Baseline Findings of PreventE4: A Double-Blind Placebo Controlled Clinical Trial Testing High Dose DHA in APOE4 Carriers before the Onset of Dementia.

INTRODUCTION: Lower blood levels of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) are correlated with worse cognitive functions, particularly among APOE ε4 carriers. Whether DHA supplementation in APOE ε4 carriers with limited DHA consumption and dementia risk factors can delay or slow down disease progression when started before the onset of clinical dementia is not known. METHODS: PreventE4 is a double-blind, single site, randomized, placebo-controlled trial in cognitively unimpaired individuals with limited omega-3 consumption and dementia risk factors (n=368). Its objectives are to determine (1) whether carrying the APOE ε4 allele is associated with lower delivery of DHA to the brain; and (2) whether high dose DHA supplementation affects brain imaging biomarkers of AD and cognitive function. RESULTS: 365 cognitively unimpaired individuals between 55 and 80 (mean age 66) were randomized to 2 grams of DHA per day or identically appearing placebo for a period of 2 years. Half the participants were asked to complete lumbar punctures at baseline and 6-month visits to obtain cerebrospinal fluid (CSF). The primary trial outcome measure is the change in CSF DHA to arachidonic acid ratio after 6 months of the intervention (n=181). Secondary trial outcomes include the change in functional and structural connectivity using resting state functional MRI at 24 months (n=365). Exploratory outcomes include the change in Repeatable Battery of the Assessment of Neuropsychological Status at 24 months (n=365). CONCLUSIONS: Findings from PreventE4 will clarify the brain delivery of DHA in individuals carrying the APOE ε4 allele with implications for dementia prevention strategies. Trial was registered as NCT03613844.

Anastomosis Groups of Rhizoctonia solani and Binucleate Rhizoctonia Associated with Potatoes in Idaho.

A survey of the relative incidence of anastomosis groups (AGs) of Rhizoctonia spp. associated with potato disease was conducted in Idaho, the leading potato producing state in the U.S.A. In total, 169 isolates of Rhizoctonia solani and seven binucleate Rhizoctonia (BNR) isolates were recovered from diseased potato plants. The AG of each isolate was determined through real-time PCR assays for AG 3-PT and phylogenetic analysis of the internal transcribed spacer region of ribosomal DNA. AG 3-PT was the predominant AG, accounting for 85% of isolates recovered, followed by AG 2-1 (5.7%) and AG 4 HG-II (4.5%). Two different subsets of AG 2-1 isolates were recovered (subset 2 and 3). Three isolates each of AG A and AG K were recovered, as well as one isolate each of AG 5 and AG W. An experiment carried out under greenhouse conditions with representative isolates of the different AGs recovered from Idaho potatoes showed differences in aggressiveness between AGs to potato stems, with AG 3-PT being the most aggressive followed by an isolate of AG 2-1 (subset 3). The three BNR isolates representative of AG A, AG K, and AG W appeared to be less aggressive to potato stems than the R. solani isolates except for the AG 2-1 (subset 2) isolate. This is the first comprehensive study of the relative incidences of Rhizoctonia species associated with Idaho potatoes and the first study to report the presence of BNR AG W outside of China.

Wind Turbine Electromagnetic Energy: Exploring Risk of Harm to Human Health.

The risk of harm to human health associated with radio/electromagnetic energy exposure is debated globally. Physicians and health practitioners may be presented with increasing numbers of patients with multisystem complaints, which may be initially confusing. Some residents living in proximity to wind energy facilities report harm they associate with exposure to radio/electromagnetic energy. Although authorities, physicians, and researchers express concerns regarding exposure to radio/electromagnetic energy in general, research specific to wind turbines is limited. Current regulations may be limited in scope and not include all devices that emit and/or utilize radio/electromagnetic energy. We recommend that government regulators advise the public of potential risks of exposure and establish limits that incorporate all sources of radio/electromagnetic energy, including wind turbines. Until these limits are established, governments should take precautionary and proactive measures to protect public health, with additional attention given to vulnerable population groups such as children and the older adults.

