Female cystic fibrosis mutation carriers and assisted reproductive technology: does carrier status affect reproductive outcomes?
To evaluate the association between female cystic fibrosis (CF) carrier status and in vitro fertilization (IVF) response and outcomes. The presence of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations in male carriers has been associated with infertility, yet possible adverse effects on the ovarian function and reproductive outcomes of female carriers have not been studied to date. Retrospective cohort study. Private academic, clinical reproductive center. Females<40 years of age who were screened for CFTR mutations and received IVF treatment between July 2002 and March 2013. Patients initiated controlled ovarian hyperstimulation with frequent monitoring, vaginal oocyte retrieval, fertilization, embryo transfer, and a pregnancy test. Various measures of IVF stimulation response and cycle outcome were evaluated for both carriers and noncarriers. Analysis was performed by logistic regression and Poisson regression. IVF cycles (n=199) from CFTR mutation carrier patients (n=112) were analyzed. No significant differences in outcome were noted when carriers of different mutation loci were compared in aggregate with the noncarrier group (n=6,420 cycles from 3,555 patients). Significant differences were noted for some metrics when the carriers were grouped by mutation loci. Overall, no significant differences in stimulation response and cycle outcome were noted between female CFTR mutation carriers and noncarriers. Further research is needed to investigate whether the differences noted between specific CFTR mutation loci are clinically relevant and whether CFTR mutations may impact reproductive outcomes outside the context of assisted reproductive technologies.


MRI-defined vascular depression.
The authors' goal was to characterize the clinical and demographic features of vascular depression. They classified 89 depressed patients into two groups-those with vascular (N = 32) and nonvascular (N = 57) depression-on the basis of examination of brain magnetic resonance images. All of the patients were enrolled in the National Institute of Mental Health Clinical Research Center for the Study of Depression in Later Life, located at Duke University. The patients with vascular and nonvascular depression were compared on several clinical and demographic risk factors. Bivariate analyses and a fully adjusted logistic regression model revealed that older age, late age at onset, and nonpsychotic subtype occurred more often in patients with vascular depression than in those with nonvascular depression. A family history of mental illness was found somewhat less often, and anhedonia and functional disability were seen somewhat more often in patients with vascular depression. The profile of patients with vascular depression needs to be developed further. This is likely to have important therapeutic and theoretical implications for the management of these patients.


Health-Seeking Behavior for Erectile Dysfunction in Methadone Maintenance Treatment Patients.
Background: Erectile dysfunction (ED) is commonly associated with methadone usage. However, little data is known regarding the health-seeking behavior for ED in the methadone maintenance treatment (MMT) population. This study aimed to determine the health-seeking behavior of MMT patients with ED who perceived themselves as having ED. We aimed to assess the attitudes and health-seeking behavior, the effectiveness of the treatment and the factors associated with treatment-seeking behavior. Methods: This was an observational questionnaire-based study. Patients were first screened for ED (n = 154) using the International Index of Erectile Function-5 (IIEF-5). Fifty patients with ED were evaluated for health-seeking behavior for ED. Results: More than half of the patients who thought they had ED (78%) believed their sex life was affected. Most patients (48%) did not seek any information regarding ED. Education level (p = 0.017) and marital status (p = 0.008) were predictive factors of health-seeking behavior. Conclusions: The health-seeking rate among MMT patients with ED needs to be improved. Measures to increase awareness of ED in MMT patients should be taken to overcome the barrier to health-seeking behavior. Health practitioners should take action to screen ED in this population to increase the detection rate and offer appropriate management according to the patients' needs.


Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial.
Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG 02-98 trial comparing anthracycline-based adjuvant chemotherapy (control arms) to anthracycline-docetaxel-based sequential or concurrent chemotherapy (experimental arms). After a median follow-up of 5 years, 403 patients had died and detailed information on CNS relapse was collected for these patients. CNS relapse occurred in 4.0% of control patients and 3.7% of docetaxel-treated patients. CNS relapse occurred in 27% of deceased patients in both treatment groups. CNS relapse was usually accompanied by neurologic symptoms (90%), and 25% of patients with CNS relapse died without evidence of extra-CNS relapse. Only 20% of patients survived 1 year from the diagnosis of CNS relapse. Prognosis of CNS relapse was worse for patients with meningeal carcinomatosis when compared with brain metastases. Unexpected findings included a higher rate of positive cerebrospinal fluid cytology (8% versus 3%) and more frequent use of magnetic resonance imaging for diagnosis (47% versus 30%) in the docetaxel-treated patients. There is no evidence that adjuvant docetaxel treatment is associated with an increased frequency of CNS relapse.


Earliest fossil record of bacterial-cyanobacterial mat consortia: the early Silurian Passage Creek biota (440 Ma, Virginia, USA).
Cyanobacteria in terrestrial and aquatic habitats are frequently associated with heterotrophic bacteria, and such associations are most often metabolically interactive. Functionally, the members of such bacterial-cyanobacterial consortia benefit from diverse metabolic capabilities of their associates, thus exceeding the sum of their parts. Such associations may have been just as ubiquitous in the past, but the fossil record has not produced any direct evidence for such associations to date. In this paper, we document fossil bacteria associated with a macrophytic cyanobacterial mat in the early Silurian (Llandovery) Massanutten Sandstone of Virginia, USA. Both the bacterial and the cyanobacterial cells are preserved by mineral replacement (pyrite subsequently replaced by iron oxyhydroxides) within an amorphous carbonaceous matrix which represents the common exopolysaccharide investment of the cyanobacterial colony. The bacteria are rod-shaped, over 370 nm long and 100 nm in diameter, and occur both as isolated cells and as short filaments. This occurrence represents the oldest fossil evidence for bacterial-cyanobacterial associations, documenting that such consortia were present 440 Ma ago, and revealing the potential for them to be recognized deeper in the fossil record.


The Effects of Sex, Limb Dominance, and Soccer Participation on Knee Proprioception and Dynamic Postural Control.
Both female athletes' participation in soccer and associated injuries have greatly increased in recent years. One issue is the 2-9 times greater incidence of noncontact anterior cruciate ligament (ACL) injuries in female athletes relative to male athletes in comparable sports. Several factors such as limb dominance and sporting history have been proposed to play a role in ACL incidence rates between male and female athletes. However, evidence about the effects of these factors and how they interact with sex is mixed, and thus no consensus exists. To quantify the effects of sports participation, limb dominance, and sex on dynamic postural control and knee-joint proprioception. Cross-sectional study. University research laboratory. 19 male soccer players, 17 female soccer players, 19 sedentary men, and 18 sedentary women. Joint-position sense was tested using reproduction of passive positioning on a Biodex isokinetic dynamometer (30°, 45°, and 60° from 90° of knee flexion). Three Star Excursion Balance Test directions were used to assess dynamic postural control. Normalized reach distance (% of leg length) in the anterior, posteromedial, and posterolateral directions on each leg quantified dynamic postural control. Average absolute error and constant error for both limbs quantified joint-position sense. Posteromedial reach distance was significantly better in soccer players than sedentary individuals (P = .006). Anterior reach distance was significantly better (P = .04) in sedentary individuals than soccer players. No limb-dominance or sex differences were identified for dynamic postural control, and no differences in absolute- or constant-error scores were identified. Sporting history has a direction-specific impact on dynamic postural control. Sporting history, sex, and limb dominance do not influence knee-joint proprioception when tested in an open kinetic chain using passive repositioning.


A case-control study on the association between chronic prostatitis/chronic pelvic pain syndrome and erectile dysfunction.
What's known on the subject? and What does the study add? In recent years, a number of studies have reported a high prevalence of erectile dysfunction (ED) among patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Several studies have reported that the prevalence of ED ranges from 15.0 to 40.5% in men in China with CP/CPPS; however, the previous studies focusing on the prevalence of ED among patients with CP/CPPS all neglected to explore the magnitude of this association. Our study found an association between ED and previously diagnosed CP/CPPS. The odds of previous CP/CPPS were 3.62 times greater for cases than for controls, after adjusting for patient socio-demographic characteristics, comorbidities, obesity, and alcohol abuse/alcohol dependence syndrome. To examine the association between erectile dysfunction (ED) and a previous diagnosis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using a population-based dataset. The data for this case-control study was obtained from the National Health Insurance database. A total of 3194 males, who were ≥18 years of age when they first received a diagnosis of ED, were identified and 15 970 controls were randomly selected. The prevalence and risk of CP/CPPS among cases and controls were calculated by using conditional logistic regression analysis. In total, 667 (3.5%) of the 19 164 sampled subjects had been diagnosed with CP/CPPS before the index date; CP/CPPS was found in 276 (8.6%) cases and in 391 (2.5%) controls (P < 0.001). Regression analysis indicated that cases were more likely to have had previous CP/CPPS (odd ratio 3.62, 95% confidence interval 3.07-4.26) after adjusting for patient monthly income, geographical location and urbanization level, as well as hypertension, diabetes, coronary heart disease, renal disease, obesity and alcohol abuse/alcohol dependence syndrome status, when compared with controls. We conclude that there was an association between ED and having been previously diagnosed with CP/CPPS. Urologists should be alert to the association between CP/CPPS and ED, and assess the erectile function of patients suffering from CP/CPPS.


Effects of a Home-Based DVD-Delivered Physical Activity Program on Self-Esteem in Older Adults: Results From a Randomized Controlled Trial.
Although center-based supervised physical activity interventions have proved to be successful in attenuating health declines in older adults, such methods can be costly and have limited reach. In the present study, we examined the effects of a DVD-delivered exercise intervention on self-esteem and its subdomains and the extent to which these effects were maintained. In addition, we examined whether psychological, demographic, and biological factors acted as determinants of self-esteem. Low-active, older adults (n = 307; mean [standard deviation] age =71.0 [5.1] years) were randomly assigned to a 6-month, home-based exercise program consisting of a DVD-delivered exercise intervention focused on increasing flexibility, toning, and balance (FlexToBa) or an attentional control DVD condition focused on healthy aging. Physical self-worth and three subdomains of self-esteem, global self-esteem, and self-efficacy were assessed at baseline, 6 months, and 12 months. There was a differential effect of time for the two groups for physical self-worth (F interaction(2,530.10) = 4.17, p = .016) and perception of physical condition (F interaction(1,630.77) = 8.31, p = .004). Self-efficacy, sex, body mass index, and age were significant predictors of changes in physical self-worth and perception of physical condition. Our findings suggest that a DVD-delivered exercise intervention is efficacious for improving and maintaining subdomain and domain levels of self-esteem in older adults. In addition, self-efficacy was the strongest predictor of changes in physical self-worth and perceptions of physical condition. This innovative method of delivering an exercise training program via DVD is practical and effective and has the potential for broad reach and dissemination. Clinicaltrials.govidentifier:NCT01030419.


