Search

Background: In onchocerciasis-endemic areas, particularly in those with a sub-optimal onchocerciasis control programme, a high prevalence of epilepsy is observed. Both onchocerciasis and epilepsy are stigmatizing conditions. The first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium (12-14 October 2017) and during this meeting, an OAE alliance was established. In this paper, we review what is known about epilepsy-associated stigma in onchocerciasis-endemic regions, and present the recommendations of the OAE alliance working group on stigma. Main body: For this scoping review, literature searches were performed on the electronic databases PubMed, Scopus and Science Direct using the search terms "epilepsy AND onchocerciasis AND stigma". Hand searches were also undertaken using Google Scholar, and in total seven papers were identified that addressed epilepsy-related stigma in an onchocercisasis-endemic area. Due to the limited number of published research papers on epilepsy-associated stigma in onchocerciasis-endemic areas, other relevant literature that describes important aspects related to stigma is discussed. The thematic presentation of this scoping review follows key insights on the barriers to alleviating the social consequences of stigma in highly affected onchocerciasis-endemic areas, which were established by experts during the working group on stigma and discrimination at the first international workshop on OAE. These themes are: knowledge gaps, perceived disease aetiology, access to education, marriage restrictions, psycho-social well-being, burden on the care-giver and treatment seeking behaviour. Based on the literature and expert discussions during the OAE working group on stigma, this paper describes important issues regarding epilepsy-related stigma in onchocerciasis-endemic regions and recommends interventions that are needed to reduce stigma and discrimination for the improvement of the psycho-social well-being of persons with epilepsy. Conclusions: Educating healthcare workers and communities about OAE, strengthening onchocerciasis elimination programs, decreasing the anti-epileptic treatment gap, improving the care of epilepsy-related injuries, and prioritising epilepsy research is the way forward to decreasing the stigma associated with epilepsy in onchocerciasis-endemic regions., SCOPUS: re.j, info:eu-repo/semantics/published

Background Recently, several epidemiological studies performed in Onchocerca volvulus-endemic regions have suggested that onchocerciasis-associated epilepsy (OAE) may constitute an important but neglected public health problem in many countries where onchocerciasis is still endemic. Main text On October 12–14th 2017, the first international workshop on onchocerciasis-associated epilepsy (OAE) was held in Antwerp, Belgium. The workshop was attended by 79 participants from 20 different countries. Recent research findings strongly suggest that O. volvulus is an important contributor to epilepsy, particularly in meso- and hyperendemic areas for onchocerciasis. Infection with O. volvulus is associated with a spectrum of epileptic seizures, mainly generalised tonic-clonic seizures but also atonic neck seizures (nodding), and stunted growth. OAE is characterised by an onset of seizures between the ages of 3–18 years. Multidisciplinary working groups discussed topics such as how to 1) strengthen the evidence for an association between onchocerciasis and epilepsy, 2) determine the burden of disease caused by OAE, 3) prevent OAE, 4) improve the treatment/care for persons with OAE and affected families, 5) identify the pathophysiological mechanism of OAE, and 6) deal with misconceptions, stigma, discrimination and gender violence associated with OAE. An OAE Alliance was created to increase awareness about OAE and its public health importance, stimulate research and disseminate research findings, and create partnerships between OAE researchers, communities, advocacy groups, ministries of health, non-governmental organisations, the pharmaceutical industry and funding organizations. Conclusions Although the exact pathophysiological mechanism underlying OAE remains unknown, there is increasing evidence that by controlling and eliminating onchocerciasis, OAE will also disappear. Therefore, OAE constitutes an additional argument for strengthening onchocerciasis elimination efforts. Given the high numbers of people with epilepsy in O. volvulus-endemic regions, more advocacy is urgently needed to provide anti-epileptic treatment to improve the quality of life of these individuals and their families. Electronic supplementary material The online version of this article (10.1186/s40249-018-0400-0) contains supplementary material, which is available to authorized users.

The high prevalence of ADHD and its associated difficulties in adaptive functioning have led to significant efforts to better understand the underlying pathophysiology of the disorder. Prominent models of ADHD have suggested that neurocognitive deficits—particularly executive dysfunction—is directly related to ADHD symptomatology. Data suggests, however, that significant heterogeneity is observed in both the cognitive and adaptive functioning of individuals with ADHD, raising questions about current theoretical models. Furthermore, many of our current models do not explain the developmental trajectory of ADHD symptoms and impairment. This chapter will explore the state of the literature and remaining questions that are driving research on the role of neuropsychological functioning in ADHD, approaching the topic from a developmental perspective. We will conclude by considering implications of this knowledge for the development of effective and long-lasting interventions for individuals with ADHD.

Background Hyperactive/Inattentive preschool children show clear evidence of neuropsychological dysfunction. We examined whether patterns and severity of test scores could reliably identify subgroups of preschoolers with differential risk for ADHD during school-age. Method Typically developing (TD: n = 76) and Hyperactive/Inattentive (HI: n = 138) 3–4 year olds were assessed annually for 6 years (T1–T6). Latent profile analysis (LPA) was used to form subgroups among the HI group based on objective/neuropsychological measures (NEPSY, Actigraph and Continuous Performance Test). Logistic regression assessed the predictive validity of empirically formed subgroups at risk for ADHD diagnosis relative to the TD group and to each other from T2 to T6. Results Latent profile analysis yielded two subgroups of HI preschoolers: (a) selectively weak Attention/Executive functions, and (b) pervasive neuropsychological dysfunction across all measures. Both subgroups were more likely to have ADHD at all follow-up time-points relative to the TD group (OR range: 11.29–86.32), but there were no significant differences between the LPA-formed subgroups of HI children at any time-point. Conclusions Objective/neuropsychological measures distinguish HI preschoolers from their TD peers, but patterns and severity of neuropsychological dysfunction do not predict risk for ADHD during school-age. We hypothesize that trajectories in at-risk children are influenced by subsequent environmental and neurodevelopmental factors, raising the possibility that they are amenable to early intervention.

Objective: Impact of speech and language therapy (ST) and occupational/physical therapy (OT/PT) on language and motor skills was examined in hyperactive/inattentive children.Methods: Preschoolers were divided into those receiving and not receiving ST or OT/PT.Results: Children receiving ST showed no gains in language functioning relative to those not receiving ST. OT/PT yielded similar results for motor functions. Hours of a service did not predict improvement. However, children who received ST showed improvement in social skills.Discussion: The apparent lack of benefit suggests the need for further investigation into efficacy of these treatments in hyperactive/inattentive preschool children.

