Association between maternal blood lipids during pregnancy and offspring growth trajectories in a predominantly macrosomic cohort: findings from the ROLO longitudinal birth cohort study.

The purpose of this study is to examine associations between maternal lipid profiles in pregnancy and offspring growth trajectories in a largely macrosomic cohort. This is a secondary analysis of the ROLO birth cohort (n = 293), which took place in the National Maternity Hospital, Dublin, Ireland. Infants were mostly macrosomic, with 55% having a birthweight > 4 kg. Maternal mean age was 32.4 years (SD 3.9 years), mean BMI was 26.1 kg/m2 (SD 4.4 kg/m2) and 48% of children born were males. Total cholesterol, high density lipoprotein cholesterol (HDL-cholesterol), low density lipoprotein cholesterol (LDL-cholesterol) and triglycerides were measured from fasting blood samples of mothers at 14 and 28 week gestation. The change in maternal lipid levels from early to late pregnancy was also examined. Offspring abdominal circumference and weight were measured at 20- and 34-week gestation, birth, 6 months, 2 years and 5 years postnatal. Linear spline multilevel models examined associations between maternal blood lipid profiles and offspring growth. We found some weak, significant associations between maternal blood lipids and trajectories of offspring growth. Significant findings were close to the null, providing limited evidence. For instance, 1 mmol/L increase in maternal triglycerides was associated with faster infant weight growth from 20- to 34-week gestation (0.01 kg/week, 95% CI - 0.02, - 0.001) and slower abdominal circumference from 2 to 5 years (0.01 cm/week, 95% CI - 0.02, - 0.001). These findings do not provide evidence of a clinically meaningful effect.    Conclusion: These findings raise questions about the efficacy of interventions targeting maternal blood lipid profiles in pregnancies at risk of macrosomia. New studies on this topic are needed. What is Known: • Maternal fat accumulation during early pregnancy may potentially support fetal growth in the third trimester by providing a reserve of lipids that are broken down and transferred to the infant across the placental barrier. • There are limited studies exploring the impact of maternal lipid profiles on infant and child health using growth trajectories spanning prenatal to postnatal life. What is New: • Maternal blood lipid profiles were not associated with offspring growth trajectories of weight and abdominal circumference during pregnancy up to 5 years of age in a largely macrosomic cohort, as significant findings were close to the null, providing limited evidence for a clinically meaningful relationship. • Strengths of this work include the use of infant growth trajectories that span prenatal to postnatal life and inclusion of analyses of the change of maternal lipid levels from early to late pregnancy and their associations with offspring growth trajectories from 20-week gestation to 5 years of age.

An exploratory study of self-reported complicated grief symptoms in parentally bereaved adults with intellectual disability.

BACKGROUND: Complicated grief involves the experience of grief-related symptoms at a time, and severity, beyond which could be considered adaptive, while persistent complex bereavement disorder (PCBD) has been identified as a condition that requires further study in the typical population. The aims of this study are to (1) explore the symptoms of complicated grief associated with parental bereavement as self-reported by adults with intellectual disabilities (IDs) who have experienced a parental bereavement and (2) conduct an initial examination of how the existing criteria for PCBD apply to this group. METHODS: This study uses a comparative group design, assessing self and staff (proxy) reports for a group of parentally bereaved individuals and a matched group of non-bereaved individuals using the Complicated Grief Questionnaire - ID Self-Report. Participants were 46 individuals with ID, 30 (65%) of whom who had experienced a parental bereavement within the previous 2 years. The age range was 23-67 years (mean = 43.8; SD = 10.3). RESULTS: The results highlight the presence of a range of symptoms of complicated grief in individuals' self-reports, although there was some evidence that separation distress-related symptoms were more apparent. An analysis of individual symptoms showed patterns of higher reports among the bereaved group as would be expected. Comparing staff and self-reports, key criteria showed higher levels in self-reports among the bereaved group. CONCLUSIONS: This study has demonstrated the capacity of people with ID to self-report personal experience of symptoms of complicated grief, when appropriate and accessible assessment tools are used. Some symptoms were more evident among bereaved individuals (compared with non-bereaved participants), and they tended to be from separation distress criteria. This may indicate the relevance of these symptoms for people with ID and question the existing criteria for PCBD in this population, which may have clinical implications for supporting people with ID experiencing a more complicated bereavement response.

