18 research outputs found

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    Biomarker changes with systolic anterior motion of the mitral valve in cats with hypertrophic cardiomyopathy.

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    BACKGROUND: N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) are biomarkers commonly evaluated in cats with suspected heart disease. Many cats with hypertrophic cardiomyopathy (HCM) have systolic anterior motion of the mitral valve (SAM), but its influence on circulating NT-proBNP or cTnI concentrations is currently unknown. HYPOTHESIS/OBJECTIVES: Cats with HCM and SAM (HCMSAM+ ) have higher NT-proBNP and cTnI concentrations than do cats with HCM but without SAM (HCMSAM- ). ANIMALS: One hundred forty cats with HCM: 70 with SAM and 70 without SAM. METHODS: Retrospective case-to-case study. Cats were recruited if diagnosed with HCM by echocardiography and results were available for NT-proBNP or cTnI concentrations or both. Cats with SAM were matched to those without SAM for clinical presentation, left atrial (LA) size and left ventricular (LV) fractional shortening. RESULTS: A total of 119 NT-proBNP and 123 cTnI results were available. The HCMSAM+ cats had higher median concentrations than did HCMSAM- cats for NT-proBNP (729 pmoL/L; interquartile range [IQR], 275-1467 versus 65 pmoL/L; IQR, 25-271; P < .001) and cTnI (0.27 ng/mL; IQR, 0.10-0.81 versus 0.07 ng/mL; IQR, 0.01-0.43; P = .002). In general linear models for both NT-proBNP and cTnI, the independent explanatory variables were SAM, congestive heart failure, maximal LV wall thickness, and LA size. CONCLUSIONS AND CLINICAL IMPORTANCE: For cats with HCM and equivalent LA size and LV systolic function, those with SAM had higher NT-proBNP and cTnI concentrations than did those without SAM. Presence of SAM should be considered when interpreting biomarker concentrations in cats with HCM

    Future restoration should enhance ecological complexity and emergent properties at multiple scales

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    Ecological restoration has a paradigm of re-establishing ‘indigenous reference' communities. One resulting concern is that focussing on target communities may not necessarily create systems which function at a high level or are resilient in the face of ongoing global change. Ecological complexity – defined here, based on theory, as the number of components in a system and the number of connections among them – provides a complementary aim, which can be measured directly and has several advantages. Ecological complexity encompasses key ecosystem variables including structural heterogeneity, trophic interactions and functional diversity. Ecological complexity can also be assessed at the landscape scale, with metrics including β diversity, heterogeneity among habitat patches and connectivity. Thus, complexity applies, and can be measured, at multiple scales. Importantly, complexity is linked to system emergent properties, e.g. ecosystem functions and resilience, and there is evidence that both are enhanced by complexity. We suggest that restoration ecology should consider a new paradigm to restore complexity at multiple scales, in particular of individual ecosystems and across landscapes. A complexity approach can make use of certain current restoration methods but also encompass newer concepts such as rewilding. Indeed, a complexity goal might in many cases best be achieved by interventionist restoration methods. Incorporating complexity into restoration policies could be quite straightforward. Related aims such as enhancing ecosystem services and ecological resilience are to the fore in initiatives such as the Sustainable Development Goals and the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. Implementation in policy and practice will need the development of complexity metrics that can be applied at both local and regional scales. Ultimately, the adoption of an ecological complexity paradigm will be based on an acceptance that the ongoing and unprecedented global environmental change requires new ways of doing restoration that is fit for the future

    Future restoration should enhance ecological complexity and emergent properties at multiple scales

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    Ecological restoration has a paradigm of re-establishing ‘indigenous reference' communities. One resulting concern is that focussing on target communities may not necessarily create systems which function at a high level or are resilient in the face of ongoing global change. Ecological complexity – defined here, based on theory, as the number of components in a system and the number of connections among them – provides a complementary aim, which can be measured directly and has several advantages. Ecological complexity encompasses key ecosystem variables including structural heterogeneity, trophic interactions and functional diversity. Ecological complexity can also be assessed at the landscape scale, with metrics including β diversity, heterogeneity among habitat patches and connectivity. Thus, complexity applies, and can be measured, at multiple scales. Importantly, complexity is linked to system emergent properties, e.g. ecosystem functions and resilience, and there is evidence that both are enhanced by complexity. We suggest that restoration ecology should consider a new paradigm to restore complexity at multiple scales, in particular of individual ecosystems and across landscapes. A complexity approach can make use of certain current restoration methods but also encompass newer concepts such as rewilding. Indeed, a complexity goal might in many cases best be achieved by interventionist restoration methods. Incorporating complexity into restoration policies could be quite straightforward. Related aims such as enhancing ecosystem services and ecological resilience are to the fore in initiatives such as the Sustainable Development Goals and the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services. Implementation in policy and practice will need the development of complexity metrics that can be applied at both local and regional scales. Ultimately, the adoption of an ecological complexity paradigm will be based on an acceptance that the ongoing and unprecedented global environmental change requires new ways of doing restoration that is fit for the future

    Prognostic value of mitral annular systolic plane excursion and tricuspid annular plane systolic excursion in cats with hypertrophic cardiomyopathy

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    Hypertrophic cardiomyopathy (HCM) has a variable prognosis; left atrial size, presence of clinical signs and left ventricular systolic function have been shown to predict outcomes. Mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) assess longitudinal ventricular systolic function and are decreased in cats with HCM. The aim of the study was to ascertain whether MAPSE and TAPSE have prognostic value in HCM and if cats with pleural effusion have lower MAPSE and TAPSE than cats with pulmonary oedema

    Mendelian gene identification through mouse embryo viability screening.

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    BACKGROUND: The diagnostic rate of Mendelian disorders in sequencing studies continues to increase, along with the pace of novel disease gene discovery. However, variant interpretation in novel genes not currently associated with disease is particularly challenging and strategies combining gene functional evidence with approaches that evaluate the phenotypic similarities between patients and model organisms have proven successful. A full spectrum of intolerance to loss-of-function variation has been previously described, providing evidence that gene essentiality should not be considered as a simple and fixed binary property. METHODS: Here we further dissected this spectrum by assessing the embryonic stage at which homozygous loss-of-function results in lethality in mice from the International Mouse Phenotyping Consortium, classifying the set of lethal genes into one of three windows of lethality: early, mid, or late gestation lethal. We studied the correlation between these windows of lethality and various gene features including expression across development, paralogy and constraint metrics together with human disease phenotypes. We explored a gene similarity approach for novel gene discovery and investigated unsolved cases from the 100,000 Genomes Project. RESULTS: We found that genes in the early gestation lethal category have distinct characteristics and are enriched for genes linked with recessive forms of inherited metabolic disease. We identified several genes sharing multiple features with known biallelic forms of inborn errors of the metabolism and found signs of enrichment of biallelic predicted pathogenic variants among early gestation lethal genes in patients recruited under this disease category. We highlight two novel gene candidates with phenotypic overlap between the patients and the mouse knockouts. CONCLUSIONS: Information on the developmental period at which embryonic lethality occurs in the knockout mouse may be used for novel disease gene discovery that helps to prioritise variants in unsolved rare disease cases

    Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

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    Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

    Patient and stakeholder engagement learnings: PREP-IT as a case study

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