This paper summarizes key, recently published research examining longitudinal outcomes for preschoolers with high levels of inattention and/or hyperactivity/impulsivity. Symptom trajectories show that hyperactivity/impulsivity declines across childhood. At the group level, the course of inattention appears more variable. However, identification of subgroups of children showing stable, rising, and falling inattention over time is promising. Early ADHD-like symptoms portend risk for academic and social difficulties, as well as comorbid emotional and behavioral problems in childhood and adolescence. Several early risk factors appear to moderate these relations, including comorbid symptoms, parental psychopathology, socioeconomic disadvantage, and perhaps neuropsychological dysfunction. Furthermore, high levels of inattention and/or hyperactivity/impulsivity during the preschool period appear to compromise development of regulatory and neuropsychological functions, which in turn increases risk for negative outcomes later in childhood. Identified risk factors are targets for novel interventions, which ideally would be delivered early to at-risk children.

Data from animal studies provide convincing evidence that physical exercise enhances brain development and neurobehavioral functioning in areas believed to be impaired in children with attention-deficit/hyperactivity disorder (ADHD). To a lesser but still compelling extent, results from studies in typically developing children and adults indicate beneficial effects of exercise on many of the neurocognitive functions that have been shown to be impaired in children with ADHD. Together, these data provide a strong rationale for why a program of structured physical exercise might serve as an effective intervention for children with ADHD.

The regulation of platelet function is finely tuned by a balance between the vasculature's redox environment and the oxidative processes that occur in it. The activation of platelets at sites of vascular damage is essential for the maintenance of normal hemostasis. In the extracellular milieu, a normal redox environment is maintained by thiol/disulfide redox couples, which include reduced and oxidized glutathione (GSH/GSSG) and cysteine (Cys/CySS). Oxidative changes in either of the plasma redox potentials are directly linked with risk factors for cardiovascular disease.Many proteins found on the surface of platelets contain cysteine residues that are targets for oxidation. These include platelet-specific integrins and thiol isomerase enzymes that respond to changes in the extracellular redox environment, thus influencing normal platelet responses.The post-translational modification of critical cysteine thiol groups is linked to alterations in redox potentials and occurs both intracellularly and extracellularly in normal platelet activation. Platelet integrins, in particular, are prime targets for redox modification due to their high cysteine content. Although the role of thiol/disulfide bond exchange in platelet activation is established, the effects of a changing redox environment on platelet reactivity are unclear.A thorough understanding of these mechanisms and how they interact with other platelet signaling events is of the utmost importance for the development of novel therapeutic targets so that we can protect against inappropriate thrombus formation.

Objective To determine whether patients from regional areas undergoing surgery for kidney cancer present with more advanced disease as a result of geographic isolation. Patients and Methods Retrospective analysis of 221 patients undergoing surgery for renal cell carcinoma (RCC) from January 2004 to June 2012, from both a metropolitan centre and a large inner regional hospital. Data was collected on age, gender, presentation (incidental or symptomatic), clinical stage and pathological features. The Australian Standard Geographical Classification-Remoteness Area (ASGC-RA) is a system developed to allow quantitative comparisons between metropolitan and rural Australia. A score was assigned to each patient based on their location of residence at the time of surgery: metropolitan, RA1; inner regional, RA2; outer regional, RA3. Statistical significance was specified as P < 0.05 on Pearson's chi-square tests. Results Patients in each ASGC-RA group did not differ significantly in age, sex or mode of presentation. Pathological T stage on presentation increased with increasing ASGC-RA and thus distance from tertiary centres (P = 0.004). The proportion of patients with ≥T3 disease rose from 30% of RA1 to 73% of RA3 patients (P = 0.016) treated at our tertiary centre. Similarly, our regional centre had a larger proportion of patients presenting with ≥T3 disease from RA3 (31% vs 5%, P = 0.003). When the 221 patients with RCC were analysed as a group, clinical T stage was significantly associated with ASGC-RA (P < 0.001), symptomatic presentation (P < 0.001), N stage (P < 0.001), M stage (P < 0.001) and Fuhrman grade (P < 0.001). Conclusions Our data quantifies the detrimental effect of physical distance on the health outcomes of regional Australians with kidney cancer. Australia's unique geography and rural culture may preclude any attempts to centralise cancer care to specialised metropolitan units, as has occurred in other countries.

Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug delivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable properties that allow them to cross biological barriers, also offer potential for interaction with other cells and blood constituents, presenting possible safety risks. While NPs investigated are predominantly based on the biodegradable, biocompatible, and FDA approved poly-lactide-co-glycolide (PLGA) polymers, pro-aggregatory and antiplatelet effects have been reported for certain NPs. The potential for toxicity of PLGA based NPs remains to be examined. The aims of this study were to determine the impact of size-selected PLGA-PEG (PLGA-polyethylene glycol) NPs on platelet activation and aggregation. PLGA-PEG NPs of three average sizes of 112, 348, and 576 nm were formulated and their effect at concentrations of 0.0&ndash, 2.2 mg/mL on the activation and aggregation of washed human platelets (WP) was examined. The results of this study show, for the first time, NPs of all sizes associated with the surface of platelets, with &gt, 50% binding, leading to possible internalisation. The NP-platelet interaction, however, did not lead to platelet aggregation nor inhibited aggregation of platelets induced by thrombin. The outcome of this study is promising, suggesting that these NPs could be potential carriers for targeted drug delivery to platelets

Purpose We used apparent co-witness intoxication as a way to examine the effect of source credibility on the acceptance of misinformation from a co-witness. Methods Alongside an experimental confederate, individual participants (N = 100) watched a clip involving two simulated thefts. Immediately beforehand, half of the participants watched the confederate consume what appeared to be three alcoholic beverages. During a subsequent discussion with the participant, the confederate introduced two pieces of misinformation about the clip. In the absence of the confederate, participants were then interviewed before completing a target-absent line-up task. Results As expected, misinformation impaired participants’ verbal reports, and misinformation about appearance impaired line-up performance. Overall susceptibility to misinformation was not significantly related to co-witness condition, or to participants’ ratings of the confederate's intoxication or ability to accurately complete the tasks. On individual items, however, co-witness condition appeared to exert some influence on misinformation acceptance if the participant's pre-misinformation response was discrepant with the misinformation, but not when it was ‘don't know’. Conclusions It is possible that effects of source credibility on misinformation acceptance may depend, at least to some extent, on the presence of a clear discrepancy between the misinformation and the witness's recollection.