Assignment of the human p27Kip1 gene to 12p13 and its analysis in leukemias.
The p27Kip1 (p27) gene encodes an inducible inhibitor of cyclin-dependent kinase activity. Using a murine p27 cDNA as probe, we obtained a human cDNA clone and subsequently used it to isolate a genomic clone of this gene. The coding region of the human p27 gene was contained in two exons. Both the amino acid sequence and intron-exon organization of p27 were similar to those previously found for the related cyclin-dependent kinase inhibitor p21Waf1 (p21). The p27 gene was localized to chromosome band 12p13 by a combination of somatic cell hybrid and fluorescence in situ hybridization analyses. The p27 gene product is thought to control the leukocyte cell cycle and the 12p13 chromosomal band is known to be deleted in leukemias, suggesting that the p27 gene may act as a tumor suppressor gene in leukemias. Although p27 was found to reside in the minimal region of chromosomal loss in hematological malignancies, no mutations of p27 were observed in leukemia samples. Haploinsufficiency of p27 may confer a growth advantage to leukemia cells.


Mini-review: Obesity in Caribbean Youth.
Our focus was on the determination of the growing number of youths of every race and ethnicity, diagnosed with obesity and its co-morbidities in the Caribbean. We reviewed the causes and strategies to combat obesity, and the implications of the fast food industry in enabling the escalation of obesity. We consulted several databases such as PubMed, MEDLINE, the Obesity Gene Map Database, and the USEPA Toxicity Reference Database. Organizations such as the World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), Organization for Economic Co-operation and Development (OECD) and the Pan American Health Organization (PAHO) were used as information sources. Transgenerational effects and triggers like obesogens, pathogens, environmental stress, antibiotics and gut microbiota are some of the causes of obesity, and some of these triggers are imprinted epigenetically early in embryonic development, leading to lifelong obesity. With an estimated population of 42 million in the Caribbean, the economic cost of obesity, including medical, absenteeism, presenteeism, insurance, disability, direct and indirect cost, was estimated cost of 68.5 billion USD with 88.2 million quality-adjusted life years lost. Genome-wide association studies have established that genetics play a role in the aetiology of this "non-communicable" disease. While the development of personalized interventions according to genotype is futuristic, we must focus on effective nutrition and physical education classes in schools and establishing monitoring programmes using simple tools such as scales and tape measures as suggested intervention. A Pigovian tax to control the fast food industry is mandatory. Nevertheless, lifestyle adjustment, including alterations in diet and increased physical activity, continues to be a sound recommendation.


Efficacy and safety of dopamine agonists in patients treated with antipsychotics and presenting a macroprolactinoma.
In patients treated with antipsychotics, the rare occurrence of a macroprolactinoma represents a therapeutic challenge. Our aim was to evaluate the efficacy and psychiatric safety of dopamine agonists (DAs) prescribed for large macroprolactinomas in patients with psychosis treated with antipsychotics. This was a multicenter (France and Belgium) retrospective study. Eighteen patients treated with antipsychotics were included. Under DA, median PRL levels decreased from 1247 (117-81 132) to 42 (4-573) ng/mL (P = 0.008), from 3850 (449-38 000) to 141 (60-6000) ng/mL (P = 0.037) and from 1664 (94-9400) to 1215 (48-5640) ng/mL (P = 0.56) when given alone (n = 8), before surgery (n = 7), or after surgery (n = 6), respectively. The prolactinoma median largest diameter decreased by 28% (0-57) in patients under DAs alone (P = 0.02) but did not change when given after surgery. Optic chiasm decompression was achieved in 82% of patients. Five patients (28%) were admitted for psychotic relapse while receiving DAs (but three of them had stopped antipsychotic treatment at that time). A more severe underlying psychosis, rather than the DA treatment itself, may explain such psychiatric admissions. Even if the DA efficacy on PRL levels and tumor volume in patients with macroprolactinoma under antipsychotic drugs is less impressive than that typically observed, it may be considered satisfactory for half of our patients, particularly in cases of optic chiasm compression. Psychotic exacerbation was unusual in these patients, occurring mostly in those with the most severe psychotic forms. DAs may therefore be used as antitumor treatment for macroprolactinoma in patients with visual involvement, severe headaches or invasion into the skull base who receive antipsychotics.


Core Outcome Domains for Clinical Trials on Somatic Symptom Disorder, Bodily Distress Disorder, and Functional Somatic Syndromes: European Network on Somatic Symptom Disorders Recommendations.
The harmonization of core outcome domains in clinical trials facilitates comparison and pooling of data, and simplifies the preparation and review of research projects and comparison of risks and benefits of treatments. Therefore, we provide recommendations for the core outcome domains that should be considered in clinical trials on the efficacy and effectiveness of interventions for somatic symptom disorder, bodily distress disorder, and functional somatic syndromes. The European Network on Somatic Symptom Disorders group of more than 20 experts in the field met twice in Hamburg to discuss issues of assessment and intervention research in somatic symptom disorder, bodily distress disorder, and functional somatic syndromes. The consensus meetings identified core outcome domains that should be considered in clinical trials evaluating treatments for somatic symptom disorder and associated functional somatic syndromes. The following core domains should be considered when defining ascertainment methods in clinical trials: a) classification of somatic symptom disorder/bodily distress disorder, associated functional somatic syndromes, and comorbid mental disorders (using structured clinical interviews), duration of symptoms, medical morbidity, and prior treatments; b) location, intensity, and interference of somatic symptoms; c) associated psychobehavioral features and biological markers; d) illness consequences (quality of life, disability, health care utilization, health care costs; e) global improvement and treatment satisfaction; and f) unwanted negative effects. The proposed criteria are intended to improve synergies of clinical trials and to facilitate decision making when comparing different treatment approaches. These recommendations should not result in inflexible guidelines, but increase consistency across investigations in this field.


Apolipoprotein E epsilon4 allele and progression of cortical Lewy body pathology in Parkinson's disease.
To elucidate whether the apolipoprotein E epsilon4 allele (APOE4) affects cortical neuropathology in Parkinson's disease (PD), we determined APOE genotypes and quantified the densities of cortical Lewy bodies (LBs), amyloid plaques and neurofibrillary tangles in 22 autopsy-proven PD cases (12 with dementia; 10 without dementia) that were not accompanied by Alzheimer's disease. The APOE4 frequency in the demented patient group was 0.21, which was significantly higher than that in Japanese controls (P < 0.04). LB densities in demented PD patients were significantly higher than those in non-demented PD patients, despite the shorter disease duration in the former. Moreover, plaque density in the temporal cortex and LB density in the cingulate cortex were significantly higher in the group with APOE4 than in that without the allele. There was no difference in tangle density between these two groups. These results suggest that APOE4 may influence the increase in the number of cortical LBs and amyloid plaques in PD. It is possible that when PD occurs in individuals with APOE4, concomitantly evolving cortical LB pathology in a proportion of cases results in limbic (transitional) or neocortical-type LB disease.


Haloperidol impairs learning and error-related negativity in humans.
Humans are able to monitor their actions for behavioral conflicts and performance errors. Growing evidence suggests that the error-related negativity (ERN) of the event-related cortical brain potential (ERP) may index the functioning of this response monitoring system and that the ERN may depend on dopaminergic mechanisms. We examined the role of dopamine in ERN and behavioral indices of learning by administering either 3 mg of the dopamine antagonist (DA) haloperidol (n = 17); 25 mg of diphenhydramine (n = 16), which has a similar CNS profile but without DA properties; or placebo (n = 18) in a randomized, double-blind manner to healthy volunteers. Three hours after drug administration, participants performed a go/no-go Continuous Performance Task, the Eriksen Flanker Task, and a learning-dependent Time Estimation Task. Haloperidol significantly attenuated ERN amplitudes recorded during the flanker task, impaired learning of time intervals, and tended to cause more errors of commission, compared to placebo, which did not significantly differ from diphenhydramine. Drugs had no significant effects on the stimulus-locked P1 and N2 ERPs or on behavioral response latencies, but tended to affect post-error reaction time (RT) latencies in opposite ways (haloperidol decreased and diphenhydramine increased RTs). These findings support the hypothesis that the DA system is involved in learning and the generation of the ERN.


[Parameters of ovulation in spontaneous ovulatory cycles].
The parameters of ovulation used at the infertility clinic of Tygerberg Hospital were evaluated in 45 spontaneously ovulating women. The mean maximum preovulatory serum oestradiol level was 1 274 pmol/l with a standard deviation of 432 pmol/l and an average daily increase of 245 pmol/l over the last 3 preovulatory days. Normal values were identified for a cervical mucus scoring system similar to the Insler system. The mean midluteal serum progesterone value was 25,5 nmol/l with a standard deviation of 7,5 nmol/l. Ultrasound examinations of the ovaries to diagnose ovulation were used for the first time in Tygerberg Hospital; the average of maximum diameters in three dimensions was used to measure follicles. The average daily pre-ovulatory growth rate was 2,3 mm and the maximum follicle size 20,5 mm with a standard deviation of 2,3 mm. The most common ultrasonic signs of ovulation were reduction in follicle size, development of irregular borders and intrafollicular echoes. In 5 patients endometrial histological dating lagged more than 2 days behind ultrasonic signs of ovulation. These were considered cases of luteal phase insufficiency. The maximum pre-ovulatory serum oestradiol levels were statistically significantly lower in these cases.


