Cognitive, behavioral and psychological functioning of children and adults with conservatively managed metopic synostosis.

Children diagnosed with metopic synostosis (MS) commonly experience poor neuropsychological outcomes, with research suggesting that children whose MS is managed conservatively (without surgery) potentially having worse outcomes than their operated peers. However, studies of children whose MS was managed conservatively are scarce. This study therefore examined the cognitive, behavioral, and psychological functioning of children/adults with conservatively managed MS (N = 38) and compares their outcomes to individually matched healthy controls (N = 38) of the same age and sex (matched-pairs design) from the general community. Age-appropriate, validated assessments measuring general cognition, verbal and visuospatial ability, attention and working memory, executive functioning, behavior, depression, anxiety, and satisfaction with appearance were utilized. Group differences were estimated using linear regression for (a) the overall sample and (b) by broad developmental stages: 2&3 yrs; ≥6-≤17. Moderate to large negative effects (g = -0.38 to -1.30) were evident before controlling for socio-economic status (SES), with the MS group performing significantly worse on 8 out of the 10 cognitive domains (general cognition, visuospatial ability, working memory, information processing, executive functioning: semantic & initial letter verbal fluency, switching, inhibition+switching). However, only initial letter verbal fluency (g = -0.99) and switching (g = -1.19) remained significant after adjusting for SES. The MS group displayed more behavioral problems, although this was not significant. Depression, anxiety, and satisfaction with appearance did not differ between the groups. Regular monitoring of cognitive functioning, particularly executive functioning, should be undertaken for those with conservatively managed MS.

Cognitive, behavioral and psychological functioning in children with metopic synostosis: a meta-analysis examining the impact of surgical status.

Neurodevelopmental delays are known to occur in children with metopic synostosis, but it is presently unclear whether the cognitive, behavioral and psychological outcomes of children with metopic synostosis differ to those of their healthy peers. This meta-analysis consolidated data from 17 studies (published prior to August 2017) that examined the cognitive, behavioral and psychological outcomes of children (n = 666; aged ≤19 yrs) with metopic synostosis. Hedges'g (gw) effect sizes compared the outcomes of samples with metopic synostosis (unoperated, operated) to healthy controls or normative data and, where available, the prevalence of problems/disorders was calculated. Children with unoperated metopic synostosis performed significantly worse than their healthy peers on measures of: general cognition (gw = -.38), motor functioning, (gw = -.81), and verbal (gw = -.82) and visuospatial (gw = -.92) abilities. Children with operated metopic synostosis performed significantly worse on measures of motor functioning (gw = -.45), visuospatial skills (gw = -.32), attention (gw = -.50), executive functioning (gw = -.36), arithmetic ability (gw = -.37), and behavior (gw = -.34). Cognitive, behavioral, and psychological problems were prevalent, but variable. Overall, the cognitive, behavioral, and psychological outcomes of children with metopic synostosis are generally worse than their healthy peers, regardless of surgical status. However, research is sparse, samples small, controls are rarely recruited, and the severity of metopic synostosis often not stated. Nevertheless, the findings suggest that children with metopic synostosis are likely to experience a variety of negative outcomes and should therefore receive ongoing monitoring and support.

Longitudinal Preterm Cerebellar Volume: Perinatal and Neurodevelopmental Outcome Associations.

Impaired cerebellar development is an important determinant of adverse motor and cognitive outcomes in very preterm (VPT) infants. However, longitudinal MRI studies investigating cerebellar maturation from birth through childhood and associated neurodevelopmental outcomes are lacking. We aimed to compare cerebellar volume and growth from term-equivalent age (TEA) to 7 years between VPT (< 30 weeks' gestation or < 1250 g) and full-term children; and to assess the association between these measures, perinatal factors, and 7-year outcomes in VPT children, and whether these relationships varied by sex. In a prospective cohort study of 224 VPT and 46 full-term infants, cerebellar volumes were measured on MRI at TEA and 7 years. Useable data at either time-point were collected for 207 VPT and 43 full-term children. Cerebellar growth from TEA to 7 years was compared between VPT and full-term children. Associations with perinatal factors and 7-year outcomes were investigated in VPT children. VPT children had smaller TEA and 7-year volumes and reduced growth. Perinatal factors were associated with smaller cerebellar volume and growth between TEA and 7 years, namely, postnatal corticosteroids for TEA volume, and female sex, earlier birth gestation, white and deep nuclear gray matter injury for 7-year volume and growth. Smaller TEA and 7-year volumes, and reduced growth were associated with poorer 7-year IQ, language, and motor function, with differential relationships observed for male and female children. Our findings indicate that cerebellar growth from TEA to 7 years is impaired in VPT children and relates to early perinatal factors and 7-year outcomes.

