Independently specified Atoh1 domains define novel developmental compartments in rhombomere 1.

The rhombic lip gives rise to neuronal populations that contribute to cerebellar, proprioceptive and interoceptive networks. Cell production depends on the expression of the basic helix-loop-helix (bHLH) transcription factor Atoh1. In rhombomere 1, Atoh1-positive cells give rise to both cerebellar neurons and extra-cerebellar nuclei in ventral hindbrain. The origin of this cellular diversity has previously been attributed to temporal signals rather than spatial patterning. Here, we show that in both chick and mouse the cerebellar Atoh1 precursor pool is partitioned into initially cryptic spatial domains that reflect the activity of two different organisers: an isthmic Atoh1 domain, which gives rise to isthmic nuclei, and the rhombic lip, which generates deep cerebellar nuclei and granule cells. We use a combination of in vitro explant culture, genetic fate mapping and gene overexpression and knockdown to explore the role of isthmic signalling in patterning these domains. We show that an FGF-dependent isthmic Atoh1 domain is the origin of distinct populations of Lhx9-positive neurons in the extra-cerebellar isthmic nuclei. In the cerebellum, ectopic FGF induces proliferation while blockade reduces the length of the cerebellar rhombic lip. FGF signalling is not required for the specification of cerebellar cell types from the rhombic lip and its upregulation inhibits their production. This suggests that although the isthmus regulates the size of the cerebellar anlage, the downregulation of isthmic FGF signals is required for induction of rhombic lip-derived cerebellar neurons.

Factors influencing suicide in older rural males: a review of Australian studies.

INTRODUCTION: Suicide remains an important public health issue in Australia, responsible for around 2500 deaths each year. Although suicide only accounts for around 1.7% of total mortality in Australia per year, 75% of suicide deaths are in males. This article reviews the factors contributing to suicide in older rural males in Australia and then categorises the papers into themes for ease of explanation. Living with experiences of drought, dramatic weather change, lower employment opportunities, out-migration, changing family dynamics, ageism in the community, economic change and competitive labour markets, all add to the diverse experience for an older person who is ageing in a rural setting. METHODS: A literature search was conducted in March 2015, using the terms 'elderly' and 'older males' and then combined with 'rural', 'suicide' and 'Australia', to investigate the amount of research that has been conducted on the factors relating to suicide in older rural Australian males. RESULTS: Reviewed articles consisted of research using either quantitative or qualitative approaches, which investigated suicide in older Australians published between 1950 and 2014. With strict adherence to the selection criteria, articles (21 in total) were removed because they were a literature review; a narrative review; they focused predominantly on youth or suicide risk, suicidal ideation or suicide attempts; or they discussed reasons for living. This article discusses the researcher's recommendations for further research into employment transitions for older Australian males, and the need to review policy change for further intervention in the future. CONCLUSIONS: This article highlights factors that may cause older rural Australians to be placed at a higher risk of suicide than their urban-dwelling counterparts. With the impact of the changing economy, unpredictable climatic conditions and dynamic changes in rural Australian families, there is a need to highlight research that has been conducted in this area. Future research should focus on identification of misclassification of suicide deaths, investigation of the possible effect that retirement pathways may have on older Australian males, suicide prevention strategies, mental wellbeing and the risk of suicidal behaviour. This will ascertain any compounding or protective factors that could influence this current trend.

The experience of living with metastatic breast cancer--a review of the literature.

Women's experiences with metastatic breast cancer have received little research attention. We reviewed published articles (1984-2013) reporting research examining women's experiences of metastatic breast cancer (n = 33). Findings from quantitative studies were categorized into three broad areas: adverse consequences, satisfaction with health care providers, and strategies for living. Themes identified from qualitative findings include living as a social outsider; importance of hope; health and quality of life; positive experiences; experiences at end of life; and strategies for living. More research is needed to explore experiences of subgroups to appropriately respond to women's diverse care needs.

Climate adversity and resilience: the voice of rural Australia.

