Bilateral intracortical inhibition during unilateral motor preparation and sequence learning.

Motor sequence learning gradually quickens reaction time, suggesting that sequence learning alters motor preparation processes. Interestingly, evidence has shown that preparing sequence movements decreases short intracortical inhibition (SICI) in the contralateral motor cortex (M1), but also that sequence learning alters motor preparation processes in both the contralateral and ipsilateral M1s. Therefore, one possibility is that sequence learning alters the SICI decreases occurring during motor preparation in bilateral M1s. To examine this, two novel hypotheses were tested: unilateral sequence preparation would decrease SICI in bilateral M1s, and sequence learning would alter such bilateral SICI responses. Paired-pulse transcranial magnetic stimulation was delivered over the contralateral and ipsilateral M1s to assess SICI in an index finger muscle during the preparation of sequences initiated by either the right index or little finger. In the absence of sequence learning, SICI decreased in both the contralateral and ipsilateral M1s during the preparation of sequences initiated by the right index finger, suggesting that SICI decreases in bilateral M1s during unilateral motor preparation. As sequence learning progressed, SICI decreased in the contralateral M1 whilst it increased in the ipsilateral M1. Moreover, these bilateral SICI responses were observed at the onset of motor preparation, suggesting that sequence learning altered baseline SICI levels rather than the SICI decreases occurring during motor preparation per se. Altogether, these results suggest that SICI responses in bilateral M1s reflect two motor processes: an acute decrease of inhibition during motor preparation, and a cooperative but bidirectional shift of baseline inhibition levels as sequence learning progresses.

Coccidian Parasites (Apicomplexa: Eimeriidae) of Arkansas Herpetofauna: A Summary with Two New State Records.

Coccidian parasites (Protista: Apicomplexa: Eimeriidae) commonly infect reptiles, and to a lesser degree, amphibians. The family Eimeriidae includes at least 18 genera and 3 of them, Caryospora, Eimeria, and Isospora have been reported previously from various Arkansas herpetofauna. Over the past 3 decades, our community collaborative effort has provided a great deal of information on these parasites found in amphibians and reptiles of Arkansas. Here, we provide a summary of all coccidians reported from herptiles of the state as well as provide 2 new state records for coccidians from non-native Mediterranean geckos, Hemidactylus turcicus.

Novel insights into maladaptive behaviours in Prader-Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation.

BACKGROUND: We report striking and unanticipated improvements in maladaptive behaviours in Prader-Willi syndrome (PWS) during a trial of vagus nerve stimulation (VNS) initially designed to investigate effects on the overeating behaviour. PWS is a genetically determined neurodevelopmental disorder associated with mild-moderate intellectual disability (ID) and social and behavioural difficulties, alongside a characteristic and severe hyperphagia. METHODS: Three individuals with PWS underwent surgery to implant the VNS device. VNS was switched on 3 months post-implantation, with an initial 0.25 mA output current incrementally increased to a maximum of 1.5 mA as tolerated by each individual. Participants were followed up monthly. RESULTS: Vagal nerve stimulation in these individuals with PWS, within the stimulation parameters used here, was safe and acceptable. However, changes in eating behaviour were equivocal. Intriguingly, unanticipated, although consistent, beneficial effects were reported by two participants and their carers in maladaptive behaviour, temperament and social functioning. These improvements and associated effects on food-seeking behaviour, but not weight, indicate that VNS may have potential as a novel treatment for such behaviours. CONCLUSIONS: We propose that these changes are mediated through afferent and efferent vagal projections and their effects on specific neural networks and functioning of the autonomic nervous system and provide new insights into the mechanisms that underpin what are serious and common problems affecting people with IDs more generally.

Coccidia (Apicomplexa: Eimeriidae) of Three-toed Box Turtles, Terrapene carolina triunguis (Reptilia: Testudines), from Arkansas and Oklahoma.

We collected 50 three-toed box turtles (Terrapene carolina triunguis) from 9 counties of Arkansas and 4 counties of Oklahoma, and examined their feces for coccidial parasites. Nine of 24 (38%) turtles from Arkansas and 8 of 26 (31%) from Oklahoma were found to be passing oocysts of Eimeria ornata. This represents two new geographic distributional records for this coccidian. Measurements of individual isolates of E. ornata as well as morphological characteristics are provided with comparison to its original description and to another Terrapene coccidian, Eimeria carri. In addition, we noted an adelid pseudoparasite being passed by a single T. c. triunguis from Oklahoma that likely represents a parasite of arthropods.

GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson's disease.

