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Given the enormous symptom relief benefit seen with cardiac myosin inhibitors, there is renewed focus to correctly identify hypertrophic cardiomyopathy (HCM) patients as obstructive versus non-obstructive. Overall, two thirds of HCM patients have clinically significant obstruction of blood flow out of the left ventricular outflow tract (LVOTO). A third of HCM patients, however, will only experience obstruction during challenging provocative maneuvers such as Valsalva, during volume depletion, or with exercise. Patients with "masked obstruction" are frequently mislabeled and subsequently mismanaged as non-obstructive. This study aims to identify features seen on cardiac magnetic resonance imaging (CMR) and on transthoracic echocardiography (TTE) that should heighten awareness that occult obstruction may be present, potentially prompting physicians to obtain exercise stress echocardiography. This study utilized retrospective data analysis from a large, single-center cohort over a six-month period. Subjects were included if both stress echocardiography and CMR were available. LVOTO was defined as peak LV outflow tract gradient ≥30 mmHg. Subjects were divided in to 1) Absent, 2) Masked and 3) Overt LVOTO. CMR was used to assess anatomical differences between groups. Continuous data was compared using ANOVA analysis, with secondary multiple comparison tests. Sixty one patients (30:31 M:F)(Age = 57.1 ± 14.4 yrs.) were included; Absent (n = 27), Masked (n = 21), Overt (n = 13). CMR data with ANOVA analysis is provided in Table 1. Multiple comparison testing of the Zone of Coaptation Length was significant between the Absent v. Masked groups (mean = 7.8 v. 10.1, 95% CI: -4.6 to -0.1, p = 0.04). (Figure 1) The height of the zone of coaptation is best understood as the length of contact between the anterior and posterior mitral leaflets in the basal to apical axis during systole. In this cohort, longer zone of coaptation lengths were more likely to associate with masked LVOTO than overt or absent LVOTO. During hyperdynamic contractility, this highly mobile region of the sub-valvular apparatus is likely pushed into the LVOT due to the Venturi Effect and/or from apical displacement of the papillary heads. Once in the LVOT, drag force is exerted on the apparatus resulting in obstruction. Anterior mitral length, a feature thought to predict obstruction from the echocardiography literature, did not predict masked or overt obstruction. Further investigation is warranted to better understand how cardiac MRI could prompt physicians to look for masked obstruction, as stress echocardiography is commonly underutilized. [ABSTRACT FROM AUTHOR]

Of the mycotoxicoses caused by molds contaminating grains or their byproducts, leukoencephalomalacia of horses and less frequently aflatoxicosis in cattle have been reported in South America. However, the most important group of mycotoxins in the region are those caused by fungi that infect forages and other types of plants and have regional distribution. In this group, ergotism is important, both caused by Claviceps purpurea infecting grains or by Epichloë coenophiala infecting Schedonorus arundinaceus. Other important mycotoxicoses are those caused by indole-diterpenes produced by Clavicipitaceous fungi including Claviceps paspali in Paspalum spp., Claviceps cynodontes in Cynodon dactylon , and by Periglandula a seed transmitted symbiont associated with the tremorgenic plant Ipomoea asarifolia. The latter is an important poisoning in the northeastern and northern Brazil. Other important mycotoxicoses are those caused by swainsonine containing plants. It was demonstrated that swainsonine contained in Ipomoea carnea var. fistulosa is produced by an epibiotic fungus of the order Chaetothyriales whose mycelia develop on the adaxial surface of the leaves. Swainsonine is also produced by the symbiotic, endobiotic fungi Alternaria section Undifilum spp., which is associated with Astragalus spp. in the Argentinian Patagonia causing poisoning. Another form of mycotoxicosis occurs in poisoning by Baccharis spp., mainly B. coridifolia , a very important toxic plant in South America that contains macrocyclic trichothecenes probably produced by an endophytic fungus that has not yet been identified. Pithomycotoxicosis caused by Pithomyces chartarum used to be an important mycotoxicosis in the region, mainly in cattle grazing improved pastures of legumes and grasses. Slaframine poisoning, diplodiosis and poisoning by barley contaminated by Aspergillus clavatus has been rarely diagnosed in Brazil, Uruguay and Argentina. [Display omitted] • Mycotoxicoses are important diseases for ruminants and equids in South America. • Aflatoxicosis and leukoencephalomalacia affect cattle and horses, respectively. • Indole-diterpenes produced by various endophytic fungi in different plant species frequently affect ruminants. • Ergotism caused by Claviceps purpurea and Neotyphodium coenophialum in Schedonorus arundinaceus are important diseases. • Poisonings by Baccharis coridifolia is also considered a mycotoxicosis. [ABSTRACT FROM AUTHOR]

The present study describes the spontaneous and experimental poisoning of goats by Festuca argentina in Argentine Patagonia. In April 2017, eight seven-month-old Creole male goats were accidentally introduced into a paddock that contained F. argentina. After four days, two of the goats were found dead and four out of the six remaining goats were clinically affected. Two of the latter had to be later euthanized in extremis. The main clinical signs were progressive nervous signs, starting with moderate muscle tremors, wide-based stance and ataxia. Postmortem examination was performed on the two euthanized goats. Epidermal fragments of F. argentina were found in the rumen samples from the necropsied goats and the fecal samples from the four affected goats. For the experimental poisoning, fresh sheaths of F. argentina collected from the paddock were offered to two goats at 10 g/kg body weight for 3 days. After 24–36 h, both animals exhibited severe muscle tremors, reluctance to move, tetanic convulsions, and opisthotonus. In both the spontaneously and experimentally poisoned goats, gross lesions were similar and consisted of dehydration, petechial hemorrhages in the epicardium and congestion. The main microscopic findings consisted of degeneration and loss of Purkinje cells and torpedoes in the granular layer of the cerebellum. The F. argentina sheaths collected from the pasture were found to contain tremorgenic indole-diterpene alkaloids. Taken together, the results of the present study suggest that the tremorgenic syndrome observed in the spontaneously poisoned goats was due to poisoning by F. argentina. • Festuca argentina causes spontaneous and experimental poisoning in goats. • Poisoning by Festuca argentina in goats is characterized by a tremorgenic syndrome. • Tremorgenic indole diterpenes are present in poisonous Festuca argentina. [ABSTRACT FROM AUTHOR]

