Structural Plasticity of GABAergic Pallidothalamic Terminals in MPTP-Treated Parkinsonian Monkeys: A 3D Electron Microscopic Analysis.

The internal globus pallidus (GPi) is a major source of tonic GABAergic inhibition to the motor thalamus. In parkinsonism, the firing rate of GPi neurons is increased, and their pattern switches from a tonic to a burst mode, two pathophysiological changes associated with increased GABAergic pallidothalamic activity. In this study, we used high-resolution 3D electron microscopy to demonstrate that GPi terminals in the parvocellular ventral anterior nucleus (VApc) and the centromedian nucleus (CM), the two main GPi-recipient motor thalamic nuclei in monkeys, undergo significant morphometric changes in parkinsonian monkeys including (1) increased terminal volume in both nuclei; (2) increased surface area of synapses in both nuclei; (3) increased number of synapses/GPi terminals in the CM, but not VApc; and (4) increased total volume, but not number, of mitochondria/terminals in both nuclei. In contrast to GPi terminals, the ultrastructure of putative GABAergic nonpallidal terminals was not affected. Our results also revealed striking morphological differences in terminal volume, number/area of synapses, and volume/number of mitochondria between GPi terminals in VApc and CM of control monkeys. In conclusion, GABAergic pallidothalamic terminals are endowed with a high level of structural plasticity that may contribute to the development and maintenance of the abnormal increase in pallidal GABAergic outflow to the thalamus in the parkinsonian state. Furthermore, the evidence for ultrastructural differences between GPi terminals in VApc and CM suggests that morphologically distinct pallidothalamic terminals from single pallidal neurons may underlie specific physiological properties of pallidal inputs to VApc and CM in normal and diseased states.

RGS14 limits seizure-induced mitochondrial oxidative stress and pathology in hippocampus.

RGS14 is a complex multifunctional scaffolding protein that is highly enriched within pyramidal cells (PCs) of hippocampal area CA2. In these neurons, RGS14 suppresses glutamate-induced calcium influx and related G protein and ERK signaling in dendritic spines to restrain postsynaptic signaling and plasticity. Previous findings show that, unlike PCs of hippocampal areas CA1 and CA3, CA2 PCs are resistant to a number of neurological insults, including degeneration caused by temporal lobe epilepsy (TLE). While RGS14 is protective against peripheral injury, similar roles for RGS14 during pathological injury in hippocampus remain unexplored. Recent studies showed that area CA2 modulates hippocampal excitability, generates epileptiform activity and promotes hippocampal pathology in animal models and patients with TLE. Because RGS14 suppresses CA2 excitability and signaling, we hypothesized that RGS14 would moderate seizure behavior and early hippocampal pathology following seizure activity, possibly affording protection to CA2 PCs. Using kainic acid (KA) to induce status epilepticus (KA-SE) in mice, we show that the loss of RGS14 (RGS14 KO) accelerated onset of limbic motor seizures and mortality compared to wild type (WT) mice, and that KA-SE upregulated RGS14 protein expression in CA2 and CA1 PCs of WT. Our proteomics data show that the loss of RGS14 impacted the expression of a number of proteins at baseline and after KA-SE, many of which associated unexpectedly with mitochondrial function and oxidative stress. RGS14 was shown to localize to the mitochondria in CA2 PCs of mice and reduce mitochondrial respiration in vitro. As a readout of oxidative stress, we found that RGS14 KO dramatically increased 3- nitrotyrosine levels in CA2 PCs, which was greatly exacerbated following KA-SE and correlated with a lack of superoxide dismutase 2 (SOD2) induction. Assessing for hallmarks of seizure pathology in RGS14 KO, we unexpectedly found no differences in neuronal injury in CA2 PCs. However, we observed a striking and surprising lack of microgliosis in CA1 and CA2 of RGS14 KO compared to WT. Together, our data demonstrate a newly appreciated role for RGS14 in limiting intense seizure activity and pathology in hippocampus. Our findings are consistent with a model where RGS14 limits seizure onset and mortality and, after seizure, is upregulated to support mitochondrial function, prevent oxidative stress in CA2 PCs, and promote microglial activation in hippocampus.

Incidence of fecal excretion of Mycobacterium avium subsp. paratuberculosis in dairy cows before and after the enrolment in the Québec voluntary program.