INTRODUCTION: Over the past decade, Australia has experienced prolonged drought and extensive flooding. It is argued that such events impact more significantly on rural communities than urban. Although there is a body of research investigating the effects of drought on mental and physical health in rural Australia, little research has examined the effects of flood and drought on wellbeing. This article explores the influence of drought and flood on the wellbeing of rural residents in New South Wales (NSW), Australia. METHODS: Forty-six individuals living in four rural communities in NSW were recruited and asked their experience of flood and drought using in-depth semi-structured face to face interviews or focus groups. The study used a grounded hermeneutic approach to contextualise participants' experiences within a rural social and cultural construct. RESULTS: Weather was found to be at the core of rural life, with flood and drought contributing to decreased wellbeing from stress, anxiety, loss and fear. Social connectedness was found to promote resilience in rural communities buffering the effects of flood and drought. CONCLUSIONS: Flood and drought have negative impacts on an individual's wellbeing. Although these negative effects were seen to be buffered by individual and community resilience, the long term emotional impact of flood and drought on rural communities needs to be further considered.

Extreme heat and cultural and linguistic minorities in Australia: perceptions of stakeholders.

BACKGROUND: Despite acclimatisation to hot weather, many individuals in Australia are adversely affected by extreme heat each summer, placing added pressure on the health sector. In terms of public health, it is therefore important to identify vulnerable groups, particularly in the face of a warming climate. International evidence points to a disparity in heat-susceptibility in certain minority groups, although it is unknown if this occurs in Australia. With cultural diversity increasing, the aim of this study was to explore how migrants from different cultural backgrounds and climate experiences manage periods of extreme heat in Australia. METHODS: A qualitative study was undertaken across three Australian cities, involving interviews and focus groups with key informants including stakeholders involved in multicultural service provision and community members. Thematic analysis and a framework approach were used to analyse the data. RESULTS: Whilst migrants and refugees generally adapt well upon resettlement, there are sociocultural barriers encountered by some that hinder environmental adaptation to periods of extreme heat in Australia. These barriers include socioeconomic disadvantage and poor housing, language barriers to the access of information, isolation, health issues, cultural factors and lack of acclimatisation. Most often mentioned as being at risk were new arrivals, people in new and emerging communities, and older migrants. CONCLUSIONS: With increasing diversity within populations, it is important that the health sector is aware that during periods of extreme heat there may be disparities in the adaptive capacity of minority groups, underpinned by sociocultural and language-based vulnerabilities in migrants and refugees. These factors need to be considered by policymakers when formulating and disseminating heat health strategies.

The impact of heat on mortality and morbidity in the Greater Metropolitan Sydney Region: a case crossover analysis.

BACKGROUND: This study examined the association between unusually high temperature and daily mortality (1997-2007) and hospital admissions (1997-2010) in the Sydney Greater Metropolitan Region (GMR) to assist in the development of targeted health programs designed to minimise the public health impact of extreme heat. METHODS: Sydney GMR was categorized into five climate zones. Heat-events were defined as severe or extreme. Using a time-stratified case-crossover design with a conditional logistic regression model we adjusted for influenza epidemics, public holidays, and climate zone. Odds ratios (OR) and 95% confidence intervals were estimated for associations between daily mortality and hospital admissions with heat-event days compared to non-heat event days for single and three day heat-events. RESULTS: All-cause mortality overall had similar magnitude associations with single day and three day extreme and severe events as did all cardiovascular mortality. Respiratory mortality was associated with single day and three day severe events (95th percentile, lag0: OR = 1.14; 95%CI: 1.04 to 1.24). Diabetes mortality had similar magnitude associations with single day and three day severe events (95th percentile, lag0: OR = 1.22; 95%CI: 1.03 to 1.46) but was not associated with extreme events. Hospital admissions for heat related injuries, dehydration, and other fluid disorders were associated with single day and three day extreme and severe events. Contrary to our findings for mortality, we found inconsistent and sometimes inverse associations for extreme and severe events with cardiovascular disease and respiratory disease hospital admissions. Controlling for air pollutants did not influence the mortality associations but reduced the magnitude of the associations with hospital admissions particularly for ozone and respiratory disease. CONCLUSIONS: Single and three day events of unusually high temperatures in Sydney are associated with similar magnitude increases in mortality and hospital admissions. The trend towards an inverse association between cardio-vascular admissions and heat-events and the strong positive association between cardio-vascular mortality and heat-events suggests these events may lead to a rapid deterioration in persons with existing cardio-vascular disease resulting in death. To reduce the adverse effects of high temperatures over multiple days, and less extreme but more frequent temperatures over single days, targeted public health messages are critical.

