Effects of intentional weight loss in patients with obesity and heart failure: a systematic review.

OBJECTIVE: Obesity is an independent risk factor for the development of heart failure, and the two commonly co-exist. The European Society of Cardiology does not provide guidance regarding weight loss strategies in heart failure. The aim of this study was to systematically review the evidence for outcomes following intentional weight loss in patients with heart failure and obesity. METHOD: A systematic review of English articles was undertaken using databases PubMed, Embase and CENTRAL. Randomized controlled trials and observational studies reporting outcomes following intentional weight loss by lifestyle, surgical or pharmacotherapy intervention in patients with obesity and heart failure were included. RESULTS: Four randomized controlled trials and seven observational studies were identified. Two randomized controlled trials used diet and exercise as an intervention, one used diet alone and one used a pharmacological intervention (orlistat). All but one reported significant weight loss. Two reported improvement in exercise capacity and quality of life. One reported improvement in New York Heart Association functional class in heart failure with preserved ejection fraction. The observational studies, five of which reported on outcomes following bariatric surgery, despite being small, heterogeneous and high risk of bias, suggested a trend in improvement of left ventricular function, quality of life and exercise capacity following weight loss. CONCLUSION: Weight loss is achievable with lifestyle intervention in those with heart failure and obesity and may result in improvements in New York Heart Association classification, quality of life and exercise capacity.

Tall fescue ergot alkaloids are vasoactive in equine vasculature.

Mares grazing endophyte-infected () tall fescue () typically exhibit reproductive dysfunction rather than problems associated with peripheral vasoconstriction as a primary sign of the fescue toxicosis syndrome. Research using Doppler ultrasonography demonstrated that consumption of endophyte-infected tall fescue seed causes measurable vasoconstriction in the medial palmar artery. The objective of this study was to evaluate contractile responses of medial palmar artery and vein to increasing concentrations of various tall fescue alkaloids. Medial palmar arteries and veins were collected immediately following euthanasia from 23 horses of mixed breed, age, and gender from both forelimbs, and uterine arteries were collected from females ( = 12). Vessels were separated, cleaned of excess connective and adipose tissue, divided into 2- to 3-mm cross-sections, and suspended in a multimyograph chamber with continuously oxygenated Krebs-Henseleit buffer (95% O/5% CO; pH 7.4; 37°C). Following a 90-min equilibration and recovery from reference compound exposure, increasing concentrations of norepinephrine, 5-hydroxytryptamine, ergotamine, and ergonovine for the palmar artery and vein and uterine artery and ergovaline, ergocryptine, ergocristine, ergocornine, and lysergic acid for the palmar artery and vein were added to assess vasoactivity. Data were normalized as a percentage of contractile response induced by the reference compound addition and analyzed as a completely randomized design. Both norepinephrine and serotonin were vasoactive in all 3 types of blood vessels. Neither ergotamine nor ergonovine were vasoactive in the uterine artery. All alkaloids tested with the palmar artery and vein produced a contractile response, except that neither the palmar artery nor the palmar vein responded to lysergic acid ( > 0.05). Ergovaline was the most vasoactive ergot alkaloid in both the palmar artery and the palmar vein ( < 0.05) followed by ergonovine, whereas out of the 4 remaining ergopeptine alkaloids tested, ergocristine induced the lowest contractile response. Although horses do not outwardly appear to be affected by peripheral vasoconstriction as observed in cattle, these data indicate that tall fescue alkaloids are vasoactive and suggest that potential exists for peripheral vascular effects of tall fescue alkaloids in horses. This does not appear to be the case for the uterine artery, and future research should be directed at understanding how ergot alkaloids cause equine reproductive dysfunction.

Informed decomposition of electroencephalographic data.