Measuring the performance of the Mental Health Continuum-Short Form (MHC-SF) in a primary care youth mental health service.

OBJECTIVES: Mental health is regarded as more than the absence of mental health difficulties, with clinical and research focus moving towards measurement of well-being. The Mental Health Continuum-Short Form (MHC-SF) was developed to assess overall and emotional, social and psychological well-being. Little is known about the use of the MHC-SF with young people engaging with mental health services. The current pilot study sought to examine the performance of the MHC-SF in an Irish primary care youth mental health service for 12-25 year olds. METHODS: A sample of 229 young people (female n=143; male n=85, unknown n=1) aged 12-24 years (M=15.87, SD=2.51) who completed the MHC-SF prior to commencing their first intervention session in Jigsaw participated in this study. The psychometric properties of the MHC-SF were investigated using confirmatory factor analysis (CFA) and Cronbach's alpha for internal consistency. RESULTS: CFA supported the three-factor structure of the MHC-SF for emotional, social, and psychological well-being, and very good internal consistency was observed. CONCLUSION: Findings provide evidence for the psychometric properties of the MHC-SF in a primary care youth mental health setting, and suggest that the MHC-SF's three-factor structure is valid for use in this context. Limitations and recommendations for future research are discussed.

Principles for the safety evaluation of cosmetic powders.

Consumer exposure to cosmetic (personal care) products is mostly by dermal contact, however additional considerations with regards to potential inhalation exposure from some cosmetics, such as sprays and powders, may be needed for a robust and reliable safety assessment. To get a deeper understanding of the exposure to airborne particles and droplets during product application, a team of international experts was founded under the umbrella of the European Association of the Cosmetic Industry "Cosmetics Europe" (CE) in Brussels. This expert team has worked out a pragmatic strategy how small and medium sized enterprises (SMEs), but also relevant authorities, could handle the safety evaluation of cosmetic powder products. Sufficient information on the aerodynamic diameter of sprayed droplets and here specifically of airborne particles is essential in addition to knowing the exposure after typical product application. The current article is focused on the determination of inhalation exposure to solids, and the derivation of safe exposure levels for cosmetic powder products found in the market. The principles described herein are very similar to spray products as published earlier and should be applied in a similar way (Steiling et al., 2014). Prediction models for the best estimate of inhalation exposure, developed with data from computer simulation programs, individual real-time measurements or finally by experience from the market were introduced and applied. Safety assessment approaches for exposure from powder spray products were developed and have been already considered in regulatory guidelines like the EC Cosmetics Regulation.

Description and outcome evaluation of Jigsaw: an emergent Irish mental health early intervention programme for young people.

OBJECTIVES: Jigsaw is an early intervention mental health service developed by Headstrong which provides support to young people, aged 12-25 years, in 10 communities across Ireland. This study aimed to profile young people who availed of Jigsaw, in one calendar year, and to provide evidence that Jigsaw's model facilitates the reduction of psychological distress. METHODS: Participants were 2420 young people who received support, directly or indirectly, from Jigsaw. Demographic details, including age, gender, presenting issues and referral pathways, captured on the Jigsaw Data System were described and psychological distress was assessed using the Clinical Outcomes in Routine Evaluation (CORE) questionnaires. RESULTS: A gender balance was almost observed and the majority of participants were between 15 and 17 years old. The most common presenting issue was anxiety and the most common referral sources were self, parent, general practitioner, school and Adult Mental Health Services (AMHS). Participants reported high levels of psychological distress pre-intervention and levels were significantly lower post intervention. CONCLUSIONS: Although a lack of control group limits interpretation of the study findings, this study provides emerging evidence that Jigsaw is an accessible and effective service which plays a key role in the continuum of mental health care for young people in Ireland.

Medical complications and outcomes at an onsite rehabilitation unit for older people.

BACKGROUND: The rehabilitation of older patients in Ireland after an acute medical event occurs at dedicated onsite hospital units or at offsite centres. Information on medical complications and outcomes is inadequate. AIMS: Enumeration of medical complications of patients admitted to a dedicated onsite rehabilitation unit for older people, and the extent of co-morbidity in the population with the effects that this had on the evolution of medical complications. METHODS: A retrospective analysis of patients admitted to a 58-bed onsite unit over a 1-year period was performed. Information collating co-morbidities, medical complications and functional outcomes was recorded. RESULTS: Medical complications occurred in almost 95% of patients, where full data were available. Over one-third required intravenous therapy. CONCLUSION: Twenty-four hour medical cover is required for older patients managed at onsite rehabilitation units. Further studies on offsite medical rehabilitation facilities for older patients are required.