Paratuberculosis is a chronic and contagious enteric disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). This disease of worldwide distribution is responsible for significant economic losses and the bacteria itself has been linked to human Crohn's disease. Paratuberculosis control programs focus on reducing MAP transmission by implementing better management practices that target infection routes. In Québec, a Voluntary Paratuberculosis Prevention and Control Program (QVPPCP) was launched in 2007. The objectives of this prospective cohort study were threefold. The first was to describe the changes in the incidence of fecal excretion of MAP in cows born before and after farm enrolment in the QVPPCP. The second was to estimate the impact of the risk of within-herd transmission of MAP (measured by the risk assessment score (RAS)) on the incidence of fecal excretion of MAP. And the third was to evaluate the impact of calf rearing practices on the incidence of fecal excretion of MAP. Eighteen MAP-positive herds were visited annually from 2011 to 2015. At each visit, individual fecal samples from all adult cows were collected. MAP was cultured using liquid media and an automated system. A risk assessment questionnaire was completed upon enrolment in the QVPPCP and at each visit. The RAS of the farm was attributed to each cow according to its birthdate. Cox proportional hazards models were used to estimate the hazard ratios (HR) for the exposure variables. Herd clustering was taken into account using robust standard errors. A total of 2158 cows were included (cohort born before n=919; cohort born after n=1239). The incidence and hazard of fecal excretion were significantly lower for the cohort-after than the cohort-before (incidence rate ratio=0.38; 95% CI: 0.18-0.78 and HR=0.48; 95% CI: 0.23-0.98). The HR of fecal excretion for cows exposed to a high RAS was 2.20 times (95% CI: 1.21-3.99) that of cows exposed to a low RAS. Poor calving cow hygiene (HR=3.41; 95% CI: 1.40-8.31) and contact between pre-weaned heifers and adult cows or their feces were significantly associated with an increased hazard of fecal excretion of MAP (HR=2.66; 95% CI: 1.08-6.56). Our results suggest that enrolment in the QVPPCP reduces the risk of MAP fecal excretion. They support the hypothesis that contact between calves and adult cows or their feces increases MAP transmission. The incidence results also suggest that MAP prevalence could be reduced to low levels regardless of initial MAP prevalence.

Organización y funcionamiento de un grupo multidisciplinario de diagnóstico y tratamiento de la endocarditis infecciosa: perspectiva de 30 años (1985–2014) / Organization and functioning of a multidisciplinary team for the diagnosis and treatment of infective endocarditis: A 30-year perspective (1985-2014)

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Diseases of captive yellow seahorse Hippocampus kuda Bleeker, pot-bellied seahorse Hippocampus abdominalis Lesson and weedy seadragon Phyllopteryx taeniolatus (Lacépède).

Seahorses, pipefish and seadragons are fish of the Family Syngnathidae. From 1998 to 2010, 172 syngnathid cases from the Toronto Zoo were submitted for post-mortem diagnostics and retrospectively examined. Among the submitted species were yellow seahorses Hippocampus kuda Bleeker (n=133), pot-bellied seahorses Hippocampus abdominalis Lesson (n=35) and weedy seadragons Phyllopteryx taeniolatus (Lacépède; n=4). The three most common causes of morbidity and mortality in this population were bacterial dermatitis, bilaterally symmetrical myopathy and mycobacteriosis, accounting for 24%, 17% and 15% of cases, respectively. Inflammatory processes were the most common diagnoses, present in 117 cases. Seven neoplasms were diagnosed, environmental aetiologies were identified in 46 cases, and two congenital defects were identified.

D1-dopamine and α1-adrenergic receptors co-localize in dendrites of the rat prefrontal cortex.

