Understanding the structure and functioning of polar pelagic ecosystems to predict the impacts of change.

The determinants of the structure, functioning and resilience of pelagic ecosystems across most of the polar regions are not well known. Improved understanding is essential for assessing the value of biodiversity and predicting the effects of change (including in biodiversity) on these ecosystems and the services they maintain. Here we focus on the trophic interactions that underpin ecosystem structure, developing comparative analyses of how polar pelagic food webs vary in relation to the environment. We highlight that there is not a singular, generic Arctic or Antarctic pelagic food web, and, although there are characteristic pathways of energy flow dominated by a small number of species, alternative routes are important for maintaining energy transfer and resilience. These more complex routes cannot, however, provide the same rate of energy flow to highest trophic-level species. Food-web structure may be similar in different regions, but the individual species that dominate mid-trophic levels vary across polar regions. The characteristics (traits) of these species are also different and these differences influence a range of food-web processes. Low functional redundancy at key trophic levels makes these ecosystems particularly sensitive to change. To develop models for projecting responses of polar ecosystems to future environmental change, we propose a conceptual framework that links the life histories of pelagic species and the structure of polar food webs.

New Zealand dentists' views on community water fluoridation.

OBJECTIVE: To determine whether New Zealand general dental practitioners support community water fluoridation (CWF), and to gauge their opinions on its possible systemic side-effects. METHODS: An online survey was conducted in 2010, involving the 1174 general dental practitioners who had email addresses on the Dental Register and were contactable in New Zealand. A total of 465 dentists (39.6%) participated. RESULTS: Most practitioners (93.5%) reported supporting community water fluoridation; the other 6.5% either were unsure or did not support it. Higher proportions of more recent graduates supported CWF. Some 85.6% of practitioners thought that drinking fluoridated water was a harmless way to prevent dental caries, but 6.2% felt that fluoridated water may cause other health problems. There were no systematic differences by sociodemographic and practice characteristics, except that a higher proportion of males and more experienced practitioners reported being confident in discussing CWF-related issues. CONCLUSIONS: Most New Zealand dental practitioners support community water fluoridation, although a very small proportion believe that it is harmful and/or does not prevent caries.

Bayesian inference of a historical bottleneck in a heavily exploited marine mammal.

Emerging Bayesian analytical approaches offer increasingly sophisticated means of reconstructing historical population dynamics from genetic data, but have been little applied to scenarios involving demographic bottlenecks. Consequently, we analysed a large mitochondrial and microsatellite dataset from the Antarctic fur seal Arctocephalus gazella, a species subjected to one of the most extreme examples of uncontrolled exploitation in history when it was reduced to the brink of extinction by the sealing industry during the late eighteenth and nineteenth centuries. Classical bottleneck tests, which exploit the fact that rare alleles are rapidly lost during demographic reduction, yielded ambiguous results. In contrast, a strong signal of recent demographic decline was detected using both Bayesian skyline plots and Approximate Bayesian Computation, the latter also allowing derivation of posterior parameter estimates that were remarkably consistent with historical observations. This was achieved using only contemporary samples, further emphasizing the potential of Bayesian approaches to address important problems in conservation and evolutionary biology.

Altered mitogen-activated protein kinase signaling, tau hyperphosphorylation and mild spatial learning dysfunction in transgenic rats expressing the beta-amyloid peptide intracellularly in hippocampal and cortical neurons.

The pathological significance of intracellular Abeta accumulation in vivo is not yet fully understood. To address this, we have studied transgenic rats expressing Alzheimer's-related transgenes that accumulate Abeta intraneuronally in the cerebral and hippocampal cortices but do not develop extracellular amyloid plaques. In these rats, the presence of intraneuronal Abeta is sufficient to provoke up-regulation of the phosphorylated form of extracellular-regulated kinase (ERK) 2 and its enzymatic activity in the hippocampus while no changes were observed in the activity or phosphorylation status of other putative tau kinases such as p38, glycogen synthase kinase 3, and cycline-dependent kinase 5. The increase in active phospho-ERK2 was accompanied by increased levels of tau phosphorylation at S396 and S404 ERK2 sites and a decrease in the phosphorylation of the CREB kinase p90RSK. In a water maze paradigm, male transgenic rats displayed a mild spatial learning deficit relative to control littermates. Our results suggest that in the absence of plaques, intraneuronal accumulation of Abeta peptide correlates with the initial steps in the tau-phosphorylation cascade, alterations in ERK2 signaling and impairment of higher CNS functions in male rats.