In Parkinson's disease (PD), elevated beta (15-35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. Recordings were then repeated following administration of sub-sedative doses of the hypnotic drug zolpidem (0.05mg/kg), which binds to the benzodiazepine site of the GABAA receptor. A beamforming based 'virtual electrode' approach was used to reconstruct oscillatory power in the primary motor cortex (M1), contralateral and ipsilateral to symptom presentation in PD patients or dominant hand in control participants. In PD patients, contralateral M1 showed significantly greater beta power than ipsilateral M1. Following zolpidem administration contralateral beta power was significantly reduced while ipsilateral beta power was significantly increased resulting in a hemispheric power ratio that approached parity. Furthermore, there was highly significant correlation between hemispheric beta power ratio and Unified Parkinson's Disease Rating Scale (UPDRS). The changes in contralateral and ipsilateral beta power were reflected in pre-movement beta desynchronization and the late post-movement beta rebound. However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem.

GPR30 is necessary for estradiol-induced desensitization of 5-HT1A receptor signaling in the paraventricular nucleus of the rat hypothalamus.

Estrogen therapy used in combination with selective serotonin reuptake inhibitor (SSRI) treatment improves SSRI efficacy for the treatment of mood disorders. Desensitization of serotonin 1A (5-HT(1A)) receptors, which takes one to two weeks to develop in animals, is necessary for SSRI therapeutic efficacy. Estradiol modifies 5-HT(1A) receptor signaling and induces a partial desensitization in the paraventricular nucleus (PVN) of the rat within two days, but the mechanisms underlying this effect are currently unknown. The purpose of this study was to identify the estrogen receptor necessary for estradiol-induced 5-HT(1A) receptor desensitization. We previously showed that estrogen receptor ß is not necessary for 5-HT(1A) receptor desensitization and that selective activation of estrogen receptor GPR30 mimics the effects of estradiol in rat PVN. Here, we used a recombinant adenovirus containing GPR30 siRNAs to decrease GPR30 expression in the PVN. Reduction of GPR30 prevented estradiol-induced desensitization of 5-HT(1A) receptor as measured by hormonal responses to the selective 5-HT(1A) receptor agonist, (+)8-OH-DPAT. To determine the possible mechanisms underlying these effects, we investigated protein and mRNA levels of 5-HT(1A) receptor signaling components including 5-HT(1A) receptor, Gαz, and RGSz1. We found that two days of estradiol increased protein and mRNA expression of RGSz1, and decreased 5-HT(1A) receptor protein but increased 5-HT(1A) mRNA; GPR30 knockdown prevented the estradiol-induced changes in 5-HT(1A) receptor protein in the PVN. Taken together, these data demonstrate that GPR30 is necessary for estradiol-induced changes in the 5-HT(1A) receptor signaling pathway and desensitization of 5-HT(1A) receptor signaling.

Genetic parameters for intramuscular fat percentage, marbling score, scrotal circumference, and heifer pregnancy in Red Angus cattle.

Selection criteria for yearling bulls commonly include indicators of fertility and carcass merit, such as scrotal circumference (SC) and intramuscular fat percentage (IMF). Genetic correlation estimates between ultrasound traits such as IMF and carcass marbling score (MS) with fertility traits SC and heifer pregnancy (HP) have not been reported. Therefore, the objective of this study was to estimate the genetic parameters among the indicator traits IMF and SC, and the economically relevant traits MS and HP. Records for IMF (n=73,051), MS (n=15,260), SC (n=43,487), and HP (n=37,802) were obtained from the Red Angus Association of America, and a 4-generation ancestral pedigree (n=10,460) was constructed from the 8,915 sires represented in the data. (Co)variance components were estimated using a multivariate sire model and average information REML to obtain estimates of heritability and genetic correlations. Fixed effects included contemporary group and the linear effect of age at measurement for all traits, and an additional effect of age of dam for both HP and SC. The random effect of sire was included to estimate additive genetic effects, which were assumed to be continuous for IMF, MS, and SC, but a probit threshold link function was fitted for HP. Generally moderate heritability estimates of 0.29 ± 0.01, 0.35 ± 0.06, 0.32 ± 0.02, and 0.17 ± 0.01 were obtained for IMF, MS, SC, and HP on the underlying scale, respectively. The confidence interval for the estimated genetic correlation between MS and HP (0.10 ± 0.15) included zero, suggesting a negligible genetic association. The genetic correlation between MS and IMF was high (0.80 ± 0.05), but the estimate for HP and SC (0.05 ± 0.09) was near zero, as were the estimated genetic correlations of SC with MS (0.01 ± 0.08) and IMF (0.05 ± 0.06), and for HP with IMF (0.13 ± 0.09). These results suggest that concomitant selection for increased fertility and carcass merit would not be antagonistic.

The role of GABAergic modulation in motor function related neuronal network activity.

