Virtual arthroplasty follow-up: five-year data from a district general hospital.

INTRODUCTION: Follow-up after hip and knee arthroplasty is advocated to identify asymptomatic loosening and improve patient satisfaction. There are, however, financial and time implications associated with regular clinic appointments. Assessment through virtual means has been suggested as an alternative. MATERIALS AND METHODS: At the West Suffolk Hospital, following arthroplasty surgery of the lower limb, patients are followed-up via a questionnaire at one and five years postoperatively, then subsequently at five-yearly intervals. Patients are recalled based on the outcome of these assessments. Using a locally compiled data base we identified all patients reviewed between 2011 and 2015 using this virtual assessment process and examined their outcomes. RESULTS: During the five years of follow-up, 5,380 patients were eligible for assessment. Compliance varied from 77% follow up for hips and 83% for knees. Ten patients were recalled following total hip replacement, eight for x-ray changes and one for a poor satisfaction score. Five went on to undergo revision surgery. Some 56 recalls to clinic following knee arthroplasty were seen; 42 due to a poor Oxford Knee Score, 6 with associated x-ray abnormalities and 6 isolated abnormal x-rays. Five subsequently underwent revision surgery; 30 (54%) were discharged after initial review and 18 (32%) were referred to different subspecialties.As a result of the virtual review process, 4,219 clinic appointments were avoided, with no documented admissions as a result of a missed complication from virtual review. DISCUSSION: A virtual arthroplasty clinic significantly reduces the number of patients attending regular follow-up clinics, without compromising safe practice.

Developmental plasticity of the stress response in female but not in male guppies.

To survive, animals must respond appropriately to stress. Stress responses are costly, so early-life experiences with potential stressors could adaptively tailor adult stress responses to local conditions. However, how multiple stressors influence the development of the stress response remains unclear, as is the role of sex. Trinidadian guppies (Poecilia reticulata) are small fish with extensive life-history differences between the sexes and population variation in predation pressure and social density. We investigated how sex and early-life experience influence hormonal stress responses by manipulating conspecific density and perceived predation risk during development. In adults, we sampled cortisol twice to measure initial release and change over time in response to a recurring stressor. The sexes differed considerably in their physiological stress response. Males released more cortisol for their body mass than females and did not reduce cortisol release over time. By contrast, all females, except those reared at high density together with predation cues, reduced cortisol release over time. Cortisol responses of males were thus less dynamic in response to current circumstances and early-life experiences than females, consistent with life-history differences between the sexes. Our study underscores the importance of early-life experiences, interacting ecological factors and sex differences in the organization of the stress response.

Evolutionary and immediate effects of crude-oil pollution: depression of exploratory behaviour across populations of Trinidadian guppies.

Human-induced perturbations such as crude-oil pollution can pose serious threats to aquatic ecosystems. To understand these threats fully it is important to establish both the immediate and evolutionary effects of pollutants on behaviour and cognition. Addressing such questions requires comparative and experimental study of populations that have evolved under different levels of pollution. Here, we compared the exploratory, activity and social behaviour of four populations of Trinidadian guppies (Poecilia reticulata) raised in common garden conditions for up to three generations. Two of these populations originated from tributaries with a long history of human-induced chronic crude-oil pollution with polycyclic aromatic hydrocarbons due to oil exploitation in Trinidad, the two others originating from non-polluted control sites. Laboratory-raised guppies from the oil-polluted sites were less exploratory in an experimental maze than guppies from the non-polluted sites and in a similar manner for the two independent rivers. We then compared the plastic behavioural responses of the different populations after an acute short-term experimental exposure to crude oil and found a decrease in exploration (but not in activity or shoaling) in the oil-exposed fish compared to the control subjects over all four populations. Taken together, these results suggest that both an evolutionary history with oil and an acute exposure to oil depressed guppy exploratory behaviour. We discuss whether the behavioural divergence observed represents adaptation to human-induced pollutants, the implications for conservation and the possible knock-on effects for information discovery and population persistence in fish groups.

Parallel and nonparallel behavioural evolution in response to parasitism and predation in Trinidadian guppies.