Substrate turnover and oxidation during moderate-intensity exercise following acute plasma volume expansion.

In previous work using prolonged, light cycle exercise, we were unable to demonstrate an effect of acute plasma volume (PV) expansion on glucose kinetics or substrate oxidation, despite a decline in whole-body lipolysis (Phillips et al., 1997). However, PV is known to decrease arterial O2 content. The purpose of this study was to examine whether substrate turnover and oxidation would be altered with heavier exercise where the challenge to O2 delivery is increased. Eight untrained males (VO2max = 3.52 +/- 0.12 l/min) twice performed 90 min of cycle ergometry at 62 % VO2peak, both prior to (CON) and following induced plasma volume expansion (Dextran [6 %] or Pentaspan [10 %]) (6.7 ml/kg) (PVX). Glucose and glycerol kinetics were determined with primed constant infusions of [6.6-(2)H2] glucose and [(2)H5] glycerol, respectively. PVX resulted in a 15.8 +/- 2.2 % increase (p < 0.05) in PV. Glucose and glycerol appearance (Ra) and utilization (Rd), although increasing progressively (p < 0.05) with exercise, were not different between conditions. Similarly, no differences in substrate oxidation, either fat or carbohydrate, were observed between the two conditions. Prolonged exercise resulted in an increase (p < 0.05) in plasma glucagon and a decrease (p < 0.05) in plasma insulin during both conditions. With PVX, the exercise-induced increase in glucagon was diminished (p < 0.05). We conclude that impairment in O2 content mediated by an elevated PV does not alter glucose, and glycerol kinetics or substrate oxidation even at moderate exercise intensity.

Acute plasma volume expansion in the untrained alters the hormonal response to prolonged moderate-intensity exercise.

To investigate the role of an increase in plasma volume (PV), characteristically observed with short-term endurance training, on the endocrine response to prolonged moderate intensity exercise, eight untrained males (VO2 peak = 3.52 +/- 0.12 l x min(-1)) performed 90 min of cycle ergometry at approximately 60% VO2peak both before (CON) and following (PVX) PV expansion. Acute PV expansion, which was accomplished using a solution of Dextran (6%) or Pentispan (10%) (6.7 ml kg(-1)), resulted in a calculated 15.8+/-2.2% increase (p<0.05) in PV. The prolonged exercise resulted in increases (p<0.05) in plasma vasopressin (AVP), plasma rennin activity (PRA), aldosterone (ALD), atrial naturetic peptide (alpha-ANP), and the catecholamines norepinephrine (NE) and epinephrine (EPI). PVX blunted the increases (p<0.05) in AVP, PRA, ALD, NE and EPI, during the exercise itself. The concentration of alpha-ANP was also lower (p<0.05) during exercise following PVX, an effect that could be attributed to the lower resting levels. No differences in osmolality was observed between conditions. These results demonstrate that PVX alters the fluid regulatory hormonal response in untrained subjects to moderate intensity dynamic exercise in a manner similar to that observed following short-term training induced alterations in PV. The specific mechanisms responsible for these alterations remain unclear, but appear to be related directly to the increase in PV.

Out-of-hours emergency dental services--development of one possible local solution.

This paper describes the development of a local solution to the problem of the provision of out-of-hours dental care in Newcastle and North Tyneside in the north east of England. Focus groups were used to review the current provision of, and problems with, dental out-of-hours emergency provision. A consensus conference involving both general dental and medical practitioners, was subsequently used to develop possible alternative methods for the provision of out-of-hours emergency dental services. A centralised service delivered from a secure location in conjunction with general medical practitioners was developed which was dependent on a nurse-led triage. The linkage with NHS Direct may be an opportunity, in some locations, to integrate dental services more fully with other out-of-hours primary care services. The method described allowed a solution to be generated by practitioners themselves, thus giving ownership and acceptance to the chosen option.

Acute plasma volume expansion alters cardiovascular but not thermal function during moderate intensity prolonged exercise.

