bluuebunny/crossref_metadata_2025 huggingface dataset:
Innovator and generic cisplatin formulations: Comparison of renal toxicity
Authors: Sekine Ikuo , Kubota Kaoru , Tamura Yosuke , Asahina Hajime , Yamada Kazuhiko , Horinouchi Hidehito , Nokihara Hiroshi , Yamamoto Noboru , Tamura Tomohide
Published: October 2010

To compare the incidence and degree of renal toxicity associated with innovator and generic cisplatin formulations, increase in the serum creatinine (CRN) levels (mg/dL) and incidence of grade 2–3 CRN elevation during the first and all cycles of chemotherapy were retrospectively evaluated in patients treated with innovator (group 1, n = 296) and generic (group 2, n = 321) cisplatin formulations. There were no differences in the sex, age, performance status or number of chemotherapy cycles between groups 1 and 2. The median increases in CRN levels during the first cycle were 0.20 mg/dL regardless of the sex or group. There was no difference in the incidence of grade 2–3 CRN elevation between groups 1 and 2 among female or male patients. The median increases in CRN levels during all cycles were 0.2 (0–1.0) and 0.3 (0–1.8) in the female patients of groups 1 and 2, respectively (P = 0.68), and 0.3 (0–2.1) and 0.5 (0–3.6) in the male patients of groups 1 and 2, respectively (P < 0.001). Grade 2–3 CRN elevation was observed in 18.1% and 24.7% of the female patients in groups 1 and 2, respectively (P = 0.33), and 9.4% and 20.9% of the male patients in groups 1 and 2, respectively (P < 0.001). Renal toxicity was slightly more severe in patients treated with the generic cisplatin formulation than in those treated with the innovator formulation, especially among the male patients. (Cancer Sci 2011; 102: 162–165)
Costs of care for Crohn’s disease following the introduction of infliximab: a single‐centre UK experience
Authors: Sprakes M. B. , Ford A. C. , Suares N. C. , Warren L. , Greer D. , Donnellan C. F. , Jennings J. S. R. , Everett S. M. , Hamlin P. J.
Published: October 2010

Aliment Pharmacol Ther 2010; 32: 1357–1363

Background  Infliximab is effective for induction and maintenance of remission in patients with Crohn’s disease. There are few data, however, examining effect of infliximab therapy on management costs of Crohn's disease.

Aim  To assess Crohn's disease‐related costs of care and resource use in a single‐centre cohort of patients with Crohn's disease 12 months pre‐ and post‐infliximab therapy.

Methods  Data on 100 consecutive patients receiving infliximab were collected. Crohn's disease‐related resource use was collected 12 months pre‐ and post‐infliximab. National Health Service reference costs were applied to these data and the total Crohn's disease‐related health service costs per patient were calculated (£UK). The cost of infliximab therapy was not included in our analysis.

Results  Cost savings were demonstrated in all areas of Crohn's disease‐related resource use following infliximab therapy. Mean total Crohn's disease‐related cost reduction, 12 months following commencement of infliximab therapy, was £2750 per patient. Mean costs at 12 months post‐infliximab in responders were lower than in nonresponders (£1656 vs. £3608, P = 0.02). The number of hospitalizations was reduced. Requirements for examination under anaesthesia were also significantly decreased.

Conclusion  Infliximab use resulted in Crohn's disease‐related cost savings and hospital resource use, although this was not sufficient to cover the cost of therapy.
Desertification alters the response of vegetation to changes in precipitation
Authors: Verón Santiago R. , Paruelo José M.
Published: October 2010

1. Desertification is of critical concern because it may affect 40% of the global land area inhabited by more than 1 billion people. During the process of desertification, defined as land degradation in arid, semi‐arid and dry subhumid areas, drylands shift to a state of reduced biological productivity that may lead to widespread loss of human well‐being. Despite recent advances, we need a better understanding of the response of ecosystems to desertification to improve the assessment and monitoring of desertification.

2. We used a published physiognomic description, MODIS monthly NDVI data for 2000–2005 and rain gauge data to characterize the long‐term effects of degradation for an area of 128 000 ha located in western Patagonia.

3. We focused on three aspects of vegetation dynamics: radiation interception, precipitation use efficiency (PUE) and the sensitivity of vegetation to interannual changes in precipitation (i.e. the slope of the relationship between the above‐ground net primary productivity and precipitation, the precipitation marginal response, PMR). In particular, we analysed the response of PMR and PUE to long‐term changes in vegetation structure due to grazing.

4. On average, NDVI decreased by 28%, ranging between 35% (grass or grass–shrub steppes to semi‐deserts) and 22% (grass or grass‐shrub steppes to low cover grass steppes) suggesting that, in Patagonia, desertification may imply a reduction in the above‐ground net primary productivity.

5. Additionally, PMR and PUE captured the functional modifications associated with vegetation structure caused by desertification. In general, grass and grass‐shrub steppes had the highest average PUE and PMR. Shrub steppes and semi‐deserts had the lowest PMR and PUE. These results support the hypothesis that PUE is more sensitive to changes in total plant cover and PMR to changes in plant functional type composition.

