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Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function.
Background/objectiveYouth with obesity have an altered high-density lipoprotein (HDL) subspecies profile characterized by depletion of large apoE-rich HDL particles and an enrichment of small HDL particles. The goal of this study was to test the hypothesis that this atherogenic HDL profile is reversible and that HDL function would improve with metabolic surgery.MethodsSerum samples from adolescent males with severe obesity mean±s.d. age of 17.4±1.6 years were studied at baseline and 1 year following vertical sleeve gastrectomy (VSG). HDL subspecies and HDL function were evaluated pre and post VSG using paired t-tests. A lean group of adolescents was included as a reference group.ResultsAfter VSG, body mass index decreased by 32% and insulin resistance as estimated by homeostatic model assessment of insulin resistance decreased by 75% (both P<0.01). Large apoE-rich HDL subspecies increased following VSG (P<0.01) and approached that of lean adolescents despite participants with considerable residual obesity. In addition, HDL function improved compared with baseline (cholesterol efflux capacity increased by 12%, HDL lipid peroxidation potential decreased by 30% and HDL anti-oxidative capacity improved by 25%, all P<0.01).ConclusionsMetabolic surgery results in a significant improvement in the quantity of large HDL subspecies and HDL function. Our data suggest metabolic surgery may improve cardiovascular risk in adolescents and young adults
Age composition, growth, and reproduction of koi carp (Cyprinus carpio L.) in the lower Waikato, New Zealand
A total of 566 koi carp (Cyprinus carpio) from the lower Waikato region were aged from scales and opercular bones, and growth was modelled with the von Bertalanffy growth function. There was no difference in growth rate between male and female carp. Growth of koi carp between zero and 3 years of age was lower than that of common carp in Europe and Australia. However, after 5 years of age the growth of koi carp was higher than that of common carp in Europe, but still below that of carp in Australia. Males rarely lived in excess of 8 years, whereas females lived to 12 years. Mean total fecundity calculated from 44 running-ripe females was 299 000 oocytes (±195 600 SD) (range 29 800–771 000). Relative fecundity ranged from 19 300 to 216 000 oocytes kg–1 total body weight, with a mean of 97 200 (±35 000 SD) oocytes kg–1. Feral koi carp in the Waikato are capable of multiple spawnings within their lifetimes. Within a spawning season, Waikato populations of feral koi carp contained females that spawned once, and females that had the potential to have spawned repeatedly. Female gonadosomatic index (GSI) varied with season and was negatively related to water temperature
Caterpillars and fungal pathogens: two co-occurring parasites of an ant-plant mutualism
In mutualisms, each interacting species obtains resources from its partner that it would obtain less efficiently if alone, and so derives a net fitness benefit. In exchange for shelter (domatia) and food, mutualistic plant-ants protect their host myrmecophytes from herbivores, encroaching vines and fungal pathogens. Although selective filters enable myrmecophytes to host those ant species most favorable to their fitness, some insects can by-pass these filters, exploiting the rewards supplied whilst providing nothing in return. This is the case in French Guiana for Cecropia obtusa (Cecropiaceae) as Pseudocabima guianalis caterpillars (Lepidoptera, Pyralidae) can colonize saplings before the installation of their mutualistic Azteca ants. The caterpillars shelter in the domatia and feed on food bodies (FBs) whose production increases as a result. They delay colonization by ants by weaving a silk shield above the youngest trichilium, where the FBs are produced, blocking access to them. This probable temporal priority effect also allows female moths to lay new eggs on trees that already shelter caterpillars, and so to occupy the niche longer and exploit Cecropia resources before colonization by ants. However, once incipient ant colonies are able to develop, they prevent further colonization by the caterpillars. Although no higher herbivory rates were noted, these caterpillars are ineffective in protecting their host trees from a pathogenic fungus, Fusarium moniliforme (Deuteromycetes), that develops on the trichilium in the absence of mutualistic ants. Therefore, the Cecropia treelets can be parasitized by two often overlooked species: the caterpillars that shelter in the domatia and feed on FBs, delaying colonization by mutualistic ants, and the fungal pathogen that develops on old trichilia. The cost of greater FB production plus the presence of the pathogenic fungus likely affect tree growth
Functional outcome and complications following surgery for Dupuytren’s disease: a multi-centre cross-sectional study