At rest, the primary motor cortex (M1) exhibits spontaneous neuronal network oscillations in the beta (15-30 Hz) frequency range, mediated by inhibitory interneuron drive via GABA-A receptors. However, questions remain regarding the neuropharmacological basis of movement related oscillatory phenomena, such as movement related beta desynchronisation (MRBD), post-movement beta rebound (PMBR) and movement related gamma synchronisation (MRGS). To address this, we used magnetoencephalography (MEG) to study the movement related oscillatory changes in M1 cortex of eight healthy participants, following administration of the GABA-A modulator diazepam. Results demonstrate that, contrary to initial hypotheses, neither MRGS nor PMBR appear to be GABA-A dependent, whilst the MRBD is facilitated by increased GABAergic drive. These data demonstrate that while movement-related beta changes appear to be dependent upon spontaneous beta oscillations, they occur independently of one other. Crucially, MRBD is a GABA-A mediated process, offering a possible mechanism by which motor function may be modulated. However, in contrast, the transient increase in synchronous power observed in PMBR and MRGS appears to be generated by a non-GABA-A receptor mediated process; the elucidation of which may offer important insights into motor processes.

A short clinical overview of Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a multifaceted developmental disorder most commonly associated with extreme hyperphagia and life-threatening obesity. PWS is a genetic disorder of imprinting with almost all cases occurring spontaneously. Behavioural and imaging studies have shown that obesity in PWS arises from overeating driven by a faulty satiety mechanism which manifests as an almost permanent state similar to starvation. With no available treatments, management of the eating behaviour is the only option and has two main strategies: restrict access to food and distract thoughts from food. In this mini review, which we have aimed at clinicians, we outline the main aspects of PWS including genetics, development of the eating behaviour and best practice approaches to management.

Development of the eating behaviour in Prader-Willi Syndrome: advances in our understanding.

Prader-Willi Syndrome (PWS) is a genetically determined neurodevelopmental disorder associated with mild to moderate intellectual disability, growth and sex-hormone deficiencies and a propensity to overeat that leads to severe obesity. The PWS phenotype changes from an early disinterest in food to an increasing pre-occupation with eating and a failure of the normal satiety response to food intake. The prevention of severe obesity is primarily through strict control of access to food and it is this aspect that most limits the independence of those with PWS. This review considers the eating disorder in PWS, specifically how the as yet uncertain genetics of the syndrome and the transition from the early to the later phenotype might account for the later hyperphagia. On the basis of behavioural and imaging studies, a failure of satiety and excessive activation of neural reward pathways have both been suggested. We speculate that the overeating behaviour, consequent upon one or other of the above, could either be due to a direct effect of the PWS genotype on the feeding pathways of the hypothalamus or a consequence of prenatal changes in the regulation of genes responsible for energy balance that sets a high satiation threshold. Understanding the overeating in PWS will lead to more focused and successful management and ultimately, treatment of this life-threatening behaviour.

Prisons and HCV: a review and a report on an experience in New South Wales Australia.

Prison populations in Western countries are characterised by a high hepatitis C prevalence. This reflects a high rate of imprisonment for drug related offences. Prison entrants who are HCV-negative face a significant risk of acquiring hepatitis C. Effective prevention strategies and successful treatment of a significant percentage of hepatitis C-positive inmates could reduce the risk of transmission in the prison context significantly. Several reports of treating hepatitis C in prisoners in major facilities have been published. We report our experience of establishing a liver clinic service in two regional prisons in New South Wales, Australia. Liver biopsy requirements to access treatment in Australia meant that only 46 of 196 reviewed patients were able to commence treatment in our 5-year experience. Treatment completion rate was 61% and end of treatment viral response was 57%. The removal of liver biopsy requirements in Australia in April 2006 has freed up access to treatment and our results encourage further effort to optimise the process of assessment and treatment in this high-risk population.

Temporal Increase and Spatial Distribution of Sugarcane Yellow Leaf and Infestations of the Aphid Vector, Melanaphis sacchari.

Yellow leaf, caused by Sugarcane yellow leaf virus (ScYLV), is a potentially important disease of sugarcane first found in Louisiana during 1996. A survey during 2002 determined that ScYLV infection was present in all sugarcane-production areas of Louisiana. Virus was detected in 48% of 42 fields, and incidence averaged 15% in these fields. Disease progress curves determined in four fields during two growing seasons indicated that the greatest temporal increase of virus infection occurred during late spring and early summer and coincided with the initial infestation and increase of the virus vector, the sugarcane aphid (Melanaphis sacchari). Aphid infestations in the experimental fields during 2002 and 2003 ranged from 1.2 to 33.0 and 1.0 to 4.2 aphids per leaf, respectively. Final disease incidences of 2.9, 5.2, and 5.2% were recorded in three fields planted with virus-free seed-cane. Distribution of ScYLV infections and aphids evaluated with spatial autocorrelation analysis indicated that ScYLV and its aphid vector both exhibited a predominantly random spatial distribution, with occasional aggregation. The low incidence and rates of disease increase observed, despite the widespread occurrence of potential vectors, suggest that inoculum pressure remains low in Louisiana. Therefore, it may be possible to keep yellow leaf at low levels by planting virus-free seed-cane.