BACKGROUND: Blind source separation techniques have become the de facto standard for decomposing electroencephalographic (EEG) data. These methods are poorly suited for incorporating prior information into the decomposition process. While alternative techniques to this problem, such as the use of constrained optimization techniques, have been proposed, these alternative techniques tend to only minimally satisfy the prior constraints. In addition, the experimenter must preset a number of parameters describing both this minimal limit as well as the size of the target subspaces. NEW METHOD: We propose an informed decomposition approach that builds upon the constrained optimization approaches for independent components analysis to better model and separate distinct subspaces within EEG data. We use a likelihood function to adaptively determine the optimal model size for each target subspace. RESULTS: Using our method we are able to produce ordered independent subspaces that exhibit less residual mixing than those obtained with other methods. The results show an improvement in modeling specific features of the EEG space, while also showing a simultaneous reduction in the number of components needed for each model. COMPARISON WITH EXISTING METHOD(S): We first compare our approach to common methods in the field of EEG decomposition, such as Infomax, FastICA, PCA, JADE, and SOBI for the task of modeling and removing both EOG and EMG artifacts. We then demonstrate the utility of our approach for the more complex problem of modeling neural activity. CONCLUSIONS: By working in a one-size-fits-all fashion current EEG decomposition methods do not adapt to the specifics of each data set and are not well designed to incorporate additional information about the decomposition problem. However, by adding specific information about the problem to the decomposition task, we improve the identification and separation of distinct subspaces within the original data and show better preservation of the remaining data.

Attempts to induce nocardioform placentitis (Crossiela equi) experimentally in mares.

REASONS FOR PERFORMING STUDY: Nocardioform placentitis in horses is poorly understood, and the development of an experimental model would be of help in understanding the pathogenesis of the disease. OBJECTIVES: To investigate whether (1) intrauterine inoculation of Crossiela equi during the periovulatory period or (2) i.v., oral or intranasopharyngeal inoculation of C. equi during midgestation would result in nocardioform placentitis, and (3) before and after mating endometrial swabs present evidence of nocardioform placentitis-associated organisms (C. equi or Amycolatopsis spp.). METHODS: In Study I, mares (n = 20) received an intrauterine inoculation of C. equi 24 h after artificial insemination. Endometrial swabs were obtained 24 h post inoculation for PCR analysis. In Study II, pregnant mares (at 180-240 days of gestation) were inoculated with C. equi by intranasopharyngeal (n = 5), oral (n = 4) or i.v. (n = 4) routes. Sixty contemporaneous pregnant mares maintained on the same farm served as control animals. In Study III, privately owned Thoroughbred mares (n = 200) had endometrial swabs collected before and within 24-48 h after mating for detection of nocardioform microorganisms. RESULTS: In Study I, C.equi was identified by PCR in 3 of 20 mares following intrauterine inoculation. Pregnancy was established in 19 of 20 treated mares. There were 2 embryonic losses and one abortion at 177 days of gestation (undetermined cause). Sixteen mares delivered a normal foal and placenta. In Study II, one mare (oral inoculation) aborted at 200 days of gestation (unidentified cause). The remaining mares delivered a normal foal and placenta. In Study III, none of the mares yielded positive endometrial PCR for nocardioform microorganisms. CONCLUSIONS: We were unable to induce nocardioform placentitis, and there was no evidence of nocardioform microorganisms in endometrial swabs of broodmares before or after mating. These findings suggest that nocardioform placentitis is not induced simply via the presence of nocardiform actinomycetes and that route, insufficient duration of exposure and dose may play a role in the development of disease. Additional predispositions may also be involved in the development of nocardioform placentitis.

Applying EEG phase synchronization measures to non-linearly coupled neural mass models.

BACKGROUND: Recent neuroimaging analyses aim to understand how information is integrated across brain regions that have traditionally been studied in isolation; however, detecting functional connectivity networks in experimental EEG recordings is a non-trivial task. NEW METHOD: We use neural mass models to simulate 10-s trials with coupling between 1-3 and 5-8s and compare how well three phase-based connectivity measures recover this connectivity pattern across a set of experimentally relevant conditions: variable oscillation frequency and power spectrum, feed forward connections with or without feedback, and simulated signals with and without volume conduction. RESULTS: Overall, the results highlight successful detection of the onset and offset of significant synchronizations for a majority of the 28 simulated configurations; however, the tested phase measures sometimes differ in their sensitivity and specificity to the underlying connectivity. COMPARISON WITH EXISTING METHODS: Prior work has shown that these phase measures perform well on signals generated by a computational model of coupled oscillators. In this work we extend previous studies by exploring the performance of these measures on a different class of computational models, and we compare the methods on 28 variations that capture a set of experimentally relevant conditions. CONCLUSIONS: Our results underscore that no single phase synchronization measure is substantially better than all others, and experimental investigations will likely benefit from combining a set of measures together that are chosen based on both the experimental question of interest, the signal to noise ratio in the EEG data, and the approach used for statistical significance.