Functional interactions between dopaminergic and noradrenergic systems occur in many brain areas, including the prefrontal cortex (PFC). Biochemical, electrophysiological and behavioral data indicate crosstalk between D1 dopamine receptor (D1R) and α1-adrenergic receptor (α1AR) signaling in the PFC. However, it is unknown whether these interactions occur within the same neurons, or between neurons expressing either receptor. In this study, we used electron microscopy immunocytochemistry to demonstrate that D1Rs and α1ARs co-localize in rat PFC neuronal elements, most prominently in dendrites (60-70%), but also significantly in axon terminals, unmyelinated axons and spines (∼20-30%). Our data also showed that the ratio of plasma membrane-bound to intracellular α1ARs is significantly reduced in D1R-expressing dendrites. Similar results were obtained using either a pan-α1AR or a selective α1bAR antibody to label noradrenergic receptors. Thus, these results demonstrate that D1Rs and α1ARs co-localize in PFC dendrites, thereby suggesting that the catecholaminergic effects on PFC function may be driven, at least in part, by cell-autonomous D1R-α1AR interactions.

Risk factors associated with transmission of Mycobacterium avium subsp. paratuberculosis to calves within dairy herd: a systematic review.

BACKGROUND: Paratuberculosis has a worldwide distribution and many countries have implemented control programs to prevent transmission among and within herds. For these programs to be efficient, knowledge of the risk factors involved in transmission is essential. OBJECTIVES: Systematically review the scientific literature concerning risk factors associated with Mycobacterium avium subsp. paratuberculosis (MAP) transmission to dairy calves. STUDY DESIGN: Systematic review. METHODS: An electronic search was done in PubMed and CAB to retrieve references relevant to answer at least 1 of the 5 questions concerning neonatal environment, colostrum, milk, housing of calves, and contact of calves with adult cow feces as risk factors in MAP transmission. A 1st screening was done using titles only, then abstracts, and finally full-length articles were reviewed for relevance. From the articles selected, risk factors and presence of a significant association between these risk factors and MAP transmission were recorded. RESULTS: Twenty-three articles from 11 different countries and published in 12 different journals were reviewed. The most common study design was cross-sectional (n = 16). The case definition and diagnostic tests used were very variable among studies, but serum ELISA was used in most studies (n = 14). The study unit was the herd in 18 studies. CONCLUSIONS AND CLINICAL IMPORTANCE: The contact of calves with adult cow feces is the most important risk factor in MAP transmission. The 5 categories of risk factors are linked to one another.

Deep fungal dermatitis caused by the Chrysosporium anamorph of Nannizziopsis vriesii in captive coastal bearded dragons (Pogona barbata).

Deep fungal dermatitis caused by the Chrysosporium anamorph of Nannizziopsis vriesii (CANV) was diagnosed in a group of coastal bearded dragons (Pogona barbata). The outbreak extended over a 6-month period, with four of six lizards from the same zoological outdoor enclosure succumbing to infection. A fifth case of dermatomycosis was identified in a pet lizard originally sourced from the wild. Diagnosis of infection with the CANV was based on similar clinical signs and histopathology in all animals and confirmed by culture and sequencing of the fungus from one animal. This is the first report of the CANV causing disease in a terrestrial reptile species in Australia and the first in the coastal bearded dragon.

Organization of postural equilibrium in several planes in ballet dancers.

This study analyzed the balance strategies of ballet dancers during postural equilibrium in three single leg balance conditions with and without vision and regard to age. Dancers participating formed two groups of 20 dancers each, one aged between 8 and 16 years (young group) and the other aged between 17 and 30 years (adult group). Ground reaction forces (GRFs) (mediolateral (ML), anteroposterior (AP) components, vertical (V)) were recorded. Results analysis enabled us to extract some spatiotemporal data for each component of the GRF (number of GRF oscillations, variability and impulses). Young dancers are characterized, compared to adult dancers, by an instability combined with an increase of oscillations number and a decrease variability mainly visible on the ML component. In the two groups, the absence of vision implies an increase of AP, ML and V impulsions and GRF variability. Balance with the gesturing limb to the rear increases the age and vision effect compared to balances with the limb forward or to the side. Young dancers are less efficient at controlling their balance than adult dancers. This observation may be related to the number of hours practicing dance, which differs between groups. The dancers have a visual dependence to control the postural balance.

Ultrastructural relationships between cortical, thalamic, and amygdala glutamatergic inputs and group I metabotropic glutamate receptors in the rat accumbens.