Natural enemies such as predators and parasites are known to shape intraspecific variability of behaviour and personality in natural populations, yet several key questions remain: (i) What is the relative importance of predation vs. parasitism in shaping intraspecific variation of behaviour across generations? (ii) What are the contributions of genetic and plastic effects to this behavioural divergence? (iii) And to what extent are responses to predation and parasitism repeatable across independent evolutionary lineages? We addressed these questions using Trinidadian guppies (Poecilia reticulata) (i) varying in their exposure to dangerous fish predators and Gyrodactylus ectoparasites for (ii) both wild-caught F0 and laboratory-reared F2 individuals and coming from (iii) multiple independent evolutionary lineages (i.e. independent drainages). Several key findings emerged. First, a population's history of predation and parasitism influenced behavioural profiles, but to different extent depending on the behaviour considered (activity, shoaling or boldness). Second, we had evidence for some genetic effects of predation regime on behaviour, with differences in activity of F2 laboratory-reared individuals, but not for parasitism, which had only plastic effects on the boldness of wild-caught F0 individuals. Third, the two lineages showed a mixture of parallel and nonparallel responses to predation/parasitism, with parallel responses being stronger for predation than for parasitism and for activity and boldness than for shoaling. These findings suggest that different sets of behaviours provide different pay-offs in alternative predation/parasitism environments and that parasitism has more transient effects in shaping intraspecific variation of behaviour than does predation.

Large-brained mammals live longer.

Many mammals have brains substantially larger than expected for their body size, but the reasons for this remain ambiguous. Enlarged brains are metabolically expensive and require elongated developmental periods, and so natural selection should have favoured their evolution only if they provide counterbalancing advantages. One possible advantage is facilitating the construction of behavioural responses to unusual, novel or complex socio-ecological challenges. This buffer effect should increase survival rates and favour a longer reproductive life, thereby compensating for the costs of delayed reproduction. Here, using a global database of 493 species, we provide evidence showing that mammals with enlarged brains (relative to their body size) live longer and have a longer reproductive lifespan. Our analysis supports and extends previous findings, accounting for the possible confounding effects of other life history traits, ecological and dietary factors, and phylogenetic autocorrelation. Thus, these findings provide support for the hypothesis that mammals counterbalance the costs of affording large brains with a longer reproductive life.

Scintigraphy can be used to compare delivery of sore throat formulations.

AIMS: Sore throat (pharyngitis) is commonly treated with over-the-counter lozenges, tablets, sprays and gargles. While the efficacy of the active ingredients has been examined, less is known about the comparative efficacy of the different delivery formats. METHODS: A pilot study was initially performed, followed by an open-label, four-way crossover study in healthy volunteers to quantitatively assess the delivery efficacy of a lozenge, tablet, spray and gargle, using technetium-99m and scintigraphy as a marker of deposition and clearance of the active ingredients. RESULTS: Initial deposition in the mouth and throat combined was significantly greater for the solid dose forms (lozenge and tablet) than for the spray or gargle. Rates of clearance were initially similar for the tablet and lozenge with low levels of radioactivity present at up to 2 h. At 10 and 20 min, significantly more of the dose remained for the lozenge than for the tablet. The mouth appeared to act as a reservoir for continued clearance to the throat. DISCUSSION AND CONCLUSION: Scintigraphy is an effective means of quantifying the delivery efficiency, and hence availability, of sore throat medications. The results presented here suggest that both lozenges and tablets offer considerable advantages over sprays or gargles, both in terms of proportion of the dose delivered to the mouth and throat, combined, and clearance from these regions. These delivery formats provide fast, effective and prolonged delivery of active ingredients, highlighting their potential benefits for sore throat medication.

Breeding for abiotic stresses for sustainable agriculture.

Using cereal crops as examples, we review the breeding for tolerance to the abiotic stresses of low nitrogen, drought, salinity and aluminium toxicity. All are already important abiotic stress factors that cause large and widespread yield reductions. Drought will increase in importance with climate change, the area of irrigated land that is salinized continues to increase, and the cost of inorganic N is set to rise. There is good potential for directly breeding for adaptation to low N while retaining an ability to respond to high N conditions. Breeding for drought and salinity tolerance have proven to be difficult, and the complex mechanisms of tolerance are reviewed. Marker-assisted selection for component traits of drought in rice and pearl millet and salinity tolerance in wheat has produced some positive results and the pyramiding of stable quantitative trait locuses controlling component traits may provide a solution. New genomic technologies promise to make progress for breeding tolerance to these two stresses through a more fundamental understanding of underlying processes and identification of the genes responsible. In wheat, there is a great potential of breeding genetic resistance for salinity and aluminium tolerance through the contributions of wild relatives.

Pro-apoptotic and immunomodulatory activity of a mycobacterial cell wall-DNA complex towards LNCaP prostate cancer cells.

