Nutrition during the periconceptional period influences postnatal cardiovascular health. We determined whether in vitro embryo culture and transfer, which are manipulations of the nutritional environment during the periconceptional period, dysregulate postnatal blood pressure and blood pressure regulatory mechanisms. Embryos were either transferred to an intermediate recipient ewe (ET) or cultured in vitro in the absence (IVC) or presence of human serum (IVCHS) and a methyl donor (IVCHS+M) for 6 days. Basal blood pressure was recorded at 19–20 weeks after birth. Mean arterial pressure (MAP) and heart rate (HR) were measured before and after varying doses of phenylephrine (PE). mRNA expression of signaling molecules involved in blood pressure regulation was measured in the renal artery. Basal MAP did not differ between groups. Baroreflex sensitivity, set point, and upper plateau were also maintained in all groups after PE stimulation. Adrenergic receptors alpha-1A (αAR1A), alpha-1B (αAR1B), and angiotensin II receptor type 1 (AT1R) mRNA expression were not different from controls in the renal artery. These results suggest there is no programmed effect of ET or IVC on basal blood pressure or the baroreflex control mechanisms in adolescence, but future studies are required to determine the impact of ET and IVC on these mechanisms later in the life course when developmental programming effects may be unmasked by age.

Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.

Fronto-temporal dementia (FTD) associated with Fused in Sarcoma (FUS) protein accumulation is an uncommon cause of FTD with a distinct syndrome of young age onset behavioral variant FTD, without a family history of FTD and caudate atrophy. We present a sporadic case of a 61-year-old patient with mixed features of both behavioral variant FTD with later semantic language dissolution associated with pathologically proven FUS. He was older than usual for FUS pathology, his course was rapidly progressive, and he had atypical language features. This case broadens the clinical spectrum caused by FUS-protein-related FTD.

The commensal bacteria Lactobacillus are widely used as probiotic organisms conferring a heath benefit on the host. They have been implicated in promoting gut health via the stimulation of host immunity and anti-inflammatory responses, as well as protecting the intestinalmucosa against pathogen invasion. Lactobacilli grow by fermenting sugars and starches and produce lactic acid as their primary metabolic product. For efficient utilisation of varied carbohydrates, lactobacilli have evolved diverse sugar transport and metabolic systems, which are specifically induced by their own substrates. Many bacteria are also capable of sensing and responding to changes in their environment. These sensory responses are often independent of transport or metabolism and are mediated through membrane-spanning receptor proteins. We employed DNA-based pyrosequencing technology to investigate the changes in the intestinal microbiota of piglets weaned to a diet supplemented with either a natural sugar, lactose or an artificial sweetener (SUCRAM®, consisting of saccharin and neohesperidin dihydrochalcone (NHDC); Pancosma SA). The addition of either lactose or saccharin/NHDC to the piglets' feed dramatically increased the caecal population abundance of Lactobacillus, with concomitant increases in intraluminal lactic acid concentrations. This is the first report of the prebiotic-like effects of saccharin/NHDC, an artificial sweetener, being able to influence the commensal gut microbiota. The identification of the underlying mechanism(s) will assist in designing nutritional strategies for enhancing gut immunity and maintaining gut health.

Background: Ideally putative disease-modifying therapies for Alzheimer's disease (AD) should be tested in patients who have minimal morbidity. Current barriers to such trials in early disease include the lack of disease-specific early biomarkers, insensitivity of quantitative cognitive outcome measures, and expensive trial designs requiring large sample sizes and long duration. This paper describes principles and progress towards a novel trial design that overcomes these problems, utilizing wide-scale cognitive performance screening to define pre-trial cognitive decline trajectories which can serve as trial outcome measures to assess AD disease-modifying efficacy.

Methods: Theoretical principles important for the detection of intra-individual cognitive decline and a practical example are described.

Results: Serial evaluations of community-based volunteers demonstrate how a screening tool method to detect subtle cognitive decline can predict in vivo amyloid pathology as a trigger for etiological evaluation. Trajectories of decline appear consistent over at least two years, suggesting they could be used as a trial inclusion criterion and ameliorable outcome measure together with other AD biomarkers. Informative trial durations could be 6–12 months, or extend to incorporate staggered random withdrawal or start designs, with as few as 20 individuals per treatment arm.

Conclusions: This trial methodology offers significant advantages over current AD trial designs, including treatment at earlier stages of disease, shorter trial duration, obviation of informed consent difficulties, smaller sample sizes, reduced cost and – given adequate screening programs – sufficient subjects for multiple simultaneous trials. Importantly, it allows the rapid evaluation of putative treatments that may only be efficacious in pre-dementia states.