Geriatric medicine in the emergency department.

Studies suggest older adults attending emergency departments(ED) benefit from specialist geriatric medicine evaluation. Findings from a pilot ED Geriatric Medicine(GM) liaison service in our 480-bed university hospital are presented. This is not a randomized controlled trial. Service comprised consultant geriatrician and senior trainee-led sessions during daytime working hours. Senior ED personnel selected appropriate patients. GM service also took over ED medical admissions aged 80, 1 in 9 days from General Internal Medicine(GIM). 49% of 284 patients (83.5 +/- 6.8 years) referred, were discharged from ED with appropriate follow-up. Inpatient analysis comprised 51% admitted to GIM, GM and specialist services as per on-call rota and 268 patients taken over from GIM. Patients under GM had shorter length of stay (p < 0.001). The findings suggest specialty specific geriatric medicine management of the older adult presenting to ED can improve service and patient outcomes.

Skin exposure to deodorants/antiperspirants in aerosol form.

Many cosmetic products are available in spray form. Even though the principal targets of these products are the skin and hair, spraying leads to the partitioning of the product between the target and the surrounding air. In the previous COLIPA study (Hall et al., 2007) the daily use of deodorant/antiperspirant (Deo/AP) in spray form was quantified in terms of the amount of product dispensed from the spray can, without specifically quantifying the product fraction reaching the skin during use. Results of the present study provide this additional information, necessary for a reliable safety assessment of sprayed Deo/AP products. In a novel experimental approach the information obtained from real-life movement analysis (automated motion imaging) of volunteers using their own products was integrated with the aerosol cloud sampling data obtained from the same products, leading to the computation of the product deposited on the skin. The 90th percentile values, expressed as percent deposition relative to the can weight loss after spraying, are 23.5% and 11.4% for ethanol-based and non-ethanol-based products, respectively. Additionally, the study has generated data on the skin area covered by the products, spray duration time, spray angle and spray distance from the skin.

Oculomotor nerve palsy following submucosal diathermy to the inferior turbinates.

Submucosal diathermy to the inferior turbinates is a common surgical procedure performed to improve the nasal airway. We present the case of a previously well six-year-old boy who underwent submucosal diathermy and developed the unusual complication of a left oculomotor nerve palsy. The possible aetiology is discussed.

Primary tumours of the vestibule and inner ear.

Seven primary tumours of the vestibule and inner ear are described, six schwannomas and one traumatic fibroma. Schwannomas in this situation may occur as sporadic tumours, or may be a feature of neurofibromatosis type 2 (NF-2). In the latter condition they may occur in isolation or in association with, but separate from, schwannomas arising in the internal meatus. Direct extension into the vestibule of an intrameatal vestibular schwannoma is well reported, but extension of an intravestibular tumour into the internal meatus is not described. Traumatic fibromas of the vestibule are rare and the trigger could be an attack of labyrinthitis. Intravestibular tumours, although rare, are likely to be diagnosed with increasing frequency with the widespread use of MR imaging.

Neurotrophins can enhance spiral ganglion cell survival after inner hair cell loss.

Following destruction of sensory cells of the organ of Corti, spiral ganglion cells (SGC) in the guinea pig degenerate. Chronic electrical stimulation via cochlear prostheses can enhance their survival, with the effect blocked by stopping the electrically elicited action potentials with tetrodotoxin. Blocking action potentials in the normal hearing ear with tetrodotoxin, however, does not cause degeneration. This suggests that in the pathological ear VIII N activity acts as a survival factor, while in the normal ear there are other survival factors that maintain SGCs. We examined neurotrophins, as survival factors in the deafened ear. Two weeks of treatment with BDNF (brain derived neurotrophic factor) administered chronically via a mini-osmotic pump into scala tympani at 50 ng/ml, provided a statistically significant enhanced SGC survival over untreated deafened ears or deafened ears treated with artificial perilymph. Neurotrophin 3 provided some enhanced survival, but this was not statistically significant over untreated deafened ears. These observations suggest there are survival factors in the inner ear, including those coupled to direct activation of the auditory nerve fibers, that may serve to maintain the auditory nerve. These factors may be applied following deafness to maintain and enhance neural populations and to increase benefits to the profoundly deaf receiving cochlear implants.