6.
Synthesis and applications. Our results indicate that the precipitation marginal response could complement current desertification assessments based only on precipitation use efficiency thereby improving our ability to monitor desertification. Enhanced monitoring programmes could provide an early warning signal for the onset of desertification allowing for timely management action.
Predation intensifies parasite exposure in a salmonid food chain
Authors: Connors Brendan M. , Hargreaves N. Brent , Jones Simon R. M. , Dill Lawrence M.
Published: October 2010

1. Parasites can influence ecosystem structure, function and dynamics by mediating predator–prey interactions. Recurrent infestations of the salmon louse Lepeophtheirus salmonis associated with salmon aquaculture may mediate interactions between juvenile salmonids. Louse infection increases pink salmon Oncorhynchus gorbuscha susceptibility to predation, resulting in the trophic transmission of lice (with an adult male bias) to coho salmon O. kisutch predators. While experimental evidence is accumulating, the extent to which trophic transmission structures the distribution of lice among juvenile salmon in the wild is unknown.

2. We used a hierarchical modelling approach to examine the abundance and sex ratio of salmon lice on juvenile pink and coho salmon, collected from a region of salmon aquaculture during sea louse infestations, to test the hypothesis that trophic transmission of salmon lice increases infection on coho that feed upon infected pink salmon prey.

3. As predicted, coho had higher adult and pre‐adult louse abundance than their pink salmon prey, and louse abundance was more adult male biased on predators than sympatric prey. We estimate that trophic transmission accounts for 53–67% of pre‐adult and adult louse infection on coho.

4.
 Synthesis and applications. These results suggest that, by evading predation, salmon lice can accumulate up juvenile salmon food webs. Predators, such as coho, can experience a two‐ to threefold increase in parasite exposure through predation on infected prey than would otherwise occur through passive exposure to infective larvae. Thus, predation may intensify parasite exposure and undermine the protection to ectoparasites conferred by the larger body size of predators. For larger predatory wild juvenile salmon, the risk of louse transmission from farmed salmon may therefore be greater than previously appreciated. These findings argue for an ecosystem perspective in monitoring and managing the marine environment in areas of intensive salmon aquaculture that includes the productivity and ecological interactions of all salmonid species.
Biological characteristics and pathogenicity of a highly pathogenic Shewanella marisflavi infecting sea cucumber, Apostichopus japonicus
Authors: Li H , Qiao G , Li Q , Zhou W , Won K M , Xu D‐H , Park S‐I
Published: October 2010

Shewanella marisflavi isolate AP629 is described as a novel pathogen of sea cucumber. The LD50 values (14 days) in sea cucumber, mice and swordtail fish were 3.89 × 106, 6.80 × 104 and 4.85 × 104 CFU g−1 body weight, respectively. Studies on S. marisflavi were conducted, including morphology, physiological and biochemical characteristics, haemolysis, whole‐cell protein and 16S rDNA gene sequence. Colonies of S. marisflavi appeared faint red on marine agar and green on thiosulphate–citrate–bile salt–sucrose media. Shewanella marisflavi had polar flagella. The cells were Gram‐negative, oxidase‐ and catalase‐positive and not sensitive to O/129. The bacterium exhibited β‐haemolysis on sheep blood agar and produced H2S. Shewanella marisflavi survived and grew at 4–35 °C, pH 6.0–9.2 and in the presence of 0–8% NaCl. The whole‐cell proteins included 13 discrete bands, and proteins of molecular weight 87, 44 and 39 kDa were found in all five strains of Shewanella spp. The difference in 16S rDNA gene sequences in S. marisflavi was at the 446 bp site: S. marisflavi (KCCM 41822) – G, isolate AP629 – A. This is the first report that Shewanella is pathogenic to sea cucumber.
Lack of evidence for vertical transmission of SAV 3 using gametes of Atlantic salmon, Salmo salar L., exposed by natural and experimental routes
Authors: Kongtorp R T , Stene A , Andreassen P A , Aspehaug V , Graham D A , Lyngstad T M , Olsen A B , Olsen R S , Sandberg M , Santi N , Wallace C , Breck O
Published: October 2010

Pancreas disease (PD) is an important cause of losses in farmed salmonids in Norway, the United Kingdom and Ireland. As the spread of salmonid alphavirus (SAV), the causal agent, to naïve populations is of major concern to the farming industry, it is important to uncover the transmission routes of the virus. This study was conducted to investigate the potential for vertical transmission of SAV subtype 3. Progeny of broodstock with signs of late‐stage PD and persistent RT‐PCR signals for SAV were followed from fertilization to smoltification in an experimental facility. Fertilized ova were either not disinfected or taken through one of three different disinfection regimes. Also, ova and milt from uninfected broodfish from a different population were exposed to a cell‐cultured strain of SAV 3 immediately before fertilization to simulate a viraemic phase in parent fish. A group of uninfected controls were also included in the study. Fertilized ova from bath exposed and negative control groups were double disinfected. Following fertilization, experimental fish went through a normal freshwater phase. However, fry were stressed at first feeding to enhance replication of possibly latent virus. Smoltification was induced by an artificial light regime, and experimental fish were followed to the late smoltification phase. Selected samples were investigated by real‐time RT‐PCR for SAV, by histology for evidence of PD and by serology for neutralising antibodies against SAV. All analysed samples of progeny were negative. This result shows that SAV 3 is not readily transmitted vertically from parents to offspring. Additional negative PCR results from salmon sampled in commercial hatcheries support these findings. Also, recent studies have shown that risk factors for the horizontal transmission route explain the vast majority of PD outbreaks in Norway. It is concluded that if it happens at all, vertical transmission is of minor importance in the spread of SAV 3.
Evidence of extreme habitat stability in a Southeast Asian biodiversity hotspot based on the evolutionary analysis of neotenic net‐winged beetles
Authors: MALOHLAVA V. , BOCAK L.
Published: October 2010