Changes in verbal and visuospatial working memory from Grade 1 to Grade 3 of primary school: Population longitudinal study.

BACKGROUND: Adaptive working memory training is being implemented without an adequate understanding of developmental trajectories of working memory. We aimed to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and visuospatial working memory and (2) whether low verbal and visuospatial working memory in Grade 1 predicts low working memory in Grade 3. METHOD: The study design includes a population-based longitudinal study of 1,802 children (66% uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and Mister X (visuospatial working memory) screening measures from the Automated Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3 (ages 6-7 and 8-9 years) students. Low working memory was defined as ≥1 standard deviation below the standard score mean. Descriptive statistics addressed Aim 1, and predictive parameters addressed Aim 2. RESULTS: One thousand seventy (59%) of 1802 Grade 1 participants were reassessed in Grade 3. As expected for typically developing children, group mean standard scores were similar in Grades 1 and 3 for verbal, visuospatial, and overall working memory, but group mean raw scores increased markedly. Compared to "not low" children, those classified as having low working memory in Grade 1 showed much larger increases in both standard and raw scores across verbal, visuospatial, and overall working memory. Sensitivity was very low for Grade 1 low working memory predicting Grade 3 low classifications. CONCLUSION: Although mean changes in working memory standard scores between Grades 1 and 3 were minimal, we found that individual development varied widely, with marked natural resolution by Grade 3 in children who initially had low working memory. This may render brain-training interventions ineffective in the early school year ages, particularly if (as population-based programmes usually mandate) selection occurs within a screening paradigm.

Alterations in mandibular morphology associated with glypican 1 and glypican 3 gene mutations.

OBJECTIVES: Glypican 1 (GPC1) and glypican 3 (GPC3) are bone co-regulators that act downstream in many of the signalling pathways associated with craniosynostosis. Morphometric data from GPC-knockout mice were analysed to determine whether elimination of GPC1 and GPC3 genes would alter mandibular morphology. SETTING AND SAMPLE POPULATION: The murine model included five male and five female mandibles in each of GPC1-knockout, GPC1/GPC3-knockout and wild-type (control) groups. Female GPC3-knockout mice had a very high rate of perinatal lethality, and therefore, only five males were included in this group. METHODS: The mandibular morphology of GPC1-knockout (n=10), GPC3-knockout (n=5), GPC1/GPC3-knockout (n=10) and wild-type (n=10) mice was compared by analysing five landmark-based linear dimensions: anterior and posterior lengths, as well as ascending, descending and posterior heights. Measurements were recorded on three-dimensional micro-CT reconstructions. RESULTS: GPC3-knockout mandibles were larger than wild-type mandibles for all dimensions (P<.05). Mandibular heights were more affected than lengths. A decreasing trend of mandibular dimensions across the mouse groups (GPC3-knockout>GPC1/GPC3-knockout>GPC1-knockout=wild-type) (P<.05) indicated that an increase in mandibular size was associated with increased GPC3 expression, but not GPC1. CONCLUSIONS: Alterations in GPC3 expression are likely to mediate changes to mandibular size in craniosynostosis. These findings have potential future applications in the prevention and treatment of craniosynostosis and associated craniofacial dysmorphology.

The prevalence of dental anomalies in an Australian population.

BACKGROUND: The aim of this study was to determine the prevalence of dental anomalies within an Australian paediatric population using panoramic radiographs. METHODS: This was a prospective review of 1050 panoramic radiographs obtained as part of a school dental screening program in suburban and rural New South Wales, Australia. RESULTS: Fifty-four (5.14%) patients had a dental anomaly present. Agenesis was noted to have occurred 69 times across 45 patients (4.28%), along with seven cases of impaction (0.6%) and three cases of supernumerary teeth (0.28%). CONCLUSIONS: Dental anomalies rarely occur in the Australian population, which possesses a wide-ranging multiethnic cohort. Despite their rarity, they can be incidentally discovered so identification and management by dental practitioners are important.