Alternative promoter usage and mRNA splicing pathways for parathyroid hormone-related protein in normal tissues and tumours.

The parathyroid hormone-related protein (PTHrP) gene consists of nine exons and allows the production of multiple PTHrP mRNA species via the use of three promoters and 5' and 3' alternative splicing; as a result of 3' alternative splicing one of three protein isoforms may be produced. This organisation has potential for tissue-specific splicing patterns. We examined PTHrP mRNA expression and splicing patterns in a series of tumours and normal tissues, using the sensitive reverse transcription-polymerase chain reaction (RT-PCR) technique. Use of promoter 3 and mRNA specifying the 141 amino acid PTHrP isoform were detected in all samples. Transcripts encoding the 139 amino acid isoform were detected in all but two samples. Use of promoters 1 and 2 was less widespread as was detection of mRNA encoding the 173 amino acid isoform. While different PTHrP splicing patterns were observed between tumours, no tissue- or tumour-specific transcripts were detected. In comparing normal and tumour tissue from the same patient, an increase in the number of promoters utilised was observed in the tumour tissue. Furthermore, mRNA for the PTH/PTHrP receptor was detected in all samples, thus the PTHrP produced by these tumours may potentially act in an autocrine or paracrine fashion.

Epidermal growth factor-stimulated parathyroid hormone-related protein expression involves increased gene transcription and mRNA stability.

Epidermal growth factor (EGF) produced rapid and striking effects on parathyroid hormone-related protein (PTHrP) gene expression in the immortalized human keratinocyte cell line, HaCaT. Steady-state levels of PTHrP mRNA and secreted PTHrP were increased 10-fold by maximally effective concentrations of EGF. EGF increased both PTHrP gene transcription and PTHrP mRNA stability. Nuclear run-on assays demonstrated a 4-fold increase in transcriptional rate in EGF-stimulated cells while transient transfection analysis indicated that the action of EGF on transcription involved both the GC-rich promoter, P2, and the downstream TATA promoter, P3, but apparently not the upstream TATA promoter, P1. In experiments where EGF treatment produced more stable PTHrP transcripts, the half-life of c-fos mRNA was unaltered, suggesting a relatively specific effect of EGF. Moreover, only those species of PTHrP mRNA containing two of the alternative 3' exons (exons VII and VIII) were stable, those containing exon IX were not. Reverse-transcription PCR demonstrated that EGF produced differential increases in the abundance of PTHrP mRNA species initiated by the three PTHrP promoters. The major effect was seen on the abundance of transcripts initiated by P1 and P2, with less marked regulation of P3-initiated transcripts. Thus EGF regulation of PTHrP gene expression in HaCaT cells is multifactorial and the combination of its actions at the 5' and 3' ends of the gene favours the accumulation of subpopulations of PTHrP mRNA containing exons I, VII and VIII.

Induction of an acute phase response in lambs causes an increase in plasma levels of GH and IGF-I.

GH and IGF-I plasma concentrations were measured in lambs during an acute phase response induced by an intrathoracic injection of yeast. The acute phase response was indicated by reduced feed intake, weight loss and an increase in plasma concentrations of the acute phase protein haptoglobin. Intensive blood sampling on day 1 revealed elevated basal concentrations of GH in the yeast-injected group compared with concentrations in pair weight and ad libitum fed control lambs. This suggests that at the beginning of an acute phase response there is an increase in either GH secretion or the half life of GH. No evidence of a specific GH-binding protein in sheep plasma could be detected. IGF-I concentrations in the yeast-injected group remained constant for 3 days then increased to a peak level at day 6. In contrast, plasma IGF-I concentrations were depressed from days 3 to 6 in the pair weight control group and they were unchanged in the ad libitum fed controls. When the IGF-I concentrations were elevated in the yeast-injected group, this group had a higher daily weight gain despite their lower feed intake compared with the ad libitum fed controls. These results suggest that IGF-I may be associated with the increase in weight in the late stage of an acute phase response during recovery from an infection or injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexamethasone regulation of parathyroid hormone-related protein (PTHrP) expression in a squamous cancer cell line.