To assess the relative ability of parent, teacher, and clinician behavioral ratings of preschoolers to predict ADHD severity and diagnosis at 6 years of age. Hyperactive/inattentive preschoolers [N = 104, 75 % boys, Mean (SD) age = 4.37 (0.47) years] were followed over 2 years (mean = 26.44 months, SD = 5.66). At baseline (BL), parents and teachers completed the ADHD-RS-IV and clinicians completed the Behavioral Rating Inventory for Children following a psychological testing session. At age 6, [Mean (SD) age = 6.62 (0.35) years], parents were interviewed with the K-SADS-PL; teachers completed the ADHD-RS-IV; and laboratory measures of hyperactivity, impulsivity, and inattention were obtained from children. Hierarchical logistic and linear regression analyses examined which combination of BL ratings best predicted 6-year-old ADHD diagnosis and severity, respectively. At age 6, 56 (53.8 %) children met DSM-IV criteria for a diagnosis of ADHD. BL ratings from parent/teacher/clinician, parent/teacher and parent/clinician combinations significantly predicted children who had an ADHD diagnosis at age 6. Parent and clinician, but not teacher, behavior ratings were significant independent predictors of ADHD diagnosis and severity at 6-years-old. However, only clinician reports of preschoolers' behaviors predicted laboratory measures of over-activity and inattention at follow-up. Cross-situationality is important for a diagnosis of ADHD during the preschool years. Among parents, teachers and clinicians, positive endorsements from all three informants, parent/teacher or parent/clinician appear to have prognostic value. Clinicians' ratings of preschoolers' inattention, impulsivity and hyperactivity are valid sources of information for predicting ADHD diagnosis and severity over time.

This longitudinal study examined if changes in neuropsychological functioning were associated with the trajectory of symptoms related to attention deficit hyperactivity disorder (ADHD) and impairment between preschool and school age.The sample consisted of 3- and 4-year-old children (N=138) who were identified as being at risk for ADHD based on parent and teacher reports. Neuropsychological functioning was measured annually using the NEPSY at four time points (mean ages, 4.19, 5.36, 6.35, and 7.35 years). ADHD symptoms and impairment were assessed with semiannual parent and teacher reports using the ADHD Rating Scale-IV and the Children's Problems Checklist at 10 time points (mean ages at baseline and final assessment, 4.19 and 8.81 years, respectively). Hierarchical linear modeling was used to assess the trajectories of change in neuropsychological functioning and ADHD severity as well as the association of change in neuropsychological functioning with change in ADHD severity over time.Baseline neuropsychological functioning was not significantly associated with the slope of change in ADHD severity. However, the magnitude of change in neuropsychological functioning was linearly associated with the trajectory of ADHD symptom severity and impairment, such that individuals with greater neuropsychological growth over time had a greater diminution of ADHD severity and impairment. Family socioeconomic status at baseline was significantly associated with initial ADHD severity and impairment, but not with change over time.Interventions that enhance neuropsychological functioning at an early age may be beneficial in attenuating long-term ADHD severity and impairment.

Recent research has suggested that a comprehensive pretrial intervention utilizing a practice–feedback approach could help children to remain accurate in the face of challenging cross-examination questioning. We do not know, however, the extent to which this type of intervention remains effective as the delay between preparation intervention and cross-examination increases. To answer this question, 5- and 6-year olds (n = 88) and 9- and 10-year olds (n = 108) participated in a staged event and were then interviewed about it (direct examination). Six months later, children watched a videotape of this interview, and were then interviewed in an attempt to talk them out of their direct examination responses, regardless of accuracy (cross-examination). One day, 1 week, or 1 month prior to cross-examination, some children took part in a preparation intervention. These children were given practice at answering cross-examination-style questions about an unrelated topic, and received feedback on their responses. Remaining children received no preparation. Children's direct examination accuracy scores were high, but accuracy decreased markedly during cross-examination, especially for younger children. The preparation intervention significantly improved cross-examination accuracy above that of the control group when the program was delivered 1 day or 1 week prior to cross-examination, but not at a 1-month delay. Although the intervention conveyed considerable benefits, cross-examination still exerted a negative effect on children's accuracy in all preparation conditions. Our findings underscore the importance of considering not only the components of pretrial preparation programs, but also the timing of their delivery.

Background The processes underlying persistence and remission of attention-deficit/hyperactivity disorder (ADHD) are poorly understood. We examined whether cognitive and neurophysiological impairments on a performance-monitoring task distinguish between ADHD persisters and remitters. Methods On average 6 years after initial assessment, 110 adolescents and young adults with childhood ADHD (87 persisters, 23 remitters) and 169 age-matched control participants were compared on cognitive-performance measures and event-related potentials of conflict monitoring (N2) and error processing (error-related negativity and positivity) from an arrow flanker task with low-conflict and high-conflict conditions. ADHD outcome was examined with parent-reported symptoms and functional impairment measures using a categorical (DSM-IV) and a dimensional approach. Results ADHD persisters were impaired compared with controls on all cognitive-performance and event-related potential measures (all p < .05). ADHD remitters differed from persisters and were indistinguishable from control participants on the number of congruent (low-conflict) errors, reaction time variability, error-related negativity, and error-related positivity (all p ≤ .05). Remitters did not differ significantly from the other groups on incongruent (high-conflict) errors, mean reaction time, and N2. In dimensional analyses on all participants with childhood ADHD, ADHD symptoms and functional impairment at follow-up were significantly correlated with congruent errors, reaction time variability, and error-related positivity (r = .19–.23, p ≤ .05). Conclusions Cognitive and neurophysiological measures of attention-vigilance and error detection distinguished ADHD remitters from persisters. These results extend our previous findings with other tasks and indicate that such measures are markers of remission and candidates for the development of nonpharmacological interventions.

O1: Assessing the protective effect of dexrazoxane against doxorubicin-induced toxicity in HL-1 cardiomyocytes

Cognition and emotion have been shown to interact and to influence psychological functioning. However, to date these interactions have only been examined cross-sectionally among inattentive and/or hyperactive/impulsive children. This study investigated the moderating effects of neuropsychological functioning at age 3–4 years on the relation between negative emotionality at age 3–4 years and global functioning one year later, at age 4–5 years. Hyperactive/inattentive (H/I; N=114) preschoolers entered the study (BL: baseline) and were seen again one year later (F1). Children’s BL scores on a neuropsychological test (NEPSY) and their temperament as rated by parents (Child Behavior Questionnaire) and teachers (Temperament Assessment Battery for Children-Revised) were obtained, as were clinicians’ ratings of their global functioning (Children’s Global Assessment Scale) at F1. Hierarchical Linear Regression analyses revealed that BL temperament variables accounted for significant variance in F1 Global Functioning. Significant interactions indicated that higher Verbal Executive abilities were associated with better child functioning when parent-rated Effortful Control was high, but not when Effortful Control was low. Additionally, high levels of Nonverbal Executive skills were associated with higher child global functioning when both parent and teacher rated negative affect was low, but not when negative affect was high.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and enduring neurodevelopmental disorder characterized by marked inattention, overactivity, and impulsivity, which causes impairment across multiple settings. Oftentimes, neurocognitive dysfunction is also evident although the pattern of weaknesses differs across individuals. Current evidence-based treatments show limited long-term benefits on the trajectory of the disorder leading to calls for novel ways to treat ADHD. Physical exercise offers potential as either an alternative mode of intervention or an additional component to a current treatment regimen. In animals and healthy individuals, physical activity has shown positive effects on brain structure and function. Several pilot studies have shown a positive impact of physical activity on cognitive functioning and behavior of individuals with ADHD. We call on the field to develop randomized controlled trials to evaluate the efficacy of exercise as a treatment for ADHD.