BACKGROUND: We have isolated a mycobacterial cell wall-DNA complex (MCC) possessing anti-cancer activity against bladder cancer cells. The anti-cancer activity of MCC appears to be due to two effects: a direct interaction with bladder cancer cells resulting in the induction of apoptosis and an indirect effect via the stimulation of monocytes and macrophages cytokine synthesis. In this study, the direct effect of MCC towards LNCaP cancer cells was evaluated. METHODS: Inhibition of proliferation, cell cycle arrest and induction of apoptosis were evaluated in vitro using LNCaP cells treated with MCC. The synthesis of IL-12, GM-CSF, and TNF-alpha by LNCaP cells in response to MCC was also determined. Experiments were performed to gain insight into the mechanism of action of MCC towards LNCaP cells. RESULTS: MCC caused a dose-dependent inhibition of the proliferation of LNCaP cells that was associated with cell cycle arrest at the G0/G1 phase. MCC-induced apoptosis of LNCaP cells was consistent with a mitochondrial pathway involving mitochondrial disruption, release of cytochrome c, and an increase in Bax protein levels leading to caspase-3 and -7 activation and cleavage of poly (ADP-ribose) polymerase and nuclear mitotic apparatus protein. Surprisingly, MCC also directly induced the synthesis of IL-12 and GM-CSF, but not TNF-alpha, by LNCaP cells. CONCLUSIONS: MCC possesses the ability to directly induce apoptosis of LNCaP cells and to trigger the synthesis of IL-12 and GM-CSF by these cells, suggesting a potential role of MCC for the treatment of prostate cancer.

The Test of Everyday Attention for Children (TEA-Ch): patterns of performance in children with ADHD and clinical controls.

The present study explores the utility of the Test of Everyday Attention for Children (TEA-Ch) as a measure of the attentional impairments displayed by children with Attention Deficit Hyperactivity Disorder (ADHD). Sixty-three children with ADHD and 23 non-ADHD Clinical Control children were compared on subtests of the TEA-Ch reflecting three attentional domains: sustained, selective, and attentional control. Results show that children with ADHD performed significantly worse than clinical controls on subtests of sustained attention and attentional control. The groups did not differ, however, on subtests of selective attention. These findings suggest that the TEA-Ch is sensitive to attentional deficits unique to ADHD and holds promise as a useful tool in the assessment of ADHD. Performance patterns and future directions are discussed.

A preliminary review of the eastern Pacific species of Elacatinus (Perciformes: Gobiidae).

Elacatinus limbaughi is described as new from the Gulf of California. Elacatimus digueti is redescribed and Elacatinus inornatus Bussing is synonymyzed with E. digueti. Data are presented on geographical variation in Elacatinus puncticulatus and E. digueti. Species of the genus Elacatimus are normally associated with coral reefs and several of the species clean parasites from other fishes. Elacatinus is regarded as distinct from Gobiosoma, based on vertebral and other characteristics.

Revision of the eastern Pacific species of Gobulus (Perciformes: Gobiidae), with description of a new species.

Gobulus birdsongi is described as a new species from the Pacific coast of Panama. The two other known species of Gobulus from the eastern Pacific, Gobulus crescentalis and G. hancocki are redescribed. Gobulus birdsongi differs from other species in the genus in having more numerous second dorsal and anal rays. Gobulus hancocki differs from G. crescentalis in having a much smaller eye. The genus is distinctive in having reversed countershading, with the ventral surface of the body darker than the dorsal surface.

Modulation of interleukin-12 synthesis by DNA lacking the CpG motif and present in a mycobacterial cell wall complex.

A mycobacterial cell wall complex prepared from the non-pathogenic microorganism Mycobacterium phlei, where mycobacterial DNA is preserved and complexed to cell wall fragments, possesses anticancer and immunomodulatory activity. DNA from a number of prokaryotes has been found to modulate the immune system and to induce cytokine synthesis. We have therefore determined whether the DNA associated with this complex has the ability to induce the synthesis of interleukin-12 (IL-12), a potent anticancer cytokine. Mycobacterial DNA complexed with cell wall fragments or DNA purified from M. phlei induced IL-12 synthesis by murine and human monocytes and macrophages in vitro, and was capable of inducing IL-12 synthesis in vivo in mice following i.p. administration. Neutralization of DNA with cationic liposomes or digestion with DNase I significantly decreased the ability of the cell wall complex to induce IL-12. CpG methylation of DNA extracted from these cell walls or from M. phlei did not affect the induction of IL-12 synthesis by monocytes and macrophages. In contrast, CpG methylation of DNA from Escherichia coli abolished its ability to induce IL-12 synthesis. These results demonstrate that unmethylated CpG motifs present in M. phlei DNA are not a prerequisite for the induction of IL-12 synthesis. The size of the mycobacterial DNA, in the range of 5 bp to genomic DNA, did not influence its capacity to induce IL-12. Our results emphasize that M. phlei DNA associated with the cell wall complex makes a significant contribution to the overall immunomodulatory and anticancer activity of this mycobacterial cell wall preparation and that these activities are not correlated with the presence of CpG motifs.

