Stepping out of secrecy: heterosexuality, quality of life, and experiences of HIV peer navigation in Australia.

Heterosexual people make up a small, but growing proportion of people living with HIV in Australia. This article draws on semi-structured interviews with thirteen heterosexual men and women living with HIV to examine the bearing that sexual identity had on their participation in a peer navigation programme. Our analyses consider the influence of sexuality and gender on the quality of peer relations and the effects of HIV-related stigma on health service engagement and quality of life. Gender and sexuality were significant factors in establishing understanding, acceptance, and community for participants. Having their heterosexuality mirrored by a peer was affirming for men. Women instead emphasised their gendered experiences of HIV. Otherwise, participants' narratives suggested that an experienced peer could reassure, guide interactions with community and services, and ease treatment-related and nonclinical aspects of life. We see peer navigation as a promising intervention to improve the quality of life for heterosexual people living with HIV. Person-centred support from a peer may be particularly important in HIV service environments adapting to the needs of heterosexual people. Peer navigation programmes should promote choice and employ peers of diverse experiences. Implications for referral and the improvement of social services for heterosexual people living with HIV are discussed.

Double-Effect Donation or Bodily Respect? A "Third Way" Response to Camosy and Vukov.

Is it possible to donate unpaired vital organs, foreseeing but not intending one's own death? We argue that this is indeed psychologically possible, and thus far agree with Charles Camosy and Joseph Vukov in their recent paper on "double effect donation." Where we disagree with these authors is that we see double-effect donation not as a morally praiseworthy act akin to martyrdom but as a morally impermissible act that necessarily disrespects human bodily integrity. Respect for bodily integrity goes beyond avoiding the aim to kill: not all side effects of deliberate bodily interventions can be outweighed by intended benefits for another even if the subject fully consents. It is not any necessary intention to kill or harm another or oneself that makes lethal donation/harvesting illicit but the more immediate intention to accept or perform surgery on an (innocent) person combined with the foresight of lethal harm and no health-related good for him or her. Double-effect donation falls foul of the first condition of double-effect reasoning in that the immediate act is wrong in itself. We argue further that the wider effects of such donation would be socially disastrous and corrupting of the medical profession: doctors should retain a sense of nonnegotiable respect for bodily integrity even when they intervene on willing subjects for the benefit of others. Summary: Lethal organ donation (for example, donating one's heart) is not a praiseworthy but a morally impermissible act. This is not because such donation necessarily involves any aim to kill oneself (if one is the donor) or to kill the donor (if one is the surgeon). Respect for bodily integrity goes beyond avoiding any hypothetical aim to kill or harm oneself or another innocent person. 'Double effect donation' of unpaired vital organs, defended by Camosy and Vukov, is in our view a form of lethal bodily abuse and would also harm the transplant team, the medical profession and society at large.

Glial Synaptobrevin mediates peripheral nerve insulation, neural metabolic supply, and is required for motor function.

Peripheral nerves contain sensory and motor neuron axons coated by glial cells whose interplay ensures function, but molecular details are lacking. SNARE-proteins mediate the exchange and secretion of cargo by fusing vesicles with target organelles, but how glial SNAREs contribute to peripheral nerve function is largely unknown. We, here, identify non-neuronal Synaptobrevin (Syb) as the essential vesicular SNARE in Drosophila peripheral glia to insulate and metabolically supply neurons. We show that tetanus neurotoxin light chain (TeNT-LC), which potently inhibits SNARE-mediated exocytosis from neurons, also impairs peripheral nerve function when selectively expressed in glia, causing nerve disintegration, defective axonal transport, tetanic muscle hyperactivity, impaired locomotion, and lethality. While TeNT-LC disrupts neural function by cleaving neuronal Synaptobrevin (nSyb), it targets non-neuronal Synaptobrevin (Syb) in glia, which it cleaves at low rates: Glial knockdown of Syb (but not nSyb) phenocopied glial TeNT-LC expression whose effects were reverted by a TeNT-LC-insensitive Syb mutant. We link Syb-necessity to two distinct glial subtypes: Impairing Syb function in subperineurial glia disrupted nerve morphology, axonal transport, and locomotion, likely, because nerve-isolating septate junctions (SJs) could not form as essential SJ components (like the cell adhesion protein Neurexin-IV) were mistargeted. Interference with Syb in axon-encircling wrapping glia left nerve morphology and locomotion intact but impaired axonal transport, likely because neural metabolic supply was disrupted due to the mistargeting of metabolite shuffling monocarboxylate transporters. Our study identifies crucial roles of Syb in various glial subtypes to ensure glial-glial and glial-neural interplay needed for proper nerve function, animal motility, and survival.