Studies have found that pairing vagus nerve stimulation (VNS) with motor activity accelerates cortical reorganization. This synchronous pairing may enhance motor recovery. To develop and validate a motor-activated auricular vagus nerve stimulation (MAAVNS) system as a potential neurorehabilitation tool. We created MAAVNS and validated its function as part of an ongoing clinical trial investigating whether taVNS-paired rehabilitation enhances oromotor learning. We compared 3 different MAAVNS EMG electrode configurations in 3 neonates. The active lead was placed over the buccinator muscle. Reference lead placements were orbital, temporal or frontal. The frontal reference lead produced the highest sensitivity (0.87 ± 0.07 (n = 8)) and specificity (0.64 ± 0.13 (n = 8)). Oral sucking reliably triggers MAAVNS stimulation with high confidence. EMG electrodes placed on target orofacial muscles can effectively trigger taVNS stimuli in infants in a closed loop fashion. • This novel, motor-activated auricular vagus nerve stimulation (MAAVNS) system pairs stimulation with motor activity. • MAAVNS is a closed-loop system that allows for uniform delivery of taVNS treatment across multiple operators. • MAAVNS is feasible and may become a promising tool for both adult and pediatric neuromodulation-based rehabilitation. [ABSTRACT FROM AUTHOR]

Larkspurs ( Delphinium , Ranunculaceae) are poisonous plants found on rangelands throughout Western North America. Two main structural groups of norditerpene alkaloids, the N -(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and the non-MSAL type, are responsible for larkspur-induced poisoning. Information on the alkaloid composition is lacking for a number of Delphinium species, including D. ramosum . Delphinium ramosum grows throughout parts of Colorado and northern New Mexico. The objective of this study was to profile the alkaloid composition of D. ramosum throughout its geographical distribution using both field and herbarium specimens. Two alkaloid profiles were identified, one that contained significantly greater concentrations of the MSAL-type alkaloids than the other. Plants containing each respective alkaloid profile were unique in their geographical distribution. Populations of these two chemotypes will likely differ in their toxic potential and consequently pose different risks of poisoning when grazed by livestock species. This information has important implications in grazing management decisions on D. ramosum- infested rangelands and demonstrates that botanical classification alone is not an adequate indicator of relative risk of toxicity. [ABSTRACT FROM AUTHOR]

Swainsonine is a toxic alkaloid found in several plant genera worldwide. The objective of this study was to screen several South American Astragalus species for the toxin swainsonine. Swainsonine was detected in 16 of 30 Astragalus species using liquid and gas chromatography coupled with mass spectrometry. Information in regard to the swainsonine content of these species may provide important information on the risk of grazing these toxic species. [ABSTRACT FROM AUTHOR]

One-fifth of the world's reptiles are currently estimated as threatened with extinction, primarily due to the immediate threats of habitat loss and overexploitation. Climate change presents an emerging slow-acting threat. However, few IUCN Red List assessments for reptiles explicitly consider the potential role of climate change as a threat. Thus, climate change vulnerability assessments can complement existing Red List assessments and highlight further, emerging priorities for conservation action. Here we present the first trait-based global climate change vulnerability assessment for reptiles to estimate the climate change vulnerability of a random representative sample of 1498 species of reptiles. We collected species-specific traits relating to three dimensions of climate change, sensitivity, low adaptability, and exposure, which we combined to assess overall vulnerability. We found 80.5% of species highly sensitive to climate change, primarily due to habitat specialisation, while 48% had low adaptability and 58% had high exposure. Overall, 22% of species assessed were highly vulnerable to climate change. Hotspots of climate change vulnerability did not always overlap with hotspots of threatened species richness, with most of the vulnerable species found in northwestern South America, southwestern USA, Sri Lanka, the Himalayan Arc, Central Asia and southern India. Most families were found to be significantly more vulnerable to climate change than expected by chance. Our findings build on previous work on reptile extinction risk to provide an overview of the risk posed to reptiles by climate change. Despite significant data gaps for a number of traits, we recommend that these findings are integrated into reassessments of species' extinction risk, to monitor both immediate and slow-acting threats to reptiles. [ABSTRACT FROM AUTHOR]

Swainsonine, an indolizidine alkaloid, is an α-mannosidase and mannosidase II inhibitor that causes lysosomal storage disease and alters glycoprotein processing. Swainsonine is found in a number of plant species worldwide, and is produced by associated endophytic fungi. Prolonged consumption of swainsonine-containing plants by livestock causes a condition characterized by weight loss, depression, altered behavior, decreased libido, infertility, and death. In contrast, Astragalus and Oxytropis that do not contain swainsonine may present a valuable food source for grazing livestock in regions where palatable forage is scarce. This study tested the hypothesis that swainsonine concentrations may be reduced by fungicide treatment or by clipping, thus reducing plant toxicity. Additionally we hypothesized that clipping plants may provide a mechanism for horizontal transmission of the endophyte. To this end, four different fungicides were applied to render the endophyte non-viable, and plant vegetative tissues were periodically clipped. Treatment of Oxytropis sericea with any of four different fungicides did not alter swainsonine concentrations in plants at any of three harvest times. Additionally, we found that individual or multiple clippings had no effect on swainsonine concentrations; plants that contained swainsonine maintained concentrations, and plants low or absent in swainsonine also remained as such at each harvest. These results suggest that there is no evidence of horizontal transmission of the endophyte among individual plants due to clipping. [ABSTRACT FROM AUTHOR]