BackgroundClinical trials require high levels of participation and low drop-out rates to be successful. However, collecting blood samples from individuals recruited into clinical trials can be challenging when there is reticence about blood-taking. In addition to concerns regarding the feasibility of medical research, fears of ‘blood-stealing’ and ‘blood-selling’ have ethical implications related to cultural sensitivity and informed consent. This study explores anxieties around blood-taking during a malaria treatment trial in the Gambia. MethodsThis case study is based on ethnographic research in one theoretically selected village due to the high reticence to screening for the clinical trial ‘Primaquine's gametocytocidal efficacy in malaria asymptomatic carriers treated with dihydroartemisinin-piperaquine’ carried out in the Gambia between 2013 and 2014. Data collection tools included in-depth interviews, participant observation, informal conversations and group discussions. ResultsIn total only 176 of 411 habitants (42%) in the village accepted having a bloodspot taken to screen for malaria. Although trial recruitment was initially high in the village, some families refused screening when rumours started spreading that the trial team was taking too much blood. Concerns about ‘loss of blood’ were equated to loss of strength and lack of good food to replenish bodily forces. Families in the study village were concerned about the weakness of their body while they had to harvest their crops at the time of recruitment for the trial.Conclusion A common recommendation to prevent and avoid rumours against public health interventions and trials is the provision of full and consistent information during the consent procedure, which is assumed to lead to more accurate knowledge of the purpose of the intervention and increased trial participation. However, even when information provision is continuous, the emergence of rumours can be related to times of uncertainty and perceptions of vulnerability, which are often a reflection of structural inequalities and diverging value orientations between communities and public health institutions.

When a witness gives evidence in an adversarial criminal trial, there are two main questioning phases: direct examination and cross-examination. Special provisions are sometimes made for children to give direct evidence, but the majority of child witnesses are still cross-examined. While several decades of research have demonstrated how to elicit children’s direct evidence in a manner that promotes completeness and accuracy, the cross-examination process directly violates many of these principles. Here, we outline the characteristics of cross-examination, particularly as it pertains to children, and we review research about its impact on children, their testimony, and their credibility. We consider options for reforming the cross-examination process and propose avenues for future research.

The negative effect of cross-examination-style questioning on children's accuracy is likely to be due to the complex and credibility-challenging questions that characterize the interview. Given that cross-examination occurs after at least one prior interview, however, it is equally possible that repeated interviewing per se impairs children's accuracy, and that the questions asked have little bearing on children's responses. To examine this issue, 5- and 6-year-old children (n= 82) and 9- and 10-year-old children (n= 103) took part in a surprise event and were then interviewed using an analogue of direct examination. Either 1 week or 6 months later, half of the children were re-interviewed with an analogue of cross-examination designed to challenge their direct examination responses. Remaining children were re-interviewed with the same questions that were asked during direct examination. Children's accuracy decreased following their second interview, irrespective of age or delay; however, delay particularly impacted younger children's second interview performance. Children's accuracy was most impaired following a cross-examination-style interview. Overall, cross-examination-style questioning appears to be particularly detrimental to obtaining accurate event reports from children.

Effective scheduling of and ready access to doctor appointments affect ambulatory patient care quality, but these are often sacrificed by patients seeking care from physicians at academic medical centers. At one center, Beth Israel Deaconess Medical Center, the authors developed interventions to improve the scheduling of appointments and to reduce the access time between telephone call and first offered appointment. Improvements to scheduling included no redirection to voicemail, prompt telephone pickup, courteous service, complete registration, and effective scheduling. Reduced access time meant being offered an appointment with a physician in the appropriate specialty within three working days of the telephone call. Scheduling and access were assessed using monthly "mystery shopper" calls. Mystery shoppers collected data using standardized forms, rated the quality of service, and transcribed their interactions with schedulers. Monthly results were tabulated and discussed with clinical leaders; leaders and frontline staff then developed solutions to detected problems. Eighteen months after the beginning of the intervention (in June 2007), which is ongoing, schedulers had gone from using 60% of their registration skills to over 90%, customer service scores had risen from 2.6 to 4.9 (on a 5-point scale), and average access time had fallen from 12 days to 6 days. The program costs $50,000 per year and has been associated with a 35% increase in ambulatory volume across three years. The authors conclude that academic medical centers can markedly improve the scheduling process and access to care and that these improvements may result in increased ambulatory care volume.

Collecting blood samples from individuals recruited into clinical research projects in sub-Saharan Africa can be challenging. Strikingly, one of the reasons for participant reticence is the occurrence of local rumors surrounding "blood stealing" or "blood selling." Such fears can potentially have dire effects on the success of research projects--for example, high dropout rates that would invalidate the trial's results--and have ethical implications related to cultural sensitivity and informed consent. Though commonly considered as a manifestation of the local population's ignorance, these rumors represent a social diagnosis and a logical attempt to make sense of sickness and health. Born from historical antecedents, they reflect implicit contemporary structural inequalities and the social distance between communities and public health institutions. We aim at illustrating the underlying logic governing patients' fear and argue that the management of these beliefs should become an intrinsic component of clinical research., The American journal of tropical medicine and hygiene, 91(2), pp.213-215; 2014

Elevated levels of plasma homocysteine (Hcy) are an independent risk factor for cardiovascular disease and thrombosis. The molecular basis for this phenomenon is not known but may relate to modification of cell surface thiols. The platelet specific integrin αIIbβ3 is a cysteine-rich cell adhesion molecule that plays a critical role in platelet aggregation and adhesion in haemostasis and thrombosis. In this study, we looked for evidence of a homocysteine-induced modification of αIIbβ3 using a fluorescently labeled PAC-1 antibody that recognizes the activated conformation of the integrin on the platelet surface. We show that exogenous Hcy (10–100 µM) and homocysteine thiolactone (HcyTL) (10–100 µM) increased PAC-1 binding to platelets in a concentration dependent manner in vitro. In parallel, we show subjects with clinical hyperhomocysteinemia exhibit a greater degree of activation of αIIbβ3 compared to age-matched controls. These findings demonstrate that circulating Hcy can modulate the activation state o...