A comparison of the bioavailability of ferrous fumarate and ferrous sulfate in non-anemic Mexican women and children consuming a sweetened maize and milk drink.

BACKGROUND/OBJECTIVES: Ferrous fumarate is recommended for the fortification of complementary foods based on similar iron absorption to ferrous sulfate in adults. Two recent studies in young children have reported that it is only 30% as well absorbed as ferrous sulfate. The objective of this study was to compare iron absorption from ferrous fumarate and ferrous sulfate in infants, young children and mothers. SUBJECTS/METHODS: Non-anemic Mexican infants (6-24 months), young children (2-5 years) and adult women were randomly assigned to receive either 4 mg Fe (women) or 2.5 mg Fe (infants and young children) as either [(57)Fe]-ferrous fumarate or [(58)Fe]-ferrous sulfate added to a sweetened drink based on degermed maize flour and milk powder. Iron absorption was calculated based on incorporation of isotopes into erythrocytes after 14 days. RESULTS: Within each population group, no significant differences (P > 0.05) in iron absorption were found between ferrous fumarate and ferrous sulfate. Mean iron absorption from ferrous fumarate vs ferrous sulfate was 17.5 vs 20.5% in women (relative bioavailability (RBV) =86), 7.0 vs 7.2% in infants (RBV = 97) and 6.3 vs 5.9% in young children (RBV = 106). CONCLUSIONS: Ferrous fumarate is as well absorbed as ferrous sulfate in non-anemic, iron sufficient infants and young children, and can be recommended as a useful fortification compound for complementary foods designed to prevent iron deficiency. Further studies are needed to clarify its usefulness in foods designed to treat iron deficiency.

A community/hospital leg ulcer service.

This paper outlines the implementation of a multidisciplinary integrated community and hospital leg ulcer service in 1993 and its effect on the health outcomes and quality of life of patients living in the area of the Hounslow and Spelthorne Community and Mental Health Trust prior to and following the establishment of the service.

Suspected herbicide toxicosis in a dog.

An 8-year-old 38-kg spayed female Golden Retriever was admitted for vomiting, signs of abdominal pain on palpation, ataxia, anorexia, and generalized weakness of 2 days' duration. Ten hours prior to onset of clinical signs, the dog was found standing in and drinking from large pools of an accidentally spilled herbicide that contained an octanoic acid ester of bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) and an isooctyl ester of (2-methyl-4-chloro) phenoxyacetic acid (MCPA). Appendicular muscles were firm on palpation and persistent muscle contraction (myotonia > 1 minute duration) was found on muscle percussion, using a reflex hammer. Electrical activity indicative of myotonia was identified on electromyographic evaluation. With supportive treatment, the dog eventually recovered from suspected MCPA toxicosis. Although rare, MCPA toxicosis should be considered as a cause of acquired myotonia in dogs.

Impact of a collaborative immunisation programme in an inner city practice.

OBJECTIVES: To describe the impact of a collaborative immunisation programme, between an inner city practice and the Eastern Health Board (EHB). DESIGN: An observational study using a computer database formed from practice and EHB records. SETTING: One Dublin inner city practice with three partners located in an area with a deprived socio-economic profile. SUBJECTS: All patients in the practice aged more than six months and less than five years identified both from practice registers and opportunistically during study period. RESULTS: 342 children, older than six months and less than five years were identified at start and 464 (a 36% increase) by end of the programme. Uptake changed for DPT from 30% before, to 57% after the programme (p < 0.0005), for DT from 15% to 13%, for Hib from 7% to 50% (p < 0.0005) and for MMR (over 15 months) from 53% to 75% (p < 0.0005). Uptake of the DPT, Hib and MMR was 35% among GMS eligible, 51% among GMS ineligible (p < 0.005). CONCLUSION: A collaborative immunisation programme significantly improved practice uptake rates. These improved rates still do not attain declared national targets. To achieve these targets, radical overhaul of the immunisation service is required.