Swainsonine, an indolizidine alkaloid with significant physiological activity, is an α-mannosidase and mannosidase II inhibitor that causes lysosomal storage disease and alters glycoprotein processing. Swainsonine is found in a number of plant species worldwide, and causes severe toxicosis in livestock grazing these plants, leading to a chronic wasting disease characterized by weight loss, depression, altered behavior, decreased libido, infertility, and death. Swainsonine has been detected in 19 Astragalus and 2 Oxytropis species in North America by thin layer chromatography, gas chromatography–mass spectrometry, liquid chromatography-mass spectrometry and a jack bean α-mannosidase inhibition assay. In addition, 5 species in North America are presumed to contain swainsonine based upon reports from field cases. Many of these plant species have not been analyzed for swainsonine using modern instrumentation such as gas or liquid chromatography coupled with mass spectrometry. To provide clarification, 22 Astragalus species representing 93 taxa and 4 Oxytropis species representing 18 taxa were screened for swainsonine using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. Swainsonine was detected in 48 Astragalus taxa representing 13 species and 5 Oxytropis taxa representing 4 species. Forty of the fifty-three swainsonine-positive taxa had not been determined to contain swainsonine previously using liquid or gas chromatography coupled with mass spectrometry. The list of swainsonine-containing taxa reported here will serve as a reference for risk assessment and diagnostic purposes. [ABSTRACT FROM AUTHOR]

Lupines ( Lupinus spp.) are a common legume found on western U.S. rangelands. Lupinus spp. may contain quinolizidine and/or piperidine alkaloids that can be toxic and/or teratogenic to grazing livestock. Lupinus leucophyllus and Lupinus polyphyllus in particular represent important species in the rangelands of southeast Washington and northeast Oregon. The objectives of this study were to identify the alkaloid profiles of these two species, and to explore the phylogenetic relationship among the different populations using amplified fragment length polymorphism (AFLP) markers. Two chemotypes were found among the 14 accessions of Lupinus leucophyllyus. Chemotype A contained anagyrine, a potent teratogen in cattle, and thus would pose a risk to cause crooked calf syndrome in grazing cattle, while Chemotype B did not contain anagyrine and poses no teratogenic risk. No alkaloids were detected in the L. polyphyllus plants collected in this area. Phylogenetic analysis showed that L. leucophyllus accessions with the same chemotype that were geographically proximal were closely grouped in the cladogram; however, accessions that were geographically proximal that represented different chemotypes did not cluster together. Taken together, these results suggest that for the studied species, chemotype is the principle factor in determining relatedness followed by geography. [ABSTRACT FROM AUTHOR]

Larkspurs ( Delphinium spp.) are poisonous plants on rangelands throughout the Western United States and Canada. Larkspur-induced poisoning in cattle is due to norditerpene alkaloids that are represented by two main structural groups of norditerpene alkaloids, the N -(methylsuccinimido) anthranoyllycoctonine type (MSAL-type) and the non-MSAL type. Information on the alkaloid composition and resulting toxicity in mice and cattle is lacking for a number of Delphinium species, including Delphinium stachydeum . The objective of this study was to determine the alkaloid composition of D. stachydeum and to characterize its relative toxicity in mice and cattle compared to two reference species Delphinium barbeyi and Delphinium occidentale . D. stachydeum contains the non-MSAL-type alkaloids but not the MSAL-type alkaloids. D. stachydeum was less toxic than D. barbeyi and D. occidentale in the mouse model. D. stachydeum was less toxic than the MSAL-containing D. barbeyi but much more toxic than the non-MSAL-containing D. occidentale in cattle as measured by heart rate and time of exercise. These results indicate that predictions of Delphinium toxicity can't be accurately made based solely on results from the mouse model or the absence of the MSAL-type alkaloids in the plant. [ABSTRACT FROM AUTHOR]

The number of cases diagnosed with Autism Spectrum Disorders is rising at an alarming rate with the Centers for Disease Control estimating the 2014 incidence rate as 1 in 68. Recently, it has been hypothesized that gut bacteria may contribute to the development of autism. Specifically, the relative balances between the inflammatory microbes clostridia and desulfovibrio and the anti-inflammatory microbe bifidobacteria may become destabilized prior to autism development. The imbalance leads to a leaky gut, characterized by a more porous epithelial membrane resulting in microbial toxin release into the blood, which may contribute to brain inflammation and autism development. To test how changes in population dynamics of the gut microbiome may lead to the imbalanced microbial populations associated with autism patients, we constructed a novel agent-based model of clostridia, desulfovibrio, and bifidobacteria population interactions in the gut. The model demonstrates how changing physiological conditions in the gut can affect the population dynamics of the microbiome. Simulations using our agent-based model indicate that despite large perturbations to initial levels of bacteria, the populations robustly achieve a single steady-state given similar gut conditions. These simulation results suggests that disturbance such as a prebiotic or antibiotic treatment may only transiently affect the gut microbiome. However, sustained prebiotic treatments may correct low population counts of bifidobacteria. Furthermore, our simulations suggest that clostridia growth rate is a key determinant of risk of autism development. Treatment of high-risk infants with supra-physiological levels of lysozymes may suppress clostridia growth rate, resulting in a steep decrease in the clostridia population and therefore reduced risk of autism development. [ABSTRACT FROM AUTHOR]