The preterm infant-parent programme for attachment-PIPPA Study: a randomised controlled trial.

BACKGROUND: There is increasing recognition of adverse mental health consequences of preterm birth and the impact on social-emotional development. However, the quality of the developing parent-infant relationship may be protective, with enhanced maternal sensitivity to infants' cues associated with improved outcomes. METHODS: Eighty mothers and their preterm infants born <32 weeks gestation were randomised to intervention and standard care groups. Intervention comprised reflective interview, observation of infant cues and video interaction guidance (VIG). The primary outcome, maternal sensitivity during play, was measured by the Child Adult Relationship Evaluation-Index. Secondary outcomes were infant social-emotional problems measured by the Ages and Stages Questionnaire-Social-Emotional version. RESULTS: There was no statistically significant difference between the intervention and standard care groups in maternal sensitivity during play at 9 months corrected age (CA). In the secondary outcome analysis at 12 months CA, infants in the intervention group had fewer self-regulation problems than infants whose mothers received standard care. Per-protocol analysis revealed that infants whose mothers completed VIG had significantly fewer communication problems. CONCLUSIONS: This early attachment-focussed intervention integrating VIG for mothers and their preterm infants did not enhance maternal sensitivity; however, there were effects on infant social-emotional problems at 12 months CA. IMPACT: Preterm birth can adversely affect infant and parent mental health and the quality of the parent-infant relationship. Early intervention to support parent-infant interaction can have positive effects on infant social-emotional development. There was no statistically significant difference in maternal sensitivity during play at 9 months CA. However, there were fewer infant self-regulation and communication problems reported by mothers at 12 months CA following intervention. Further evaluations of attachment-focussed interventions in the neonatal intensive care unit are needed.

Dumbell atypical teratoid/rhabdoid tumour (AT/RT) of the cervical spine.

Spinal Atypical Teratoid/Rhabdoid Tumour (AT/RT) is a highly malignant tumour, and its prognosis is dismal especially for very young patients. In this article, we present the case of a teenage boy with AT/RT in the cervical spine and its multimodality management. A review of the literature on ATRT of the spine is also presented.

Targeting the Fetal Body and/or Mother-Child Connection: Vital Conflicts and Abortion.

Is the "act itself" of separating a pregnant woman and her previable child neither good nor bad morally, considered in the abstract? Recently, Maureen Condic and Donna Harrison have argued that such separation is justified to protect the mother's life and that it does not constitute an abortion as the aim is not to kill the child. In our article on maternal-fetal conflicts, we agree there need be no such aim to kill (supplementing aims such as to remove). However, we argue that to understand "abortion" as performed only where the death of the child is intended is to define the term too narrowly. Respect for the mother, the fetus, and the bond between them goes well beyond avoiding any such aim. We distinguish between legitimate maternal treatments simply aimed at treating or removing a damaged part of the woman and illegitimate treatments that focus harmfully on the fetal body and its presence within the mother's body. In obstetrics as elsewhere, not all side effects for one subject of intervention can be outweighed by intended benefits for another. Certain side effects of certain intended interventions are morally conclusive. SUMMARY: How should one respond to "vital conflicts" in pregnancy where the mother's life or health is at risk? We argue that, in addition to avoiding any aim of ending life, one must avoid the similarly unacceptable aims of evicting the baby pre-viability and invading its body, including its placenta, in a lethally harmful way. Even at the cost of real and important benefits for the mother such as increased safety and protection of fertility, we must manage cases always in a way that respects the inviolable bodily rights of both mother and child and crucially, the unique bond between them.

A population survey of prevalence rates of antenatal depression in the Irish obstetric services using the Edinburgh Postnatal Depression Scale (EPDS).