Dexamethasone regulation of PTHrP expression has been studied in an epidermal squamous cancer cell line COLO 16, which secretes immunoreactive PTHrP into conditioned medium. Dexamethasone was found to suppress PTHrP expression in a time- and dose-dependent manner, which was reversible upon removal of dexamethasone. The half-maximal effective concentration of dexamethasone was 1 nM and an effect of dexamethasone on PTHrP mRNA was first observed after 2 h of treatment, with maximal inhibition by 6 h. Dexamethasone action on PTHrP expression was steroid specific since progestin, 5alpha-dihydroxytestosterone and oestrogen did not regulate PTHrP expression in COLO 16 cells. The gluocorticoid/progesterone receptor antagonist RU486 inhibited the dexamethasone effect, indicating glucocorticoid receptor-mediated regulation of PTHrP expression. The half-life of PTHrP mRNA in COLO 16 cells was approximately 120 min and was not altered by treatment of cells with dexamethasone. Nuclear run-on assays revealed that dexamethasone reduced PTHrP gene transcription in COLO 16 cells. Transient transfection assays with a series of reporter gene constructs encompassing 3.5 kb of the 5' end of the PTHrP gene failed to identify a region of the gene responsible for glucocorticoid down-regulation. PCR of reverse-transcribed RNA from COLO 16 cells revealed that dexamethasone down-regulated transcripts driven from all three promoters (i.e., the TATA promoters 5' to exons I and IV and the GC-rich promoter 5' to exon III) of the human PTHrP gene.

Primary synovial sarcoma of the middle ear.

Synovial sarcoma is a soft tissue malignancy which most commonly affects the lower limbs of young adults and rarely occurs in the head and neck region. The term synovial sarcoma may be a misnomer as most of these tumours occur in tissues not known to contain synovial tissue. There has only been one previously reported case affecting the middle ear, which was metastatic, and we report the first case of primary synovial sarcoma of the middle ear.

Acute phase protein response, food intake, liveweight change and lesions following intrathoracic injection of yeast in sheep.

Acute phase protein concentrations in blood, food intake and liveweight changes were compared in 10 sheep given intrathoracic injections of yeast and 10 control sheep over a period of 61 days. The yeast injections caused acute pleuritis and limited necrotising lung lesions which progressed to fibrous pleural adhesions and walled-off abscesses. The responses of ceruloplasmin, fibrinogen and haptoglobin were closely correlated (r = 0.87 to 0.91) in the yeast-injected sheep with peaks on days 5 or 7 after treatment (4, 4.6 and over 130 times control, respectively). Albumin concentration fell to a nadir of 89 per cent of control on day 12 after treatment. Depression of food intake was temporally related to the 'positive' acute phase protein responses with a nadir on day 5 after treatment (30 per cent of control). Liveweight showed a pronounced fall to five days after treatment and thereafter remained depressed relative to the controls for most of the experimental period. The data suggest that the 'positive' acute phase proteins may be useful indicators of production losses due to inflammatory diseases in sheep.

Identification of brain isoforms of the rat calcitonin receptor.

Two rat calcitonin receptor isoforms have been identified by cDNA cloning from a hypothalamic library. The clones, C1a and C1b, specified proteins of 478 and 515 amino acids, respectively. The clones were identical, except that the C1b sequence encoded a 37-amino acid insert in the second extracellular domain, which conferred altered ligand recognition. Compared to the C1a receptor, expressed C1b receptors exhibited decreased affinity for porcine CT, relative to salmon CT, and negligible affinity for human CT. Clone C1b mRNA was predominately expressed in the brain, whereas mRNA for the C1a clone was present in both brain and peripheral tissues. Both receptors were able to couple functionally to adenylate cyclase. Thus, clone C1b represents a novel brain isoform of the CT receptor with different affinity for CT analogs resulting from an altered second extracellular domain.

Cerebellopontine angle lipoma.

A case of a cerebellopontine angle lipoma is presented with a typical clinical, audiometric and radiological features of an acoustic neuroma. The correct pre-operative diagnosis was elusive even with the aid of magnetic resonance imaging.