The diversification of neotenic beetle lineages has not been studied, despite the potential for defining biodiversity hotspots and elucidating the history of regional faunas. Additionally, neotenics may provide insight into the process of speciation in small populations with extremely low dispersal ability and a limited range. Here, we used two rDNA and three mtDNA markers to investigate the phylogeny of Scarelus, a neotenic lineage endemic to Southeast Asian rainforests. Most genetic differentiation was associated with Palaeogene geographical divisions, which remain distinct despite temporary connections. Dispersal events were rare, with only two inferred for Scarelus: from Borneo to the Philippines 28.3 million years ago (Ma) and from Sumatra to Java 13.9 Ma. We suggest that speciation resulted from allopatric range fragmentation, and Scarelus diversified readily when conditions were favourable; in this case, at different times in the eastern (19.3–39.1 Ma) and western (3.5–13.9 Ma) parts of Sundaland. The observed strong phenotypic similarity was preserved under speciation through complete allopatry. Neotenic Lycidae have survived for a long time in very stable habitats, and extremely low dispersal activity has not limited their persistence; however, the long‐term diversification rate of neotenics is low and diversification is nonexistent under stable conditions. The modern ranges of neotenic lineages are indicative of ancient rainforest refugia and may be used in biodiversity conservation management. Most neotenics are at risk of extinction because of their small ranges and a low dispersal potential.
Claw histopathology and parasitic load in natural cases of canine leishmaniosis associated with Leishmania infantum
Authors: Koutinas Alexander F. , Carlotti Didier N. , Koutinas Christos , Papadogiannakis Emmanouil I. , Spanakos Gregory K. , Saridomichelakis Manolis N.
Published: October 2010

Histological lesions and the presence of Leishmania spp. amastigotes in claw tissues were investigated in 40 dogs with leishmaniosis, with (16/40 – group A) or without (24/40 – group B) generalized onychogryphosis. Following euthanasia, the entire third phalanx with intact claw was amputated, formalin fixed, decalcified in a formic acid solution, embedded in paraffin, sectioned longitudinally and stained with haematoxylin and eosin, and acid orcein‐Giemsa. Nested polymerase chain reaction (PCR) was used for the detection of Leishmania amastigotes. Lichenoid mononuclear infiltration (all dogs in group A, 21 of 24 dogs in group B), basal keratinocyte vacuolation (nine of 16 dogs in group A, 15 of 24 dogs in group B) and dermoepidermal clefting (13 of 16 dogs in group A, 18 of 24 dogs in group B) were the most prominent histopathological findings. There was no difference in the frequency and severity of these lesions between the two groups. Leishmania amastigotes could not be visualized in the dermis of any of the H&E sections, but their presence was demonstrated by nested PCR in three of 16 dogs in group A and two of 24 dogs in group B. However, the frequency of positive nested PCRs was not significantly different between the two groups. In conclusion, claw histopathology in symptomatic dogs with leishmaniosis, either with or without onychogryphosis is mainly characterized by mononuclear lichenoid dermatitis with or without interface dermatitis and dermoepidermal clefting, and is not accompanied by substantial local parasitism.
Strategies for prevention of scars: what can we learn from fetal skin?
Authors: Namazi Mohammad Reza , Fallahzadeh Mohammad Kazem , Schwartz Robert A.
Published: October 2010

Fetal wound healing occurs rapidly and without scar formation early in gestation. Studying the mechanisms of scarless repair can lead to novel scar‐preventive approaches. In fetal wounds, collagen is deposited early and is fine and reticular with less cross‐linking. Several important differences of fetal vs. postgestational wound‐healing response have been determined, such as the presence of less inflammation, higher hyaluronic acid concentration and a greater ratio of collagen type III to type I. Compared with typical wounds, there are also altered ratios of signaling molecules, such as higher ratios of transforming growth factor (TGF)‐β3 to TGF‐β1 and ‐β2, and matrix metalloproteinases to tissue inhibitors of metalloproteinases. Furthermore, fetal fibroblasts do not exhibit TGF‐β1‐induced collagen production compared with their mature counterparts. Patterning genes (homeobox genes) involved in organogenesis are more active in the fetal period and are believed to be the “first domino” in the fetal cutaneous wound repair regulatory cascade. The recommended scar‐preventive agents, such as Scarguard MD®, silicone gel and sheet, Seprafilm® Bioresorbable Membrane, topical hyaluronan, onion extract, oral tamoxifen and 585‐nm pulsed dye laser are reviewed in this study. Despite the lack of supporting evidence, there is a widespread false presumption that the acceleration of healing with the widely assumed scar‐preventive commercial agents is associated with decreased scar formation. Humans are erroneously inclined to make a negative correlation between the healing rate and the degree of scar formation, while such a correlation does not exist in reality. Despite the importance of scar prevention, no FDA‐approved therapy for this purpose is available in the 21st century, which reflects the important challenges, such as the presence of redundant pathways, that these approaches are facing.
Human opioid μ‐receptor A118G polymorphism may protect against central pruritus by epidural morphine for post‐cesarean analgesia
Authors: TSAI F.‐F. , FAN S.‐Z. , YANG Y.‐M. , CHIEN K.‐L. , SU Y.‐N. , CHEN L.‐K.
Published: October 2010

Background:Intrathecal or epidural morphine used for post‐operative analgesia frequently induces central type pruritus. The purpose of this study was to investigate the association between the severity of central type pruritus induced by epidural morphine for post‐cesarean analgesia and the A118G polymorphism of the human μ‐opioid receptor gene (OPRM1).