Ireland has the second-highest birth rate in Europe and poorly developed perinatal psychiatry services. There are no screening services for antenatal depression and no data available on prevalence rates of depression among women attending the Irish obstetric services. The aim of this study was to assess the prevalence rates of depression during pregnancy in a population sample in Ireland using the Edinburgh Postnatal Depression Scale (EPDS) as a screening tool. Pregnant women during all stages of pregnancy were recruited from five maternity hospitals throughout the Republic of Ireland. Approximately 5000 EPDS questionnaires were collected. Information on the participant's age, gestational week, gravidity, parity, and level of education attained was also collected. A score of > 12 was used as a measure of probable depression. Overall, 15.8% of pregnant women scored > 12 in the EPDS. There was a significant association between gestational week and rates of depression, with increasing rates occurring with advancing pregnancy (p < 0.001). Overall, higher socioeconomic groups were over-represented in the sample although we replicated the well-established findings of higher EPDS scores in women with lower educational attainment (p < 0.005). This study demonstrates that prevalence rates of probable antenatal depression are high among women attending the obstetric services in Ireland and highlight the importance of increasing awareness of antenatal depression. These high rates of antenatal depression may be related to certain conditions that are specific to an Irish setting: the absence of screening for depression in the context of grossly under-resourced perinatal psychiatry services. These findings provide indirect confirmatory evidence for the need for streamlined mental health services within reproductive health services.

Fifteen-minute consultation: Assessment, surveillance and management of hemihypertrophy.

This article aims to provide a structured and concise guide for the general paediatrician managing a child with hemihypertrophy. Hemihypertrophy is a relatively uncommon condition. The significance is that a proportion of those affected are at risk of developing malignancies in childhood. For these children regular surveillance is required. We have outlined how one might assess and investigate a child presenting with hemihypertrophy. We have also formulated a practicable surveillance strategy which is in line with the current Royal College of Paediatrics and Child Health (RCPCH) guideline 'Wilms' tumour surveillance in at-risk children'.

SUPPORTING PRETERM INFANT ATTACHMENT AND SOCIOEMOTIONAL DEVELOPMENT IN THE NEONATAL INTENSIVE CARE UNIT: STAFF PERCEPTIONS.

The infant-parent relationship has been shown to be of particular significance to preterm infant socioemotional development. Supporting parents and infants in this process of developing their relationships is an integral part of neonatal intensive care; however, there is limited knowledge of NICU staff perceptions about this aspect of care. To explore NICU staff perceptions about attachment and socioemotional development of preterm infants, experience of training in this area and the emotional impact of their work. A cross-sectional questionnaire survey of staff perceptions of the emotional experiences of parents and the developing parent-infant relationship in an NICU was conducted in a Level III NICU, after pilot testing, revision, and ethical approval. Fifty-seven (68%) of NICU staff responded to the survey. Respondents identified parents' emotional experiences such as "anxiety," "shock," "loss of control," and "lack of feelings of competence as parents" as highly prevalent. Infant cues of "responding to parent's voice" and "quieting-alerting" were ranked most highly; "crying" and "physiological changes" were ranked lowest. Preterm infant medical risk, maternal emotional state, and mental health are perceived to impact most highly on the developing relationship, as compared with infant state or behavior and socioeconomic factors. Fifty-three (93%) respondents felt confident, and 50 (87.8%) felt competent discussing their emotional experiences with parents. Fifty-four (95%) responded that attending to these areas was an integral part of their role; however, staff had seldom received education in this area. Respondents also perceived that specific psychological support for parents was lacking both during and after the infant's discharge. While all staff surveyed perceived the nature of their work to be emotionally stressful, there were differences among NICU staff disciplines and with years of experience in the NICU in terms of their perceptions about education in this area, the place of supervision for staff, and in relation to opportunities to discuss the emotional impact of the work on staff. NICU staff perceive their role as integral to supporting the developing parent-infant relationship and preterm infant socioemotional development; however, education in this area and provision of specific psychological support are lacking. Opportunities for staff to discuss and reflect on this aspect of their work should be developed and evaluated given the essential, but emotionally challenging, nature of their work with preterm babies and their parents.

A severe bleeding diathesis in a 6-year-old girl secondary to a composite diagnosis of splenic hemangiomatosis and small bowel lymphangiomatosis.