There is relatively little research on the relationships between adults with intellectual disability and their siblings, despite the potential importance of these relationships for either individual's psychological well-being and future care roles that might be adopted by adult siblings. In the present study, sibling relationships of adults with adult siblings with (N = 63) and without (N = 123) intellectual disability were explored. Contact, warmth, conflict, and rivalry were measured using questionnaires available as an on-line survey. Expressed emotion was measured using the Five Minute Speech Sample over the telephone to establish an independently coded measure of criticism from the participant towards their sibling. Overall, there were few group differences in contact and sibling relationship. There was less telephone contact in the intellectual disability group, and less reported warmth in the relationship with siblings with intellectual disability although this was mainly associated with severe/profound intellectual disability. Exploratory analyses were conducted of the correlates of sibling relationships in both the intellectual disability and control groups. These analyses revealed a small number of different associations especially for conflict, which was lower when either the participant or sibling was younger in the control group but associated with relative age in the intellectual disability group.

The goal of the present study was to ascertain whether individual differences in self-esteem, self-confidence, assertiveness and number of siblings could predict young children's responses to cross-examination style questioning. Five- and 6-year-old children (N = 137) participated in a unique staged event and were then interviewed with analogues of direct and cross-examination. Despite highly accurate direct examination reports, children made a large number of changes to these reports during cross-examination, resulting in a significant decrease in accuracy. Poor cross-examination performance was associated with low levels of teacher-rated self-confidence, self-esteem and assertiveness, raising concern that the children who are likely to fare poorly during cross-examination may be the very children who are most likely to appear as witnesses in the courtroom. Furthermore, number of siblings was inversely related to cross-examination performance. Further research is required to pinpoint the specific mechanism(s) behind this finding. Copyright © 2008 John Wiley & Sons, Ltd. Language: en

A synthetic cell-permeable peptide corresponding to the highly conserved alpha-integrin signature motif, Palmityl-K(989)VGFFKR(995) (Pal-FF), induces integrin activation and aggregation in human platelets. Systematic replacement of the F(992)-F(993) with amino acids of greater or lesser hydrophobicity to create Pal-KVGxxKR peptides demonstrate that hydrophobic amino acids (isoleucine, phenylalanine, tyrosine, tryptophan) are essential for agonist potency. In marked contrast, substitution with small and/or hydrophilic amino acids (glycine, alanine, serine) causes a switch in the biological activity resulting in inhibition of platelet aggregation, adhesion, ADP secretion, and thromboxane synthesis. These substituted, hydrophilic peptides are not true pharmacological antagonists, as they actively induce a phosphotyrosine signaling cascade in platelets. Singly substituted peptides (Pal-AF and Pal-FA) cause preferential retention of pro- or anti-thrombotic properties, respectively. Because the alpha-integrin signature motif is an established docking site for a number of diverse cytoplasmic proteins, we conclude that eliminating critical protein-protein interactions mediated through the hydrophobic amino acids, especially F(993), favors an anti-thrombotic pathway in platelets. Agents derived from the inhibitory peptides described in this study may represent a new therapeutic strategy for anti-platelet or anti-integrin drug development.

Objective.To describe the method used to develop a flexible, computerized database for recording and reporting rates of influenza vaccination among healthcare personnel who were classified by their individual levels (hereafter, “tiers”) of direct patient contact.Design.Three-year descriptive summary.Setting.Large, academic, tertiary care medical center in the United States.Participants.All of the medical center's healthcare personnel.Methods.The need to develop a computer-based system to record direct patient care tiers and vaccination data for healthcare personnel was identified. A plan that was to be implemented in stages over several seasons was developed.Results.Direct patient care tiers were defined by consensus opinion on the basis of the extent, frequency, and intensity of direct contact with patients. The definitions of these tiers evolved over 3 seasons. Direct patient care classifications were assigned and recorded in a computerized database, and data regarding the receipt of vaccination were tracked by using the same database. Data were extracted to generate reports of individual, departmental, and institutional vaccination rates, both overall and according to direct patient care tiers.Conclusions.Development of a computerized database to record direct patient care tiers for individual healthcare workers is a daunting but manageable task. Widespread use of these direct patient care definitions will facilitate uniform comparisons of vaccination rates between institutions. This computerized database can easily be used by infection control personnel to accomplish several other key tasks, including vaccination triage in the context of shortage or delay, prioritization of personnel to receive interventions in times of crisis, and monitoring the status of other employee health or occupational health measures.

Objective Early inattention is associated with later reading problems in children, but the mechanism by which this occurs is unclear. We investigated whether the negative relation between preschoolers' ADHD symptoms and 8-year-old reading achievement is directly related to the severity of inattention or is mediated by early language skills. Method Children (n = 150; 76% boys) were evaluated at 3 time points: preschool (T1), mean (SD) age = 4.24 (.49) years; 1 year later (T2), mean (SD) age = 5.28 (.50) years; and during school age (T3), mean (SD) age = 8.61 (.31) years. At T1, parents' Kiddie-SADS responses were dimensionalized to reflect ADHD severity. Children completed the Language domain of the NEPSY (i.e., A Developmental Neuropsychological Assessment) at T1 and again at T2. At T3, children completed the Wechsler Individual Achievement Test, Second Edition Word Reading, Pseudoword Decoding, Reading Comprehension, and Spelling subtests, and their teachers completed ratings of Reading and Written Expression performance in school. The mediating effect of T2 Language on the relation between preschool Inattention and age 8 Reading was examined using the nonparametric bootstrapping procedure, while controlling for T1 Language. Results Language ability at T2 mediated the path from preschool inattention (but not hyperactivity/impulsivity) to 8-year-old reading achievement (both test scores and ratings) after controlling for preschoolers' language ability. Conclusions Early attentional deficits may negatively impact school-age reading outcomes by compromising the development of language skills, which in turn imperils later reading achievement. Screening children with attentional problems for language impairment, as well as implementing early intervention for both attentional and language problems may be critical to promote reading achievement during school years. (PsycINFO Database Record

The platelet-specific integrin alphaIIb beta3 has endogenous thiol isomerase activity associated with the CXXC motifs within the beta subunit. Using a highly purified form of bacitracin, a thiol isomerase inhibitor, we now provide further evidence of the functional significance of this enzymatic activity in integrin activation. In addition, we demonstrate a role for multiple thiol isomerases in platelet function. This bacitracin prevented platelet aggregation to thrombin and collagen, and directly inhibited alphaIIb beta3 activation, as detected by PAC-1 binding. In parallel, bacitracin inhibited the endogenous thiol isomerase activity of purified alphaIIb beta3 with a 50% inhibitory concentration of 15.5 micromol/l. In order to determine whether the effects of bacitracin are solely mediated by inhibition of integrin enzymatic activity, we examined integrin-independent indices of platelet activation. We found bacitracin inhibited both platelet secretion (CD62P and CD63) and thromboxane (TxA2) production, with complete inhibition at different concentrations. Thus, we demonstrated a role for multiple thiol isomerases in platelet function. Taken together, these studies support a role for the endogenous integrin thiol isomerase activity in activation of alphaIIb beta3 and highlight the novel regulation of platelet function by other, as yet undefined thiol isomerases.