Variables associated with recurrent Dupuytren’s disease, or a ‘diathesis’, have been investigated, but those associated with functional outcome and complications are less well studied. Outcomes 1 or 5 years after an aponeurotomy, fasciectomy or dermofasciectomy were assessed by patient interview and examination at five UK centres. A total of 432 procedures were studied. The reoperation rate did not differ at 1 year (p = 0.396, Chi-square test with Monte Carlo simulation), but was higher after aponeurotomy in the 5-year group (30%, versus 6% after fasciectomy and 0% after dermofasciectomy, p = 0.003, Chi square test with Monte Carlo simulation). Loss of function (DASH>15) did not differ between procedures at 5 years, even when reoperation and other variables were controlled. Diabetes, female gender and previous ipsilateral surgery were associated with poorer function in logistic regression analysis. The variables associated with poor function after treatments differ from diathesis variables. Aponeurotomy had lower complication rates than fasciectomy and dermofasciectomy. This may counterbalance the former’s higher recurrence rate and explain why aponeurotomy demonstrated similar long-term functional outcome compared with excisional surgery in this study
Upper gastrointestinal Crohn's disease
Symptomatic gastroduodenal manifestations of Crohn's disease are rare, with less than 4% of patients being clinically symptomatic. Gastroduodenal involvement may, however, be found endoscopically in 20% and in up to 40% of cases histologically, most frequently as Helicobacter pylori-negative focal gastritis, usually in patients with concomitant distal ileal disease. In practice, the activity of concomitant distal Crohn's disease usually determines the indication for therapy, except in the presence of obstructive gastroduodenal symptoms. With the few data available, it seems correct to say that localized gastroduodenal disease should be treated with standard medical therapy used for more distal disease, with the exception of the galenic formulation of sulfasalazine and mesalazine with pH-dependent release. The presence of symptoms of obstruction needs aggressive therapy. If medical therapy with steroids and immunomodulatory drugs does not alleviate the symptoms, balloon dilation and surgery are the options to consider. [Ed.]]]>
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Agniṣṭoma and the nature of sacrifice
Bronkhorst, Johannes
info:eu-repo/semantics/bookPart
incollection
2016
On Meaning and Mantras: Essays in Honor of Frits Staal, pp. 79-99
Thompson, George (ed.)
Payne, Richard K. (ed.)
info:eu-repo/semantics/altIdentifier/isbn/978-1-886439-64-1
eng
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oai:serval.unil.ch:BIB_5E8C17A3E220
2022-05-07T01:18:50Z
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Selective regulation of acid-sensing ion channel 1 by serine proteases.
info:doi:10.1074/jbc.M407381200
info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M407381200
info:eu-repo/semantics/altIdentifier/pmid/15247234
Poirot, O.
Vukicevic, M.
Boesch, A.
Kellenberger, S.
info:eu-repo/semantics/article
article
2004
Journal of Biological Chemistry, vol. 279, no. 37, pp. 38448-38457
info:eu-repo/semantics/altIdentifier/pissn/0021-9258[print], 0021-9258[linking]
<![CDATA[Acid-sensing ion channels (ASICs) are neuronal Na(+) channels that belong to the epithelial Na(+) channel/degenerin family. ASICs are transiently activated by a rapid drop in extracellular pH. Conditions of low extracellular pH, such as ischemia and inflammation in which ASICs are thought to be active, are accompanied by increased protease activity. We show here that serine proteases modulate the function of ASIC1a and ASIC1b but not of ASIC2a and ASIC3. We show that protease exposure shifts the pH dependence of ASIC1a activation and steady-state inactivation to more acidic pH. As a consequence, protease exposure leads to a decrease in current response if ASIC1a is activated by a pH drop from pH 7.4. If, however, acidification occurs from a basal pH of approximately 7, protease-exposed ASIC1a shows higher activity than untreated ASIC1a. We provide evidence that this bi-directional regulation of ASIC1a function also occurs in neurons. Thus, we have identified a mechanism that modulates ASIC function and may allow ASIC1a to adapt its gating to situations of persistent extracellular acidification
Clinical Effectiveness of the Queen Square Intensive Comprehensive Aphasia Service for Patients With Poststroke Aphasia
BACKGROUND AND PURPOSE: Poststroke aphasia has a major impact on peoples' quality of life. Speech and language therapy interventions work, especially in high doses, but these doses are rarely achieved outside of research studies. Intensive Comprehensive Aphasia Programs (ICAPs) are an option to deliver high doses of therapy to people with aphasia over a short period of time. METHODS: Forty-six people with aphasia in the chronic stage poststroke completed the ICAP over a 3-week period, attending for 15 days and averaging 6 hours of therapy per day. Outcome measures included the Comprehensive Aphasia Test, an impairment-based test of the 4 main domains of language (speaking, writing, auditory comprehension, and reading) which was measured at 3 time points (baseline, immediately posttreatment at 3 weeks and follow-up at 12-week post-ICAP); and, the Communicative Effectiveness Index, a carer-reported measure of functional communication skills collected at baseline and 12 weeks. RESULTS: A 2-way repeated measures