Flightless I is a key regulator of the fibroproliferative process in hypertrophic scarring and a target for a novel antiscarring therapy.

BACKGROUND: Hypertrophic scarring carries a large burden of disease, including disfigurement, pain and disability. There is currently no effective medical treatment to reduce or prevent hypertrophic scarring. Flightless I (Flii), a member of the gelsolin family of actin remodelling proteins, is an important negative regulator of wound repair. OBJECTIVES: The objective of this study was to investigate the role of Flii as a potential regulator of hypertrophic scarring. METHODS: Using human skin samples and an animal model of bleomycin-induced hypertrophic scarring in mice that overexpress or have reduced expression of Flii, we investigated its effect on dermal fibrosis and hypertrophic scarring. RESULTS: Flii expression was increased in human burns and hypertrophic scars. A similar increase in Flii was observed in hypertrophic scars formed in mice post-treatment with bleomycin. However, Flii-deficient (Flii(+/-) ) mice had reduced scarring in response to bleomycin evidenced by decreased dermal thickness, smaller cross-sectional scar areas, fewer myofibroblasts and a decreased collagen I/III ratio. In contrast, bleomycin-treated Flii-overexpressing mice (Flii(Tg/Tg) ) showed increased scar dermal thickness, larger cross-sectional scar areas, more myofibroblasts and an increased collagen I/III ratio. Injecting developing scars with a Flii neutralizing antibody led to a significant reduction in the size of the scars and a reduction in the collagen I/III ratio. CONCLUSIONS: This study identifies Flii as a profibrotic agent that contributes to excessive scar formation. Reducing its activity using neutralizing antibodies is a promising approach for reducing hypertrophic scarring.

Sleep disordered breathing and acute mountain sickness in workers rapidly transported to the South Pole (2835 m).

BACKGROUND: Sleep disordered breathing may be a risk factor for high altitude illness. Past Antarctic sleep studies suggest that rapid transport from sea level (SL) to the Amundsen Scott South Pole Station (SP, 2835 m) increases risk of Acute Mountain Sickness (AMS). We analyzed sleep studies in 38 healthy polar workers to explore the association between sleep disordered breathing and AMS after rapid transport to the South Pole. METHODS: Subjects completed a baseline questionnaire, performed basic physiology tests, and were evaluated for AMS and medication use using an extended Lake Louise Questionnaire (LLQ) during their first week at the South Pole. Participants were included in this study if they took no medications and underwent polysomnography on their first nights at Sea Level and the South Pole using the Vivometrics LifeShirt(®). Within group changes were assessed with Wilcoxon signed rank tests and between group differences were assessed with Kruskal-Wallis rank sum tests. RESULTS: Overall, 21/38 subjects met criteria for AMS at some time on or prior to the third morning at the South Pole. Subjective poor sleep quality was reported by both AMS (65%) and no AMS (41%) groups. The Apnea Hypopnea Index (AHI) increased significantly in both the AMS and no AMS groups, but the difference in the increase between the two groups was not statistically significant. Increased AHI was not associated with increased AMS symptoms. Previous altitude illness (p=0.06) and residence at low altitudes (p = 0.02) were risk factors for AMS. CONCLUSION: AMS was not significantly associated with sleep architecture changes or increased AHI. However, AHI sharply increased at South Pole (19/38 participants) primarily due to central apneas. Those developing AMS were more likely to have experienced previous problems at altitude and reported living at lowland altitudes within the 3 months prior to rapid transport to the South Pole than those without AMS.

Application of three-dimensional computed tomography in craniofacial clinical practice and research.

