3. What indicators can be used, or collected, to establish the magnitude of the problem and to measure progress in addressing it? 4. What comparisons can be made to establish the magnitude of the problem and to measure progress in addressing it? 5. How can the problem be framed (or described) in a way that will motivate different groups?


Immunoregulatory changes in Kawasaki disease.
Kawasaki disease (KD) is an acute vasculitis of unknown etiology, occurring in young children and treated with intravenous gamma globulin (IVIG) to prevent significant cardiac morbidity and mortality. We studied KD patients pre- and post-IVIG therapy and at >40 days posttherapy, additionally comparing them with matched pediatric control patients and parents. Using three-color flow cytometry, we examined immune changes in KD, especially previously unassessed markers of T-lymphocyte activation, memory, and adhesion. The percentage of cells positive for CD19, CD25, CD38, and CD71 was significantly lower during convalescence compared with pre-IVIG (medians: CD19, 18% vs 26%, P = 0.0004; CD25, 6% vs 9% for CD3(+) cells, P = 0.0074; CD38, 78% vs 89% for CD8(+) cells, P = 0.0015; CD71, 1% vs 6% for CD4(+) cells, P = 0.0024). The proportion of CD3(+) cells increased (medians: CD3, 66% vs 45%, P < 0.0001). Values for all parameters varied greatly pre- and post-IVIG, but not in a consistent direction. The sole patient with cardiac abnormalities had the greatest pre-/post-IVIG variability. These changes support the involvement of T-lymphocytes in the acute KD vasculitic process. They also suggest that T-lymphocytes involved in endothelial damage during acute KD may be subsequently removed or eliminated from the peripheral blood.


Cytological, genetic, and molecular analysis to characterize compatible and incompatible interactions between Medicago truncatula and Colletotrichum trifolii.
In this study, a new pathosystem was established using the model plant Medicago truncatula and Colletotrichum trifolii, the causal agent of anthracnose on Medicago sativa. Screening of a few M. truncatula lines identified Jemalong and F83005.5 as resistant and susceptible to Colletotrichum trifolii race 1, respectively. Symptom analysis and cytological studies indicated that resistance of Jemalong was associated with a hypersensitive response of the plant. The two selected lines were crossed, and inoculations with C. trifolii were performed on the resulting F1 and F2 progenies. Examination of the disease phenotypes indicated that resistance was dominant and was probably due to a major resistance gene. Molecular components of the resistance were analyzed through macroarray experiments. Expression profiling of 126 expressed sequence tags corresponding to 92 genes, which were selected for their putative functions in plant defense or signal transduction, were compared in Jemalong and F83005.5 lines. A strong correlation was observed between the number of up-regulated genes and the resistance phenotype. Large differences appeared at 48 h postinoculation; more than 40% of the tested genes were up-regulated in the Jemalong line compared with only 10% in the susceptible line. Interestingly, some nodulin genes were also induced in the resistant line upon inoculation with C. trifolii.


Peptide KE in Human Proteome.
Peptide KE exhibits immunoprotective, geroprotective, and oncostatic activities and stimulates functional activity of fibroblasts. The KE motif is present in amino acid sequences of some cytokines and peptide hormones functionally similar to KE peptide. However, the relationship between the presence of KE motif and protein functions on the scale of known human proteome has not yet received sufficient attention. The incidence of bioregulatory peptide KE in proteins of various functional groups constituting human proteome is studied. The study is carried out with the use of the available data on the human proteome (UniProt portal) comprising 20,417 proteins. The levels of KE motifs were maximum in cytoplasmic and nuclear proteins, while the presence of KE in the membrane and all other proteins was the minimum. KE peptide molecules released from nuclear proteins during limited proteolysis can bind to DNA and regulate gene expression.