Vasoconstriction in horses caused by endophyte-infected tall fescue seed is detected with Doppler ultrasonography.

The hypotheses that endophyte (Neotyphodium coenophialum)-infected tall fescue (TF) seed causes vasoconstriction in horses in vivo and that ground seed would cause more pronounced vasoconstriction than whole seed were tested. Ten horses each received 1 of 3 treatments: endophyte-free ground (E-G; n = 4 horses) seed, endophyte-positive whole (E+W; n = 3) seed, or endophyte-positive ground (E+G; n = 3) seed. There were two 14-d periods, P1 and P2. During P1, animals were adapted to a concentrate (0.2% BW, as fed, twice daily) and alfalfa cubes. During P2, the seed was mixed into the concentrate portion of the diet and alfalfa cubes were offered ad libitum. Fescue seed was fed in increasing amounts ranging from 0.02% BW on d 1 (averaging 76 ug/kg ergovaline + ergovalinine) to 0.22% BW on d 11 to 14 (averaging 713 ug/kg ergovaline + ergovalinine). The distal palmar artery of the left foreleg of each horse was scanned via Doppler ultrasonography for 4 d during each period, with 5 replicate scans performed on each scanning day. The measurements taken at each scan included artery luminal diameter, area, and circumference, peak systolic velocity, end diastolic velocity and blood flow variables. Animal temperature, heart rate, and respiration rate and ambient temperature and humidity were also recorded. Blood samples were taken on each scanning day to measure inflammatory cytokine mRNA abundances, and blood samples were collected on d 0, 4, 8, and 14 of P2 to measure prolactin concentrations. Consumption of E+G TF seed caused decreased artery lumen diameter (P = 0.0033), area (P = 0.0406), and circumference (P = 0.0480) compared with E-G seed, and E+W seed produced an intermediate response. Blood flow volume was reduced (P < 0.05) during P2 in horses receiving E+G seed compared with horses receiving E-G seed. Other ultrasound variables were not different (P > 0.05) among treatment groups, and neither were cytokine mRNA or prolactin concentrations. Treatment did not alter (P > 0.05) animal temperature, heart rate, or respiration rate, and neither ambient temperature nor relative humidity was consistently correlated with any response variable measured. Taken together, these data confirm that consumption of E+G fescue seed caused vasoconstriction in horses, which could be readily measured by Doppler ultrasonography. Use of Doppler ultrasound to monitor the diameter of the palmar artery of horses grazing endophyte-infected (E+) fescue pastures may provide a convenient and satisfactory biomarker to determine premonitory signs of fescue toxicosis.

Comparing parametric and nonparametric methods for detecting phase synchronization in EEG.

Detecting significant periods of phase synchronization in EEG recordings is a non-trivial task that is made especially difficult when considering the effects of volume conduction and common sources. In addition, EEG signals are often confounded by non-neural signals, such as artifacts arising from muscle activity or external electrical devices. A variety of phase synchronization analysis methods have been developed with each offering a different approach for dealing with these confounds. We investigate the use of a parametric estimation of the time-frequency transform as a means of improving the detection capability for a range of phase analysis methods. We argue that such an approach offers numerous benefits over using standard nonparametric approaches. We then demonstrate the utility of our technique using both simulated and actual EEG data by showing that the derived phase synchronization estimates are more robust to noise and volume conduction effects.

Invited review: the role of caterpillars in mare reproductive loss syndrome: a model for environmental causes of abortion.