To investigate the hypothesis that the increase in plasma volume (PV) that typically occurs with training results in improved cardiovascular and thermal regulation during prolonged exercise, eight untrained males (V(O2)peak = 3.52 +/- 0.12 L x min(-1)) performed 90 min of cycle ergometry at 62% V(O2)peak before and after acute PV expansion. Subjects were infused with a PV-expanding solution (dextran (6%) or Pentaspan (10%)) equivalent to 6.7 mL x kg(-1) body mass (PVX) or acted as their own control (CON) in a randomized order. PVX resulted in a calculated 15.8% increase in resting PV, which relative to CON, was maintained throughout the exercise (P < 0.05). During PVX, heart rate was lower (P < 0.05) and stroke volume and cardiac output were higher (P < 0.05) during the exercise. Mean arterial pressure and total peripheral resistance, although altered by exercise (P < 0.05), were not different between the two conditions. Core temperature, which was progressively increased by the exercise (P < 0.01), was not affected by PVX. A similar decrease in body weight was observed between the conditions as a result of the exercise (P < 0.01). These results indicate that acute PVX alters cardiovascular performance without affecting the thermoregulatory response to prolonged cycle exercise.

Abeta immunoreactive material is present in several intracellular compartments in transfected, neuronally differentiated, P19 cells expressing the human amyloid beta-protein precursor.

Processing of the amyloid beta-protein precursor is believed to play a critical role in the development of Alzheimer's disease neuropathology. The localization of the human Abeta epitope within mature neuroectodermally differentiated embryonal carcinoma (P19) cells, stably transfected with the cDNA coding for a wild form human amyloid beta-protein precursor (AbetaPP 751) was investigated. For this, we applied high resolution electron microscopy and immunocytochemistry with a newly developed, highly specfic monoclonal antibody (McSA1). We observed immunoreactive signals in a number of subcellular organelles such as early endosomes, the trans-Golgi network and in the dilated rough endoplasmic reticulum, but not in lysosomes. Occasionally Abeta immunoreactivity was associated with microtubules and filaments, with the outer mitochondrial membrane, and with the nuclear envelope. These observations expand on current data regarding intracellular trafficking of AbetaPP fragments and provoke further questions regarding the role of intracellular Abeta peptides in basal conditions and pathological states.

Phosphorylation of mitogen-activated protein kinase is altered in neuroectodermal cells overexpressing the human amyloid precursor protein 751 isoform.

The aberrant expression or processing of the amyloid precursor protein (APP) is the only known genetic basis for presenile familial Alzheimer's disease, and the molecular connection between APP and tau has been perplexing. Attention has focused on proline-directed serine/threonine kinases as mediating the cytoskeletal modifications of Alzheimer's disease, and we show that overexpression of APP can influence the activation of a candidate kinase, the mitogen-activated protein kinase (MAPK). In murine embryonal carcinoma cells stably transfected with the human 751 isoform of APP, we observed steady-state hyperactivation of p42(MAPK) concomitant with APP overexpression 3 days after neuroectodermal differentiation. In more mature differentiated cells, immunocytochemical analysis revealed enhanced basal somatic and nuclear immunoreactivity for phosphorylated MAPK coupled with an attenuated phosphorylation response to growth factor stimulation. Our results suggest that APP can influence the MAPK signaling pathway in such a way that the absolute and time-dependent activation required for discrimination of the appropriate downstream response are compromised. Such an effect would have important consequences for the functioning of cells coincidentally expressing both proteins, a situation that occurs in neuronal populations vulnerable to Alzheimer's disease pathology.

Mitochondrial abnormalities in neuroectodermal cells stably expressing human amyloid precursor protein (hAPP751).

Metabolic hypofunction is a common finding in a number of neurodegenerative diseases, including Alzheimer's disease (AD). The strong linkage between the amyloid precursor protein (APP) and AD led us to examine whether over-expression of this protein in CNS-type cells had an effect on mitochondria. We found abnormal morphology in mitochondria of the neuroectodermal progeny of P19 cells stably transfected with human APP751. In addition, the mitochondria of APP-transfected clones had a decreased mitochondrial membrane potential. These changes were independent of Abeta toxicity and distinct from complex I inhibition. Our results have important implications for the earliest events in the pathophysiology of AD and, by extrapolation, for intervention therapies.

Diver's mouth syndrome: a report of two cases and construction of custom-made regulator mouthpieces.