Following the invention of the first computed tomography (CT) scanner in the early 1970s, many innovations in three-dimensional (3D) diagnostic imaging technology have occurred, leading to a wide range of applications in craniofacial clinical practice and research. Three-dimensional image analysis provides superior and more detailed information compared with conventional plain two-dimensional (2D) radiography, with the added benefit of 3D printing for preoperative treatment planning and regenerative therapy. Current state-of-the-art multidetector CT (MDCT), also known as medical CT, has an important role in the diagnosis and management of craniofacial injuries and pathology. Three-dimensional cone beam CT (CBCT), pioneered in the 1990s, is gaining increasing popularity in dental and craniofacial clinical practice because of its faster image acquisition at a lower radiation dose, but sound guidelines are needed to ensure its optimal clinical use. Recent innovations in micro-computed tomography (micro-CT) have revolutionized craniofacial biology research by enabling higher resolution scanning of teeth beyond the capabilities of MDCT and CBCT, presenting new prospects for translational clinical research. Even after four decades of refinement, CT technology continues to advance and broaden the horizons of craniofacial clinical practice and phenomics research.

Extremely preterm birth and adolescent mental health in a geographical cohort born in the 1990s.

BACKGROUND: Preterm birth confers risk for poor outcome, including mental health problems. Survival of extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g) infants increased in the 1990s but psychiatric outcomes in older adolescents born preterm since 1990 are not well documented. This study aimed to characterize mental health and personality traits in a prospective geographical cohort of adolescents born EP/ELBW in Victoria, Australia in 1991 and 1992. METHOD: At age 18 years, 215 EP/ELBW and 157 normal birthweight (>2499 g) control adolescents completed the Structured Clinical Interview for DSM-IV Disorders, Axis 1 Non-Patient version (SCID-I/NP), the Children's Interview for Psychiatric Syndromes (ChIPS) attention deficit hyperactivity disorder (ADHD) module, and questionnaires assessing recent depression and anxiety symptoms and personality traits. RESULTS: ADHD prevalence was significantly elevated in EP/ELBW adolescents compared with controls [15% v. 7%; odds ratio (OR) 2.67, 95% confidence interval (CI) 1.08-6.58]. Aside from ADHD, however, EP/ELBW and control adolescents reported very similar outcomes, with other lifetime diagnoses identified in 23% of EP/ELBW and 21% of controls. These were predominantly mood and anxiety disorders (21% EP/ELBW, 20% controls). The groups did not differ in recent depression or anxiety symptoms assessed using questionnaires, and personality traits were also similar. CONCLUSIONS: ADHD was more prevalent in EP/ELBW adolescents than controls, which is consistent with some, but not all, reports on preterm survivors born before the 1990s, and younger preterm children born in the 1990s. The high rates of anxiety and mood disorders were similar in both groups, and comparable with population-based estimates.

New stable isotope method to measure protein digestibility and response to pancreatic enzyme intake in cystic fibrosis.

BACKGROUND & AIMS: Adequate protein intake and digestion are necessary to prevent muscle wasting in cystic fibrosis (CF). Accurate and easy-to-use methodology to quantify protein maldigestion is lacking in CF. OBJECTIVE: To measure protein digestibility and the response to pancreatic enzyme intake in CF by using a new stable isotope methodology. DESIGN: In 19 CF and 8 healthy subjects, protein digestibility was quantified during continuous (sip) feeding for 6 h by adding (15)N-labeled spirulina protein and L-[ring-(2)H5]phenylalanine (PHE) to the nutrition and measuring plasma ratio [(15)N]PHE to [(2)H5]PHE. Pancreatic enzymes were ingested after 2 h in CF and the response in protein digestibility was assessed. To exclude difference in mucosal function, postabsorptive whole-body citrulline (CIT) production rate was measured by L-[5-(13)C-5,5-(2)H2]-CIT pulse and blood samples were taken to analyze tracer-tracee ratios. RESULTS: Protein digestibility was severely reduced in the CF group (47% of healthy subjects; P < 0.001). Intake of pancreatic enzymes induced a slow increase in protein digestibility in CF until 90% of values obtained by healthy subjects. Maximal digestibility was reached at 100 min and maintained for 80 min. Stratification into CF children (n = 10) and adults showed comparable values for protein digestibility and similar kinetic responses to pancreatic enzyme intake. Whole-body citrulline production was elevated in CF indicating preserved mucosal function. CONCLUSION: Protein digestibility is severely compromised in patients with CF as measured by this novel and easy-to-use stable isotope approach. Pancreatic enzymes are able to normalize protein digestibility in CF, albeit with a severe delay. Registration ClinicalTrials.gov = NCT01494909.

Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients.

Craniosynostosis is one of the most common craniofacial disorders encountered in clinical genetics practice, with an overall incidence of 1 in 2,500. Between 30% and 70% of syndromic craniosynostoses are caused by mutations in hotspots in the fibroblast growth factor receptor (FGFR) genes or in the TWIST1 gene with the difference in detection rates likely to be related to different study populations within craniofacial centers. Here we present results from molecular testing of an Australia and New Zealand cohort of 630 individuals with a diagnosis of craniosynostosis. Data were obtained by Sanger sequencing of FGFR1, FGFR2, and FGFR3 hotspot exons and the TWIST1 gene, as well as copy number detection of TWIST1. Of the 630 probands, there were 231 who had one of 80 distinct mutations (36%). Among the 80 mutations, 17 novel sequence variants were detected in three of the four genes screened. In addition to the proband cohort there were 96 individuals who underwent predictive or prenatal testing as part of family studies. Dysmorphic features consistent with the known FGFR1-3/TWIST1-associated syndromes were predictive for mutation detection. We also show a statistically significant association between splice site mutations in FGFR2 and a clinical diagnosis of Pfeiffer syndrome, more severe clinical phenotypes associated with FGFR2 exon 10 versus exon 8 mutations, and more frequent surgical procedures in the presence of a pathogenic mutation. Targeting gene hot spot areas for mutation analysis is a useful strategy to maximize the success of molecular diagnosis for individuals with craniosynostosis.

A long-term evaluation of 150 costochondral nasal grafts.

INTRODUCTION: This paper reviewed the outcome of cantilevered costochondral grafts used for dorsal nasal augmentation in the management of patients treated at the Australian Craniofacial Unit (ACFU), Adelaide over a 29-year period. MATERIALS AND METHODS: All patients undergoing dorsal nasal augmentation with costochondral grafts as part of their craniofacial management between 1981 and 2009 were identified using the ACFU database, and their medical notes were reviewed. RESULTS: 107 patients (50 M, 57 F), with a mean age of 12.3 years (range: 2-62 years) and requiring a total of 150 costochondral grafts, were identified from the departmental database. Mean follow-up after nasal augmentation was 5.6 years (1 month-31.5 years). 46% of the patients were diagnosed with Binder syndrome/Chondrodysplasia punctata; other diagnoses included Tessier midline clefts, cleft lip and palate and frontonasal dysplasia. A dorsal midline incision (49%) was the commonest method of access, with 84% of patients having mini-screw fixation for graft stabilisation. Complications included screw palpability, infection, skin necrosis and graft fracture. The commonest reasons for a replacement graft were graft atrophy and fracture, infection and persistent deformity. CONCLUSION: Cantilevered nasal costochondral grafting is an excellent technique for improving nasal contour and function in a wide variety of clinical situations.

Binder syndrome.

UNLABELLED: Patients with chondrodysplasia punctata (CDP) usually present with Binder-type features, and often CDP is misdiagnosed as Binder syndrome. This study reviewed the management and outcome of patients with Binder syndrome and CDP in a multidisciplinary setting. METHODS: The notes and radiographs of the patients managed at the Australian Craniofacial Unit with a multidisciplinary setting since 1976 were reviewed, and data were collected on patient demographics, associated medical and surgical problems, subsequent management, and complications. RESULTS: Seventy-seven patients were treated over the 30-year period (5 patients were lost to follow-up); of the remaining 72 patients, 60 (83%) had Binder syndrome, and 12 (17%) were patients with CDP. Forty were males, and 32 were females, with an age range of 6 months to 47 years. Thirteen patients (18%) had a strong family history, and 65 patients (90%) have so far undergone surgical correction, and of those, 35 (54%) have completed their treatment, the longest follow-up time being 18 years. The mean number of surgical procedures was 2.4, and 18 patients (28%) had postoperative complications, which included partial necrosis of the maxilla, osteomyelitis of the mandible, facial nerve and inferior alveolar nerve neuropraxia, nasal bone graft exposure, and cellulitis. DISCUSSION: Because of the phenotypic characteristics shared by both Binder syndrome and CDP, it is most likely that Binder syndrome is not a syndrome, nor is it an entity, but most likely to be an "association." We would advocate that these patients should be managed in a multidisciplinary setting.