A 6-year-old girl presented with presumed relapse of childhood immune thrombocytopenia. Investigations revealed deranged coagulation parameters, abnormal small bowel thickening, and splenomegaly. A clinically significant bleeding diathesis emerged which was refractory to most hemostatic interventions. Laparatomy revealed a composite diagnosis of splenic hemangiomatosis and small bowel lymphangiomatosis. Splenectomy resulted in complete resolution of the coagulopathy. The diagnosis and management of these conditions is inherently complex and without clear guidance. We discuss our perioperative management of the bleeding diathesis. There is a need for long-term follow-up of the underlying pathologies particularly as potentially useful therapeutic agents have emerged.

Childbearing, abortion and regret: a response to Kate Greasley.

Is moral or other regret for abortion an indicator that abortion may not be morally or prudentially choice worthy? This paper examines the work of Kate Greasley in this area, who offers an explanation of any asymmetry in openness to regret between women who have abortions and women who give birth. The latter, not unlike Derek Parfit's 14-year-old who conceives deliberately, may feel duty-bound not to regret their decision (in their case, to continue their pregnancy) and to affirm the life of their child. In response to Greasley, testimonial evidence of one group cannot be dismissed simply because regret may be less available to another group of decision-makers. Moreover, if moral regret for childbearing is uncommon, this is not because mothers have a moral duty, as Greasley argues, not to regret even a morally mistaken choice to conceive. On the contrary, one must separate the evaluation of choices and of the results of these choices, whether positive or negative. Regret, while not infallible, can elucidate values at stake in choices, and testimonial evidence in the form of regret should be taken more seriously in regard to certain kinds of choice.

Spontaneous neurotransmission at evocable synapses predicts their responsiveness to action potentials.

Synaptic transmission relies on presynaptic neurotransmitter (NT) release from synaptic vesicles (SVs) and on NT detection by postsynaptic receptors. Transmission exists in two principal modes: action-potential (AP) evoked and AP-independent, "spontaneous" transmission. AP-evoked neurotransmission is considered the primary mode of inter-neuronal communication, whereas spontaneous transmission is required for neuronal development, homeostasis, and plasticity. While some synapses appear dedicated to spontaneous transmission only, all AP-responsive synapses also engage spontaneously, but whether this encodes functional information regarding their excitability is unknown. Here we report on functional interdependence of both transmission modes at individual synaptic contacts of Drosophila larval neuromuscular junctions (NMJs) which were identified by the presynaptic scaffolding protein Bruchpilot (BRP) and whose activities were quantified using the genetically encoded Ca2+ indicator GCaMP. Consistent with the role of BRP in organizing the AP-dependent release machinery (voltage-dependent Ca2+ channels and SV fusion machinery), most active BRP-positive synapses (>85%) responded to APs. At these synapses, the level of spontaneous activity was a predictor for their responsiveness to AP-stimulation. AP-stimulation resulted in cross-depletion of spontaneous activity and both transmission modes were affected by the non-specific Ca2+ channel blocker cadmium and engaged overlapping postsynaptic receptors. Thus, by using overlapping machinery, spontaneous transmission is a continuous, stimulus independent predictor for the AP-responsiveness of individual synapses.

The experience of fatherhood following childhood cancer survival.

This study explored the experience of becoming a father following childhood cancer survival. Semi-structured interviews were conducted with five fathers and analysed using interpretative phenomenological analysis. Three superordinate themes emerged: 'moving away from and revisiting the experience of cancer', 'making sense of fortune and loss following a life-threatening illness' and 'valuing the opportunity to be a father'. The transition to fatherhood brought unique and specific challenges to fathers. Nevertheless, all appeared to have positively adjusted to this transition. Findings recommended providing information and support to childhood survivors who wish to or who are about to become fathers.

The hypothalamic-pituitary-adrenal axis in the perinatal period: Its relationship with major depressive disorder and early life adversity.