Determinants of bovine thermal response to heat and solar radiation exposures in a field environment.
Continuous exposure of cattle to summer heat in the absence of shade results in significant hyperthermia and impairs growth and general health. Reliable predictors of heat strain are needed to identify this condition. A 12-day study was conducted during a moderate summer heat period using 12 Angus x Simmental (Bos taurus) steers (533 ± 12 kg average body weight) to identify animal and ambient determinations of core body temperature (T(core)) and respiration rate (RR) responses to heat stress. Steers were provided standard diet and water ad libitum, and implanted intraperitoneally with telemetric transmitters to monitor T(core) hourly. Visual count of flank movement at 0800 and 1500 hours was used for RR. Dataloggers recorded air temperature (T(a)), and black globe temperatures (T(bg)) hourly to assess radiant heat load. Analysis was across four periods and 2 consecutive days averaged within each period. Average T(a) and T(bg) increased progressively from 21.7 to 30.3°C and 25.3 to 34.0°C, respectively, from the first to fourth periods. A model utilizing a quadratic function of T(a) explained the most variation in T(core) (R(2) = 0.56). A delay in response from 1 to 3 h did not significantly improve R(2) for this relationship. Measurements at 0800 and 1500 hours alone are sufficient to predict heat strain. Daily minimum core body temperature and initial 2-h rise in T(a) were predictors of maximum core temperature and RR. Further studies using continuous monitoring are needed to expand prediction of heat stress impact under different conditions.


Sarcoidosis: a disorder commoner in non-smokers?
The smoking habits of 202 patients presenting with sarcoidosis, as recorded in the clinical case records, were compared with figures from the General Household Surveys (GHS) to determine whether there was any association between smoking habit and sarcoidosis. In 19 there was no record of smoking habit. Of the remaining 183 patients, 40 (21.9%) were smokers, which was significantly less than expected from the GHS figures (p less than 0.001). This association between non-smoking and sarcoidosis persisted despite further analysis by sex and age distribution and socioeconomic grouping. Statistical likelihood models showed that ex-smokers were similar to current smokers with respect to the association between smoking and sarcoidosis. This association was greatest in those patients with stage I sarcoidosis and less for those with other stages of the disease.


Implant neck configurations for preservation of marginal bone level: a systematic review.
The aim of this article was to evaluate the effectiveness of various implant neck configurations in the preservation of marginal bone level as well as to identify the available scientific evidence. Online and hand searches of the literature published from 1976 through 2009 were conducted to identify studies dealing with modifications in the implant neck area and marginal bone loss for at least a 5-year observation period. The search terms that were used, alone or in combination, were "implant neck," "marginal bone loss," "neck design," "bone resorption," "bone remodeling," and "implant collar." Relevant studies were selected according to predetermined inclusion and exclusion criteria. The initial search yielded 3,517 relevant titles and revealed eight different implant neck configurations and/or methods suggested for the preservation of marginal bone. These methods included changes in implant neck length and design, implant surface characteristics, implant diameter, and/or insertion depth; the addition of microthreads; the use of one-piece implants; and the concept of platform switching. After subsequent filtering, 20 studies were finally selected and involved the following methods: the use of microthreads (1 study); modifications in implant surface characteristics (11 studies), implant diameter (4 studies), or insertion depth (2 studies); the use of one-piece implants (3 studies); and platform switching (1 study). Because of the heterogeneity of the studies, it was not possible to analyze the data statistically. No evidence was found regarding the effectiveness of any specific modification in the implant neck area in preserving marginal bone or preventing marginal bone loss. The current literature provides insufficient evidence about the effectiveness of different implant neck configurations in the preservation of marginal bone. Long-term randomized controlled clinical trials are needed to elucidate the effects of such modifications.


Psychological treatments for common mental health problems experienced by informal carers of adults with chronic physical health conditions (Protocol).
Improved life expectancy is resulting in increased outpatient treatment of people with chronic physical health conditions and reliance on the provision of informal care in the community. However, informal care is also associated with increased risk of experiencing common mental health difficulties such as depression and anxiety. Currently there is a lack of evidence-based treatments for such difficulties, resulting in poor health outcomes for both the informal carer and care recipient. Electronic databases will be systemically searched for randomised controlled trials examining the effectiveness of psychological interventions targeted at treating depression or anxiety experienced by informal carers of patients with chronic physical health conditions. Database searches will be supplemented by contact with experts, reference and citation checking and grey literature. Both published and unpublished research in English language will be reviewed with no limitations on year or source. Individual, group and patient-carer dyad focused interventions will be eligible. Primary outcomes of interest will be validated self-report or clinician administered measures of depression or anxiety. If data allows a meta-analysis will examine: (1) the overall effectiveness of psychological interventions in relation to outcomes of depression or anxiety; (2) intervention components associated with effectiveness. This review will provide evidence on the effectiveness of psychological interventions for depression and anxiety experienced by informal carers of patients with chronic physical health conditions. In addition, it will examine intervention components associated with effectiveness. Results will inform the design and development of a psychological intervention for carers of people with chronic physical health conditions experiencing depression and anxiety. PROSPERO registration number: CRD42012003114.


Inflammatory markers in pediatric stroke: An attempt to better understanding the pathophysiology.
The mechanisms of childhood and perinatal arterial ischemic stroke (AIS) are poorly understood. Multiple risk factors include cerebral arteriopathy, congenital cardiac disease, infection, sickle cell disease, and maternal-fetal conditions in neonates. For infections and parainfectious conditions being the most important a possible inflammatory pathophysiology has long been suspected. This pilot study aims to detect, whether there are any abnormalities of inflammatory markers associated with childhood and neonatal stroke. The concentration of 23 different metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), endothelial factors, vascular cell adhesion proteins, and cytokines in plasma were measured in 12 children with AIS, 7 healthy age matched controls and 6 full term neonates with perinatal AIS. At the time of the acute event children with AIS had significantly elevated levels of MMP-9, TIMP4, IL-6, IL-8 and CRP compared to controls (p < 0.05). Except for lower IL-6 and CRP levels the pattern of children with a history of varizella-zoster virus (VZV) and other viral infections did not differ to the non-infectious group. Median levels of MMP-1, MMP-2, TIMP-1, TIMP-2, sE-selectin, sICAM-1, sVCAM-1, IL-8, IL-10, TNF-alpha, VEGF, Fetuin A were found to be higher in the neonatal group when compared with older children. This pilot study supports the assumption of an inflammatory process and up-regulation of metalloproteinases and their inhibitors, and altered pattern of circulating pro-inflammatory cytokines, CRP and vWF levels in pediatric and neonatal AIS. It highlights the feasibility but also difficulties for similar larger future studies that should aim to clarify childhood stroke etiopathogenesis and consecutive further therapeutic options.


Crystal structure of human BPI and two bound phospholipids at 2.4 angstrom resolution.
Bactericidal/permeability-increasing protein (BPI), a potent antimicrobial protein of 456 residues, binds to and neutralizes lipopolysaccharides from the outer membrane of Gram-negative bacteria. At a resolution of 2.4 angstroms, the crystal structure of human BPI shows a boomerang-shaped molecule formed by two similar domains. Two apolar pockets on the concave surface of the boomerang each bind a molecule of phosphatidylcholine, primarily by interacting with their acyl chains; this suggests that the pockets may also bind the acyl chains of lipopolysaccharide. As a model for the related plasma lipid transfer proteins, BPI illuminates a mechanism of lipid transfer for this protein family.


Ageing studies on bats: a review.
Bat biologists have long known about the exceptional longevity of bats (Order: Chiroptera), which is unusual for mammals of such a small size and a high metabolic rate. Yet relatively few mechanistic studies have focused on this longevity. On average, species of Chiroptera live three times longer than predicted by their body size. In addition, bats have other life history traits that are characteristic of large, long-lived mammals such as few and large offspring and slow growth rates. Bats fit the evolutionary theory of ageing, as their extended longevity is predicted by their ability to escape extrinsic mortality through flight and, in some species, hibernation. They also show tradeoffs between longevity and reproduction, as predicted by the disposable soma theory of ageing. From a physiological perspective, bat longevity reportedly correlates with replicative longevity, low brain calpain activity, and reduced reactive oxygen species production. As long-lived and physiologically interesting organisms, bats may prove to be an informative model system for ageing research.


Artificial intelligence for advance requesting of immunohistochemistry in diagnostically uncertain prostate biopsies.
The use of immunohistochemistry in the reporting of prostate biopsies is an important adjunct when the diagnosis is not definite on haematoxylin and eosin (H&E) morphology alone. The process is however inherently inefficient with delays while waiting for pathologist review to make the request and duplicated effort reviewing a case more than once. In this study, we aimed to capture the workflow implications of immunohistochemistry requests and demonstrate a novel artificial intelligence tool to identify cases in which immunohistochemistry (IHC) is required and generate an automated request. We conducted audits of the workflow for prostate biopsies in order to understand the potential implications of automated immunohistochemistry requesting and collected prospective cases to train a deep neural network algorithm to detect tissue regions that presented ambiguous morphology on whole slide images. These ambiguous foci were selected on the basis of the pathologist requesting immunohistochemistry to aid diagnosis. A gradient boosted trees classifier was then used to make a slide-level prediction based on the outputs of the neural network prediction. The algorithm was trained on annotations of 219 immunohistochemistry-requested and 80 control images, and tested by threefold cross-validation. Validation was conducted on a separate validation dataset of 222 images. Non IHC-requested cases were diagnosed in 17.9 min on average, while IHC-requested cases took 33.4 min over multiple reporting sessions. We estimated 11 min could be saved on average per case by automated IHC requesting, by removing duplication of effort. The tool attained 99% accuracy and 0.99 Area Under the Curve (AUC) on the test data. In the validation, the average agreement with pathologists was 0.81, with a mean AUC of 0.80. We demonstrate the proof-of-principle that an AI tool making automated immunohistochemistry requests could create a significantly leaner workflow and result in pathologist time savings.