Changes in glutamatergic transmission in the nucleus accumbens play a key role in mediating reward-related behaviors and addiction to psychostimulants. Glutamatergic inputs to the accumbens originate from multiple sources, including the prefrontal cortex, basolateral amygdala, and midline thalamus. The group I metabotropic glutamate receptors (mGluRs) are found throughout the core and shell of the nucleus accumbens, but their localization and function at specific glutamatergic synapses remain unknown. To further characterize the substrate that underlies group I mGluR functions in the accumbens, we combined anterograde tract tracing method with electron microscopy immunocytochemistry to study the ultrastructural relationships between specific glutamatergic afferents and mGluR1a- or mGluR5-containing neurons in the rat nucleus accumbens. Although cortical, thalamic, and amygdala glutamatergic terminals contact both mGluR1a- and mGluR5-immunoreactive dendrites and spines in the shell and core of the accumbens, they do so to varying degrees. Overall, glutamatergic terminals contact mGluR1a-positive spines about 30% of the time, whereas they form synapses twice as frequently with mGluR5-labeled spines. At the subsynaptic level, mGluR5 is more frequently expressed perisynaptically and closer to the edges of glutamatergic axospinous synapses than mGluR1a, suggesting a differential degree of activation of the two group I mGluRs by transmitter spillover from glutamatergic synapses in the rat accumbens. These results lay the foundation for a deeper understanding of group I mGluR-mediated effects in the ventral striatum, and their potential therapeutic benefits in drug addiction and other neuropsychiatric changes in reward-related behaviors.

Remarks on various applications of microwave energy.

Microwave energy is an alternative energy source that is receiving a considerable amount of attention from researchers for a wide spectrum of applications. The fundamentally different method of transferring energy from the source to the sample is the main benefit of utilizing microwave energy; by directly delivering energy to microwave-absorbing materials, conventional issues such as long heating periods, thermal gradients, and energy lost to the system environment can be minimized or avoided. Furthermore, the penetrating capacity of microwave allows volumetric heating of samples. These attributes of microwave energy make utilizing it very attractive for industrial applications as an alternative to conventional processing methods. The reality is otherwise however, and limited literature is found in any given area of work. Despite the lack of focus, in most published cases, the utilization of microwave energy has produced improved results compared to conventional methods with reduced heating times or reaction temperatures. This review provides a general overview of reported applications of microwave energy in the open literature. It also attempts to summarize the results obtained for various common uses and highlights some applications that have not gathered as much attention as anticipated.

Evaluation of Microwave-Assisted Process technology for HAPSITE's headspace analysis of volatile organic compounds (VOCs).

The use of microwave energy as a heating source for the field-based headspace sampling and the subsequent determination of various volatile organic compounds (VOCs) using a field-portable HAPSITE gas chromatograph-mass spectrometer has been evaluated. A significant advantage in time reduction has been observed when using microwave energy when compared to conventional resistive-based heating. Such time savings are critical in field operations involving equipment such as the HAPSITE where non-routine sampling is commonly performed and very quick turnaround time is usually needed. Further, the technology also showed significant improvements in terms of sensitivity, thus suggesting its applicability to a broader range of compounds and detection levels than current technologies.

Cerebral beta-amyloid angiopathy in aged squirrel monkeys.

Cerebral beta-amyloid angiopathy (CAA) is an age-related disorder of the brain vasculature that is involved in up to 20% of non-traumatic cerebral hemorrhage in humans. CAA is a risk factor for cognitive decline, and may exacerbate the dementia of Alzheimer's disease. Progress in discovering the cause and potential therapies for this disorder has been hindered by the paucity of animal models, particularly models of idiopathic CAA. The squirrel monkey (Saimiri spp) develops significant CAA in the natural course of aging. To evaluate the suitability of Saimiri as a model of human CAA, we studied the distribution and composition of Abeta subtypes in CAA and parenchymal (senile plaque) deposits in the brains of aged squirrel monkeys, as well as the relationship between vascular beta-amyloid deposition and comorbid vasculopathies that occur in aged humans. Our findings show that: 1) CAA consists ultrastructurally of classical amyloid fibrils and is the principal type of cerebral beta-amyloidosis in squirrel monkeys; 2) The two primary isoforms of Abeta (Abeta40 and Abeta42) coexist in most microvascular and parenchymal lesions of Saimiri, although Abeta40 tends to predominate in larger arterioles; 3) CAA and parenchymal plaques overlap to a considerable degree in most affected brain areas, and are distributed symmetrically in the two hemispheres; 4) Both CAA and plaques are particularly abundant in rostral regions and comparatively sparse in the occipital lobe; 5) Capillaries are especially vulnerable to CAA in squirrel monkeys; and 6) When CAA is severe, it is associated with a small, but significant, increase in other vasculopathies, including microhemorrhage, fibrinoid extravasation and focal gliosis. These findings, in the context of genetic, vascular and immunologic similarities between squirrel monkeys and humans, support the squirrel monkey as a biologically advantageous model for studying the basic biology of idiopathic, age-related CAA, and for testing emerging therapies for human beta-amyloidoses such as Alzheimer's disease.