Methods:Pregnant women (212) received pure epidural morphine (2 mg) twice per day for post‐cesarean analgesia. Blood samples were collected and sequenced with high‐resolution melting analysis to detect three different genotypes ofOPRM1(AA, AG and GG). We interviewed all candidates 24 h post‐operatively to record the clinical phenotype with subjective complaints and objective observations.

Results:The genotyping revealed that 99 women (46.7%) were AA, 88 (41.5%) were AG and 25 (11.8%) were GG. Sixty‐two of 212 women suffered from significant pruritus (29.2%), and 150 of 212 women had non‐significant pruritus (70.8%). In genotype AA, 33 patients (53.2%) experienced significant pruritus, 26 (41.9%) in genotype AG and 3 (4.8%) in genotype GG. The G allele was a statistically independent protective factor for individuals developing pruritus, and the multivariate‐adjusted odds ratio was 0.27. There was a trend for progressively decreasing severity scores among the three groups, with the lowest severity score (0.72) for pruritus in the GG group.

Conclusions:The incidence of significant pruritus in the recessive type (GG) was significantly lower compared with the dominant types (AA+AG). The recessive G allele in the A118G polymorphism may have protective effects against significant pruritus after epidural morphine for post‐cesarean analgesia.
Ischaemic pre‐conditioning means an increased adenosine metabolism with decreased glycolytic flow in ischaemic pig myocardium
Authors: ÅBERG A. M. , AHLSTRÖM K. , ABRAHAMSSON P. , WALDENSTRÖM A. , RONQUIST G. , HAUCK P. , JOHANSSON G. , BIBER B. , HANEY M.
Published: October 2010

Background: Ischaemic pre‐conditioning (IP) is a potent protective mechanism for limiting the myocardial damage due to ischaemia. It is not fully known as to how IP protects. The metabolism of adenosine may be an important mechanistic component. We study the role of adenosine turnover together with glycolytic flow in ischaemic myocardium subjected to IP.

Methods: An acute myocardial ischaemia pig model was used, with microdialysis sampling of some metabolites (lactate, adenosine, glucose, glycerol, taurine) of ischaemic myocardium. An IP group was compared with a control group before and during a prolonged ischaemia. 14C‐labelled adenosine and glucose were infused through microdialysis probes, and lactate, 14C‐labelled lactate, glucose, taurine and glycerol were analysed in the effluent. The glycogen content in myocardial biopsies was determined.

Results: The 14C‐adenosine metabolism was higher as there was a higher production of 14C‐lactate in IP animals compared with the controls. The glycolytic flow, measured as myocardial lactate formation, was retarded during prolonged ischaemia in IP animals. Myocardial free glucose and glycogen content decreased during the prolonged ischaemia in both groups, with higher free glucose in the IP group. We confirmed the protective effects of IP with lower myocardial concentrations of markers for cellular damage (glycerol).

Conclusions: This association between increased adenosine turnover and decreased glycolytic flow during prolonged ischaemia in response to IP can possibly be explained by the competitive effect for the metabolites from both glucose and adenosine metabolism for entering glycolysis. We conclude that this study provides support for an energy‐metabolic explanation for the protective mechanisms of IP.
Perisciatic infusion of ropivacaine and analgesia after hallux valgus repair
Authors: ZARIC D. , JØRGENSEN B. G. , LAIGAARD F. , CHRISTIANSEN J. , BURCHARD E.
Published: October 2010

Background: Moderate to severe pain after hallux valgus repair can be successfully treated with a continuous popliteal sciatic nerve block in ambulatory patients. Different anesthesiologists use various infusion rates for this purpose. The aim of this study was to compare the analgesic efficacy of two infusion rates of ropivacaine 2 mg/ml: 5 and 8 ml/h.

Methods: Forty ambulatory patients who underwent chevron osteotomy for hallux valgus were randomized to receive perisciatic infusion of ropivacaine 2 mg/ml at a rate of either 5 ml/h (5 ml group) or 8 ml/h (8 ml group). All patients received standard general anesthesia for surgery after the sciatic popliteal and the single‐shot saphenus nerve blocks were performed. Verbal rating scale (VRS) scores for pain, sleep disturbances, opioid consumption and side effects were monitored for 3 post‐operative days.

Results: No significant difference was found in the primary end point worst pain on the first post‐operative day with VRS scores of 2.5 (0–8) vs. 5.5 (0–10) for the 5 and 8 ml/h groups, respectively (P=0.53). Post‐operative pain was satisfactory in both groups, with an average VRS score ≤4 for 60–62 h.