Ipomoea carnea , a swainsonine containing plant, is known to cause a neurologic disease in grazing livestock in Brazil and other parts of the world. To better understand the relative toxicity and nutritional content of I. carnea we investigated swainsonine, calystegine, and crude protein concentrations in leaves of I. carnea on a monthly basis for one year in northern and northeastern Brazil. Swainsonine concentrations were detected at concentrations that could potentially poison an animal throughout the year although there was some variation between months. At one location swainsonine concentrations were generally the highest during the rainy season or the months immediately following the rainy season. Total calystegine concentrations were similar to those reported previously while crude protein concentrations were similar to those found in other Ipomoea species and are such that they may explain why I. carnea becomes desirable to grazing livestock as forage becomes limited during the dry season. [ABSTRACT FROM AUTHOR]

Regressive autism is a devastating disorder affecting children between the ages of 15–30 months. The disorder is characterized by the loss of social interaction and communication ability following otherwise healthy development. In spite of rising autism prevalence, current detection methods and treatment options for this disease are lacking. Therefore, this study introduces a systems-level model, which suggests that gut microbes and intestinal inflammation influence the onset of regressive autism through increasing gut permeability. This computational model provides a framework for quantitative understanding of how imbalances in populations of gut microbes alters the whole-body and brain distributions of neurotoxins produced by GI tract bacteria. Our results indicate that increased levels of the bacteria Bacteroides vulgatus lead to increased brain levels of propionic acid, a neurotoxin which has been known to cause symptoms characteristic of autism when injected into the brain of rats. Our results further indicate that immune response to virulence factors produced by bacteria in the gut leads to increased systemic levels of inflammatory cytokines, such as IL-1β, which significantly alter the permeability of the gut epithelial layer and the blood–brain barrier. Due to the large size of cytokines, however, we predict the time required for concentrations in the brain to stabilize to be on the order of years. This suggests that treatments preventing autism development could be administered after identifying microbial biomarkers of disease but before debilitating brain inflammation leads to regressive autism progression. Future research extending this work could provide new treatment options and diagnostic techniques to help combat regressive autism. [ABSTRACT FROM AUTHOR]

Over the years various tissues of almond and pistachio have been evaluated for their ability to attract the navel orangeworm moth, a major insect pest in California tree nut orchards. Almond meal, which typically consists of ground almond kernels, is a monitoring tool for navel orangeworm populations in almond and pistachio orchards. Recently, ground pistachio and almond mummies have been re-visited in field trapping studies for their potential to attract navel orangeworm moths. Surprisingly, the volatile profiles of these two systems have not been reported. The objective of this study was to survey and then compare and contrast the volatile profiles of both ground almond and pistachio mummies over the course of a week. Principal component analysis (PCA) of the headspace volatiles showed a distinct difference between ground almond and pistachio mummies. The volatile emission profile of the almond mummies remained consistent over the one-week period, albeit in low content and composition; whereas the profile of the pistachio mummies changed over time as shown by PCA. Seven compounds were identified as being common volatiles to both matrices. These data may help explain results from recent navel orangeworm field trapping studies using almond and pistachio mummies, as well as with the formulation of future synthetic blends. [ABSTRACT FROM AUTHOR]

Highlights: [•] The alkaloid composition of Sophora leachiana was investigated. [•] S. leachiana contains quinolizidine alkaloids. [•] The alkaloid profile of S. leachiana is different from other Sophora spp. [ABSTRACT FROM AUTHOR]

Highlights: [•] Volatile analysis of ground and wet almond and pistachio mummies. [•] Pistachio mummy volatile profile comprises 86 volatiles, 22 unique to wet matrix. [•] Almond mummy volatile profile comprises 57 volatiles, 37 unique to wet matrix. [•] The two wet matrices have 19 compounds in common. [Copyright &y& Elsevier]

Abstract: Numerous plant species worldwide including some Palicourea (Rubiaceae), Tanaecium (Bignoniaceae), and Amorimia (Malpighiaceae) species in Brazil cause sudden death and are known to contain monofluoroacetate (MFA). Two species of Palicourea, Palicourea aenofusca and Palicourea marcgravii, cause sudden death and are reported to contain MFA while other Palicourea species are reported to cause sudden death in livestock and are suspected to contain MFA due to the similarity in clinical signs. Using an HPLC–APCI–MS method to detect MFA, herbarium specimens representing 46 Palicourea taxa were screened for the presence of MFA. Additionally we screened five Psychotria taxa that are closely related to Palicourea species. Ten species of Palicourea were identified that contained MFA, two previously reported and eight newly reported here; these are closely related to each other, though some other related species did not contain MFA. [Copyright &y& Elsevier]

Abstract: Background context: Traditional methods for the evaluation of in vivo spine kinematics introduce significant measurement variability. Digital videofluoroscopic techniques coupled with computer-assisted measurements have been shown to reduce such error, as well as provide detailed information about spinal motion otherwise unobtainable by standard roentgenograms. Studies have evaluated the precision of computer-assisted fluoroscopic measurements; however, a formal clinical evaluation and comparison with manual methods is unavailable. Further, it is essential to establish reliability of novel measurements systems compared with standard techniques. Purpose: To determine the repeatability and reproducibility of sagittal lumbar intervertebral measurements using a new system for the evaluation of lumbar spine motion. Study design: Reliability evaluation of digitized manual versus computer-assisted measurements of the lumbar spine using motion sequences from a videofluoroscopic technique. Patient sample: A total of 205 intervertebral levels from 61 patients were retrospectively evaluated in this study. Outcome measures: Coefficient of repeatability (CR), limits of agreement (LOA), intraclass correlation coefficient (ICC; type 3,1), and standard error of measurement. Methods: Intervertebral rotations and translations (IVR and IVT) were each measured twice by three physicians using the KineGraph vertebral motion analysis (VMA) system and twice by three different physicians using a digitized manual technique. Each observer evaluated all images independently. Intra- and interobserver statistics were compiled based on the methods of Bland-Altman (CR, LOA) and Shrout-Fleiss (ICC, standard error of measurement). Results: The VMA measurements demonstrated substantially more precision compared with the manual technique. Intraobserver measurements were the most reliable, with a CR of 1.53 (manual, 8.28) for IVR, and 2.20 (manual, 11.75) for IVT. The least reliable measurements were interobserver IVR and IVT, with a CR of 2.15 (manual, 9.88) and 3.90 (manual, 12.43), respectively. The ICCs and standard error results followed the same pattern. Conclusions: The VMA system markedly reduced variability of lumbar intervertebral measurements compared with a digitized manual analysis. Further, computer-assisted fluoroscopic imaging techniques demonstrate precision within the range of computer-assisted X-ray analysis techniques. [Copyright &y& Elsevier]