Applications of microwave-assisted processes (MAP) to environmental analysis.

The use of microwave-assisted extraction has gained wide acceptance as a powerful tool for the recovery of environmental contaminants and their subsequent analysis. This paper reviews the historical and fundamental basis of the technology. It also provides a cursory review of the current state-of-the-art and literature (2000-2006) in the area of environmental analysis in addition to providing a critical review of the level of efforts being devoted to its further development.

Cryopreserved mitral homograft in the tricuspid position for infective endocarditis: a valve that can be repaired in the long-term (13 years).

Herein is reported the long-term repair of a cryopreserved mitral homograft in the tricuspid position. A 34-year-old HIV-infected patient underwent tricuspid valve replacement in 1991 with a cryopreserved mitral homograft because of infective endocarditis. Chronic tricuspid regurgitation secondary to repeated endocarditis led to reoperation 13 years later. Mitral valve repair was performed with a rigid ring as there was annular dilatation; the valve tissue was intact. One year later, transthoracic echocardiography showed no tricuspid regurgitation. The cryopreserved mitral homograft is a potentially repairable valve in the long-term.

Synaptic and extrasynaptic GABA-A and GABA-B receptors in the globus pallidus: an electron microscopic immunogold analysis in monkeys.

GABA-A and GABA-B receptors mediate differential effects in the CNS. To better understand the role of these receptors in regulating pallidal functions, we compared their subcellular and subsynaptic localization in the external and internal segments of the globus pallidus (GPe and GPi) in monkeys, using pre- and post-embedding immunocytochemistry with antibodies against GABA-A (alpha1, beta2/3 subunits) and GABA-BR1 receptor subtype. Our results demonstrate that GABA-A and GABA-B receptors display a differential pattern of subcellular and subsynaptic localization in both segments of the globus pallidus. The majority of GABA-BR1 immunolabeling is intracellular, whereas immunoreactivity for GABA-A receptor subunits is mostly bound to the plasma membrane. A significant proportion of both GABA-BR1 and GABA-A receptor immunolabeling is extrasynaptic, but GABA-A receptor subunits also aggregate in the main body of putative GABAergic symmetric synapses established by striatal- and pallidal-like terminals. GABA-BR1 immunoreactivity is expressed presynaptically in putative glutamatergic terminals, while GABA-A alpha1 and beta2/3 receptor subunits are exclusively post-synaptic and often coexist at individual symmetric synapses in both GPe and GPi. In conclusion, our findings corroborate the concept that ionotropic and metabotropic GABA receptors are located to subserve different effects in pallidal neurons. Although the aggregation of GABA-A receptors at symmetric synapses is consistent with their role in fast inhibitory synaptic transmission, the extrasynaptic distribution of both GABA-A and GABA-B receptors provides a substrate for complex modulatory functions that rely predominantly on the spillover of GABA.

Native valve endocarditis due to Candida glabrata treated without valvular replacement: a potential role for caspofungin in the induction and maintenance treatment.

Conventional antifungal therapy for fungal endocarditis has been associated with a poor cure rate. Therefore, combined medical and surgical therapy has been recommended. However, new potent antifungal agents, such as echinocandins, could increase the medical options and, in some cases, avoid the need for surgery. We report a case of Candida endocarditis treated successfully without valve replacement with intravenous liposomal amphotericin B (total dose, 4 g) and intravenous caspofungin (a 100-mg loading dose followed by 50 mg per day for 8 weeks) as induction therapy and intravenous caspofungin (100 mg 3 times per week for 12 weeks) as maintenance therapy.