Conclusion: We found no significant difference in the analgesic effect between two perisciatic infusion rates of ropivacaine 2 mg/ml (5 vs. 8 ml/h) in ambulatory patients who underwent chevron osteotomy.
Cytoplasmic feminizing elements in a two‐population model: infection dynamics, gene flow modification, and the spread of autosomal suppressors
Authors: KOBAYASHI Y. , TELSCHOW A.
Published: October 2010

We investigate the dynamics of a cytoplasmic parasitic element with feminizing effect in a two‐population model. We assume that the host species has a ZZ/ZW sex determination system. Our analysis reveals that the feminizer and the W chromosome can stably coexist by dominating different populations if the transmission rate differs significantly between the populations and migration is sufficiently weak. In the equilibrium of coexistence, genetic influx at any host autosomal locus is strongly enhanced in the population where infection is prevalent but not modified in the other population. We further explore conditions for the spread of autosomal suppressor genes that reduce transmission of feminizing elements to the cost of host viability, and compute their equilibrium frequencies. Our results confirm the hypothesis that selfish genetic elements convert infected host populations into genetic sinks, thereby restricting the spread of transmission suppressors.
Phenotypic plasticity in sexual communication signal of a noctuid moth
Authors: GROOT A. T. , CLAβEN A. , STAUDACHER H. , SCHAL C. , HECKEL D. G.
Published: October 2010

Variability within sex pheromone signalling systems is generally believed to be low because of strong stabilizing selection; yet the noctuid moth Heliothis subflexa (Hs) shows significant intraspecific variation. One possible explanation is that females may alter their sex pheromone blend depending on prevailing olfactory cues in the habitat, which we termed the ‘experience hypothesis’. This could be adaptive if Hs females experiencing the pheromone of another species, Heliothis virescens (Hv), responded to reduce the frequency of heterospecific matings. We exposed Hs females to no pheromone, Hs pheromone or Hv pheromone in the first 3 days of their adult lives. Hs females in the latter treatment produced significantly more of the acetate Z11‐16:OAc, which inhibits the attraction of Hv males. To our knowledge, this is the first study showing adaptive phenotypic plasticity in a moth sex pheromone and suggests that behavioural differentiation may precede genetic divergence in the sexual signals of moths.
Developmental outcomes following major surgery: What does the literature say?
Authors: Walker Karen , Badawi Nadia , Holland Andrew JA , Halliday Robert
Published: October 2010

Relative to the wealth of information in the medical literature regarding developmental outcome for infants who have had cardiac surgery available, few studies specifically detail how those who have undergone major surgery grow and develop. The few published studies tend to be disease specific, making their results difficult to translate to a more general setting. As mortality for most infants who require surgery in infancy continues to decrease, the focus for researchers and clinicians should be on how these children will grow and develop. As parents realise that their infant will survive, this becomes their next major concern. The most common conditions requiring early major surgery have been reviewed in relation to data on infant developmental outcomes.
Universal post‐arrival screening for child refugees in Australia: Isn't it time?
Authors: Patradoon‐Ho Patrick S , Ambler Rosemary W
Published: October 2010

It is known that the refugee population in Australia is at risk of tuberculosis (TB) and children with TB infection can develop active disease with devastating consequence. Currently, in New South Wales (NSW) and possibly other Australian States and Territories, there are different and complex health‐screening pathways for newly arrived refugees. This is compounded by various factors, such as social and language difficulties for refugees to access healthcare and limited pre‐embarkation screening. In this Viewpoint article, we present a child refugee in Australia with TB and use this case to reason why a universal post‐arrival health screening programme should be established.
Feedback modulation of transduction by calcium in a spider mechanoreceptor
Authors: Höger Ulli , Torkkeli Päivi H. , French Andrew S.
Published: October 2010

Calcium ions play important roles in the adaptation of auditory hair cells, and there is evidence that they are involved in modifying the sensitivity and adaptation of a variety of vertebrate and invertebrate mechanoreceptors. However, there is little direct evidence concerning the concentration changes, signaling pathways or ultimate effects of these proposed modulatory mechanisms. We measured receptor potential, receptor current and action potentials intracellularly during mechanotransduction in a group of sensory neurons of the spider Cupiennius salei, which possesses low‐voltage‐activated calcium channels. Simultaneously, we elevated intracellular [Ca2+] by UV light release from cage molecules, and observed increases in [Ca2+] as changes in calcium‐sensitive dye fluorescence. Increases of 10–15% in [Ca2+] caused reductions of approximately 40% in receptor potential and approximately 20% in receptor current. Mechanically evoked action potential firing caused much larger increases in [Ca2+], and the firing rate fell as [Ca2+] rose during mechanical stimulation. Release of caged calcium just before mechanical stimulation significantly reduced peak firing. Dose–response measurements suggested that the binding of one or two intracellular calcium ions per channel reduces the probability of the mechanotransduction channel being open. Our data indicate that calcium regulates sensitivity in these mechanoreceptor neurons by negative feedback from action potentials onto transduction channels.
Sight and sound of actions share a common neural network
Authors: Giusti M. A. , Bozzacchi C. , Pizzamiglio L. , Di Russo F.
Published: October 2010

The mirror‐neuron system (MNS) connects sensory information that describes an action with a motor plan for performing that action. Recently, studies using the repetition‐suppression paradigm have shown that strong activation occurs in the left premotor and superior temporal areas in response to action‐related, but not non‐action‐related, stimuli. However, few studies have investigated the mirror system by using event‐related potentials (ERPs) and employing more than one sensory modality in the same sample. In the present study, we compared ERPs that occurred in response to visual and auditory action/non‐action‐related stimuli to search for evidence of overlapping activations for the two modalities. The results confirmed previous studies that investigated auditory MNS and extended these studies by showing that similar activity existed for the visual modality. Furthermore, we confirmed that the responses to action‐ and non‐action‐related stimuli were distinct by demonstrating that, in the case of action‐related stimuli, activity was restricted mainly to the left hemisphere, whereas for non‐action‐related stimuli, activity tended to be more bilateral. The time course of ERP brain sources showed a clear sequence of events that subtended the processing of action‐related stimuli. This activity seemed to occur in the left temporal lobe and, in agreement with findings from previous studies of the mirror‐neuron network, the information involved appeared to be conveyed subsequently to the premotor area. The left temporo‐parietal activity observed following a delay might reflect processing associated with stimulus‐related motor preparation.
At the limbic–motor interface: disconnection of basolateral amygdala from nucleus accumbens core and shell reveals dissociable components of incentive motivation
Authors: Shiflett Michael W. , Balleine Bernard W.
Published: October 2010