The molecular mechanisms involved in regulating the activation-dependent conformational switch in integrins are not known although recent evidence suggests that integrins are a direct target for redox modulation. We have identified an endogenous integrin thiol isomerase activity that may be responsible for regulating integrin activation states. The purpose of this study was to examine the effects of redox conditions elicited by nitric oxide and glutathione on the thiol isomerase activity of the platelet integrin alphaIIbbeta3 and also on the activation status of this integrin in intact platelets. The universal integrin activator, Mn2+, stimulates the thiol isomerase activity in purified alphaIIbbeta3. Kinetic analysis reveals that alphaIIbbeta3 is an allosteric enzyme which displays positive cooperativity in the presence of Mn2+ with an apparent Hill coefficient of 1.9. Also, addition of Mn2+ to platelets results solely in activation of the integrin as demonstrated by the binding of the antibody PAC-1. The addition of the nitric oxide donors SNP, SIN-1, and SNOAC in combination with glutathione can directly reverse the activation state of the platelet integrin induced by Mn2+. These compounds have no effect on platelet secretory responses indicating a direct effect on the integrin. In the presence of nitric oxide and glutathione, the enzymatic activity of alphaIIbbeta3 also displays positive cooperativity (apparent Hill coefficient of 1.9), and a significant increase in the saturability of the enzyme was observed. Thus, redox agents simultaneously modulate the thiol isomerase activity of purified alphaIIbbeta3 and its active conformation in intact platelets, suggesting a molecular mechanism for integrin regulation.

Cooperation depends upon high relatedness, the high genetic similarity of interacting partners relative to the wider population. For pathogenic bacteria, which show diverse cooperative traits, the population processes that determine relatedness are poorly understood. Here, we explore whether within-host dynamics can produce high relatedness in the insect pathogen Bacillus thuringiensis. We study the effects of host/pathogen interactions on relatedness via a model of host invasion and fit parameters to competition experiments with marked strains. We show that invasibility is a key parameter for determining relatedness and experimentally demonstrate the emergence of high relatedness from well-mixed inocula. We find that a single infection cycle results in a bottleneck with a similar level of relatedness to those previously reported in the field. The bottlenecks that are a product of widespread barriers to infection can therefore produce the population structure required for the evolution of cooperative virulence.

Background As the disease burden in the Gambia has reduced considerably over the last decade, heterogeneity in malaria transmission has become more marked, with infected but asymptomatic individuals maintaining the reservoir. The identification, timely diagnosis and treatment of malaria-infected individuals are crucial to further reduce or eliminate the human parasite reservoir. This ethnographic study focused on the relationship between local beliefs of the cause of malaria and treatment itineraries of suspected cases. Methods An ethnographic qualitative study was conducted in twelve rural communities in the Upper River Region and the Central River Region in the Gambia. The data collection methods included in-depth interviews, participant observation, informal conversations, and focus group discussions. Results While at first glance, the majority of people seek biomedical treatment for ‘malaria’, there are several constraints to seeking treatment at health centres. Certain folk illnesses, such as Jontinooje and Kajeje, translated and interpreted as ‘malaria’ by healthcare professionals, are often not considered to be malaria by local populations but rather as self-limiting febrile illnesses ? consequently not leading to seeking care in the biomedical sector. Furthermore, respondents reported delaying treatment at a health centre while seeking financial resources, and consequently relying on herbal treatments. In addition, when malaria cases present symptoms, such as convulsions, hallucinations and/or loss of consciousness, the illness is often interpreted as having a supernatural aetiology, leading to diagnosis and treatment by traditional healers. Conclusion Although malaria diagnostics and treatment-seeking in the biomedical sector has been reported to be relatively high in the Gambia compared to other sub-Saharan African countries, local symptom interpretation and illness conceptions can delay or stop people from seeking timely biomedical treatment, which may contribute to maintaining a parasite reservoir of undiagnosed and untreated malaria patients., Malaria Journal, 14, 167; 2015

Data from animal studies provide convincing evidence that physical exercise enhances brain development and neurobehavioral functioning in areas believed to be impaired in children with attention-deficit/hyperactivity disorder (ADHD). To a lesser but still compelling extent, results from studies in typically developing children and adults indicate beneficial effects of exercise on many of the neurocognitive functions that have been shown to be impaired in children with ADHD. Together, these data provide a strong rationale for why a program of structured physical exercise might serve as an effective intervention for children with ADHD.

We have identified a patient designated as (GTa) with Glanzmann's Thrombasthenia (GT) diagnosed on the basis of a prolonged bleeding time and failure of the patient's platelets to aggregate. The number of glycoprotein (GP)IIb/IIIa receptors on the platelet surface was 37% of normal and those receptors displayed a defect in soluble fibrinogen binding. Nevertheless, GTa platelets showed increased adhesion to solid-phase fibrinogen and binding affinity for the RGD-mimetic 3H-SC52012, a non-peptide GPIIb/IIIa antagonist. Dithiothreitol (DTT) and ADP enhanced the affinity for [3H]-SC52012 in normal platelets, but had little effect in GTa platelets. These findings suggested that GTa platelets were locked in an altered affinity state. Genetic analysis showed that GTa was a compound heterozygote for the GPIIIa gene. One allele showed a deletion at the 3′ end of exon 3 resulting in a premature stop codon. The second GPIIIa allele had a G to A transition at nucleotide 577, resulting in a Val193Met substitution. HEK 293T cells transfected with mutant GPIIb/IIIaV193M bound [3H]-SC52012 with a higher affinity than wild-type GPIIb/IIIa, and this was not increased by DTT. The mutant receptor distinguishes between platelet adhesion and aggregation, and demonstrates the phenotype that may be expected when platelet aggregation alone is inhibited.

peer-reviewed The specific immobilisation of a histidine-tagged protein, Spi, onto mono-anchored nickel(II)-cyclam functionalised SBA-15 is reported. ACCEPTED peer-reviewed