Developmental hemodynamic changes in the chick embryo from stage 18 to 27.
We report the hemodynamic parameters of stage 18, 21, 24, and 27 chick embryos (from 3 to 5 days of incubation). Dorsal aortic blood velocity and mean vitelline artery blood pressure are measured with a 20 MHz pulsed-Doppler meter and servo-null pressure system respectively. We also measure heart rate, dorsal aortic diameter and embryo weight of each developmental stage. From these data, we calculate mean dorsal aortic blood flow, mean dorsal aortic blood flow per cardiac cycle, mean dorsal aortic blood flow per milligram embryo weight, vascular resistance and cardiac work. Blood flow increases geometrically with each embryo stage but remains constant when normalized for embryo weight. Mean arterial pressure increases linearly and vascular resistance decreases geometrically. Cardiac work increases in proportion to embryo weight. These results define the parameters of normal hemodynamic function during early embryonic development.


Safety and Immunogenicity of a Parenterally Administered, Structure-Based Rationally Modified Recombinant Staphylococcal Enterotoxin B Protein Vaccine, STEBVax.
Staphylococcus aureus produces several enterotoxins and superantigens, exposure to which can elicit profound toxic shock. A recombinant staphylococcal enterotoxin B (rSEB) containing 3 distinct mutations in the major histocompatibility complex class II binding site was combined with an alum adjuvant (Alhydrogel) and used as a potential parenteral vaccine named STEBVax. Consenting healthy adult volunteers (age range, 23 to 38 years) participated in a first-in-human open-label dose escalation study of parenteral doses of STEBVax ranging from 0.01 μg up to 20 μg. Safety was assessed by determination of the frequency of adverse events and reactogenicity. Immune responses to the vaccination were determined by measurement of anti-staphylococcal enterotoxin B (anti-SEB) IgG by enzyme-linked immunosorbent assay and a toxin neutralization assay (TNA). Twenty-eight participants were enrolled in 7 dosing cohorts. All doses were well tolerated. The participants exhibited heterogeneous baseline antibody titers. More seroconversions and a faster onset of serum anti-SEB IgG toxin-neutralizing antibodies were observed by TNA with increasing doses of STEBVax. There was a trend for a plateau in antibody responses with doses of STEBVax of between 2.5 and 20 μg. Among the participants vaccinated with 2.5 μg to 20 μg of STEBVax, ∼93% seroconverted for SEB toxin-neutralizing antibody. A strong correlation between individual SEB-specific serum IgG antibody titers and the neutralization of gamma interferon production was found in vitro STEBvax appeared to be safe and immunogenic, inducing functional toxin-neutralizing antibodies. These data support its continued clinical development. (This study has been registered at ClinicalTrials.gov under registration no. NCT00974935.).


Becoming a psychiatric/mental health nurse in the UK: a qualitative study exploring processes of identity formation.
Identity studies are well established across the social science literature with mental health nursing beginning to offer evidenced insights into what may, or may not, constitute key identity performances. For mental health nursing these performances remain contested, both from within the profession and from international contexts that favour generic constructions of mental health. This paper offers findings from a qualitative study that focused upon the process of how mental health nursing identity development is influenced, rather than what that identity may or may not be. These findings highlight that mental health nurses (MHNs) not only form their identity around service user centred education and training, but that many also use the education as a means to leave the profession. Through highlighting the impact of informal education (i.e., through work), formal education, and training upon the formation of mental health nursing identity, nurses are potentially alerted to the importance of clinically focussed mental health being prominent within curricula, rewarding mental health nursing skills specialisation, and the importance of the role of the service user in mental health nurse education and, hence, identity formation.