Although it has long been hypothesized that the nucleus accumbens (NAc) acts as an interface between limbic and motor regions, direct evidence for this modulatory role on behavior is lacking. Using a disconnection procedure in rats, we found that basolateral amygdala (BLA) input to the core and medial shell of the NAc separately mediate two distinct incentive processes controlling the performance of goal‐directed instrumental actions, respectively: (i) the sensitivity of instrumental responding to changes in the experienced value of the goal or outcome, produced by specific satiety‐induced outcome devaluation; and (ii) the effect of reward‐related cues on action selection, observed in outcome‐specific Pavlovian–instrumental transfer. These results reveal, therefore, that dissociable neural circuits involving BLA inputs to the NAc core and medial shell mediate distinct components of the incentive motivational processes controlling choice and decision‐making in instrumental conditioning.
Evidence for trans‐generational medication in nature
Authors: Lefèvre Thierry , Oliver Lindsay , Hunter Mark D. , De Roode Jacobus C.
Published: October 2010

Ecology Letters(2010) 13: 1485–1493

Parasites pose a serious threat to host fitness, and natural selection should favour host traits that reduce infection or disease symptoms. Here, we provide the first evidence of trans‐generational medication, in which animals actively use medicine to mitigate disease in their offspring. We studied monarch butterflies and their virulent protozoan parasites, and found that neither caterpillars nor adult butterflies could cure themselves of disease. Instead, adult butterflies preferentially laid their eggs on toxic plants that reduced parasite growth and disease in their offspring caterpillars. It has often been suggested that sick animals may use medication to cure themselves of disease, but evidence for the use of medication in nature has so far been scarce. Our results provide evidence that infected animals may indeed use medicine as a defence against parasites, and that such medication may target an individual’s offspring rather than the individual itself.
Glucose control and outcome in patients with stable diabetes and previous coronary, cerebrovascular or peripheral artery disease. Findings from the FRENA Registry
Authors: Camafort M. , Álvarez‐Rodríguez L. R. , Muñoz‐Torrero J. F. S. , Sahuquillo J. C. , López‐Jiménez L. , Coll R. , Monreal M. ,   the FRENA Investigators
Published: October 2010

Diabet. Med. 28, 73–80 (2011)

Aim  The aim of this study was to address the controversy over the influence of intensive glucose control on the risk for cardiovascular events in patients with Type 2 diabetes.

Methods  FRENA is an ongoing registry of stable outpatients with symptomatic coronary artery disease, cerebrovascular disease or peripheral artery disease. We compared the incidence of subsequent ischaemic events (myocardial infarction, stroke or critical limb ischaemia) in patients with Type 2 diabetes and mean HbA1c levels < 7.0% (< 53 mmol/mol) vs. those with HbA1c levels > 7.0% (> 53 mmol/mol).

Results  Of 974 patients with Type 2 diabetes, 480 (49%) had mean HbA1c levels < 7% (< 53 mmol/mol). Over a mean follow‐up of 14 months, 126 patients (13%) had subsequent ischaemic events: myocardial infarction (43), stroke (29) and critical limb ischaemia (64). The incidence of subsequent ischaemic events was significantly lower in patients with mean HbA1c levels < 7.0% (< 53 mmol/mol) than in those with HbA1c levels > 7.0% (> 53 mmol/mol) (8.6 vs. 14 per 100 patient‐years; rate ratio 0.6; 95% CI 0.4–0.9). These differences persisted after adjusting for potential confounders. However, this better outcome was only found in patients presenting with coronary artery disease (rate ratio 0.4; 95% CI 0.2–0.8), not in those with cerebrovascular disease (rate ratio 0.9; 95% CI 0.4–2.0) or peripheral artery disease (rate ratio 0.8; 95% CI 0.5–1.3). Patients with mean HbA1c levels < 7.0% (< 53 mmol/mol) also had a lower mortality (rate ratio 0.6; 95% CI 0.3–0.99).

Conclusions  In secondary prevention, patients with diabetes and HbA1c levels < 7.0% (< 53 mmol/mol) had a lower incidence of subsequent ischaemic events and a lower mortality than those with HbA1c levels > 7.0% (> 53 mmol/mol). These differences appeared only in patients with coronary artery disease.
Characterizing sudden death and dead‐in‐bed syndrome in Type 1 diabetes: analysis from two childhood‐onset Type 1 diabetes registries
Authors: Secrest A. M. , Becker D. J. , Kelsey S. F. , LaPorte R. E. , Orchard T. J.
Published: October 2010

Diabet. Med. 28, 293–300 (2011)

Aims  Type 1 diabetes mellitus increases the risk for sudden unexplained death, generating concern that diabetes processes and/or treatments underlie these deaths. Young (< 50 years) and otherwise healthy patients who are found dead in bed have been classified as experiencing ‘dead‐in‐bed’ syndrome.