The production and characterization of recombination between chromosome 3N of Aegilops uniaristata and chromosome 3A of wheat.

Six wheat lines with recombination between Aegilops uniaristata chromosome 3N and wheat chromosome 3A were produced. These were characterized in terms of exchange points by RFLP analysis. Chromosome 3N carries an undesirable brittle rachis gene and three of the recombinant lines had lost this character. The results also support previously published evidence of a pericentric inversion in chromosome 3N relative to the wheat homoeologous group 3 chromosomes.

Using survival analysis to study spatial point patterns in geographical epidemiology.

The spatial K-function has become a well accepted method of investigating whether significant clustering can be detected in spatial point patterns. Unlike nearest neighbor-based methods, the K-function approach has the advantage of exploring spatial pattern across a range of spatial scales. However, K-functions still have a number of drawbacks. For instance, although K-functions are based on inter-event distances, they only use a count of the number of point events within successive distance bands. This represents data aggregation and information loss. Secondly, and perhaps more significantly, K-functions are based on a cumulative count of point events with distance. This feature raises the possibility that the investigation of pattern at different scales is compromised by the dependency of any one count to previous counts. This paper proposes a new approach to the analysis of spatial point patterns based upon survival analysis. Although typically used in the temporal domain, there is no reason why survival analysis cannot be applied to any positively-valued, continuous variable as well as time. In this paper, survival analysis is applied to the inter-event distance measures of bivariate spatial point patterns to investigate the 'random labeling' hypothesis. It is shown, through both a controlled data situation and empirical epidemiological applications, that such an approach may be a very useful complement to K-function analysis.

Induction and characterization of Ph1 wheat mutants.

The cloning of genes for complex traits in polyploid plants that possess large genomes, such as hexaploid wheat, requires an efficient strategy. We present here one such strategy focusing on the homologous pairing suppressor (Ph1) locus of wheat. This locus has been shown to affect both premeiotic and meiotic processes, possibly suggesting a complex control. The strategy combined the identification of lines carrying specific deletions using multiplex PCR screening of fast-neutron irradiated wheat populations with the approach of physically mapping the region in the rice genome equivalent to the deletion to reveal its gene content. As a result, we have located the Ph1 factor controlling the euploid-like level of homologous chromosome pairing to the region between two loci (Xrgc846 and Xpsr150A). These loci are located within 400 kb of each other in the rice genome. By sequencing this region of the rice genome, it should now be possible to define the nature of this factor.

Homologous chromosome pairing in wheat.

Bread wheat is a hexaploid (AABBDD, 2n=6x=42) containing three related ancestral genomes, each having 7 chromosomes, giving 42 chromosomes in diploid cells. During meiosis true homologues are correctly associated in wild-type wheat, but a degree of association of related chromosomes (homoeologues) occurs in a mutant (ph1b). We show that the centromeres are associated in non-homologous pairs in all floral tissues studied, both in wild-type wheat and the ph1b mutant. The non-homologous centromere associations then become homologous premeiotically in wild-type wheat in both meiocytes and the tapetal cells, but not in the mutant. In wild-type wheat, the homologues are colocalised along their length at this stage, but the telomeres remain distinct. A single telomere cluster (bouquet) is formed in the meiocytes only by the onset of leptotene. The sub-telomeric regions of the homologues associate as the telomere cluster forms. The homologous associations at the telomeres and centromeres are maintained through meiotic prophase, although, during leptotene, the two homologues and also the sister chromatids within each homologue are separate along the rest of their length. As meiosis progresses, first the sister chromatids and then the homologues associate intimately. In wild-type wheat, first the centromere grouping, then the bouquet disperse by the end of zygotene.

Tributyltin triggers apoptosis in trout hepatocytes: the role of Ca2+, protein kinase C and proteases.