Finite Element Analysis of the Mouse Distal Femur with Tumor Burden in Response to Knee Loading.
Breast cancer-associated bone metastasis induces bone loss, followed by an increased risk of bone fracture. To develop a strategy for preventing tumor growth and protecting bone, an understanding of the mechanical properties of bone under tumor burden is indispensable. Using a mouse model of mammary tumor, we conducted finite element analysis (FEA) of two bone samples from the distal femur. One sample was from a placebo-treated mouse, and the other was from a mouse treated with the investigational drug candidate, PD407824, an inhibitor of checkpoint kinases. Mechanical testing and microCT images revealed that bone strength is improved by administration of PD407824. In response to loading to the knee, FEA predicted that the peaks of von Mises stress, an indicator of fracture yielding, as well as the third principal compressive stress, were higher in the placebo-treated femur than the drug-treated femur. Higher peak stresses in trabecular segments were observed in the lateral condyle, a critical region for integrity of the knee joint. Collectively, this FE study supports the notion that mechanical weakening of the femur was observed in the tumor-invaded trabecular bone, and chemical agents such as PD407824 may potentially assist in preventing bone loss and bone fracture.


Re-assembly, quality evaluation, and annotation of 678 microbial eukaryotic reference transcriptomes.
De novo transcriptome assemblies are required prior to analyzing RNA sequencing data from a species without an existing reference genome or transcriptome. Despite the prevalence of transcriptomic studies, the effects of using different workflows, or "pipelines," on the resulting assemblies are poorly understood. Here, a pipeline was programmatically automated and used to assemble and annotate raw transcriptomic short-read data collected as part of the Marine Microbial Eukaryotic Transcriptome Sequencing Project. The resulting transcriptome assemblies were evaluated and compared against assemblies that were previously generated with a different pipeline developed by the National Center for Genome Research. New transcriptome assemblies contained the majority of previous contigs as well as new content. On average, 7.8% of the annotated contigs in the new assemblies were novel gene names not found in the previous assemblies. Taxonomic trends were observed in the assembly metrics. Assemblies from the Dinoflagellata showed a higher number of contigs and unique k-mers than transcriptomes from other phyla, while assemblies from Ciliophora had a lower percentage of open reading frames compared to other phyla. Given current bioinformatics approaches, there is no single "best" reference transcriptome for a particular set of raw data. As the optimum transcriptome is a moving target, improving (or not) with new tools and approaches, automated and programmable pipelines are invaluable for managing the computationally intensive tasks required for re-processing large sets of samples with revised pipelines and ensuring a common evaluation workflow is applied to all samples. Thus, re-assembling existing data with new tools using automated and programmable pipelines may yield more accurate identification of taxon-specific trends across samples in addition to novel and useful products for the community.


Diagnosis of Takotsubo cardiomyopathy.
Takotsubo cardiomyopathy, also known as left ventricular apical ballooning syndrome and stress-induced cardiomyopathy, is typically characterized by transient systolic dysfunction of the apical and mid-segments of the left ventricle, in the absence of obstructive coronary artery lesions. Patients may present with symptoms and signs of acute coronary syndrome, and the provider is challenged to differentiate between these conditions. In this review, we guide the reader through the diagnostic pathway, focusing on differential diagnoses and diagnostic criteria for takotsubo cardiomyopathy.


Cell-based therapy for myocardial repair in patients with acute myocardial infarction: rationale and study design of the SWiss multicenter Intracoronary Stem cells Study in Acute Myocardial Infarction (SWISS-AMI).
Recent studies report that intracoronary administration of autologous bone marrow mononucleated cells (BM-MNCs) may improve remodeling of the left ventricle after acute myocardial infarction (AMI). Subgroup analysis suggest that early treatment between days 4 and 7 after AMI is probably most effective; however, the optimal time point of intracoronary cell administration has never been addressed in clinical trials. Furthermore, reliable clinical predictors are lacking for identifying patients who are thought to have most benefit from cellular therapy. In a multicenter trial, 192 patients with AMI successfully treated by percutaneous coronary intervention (PCI) of the infarct-related artery will be randomized in a 1:1:1 pattern to 1 control and 2 BM-MNC treatment groups. The control group will be treated with state-of-the-art medical management. The treatment groups will receive intracoronary administration of autologous BM-MNC at 5 to 7 days or 3 to 4 weeks after the initial event, respectively. Left ventricular function as well as scar size, transmural extension, and regional wall motion score will be assessed by cardiac magnetic resonance (CMR) studies at baseline and after 4 and 12 months. Fifty milliliters of bone marrow will be harvested by aspiration from the iliac crest and then carried by courier to a centralized cell processing facility. The mononucleated cell fraction will be isolated by density gradient centrifugation, washed, and resuspended in 10 mL of injection medium. The cells will be characterized by fluorescence-activated cell sorting analysis and tested for sterility and potency both "in vitro" and "in vivo." Bone marrow MNC will then be reinfused directly in the infarct-related coronary artery. The primary end point is the change in global left ventricular (LV) ejection fraction by CMR at 4 months as compared to baseline. Comparisons will then be made between each of the prespecified therapy subgroups (early and late after AMI) and the control group. Secondary end points include change in infarct size, change in regional myocardial thickness, and wall motion at 4 and 12 months compared to baseline. Infarct extension (size and transmural extension), time delay to PCI, and coronary flow characteristics after PCI will be assessed as potential predictors of LV remodeling and change after cell therapy. Major adverse cardiac events (MACE) (death, myocardial infarction, coronary revascularization, rehospitalization for heart failure) will be assessed at 4, 12, and 24 months and time to MACE will be estimated. With the present study, we aim to determine the optimal time point of intracoronary administration of autologous BM-MNC after AMI on LV remodeling.


Concentration-dependent tubular secretion of acetazolamide and its inhibition by salicylic acid in the isolated perfused rat kidney.
An isolated perfused rat kidney (IPK) technique was used to study the effect of salicylic acid (SA) on the excretion of acetazolamide (AZ). Initial experiments were conducted in the absence of interactants at three nominal AZ concentrations (50, 100, and 250 micrograms/ml). Over the concentration range studied, AZ demonstrated net tubular secretion in the IPK. Significant decreases in excretion ratio (4.97 +/- 0.79-2.66 +/- 1.1) and secretory clearance (0.809 +/- 0.23-0.541 +/- 0.28) were observed with increasing AZ concentration, consistent with saturation of tubular secretion. Using a facilitated model for renal secretion, values of tubular transport parameters were obtained from a plot of excretion ratio vs. unbound AZ concentration: tmax = 118 +/- 29.4 micrograms/min, KM = 53.4 +/- 22.4 micrograms/ml, and tmax(A) = 6.31 +/- 2.82 micrograms/min. In the presence of SA (200 micrograms/ml), renal secretion of AZ was inhibited, as demonstrated by significant decreases in renal clearance (0.731 +/- 0.21-0.147 +/- 0.03) and excretion ratio (3.77 +/- 0.82-0.378 +/- 0.07). Although these findings were indicative of a reabsorption component to AZ excretion in the IPK that had not been previously proposed, the results were consistent with a previous investigation of concomitant administration of AZ and SA in humans (Br. J. Clin. Pharmacol. 27, 866, 1989), thereby endorsing utilization of the IPK as a screening tool for renal clearance mechanisms in humans.


Optimizing hot carrier effects in Pt-decorated plasmonic heterostructures.
Hot carrier generation by light in various semiconductors and metallic nanostructures is important for many photocatalytic and photochemical processes, including water and hydrogen splitting. Here, we report on investigations of hot electron generation and extraction from Pt decorated SiO2-Au nanoparticles using the degradation of methylene blue dye as a test-bed. Enhanced catalytic activity was found with an increase of Pt loading on the surface of the heterostructures. The small size of the Au nanoparticles (∼12 nm) decorating the silica nanoparticles reduces hot electron collisions and related thermalization processes, since charge carriers have short paths to the surface where reactions take place and where Pt is situated. The heterostructures exhibit a broad plasmonic resonance in the visible wavelength range from 500 to 700 nm and hot carrier generation predominately takes place under resonant excitation. Electron-microscopy characterization and numerical modelling have allowed the optimization of Pt coverage for hot-electron transfer, consisting of a thin Pt shell covering the Au nanoparticle with Pt nanoparticles additionally placed on top. This geometry provides an increased number of active sites for methylene blue degradation and promotes separation of charge carriers generated by plasmonic excitations in Au. Such SiO2-Au-Pt nanoparticles are attractive for hot-electron production due to the tunability of their plasmonic resonance and enhanced catalytic activity.


Paradoxical gait at a narrowed entrance in a patient with Hoehn-Yahr stage III Parkinson's disease.
Recently, we studied fallers and non-fallers with Hoehn-Yahr stage III Parkinson's disease (PD) using a path that suddenly narrowed, which we originally designed and produced. A risk of future falls was suggested to be related to slow gait with freezing (SGF) elicited by a fear of falling before arrival at a narrowed entrance or while walking on a narrow path, as well as to the Unified Parkinson's Disease Rating Scale part II score, associated with SGF. In the same study, we had faller patients walk on a path that narrowed in a straight-line fashion to determine whether SGF could be improved. In one patient, who showed a unique paradoxical gait, SGF resolved. We describe this patient in the hope that our experience will provide potential clues to effective ways to prevent future falls in patients with Hoehn-Yahr stage III PD. To prevent gait instability elicited by fear of falling in patients with Hoehn-Yahr stage III PD, it might be useful to remove narrowed entrances.


Strategy for cryptanalysis of optical encryption in the Fresnel domain.
Traditionally, cryptanalysis of optical security systems attempts to find original keys. Usually, by use of this kind of method, one can find a set of keys located close to the original keys in the key space. We call such a set the region of original key (ROK). For an optical encryption system in the Fresnel domain, such a strategy is ineffective since it needs to perform an exhaustive search to determine the system geometry or to solve an extremely large set of system equations. We propose to employ an alternative search strategy: to find a region of possible key (RPK). Since there is only one ROK for a cypher system but there are many RPKs, the probability to find a key in the RPK would be higher than in the ROK. Our analysis reveals that even a Fresnel-based encryption system has larger key space, but there are also serious security problems to be resolved.