Methods  We thus identified all unwitnessed deaths in two related registries (the Children’s Hospital of Pittsburgh and Allegheny County) yielding 1319 persons with childhood‐onset (age < 18 years) Type 1 diabetes diagnosed between 1965 and 1979. Cause of death was determined by a Mortality Classification Committee (MCC) of at least two physician epidemiologists, based on the death certificate and additional records surrounding the death.

Results  Of the 329 participants who had died, the Mortality Classification Committee has so far reviewed and assigned a final cause of death to 255 (78%). Nineteen (8%) of these were sudden unexplained deaths (13 male) and seven met dead‐in‐bed criteria. The Mortality Classification Committee adjudicated cause of death in the seven dead‐in‐bed persons as: diabetic coma (n = 4), unknown (n = 2) and cardiomyopathy (n = 1, found on autopsy). The three dead‐in‐bed individuals who participated in a clinical study had higher HbA1c, lower BMI and higher daily insulin dose compared with both those dying from other causes and those surviving.

Conclusions  Sudden unexplained death in Type 1 diabetes seems to be increased 10‐fold and associated with male sex, while dead‐in‐bed individuals have a high HbA1c and insulin dose and low BMI. Although sample size is too small for definitive conclusions, these results suggest specific sex and metabolic factors predispose to sudden unexplained death and dead‐in‐bed death.
SOCIO‐ECONOMIC STUDIES ON SUICIDE: A SURVEY
Authors: Chen Joe , Choi Yun Jeong , Mori Kohta , Sawada Yasuyuki , Sugano Saki
Published: October 2010

Abstract In this paper, we review economic theories and empirical studies on the socio‐economic aspects of suicide. Through our survey, we would like to emphasize the importance of studying suicide by employing a ‘rational’ approach that complements the medical perspective on suicide. We first introduce major economic theories of suicide and then present a summary of a variety of empirical studies from the socio‐economic perspective. To shed light on the mixed empirical evidence, we employ a meta‐regression method to investigate how the existing empirical results vary. We have identified a publication bias, not highlighted previously, in the existing literature with respect to several commonly employed socio‐economic factors. Several characteristics of existing studies have been identified as influencing the qualitative outcome. We then discuss the recent developments in economic studies on suicide, on the basis of the authors’ ongoing project on suicide. In the concluding section, we point out some issues for further studies.
Growing Pains: The Developing Relationship of Animal Welfare Standards and the World Trade Rules
Authors: Cook Kate , Bowles David
Published: October 2010

This article looks at the reasons why animal welfare is likely to be an important issue in trade disputes in the future and in the clarification of policy on the World Trade Organization's (WTO's) Article XX exemptions. Trade disputes that are based on animal welfare issues, such as product differentiation, have historically been settled before discussion at the WTO. The growth in legislation based on animal welfare has increased the likelihood of a dispute being considered by a panel. A dispute is likely to look at cultural differences between countries, which is an area that the WTO is increasingly looking at. It is probable that any dispute will see further clarification on the use and limits of the Article XX exemptions and these are explored in the article.
Assessment of Genetic Ancestry and Population Substructure in Costa Rica by Analysis of Individuals with a Familial History of Mental Disorder
Authors: Segura‐Wang Maia , Raventós Henriette , Escamilla Michael , Barrantes Ramiro
Published: October 2010

The population of Costa Rica has been considered valuable for locating susceptibility genes of complex disorders because of historical events and a gradual admixture process. We present an assessment of 426 unrelated individuals with a familial history of mental disorder and with ancestors born in the Central Valley, genotyped at 730 microsatellites to evaluate genetic diversity, ancestry, and substructure at the general and regional population levels using quantitative methods. Low population substructure was found. Estimated mean ancestry proportions were 54%, 32%, and 13% for European, Amerindian, and African components, respectively, with some regional variation. The FSTvalues obtained confirm the largest genetic similarity to Europeans. Subdivision of the Amerindians into individual populations revealed strong similarity to Chibchan groups. Analysis of the African ancestry showed high similarity to West and Central African populations. Gene ancestries from other African areas were also detected, probably resulting from ancestral admixture within Africa prior to colonial times. Our analyses show, in an ethnohistorical‐genetic context, that gene flow and admixture are important components of Costa Rican population history. The results confirm the need to consider the particular regional genetic structure, the effects of genetic drift and the ancestry when designing and interpreting investigations of genetic traits in this population.
Analysis of a commercial dimethyl‐sulfoxide‐stabilized frozen canine platelet concentrate by turbidimetric aggregometry
Authors: Guillaumin Julien , Jandrey Karl E. , Norris Jeffrey W. , Tablin Fern
Published: October 2010

Objectives –To assess platelet function of a commercial dimethyl‐sulfoxide (DMSO)‐stabilized frozen platelet concentrate (PC) using turbidimetric aggregometry.

Design –In vitro analysis.

Setting –Research laboratory in a school of veterinary medicine.

Animals –Five units of frozen PC in 6% DMSO were studied. Fresh platelet‐rich plasma (PRP), with and without 6% DMSO, from 6 healthy dogs were used as controls.

Interventions –Turbidimetric platelet aggregation was measured after initiation of platelet aggregation by addition of adenosine diphosphate (ADP), collagen, or thrombin at concentrations of 30 μM, 20 μg/mL, and 0.5 U/mL, respectively. Measures were performed at thaw and repeated 2 hours after thaw for the frozen PC.