Scuba diving is becoming more and more popular and dentists are increasingly likely to encounter patients with diving-related problems. Protruded mandibular positions and the biting forces exercised on the anterior occlusion during diving can cause pain and dysfunction, particularly where a predisposing factor such as bruxism exists. In this article, two cases are reported of patients with diving-exacerbated pain dysfunction syndrome, which improved following the construction of custom-made mouthpieces which distributed the forces more evenly. Laboratory procedures are described for construction of a custom-made scuba regulator mouthpiece that allows more comfortable diving.

Trends in exodontia under general anaesthesia at a dental teaching hospital.

AIMS: To survey the use of simple exodontia for children under general anaesthesia on an out-patient basis at a Northern Dental Hospital. To monitor any effects resulting from the introduction of the Poswillo guidelines on the referral for and treatment of patients under general anaesthesia. DESIGN: A retrospective longitudinal analysis. SETTING: A Northern Dental Hospital in England. MATERIALS: Information was recorded from original case records of children undergoing exodontia under general anaesthesia on an out-patient basis during October between 1989 and 1997. RESULTS: The mean and modal age of the children decreased from 7.7 years to 6.0 years respectively in 1989 to 5.7 years and 4.0 years in 1997. The proportion receiving a general anaesthetic for orthodontic extractions substantially decreased from 18.0% in 1989 to 0.7% in 1997 and the need for repeat dental general anaesthetics within 18 months was eliminated with the introduction of a pre-general anaesthetic screening service. CONCLUSION: Dental treatment under general anaesthesia should continue to be available where it is justified. A separate assessment appointment reduces the prescription of general anaesthesia and minimises its usage for orthodontic extractions and the necessity for repeat general anaesthesia.

Cellular immune responses to four doses of percutaneous bacille Calmette-Guérin in healthy adults.

To explore the hypothesis that low-dose immunization might induce preferential Th1 cell immunity, 76 adults were vaccinated with one of four doses of bacille Calmette-Guérin (BCG): The doses contained very low (1.6 x 10(5) cfu), low (3.2 x 10(6) cfu), standard (1.6 x 10(8) cfu), or high (3.2 x 10(8) cfu) levels of BCG. Delayed-type hypersensitivity responses occurred 8 weeks after vaccination in 10% of persons given very low or low doses of BCG, compared with 95% and 100% of persons given standard or high doses, respectively. Lymphoproliferative responses, which were increased only for high-dose vaccinees, peaked 2 weeks after vaccination and were directed chiefly against Mycobacterium tuberculosis-secreted proteins, particularly the antigen 85 complex. Significant increases in mycobacteria-specific interferon-gamma expression were present 16 weeks after vaccination only for persons given standard or high doses of BCG. Percutaneous BCG appears capable of inducing a temporary Th1-like immune response, but standard or higher dosages are required.

Effect of acute plasma volume expansion on substrate turnover during prolonged low-intensity exercise.

We investigated the effect of acute, graded increases in plasma volume (PV) by use of dextran on substrate turnover and oxidation during exercise. Eight untrained males [peak aerobic power (VO2peak) = 45.2 +/- 2.2 (SE) ml.kg-1.min-1] performed 2 h of cycle ergometry at 46 +/- 4% of VO2peak on three occasions in a randomized order: 0% PV expansion (CON) and after 14% (LOW) and 21% (HIGH) PV expansion. Glucose and glycerol turnover were measured using primed continuous infusions of [6,6-2H2]glucose and [2H5]glycerol, respectively. Glycerol rate of appearance (Ra) was taken as a relative index of whole body lipolysis. Increases in PV had no effect on glucose Ra or disappearance (Rd) either at rest or during exercise. At the onset of exercise, both glucose Ra and Rd increased approximately 100% (P < 0.01). Glucose Ra and Rd continued to increase with exercise duration (P < 0.05) so that, at 120 min of exercise, they were > 330% higher than at rest (P < 0.01). Glycerol Ra also increased with exercise duration (P < 0.05). Total lipolysis during exercise, calculated as the area under the glycerol Ra vs. time curve, was reduced during LOW vs. CON (P < 0.01). Further expansion of PV (HIGH) had no additional effect on whole body lipolysis. No effect of hypervolemia was observed on whole body fat or carbohydrate oxidation. These results indicate that acute PV expansion can alter whole body lipolysis, possibly via a reduction in catecholamine secretion.