Longitudinal predictors of psychiatric disorders in very low birth weight adults.

The purpose of this study was to determine risk and protective factors for adult psychiatric disorders in very low birth weight (VLBW, birth weight <1,501 g) survivors. 79 of 154 (51%) VLBW subjects recruited at birth were assessed in early adulthood (24-27 years). Participants were screened for a psychiatric disorder; those elevated were invited to attend a structured clinical interview to determine a clinical diagnosis. Longitudinal variables measured from birth and at ages 2, 5, 14 and 18 years were included in analyses. Perinatal, developmental and social environmental risk factors failed to predict psychiatric disorder in adulthood in this cohort of VLBW survivors. Instead, low self-esteem at age 18 (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1, 1.11, p = 0.05) and the adult social environment (high rates of negative life event stress at the time of assessment: OR = 1.39, CI = 1.10, 1.76, p = 0.02), contributed significantly to adult psychiatric outcomes.

High signal intensity on T2-weighted MR imaging at term-equivalent age in preterm infants does not predict 2-year neurodevelopmental outcomes.

BACKGROUND AND PURPOSE: DEHSI on T2-weighted MR imaging in preterm infants at term-equivalent age has been regarded as an unfavorable marker for neurodevelopmental outcome. The aim of this study was to examine the relationship between the presence and extent of DEHSI and neurodevelopmental outcomes. MATERIALS AND METHODS: We evaluated the MR images of 160 preterm infants at term-equivalent age. The presence of DEHSI was evaluated in separate regions and classified into 5 grades based on the extent of DEHSI. We also examined within those infants with DEHSI, whether typical signal-intensity characteristics of the posterior periventricular crossroads region were visible. Finally, ADC and FA values within the white matter were analyzed. Neurodevelopmental outcomes were assessed at 2-year corrected age with a standardized neurologic examination and the BSID-II. RESULTS: The grade of DEHSI had significant linear trends with increasing ADC and a trend toward lower FA values. However, there was no relationship between the degree of DEHSI and 2-year neurodevelopmental outcomes. In contrast, 13 infants with DEHSI who did not have visible posterior crossroads had poorer neurodevelopmental outcomes compared with infants with visible posterior crossroads. CONCLUSIONS: Although DEHSI may represent disturbances in white matter structure, as illustrated by its relationship to altered ADC and FA values, there is no relationship to short-term neurodevelopment outcome unless there are invisible posterior crossroads, representing a severe form of global high T2 signal intensity.

Tooth size and dental arch dimensions: a stereophotogrammetric study in Southeast Asian Malays.

OBJECTIVE: To investigate tooth size and dental arch dimensions in Malays using a stereophotogrammetric system. SETTING AND SAMPLE POPULATION: The sample consisted of 252 subjects with ages ranged from 13 to 30 years. MATERIALS AND METHODS: Images of dental casts were captured by stereophotogrammetry and selected variables were measured using a three-dimensional (3D) imaging system. Sex differences and changes associated with age were assessed, and interrelationships between different variables were explored within the study group. RESULTS: Men had significantly larger mesio-distal crown widths and dental arch dimensions than women (p < 0.05). None of the dental arch dimensions or mesio-distal crown widths showed a significant change because of age except the widths of the upper canine, lower first molar and central incisor. Significant correlations of tooth size with dental arch dimensions were found, particularly with arch lengths and perimeters. A principal component analysis showed interrelationships between the majority of tooth size variables with inter-canine width, arch length and perimeter distances. CONCLUSION: This study has established new reference data for tooth size and arch dimensions in Malays and demonstrated patterns of variation that are relevant to anthropologists interested in making comparisons within and between different populations and also to clinicians developing treatment plans for their patients. The study confirmed the accuracy of the 3D photogrammetric method for measuring dental casts.

Characterisation of amyloid-induced inflammatory responses in the rat retina.

