Determinants of cerebellar and cerebral volume in the general elderly population

In a population-based study of 3962 community-dwelling nondemented elderly we investigated the relation of age, sex, cardiovascular risk factors, and the presence of infarcts with cerebellar volume, and its interrelationship with cerebral volumes. Cerebellar and cerebral gray and white matter were segmented using Freesurfer version 4.5 (http://surfer.nmr.mgh.harvard.edu/). We used linear regression analyses to model the relationship between age, sex, cardiovascular risk factors, brain infarcts, white matter lesions (WMLs) and cerebellar and cerebral volume. Smaller cerebellar volumes with increasing age were mainly driven by loss of white matter. Diabetes, higher serum glucose and lower cholesterol levels were related to smaller cerebellar volume. No association was found between hypertension, smoking, apolipoprotein E (ApoE) genotype, and cerebellar volume. Supratentorial lacunar infarcts and WMLs were related to smaller cerebellar volume. Infratentorial infarcts were related to smaller cerebellar white matter volume and total cerebral volume. This study suggests that determinants of cerebellar volume do not entirely overlap with those established for cerebral volume. Furthermore, presence of infarcts or WMLs in the cerebrum can affect cerebellar volume.     

Functional analysis of two inhibitor of apoptosis (iap) orthologs from Helicoverpa armigera nucleopolyhedrovirus

Baculoviruses induce apoptotic responses in cultured insect cells, which can severely limit viral replication. To overcome this host response baculoviruses carry anti-apoptotic genes, including members of the p35 and inhibitor of apoptosis (iap) gene families. The baculovirus Helicoverpa armigera nucleopolyhedrovirus (HearNPV) carries two putative apoptosis suppressor genes (iap2 and iap3), which we studied in more detail. IAPs are believed to be functional in the cytoplasm, but surprisingly, when transiently expressed as EGFP fusions, IAP2 was evenly distributed throughout the cell, while IAP3 was mainly found in the nucleus. The latter became evenly distributed in both compartments in HearNPV infected cells. When iap2 was deleted, HearNPV could be propagated in Hz2e5 cells, while an iap3 deletion was lethal. The HearNPV Δiap3 mutant could be rescued by reinsertion of the HearNPV iap3 gene and by the well-studied anti-apoptotic genes Autographa californica (Ac)MNPV p35 or Orgyia pseudotsugata (Op)MNPV iap3. RNAi analysis showed that HearNPV induced apoptosis in Hz2e5 cells transfected with iap3 dsRNA, while silencing of iap2 did not lead to apoptosis. Finally, IAP3 was able to inhibit actinomycin-D induced apoptosis when transiently expressed in Sf21 cells. These results together indicate that HearNPV IAP3 is a functional apoptosis suppressor, while the function of IAP2 remains elusive.     

Cognitive response to estradiol in postmenopausal women is modified by high cortisol

Estradiol has potent favorable effects on brain function and behavior in animals while in human trials, the results are inconsistent. A number of potential mediating variables influencing response to estradiol have been proposed to account for this variability, 1 of which includes stress. We conducted a placebo-controlled study to examine joint and independent effects of estradiol and elevated levels of the stress hormone cortisol on cognition and biomarkers of aging and neurodegenerative disease. Thirty-nine healthy postmenopausal women (56-84 years) received 0.10 mg/dL of transdermal 17β-estradiol (E2) or placebo for 8 weeks. During the last 4 days of the trial, subjects also received 90 mg/day (30 mg 3×/day) of oral hydrocortisone (CORT) to induce stress-level elevations in cortisol, or a matched placebo. The 4 groups thus included placebo (placebo patch/placebo pill), CORT-alone (placebo patch/hydrocortisone), E2-alone (estradiol patch/placebo pill), and E2+CORT (estradiol patch/hydrocortisone). Eight weeks of E2 increased plasma estradiol by 167%, and 4 days of CORT increased plasma cortisol by 119%. Overall, E2 had favorable effects on verbal memory (p = 0.03), working memory (p = 0.02), and selective attention (p = 0.04), and the magnitude of these effects was attenuated for E2+CORT. E2-alone and E2+CORT had opposing effects on plasma levels of the amyloid-β (Aβ) biomarker (Aβ40/42 ratio, p < 0.05), with the more favorable response observed for E2-alone. CORT-induced increases in insulin-like growth factor-1 were blunted by E2 coadministration. Our findings indicate that cognitive and physiological responses to estradiol are adversely affected by elevated stress hormone levels of cortisol in healthy postmenopausal women.     

A review of consumer awareness, understanding and use of food-based dietary guidelines

Food-based dietary guidelines (FBDG) have primarily been designed for the consumer to encourage healthy, habitual food choices, decrease chronic disease risk and improve public health. However, minimal research has been conducted to evaluate whether FBDG are utilised by the public. The present review used a framework of three concepts, awareness, understanding and use, to summarise consumer evidence related to national FBDG and food guides. Searches of nine electronic databases, reference lists and Internet grey literature elicited 939 articles. Predetermined exclusion criteria selected twenty-eight studies for review. These consisted of qualitative, quantitative and mixed study designs, non-clinical participants, related to official FBDG for the general public, and involved measures of consumer awareness, understanding or use of FBDG. The three concepts of awareness, understanding and use were often discussed interchangeably. Nevertheless, a greater amount of evidence for consumer awareness and understanding was reported than consumer use of FBDG. The twenty-eight studies varied in terms of aim, design and method. Study quality also varied with raw qualitative data, and quantitative method details were often omitted. Thus, the reliability and validity of these review findings may be limited. Further research is required to evaluate the efficacy of FBDG as a public health promotion tool. If the purpose of FBDG is to evoke consumer behaviour change, then the framework of consumer awareness, understanding and use of FBDG may be useful to categorise consumer behaviour studies and complement the dietary survey and health outcome data in the process of FBDG evaluation and revision.     