Integrins are cysteine-rich heterodimeric cell-surface adhesion molecules that alter their affinity for ligands in response to cellular activation. The molecular mechanisms involved in this activation of integrins are not understood. Treatment with the thiol-reducing agent, dithiothreitol, can induce an activation-like state in many integrins suggesting that cysteine-cysteine dithiol bonds are important for the receptor's tertiary structure and may be involved in activation-induced conformational changes. Here we demonstrate that the platelet-specific integrin, alpha(IIb)beta(3), contains an endogenous thiol isomerase activity, predicted from the presence of the tetrapeptide motif, CXXC, in each of the cysteine-rich repeats of the beta(3) polypeptide. This motif comprises the active site in enzymes involved in disulfide exchange reactions, including protein-disulfide isomerase (EC ) and thioredoxin. Intrinsic thiol isomerase activity is also observed in the related integrin, alpha(v)beta(3), which shares a common beta-subunit. Thiol isomerase activity within alpha(IIb)beta(3) is time-dependent and saturable, and is inhibited by the protein-disulfide isomerase inhibitor, bacitracin. Furthermore, this activity is calcium-sensitive and is regulated in the EDTA-stabilized conformation of the integrin. This novel demonstration of an enzymatic activity associated with an integrin subunit suggests that altered thiol bonding within the integrin or its substrates may be locally modified during alpha(IIb)beta(3) activation.

Children with attention deficit/hyperactivity disorder (ADHD) have poorer neuropsychological functioning relative to their typically developing peers. However, it is unclear whether early neuropsychological functioning predicts later ADHD severity and/or the latter is longitudinally associated with subsequent neuropsychological functioning; and whether these relations are different in children with and without early symptoms of ADHD. This study aimed to examine the longitudinal associations between ADHD severity and neuropsychological functioning among children at high and low risk of developing ADHD. Hyperactive/Inattentive (H/I; n = 140) and Typically developing (TD; n = 76) preschoolers (age 3-4 years) were recruited (BL) and followed annually for 3 years (F1, F2, and F3). Teachers rated the children's ADHD severity and impairment using the Behavior Assessment System for Children-2 and the Children's Problem Checklist, respectively. Parent reports of children's ADHD severity were obtained using the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version. Neuropsychological functioning was assessed using the NEPSY. In the full sample, there were bidirectional longitudinal associations between neuropsychological functioning and ADHD severity between F1 and F3. Among H/I children, neuropsychological functioning at F1 and F2 predicted ADHD severity at F2 and F3, respectively. In contrast, among TD children the only significant relationship observed was that elevated ADHD symptoms at F2 were associated with poorer neuropsychological functioning at F3. Improved neuropsychological functioning may attenuate ADHD symptoms and associated impairment among H/I children during the early school years. Interventions designed to improve neuropsychological functioning among young H/I children may be beneficial in reducing their ADHD severity.

This study investigated whether preinterview interventions could help to facilitate children's accuracy under cross-examination-style questioning. Five- and 6-year-olds (n = 77; mean [SD] age = 5.84 [0.48] years; 57% boys) and 9- and 10-year-olds (n = 87; mean [SD] age = 10.30 [0.54] years; 56% boys) took part in a staged event and were then interviewed with analogues of direct examination and cross-examination. In a pilot study, we ascertained that a brief verbal warning about the nature of cross-examination-given immediately prior to the cross-examination interview-did not influence children's cross-examination accuracy, regardless of whether it was delivered by an unfamiliar interviewer or the cross-examining interviewer. In the main experiment, some children participated in a brief intervention involving practice and feedback with cross-examination questions. Relative to control children, those who underwent this preparation intervention made fewer changes to their direct-examination responses under cross-examination, changed a smaller proportion of their correct responses, and obtained higher ultimate accuracy levels. These findings provide some support for the notion that pretrial interventions, if sufficiently comprehensive, could help children to maintain accuracy during cross-examination.

To determine whether patients from regional areas undergoing surgery for kidney cancer present with more advanced disease as a result of geographic isolation.Retrospective analysis of 221 patients undergoing surgery for renal cell carcinoma (RCC) from January 2004 to June 2012, from both a metropolitan centre and a large inner regional hospital. Data was collected on age, gender, presentation (incidental or symptomatic), clinical stage and pathological features. The Australian Standard Geographical Classification-Remoteness Area (ASGC-RA) is a system developed to allow quantitative comparisons between metropolitan and rural Australia. A score was assigned to each patient based on their location of residence at the time of surgery: metropolitan, RA1; inner regional, RA2; outer regional, RA3. Statistical significance was specified as P0.05 on Pearson's chi-square tests.Patients in each ASGC-RA group did not differ significantly in age, sex or mode of presentation. Pathological T stage on presentation increased with increasing ASGC-RA and thus distance from tertiary centres (P = 0.004). The proportion of patients with ≥T3 disease rose from 30% of RA1 to 73% of RA3 patients (P = 0.016) treated at our tertiary centre. Similarly, our regional centre had a larger proportion of patients presenting with ≥T3 disease from RA3 (31% vs 5%, P = 0.003). When the 221 patients with RCC were analysed as a group, clinical T stage was significantly associated with ASGC-RA (P0.001), symptomatic presentation (P0.001), N stage (P0.001), M stage (P0.001) and Fuhrman grade (P0.001).Our data quantifies the detrimental effect of physical distance on the health outcomes of regional Australians with kidney cancer. Australia's unique geography and rural culture may preclude any attempts to centralise cancer care to specialised metropolitan units, as has occurred in other countries.

To investigate the potential bidirectional relationships between severity of inattention and depression across early childhood.Children (N = 216) from the New York, NY, metropolitan area were recruited when they were aged 3 to 4 years (T1) and studied again at age 6 (T2) and 7 (T3) years. Child inattention symptoms were measured using the Kiddie-Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime, along with both parent and teacher reports on the Behavior Assessment System for Children, Second Edition (BASC-2). Severity of child depression was assessed at each time point using parent and teacher reports on the BASC-2. After examining correlations between child inattention and depression, structural equation modeling was used to investigate whether child inattention was longitudinally related to child depression, and whether child depression symptoms were associated with later child inattention.Severity of child inattention at T1 and T2 was longitudinally associated with increased severity of child depression at T2 and T3, respectively. Early child depression was not longitudinally associated with later child inattention.Child inattention is a risk factor for increased levels of child depression. Pediatricians and clinicians who assess children's inattention symptoms also need to investigate symptoms of depression. This study makes a case for treating children's inattention symptoms at preschool and early childhood, before emotional problems become more severe.