Abstract: Sophora arizonica, Sophora gypsophila, Sophora secundiflora, Sophora affinis, and Sophora japonica were recently reclassified as Dermatophyllum arizonicum, Dermatophyllum gypsophilum, Dermatophyllum secundiflorum, Styphnolobium affine, and Styphnolobium japonicum, respectively. Some legumes of the sub family Papilionoideae including Sophora species are reported to contain a variety of quinolizidine alkaloids. The quinolizidine alkaloid profiles of D. arizonicum, D. gypsophilum, D. secundiflorum, S. affine, and S. japonicum were investigated qualitatively and quantitatively using field collections and herbarium specimens throughout their range of geographical distribution for the native species. This is the first report of the alkaloid profiles of D. arizonicum and D. gypsophilum. Alkaloid profiles of the other species were compared to previous reports. The Dermatophyllum species contain quinolizidine alkaloids, and the teratogen anagyrine (11), while the Styphnolobium species do not contain quinolizidine alkaloids. The chemotaxonomic data are consistent with the reclassification of each species. [Copyright &y& Elsevier]

Abstract: Plant secondary compounds mediate interactions with insects and other animals. The norditerpene alkaloids are significant secondary compounds in Delphinium (larkspur) species which are divided into two classes: the 7, 8-methylenedioxylycoctonine (MDL-type) and N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type), and are known to be toxic to herbivorous insects and livestock. Alkaloid concentrations were measured in a whole plant context in vegetative and floral tissues as well as rewards (pollen and nectar) in Delphinium barbeyi and Delphinium nuttallianum. Alkaloid concentrations differed between vegetative tissues, floral tissues and floral rewards. Alkaloid concentrations in floral parts were consistent with optimal defense theory, with tissues more closely tied to plant fitness, such as fruits, being more heavily defended than foliage. However, alkaloid concentrations were significantly lower in nectar compared to other tissues. The norditerpene alkaloids influenced the activity of bumble bees, the dominant pollinator of larkspur, but the effects were concentration dependent. Alkaloids in nectar are found at concentrations that have no effect on bee activity; however, if alkaloid concentrations in nectar were similar to those in foliage bee activity would be reduced significantly. These results suggest that nectar with low alkaloid concentrations may be beneficial to plant fitness by limiting adverse effects on pollinator activity. [Copyright &y& Elsevier]

Abstract: Sophora is a diverse genus in the family Fabaceae, comprised of herbs, shrubs, and trees that occurs throughout the world, primarily in the northern hemisphere. Species of Sophora are known to contain quinolizidine alkaloids that are toxic and potentially teratogenic. Two perennial herbaceous species occur in North America, Sophora stenophylla and Sophora nuttalliana. The quinolizidine alkaloid composition of these two species was investigated throughout their geographical distribution using field collections and herbarium specimens. Both species contain quinolizidine alkaloids, and S. nuttalliana contains the teratogen anagyrine. Lastly, neither species contains the neurotoxin swainsonine as implied by the common name “white loco” for S. nuttalliana. [Copyright &y& Elsevier]

Abstract: Locoism is a toxic syndrome of livestock caused by the ingestion of a subset of legumes belonging to the Astragalus and Oxytropis genera known as “locoweeds”. Locoweeds contain the toxic indolizidine alkaloid swainsonine, which is produced by the endophytic fungi Undifilum species. Previously we reported that swainsonine concentrations differ between populations of Oxytropis sericea. We hypothesized that the genotype of the plant, endophyte, or an interaction of the two may be responsible for the differences in swainsonine concentration between populations of O. sericea. To test this hypothesis, plants derived from seeds collected at each location were grown in a common garden, Undifilum oxytropis isolates from each location were cultured and grown in a common environment, and a plant genotype by endophyte cross inoculation was performed. Here we show that the genotype of the endophyte is responsible for the differences in swainsonine concentrations observed in the two populations of O. sericea. [Copyright &y& Elsevier]

Abstract: Locoweeds are Astragalus and Oxytropis species that contain the toxic alkaloid swainsonine, causing widespread poisoning of livestock in Inner Mongolia. Taxa (Astragalus, Oxytropis, Sphaerophysa, and Sophora species) suspected of causing locoism and/or poisoning in Inner Mongolia were surveyed for swainsonine and Undifilum, the fungal endophyte responsible for the production of swainsonine. Swainsonine was detected at concentrations greater than 0.01% in Astragalus variabilis and Oxytropis glabra. The endophyte Undifilum was detected by culturing and PCR in samples containing swainsonine concentrations greater than 0.01%. In some specimens of A. variabilis and O. glabra swainsonine was not detected or concentrations were less than 0.01%. In these samples the endophyte could not be cultured, but was detected by PCR. Additionally, contrary to previous reports the quinolizidine alkaloids, thermopsine, anagyrine, and lupanine, were not detected in O. glabra and Oxytropis ochrocephala, however the quinolizidine alkaloids, sophoridine, sophocarpine, and sophoramine were detected in Sophora alopecuroides as previously reported. [Copyright &y& Elsevier]