Neuropeptide Y phase shifts the circadian clock in vitro via a Y2 receptor.

The suprachiasmatic nuclei (SCN) contain a circadian clock whose activity can be recorded in vitro for several days. This clock can be reset by the application of neuropeptide Y. In this study, we focused on determination of the receptor responsible for neuropeptide Y phase shifts of the hamster circadian clock in vitro. Coronal hypothalamic slices containing the SCN were prepared from Syrian hamsters housed under a 14 h:10 h light:dark cycle. Tissue was bathed in artificial cerebrospinal fluid (ACSF), and the firing rates of individual cells were sampled throughout a 12 h period. Control slices received either no application or application of 200 nl ACSF to the SCN at zeitgeber time 6 (ZT6; ZT12 was defined as the time of lights off). Application of 200 ng/200 nl of neuropeptide Y at ZT6 resulted in a phase advance of 3.4 h. Application of the Y2 receptor agonist, neuropeptide Y (3-36), induced a similar phase advance in the rhythm, while the Y1 receptor agonist, [Leu31, Pro34]-neuropeptide Y had no effect. Pancreatic polypeptide (rat or avian) also had no measurable phase-shifting effect. Neuropeptide Y applied at ZT20 or 22 had no detectable phase-shifting effect. These results suggest that the phase-shifting effects of neuropeptide Y are mediated through a Y2 receptor, similar to results found in vivo.

A phase-response curve to the benzodiazepine chlordiazepoxide and the effect of geniculo-hypothalamic tract ablation.

The geniculo-hypothalamic tract (GHT) provides input to the mammalian circadian pacemaker in the suprachiasmatic nucleus. Several recent reports indicate that GHT ablation blocks phase shifts to the benzodiazepines triazolam and chlordiazepoxide at circadian times (CTs) 6 and 21. In this study we tested if GHT ablation blocks phase shifts to chlordiazepoxide at a wide range of circadian phases. Syrian hamsters were housed under constant dim light, and running-wheel activity rhythms were monitored. Intraperitoneal injections of either chlordiazepoxide (100 mg/kg) or saline were administered at various circadian times, and a phase-response curve was constructed. In intact animals, chlordiazepoxide produced phase-advance shifts at CTs 0, 4, 6, and 8, and phase-delay shifts between CTs 12-14. Although bursts of increased activity were sometimes observed on the day of injection, activity does not appear to mediate chlordiazepoxide-induced phase shifts. Hamsters with > 45% GHT ablation showed no phase shifts > 20 min to chlordiazepoxide. Our results indicate that the geniculo-hypothalamic tract is necessary for the phase-shifting effects of the benzodiazepine chlordiazepoxide throughout the circadian cycle.

Geniculo-hypothalamic tract lesions block chlordiazepoxide-induced phase advances in Syrian hamsters.

Administration of the benzodiazepine triazolam at the appropriate time in the circadian cycle has been shown to induce phase shifts in hamster circadian rhythms. These phase shifts can be blocked by geniculo-hypothalamic tract (GHT) ablation or by restraint of activity. The present study examined the effects of the benzodiazepine chlordiazepoxide on running-wheel activity rhythms of hamsters. The phase-advancing effect of intraperitoneal injections of chlordiazepoxide administered at circadian time 6 (CT 6) was dose-dependent. Average shifts ranged from 6 min at a dose of 0.05 mg/kg to 135 min at a dose of 200 mg/kg. Four of twenty hamsters did not show a phase shift to any dose tested. Phase advance shifts to chlordiazepoxide (CT 6; 100 mg/kg) were blocked by GHT lesions. Chlordiazepoxide injections at doses which induced phase shifts were often followed by sedation. These results indicate that chlordiazepoxide is similar to triazolam, in that its ability to induce phase shifts at circadian time 6 is blocked by GHT lesions.