A new abortigenic disease, now known as mare reproductive loss syndrome (MRLS), significantly affected the horse industry in the Ohio River Valley of the United States in late April and early May of 2001 and 2002. In 2001, approximately 25% of all pregnant mares aborted within several weeks (over 3,000 mares lost pregnancies), and abortion rates exceeded 60% on some farms. Mare reproductive loss syndrome struck hard and without warning, it was caused by something in the environment, it was not transmitted between animals, and it was not associated with any known abortigenic agent or disease. These experiments demonstrated that horses will inadvertently consume Eastern tent caterpillars (ETC) when the insects are present in the pasture or other feedstuffs, and MRLS-type abortions were induced in experimental animals (mares and pigs) by mixing ETC with the feed of the animals. Eastern tent caterpillars are hirsute (hairy) caterpillars, and the only part of the caterpillar that caused MRLS abortions was the cuticle. The experiments revealed that the setae (hairs) embed into the submucosa of the alimentary tract creating microgranulomatous lesions. It is hypothesized that the alimentary tract lesions allow bacteria from the alimentary tract of the mare, principally streptococci, actinobacilli, and to a lesser extent enterococci, to invade the circulatory system of the mare. The bacteria then establish infections in tissues where the immune surveillance of the mare is reduced, such as the fetus and placenta. Fetal and placental fluid bacterial infections lead to fetal death and abortion characteristic of MRLS. Inadvertent ingestion of ETC by pregnant mares causes MRLS. Currently the only known means to prevent MRLS is to avoid exposure of horses, particularly pregnant mares, to ETC and probably most hirsute caterpillars.

The psychometric properties of the Hospital Anxiety and Depressions Scale adapted for use with people with intellectual disabilities.

BACKGROUND: There is increasing recognition of depression in people with intellectual disabilities (ID). There is a need to develop well-standardised self-report measures for both clinical and research purposes. This paper presents some psychometric properties of the Hospital Anxiety and Depression Scale (HADS) adapted for use with people with ID. The anhedonic emphasis in the depression scale of the HADS may be particularly useful for people with ID who present with high rates of physical co-morbidity. METHOD: A total of 197 people with ID completed an adapted HADS; 32 participants also completed the Zung Depression Scale and 42 also completed the Glasgow Depression Scale. RESULTS: The obtained factor structure is similar to the original form of the scale used with people without ID. However, the underlying question wording of the HADS, where most depression items are phrased positively and most anxiety items are phrased negatively, makes clear interpretation of the factor structure difficult. The HADS has an adequate internal reliability and correlates well with other self-report measures of depression. CONCLUSIONS: The HADS may need further adaptation; however, the measurement of anhedonia is a useful addition to the self-report measures of depression available for people with ID.

Modificaciones en la distribución de potencia en función de la consolidación de la memoria implícita mediante una tarea de dactilografía / Modification of the power distribution according to the consolidation of implicity memory by means of a typing task

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Development of somatosensory-motor integration: an event-related analysis of infant posture in the first year of independent walking.

The ability to integrate sensation with action is considered an important factor underlying the development of upright stance and locomotion. While many have studied sensory influences on posture, the nature of these influences and how they change with development have yet to be thoroughly characterized in infancy. Six infants were examined from 1 month prior to walk onset until 9 months of independent walking experience while standing quietly and touching either a static or a dynamic surface. Five adults were examined performing an analogous task. An event-related, time-frequency analysis was used to assess the relationship between postural sway and the motion of the somatosensory stimulus. Phase consistency between sway and stimulus was observed for both adults and infants, and with walking experience the infants increased their phase consistency rather than changing aspects of response amplitude. It is concluded that walking experience provides opportunities for an active tuning of sensorimotor relations for adequate estimation of body position in space and thus facilitates refined control over temporal aspects of postural sway.

The temporal organization of posture changes during the first year of independent walking.