Abstract: Numerous plant species worldwide including Palicourea marcgravii and Tanaecium bilabiatum in Brazil cause sudden death and are known to contain monofluoroacetate (MFA). Other species in Brazil including some species traditionally assigned to Mascagnia but now properly called Amorimia species and other Palicourea species are reported to cause sudden death in livestock and are suspected to contain MFA due to the similarity of clinical signs. In this study, an HPLC–APCI–MS method to detect and quantify MFA was developed and was used to investigate plant material from field collections and/or herbarium specimens of Mascagnia, Amorimia, and Palicourea species suspected of causing sudden death. MFA was detected in Amorimia amazonica, Amorimia camporum, Amorimia exotropica, Amorimia pubiflora, Amorimia rigida, and Amorimia septentrionalis as well as Palicourea aeneofusca. MFA concentrations differ greatly between Palicourea species and Amorimia species, which may explain the incidence of poisoning and the amount of plant material required to cause sudden death between these taxa. [Copyright &y& Elsevier]

Abstract: Background: Medication therapy management (MTM) services provide essential reviews of drug regimens and are increasingly recognized as beneficial to patient safety, improved health outcomes, and cost savings. Objective: To assess patient behavioral outcomes from an MTM service, including actions following receipt of a pharmacist report. Methods: A retrospective analysis of an MTM program at the Sanford Center for Aging (NV, USA) was conducted. Outcome measures included whether the patient discussed the review with the physician, whether any changes in the client’s drug regimen occurred, and whether the client feels more knowledgeable about his or her medications. Predictor variables included basic demographics, prescription insurance status, number of prescriptions taken, self-reported health status, and use of medications considered to be high risk. The analysis plan involved the use of multivariate logistic regression models. Results: The odds of discussing the medication review with physicians, making changes recommended in the report, and both discussing and making a change were 65%, 60%, and 67%, respectively, lower among those below poverty level than among those above poverty level; 95% confidence intervals (CIs): 0.15, 0.80; 0.18, 0.85; and 0.15, 0.73, respectively. The odds of those using high-risk drugs of making changes in drug regimens, and of discussing with physicians and making changes together, were 2 times higher than the odds of those not using these drugs, 95% CIs: 1.02, 4.31 and 1.20, 4.87, respectively. The likelihood of those reporting good or excellent health of doing the combination of discussing the MTM report with physicians and to make a drug regimen change was 2 times greater than for those reporting poor to fair health, 95% CI: 1.08, 3.65. Gender, ethnicity, age group, rural status, prescription drug insurance, and high polypharmacy were not significant factors for acting on the medication review in the adjusted model. Conclusion: MTM services are associated with enhanced patient self-advocacy, but like other interventions, they are constrained by social disparities. Greater attention to the resources of target populations to respond to pharmacy services is merited. [Copyright &y& Elsevier]

Abstract: Background context: The three-joint-complex, which includes the two facet joints and the intervertebral disc, significantly directs the movement of the lumbar spine. When studying the biomechanics of this complex, kinematics have traditionally been measured relative to a vertebral body-based reference frame. Recently, a facet-based reference system has been used to describe the same motions, but relative to the facets. Purpose: To describe in-plane and out-of-plane motion during flexion-extension (FE), lateral bending (LB), and axial rotation (AR) in the lumbar facets of cadaveric spines. Study design: Biomechanical in vitro study. Methods: Seven fresh-frozen and noninstrumented human cadaveric lumbar spines from L1 to sacrum were tested in FE, AR, and LB. Three coordinate systems were assigned to each vertebral body from L1 to L5: one corresponding to the vertebral body reference frame (X, Y, Z) and two corresponding to the left and right facet reference frames (A, B, C). The facet-based reference frame was aligned to each facet surface to provide descriptions of in-plane (articulation) and out-of-plane (separation) motion. For each of the three modes of loading, the magnitude of the translational range of motion (ROM) vector was calculated for the three reference frames. Results: During FE, there was a significant difference in the magnitude of the translational ROM vector of the right facet as compared with the vertebral body at L1–L2. During AR, there was a significant difference between the magnitude of translational ROM vector at L2–L3, L3–L4, L4–L5, and L1–L2 trended toward significance. During LB, there was a significant difference in the magnitude of the translational ROM vector at L1–L2, L2–L3, L3–L4, and L4–L5. Conclusions: A facet-based reference frame accounts for variations in facet orientation and provides a valuable characterization of facet articulation and separation that is not possible to derive from translations in a vertebral body–based reference frame. [Copyright &y& Elsevier]

Abstract: Background: Disc protrusion has been proposed to be a possible cause of both pain and stenosis in the lower spine. No previous study has described the amount of disc occlusion of the spinal canal and intervertebral foramen that occurs under different loading conditions. The objective of this study was to quantitatively assess the percent occlusion of the spinal canal and intervertebral foramen by disc bulge under different loading conditions. Methods: Spinal canal depth and foraminal width were measured on computed tomography–scanned images of 7 human lumbar spine specimens. In vitro disc bulge measurements were completed by use of a previously described method in which single functional spinal units were subjected to 3 separate load protocols in a spine test machine and disc bulge was recorded with an optoelectric motion system that tracked active light-emitting diodes placed on the posterior and posterolateral aspects of the intervertebral disc. Occlusion was defined as percentage of encroachment into area of interest by maximum measured disc bulge at corresponding point of interest (the spinal canal is at the posterior point; the intervertebral foramen is at the posterolateral point). Results: The mean spinal canal depth and mean foraminal width were 19 ± 4 mm and 5 ± 2 mm, respectively. Mean spinal canal occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 2.5% ± 1.9%, 2.5% ± 1.6%, and 1.5% ± 0.8%, respectively. Mean intervertebral foramen occlusion under a 250-N axial load, ± 2.5 Nm of flexion/extension, and ± 2.5 Nm of lateral bend was 7.8% ± 4.7%, 9.5% ± 5.7%, and 11.3% ± 6.2%, respectively. Conclusion: Percent occlusion of the spinal canal and intervertebral foramen is dependent on magnitude and direction of load. Exiting neural elements at the location of the intervertebral foramen are the most vulnerable to impingement and generation of pain. [Copyright &y& Elsevier]