Objectives: Effects of major depressive disorder and early life adversity (ELA) on the maternal HPA axis in the perinatal period were examined.Methods: Four groups of women (n = 127) were recruited, with the perinatal groups being compared during pregnancy (Preg) and at two months postpartum (PP) - [1] Depressed during pregnancy (Depressed-Preg/PP), [2] Prior history of depression but euthymic during pregnancy (History-Preg/PP), [3] Healthy pregnant women (Control-Preg/PP), and [4] Healthy non-pregnant women (Non-pregnant Control). Serial saliva samples were collected over the course of a day and waking and evening cortisol, total cortisol output and the cortisol awakening response were examined.Results: There were no HPA axis differences among the three groups during pregnancy. A history of ELA, regardless of comorbid depression, was associated with higher evening cortisol levels during pregnancy (p = 0.015). Women in the Depressed-PP group had had higher evening cortisol levels compared to the History-PP group (p < 0.017).Conclusions: Evening cortisol measures are a potential marker for both ELA and depression, with higher levels during pregnancy being associated with ELA and higher levels postpartum being associated with antenatal depression.

The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia--an exploratory study.

AIMS: To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP). METHODS: A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire. RESULTS: Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing "carelessness at times about taking medication" as the primary reason for non-adherence followed by "forgetting to take the medication" (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored > or = 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P < 0.05). CONCLUSIONS: The present study explored various ways to assess adherence rates to thiopurine medication in ALL patients and highlighted the importance of combining both objective and subjective measures as a better way to assess adherence to oral thiopurines.

Rapid active zone remodeling consolidates presynaptic potentiation.

Neuronal communication across synapses relies on neurotransmitter release from presynaptic active zones (AZs) followed by postsynaptic transmitter detection. Synaptic plasticity homeostatically maintains functionality during perturbations and enables memory formation. Postsynaptic plasticity targets neurotransmitter receptors, but presynaptic mechanisms regulating the neurotransmitter release apparatus remain largely enigmatic. By studying Drosophila neuromuscular junctions (NMJs) we show that AZs consist of nano-modular release sites and identify a molecular sequence that adds modules within minutes of inducing homeostatic plasticity. This requires cognate transport machinery and specific AZ-scaffolding proteins. Structural remodeling is not required for immediate potentiation of neurotransmitter release, but necessary to sustain potentiation over longer timescales. Finally, mutations in Unc13 disrupting homeostatic plasticity at the NMJ also impair short-term memory when central neurons are targeted, suggesting that both plasticity mechanisms utilize Unc13. Together, while immediate synaptic potentiation capitalizes on available material, it triggers the coincident incorporation of modular release sites to consolidate synaptic potentiation.

Population pharmacokinetic and pharmacogenetic analysis of 6-mercaptopurine in paediatric patients with acute lymphoblastic leukaemia.

AIMS: To investigate the population pharmacokinetics of 6-mercaptopurine (6-MP) active metabolites in paediatric patients with acute lymphoblastic leukaemia (ALL) and examine the effects of various genetic polymorphisms on the disposition of these metabolites. METHODS: Data were collected prospectively from 19 paediatric patients with ALL (n = 75 samples, 150 concentrations) who received 6-MP maintenance chemotherapy (titrated to a target dose of 75 mg m(-2) day(-1)). All patients were genotyped for polymorphisms in three enzymes involved in 6-MP metabolism. Population pharmacokinetic analysis was performed with the nonlinear mixed effects modelling program (nonmem) to determine the population mean parameter estimate of clearance for the active metabolites. RESULTS: The developed model revealed considerable interindividual variability (IIV) in the clearance of 6-MP active metabolites [6-thioguanine nucleotides (6-TGNs) and 6-methylmercaptopurine nucleotides (6-mMPNs)]. Body surface area explained a significant part of 6-TGNs clearance IIV when incorporated in the model (IIV reduced from 69.9 to 29.3%). The most influential covariate examined, however, was thiopurine methyltransferase (TPMT) genotype, which resulted in the greatest reduction in the model's objective function (P < 0.005) when incorporated as a covariate affecting the fractional metabolic transformation of 6-MP into 6-TGNs. The other genetic covariates tested were not statistically significant and therefore were not included in the final model. CONCLUSIONS: The developed pharmacokinetic model (if successful at external validation) would offer a more rational dosing approach for 6-MP than the traditional empirical method since it combines the current practice of using body surface area in 6-MP dosing with a pharmacogenetically guided dosing based on TPMT genotype.