Although the development of upright posture has received considerable attention, the quiet stance of infants in their first months of learning this fundamental behavior has not been well studied. The purpose of the present study was to characterize the time evolutionary properties, or temporal organization, of these infants' unperturbed upright stance as well as to elucidate how somatosensory information influences that organization. Six healthy, full-term infants were tested monthly from walk onset until 9 months of independent walking experience while standing either independently or touching a static surface. The structure of sway was assessed through stabilogram-diffusion analysis using an exponential Ornstein-Uhlenbeck characterization. The results of this analysis revealed two new insights into postural development. First, the developmental changes in quiet stance involved a decreased rate at which sway decays to maximal variance, rather than an attenuation of the magnitude of that variance. Specifically, measures indexing amount of sway variance were significantly reduced when touching a static surface as compared with an independent stance condition, but revealed no change with increased walking experience. Further, a reduction in the average rate constant of decay indicated an increased influence of long time-scale sway corrections on the overall sway trajectory. Second, it was shown that, at early walk ages, the use of touch both reduced the amount of variance and shifted the rate constant of sway towards longer time-scale displacements. Taken in the context of previous research, these results support our conclusion that early postural development embodies the dual tasks of calibrating sensorimotor relations for estimation of self-motion as well as identification and tuning of control system properties.

Aging, physical activity, and cognitive processing: an examination of P300.

Physical activity appears to attenuate the decline of cognitive function typically observed in older men and women. The P300 component of the event-related potential (ERP) is particularly affected by aging and allows for basic neurobiological assessment of cognitive function. Three aspects of the P300 component (i.e. latency, amplitude, and area under the curve (AUC)), elicited by an oddball task, were derived to assess cognitive function in young and older participants (N=73) who were further classified as high- and low-active. The low-active elderly participants exhibited larger AUC values than those observed in all other groups which were undifferentiated. That is, the high-active elderly and the young participants exhibited smaller AUC values than the low-active older group. In conclusion, higher levels of physical activity in the elderly may be associated with a reduction in the neural resources allocated in response to simple cognitive challenge. This interpretation is consistent with the concept of psychomotor efficiency proposed by Hatfield and Hillman [The psychophysiology of sport: a mechanistic understanding of the psychology of superior performance. In: Singer RN, Hausenbias HA, Janelle CM, editors. Handbook of sport psychology. 2nd ed. New York: Wiley; 2001, p. 362-88].

The role of the left temporal region under the cognitive motor demands of shooting in skilled marksmen.

A number of investigators have reported elevated left temporal alpha power in marksmen during response preparation. This finding has been interpreted to indicate the suppression of irrelevant cognitive processes. However, lower-order motor processes have not been excluded as a possible explanation. Event-related alpha power (11-13 Hz) was examined at sites T3, T4, C3, and C4 in eight skilled marksmen during shooting and two control tasks varying in perceptual-motor complexity. Over an 8-s period preceding the trigger pull, the marksmen exhibited higher power and slope at T3 than at all other sites during shooting compared with the control conditions. No such difference between conditions was detected at C3 and C4. The relative synchrony of left temporal alpha power during shooting, in conjunction with the lack of change at central sites, is inconsistent with the explanation that the effect is accounted for by 'lower-order' motor processes exclusively involving the central region.

The U8 snoRNA gene family: identification and characterization of distinct, functional U8 genes in Xenopus.

U8 snoRNA is the RNA component of a small nucleolar ribonucleoprotein (U8 snoRNP) required for accumulation of mature 5.8S and 28S rRNAs, components of the large ribosomal subunit. We have identified two putative U8 genes in Xenopus laevis. Sequence analysis of the coding regions of these two genes indicate that both differ at several positions from the previously characterized U8 RNA and that the two differ from each other. Functional analysis of these genes indicates that both are transcribed in vivo, produce stable U8 transcripts, and are capable of facilitating pre-rRNA processing in vivo. These data demonstrate that natural sequence variation exists among the U8 snoRNA genes in Xenopus. Alignment of these three Xenopus U8 sequences with the previously described mammalian U8 homologues in mouse, rat and human has provided information about evolutionarily conserved sequence and structural elements in U8 RNA. Identification and functional characterization of these naturally occurring variants in Xenopus has helped identify regions in U8 RNA that may be critical for function.

Immortalization of equine trophoblast cell lines of chorionic girdle cell lineage by simian virus-40 large T antigen.