The purpose of the present study was to study the mechanisms involved in the induction of apoptosis and by tributyltin (TBT) in rainbow trout hepatocytes, and to examine the role of intracellular Ca2+, protein kinase C (PKC) and proteases in the apoptotic process. The intracellular Ca2+ chelator BAPTA-AM has a suppressive effect on TBT-mediated apoptosis. However, exposure to the ionophore A23187 is not sufficient to induce apoptosis in trout hepatocytes. The results obtained also show that TBT stimulates PKC gamma and delta translocation from cytosol to the plasma membrane in trout hepatocytes after 30 min of exposure. However, PKC gamma translocation is down-regulated after 90 min of treatment. The addition of protein kinase inhibitors (staurosporine and H-7) not only fails to inhibit apoptosis induced by TBT, but also leads to enhancement of DNA fragmentation. These inhibitors also afford a remarkable protection against the loss of plasma membrane integrity caused by TBT exposure. PMA, a direct activator of PKC, fails to stimulate DNA fragmentation. In addition, Z-VAD.FMK is an extremely potent inhibitor of TBT-induced apoptosis in trout hepatocytes, indicating that the activation of ICE-like proteases is a key event in this process. The cysteine protease inhibitor N-ethylmaleimide also prevented TBT-induced DNA fragmentation. Taken together, these data allow for the first time to suggest a mechanistic model of TBT-induced apoptosis. We propose that TBT could trigger apoptosis through a step involving Ca2+ efflux from the endoplasmic reticulum or other intracellular pools and by mechanisms involving cysteine proteases, such as calpains, as well as the phosphorylation status of apoptotic proteins such as Bcl-2 homologues.

Light-emitting diodes: a novel light source for phototherapy.

High intensity light-emitting diodes (LEDs) are being studied as possible light sources for the phototherapy of hyperbilirubinemic neonates. These power-efficient, low heat-producing light sources have the potential to deliver high intensity light of narrow wavelength band in the blue-green portion of the visible light spectrum, which overlaps the absorption spectrum of bilirubin (BR). We compared the efficacy between single LEDs of different color and then constructed a prototype phototherapy device using 300 blue LEDs. The efficacy of this device was compared with that of conventional phototherapy devices by measuring the in vitro photodegradation of BR in human serum albumin. When blue, blue-green, green, and white LEDs were compared, the blue light was the most effective in degrading BR by 28% of dark control, followed by blue-green (18% of control), and then white light (14% of control). Green light was the least effective (11% of control). The prototype device with three focused arrays, each with 100 blue LEDs, generated greater irradiance (> 200 microW.cm-2.nm-1) than any of the conventional devices tested. It also supported the greatest rate of BR photodegradation. We conclude that light from LEDs should be considered a more effective treatment for hyperbilirubinemia than light from presently used phototherapy devices. Furthermore, the unique characteristics of this light source may make it especially suitable for use in safe and lightweight home phototherapy devices.

Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines: comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices.

STUDY OBJECTIVES: To compare lung deposition of fenoterol or flunisolide administered from a novel, multidose inhalation device delivering liquid droplets (RESPIMAT; Boehringer Ingelheim Ltd; Bracknell, UK) or from conventional metered-dose inhalers (MDIs) with and without spacers. DESIGN: Two randomized, three-way crossover studies. SETTING: Clinical research laboratory. PARTICIPANTS: Healthy, nonsmoking volunteers. INTERVENTIONS: In one study, radiolabeled aerosols of fenoterol from the RESPIMAT device and from a conventional MDI with or without an Aerochamber spacer (Trudell Medical; London, Ontario Canada). In the second study, radiolabeled aerosols of flunisolide from a RESPIMAT device, from a RESPIMAT device modified by inclusion of a baffle/impactor in the mouthpiece, and from a conventional MDI with an Inhacort spacer (Boehringer Ingelheim; Ingelheim, Germany). MEASUREMENTS AND RESULTS: Assessment of the deposition of fenoterol or flunisolide in the lung and oropharynx using gamma scintigraphy. Safety was assessed based on reported adverse effects and spirometry (FEV1, FVC, and peak expiratory flow rate) to detect any paradoxical bronchoconstriction. The RESPIMAT device delivered significantly more fenoterol to the lungs than either an MDI alone or an MDI with Aerochamber (39.2% vs 11.0% and 9.9% of metered dose, respectively; p<0.01). Oropharyngeal deposition of fenoterol from the new device was lower than that from the MDI (37.1% vs 71.7%, respectively; p<0.01). The RESPIMAT device deposited significantly more flunisolide in the lungs compared with MDI plus spacer (44.6% vs 26.4%, respectively; p<0.01), while resulting in similar oropharyngeal deposition (26.2% vs 31.2%, respectively). Introduction of a baffle into the RESPIMAT system reduced lung deposition of flunisolide to 29.5%, and oropharyngeal deposition to 7.8% (p<0.01). CONCLUSION: The RESPIMAT device may prove to be an effective alternative to MDIs for the administration of inhaled bronchodilators and corticosteroids. The high lung deposition and low oropharyngeal deposition may lead to improved efficacy and tolerability of inhaled medications, especially corticosteroids.