The negative effect of cross-examination-style questioning on children's accuracy is likely to be due to the complex and credibility-challenging questions that characterize the interview. Given that cross-examination occurs after at least one prior interview, however, it is equally possible that repeated interviewing per se impairs children's accuracy, and that the questions asked have little bearing on children's responses. To examine this issue, 5- and 6-year-old children (n= 82) and 9- and 10-year-old children (n= 103) took part in a surprise event and were then interviewed using an analogue of direct examination. Either 1 week or 6 months later, half of the children were re-interviewed with an analogue of cross-examination designed to challenge their direct examination responses. Remaining children were re-interviewed with the same questions that were asked during direct examination. Children's accuracy decreased following their second interview, irrespective of age or delay; however, delay particularly impacted younger children's second interview performance. Children's accuracy was most impaired following a cross-examination-style interview. Overall, cross-examination-style questioning appears to be particularly detrimental to obtaining accurate event reports from children.

SUMMARYAccessory molecules play a crucial role in the development of the T cell response to antigenic challenge. We have examined the role of CD28 in modulating the‘naive’ neonatal T cell response to anti-CD2-mediated activation. To compare the role of CD28, neonatal and adult T cells were stimulated with a pair of mitogenic anti-CD2 antibodies in the presence or absence or anti-CD28 MoAb. With anti-CD2 alone, neonatal T cells proliferated slightly but produced no detectable IL-2, whereas adult T cells proliferated vigorously, with significant IL-2 production. Costimulation with anti-CD28 MoAb greatly enhanced the proliferative response of neonatal T cells to levels equivalent to those of adult T cells, whereas adult T cells showed only slight increases. Although IL-2 secretion was increased in the presence of anti-CD28 MoAb. neonatal T cell IL-2 production remained lower than in adults. In contrast, enhancement of IL-2 mRNA expression in neonates was similar to adult levels. Anti-CD28 MoAb costimulation increased NFkB levels in neonates, albeit to levels lower than that of adults. The cellular mechanism governing the diminished proliferative response of neonatal T lymphocytes to anti-CD2 may therefore be due to decreased NFkB induction, reduced IL-2 mRNA expression and deficient IL-2 production. Although anti-CD28 MoAb costimulation enhances all of the above signals, NFkB and IL-2 levels remain lower than in adults, suggesting the need for further activation requirements in the neonate.

Introduction: The potential benefits of Mass Drug Administration (MDA) for malaria elimination are being considered in several malaria endemic countries where a decline in malaria transmission has been reported. For this strategy to work, it is important that a large proportion of the target population participates, requiring an in-depth understanding of factors that may affect participation and adherence to MDA programs. Methodology: This social science study was ancillary to a one-round directly observed MDA campaign with dihydroartemisinin-piperaquine, carried out in 12 villages in rural Gambia between June and August 2014. The social science study employed a mixed-methods approach combining qualitative methods (participant observation and in-depth interviewing) and quantitative methods (structured follow-up interviews among non-participating and nonadhering community members). Results: Of 3942 people registered in the study villages, 67.9% adhered to the three consecutive daily doses. For the remaining villagers, 12.6%did not attend the screening, 3.5% was not eligible and 16% did not adhere to the treatment schedule. The main barriers for non-participation and adherence were long and short-term mobility of individuals and specific subgroups, perceived adverse drug reactions and rumors, inconveniences related to the logistics of MDA (e.g. waiting times) and the perceived lack of information about MDA. Conclusion: While, there was no fundamental resistance from the target communities, adherence was 67.9%. This shows the necessity of understanding local perceptions and barriers to increase its effectiveness. Moreover, certain of the constraining factors were socio-spatially clustered which might prove problematic since focal areas of residual malaria transmission may remain allowing malaria to spread to adjacent areas where transmission had been temporarily interrupted., PLOS ONE, 11(2), e0148627; 2016

Premature ovarian failure and infertility following chemotherapy in early breast cancer (EBC) are major concerns for young women. The role of gonadotrophin-releasing hormone (GnRH) agonists with chemotherapy in EBC in reducing the incidence of chemotherapy-induced early menopause remains uncertain, and long-term data on the recovery of fertility are sparse. We report an audit of our experience with the GnRH agonist, goserelin (Zoladex((R))), used with chemotherapy to preserve ovarian function and maintain fertility. Pre-menopausal women were given goserelin subcutaneously every 28 days during chemotherapy, starting 0-14 days before treatment. The main clinical end point was recovery of menstruation after chemotherapy. The other end points were rate of successful conception and median time to recovery of menses. About 84% of 125 women recovered menstruation with the median time to recovery of 6 months (1-43 months), including 76% of 71 patients aged over 35. Of the 42 patients who attempted pregnancy, 71% (n = 30) managed to achieve pregnancies. At the time of analysis, there were 42 pregnancies and 30 healthy deliveries. The GnRH agonist, goserelin, given with chemotherapy for EBC is associated with a low risk of long-term chemotherapy-induced amenorrhoea and a high chance of pregnancy. Further randomised trials are needed.

Platelets are well-established mediators of inflammatory responses throughout the body. Increased platelet activity occurs in the intestinal mucosa in conditions of Inflammatory Bowel Disease (IBD), where it may contribute to the mucosal fibrosis associated with these diseases. The bile acids, ursodeoxycholic acid (UDCA), deoxycholic acid (DCA) and tauroursodeoxycholic acid (TUDCA) were shown to regulate inflammatory responses in the intestine. The aim of this study is to analyse the impact of these bile acids on platelet activation.

Platelets bind annexin V when stimulated with combinations of platelet agonists such as collagen and thrombin. Previous studies have demonstrated significant heterogeneity of platelets binding annexin V. The relative role of the thrombin protease-activated receptors (PARs), PAR1 and PAR4, together with different methods of platelet preparation on annexin V binding to platelets is unclear. We therefore investigated the role of PAR1- and PAR4-activating peptides in combination with collagen-related peptide on annexin V binding. In diluted whole blood, PAR1- and PAR4-activating peptides were as effective as thrombin in inducing annexin V binding. However, in washed platelets, PAR-activating peptides were less potent than thrombin at inducing annexin V binding. This difference was more pronounced when experiments were performed at 37 degrees C compared to room temperature. In studies of diluted whole blood, platelet rich plasma and washed platelets, platelets incubated at room temperature bound more annexin V than platelets incubated at 37 degrees C. We also saw a significant effect of time on annexin V binding, in that more annexin V bound to platelets with longer incubation times. In conclusion, PAR1 and PAR4-activating peptides were as effective as thrombin in inducing annexin V binding in combination with collagen-related peptide in diluted whole blood and platelet rich plasma, but not in washed platelets. In addition, incubation temperature and time has a strong influence on annexin V binding to platelets. Thus variations in these conditions may explain the differences observed between previous studies.