Role of InsP3 and ryanodine receptors in the activation of capacitative Ca2+ entry by store depletion or hypoxia in canine pulmonary arterial smooth muscle cells.

BACKGROUND AND PURPOSE: Experiments were performed to determine if capacitative Ca(2+) entry (CCE) in canine pulmonary arterial smooth muscle cells (PASMCs) is dependent on InsP(3) receptors or ryanodine receptors as induction of CCE is dependent on simultaneous depletion of the functionally separate InsP(3)- and ryanodine-sensitive sarcoplasmic reticulum (SR) Ca(2+) stores in these cells. EXPERIMENTAL APPROACH: Myocytes were isolated from canine pulmonary arteries using enzymatic procedures and were used within 8 h of preparation. Measurements of cytosolic Ca(2+) were made by imaging fura-2 loaded individual myocytes that were perfused with physiological buffered saline solution with or without Ca(2+). KEY RESULTS: Treating myocytes with 10 microM cyclopiazonic acid (CPA), removing extracellular Ca(2+), and briefly applying 10 mM caffeine and 10 microM 5-hydroxytryptamine (5-HT) depleted SR Ca(2+) stores. Extracellular Ca(2+) reintroduction caused cytosolic [Ca(2+)] to elevate above baseline signifying CCE. The InsP(3) receptor inhibitors 2-aminobiphenylborate (50-75 microM; 2-APB) and xestospongin-C (20 microM; XeC) abolished CCE. Yet, CCE was unaffected by 10 microM or 300 microM ryanodine or 10 microM dantrolene, which modify ryanodine receptor activity. Higher dantrolene concentrations (50 microM), however, can inhibit both ryanodine receptors and InsP(3) receptors, did reduce CCE. In contrast, CCE activated by hypoxia was unaffected by XeC (20 microM). CONCLUSIONS AND IMPLICATIONS: The results provide evidence that CCE activated by depletion of both InsP(3) and ryanodine SR Ca(2+) stores in canine PASMCs is dependent on functional InsP(3) receptors, whereas the activation of CCE by hypoxia appears to be independent of functional InsP(3) receptors.

Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients.

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

Multidrug-resistant Acinetobacter extremity infections in soldiers.

War wound infection and osteomyelitis caused by multidrug-resistant (MDR) Acinetobacter species have been prevalent during the 2003-2005 military operations in Iraq. Twenty-three soldiers wounded in Iraq and subsequently admitted to our facility from March 2003 to May 2004 had wound cultures positive for Acinetobacter calcoaceticus-baumannii complex. Eighteen had osteomyelitis, 2 burn infection, and 3 deep wound infection. Primary therapy for these infections was directed antimicrobial agents for an average of 6 weeks. All soldiers initially improved, regardless of the specific type of therapy. Patients were followed up to 23 months after completing therapy, and none had recurrent infection with Acinetobacter species. Despite the drug resistance that infecting organisms demonstrated in this series, a regimen of carefully selected extended antimicrobial-drug therapy appears effective for osteomyelitis caused by MDR Acinetobacter spp.

Reduced susceptibility to tebufenozide in populations of the sugarcane borer (Lepidoptera: Crambidae) in Louisiana.

Susceptibility of the sugarcane borer, Diatraea saccharalis (F.), to tebufenozide was measured using a feeding bioassay, and values obtained were compared with baselines generated before the use of this insecticide in Louisiana sugarcane, Saccharum spp. Results from our study suggest that susceptibility to tebufenozide is decreasing in field-collected sugarcane borers. Inflections in the log dosage-probit lines were detected for many of the field collections, indicating increased heterogeneity within these populations in response to tebufenozide. Where appropriate, probit transformation was used to estimate susceptibility, and significant differences (1.6 - 2.7-fold) were measured in LC50 values between some field-collected cohorts and the previously measured baseline. In addition, a discriminating concentration (0.5 ppm) was used to estimate resistance frequencies in cohorts for which probit transformation was not appropriate. Results from these tests suggest that frequencies of resistance were high (49% in one cohort) in populations from some locations. Lighter weight pupae of the survivors from one of the more resistant cohorts suggests that tebufenozide resistance mechanisms may have a biological cost in terms of ecological fitness at early stages of resistance development. As a result of continued resistance monitoring, alternation of management chemistry is expected to help preserve this valuable sugarcane integrated pest management tactic.