Measurements and Main Results –Compared with PRP, the frozen PC showed decreased aggregation in response to thrombin (amplitude of 84% versus 25%,P=0.01), and collagen (amplitude of 13% versus 3%,P=0.05) but not ADP (6.5% versus 18%,P=0.2). Compared with frozen PC at thaw, the frozen PC at 2 hours after thaw showed decreased aggregation in response to thrombin, collagen, and ADP (P<0.05). There was no difference in aggregation between PRP in 6% DMSO and frozen PC.

Conclusions –These in vitro data suggest there is a decrease in platelet response to agonists associated with the freeze‐thaw process in the commercially available 6% DMSO canine frozen PC.
Anaphylaxis and systemic inflammatory response syndrome induced by inadvertent intravenous administration of mare's milk in a neonatal foal
Authors: Alcott Cody J. , Wong David M.
Published: October 2010

Objective –To describe the diagnostic procedures, therapeutic management and successful outcome of a case of anaphylaxis induced by the inadvertent intravenous (IV) administration of mare's milk to a neonatal foal.

Case Summary –A 3‐day‐old Thoroughbred colt was presented for treatment of bilateral flexural limb deformities of the forelimbs. Because the foal was unable to ambulate initially, mare's milk was administered via nasoesophageal tube feedings during treatment of the musculoskeletal disorder. Anaphylaxis resulted after unintentional administration of a bolus of 150 mL of mare's milk through a jugular catheter. Aggressive therapy for anaphylaxis and careful monitoring resulted in the successful recovery of the foal after 9 days of intensive care.

New or Unique Information Provided –This case is the first published report to describe the effects of accidental IV administration of mare's milk to a neonatal foal. Medical errors are commonly reported in pediatric medicine; the intent of this report is to raise awareness of medical errors and student education in equine medicine as well as describe the therapy and outcome of anaphylaxis induced by IV administration of mare's milk in a neonatal foal.
Sleep Disturbances and Adverse Driving Events in a Predominantly Male Cohort of Active Older Drivers
Authors: Vaz Fragoso Carlos A. , Araujo Katy L.B. , Van Ness Peter H. , Marottoli Richard A.
Published: October 2010

OBJECTIVES: To evaluate the association between sleep disturbances and adverse driving events in active older drivers.

DESIGN: Longitudinal.

SETTING: Clinic and community sites in greater New Haven, Connecticut.

PARTICIPANTS: Four hundred thirty older persons (mean age 78.5, 84.9% male) who drove at least once a week.

MEASUREMENTS: Baseline measures included self‐reported driving patterns and sleep questionnaires (Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), and Sleep Apnea Clinical Score (SACS)). The primary outcome was an adverse driving event based on self‐report and driving records and categorized as a crash or traffic infraction (composite I) or as a crash, traffic infraction, near crash, or getting lost (composite II).

RESULTS: Participants reported driving a median of 17.0 miles per day, with 96.7% (416/430) driving daily or every other day. Although 26.0% (112/430) had insomnia (ISI≥8), 19.3% (83/430) had daytime drowsiness (ESS≥10), and 19.9% (84/422) had high sleep apnea risk (SACS>15), the median scores for the ISI, ESS, and SACS were normal at 3.0, 6.0, and 8.0, respectively, and only 5.1% reported drowsy driving. Over a period of up to 2 years, 24.9% (104/418) and 51.4% (215/418) of participants had a composite I and II driving event, respectively. In unadjusted and adjusted multivariable models, insomnia, daytime drowsiness, and high sleep apnea risk were not associated with a composite I or II driving event.

CONCLUSION: In a predominantly male cohort of active older drivers, sleep disturbances were mild and not associated with adverse driving events. Accordingly, and because older persons are known to self‐regulate driving practices, future studies should evaluate whether sleep disturbances are more important as a mechanism that underlies driving cessation rather than compromising driving safety.
Physician Consultation, Multidisciplinary Care, and 1‐Year Mortality in Medicare Recipients Hospitalized with Hip and Lower Extremity Injuries
Authors: Adams Annette L. , Schiff Melissa A. , Koepsell Thomas D. , Rivara Frederick P. , Leroux Brian G. , Becker Thomas M. , Hedges Jerris R.
Published: October 2010

OBJECTIVE:To determine whether routine surgeon consultation with medicine specialists and multidisciplinary care conferences—potentially modifiable hospital characteristics—are associated with lower 1‐year mortality in older adults with hip and lower extremity injuries.

DESIGN:Retrospective cohort study.

SETTING:Oregon hospitals.

PARTICIPANTS:Two thousand five hundred thirty‐eight Medicare recipients aged 67 and older hospitalized in Oregon hospitals in 2002 with hip or lower extremity injuries.

MEASUREMENTS:Demographic, injury, comorbidity, and survival information were gathered from Medicare records for 2000 to 2003. All Oregon hospitals with a qualifying case were surveyed using a structured telephone interview to collect information about routine surgeon consultations and multidisciplinary care conferences for older adult orthopedic patients. Multivariable generalized estimating equation models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between hospital characteristics and mortality.

RESULTS:After adjusting for age, injury severity, comorbid conditions, trauma center status, and hospital annual volume of patients with hip fracture, the relative odds of dying in the year after injury for inpatients treated in settings with routine surgeon consultation with medical staff was 0.69 (95% CI 0.57–0.83) compared with patients not treated in such settings. Inpatient treatment in settings with routine multidisciplinary care conferences did not significantly affect the relative odds of dying in the year after injury (OR=1.06, 95% CI=0.89–1.26).

CONCLUSION:Routine consultation by attending orthopedic surgeons with medicine or primary care specialists for Medicare inpatients is associated with better survival 1 year after injury.