Genomic Selection for Wheat Blast in a Diversity Panel, Breeding Panel and Full-Sibs Panel.
Wheat blast is an emerging threat to wheat production, due to its recent migration to South Asia and Sub-Saharan Africa. Because genomic selection (GS) has emerged as a promising breeding strategy, the key objective of this study was to evaluate it for wheat blast phenotyped at precision phenotyping platforms in Quirusillas (Bolivia), Okinawa (Bolivia) and Jashore (Bangladesh) using three panels: (i) a diversity panel comprising 172 diverse spring wheat genotypes, (ii) a breeding panel comprising 248 elite breeding lines, and (iii) a full-sibs panel comprising 298 full-sibs. We evaluated two genomic prediction models (the genomic best linear unbiased prediction or GBLUP model and the Bayes B model) and compared the genomic prediction accuracies with accuracies from a fixed effects model (with selected blast-associated markers as fixed effects), a GBLUP + fixed effects model and a pedigree relationships-based model (ABLUP). On average, across all the panels and environments analyzed, the GBLUP + fixed effects model (0.63 ± 0.13) and the fixed effects model (0.62 ± 0.13) gave the highest prediction accuracies, followed by the Bayes B (0.59 ± 0.11), GBLUP (0.55 ± 0.1), and ABLUP (0.48 ± 0.06) models. The high prediction accuracies from the fixed effects model resulted from the markers tagging the 2NS translocation that had a large effect on blast in all the panels. This implies that in environments where the 2NS translocation-based blast resistance is effective, genotyping one to few markers tagging the translocation is sufficient to predict the blast response and genome-wide markers may not be needed. We also observed that marker-assisted selection (MAS) based on a few blast-associated markers outperformed GS as it selected the highest mean percentage (88.5%) of lines also selected by phenotypic selection and discarded the highest mean percentage of lines (91.8%) also discarded by phenotypic selection, across all panels. In conclusion, while this study demonstrates that MAS might be a powerful strategy to select for the 2NS translocation-based blast resistance, we emphasize that further efforts to use genomic tools to identify non-2NS translocation-based blast resistance are critical.


Tarp-Assisted Cooling as a Method of Whole-Body Cooling in Hyperthermic Individuals.
We investigated the efficacy of tarp-assisted cooling as a body cooling modality. Participants exercised on a motorized treadmill in hot conditions (ambient temperature 39.5°C [103.1°F], SD 3.1°C [5.58°F]; relative humidity 38.1% [SD 6.7%]) until they reached exercise-induced hyperthermia. After exercise, participants were cooled with either partial immersion using a tarp-assisted cooling method (water temperature 9.20°C [48.56°F], SD 2.81°C [5.06°F]) or passive cooling in a climatic chamber. There were no differences in exercise duration (mean difference=0.10 minutes; 95% CI -5.98 to 6.17 minutes or end exercise rectal temperature (mean difference=0.10°C [0.18°F]; 95% CI -0.05°C to 0.25°C [-0.09°F to 0.45°F] between tarp-assisted cooling (48.47 minutes [SD 8.27 minutes]; rectal temperature 39.73°C [103.51°F], SD 0.27°C [0.49°F]) and passive cooling (48.37 minutes [SD 7.10 minutes]; 39.63°C [103.33°F], SD 0.40°C [0.72°F]). Cooling time to rectal temperature 38.25°C (100.85°F) was significantly faster in tarp-assisted cooling (10.30 minutes [SD 1.33 minutes]) than passive cooling (42.78 [SD 5.87 minutes]). Cooling rates for tarp-assisted cooling and passive cooling were 0.17°C/min (0.31°F/min), SD 0.07°C/min (0.13°F/min) and 0.04°C/min (0.07°F/min), SD 0.01°C/min (0.02°F/min), respectively (mean difference=0.13°C [0.23°F]; 95% CI 0.09°C to 0.17°C [0.16°F to 0.31°F]. No sex differences were observed in tarp-assisted cooling rates (men 0.17°C/min [0.31°F/min], SD 0.07°C/min [0.13°F/min]; women 0.16°C/min [0.29°F/min], SD 0.07°C/min [0.13°F/min]; mean difference=0.02°C/min [0.04°F/min]; 95% CI -0.06°C/min to 0.10°C/min [-0.11°F/min to 0.18°F/min]). Women (0.04°C/min [0.07°F/min], SD 0.01°C/min [0.02°F/min]) had greater cooling rates than men (0.03°C/min [0.05°F/min], SD 0.01°C/min [0.02°F/min]) in passive cooling, with negligible clinical effect (mean difference=0.01°C/min [0.02°F/min]; 95% CI 0.001°C/min to 0.024°C/min [0.002°F/min to 0.04°F/min]). Body mass was moderately negatively correlated with the cooling rate in passive cooling (r=-0.580) but not in tarp-assisted cooling (r=-0.206). In the absence of a stationary cooling method such as cold-water immersion, tarp-assisted cooling can serve as an alternative, field-expedient method to provide on-site cooling with a satisfactory cooling rate.


Inhibitory effects of crude extracts from some edible Thai plants against replication of hepatitis B virus and human liver cancer cells.
Edible plants such as Cratoxylum formosum (Jack) Dyer, Curcumin longa Lin, Momordica charantia Lin and Moringa oleifera Lam have long been believed in Thai culture to relieve ulcers and the symptoms of liver disease. However, little is known about their anti-liver cancer properties and antiviral activity against hepatitis B virus (HBV). The aim of this study was to investigate the anti-liver cancer and anti-HBV activities of crude extracts from these edible plants on human liver cancer cells. Plant samples were prepared and extracted using buffer and hydro-alcoholic solvents. The MTT assay was performed to investigate the effects of the plant extracts on the cell viability of HepG2 cells. The inhibitory effect on replication of HBV was analysed by determining the level of HBV covalently closed circular DNA (cccDNA) in transiently transfected HepG2 cells with the DNA expression plasmid of the HBV genome using a quantitative real-time PCR. Buffer and hydroalcoholic extracts from C. formosum (leaf) reduced cell viability of HepG2 cells and they also inhibited HBV cccDNA. Crude extracts from C. longa (bulb) in both solvents did not have any cytotoxic effects on the HepG2 cells, but they significantly decreased the level of HBV cccDNA. Buffer extracts from the leaves of M. charantia and the fruits of M. oleifera showed to have anti-HBV activity and also a mild cytotoxicity effect on the HepG2 cells. In addition, leaves of M. Oleifera extracted by hydroalcoholic solvent drastically decreased the level of cccDNA in transiently transfected HepG2 cells. Some crude extracts of edible plants contain compounds that demonstrate anti-liver cancer and anti-HBV activities.


Sex difference and factors associated with outcome in patients with sustained ventricular arrhythmias.
To describe gender differences and factors of importance for outcome in patients referred for sustained ventricular arrhythmias. Two hundred and fifty three patients took part in the survey, 126 (20 women) had sustained monomorphic ventricular tachycardia (VT) and 127 (31 women) had polymorphic VT/ventricular fibrillation. Ischemic heart disease was less common in women than in men (47 vs. 80%). At discharge, an ICD implant was similarly common in women (33%) and men (29%). One hundred and twenty five (65%) men and 37 (79%) women were alive at follow-up, p =0.08 (median follow-up 53 months). Independent predictors of long-term mortality were: 1) PVT/VF as the presenting arrhythmia, 2) a low ejection fraction, 3) increased QRS duration and 4) diabetes mellitus. The lower proportion of women compared to men being referred for evaluation of sustained ventricular arrhythmias may contribute to the lower number of ICD implants in women. The long-term survival in women and men did not differ significantly.


A unifying hypothesis for hydrocephalus, Chiari malformation, syringomyelia, anencephaly and spina bifida.
This work is a modified version of the Casey Holter Memorial prize essay presented to the Society for Research into Hydrocephalus and Spina Bifida, June 29th 2007, Heidelberg, Germany. It describes the origin and consequences of the Chiari malformation, and proposes that hydrocephalus is caused by inadequate central nervous system (CNS) venous drainage. A new hypothesis regarding the pathogenesis, anencephaly and spina bifida is described.Any volume increase in the central nervous system can increase venous pressure. This occurs because veins are compressible and a CNS volume increase may result in reduced venous blood flow. This has the potential to cause progressive increase in cerebrospinal fluid (CSF) volume. Venous insufficiency may be caused by any disease that reduces space for venous volume. The flow of CSF has a beneficial effect on venous drainage. In health it moderates central nervous system pressure by moving between the head and spine. Conversely, obstruction to CSF flow causes localised pressure increases, which have an adverse effect on venous drainage.The Chiari malformation is associated with hindbrain herniation, which may be caused by low spinal pressure relative to cranial pressure. In these instances, there are hindbrain-related symptoms caused by cerebellar and brainstem compression. When spinal injury occurs as a result of a Chiari malformation, the primary pathology is posterior fossa hypoplasia, resulting in raised spinal pressure. The small posterior fossa prevents the flow of CSF from the spine to the head as blood enters the central nervous system during movement. Consequently, intermittent increases in spinal pressure caused by movement, result in injury to the spinal cord. It is proposed that posterior fossa hypoplasia, which has origins in fetal life, causes syringomyelia after birth and leads to damage to the spinal cord in spina bifida. It is proposed that hydrocephalus may occur as a result of posterior fossa hypoplasia, where raised pressure occurs as a result of obstruction to flow of CSF from the head to the spine, and cerebral injury with raised pressure occurs in anencephaly by this mechanism.The current view of dysraphism is that low central nervous system pressure and exposure to amniotic fluid, damage the central nervous system. The hypothesis proposed in this essay supports the view that spina bifida is a manifestation of progressive hydrocephalus in the fetus. It is proposed that that mesodermal growth insufficiency influences both neural tube closure and central nervous system pressure, leading to dysraphism.


Structure and function of lysosomal phospholipase A2 and lecithin:cholesterol acyltransferase.
Lysosomal phospholipase A2 (LPLA2) and lecithin:cholesterol acyltransferase (LCAT) belong to a structurally uncharacterized family of key lipid-metabolizing enzymes responsible for lung surfactant catabolism and for reverse cholesterol transport, respectively. Whereas LPLA2 is predicted to underlie the development of drug-induced phospholipidosis, somatic mutations in LCAT cause fish eye disease and familial LCAT deficiency. Here we describe several high-resolution crystal structures of human LPLA2 and a low-resolution structure of LCAT that confirms its close structural relationship to LPLA2. Insertions in the α/β hydrolase core of LPLA2 form domains that are responsible for membrane interaction and binding the acyl chains and head groups of phospholipid substrates. The LCAT structure suggests the molecular basis underlying human disease for most of the known LCAT missense mutations, and paves the way for rational development of new therapeutics to treat LCAT deficiency, atherosclerosis and acute coronary syndrome.