Early docosahexaenoic acid supplementation of mothers during lactation leads to high plasma concentrations in very preterm infants

Very preterm infants are vulnerable to deficiency in DHA. In a longitudinal study, 10 mothers who delivered ≤29 wk gestation and planned to breast-feed received DHA (1200 mg/d) until 36 wk after conception. The plasma DHA status was assessed in their 12 infants (including 2 pairs of twins) from birth to d 49. Fatty acid profiles were measured weekly in breast milk, and in plasma of mothers and infants at baseline and at d15 and 49. Plasma and breast milk fatty acid concentrations in the DHA-supplemented group at d 49 were compared with a reference group of very preterm infants (n = 24, including triplets) whose mothers (n = 22) did not receive DHA during lactation. The infants' plasma DHA concentration tended to be greater in the DHA group than in the reference group (P = 0.10) and was greater when expressed as a percentage of total fatty acids (P = 0.009). At d 49, maternal milk DHA in the DHA group (1.92 ± 1.10 mmol/L) was ~12 times higher than in the reference group (0.15 ± 0.27 mmol/L) (P < 0.001). The amount of DHA provided to the infants increased from wk 1 through wk 7 in the DHA group (P < 0.001). Although enteral intake at wk 7 did not differ between the DHA group [119 ± 51 mL/(kg·d)] and the reference group [113 ± 66 mL/(kg·d)], DHA group infants received 55 ± 38 mg/(kg·d) of DHA, and the reference group infants received 7 ± 11 mg/(kg·d) (P < 0.001). Early supplementation with DHA to lactating mothers with low dietary DHA intake successfully increased the plasma DHA status in very preterm infants.     

Inactivated polio vaccine development for technology transfer using attenuated Sabin poliovirus strains to shift from Salk-IPV to Sabin-IPV

Industrial-scale inactivated polio vaccine (IPV) production dates back to the 1960s when at the Rijks Instituut voor de Volksgezondheid (RIV) in Bilthoven a process was developed based on micro-carrier technology and primary monkey kidney cells. This technology was freely shared with several pharmaceutical companies and institutes worldwide. In this contribution, the history of one of the first cell-culture based large-scale biological production processes is summarized. Also, recent developments and the anticipated upcoming shift from regular IPV to Sabin-IPV are presented. Responding to a call by the World Health Organization (WHO) for new polio vaccines, the development of Sabin-IPV was continued, after demonstrating proof of principle in the 1990s, at the Netherlands Vaccine Institute (NVI). Development of Sabin-IPV plays an important role in the WHO polio eradication strategy as biocontainment will be critical in the post-OPV cessation period. The use of attenuated Sabin strains instead of wild-type Salk polio strains will provide additional safety during vaccine production. Initially, the Sabin-IPV production process will be based on the scale-down model of the current, and well-established, Salk-IPV process. In parallel to clinical trial material production, process development, optimization and formulation research is being carried out to further optimize the process and reduce cost per dose. Also, results will be shown from large-scale (to prepare for future technology transfer) generation of Master- and Working virus seedlots, and clinical trial material (for phase I studies) production. Finally, the planned technology transfer to vaccine manufacturers in low and middle-income countries is discussed.     

Focusing the focus group: impact of the awareness of major factors contributing to non‐adherence to acute paediatric asthma guidelines

Rationale The administration of oral corticosteroids within the first hour in the emergency department is associated with reduced hospitalization rates in children with moderate and severe asthma, yet less than half of patients benefit from this recommendation. To ensure patients receive recommended treatment, a clear understanding of what is causing suboptimal care management is needed. The assessment of barriers and solutions to optimal care is often done without a thorough examination of the factors associated with non‐adherence. Objective To evaluate whether knowledge of factors associated with delayed administration of systemic corticosteroids modifies the focus and prioritization of barriers and solutions identified by focus groups. Methods We conducted two parallel focus groups of emergency health care professionals – one group informed and the other non‐informed of key factors. Both groups received a presentation on the acute asthma guidelines, the evidence supporting its recommendations, and current practice. In addition, the informed group was provided with the factors associated and not associated with delayed administration. The groups were given 20 minutes to discuss barriers and solutions, with 5 minutes each for voting for the main barriers and solutions. Group difference in the misdirection of discussion was measured as time spent discussing barriers that were shown not to be associated with systemic corticosteroids. Prioritization of barriers and solutions was based on group endorsement. Results The non‐informed group spent more time discussing barriers not associated with delayed administration (15 vs. 2 minutes, P = 0.05). Although the non‐informed group proposed more solutions, most were to overcome barriers not associated with delayed administration. Of the main barriers and solutions identified by each group, only one barrier and solution were similar between the two groups: emergency department overcrowding and administrating corticosteroids at triage. Conclusion The awareness of objective factors of non‐adherence enabled a more directed discussion on relevant barriers and solutions, affecting prioritization of each. The administration of oral corticosteroids at triage appears to be the best solution to overcome delayed administration.