Background: The Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging aimed to recruit 1000 individuals aged over 60 to assist with prospective research into Alzheimer's disease (AD). This paper describes the recruitment of the cohort and gives information about the study methodology, baseline demography, diagnoses, medical comorbidities, medication use, and cognitive function of the participants.

Methods: Volunteers underwent a screening interview, had comprehensive cognitive testing, gave 80 ml of blood, and completed health and lifestyle questionnaires. One quarter of the sample also underwent amyloid PET brain imaging with Pittsburgh compound B (PiB PET) and MRI brain imaging, and a subgroup of 10% had ActiGraph activity monitoring and body composition scanning.

Results: A total of 1166 volunteers were recruited, 54 of whom were excluded from further study due to comorbid disorders which could affect cognition or because of withdrawal of consent. Participants with AD (211) had neuropsychological profiles which were consistent with AD, and were more impaired than participants with mild cognitive impairment (133) or healthy controls (768), who performed within expected norms for age on neuropsychological testing. PiB PET scans were performed on 287 participants, 100 had DEXA scans and 91 participated in ActiGraph monitoring.

Conclusion: The participants comprising the AIBL cohort represent a group of highly motivated and well-characterized individuals who represent a unique resource for the study of AD. They will be reassessed at 18-month intervals in order to determine the predictive utility of various biomarkers, cognitive parameters and lifestyle factors as indicators of AD, and as predictors of future cognitive decline.

Performance on many cognitive and neuropsychological tests may be improved by prior exposure to testing stimuli and procedures. These beneficial practice effects can have a significant impact on test performance when conventional neuropsychological tests are administered at test–retest intervals of weeks, months or years. Many recent investigations have sought to determine changes in cognitive function over periods of minutes or hours (e.g., before and after anesthesia) using computerized tests. However, the effects of practice at such brief test–retest intervals has not been reported. The current study sought to determine the magnitude of practice effects in a group of 113 individuals assessed with an automated cognitive test battery on 4 occasions in 1 day. Practice effects were evident both between and within assessments, and also within individual tests. However, these effects occurred mostly between the 1st and 2nd administration of the test battery, with smaller, nonsignificant improvements observed between the 2nd, 3rd, and 4th administrations. On the basis of these results, methodological and statistical strategies that may aid in the differentiation of practice effects from drug-induced cognitive changes are proposed. (JINS, 2003, 9, 419–428.)

Hyposmia is a neglected symptom in patients with rhinitis. We studied 25 patients presenting with perennial rhinitis. Fifteen patients expressed hyposmia as a significant symptom. University of Pennsylvania smell identification test (UPSIT) and visual analogue scales (VAS) were used to score the symptoms of hyposmia, nasal obstruction and nasal discharge before and after six weeks treatment with betamethasone sodium phosphate drops. Those patients with initial symptoms of hyposia significantly improved their UPSIT scores (p = 0.00009) and their VAS scores for hyposmia (p = 0.00133). Despite a significant decrease in the sensation of nasal obstruction, the non-hyposmics showed no increase in UPSIT scores after betamethasone therapy. There was no clear correlation between UPSIT results and other symptom scores. The judicious use of betamethasone drops in the treatment of rhinogenic hyposmia can be recommended.

Magnetic and resistivity geophysical surveys conducted across the only known exposure of the East Kirkton Limestone have produced new information upon its extent. This is important to determine because of its unique faunal assemblage and possible hot spring deposition, suggesting a potential for precious metal mineralisation. Magnetic anomalies are attributed to basalts within the Bathgate Hills Volcanic Formation. Modelling of the magnetic data demonstrates a general dip to the west of about 25°, and the presence of significant local faulting. Modelling of vertical electrical sounding data shows the East Kirkton sequence (the limestone and associated beds) to be a low resistivity layer within the more highly resistive volcanic sequence. The East Kirkton sequence is seen to deepen to the west, and also to the north probably by faulting. Therefore the present exposure is the only near surface occurrence of the East Kirkton Limestone locally, but within the area of the survey no lateral limits to the formation are observed.

The present study compared families of patients with anorexia nervosa with families of non-anorexic adolescent daughters of a similar social class. All anorexics and adolescent comparison girls and their parents were studied using a variety of psychometric measures. Body size estimation and physical anhedonia were also measured. Family characteristics were assessed using the Family Assessment Measure (FAM). Contrary to the hypotheses, no abnormalities were found in terms of parental attitudes to weight control or dieting. The mothers of anorexics displayed no increase in psychopathology on any of the measures. The fathers scored very similarly to controls but with higher degrees of conscientiousness. Neither fathers nor mothers displayed abnormalities of their own body size estimates or body satisfaction. On the FAM the anorexic families reported an increased pathology on several sub-scales. It is not possible to say whether these disturbances are part of the pathogenesis or are sequelae to the illness.