Assessing the effect of hypoxia on cardiac metabolism using hyperpolarized 13 C magnetic resonance spectroscopy.
Hypoxia plays a role in many diseases and can have a wide range of effects on cardiac metabolism depending on the extent of the hypoxic insult. Noninvasive imaging methods could shed valuable light on the metabolic effects of hypoxia on the heart in vivo. Hyperpolarized carbon-13 magnetic resonance spectroscopy (HP 13 C MRS) in particular is an exciting technique for imaging metabolism that could provide such information. The aim of our work was, therefore, to establish whether hyperpolarized 13 C MRS can be used to assess the in vivo heart's metabolism of pyruvate in response to systemic acute and chronic hypoxic exposure. Groups of healthy male Wistar rats were exposed to either acute (30 minutes), 1 week or 3 weeks of hypoxia. In vivo MRS of hyperpolarized [1-13 C] pyruvate was carried out along with assessments of physiological parameters and ejection fraction. Hematocrit was elevated after 1 week and 3 weeks of hypoxia. 30 minutes of hypoxia resulted in a significant reduction in pyruvate dehydrogenase (PDH) flux, whereas 1 or 3 weeks of hypoxia resulted in a PDH flux that was not different to normoxic animals. Conversion of hyperpolarized [1-13 C] pyruvate into [1-13 C] lactate was elevated following acute hypoxia, suggestive of enhanced anaerobic glycolysis. Elevated HP pyruvate to lactate conversion was also seen at the one week timepoint, in concert with an increase in lactate dehydrogenase (LDH) expression. Following three weeks of hypoxic exposure, cardiac metabolism of pyruvate was comparable with that observed in normoxia. We have successfully visualized the effects of systemic hypoxia on cardiac metabolism of pyruvate using hyperpolarized 13 C MRS, with differences observed following 30 minutes and 1 week of hypoxia. This demonstrates the potential of in vivo hyperpolarized 13 C MRS data for assessing the cardiometabolic effects of hypoxia in disease.


The role of pineal gland and exogenous melatonin on the irradiation stress response of suprarenal gland.
Pineal gland has and antistressogenic role. Its main hormone, melatonin, has radio protective effect on endocrine and other dynamic tissues. In our previous study, we have shown that pinealectomy changes the behavior of suprarenal gland in totally irradiated rats. The aim of this study is to evaluate the effect of exogenous melatonin on suprarenal gland of rats with or without pineal gland. Four months after pinealectomy (experimental group) or shampinealectomy (control group), adult Wistar male rats were daily treated with 0,2 mg of melatonin intraperitoneally, during two weeks. Thereafter, all animals were totally irradiated with 8 Gy of Gamma rays produced from Cobalt 60. Animals who survived were sacrificed on the 17(th) post irradiation day. Qualitative and quantitative characteristics of the suprarenal gland were studied using histological methods. The results show that exogenous melatonin had protective role on suprarenal gland in totally irradiated rats and that those effects were more pronounced in the presence of pineal gland.


Indoleamine 2,3-dioxigenase (IDO) is critical for host resistance against Trypanosoma cruzi.
Indoleamine 2,3-dioxygenase (IDO) is an inflammatory cytokine-inducible rate-limiting enzyme of the tryptophan (Trp) catabolism, which is involved in the inhibition of intracellular pathogen replication as well as in immunomodulation. Here we demonstrated the effect of IDO-dependent Trp catabolism on Trypanosoma cruzi resistance to acute infection. Infection with T. cruzi resulted in the systemic activation of IDO. The blocking of IDO activity in vivo impaired resistance to the infection and exacerbated the parasite load and infection-associated pathology. In addition, IDO activity was critical to controlling the parasite's replication in macrophages (Mos), despite the high production of nitric oxide produced by IDO-blocked T. cruzi-infected Mos. Analysis of the mechanisms by which IDO controls the parasite replication revealed that T. cruzi amastigotes were sensitive to L-kynurenine downstream metabolites 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid, while 3-HK also affected the trypomastigote stage. Finally, 3-HK treatment of mice acutely infected with T. cruzi was able to control the parasite and to improve the survival of lethally infected mice. During infection, IDO played a critical role in host defense against T. cruzi; therefore, the intervention of IDO pathway could be useful as a novel antitrypanosomatid therapeutic strategy.


The pregnancy decisions of HIV-positive women: the state of knowledge and way forward.
Despite the growing number of women living with and affected by HIV, there is still insufficient attention to their pregnancy-related needs, rights, decisions and desires in research, policy and programs. We carried out a review of the literature to ascertain the current state of knowledge and highlight areas requiring further attention. We found that contraceptive options for pregnancy prevention by HIV-positive women are insufficient: condoms are not always available or acceptable, and other options are limited by affordability, availability or efficacy. Further, coerced sterilization of women living with HIV is widely reported. Information gaps persist in relation to effectiveness, safety and best practices regarding assisted reproductive technologies. Attention to neonatal outcomes generally outweighs attention to the health of women before, during and after pregnancy. Access to safe abortion and post-abortion care services, which are critical to women's ability to fulfill their sexual and reproductive rights, are often curtailed. There is inadequate attention to HIV-positive sex workers, injecting drug users and adolescents. The many challenges that women living with HIV encounter in their interactions with sexual and reproductive health services shape their pregnancy decisions. It is critical that HIV-positive women be more involved in the design and implementation of research, policies and programs related to their pregnancy-related needs and rights.


Comparing Yin-Yang, the Chinese symbol of creation, with Ouroboros of Greek alchemy.
The universe was early divided into Earth below and Heaven above. These, two as one, gave the idea of opposites but forming a unity. Each opposite was assumed to be powerful and so was their final unity. For creation of the universe they projected reproduction to conceive creation. Now reproduction results in the union of two opposites as male and female. Correspondingly, the Chinese believed Light and Darkness, as the ideal opposites, when united, yielded creative energy. The two opposites were further conceived as matter and energy which became dual-natured but as one. The two opposites were yin-yang and their unity was called Chhi. Yin-Yang was treated separately in Chinese cosmology which consisted of five cosmic elements. Since Chinese alchemy did reach Alexandria probably the symbol Yin-Yang, as dual-natured, responsible for creation, was transformed into a symbol called Ouroboros. It is a snake and as such as symbol of soul. Its head and anterior portion is red, being the colour of blood as soul; its tail and posterior half is dark, representing body. Ouroboros here is depicted white and black, as soul and body, the two as "one which is all." It is cosmic soul, the source of all creation. Ouroboros is normally depicted with its anterior half as black but it should be the reverse as shown here. With the name Chemeia taken to Kim-Iya, the last word would take Ouroboros to Yin-Yang.


Evaluating the Efficacy of Monobloc Distraction in the Crouzon-Pfeiffer Craniofacial Deformity Using Geometric Morphometrics.
Crouzon-Pfeiffer syndrome is caused by mutations predominantly in the FGFR2 gene leading to syndromic craniosynostosis and midfacial hypoplasia. Monobloc distraction aims to correct both functional and aesthetic disharmony as a result of midfacial hypoplasia. This study evaluates the corrective effects and effectiveness of monobloc distraction in Crouzon-Pfeiffer patients. Preoperative and postoperative scans were collected from 20 Crouzon and two Pfeiffer patients aged 7 to 20 years. Fifty-six normal skulls were used as a control group. Geometric morphometrics using 52 frontofacial landmarks were used to analyze the normal skull and preoperative and postoperative patient skulls. Color maps were created to visualize differences among the average normal, preoperative, and postoperative Crouzon-Pfeiffer patients. In the studied patient population, monobloc distraction with the use of an external distractor advanced the upper half of the midface more than the lower half of the midface. There was an anteroinferior rotation in the monobloc segment. The zygomatic arch length improved on average to 88 and 90 percent of normal (right and left, respectively), whereas globe protrusion was corrected from 134 percent to 84 percent and from 131 percent to 87 percent of normal (right and left, respectively) in the studied patient population. Compared with a normal skull, the maxillary region remained retruded. The advancement achieved by monobloc distraction is effective in the upper half of the midface; the lower half of the midface is advanced but remains retruded in comparison with the normal population. The midface is rotated anteroinferiorly. Therapeutic, IV.


Glycerol monolaurate inhibits the effects of Gram-positive select agents on eukaryotic cells.
Many exotoxins of Gram-positive bacteria, such as superantigens [staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxins] and anthrax toxin are bioterrorism agents that cause diseases by immunostimulation or cytotoxicity. Glycerol monolaurate (GML), a fatty acid monoester found naturally in humans, has been reported to prevent synthesis of Gram-positive bacterial exotoxins. This study explored the ability of GML to inhibit the effects of exotoxins on mammalian cells and prevent rabbit lethality from TSS. GML (>or=10 microg/mL) inhibited superantigen (5 microg/mL) immunoproliferation, as determined by inhibition of (3)H-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 x 10(6) cells/mL) as well as phospholipase Cgamma1, suggesting inhibition of signal transduction. The compound (20 microg/mL) prevented superantigen (100 microg/mL) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 microg) inhibited rabbit lethality as a result of TSST-1 administered vaginally. GML (10 microg/mL) inhibited HVEC and macrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal alpha and beta) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and was nontoxic to mammalian cells (up to 100 microg/mL) and rabbits (250 microg). GML stabilized mammalian cell membranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0-0.05 M saline) or staphylococcal alpha- and beta-hemolysins when erythrocytes were pretreated with GML. GML may be useful in the management of Gram-positive exotoxin illnesses; its action appears to be membrane stabilization with inhibition of signal transduction.