Background: Angiotensin II receptor sub-type 1 (AGTR1) plays an important role in the regulation of the cellular immune process. We hypothesized that recurrent acute rejection is associated with increased gene expression of AGTR1 in human heart transplantation. Methods: We identified a group of 14 heart transplant recipients who had recurrent acute cellular rejection (RAR), defined as three consecutive episodes of acute rejection (Grade ≥3A). These patients were matched to a control group (n = 15). mRNA gene expression of AGTR1 was measured in heart biopsy specimens of controls at 1 week post-transplant. AGTR1 mRNA was determined serially in the RAR group at baseline, each rejection episode, and after resolution of rejection. Angiotensin-converting enzyme (ACE) polymorphism was also evaluated. Results: Both the control and RAR groups had similar mRNA AGTR1 expression at baseline. Compared with baseline, the RAR group had significantly increased mRNA expression of AGTR1 at the first episode of rejection (9-fold, p < 0.001), which increased further at the second episode (12-fold, p < 0.001) and peaked at the third episode (35-fold, p < 0.001). After resolution of rejection, AGTR1 expression was decreased significantly (p < 0.001), but remained elevated above baseline (6-fold, p < 0.001). No difference in ACE polymorphism was noted between the two groups. Compared with controls, the RAR patients had an increased incidence of hypertension, diabetes mellitus, chronic renal insufficiency and transplant vasculopathy during a mean follow-up period of 51.5 ± 12 months. Conclusions: This is the first report to describe increased mRNA expression of AGTR1 in response to recurrent cellular rejection. Up-regulation of AGTR1 responds to treatment of rejection but not to complete recovery, a phenomenon that may potentially explain the link between rejection and subsequent clinical outcome. [Copyright &y& Elsevier]

Abstract: Background:: The US Food and Drug Administration (FDA) and FDA advisory committees have been under increasing scrutiny as a result of media attention to safety concerns. Objective:: This article compares the decision-making process of the FDA''s Nonprescription Drugs Advisory Committee (NDAC) in 3 cases of a proposed switch from prescription to over-the-counter (OTC) status involving a nicotine replacement therapy product, 2 statins, and an emergency oral contraceptive. Methods:: This comparative case study reviewed written transcripts and slides from 4 NDAC committee meetings and a digital video disc recording of a later meeting held to reconsider one of the proposed switches. The focus was on the committee''s discussion and deliberation processes. Content analysis and iterative coding were used to assess the level of participation by committee members and the extent to which committee discussion adhered to both the key draft list questions provided by the FDA and the published DeLap criteria for switches from prescription to OTC status. Other major themes and discussion topics were identified, and the voting process was analyzed. Results:: In the absence of clearly defined meeting procedures, the advisory committees developed their own procedural standards. There were major differences between meetings in terms of the extent of discussion of the key draft list questions and adherence to the DeLap principles, discussion of other themes and topics, and voting methods. In each case, at least 1 major topic of discussion was not directly related to safety, efficacy, or self-use. Additional identified themes were the public health significance of a switch to OTC status, costs, and access. Conclusions:: Variability in processes created discrepancies in the decision-making criteria used by the NDAC committees. There is a need to establish structured procedures to achieve an optimal level of uniformity and transparency in advisory committee processes. [Copyright &y& Elsevier]

Background: Patients bridged to heart transplantation with a ventricular assist device (VAD) developed coronary vasculopathy at the same rate as non-bridged patients despite having higher levels of pre-formed antibodies. We hypothesized that allosensitized VAD patients have higher levels of immunosuppression and thus different morbidity and causes of mortality. Methods: Patients who received a transplant between January 1996 and May 2002 were separated into 2 groups based on the need for VAD support as a bridge to transplantation. Transplant and Inpatient Pharmacy Databases and charts were queried for date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, number of treated rejection episodes, and specific causes of death. Results: This study investigated 238 patients (125 VAD patients, 113 non-VAD patients). VAD patients were more likely to be allosensitized than non-VAD patients (20% vs 5%, p < 0.01). OKT3 was given to 22% of VAD patients as anti-rejection prophylaxis and 14% received pre-transplant plasmapheresis. Non-VAD patients rarely were desensitized (2.6% of non-VAD patients). After transplantation, 68 VAD patients (54%) and 44 non-VAD patients (39%) had episodes of severe rejection requiring therapy. Episodes of rejection in VAD patients were commonly treated with steroids (90%), plasmapheresis (10%), and OKT3 (7%), and episodes of rejection in non-VAD patients were treated with steroids (76%) and OKT3 (8%). The 5-year survival for both groups was similar (90% and 86% respectively, p = 0.31). VAD patients commonly died of sepsis (75%), and non-VAD patients died of rejection (39%) and ischemic transplant cardiomyopathy (30%). Conclusion: When short-term outcomes between bridged and non-bridged heart transplant recipients were compared, overall survival was similar but causes of death differed. Findings in this study might aid in the post-operative management of patients bridged to transplantation with a VAD. [Copyright &y& Elsevier]