Immortalized cell lines have many potential experimental applications including the analysis of molecular mechanisms underlying cell-specific gene expression. We have utilized a recombinant retrovirus encoding the simian virus-40 (SV-40) large T antigen to construct several immortalized cell lines of equine chorionic girdle cell lineage - the progenitor cells that differentiate into the equine chorionic gonadotropin (eCG) producing endometrial cups. Morphologically, the immortalized cell lines appear similar to normal chorionic girdle cells. Derivation of the immortalized cell lines from a chorionic girdle cell lineage was verified by immunological detection of cell-surface antigens specific to equine invasive trophoblasts. The cell lines differed, however, from mature chorionic girdle cells or endometrial cup cells in that they did not produce eCG and did express MHC class I molecules. Thus, these cell lines appear to have been arrested at a stage of development prior to final differentiation into endometrial cup cells. It was also determined that some of these cell lines as well as endometrial cups express the estrogen receptor-related receptor beta gene, but not the glial cell missing gene (GCMa) both of which are expressed in the murine and human placenta. Among these cell lines, three (eCG 50.5, 100.6 and 500.1) express eCG alpha mRNA. Since regulation of eCG alpha subunit gene is largely unknown, we investigated the signal transduction pathways regulating the eCG alpha subunit gene. Both activators of protein kinase A (PKA) and protein kinase C (PKC) induced the expression of eCG alpha subunit expression 3.2 (P<0.05)- and 1.9 (P<0.05)-fold respectively, in the eCG 500.1 cell line. However, activation of these pathways failed to induce eCG beta subunit expression. In conclusion, lines of equine trophoblast cells have been immortalized that display markers characteristic of those with the equine chorionic girdle and endometrial cup cell lineage. A subset of these cells expresses the eCG alpha subunit gene which is responsive to activators of the PKA and PKC signal transduction pathways.

A phase II study of biochemotherapy for the treatment of metastatic malignant melanoma.

The use of interleukin-2 (IL-2) and interferon-alpha (IFNalpha) in combination with chemotherapy for the treatment of advanced malignant melanoma has generated considerable interest. In particular, the relatively high number of durable complete responses has suggested this may be a significant advance in the treatment of malignant melanoma. We report our experience at the University of Colorado in 43 patients, including many with poor prognostic factors. Patients received cisplatin 20 mg/m2 on days 1-4, vinblastine 1.6 mg/m2 on days 1-4, dacarbazine 800 mg/m2 on day 1, IL-2 9 x 10(6) IU/m2 per day intravenously over 24h on days 1-4 and IFNalpha 5 x 10(6) IU/m2 per day subcutaneously on days 1-5 every 3 weeks. The median follow-up for all patients was 34 months. Responses were seen in 20 patients (47%, 95% confidence interval 31-62%) and comprised five complete responses (CRs) (12%) and 15 partial responses (PRs) (35%). Two patients achieving a CR remain disease free at 45 and 47 months follow-up. In addition three patients who obtained a surgical CR and another with only minor residual changes on computed tomography scan have not progressed at 27, 30, 40 and 27 months, respectively. Toxicity was manageable, but all patients had at least one grade 3 or 4 toxicity, predominantly hypotension and neutropenia. There were no treatment-related deaths. In conclusion, the response rate and duration is within the range previously reported for biochemotherapy. The results of ongoing randomized studies are awaited to better define the value of biochemotherapy in the treatment of advanced melanoma.

Pathophysiology of asthma.

Asthma is a complex, multifactorial disease. Although airway reactivity, inflammation, and increased mucus secretion are agreed on universally as the central components of asthma, the pathophysiology of each of these is complex. This Article reviews the physiologic events resulting in symptoms of asthma. The contributions of genetics and environment to the development of the asthma phenotype are discussed. Gastroesophageal reflux and environmental allergies are prevalent conditions in asthmatic patients and often act as significant triggers for asthma symptoms.

Wounds and pain management.

Practice profiles are reflective pieces written by nurses in practice and based on continuing professional development articles. This week Karen McDowell discusses wound management and pain control. CPD article NS14, Gould D (1999) Wound management and pain control. Nursing Standard. 14, 6, 47-54.