Two-step tuberculin skin testing of injection drug users recruited from community-based settings.

SETTING: Cross-sectional study of drug users recruited from street-based settings in four US cities: Denver, Portland, Oakland and San Francisco. OBJECTIVE: To evaluate responses to two-step tuberculin skin testing among HIV-positive and HIV-negative injection drug users. DESIGN: Subjects were recruited from existing studies of HIV and risk behaviors for tuberculin skin testing. Those with a negative initial tuberculin test were referred for a second skin test 1-3 weeks later. A positive tuberculin test was defined as > or = 10 mm, or > or = 5 mm if the subject was HIV-positive. RESULTS: Of 997 persons receiving an initial tuberculin test, 13% had a positive response. Of 644 persons receiving a second tuberculin test, 8% had a positive response, with rates as high as 14% among those from Oakland and 12% among African Americans. HIV-positive subjects were less likely to have skin test responses > or = 10 mm on the initial test (P = 0.03), or increases between the initial and second test of > or = 10 mm (P = 0.06). CONCLUSION: Boosting occurred in both HIV-positive and HIV-negative injection drug users. Two-step testing should be considered for this population, particularly those on whom repeat tuberculin testing will be performed.

Effects of acute expansion of plasma volume on cardiovascular and thermal function during prolonged exercise.

To investigate the hypothesis that an increase in plasma volume (PV) is obligatory in reducing the cardiovascular drift that is associated with prolonged exercise following training, a plasma expander (Macrodex) was used to acutely elevate PV. Eight untrained volunteers [maximal oxygen consumption; VO2max 45.2 (2.2) ml x kg(-1) x min(-1), mean (SE)] cycled for 2 h [at 46 (4)% VO2max] in ambient conditions either with no PV expansion (CON) or following PV expansions of either 14% (LOW) or 21% (HIGH). During CON, heart rate (HR) increased (P < 0.05) from 147 (2.4) beats x min(-1) to 173 (3.6) beats x min(-1) from 15 to 120 min of exercise. Both LOW and HIGH conditions depressed (P < 0.05) HR, an effect that was manifested following 15 min of exercise. In contrast, stroke volume (SV) was elevated following PV expansion, with values (ml) of 89.6 (6.8), 97.8 (5.9) and 104 (4.6) noted by 15 min of exercise for CON, LOW and HIGH conditions, respectively. Acute PV expansion, regardless of magnitude, also resulted in elevations in cardiac output (Qc). These differences between conditions persisted throughout the exercise, as did the elevation in Qc that was noted with LOW and HIGH conditions. No difference between Qc, HR or SV was found between LOW and HIGH. In addition, neither LOW nor HIGH conditions altered the change in rectal temperature that was observed during exercise. These results demonstrate that, at least for moderate exercise performed in ambient conditions, PV expansion serves only to alter cardiac function (Qc, HR, SV) early in exercise, and not to attenuate the drift that occurs as the exercise is prolonged.

Psychological evaluations, referrals, and follow-up of adolescents after their exposure to Hurricane Hugo.

PROBLEM: There is little understanding of adolescent appraisal of stress and crisis intervention for adolescents who are exposed to major stress such as that of a natural disaster. METHODS: A description of the psychological evaluations, referrals, and follow-up assessments made by nurse practitioners (NPs) and a nurse psychotherapist (NPT) of adolescents (N = 507) in two South Carolina high schools who experienced Hurricane Hugo. FINDINGS: The NPs' evaluations concluded that 63 adolescents (12%) exhibited symptoms of psychological distress. The NPs referred 36 of these adolescents to high school counselors for minor distress or school-related problems and 27 for more intensive clinical evaluation by an NPT. Of the 27 adolescents who were referred to the NPT, 10 had symptoms associated with adolescent adjustment reaction, 8 showed symptoms of depression, 5 revealed symptoms of posttraumatic stress disorder, and 4 complained of serious family problems. CONCLUSIONS: Based on these data and the mental processes described by these adolescents, the authors propose a model and suggest adolescent appraisal of stress and crisis is a critical issue to consider when intervening with adolescents who are exposed to major stressors, including those associated with a disaster.