multivariate ANOVA was conducted. We found a significant domain-by-time interaction, F=12.7, P<0.0005, indicating that the ICAP improved people with aphasia's language scores across all 4 domains, with the largest gains in speaking (Cohen's d=1.3). All gains were maintained or significantly improved further at 12-week post-ICAP. Importantly, patients' functional communication, as indexed by changes on the Communicative Effectiveness Index, also significantly improved at 12-week post-ICAP, t=5.4, P<0.0005, also with a large effect size (Cohen's d=0.9). CONCLUSIONS: People with aphasia who participated in the Queen Square ICAP made large and clinically meaningful gains on both impairment-based and functional measures of language. Gains were sustained and in some cases improved further over the subsequent 12 weeks
Asymmetric Dark Matter from Leptogenesis
We present a new realization of asymmetric dark matter in which the dark
matter and lepton asymmetries are generated simultaneously through two-sector
leptogenesis. The right-handed neutrinos couple both to the Standard Model and
to a hidden sector where the dark matter resides. This framework explains the
lepton asymmetry, dark matter abundance and neutrino masses all at once. In
contrast to previous realizations of asymmetric dark matter, the model allows
for a wide range of dark matter masses, from keV to 10 TeV. In particular, very
light dark matter can be accommodated without violating experimental
constraints. We discuss several variants of our model that highlight
interesting phenomenological possibilities. In one, late decays repopulate the
symmetric dark matter component, providing a new mechanism for generating a
large annihilation rate at the present epoch and allowing for mixed warm/cold
dark matter. In a second scenario, dark matter mixes with the active neutrinos,
thus presenting a distinct method to populate sterile neutrino dark matter
through leptogenesis. At late times, oscillations and dark matter decays lead
to interesting indirect detection signals.Comment: 32 pages + appendix, references added, minor change
Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial
Background
Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges.
Methods
We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented).
Results
At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points.
Conclusion
In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes
High platelet reactivity in patients with acute coronary syndromes undergoing percutaneous coronary intervention: Randomised controlled trial comparing prasugrel and clopidogrel
Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited. Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS). Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. “poor responders” were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors. Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively. Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity (“poor responders”) on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit
Prioritising surveillance for alien organisms transported as stowaways on ships travelling to South Africa
The global shipping network facilitates the transportation and introduction of marine and terrestrial organisms to regions where they are not native, and some of these organisms become invasive. South Africa was used as a case study to evaluate the potential for shipping to contribute to the introduction and establishment of marine and terrestrial alien species (i.e. establishment debt) and to assess how this varies across shipping routes and seasons. As a proxy for the number of species introduced (i.e. 'colonisation pressure') shipping movement data were used to determine, for each season, the number of ships that visited South African ports from foreign ports and the number of days travelled between ports. Seasonal marine and terrestrial environmental similarity between South African and foreign ports was then used to estimate the likelihood that introduced species would establish. These data were used to determine the seasonal relative contribution of shipping routes to South Africa's marine and terrestrial establishment debt. Additionally, distribution data were used to identify marine and terrestrial species that are known to be invasive elsewhere and which might be introduced to each South African port through shipping routes that have a high relative contribution to establishment debt. Shipping routes from Asian ports, especially Singapore, have a particularly high relative contribution to South Africa's establishment debt, while among South African ports, Durban has the highest risk of being invaded. There was seasonal variation in the shipping routes that have a high relative contribution to the establishment debt of the South African ports. The presented method provides a simple way to prioritise surveillance effort and our results indicate that, for South Africa, port-specific prevention strategies should be developed, a large portion of the available resources should be allocated to Durban, and seasonal variations and their consequences for prevention strategies should be explored further. (Résumé d'auteur
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