Background: Recipients of hearts from donors with spontaneous intracerebral hemorrhage (ICH) are at increased risk of allograft vasculopathy compared with trauma donors. We have recently shown that the vitronectin receptor (integrin αVβ3) is upregulated in transplant vasculopathy. We hypothesized that donor ICH is associated with systemic activation of αVβ3 in the donor before transplantation. Methods: We evaluated mRNA expressions of αVβ3 (TaqMan PCR) in endomyocardial biopsy samples at 1-week post-transplant in 20 recipients from ICH donors and 20 recipients from trauma donors. To investigate whether systemic activation of αVβ3 was present in the donor before transplantation, αVβ3 expression was also evaluated in the corresponding donor spleen lymphocytes. All patients underwent serial coronary intravascular ultrasound to evaluate for coronary vasculopathy. The baseline characteristics were similar except for increased donor age in the ICH Group. Results: The ICH Group showed significant increased mRNA expression of αVβ3 in the heart biopsy samples (3.8-fold, p = 0.012) and in the corresponding donor spleen lymphocytes (3.5-fold, p = 0.014) compared with the Trauma Group. At 1 year, the ICH Group also showed increased progression of coronary vasculopathy. Multivariate regression analysis found that donor lymphocytic αVβ3 mRNA expression was independently associated with increased risk of vasculopathy (odds ratio, 1.9; 95% CI, 1.21–3.98, p = 0.03). Conclusions: Our report demonstrates the presence of systemic activation of αVβ3 in donors with spontaneous intracerebral hemorrhage and its association with the subsequent development of allograft vasculopathy in the recipient. [Copyright &y& Elsevier]

: ObjectivesWe evaluated whether the angiotensin II (Ang II) receptors from perioperation through one-year post-transplantation predict the transplant coronary artery disease (TCAD) progression.: BackgroundThe role of Ang II receptors (type 1: AT1R; type 2: AT2R) in TCAD is uncertain.: MethodsWe investigated 28 heart donors and the corresponding recipients. The levels of AT1R and AT2R messenger ribonucleic acid (mRNA) were examined in lymphocytes from the donor spleen and in the donor heart at one-week and one-year posttransplantation to determine their association with the progression of TCAD, measured as changes in maximal intimal thickness (CMIT) and plaque volume (CPV) by intravascular ultrasound (IVUS) examinations.: ResultsThe AT1R mRNA in lymphocytes from the donor spleen (CMIT: r = 0.73, p < 0.0001; CPV: r = 0.69, p < 0.0001) and in the donor hearts at one-week (CMIT: r = 0.52, p = 0.005; CPV: r = 0.56, p = 0.002) and at one-year (CMIT: r = 0.63, p < 0.0001; CPV: r = 0.43, p = 0.004) post-transplantation along with AT2R mRNA in the donor hearts at one-year post-transplantation (CMIT: r = 0.3, p < 0.0001; CPV: r = 0.53, p = 0.009) were univariate predictors, whereas AT1R mRNA in lymphocytes and in the donor hearts at one-year post-transplantation proved to be multivariate predictors of the progression of TCAD.: ConclusionsThese data suggest a role for Ang II receptors in the pathogenesis of TCAD and support a novel concept that TCAD may have its origin in the donor per se and may be modulated by the recipient''s inherent biological factors. [Copyright &y& Elsevier]

Numerous monofluoroacetate (MFA)-containing plants in Brazil cause sudden death syndrome precipitated by exercise in livestock, which is characterized by loss of balance, ataxia, labored breathing, muscle tremors, and recumbence leading to death. Four species of Palicourea collected at six farms were tested for the presence of MFA and their toxicity to rabbits. Palicourea longiflora and Palicourea barraensis contained MFA and caused sudden death in the rabbits. Palicourea croceoides and Palicourea nitidella did not contain MFA and were not toxic to rabbits. P. longiflora and P. barraensis were collected at three farms with a history of sudden death in their cattle. This is the first report of toxicity in regard to these two species. [ABSTRACT FROM AUTHOR]

One of the main intoxications to livestock in the Patagonia region of Argentina is the tremorgenic disease "Mal de Huecú", attributed to the consumption of the native grasses Poa huecu and/or Festuca argentina. In this report, five outbreaks of spontaneous intoxications were investigated. Several indole-diterpene alkaloids were identified in Poa huecu and Festuca argentina including the known tremorgen terpendole C and are likely the cause of "Mal de Huecú" disease. [Display omitted] • Poa huecu and Festuca argentina cause the tremorgenic syndrome known as Mal de Huecú. • An Epichloë -like fungal endophyte was detected in both plants. • Tremorgenic indole-diterpene alkaloids were detected in Poa huecu and Festuca argentina. [ABSTRACT FROM AUTHOR]

Broom snakeweed (Gutierrezia sarothrae) and threadleaf snakeweed (G. microcephala) are suffrutescent plants found in many parts of western US rangelands and are possibly toxic to grazing livestock. The toxic components are not known, but it has been suggested that the diterpene acids may be both toxic and abortifacient. One hundred sixty-two samples of snakeweed were collected from 55 locations in Colorado, Oklahoma, New Mexico, Texas, Wyoming and Utah and were taxonomically classified. Samples were analyzed by GC-MS in a chemophenetic analysis and grouped into individual chemotypes based on diterpene acid content. The GC-MS profiles were found to be diverse showing at least eight different chemotypes. From each of the chemotypes the major diterpene acids were isolated and characterized by IR, MS and NMR spectroscopy. Twenty-one diterpenoids were identified and found to be a mix of furano, lactone, di-acid and esters of labdane, ent -labdane and chlerodane acids and alcohols. Only four of the 21 compounds isolated had been previously reported as occurring in G. sarathorea or G. microcephala , while another eight compounds were previously reported from other Gutierrezia or related species. Nine of the isolated diterpenoids have not been previously reported and their structure elucidation is reported. Image 1 • A chemophenetic analysis of two Gutierrezia (snakeweed) species is reported. • Eight chemotypes were found from Gutierrezia sarothrae and G. microcephala. • Twenty-one diterpenoids were characterized from G. sarothrae or G. microcephala. • The structure elucidation of nine undescribed diterpenoids is reported. [ABSTRACT FROM AUTHOR]