Human scalp dermal papilla and fibrous sheath cells have a different expression profile of matrix metalloproteinases in vitro when compared to scalp dermal fibroblasts.
The dermal papilla is a cluster of specialised mesenchymal cells at the bottom of the mammalian hair follicle, embedded in a loose extracellular matrix. These cells have the capability to induce and support hair growth via close epithelial-mesenchymal interactions with the keratinocytes surrounding the hair matrix. The extracellular matrix of the dermal papilla differs markedly from the interfollicular matrix and plays a key role in the maintenance of hair growth. In this study we investigated the expression pattern and activity of matrix metalloproteinases (MMP) and their tissue inhibitor in in vitro cultures of cells derived from scalp dermal papilla and fibrous sheath. Expression and activity of MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, TIMP-2 and MT1-MMP were analysed in those cells cultured in contact with one of the relevant protein component of the dermal matrix, collagen type I as well as in monolayer. Zymographic analysis showed activation of MMP-2 in all cells grown in three-dimensional collagen lattices whereas MMP-9 was activated only in three-dimensional collagen cultures of dermal fibroblasts and weakly in follicular cells. Expression of MMP-1, TIMP-1, TIMP-2 and MT1-MMP was similar in all cells, in both culture conditions, whereas expression of MMP-3 was absent in dermal papilla cells. In addition to a series of reported morphological and functional differences between dermal fibroblasts and the dermal mesenchyme-derived cells of the hair follicle, we reported differences in MMP expression in dermal papilla and fibrous sheath cells within the mesenchymal population of the hair follicle.


From single particle to superfluid excitations in a dissipative polariton gas.
Using an angle-resolved heterodyne four-wave-mixing technique, we probe the low momentum excitation spectrum of a coherent polariton gas. The experimental results are well captured by the Bogoliubov transformation which describes the transition from single particle excitations of a normal fluid to soundlike excitations of a superfluid. In a dense coherent polariton gas, we find all the characteristics of a Bogoliubov transformation, i.e., the positive and negative energy branch with respect to the polariton gas energy at rest, soundlike shapes for the excitations dispersion, intensity, and linewidth ratio between the two branches in agreement with the theory. The influence of the nonequilibrium character of the polariton gas is shown by a careful analysis of its dispersion.


Digenean parasites of the great antshrike, Taraba major (Aves: Thamnophilidae), from Argentina, with a description of a new species of the genus Strigea (Strigeidae).
During a survey of birds from Argentina, two species of Digenea, one of them new, were found parasitizing the great antshrike, Taraba major (Vieillot) (Aves: Thamnophilidae). The strigeid, Strigea orbiculata sp. n. is characterized by having a body plump, a copulatory bursa without a membraneous fold ('Ringnapf'), entire testes, eggs with miracidia with eye-spots, by the arrangement of vitelline follicles in the forebody, which are densely distributed from its anterior edge, and by the absence of a neck region in the hindbody. Among the known Neotropical species of Strigea Abildgaard, 1790, only five share with Strigea orbiculata sp. n. the body shape and the distribution ofvitelline follicles in the forebody: Strigea caluri Dubois, 1962, S. elliptica (Brandes, 1888), S. inflecta Lunaschi et Drago, 2012, S. nugax Szidat, 1928 and S. sphaerocephala (Westrumb, 1823 nec Brandes 1888). However, S. caluri can be easily distinguished by having a membraneous fold in the copulatory bursa originated from 'Ringnapf', and multilobed testes. Strigea elliptica differs mainly by having a well developed 'Ringnapf' and the remaining species differ principally by metrical characters. The dicrocoeliid, Lyperosomum oswaldoi (Travassos, 1919) is reported for the first time from Argentina and T. major represents its new definitive host. The host specificity ofNeotropical Strigea spp. is discussed and an updated list of records of their hosts is provided.


Premature ovarian failure and gene polymorphisms.
Premature ovarian insufficiency (POI) is a common disorder affecting approximately 1% of women under the age of 40 years. Until now, research aiming to identify genetic causes of POI was mostly based on candidate gene approaches. Recently, several genes have been identified using this approach, and genome-wide searches were conducted. In this review, we discuss these studies and propose future direction for further research in this field. Candidate gene approach revealed NOBOX, NR5A1, FIGLA and PGRMC1 as POI-genes. Genome-wide searches (linkage and association studies) are revealing new loci/genes as well. The role in POI for most reported candidate genes is still under discussion. Because POI families with several affected cases are rare, linkage studies are difficult to conduct; however, the reported loci needs further exploration/replication. In the only genome-wide association studies conducted, the patient cohort used is very small and the reported results are awaiting replication. Unravelling the genetics of POI will need the establishment of a large international consortium.