Risk factors for unintentional poisoning in children aged 1-3 years in NSW Australia: a case-control study.

BACKGROUND: Unintentional poisoning in young children is an important public health issue. Age pattern studies have demonstrated that children aged 1-3 years have the highest levels of poisoning risk among children aged 0-4 years, yet little research has been conducted regarding risk factors specific to this three-year age group and the methodologies employed varied greatly. The purpose of the current study is to investigate a broad range of potential risk factors for unintentional poisoning in children aged 1-3 years using appropriate methodologies. METHODS: Four groups of children, one case group (children who had experienced a poisoning event) and three control groups (children who had been 'injured', 'sick' or who were 'healthy'), and their mothers (mother-child dyads) were enrolled into a case-control study. All mother-child dyads participated in a 1.5-hour child developmental screening and observation, with mothers responding to a series of questionnaires at home. Data were analysed as three case-control pairs with multivariate analyses used to control for age and sex differences between child cases and controls. RESULTS: Five risk factors were included in the final multivariate models for one or more case-control pairs. All three models found that children whose mothers used more positive control in their interactions during a structured task had higher odds of poisoning. Two models showed that maternal psychiatric distress increased poisoning risk (poisoning-injury and poisoning-healthy). Individual models identified the following variables as risk factors: less proximal maternal supervision during risk taking activities (poisoning-injury), medicinal substances stored in more accessible locations in bathrooms (poisoning-sick) and lower total parenting stress (poisoning-healthy). CONCLUSIONS: The findings of this study indicate that the nature of the caregiver-child relationship and caregiver attributes play an important role in influencing poisoning risk. Further research is warranted to explore the link between caregiver-child relationships and unintentional poisoning risk. Caregiver education should focus on the benefits of close interaction with their child as a prevention measure.

Quality of life and functional health status of long-term meditators.

Background. There is very little data describing the long-term health impacts of meditation. Aim. To compare the quality of life and functional health of long-term meditators to that of the normative population in Australia. Method. Using the SF-36 questionnaire and a Meditation Lifestyle Survey, we sampled 343 long-term Australian Sahaja Yoga meditation practitioners and compared their scores to those of the normative Australian population. Results. Six SF-36 subscales (bodily pain, general health, mental health, role limitation-emotional, social functioning, and vitality) were significantly better in meditators compared to the national norms whereas two of the subscales (role limitation-physical, physical functioning) were not significantly different. A substantial correlation between frequency of mental silence experience and the vitality, general health, and especially mental health subscales (P < 0.005) was found. Conclusion. Long-term practitioners of Sahaja yoga meditation experience better functional health, especially mental health, compared to the general population. A relationship between functional health, especially mental health, and the frequency of meditative experience (mental silence) exists that may be causal. Evidence for the potential role of this definition of meditation in enhancing quality of life, functional health and wellbeing is growing. Implications for primary mental health prevention are discussed.

Impact of Hydroxyurea Starting Dose on Pain Outcomes in Patients with Sickle Cell Disease.

In patients with sickle cell disease, hydroxyurea decreases the number of pain crises experienced. This study aimed to evaluate the difference in pain outcomes between patients started on a guideline concordant, weight-based starting dose of at least 15 mg/kg/day of hydroxyurea and those not. The first prescription of hydroxyurea was the baseline date, follow-up was a visit 60-120 days after baseline. The primary outcome was the change in opioid prescribing between baseline and follow-up. 138 patients met inclusion criteria; of these, 55 were started on a guideline concordant dose of hydroxyurea. Greater white blood cell count (9.5 vs 12.0; p < 0.01) was statistically associated with subtherapeutic dosing. Greater actual body weight (68.0 vs 72.1 kg; p = 0.16) also appeared higher in the non-guideline concordant group. No statistically significant difference in opioid prescribing was observed between those started on a guideline concordant dose of hydroxyurea and those who were not. In the guideline concordant starting dose group, 42% had a reduction in pain scores at first follow up, compared to 35% with a non-guideline recommended starting dose. (p = 0.41). While this difference is in the direction that would be expected based on the guidelines, the difference does not appear to be clinically meaningful.

Heatwaves and the elderly - The role of the GP in reducing morbidity.