Hamster circadian rhythms are phase-shifted by electrical stimulation of the geniculo-hypothalamic tract.

The suprachiasmatic nuclei (SCN) contain the major pacemaker for mammalian circadian rhythms. The SCN receive photic input both directly, via the retinohypothalamic tract (RHT), and indirectly, via the geniculohypothalamic tract (GHT), which originates in cells in the intergeniculate leaflet (IGL) and anterior portions of the ventral lateral geniculate nucleus (vLGN). We tested whether electrical stimulation of the GHT would induce phase shifts in wheel-running activity rhythms of Syrian hamsters housed in continuous darkness or continuous illumination. In both lighting conditions, electrical stimulation of the GHT induced mainly phase advances when given during the late subjective day and small phase delays when given during the late subjective night and early subjective day. Stimulation in the thalamus outside the GHT failed to produce similar phase shifts. Repeated daily stimulation had only a weak entraining effect on the activity rhythm. Activation of GHT neurons appears to influence the pacemaker for activity rhythms in a phase-dependent manner.

Photic responses of geniculo-hypothalamic tract neurons in the Syrian hamster.

The putative neural pacemaker controlling circadian rhythms in mammals is contained in the suprachiasmatic nuclei of the hypothalamus. These nuclei receive a projection, the geniculo-hypothalamic tract (GHT), from neurons in the intergeniculate leaflet (IGL) and portions of the ventral lateral geniculate nucleus (vLGN) of the thalamus. We examined the responses of putative GHT neurons to diffuse illumination using extracellular electrophysiological recordings. The great majority of IGL neurons showed sustained ON responses to diffuse retinal illumination; vLGN neurons showed more variation in their responses. Discharge rates of sustained ON neurons increased monotonically as light intensity was increased and saturated over 2-3 log units of intensity changes. Many IGL neurons had binocular input, and input from the ipsilateral eye was often inhibitory. These results indicate that GHT neurons may provide information about ambient light intensity to the suprachiasmatic nuclei.

Ablation of the geniculo-hypothalamic tract alters circadian activity rhythms of hamsters housed under constant light.

Retino-recipient cells in the hamster lateral geniculate nucleus project to the suprachiasmatic nucleus via the geniculo-hypothalamic tract (GHT). GHT-ablation alters phase advance shifts to light pulses in a hamster's late subjective night. In this study, the effects of GHT-ablation on wheel-running rhythms of hamsters housed under continuous illumination (LL) were assessed. In the first experiment, hamsters received GHT-ablation or sham surgery while under a light:dark schedule and were subsequently exposed to 250 days of LL. GHT-ablated hamsters showed rhythms with shorter periods and were less likely to show split activity rhythms than sham-operated or partial-lesion controls. In the second experiment, hamsters were housed under LL until rhythms split into two components; hamsters then received either GHT-ablation or sham surgery. Four of seven GHT-ablated hamsters showed re-fusion of their activity pattern into one component, while none of the eight sham-operated animals showed such re-fusion. The results of these two experiments indicate that GHT-ablation alters the responsiveness of the activity rhythm pacemaker to LL exposure.

Uptake and release of putative neurotransmitters. Measurements in regions of the normal and Newcastle disease virus-infected mouse brain.

The capacity of various regions of the mouse brain to accumulate a series of putative neurotransmitter compounds has been studied in cerebral homogenates. This uptake is selective, sodium dependent, energy dependent, and exhibits characteristics of high affinity transport. Calcium-stimulated release under depolarizing conditions of accumulated radioactive compounds was also examined. Large regional variations of uptake and release capacity existed. No clear relation between intensity of uptake and releasability of transported compounds was seen. The effect of infection of mice with Newcastle disease virus on these processes was investigated. No significant differences were seen in infected mice despite their depressed metabolic rate.