Demonstration of electro-optic half-adder using silicon photonic integrated circuits.
We report a silicon photonic integrated circuit which can perform the operation of half-adder based on two cascaded microring resonators (MRRs). PIN diodes embedded around MRRs are employed to achieve the carrier injection modulation. Two electrical pulse sequences representing the two operands of the half-add operation are applied to PIN diodes to modulate two MRRs through the plasma dispersion effect. The final operation results of bitwise Sum and Carry operation are output at two different output ports of the device. Microheaters fabricated on the top of MRRs are employed to compensate two MRRs resonance mismatch caused by the fabrication error through the thermo-optic effect. Addition operation of two bits with the operation speed of 100 Mbps is demonstrated.


The expanded endonasal approach for an endoscopic transnasal clipping and aneurysmorrhaphy of a large vertebral artery aneurysm: technical case report.
Aneurysms of the vertebral artery are rare, comprising less than 5% of all aneurysms. They can present with subarachnoid hemorrhage, medullary compression, and cranial neuropathies. In consideration of their surrounding regional anatomy, they present a formidable surgical challenge to the neurosurgeon using traditional techniques. Recent advances in endoscopic transnasal surgery have provided an additional approach for the treatment of these difficult lesions. We present a case of a large vertebral artery aneurysm causing mass effect on the medulla. Initial treatment consisted of endovascular trapping of the aneurysm; however, because of concerns that the remaining aneurysm and intraluminal thrombus was causing mass effect and continued brainstem compression, a decompressive procedure was required. After the endovascular trapping, the patient underwent a completely endoscopic transnasal surgical clipping and aneurysmorrhaphy. After exposure of the aneurysm, distal and proximal clips were applied transnasal, and the aneurysmorrhaphy completed using suction and ultrasonic aspiration. In consideration of their surrounding regional anatomy, aneurysms of the vertebral artery present a formidable surgical challenge to the neurosurgeon. Although endovascular techniques have proven to be extremely valuable for the treatment of these lesions, they are limited when patients have significant mass effect with brainstem compression or cranial neuropathy. Advances in endoscopic transnasal surgery have provided an additional approach for the treatment of these difficult lesions. This case report represents, to our knowledge, the first literature report of a transnasal endoscopic aneurysm clipping and thrombectomy.


Surviving the cold: molecular analyses of insect cryoprotective dehydration in the Arctic springtail Megaphorura arctica (Tullberg).
Insects provide tractable models for enhancing our understanding of the physiological and cellular processes that enable survival at extreme low temperatures. They possess three main strategies to survive the cold: freeze tolerance, freeze avoidance or cryoprotective dehydration, of which the latter method is exploited by our model species, the Arctic springtail Megaphorura arctica, formerly Onychiurus arcticus (Tullberg 1876). The physiological mechanisms underlying cryoprotective dehydration have been well characterised in M. arctica and to date this process has been described in only a few other species: the Antarctic nematode Panagrolaimus davidi, an enchytraied worm, the larvae of the Antarctic midge Belgica antarctica and the cocoons of the earthworm Dendrobaena octaedra. There are no in-depth molecular studies on the underlying cold survival mechanisms in any species. A cDNA microarray was generated using 6,912 M. arctica clones printed in duplicate. Analysis of clones up-regulated during dehydration procedures (using both cold- and salt-induced dehydration) has identified a number of significant cellular processes, namely the production and mobilisation of trehalose, protection of cellular systems via small heat shock proteins and tissue/cellular remodelling during the dehydration process. Energy production, initiation of protein translation and cell division, plus potential tissue repair processes dominate genes identified during recovery. Heat map analysis identified a duplication of the trehalose-6-phosphate synthase (TPS) gene in M. arctica and also 53 clones co-regulated with TPS, including a number of membrane associated and cell signalling proteins. Q-PCR on selected candidate genes has also contributed to our understanding with glutathione-S-transferase identified as the major antioxdidant enzyme protecting the cells during these stressful procedures, and a number of protein kinase signalling molecules involved in recovery. Microarray analysis has proved to be a powerful technique for understanding the processes and genes involved in cryoprotective dehydration, beyond the few candidate genes identified in the current literature. Dehydration is associated with the mobilisation of trehalose, cell protection and tissue remodelling. Energy production, leading to protein production, and cell division characterise the recovery process. Novel membrane proteins, along with aquaporins and desaturases, have been identified as promising candidates for future functional analyses to better understand membrane remodelling during cellular dehydration.


Beyond health messaging: a behavioural economics approach to increasing self-selected distance during an acute bout of cycling.
The purpose of this study was to explore the effects of the perceived purpose of exercising on the self-selected distance peddled during an acute cycling task. Participants were randomly assigned to one of three groups (health, wealth, charity). All participants watched a video emphasizing the health benefits of performing at least 30 min of daily exercise. Those in the health group were not provided any additional information. Those in the wealth group were then informed that they would earn money for every two kilometres cycled. Those in the charity group were informed that they would earn money for a charity for every two kilometres cycled. Participants were not given a time/distance limit and were instructed to cycle until they chose to stop. Analyses revealed that participants in the wealth and charity group cycled significantly farther than those in the health group (approximately twice as far). Additionally, a significant sex by group interaction showed that women cycled farther for charity while men cycled farther for wealth. These results suggest that health messages used to increase exercise behaviour may benefit from exploring how paradigms from behavioural economics influence behaviors that have relevance to public health.


On the taxonomy of optimization problems under estimation of distribution algorithms.
Understanding the relationship between a search algorithm and the space of problems is a fundamental issue in the optimization field. In this paper, we lay the foundations to elaborate taxonomies of problems under estimation of distribution algorithms (EDAs). By using an infinite population model and assuming that the selection operator is based on the rank of the solutions, we group optimization problems according to the behavior of the EDA. Throughout the definition of an equivalence relation between functions it is possible to partition the space of problems in equivalence classes in which the algorithm has the same behavior. We show that only the probabilistic model is able to generate different partitions of the set of possible problems and hence, it predetermines the number of different behaviors that the algorithm can exhibit. As a natural consequence of our definitions, all the objective functions are in the same equivalence class when the algorithm does not impose restrictions to the probabilistic model. The taxonomy of problems, which is also valid for finite populations, is studied in depth for a simple EDA that considers independence among the variables of the problem. We provide the sufficient and necessary condition to decide the equivalence between functions and then we develop the operators to describe and count the members of a class. In addition, we show the intrinsic relation between univariate EDAs and the neighborhood system induced by the Hamming distance by proving that all the functions in the same class have the same number of local optima and that they are in the same ranking positions. Finally, we carry out numerical simulations in order to analyze the different behaviors that the algorithm can exhibit for the functions defined over the search space [Formula: see text].


Phenological changes in the Northwestern Mediterranean copepods Centropages typicus and Temora stylifera linked to climate forcing.
Planktonic copepods play a major role in the fluxes of matter and energy in the marine ecosystem, provide a biological pump of carbon into the deep ocean, and play a role in determining fish recruitment. Owing to such ecological considerations, it is essential to understand the role that climate might play in the interannual variability of these organisms and the mechanisms by which it could modify the ecosystem functioning. In this study, a causal chain of meteorological, hydrological and ecological processes linked to the North Atlantic Oscillation (NAO) was identified in the Ligurian Sea, Northwestern Mediterranean. The forcing by the NAO drives most of the hydro-climatic variability during winter and early spring. Subsequently, interannual and decadal changes of the dominant copepods Centropages typicus and Temora stylifera were significantly correlated to the state of the hydro-climatic signal and tightly coupled to the NAO. Direct and indirect effects whose influence promoted phenological changes in the two copepod populations drove the species' responses to climatic forcing. Opposite responses of the analysed species were also highlighted by these results. While years characterized by the positive phase of the NAO leads to enhancement of the strength and the forward move of the C. typicus peak, they act negatively on the annual cycle of T. stylifera, the abundance of which drops twofold and the annual peak appears delayed in time. In contrast, low NAO years lead to high abundance of T. stylifera and a forward timing of its peak, and acts in turn negatively on the C. typicus annual cycle in both abundance (low) and timing (delayed). Owing to the synchronism between hydro-climatic conditions and the NAO, and the major role of these species in the pelagic ecosystem of the studied area, these results provide key elements for interpreting and forecasting decadal changes of planktonic populations in the Ligurian Sea.


Essential oils in the management of the donkey louse, Bovicola ocellatus.
Chewing lice are widespread and clinically compromising parasites of livestock and equids. Their management is complicated by growing levels of resistance to commonly applied insecticides. Hence, the development of novel approaches to their control is of major clinical interest. To assess the effects of incorporating the essential oils of tea tree and lavender into a grooming programme for populations of donkeys with natural infestations of Bovicola ocellatus in the UK and Ireland when louse populations were at their winter seasonal peak. In vivo field trial. Suspensions of 5% (v/v) tea tree or lavender oil or an excipient only control were groomed into the coats of winter-housed donkeys (n = 198) on 2 occasions, 2 weeks apart. Louse counts were conducted before each application and 2 weeks later. After 2 applications, the groups groomed with lavender or tea tree oil suspensions had a significant reduction in louse intensity, with a mean decline in louse abundance of 78% (95% confidence interval 76-80%). Louse numbers in the groups groomed with excipient only either did not change or increased significantly. Donkey hair length had no effect on the decline in louse numbers. These results demonstrate that the inclusion of essential oil suspensions during grooming can be used to manage louse populations successfully.


[Knowledge is prevention: a novel approach to breast cancer prevention].
Data from the Brazilian Ministry of Health shows that the breast cancer is one of the leading causes of women's death, despite the enhancements in treatment and diagnosis of this disease. Successive explanatory advertising campaigns emphasized the methods available for prevention: auto examination, clinical examination by a health care professional and mammography. Regardless of their relevance, only these strategies did not reduced incidence of breast cancer, since they do not impact on the oncogenesis factors. The objective of this article is to develop a health promotion activity through the reinforcement of the previous knowledge and aggregation of new information about breast cancer of a basic health unit. The methodology used was a transversal study of pedagogical intervention in the waiting rooms of a basic health unit. The pedagogical intervention was composed by an interactive questionnaire, lecture and discussion about the topic associated with a qualitative and quantitative evaluation of the activity. The proposed activity had positive results since the participants had qualitative and quantitative improvement in their knowledge and also a good interactivity with the researchers.