BACKGROUND Heatwaves are increasing in frequency, intensity and duration, and are associated with an increase in mortality and morbidity, particularly in the very young and the very old. Concurrently, the Australian population is aging, with the prediction that by 2036 approximately 27% of Australians will be aged over 65 years. OBJECTIVE This article reviews the evidence on heat related health risk and discusses the role of the general practitioner in reducing morbidity in older people as a result of heatwaves. DISCUSSION Heatwaves are associated with increased mortality and morbidity in people aged over 65 years, and more so in those aged over 75 years. Older people are more vulnerable to the effects of extreme heat through a range of physiological and physical factors. As key providers of healthcare to older people, GPs play a crucial role in identifying those at risk and implementing strategies to minimise the risks of mortality and morbidity during periods of extreme heat.

Using a smartphone application (App) to assist older adults to navigate their local area during extreme weather events and changing environmental conditions: A qualitative study.

OBJECTIVE: To explore the views of those in later life on the usability of a smartphone application (app) which could assist in negotiating the external environment, particularly during extreme weather and local environmental changes. METHODS: Seven adults aged over 55 years (four women, three men) living in Sydney, Australia, participated in focus groups. Responses were analysed thematically. RESULTS: The findings demonstrate older adults would use a reliable and relevant app to assist in accessing their external environment if it could provide assistance with accurate, up-to-date transport options, road closures, community events and weather. CONCLUSION: If relevant, in real time and locally focussed adults aged over 55 could find value in a mobile app to assist them to navigate their external environment. These results suggest an age-friendly, specifically designed app will have an impact on accessibility to the local environment with the potential to lead to increased walking and social engagement.

Relationship between breastfeeding duration and undernutrition conditions among children aged 0-3 Years in Pakistan.

BACKGROUND: The World Health Organization recommends that a child should be breastfed up to 2 years of age as it is essential for proper growth and development but population-based studies around the world have found conflicting results on the subject. Our study aims to analyze whether there is a relationship between the duration of breastfeeding and undernutrition among children aged from birth up to 3 years of age in Pakistan. METHODS: A secondary analysis of the Pakistan Demographic and Health Survey 2013-2014 with 1072 children aged 3 years and under was conducted. The relationship between breastfeeding duration and undernutrition status was estimated through multiple logistic regression analysis. RESULTS: The prevalence of stunting, wasting and underweight were 40.6%, 15.8% and 33.9% respectively, while prevalence of severe stunting is at 22.5%; severe wasting at 4.5% and severe underweight at 12.2% in children in our study. Odds of being stunted were significantly higher for children in their 3rd year of life [AOR: 4.35, CI 95% = (2.01, 9.33)] compared to children being breastfed in their 2nd year of life [AOR: 2.43, CI 95% = (1.55, 3.79) after being adjusted for maternal, child, demographic and healthcare access variables. Similarly, children being breastfed in their third year of life were more susceptible to developing severe stunting [AOR: 6.19, CI 95% = (3.31, 11.56)] in comparison to children in their second year [AOR: 2.84, CI 95% = (1.81, 4.46)]. There was no significant association between breastfeeding and wasting/severe wasting, or between breastfeeding and underweight/severe underweight. CONCLUSION: Breastfeeding in the 2nd and 3rd year of life was found to have significant relationship with stunting and severe stunting. Mothers need to be educated about the risks of prolonged breastfeeding to reduce the burden of undernutrition in the country.

Factors associated with non-utilization of postnatal care among newborns in the first 2 days after birth in Pakistan: a nationwide cross-sectional study.

BACKGROUND: Recent data indicated that approximately four in every ten newborns in Pakistan do not receive postnatal care (PNC) services in the first 48 hours after delivery. OBJECTIVES: This study aimed to identify factors associated with the non-utilization of PNC for newborns in Pakistan using the 2017-18 Pakistan Demographic and Health Survey (PDHS). METHODS: This was a cross-sectional analytical study utilizing data from 3887 live-born newborns recorded in the 2017-18 PDHS. Non-utilization of PNC was assessed against a set of independent factors using multilevel logistic regression analysis, and the population attributable risk estimates of factors associated with non-utilization of PNC were also calculated. RESULTS: There were 1443 newborns (37%) in Pakistan whose mothers did not utilize PNC check-ups in the first 2 days after delivery. The non-utilization of PNC was largely attributable to newborns delivered at non-health facilities 53% (47% to 59%) and those born to uneducated women 27% (13% to 38%). Adjusted analyses indicated that newborns with higher birth order and with a birth interval of more than 2 years, women who perceived their baby to be small at birth, women with no formal education and those living in regional areas of Khyber Pakhtunkhwa and Federally Administered Tribal Areas were significantly associated with non-utilization of PNC services. CONCLUSIONS: Tailored health messages by community health workers, including door-to-door visits on utilizing health facilities through pregnancy to the postnatal periods, are needed and should target places of low socioeconomic status, including educationally disadvantaged women from regional areas of Pakistan.

VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail.

The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin.

Mechanisms associated with mitochondrial-generated reactive oxygen species in cancer.

The mitochondria are unique cellular organelles that contain their own genome and, in conjunction with the nucleus, are able to transcribe and translate genes encoding components of the electron transport chain (ETC). To do so, the mitochondria must communicate with the nucleus via the production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), which are produced as a byproduct of aerobic respiration within the mitochondria. Mitochondrial signaling is proposed to be altered in cancer cells, where the mitochondria are frequently found to harbor mutations within their genome and display altered functional characteristics leading to increased glycolysis. As signaling molecules, ROS oxidize and inhibit MAPK phosphatases resulting in enhanced proliferation and survival, an effect particularly advantageous to cancer cells. In terms of transcriptional regulation, ROS affect the phosphorylation, activation, oxidation, and DNA binding of transcription factors such as AP-1, NF-kappaB, p53, and HIF-1alpha, leading to changes in target gene expression. Increased ROS production by defective cancer cell mitochondria also results in the upregulation of the transcription factor Ets-1, a factor that has been increasingly associated with aggressive cancers.

Sleeping infants safely - considerations for GPs.

The sudden death of an infant is a traumatic experience for both families and health practitioners. The most common cause of sudden infant death is SIDS, defined as 'the sudden and unexpected death of an infant under 1 year of age, with onset of lethal episode apparently occurring during sleep, that remains unexplained after a thorough investigation including performance of a complete autopsy review of the circumstances of death and clinical history'. In 2004, SIDS accounted for 4.5% of deaths in infants aged less than 1 year in New South Wales. Evidence suggests the most common age of death from SIDS is 2-5 months, with a peak incidence at around 3-4 months.

Association of a Targeted Population Health Management Intervention with Hospital Admissions and Bed-Days for Medicaid-Enrolled Children.

Importance: As the proportion of children with Medicaid coverage increases, many pediatric health systems are searching for effective strategies to improve management of this high-risk population and reduce the need for inpatient resources. Objective: To estimate the association of a targeted population health management intervention for children eligible for Medicaid with changes in monthly hospital admissions and bed-days. Design, Setting, and Participants: This quality improvement study, using difference-in-differences analysis, deployed integrated team interventions in an academic pediatric health system with 31 in-network primary care practices among children enrolled in Medicaid who received care at the health system's hospital and primary care practices. Data were collected from January 2014 to June 2017. Data analysis took place from January 2018 to June 2019. Exposures: Targeted deployment of integrated team interventions, each including electronic medical record registry development and reporting alongside a common longitudinal quality improvement framework to distribute workflow among interdisciplinary clinicians and community health workers. Main Outcomes and Measures: Trends in monthly inpatient admissions and bed-days (per 1000 beneficiaries) during the preimplementation period (ie, January 1, 2014, to June 30, 2015) compared with the postimplementation period (ie, July 1, 2015, to June 30, 2017). Results: Of 25 460 children admitted to the hospital's health system during the study period, 8418 (33.1%) (3869 [46.0%] girls; 3308 [39.3%] aged ≤1 year; 5694 [67.6%] black) were from in-network practices, and 17 042 (67.9%) (7779 [45.7%] girls; 6031 [35.4%] aged ≤1 year; 7167 [41.2%] black) were from out-of-network practices. Compared with out-of-network patients, in-network patients experienced a decrease of 0.39 (95% CI, 0.10-0.68) monthly admissions per 1000 beneficiaries (P = .009) and 2.20 (95% CI, 0.90-3.49) monthly bed-days per 1000 beneficiaries (P = .001). Accounting for disproportionate growth in the number of children with medical complexity who were in-network to the health system, this group experienced a monthly decrease in admissions of 0.54 (95% CI, 0.13-0.95) per 1000 beneficiaries (P = .01) and in bed-days of 3.25 (95% CI, 1.46-5.04) per 1000 beneficiaries (P = .001) compared with out-of-network patients. Annualized, these differences could translate to a reduction of 3600 bed-days for a population of 93 000 children eligible for Medicaid. Conclusions and Relevance: In this quality improvement study, a population health management approach providing targeted integrated care team interventions for children with medical and social complexity being cared for in a primary care network was associated with a reduction in service utilization compared with an out-of-network comparison group. Standardizing the work of care teams with quality improvement methods and integrated information technology tools may provide a scalable strategy for health systems to mitigate risk from a growing population of children who are eligible for Medicaid.