Amyloid-induced inflammation is thought to play a critical and early role in the pathophysiology of Alzheimer's disease. As such, robust models with relevant and accessible compartments that provide a means of assessing anti-inflammatory agents are essential for the development of therapeutic agents. In the present work, we have characterised the induction of inflammation in the rat retina following intravitreal administration of amyloid-beta protein (Aß). Histology and mRNA endpoints in the retina demonstrate Aß1-42-, but not Aß42-1-, induced inflammatory responses characterised by increases in markers for microglia and astrocytes (ionised calcium-binding adaptor molecule 1 (iba-1), GFAP and nestin) and increases in mRNA for inflammatory cytokines and chemokines such as IL1-ß, MIP1α and TNFα. Likewise, analysis of vitreal cytokines also revealed increases in inflammatory cytokines and chemokines, including IL1-ß, MIP1α and MCP1, induced by Aß1-42 but not Aß42-1. This profile of pro-inflammatory gene and protein expression is consistent with that observed in the Alzheimer's disease brain and suggest that this preclinical model may provide a useful relevant tool in the development of anti-inflammatory approaches directed towards Alzheimer's disease therapy.

Prevalence of psychiatric diagnoses in preterm and full-term children, adolescents and young adults: a meta-analysis.

BACKGROUND: Preterm (PT) birth and low birth weight (LBW) are high-prevalence events that are associated with adverse outcomes in the longer term, with vulnerability increasing as maturity at birth decreases. Psychiatric symptomatology appears heightened in PT/LBW survivors, though there are some discordant findings from studies using questionnaire measures, particularly with respect to anxiety and depressive symptoms. METHOD: This article synthesises findings from research using clinical psychiatric diagnostic criteria in PT/LBW individuals aged 10-25 years compared with term-born peers. Key outcomes of interest were the rates of individuals receiving any psychiatric diagnosis and the number of diagnoses of anxiety or depressive disorders. RESULTS: A literature search for studies reporting prevalence of 'any diagnosis' yielded five studies that met inclusion criteria, with a total of 565 PT/LBW and 533 control individuals. Also, five studies were found that reported rates of anxiety/depression (692 PT/LBW and 605 control individuals). The risk of these outcomes was increased for PT/LBW individuals compared with controls [any diagnosis: odds ratio (OR) 3.66, 95% confidence interval (CI) 2.57-5.21; anxiety or depressive disorder: OR 2.86, 95% CI 1.73-4.73]. CONCLUSIONS: The studies reviewed here indicate that, in addition to monitoring and management of medical and cognitive sequelae, the psychological well-being of PT/LBW individuals should be a key part of ongoing care.

Changing long-term outcomes for infants 500-999 g birth weight in Victoria, 1979-2005.

OBJECTIVE: To determine the survival and neurological outcome at 2 years of age of extremely low birthweight (ELBW, birth weight 500-999 g) infants born in the state of Victoria compared with term controls, and contrasted with ELBW cohorts from previous eras. DESIGN AND SETTING: A population-based cohort study of consecutive ELBW infants born during 2005 in the state of Victoria, and also in 1979-1980, 1985-1987, 1991-1992 and 1997. PARTICIPANTS: All 257 live births free of lethal malformations weighing 500-999 g in 2005, 220 randomly selected term, normal birthweight (birth weight >2499 g) controls, and equivalent cohorts born in earlier eras. MAIN OUTCOME MEASURES: Survival rates and quality-adjusted survival rates at 2 years of age, contrasted between cohorts. RESULTS: Of 257 ELBW live births in 2005, 66.9% survived to 2 years of age, significantly lower than the survival rate of 75.2% for 1997 (odds ratio (OR) 0.67, 95% CI 0.45 to 0.99, p=0.046), but not after adjustment for confounders of birth weight, gestational age and gender (adjusted OR 0.73, 95% CI 0.46 to 1.16, p=0.18). This was a reversal of the steady increase in survival rates up to 1997. Rates of blindness, severe developmental delay and severe disability were significantly lower in 2005 than in ELBW survivors from previous eras. Consequently the difference in the quality-adjusted survival rates between 2005 and 1997 was only -3.8% (95% CI -11.4% to 3.7%, p=0.32). CONCLUSIONS: Regional survival rates for ELBW infants have plateaued since the late 1990s, but the neurosensory outcome in survivors has improved in 2005.