Therapeutic actions of melatonin on gastrointestinal cancer development and progression.
Melatonin exerts a multitude of physiological functions including the regulation of the sleep cycle and circadian rhythm. Although the synthesis of melatonin in the pineal gland is regulated by changes in the light/dark cycle, the release of melatonin in the gastrointestinal tract is related to food consumption. Melatonin regulates antioxidative processes and it improves T-helper cell response by stimulating the production of specific cytokines. Melatonin is directly involved in preventing tumor initiation, promotion, and progression in a variety of cancers of the gastrointestinal tract including colorectal cancer, cholangiocarcinoma, hepatocarcinoma, and pancreatic carcinoma. This paper is a review of the literature regarding melatonin in the gastrointestinal tract and as a potential therapy for gastrointestinal cancers.


DNA recombination and natural selection pressure sustain genetic sequence diversity of the feline MHC class I genes.
Sequence comparisons of seven distinct MHC class I cDNA clones revealed that feline class I molecules have a remarkable similarity to human HLA genes in their organization of functional domains as well as in the nonrandom partitioning of genetic variability according to the functional constraints ascribed to different regions of the MHC molecule. The distribution of the pattern of sequence polymorphism in the cat as compared with genetic diversity of human and mouse class I genes provides evidence for four coordinate factors that contribute to the origin and sustenance of abundant allele diversity that characterizes the MHC in the species. These include: (a) a gradual accumulation of spontaneous mutational substitution over evolutionary time; (b) selection against mutational divergence in regions of the class I molecule involved in T cell receptor interaction and also in certain regions that interact with common features of antigens; (c) positive selection pressure in favor of persistence of polymorphism and heterozygosity at 57 nucleotide residues that comprise the antigen recognition site; and (d) periodic intragenic (interallelic) and intergenic recombination within the class I genes. We describe a highly conserved 23-bp nucleotide sequence within the coding region of the first alpha-helix that separates two relatively polymorphic segments located in the alpha 1 domain that may act as a template or "hot spot" for homologous recombination between class I alleles.


Neurobehavioral effects of cyanobacterial biomass field extracts on zebrafish embryos and potential role of retinoids.
Cyanobacteria are known for their ability to produce and release mixtures of up to thousands of compounds into the environment. Recently, the production of novel metabolites, retinoids, was reported for some cyanobacterial species along with teratogenic effects of samples containing these compounds. Retinoids are natural endogenous substances derived from vitamin A that play a crucial role in early vertebrate development. Disruption of retinoid signalling- especially during the early development of the nervous system- might lead to major malfunctions and malformations. In this study, the toxicity of cyanobacterial biomass samples from the field containing retinoids was characterized by in vivo and in vitro bioassays with a focus on the potential hazards towards nervous system development and function. Additionally, in order to identify the compounds responsible for the observed in vitro and in vivo effects the complex cyanobacterial extracts were fractionated (C18 column, water-methanol gradient) and the twelve obtained fractions were tested in bioassays. In all bioassays, all-trans retinoic acid (ATRA) was tested along with the environmental samples as a positive control. Retinoid-like activity (mediated via the retinoic acid receptor, RAR) was measured in the transgenic cell line p19/A15. The in vitro assay showed retinoid-like activity by specific interaction with RAR for the biomass samples. Neurotoxic effects of selected samples were studied on zebrafish (Danio rerio) embryos using the light/dark transition test (Viewpoint, ZebraLab system) with 120 hpf larvae. In the behavioural assay, the cyanobacterial extracts caused significant hyperactivity in zebrafish at 120 hpf after acute exposure (3 h prior to the measurement) at concentrations below the teratogenicity LOEC (0.2 g dw L-1). Similar effect was observed after exposure to fractions of the extracts with detected retinoid-like activity and additive effect was observed after combining the fractions. However, the effect on behaviour was not observed after exposure to ATRA only. To provide additional insight into the behavioural effects and describe the underlying mechanism gene expression of selected biomarkers was measured. We evaluated an array of 28 genes related to general toxicity, neurodevelopment, retinoid and thyroid signalling. We detected several affected genes, most notably, the Cyp26 enzymes that control endogenous ATRA concentration, which documents an effect on retinoid signalling.


Postteneral protein feeding may improve biological control efficiency of Aphytis lingnanensis and Aphytis melinus.
The augmentative releases of mass-reared Aphytis spp. (Hymenoptera: Aphelinidae) parasitoids are widely used against armored scales. The nutritional status and the initial egg load of Aphytis spp. females are key to their success as biological control agents. For these reasons, this work focuses on the study of providing a protein feed to Aphytis lingnanensis (Compere) and A. melinus DeBach to improve the egg load before their release. The addition of protein to a honey diet during the first 2 d after the adult parasitoid emergence increased the initial egg load in both species of parasitoids by more than five eggs. Furthermore, the addition of protein increased the total number of eggs laid by A. lingnanensis on oleander scale, Aspidiotus nerii Bouché (Hemiptera: Diaspididae). In contrast, this effect was not observed on A. melinus probably because A. nerii is considered a suboptimal host for this parasitoid. The host-feeding activities of the two Aphytis species were differentially affected by the addition of protein to their diets. These results may have direct implications for augmentative biological control programs, especially during transportation from insectaries to the field, a period of time when parasitoids are deprived of hosts.


Dopamine reuptake inhibition in the rostral agranular insular cortex produces antinociception.
We provide evidence for an antinociceptive effect of dopamine in the rat cerebral cortex that is mediated through descending nociceptive inhibition of spinal neurons. Injection of the dopamine reuptake inhibitor GBR-12935 in the rostral agranular insular cortex (RAIC), a cortical area that receives a dense dopaminergic projection and is involved in descending antinociception (Burkey et al.,1996), resulted in dose-dependent inhibition of formalin-induced nociceptive behavior, without any alteration of motor function. Injection of the dopamine reuptake inhibitor in the surrounding cortical areas had no effect on nociceptive behaviors. GBR-12935 also produced a reduction in noxious stimulus-induced c-fos expression in nociceptive areas of the spinal dorsal horn, suggesting that dopamine in the RAIC acts in part through descending antinociception. Electrophysiological recording from single wide dynamic range-type spinal dorsal horn neurons confirmed the descending nociceptive inhibitory effect. GBR-12935 in the RAIC significantly reduced neuronal responses evoked by noxious thermal stimulation of the skin, an effect that was reversed by local administration of the selective D1 receptor antagonist SCH-23390. Finally, administration of SCH-23390 alone in the RAIC decreased paw withdrawal latencies from noxious heat, suggesting that dopamine acts tonically in the cortex to inhibit nociception.


Comparative chemical sensitivity between marine Australian and Northern Hemisphere ecosystems: is an uncertainty factor warranted for water-quality-guideline setting?
The lack of Australian species data has pragmatically led to the use of toxicological data from the Northern Hemisphere to develop water-quality guidelines. However, it is unknown whether Australian species and ecosystems are equally as sensitive and if an uncertainty factor is warranted for Australian guideline setting. In the present study, it is hypothesized that an uncertainty factor is not required. This was tested by generating species sensitivity distributions by 2 parametric methods using marine Northern Hemisphere and Australian/New Zealand data. Sufficient acute data were found for only 3 compounds: 4-chlorophenol, phenol, and ammonia. For ammonia and 4-chlorophenol, the 95% species protection levels generated with Australian and Northern Hemisphere data were essentially the same. For phenol, protection levels derived from Australian data were approximately 10-fold higher. Therefore, the derived benchmark concentration from Northern Hemisphere data should be protective. It is tentatively concluded that there is no need for an uncertainty factor when deriving water-quality guidelines for marine Australian ecosystems using Northern Hemisphere data. It is, however, noted that this is based on only 3 compounds.


Evaluation of plateau-potential-mediated 'warm up' in human motor units.
Spinal motor neurones can exhibit sustained depolarization in the absence of maintained synaptic or injected current. This phenomenon, referred to as a plateau potential, is due to the activation of monoamine-dependent persistent inward currents. Accordingly, activation of a plateau potential should result in a decrease in the excitatory synaptic drive required to activate a motor unit. This, in turn, has been suggested to cause a progressive decline in the muscle force at which motor units are recruited during repeated voluntary contractions. Such a progressive decrease in threshold force associated with preceding activation of a plateau potential is referred to as 'warm up'. Furthermore, activation of a plateau potential is thought to manifest itself as a decrease in the derecruitment force compared to recruitment force. Multiple muscles, however, can contribute to the detected force and their relative contributions may vary over time, which could confound measures of recruitment and derecruitment force. Therefore, the purpose of this study was to compare the recruitment and derecruitment forces of single motor units in the human extensor digitorum and tibialis anterior during repetitive triangular-force contractions in which the contributions of other muscles had been minimized. In both muscles, we found that the recruitment thresholds of single motor units were unchanged during repeated contractions, and that the derecruitment force was consistently greater than the recruitment force. These results suggest either that plateau potentials were not engaged (or were rapidly extinguished) under these experimental conditions or that changes in recruitment and derecruitment force are not suitable criteria for detecting them.


Environmental Induction of Polyembryony in Echinoid Echinoderms.
Polyembryony, or the production of multiple offspring from a single zygote, is a widespread phenomenon in the animal kingdom. Various types of polyembryony have been described in arthropods, bryozoans, chordates, cnidarians, echinoderms, and platyhelminthes. We describe the induction of polyembryony in embryos of the sand dollar Echinarachnius parma and the pencil urchin Eucidaris tribuloides in response to elevated temperature and reduced salinity. Data on the environmental variation in temperature and salinity that normally occurs during the spawning season, combined with the range of laboratory conditions over which polyembryony was induced, suggest that polyembryony may occur frequently in these species under natural conditions. We tested an additional two species of echinoids for similar responses, but found little evidence for polyembryony in the green urchin Strongylocentrotus droebachiensis or the variegated urchin Lytechinus variegatus, suggesting that polyembryony is not a universal response of echinoids to fluctuations in temperature and salinity. The unexpected developmental changes that we observed in response to present-day fluctuations in temperature and salinity suggest that ongoing and future environmental shifts may drive substantial changes in marine invertebrate developmental patterns, and that these changes will be different across taxa.