Medication abortion in Canada: a right-to-health perspective.

The right to health under the International Covenant on Economic, Social, and Cultural Rights, to which Canada is a signatory, entitles women to available, accessible, and acceptable abortion care. Abortion care in Canada currently fails this standard. Medication abortion (the use of drugs to terminate a pregnancy) could improve abortion care in Canada, but its potential remains unrealized. This is in part attributable to the unavailability of mifepristone, the safest and most effective pharmaceutical for medication abortion. Given that it could improve abortion care, we investigated why mifepristone remains unapproved in Canada, whether its unavailability is attributable to government inaction, and whether Canada is therefore failing to fulfill its obligations under the right to health.

Climate change and the health of older people in Australia: A scoping review on the role of mobile applications (apps) in ameliorating impact.

OBJECTIVES: Due to the impact of climate change, mobile applications (apps) providing information about the external environment have the potential to improve the health of older people. The purpose of this research was to undertake a scoping review of the evidence on the usability, feasibility and effectiveness of mobile apps to encourage access to activities outside the home in older people. METHODS: A search of databases was undertaken with relevant keywords. Selected manuscripts were judged for relevance to the inclusion criteria and assessed for quality. RESULTS: Very few published studies examined mobile apps specifically designed to prevent, or to treat, chronic disease in ageing populations, and fewer had rigorous designs. No study addressed accessing the external environment in the context of climate change. CONCLUSION: This study demonstrates that there is a gap in the evidence about the mobile apps designed for healthy ageing and, more specifically, to improve access to the external environment.

Retinoic acid is a potential dorsalising signal in the late embryonic chick hindbrain.

BACKGROUND: Human retinoic acid teratogenesis results in malformations of dorsally derived hindbrain structures such as the cerebellum, noradrenergic hindbrain neurons and the precerebellar system. These structures originate from the rhombic lip and adjacent dorsal precursor pools that border the fourth ventricle roofplate. While retinoic acid synthesis is known to occur in the meninges that blanket the hindbrain, the particular sensitivity of only dorsal structures to disruptions in retinoid signalling is puzzling. We therefore looked for evidence within the neural tube for more spatiotemporally specific signalling pathways using an in situ hybridisation screen of known retinoic acid pathway transcripts. RESULTS: We find that there are highly restricted domains of retinoic acid synthesis and breakdown within specific hindbrain nuclei as well as the ventricular layer and roofplate. Intriguingly, transcripts of cellular retinoic acid binding protein 1 are always found at the interface between dividing and post-mitotic cells. By contrast to earlier stages of development, domains of synthesis and breakdown in post-mitotic neurons are co-localised. At the rhombic lip, expression of the mRNA for retinoic acid synthesising and catabolising enzymes is spatially highly organised with respect to the Cath1-positive precursors of migratory precerebellar neurons. CONCLUSION: The late developing hindbrain shows patterns of retinoic acid synthesis and use that are distinct from the well characterised phase of rostrocaudal patterning. Selected post-mitotic populations, such as the locus coeruleus, appear to both make and break down retinoic acid suggesting that a requirement for an autocrine, or at least a highly localised paracrine signalling network, might explain its acute sensitivity to retinoic acid disruption. At the rhombic lip, retinoic acid is likely to act as a dorsalising factor in parallel with other roofplate signalling pathways. While its precise role is unclear, retinoic acid is potentially well placed to regulate temporally determined cell fate decisions within the rhombic lip precursor pool.