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AIMS: To evaluate the prevalence of subclinical cardiomyopathy and cardiac mortality in a research colony of non-purebred cats, established as a model of the wider cat population in New Zealand. METHODS: All apparently healthy, compliant, non-pregnant, non-neonatal cats in the colony at the Centre for Feline Nutrition (Massey University, Palmerston North, NZ) underwent physical examination and echocardiography using a 4.4-6.2-MHz probe by a board-certified veterinary cardiologist. Cardiac phenotype was classified following current guidelines. Hypertrophic cardiomyopathy (HCM) phenotype was defined as an end-diastolic left ventricular wall thickness ≥ 6 mm. Colony mortality data from February 2012 to February 2022 was reviewed to determine cardiac mortality. RESULTS: Cats (n = 132; 65 females and 67 males) included in the study had a median age of 4.1 (IQR 3.0-8.0) years. Thirty-two (24%) cats had a heart murmur, and three (2%) cats had an arrhythmia. Echocardiography revealed heart disease in 24 (18.2%) cats, including 23 with an HCM phenotype and one with a restrictive cardiomyopathy phenotype. Of the cats with the HCM phenotype, 3/23 had systemic hypertension or hyperthyroidism or both, and these cats were excluded from the final diagnosis of HCM (20/132; 15.2 (95% CI = 9.5-22.4)%).Between 2012 and 2022, 168 colony cats died, with 132 undergoing post-mortem examination. Heart disease was considered the cause of death in 7/132 (5.3%; 95% CI = 2.2-10.6%) cats; five had HCM, one a congenital heart defect, and one myocarditis. The overall prevalence of death related to HCM in the colony during this period was 3.8% (95% CI = 1.2-8.6%). Three cats with HCM and the cat with a congenital heart defect died unexpectedly without prior clinical signs, while congestive heart failure was observed prior to death in two cats with HCM and the cat with myocarditis. Additionally, 30/132 (22.7%) cats had cardiac abnormalities but died for non-cardiac reasons. CONCLUSIONS: Subclinical cardiomyopathy, specifically HCM, was common in cats in the colony. Given that the colony originated as a convenience selection of non-purebred cats in New Zealand, the true prevalence of HCM in the wider New Zealand population is likely to fall within the 95% CI (9.5-22%). The proportion of deaths of colony cats due to HCM was lower (3.8%) supporting the conclusion that subclinical cardiomyopathy may not progress to clinical disease causing death. CLINICAL RELEVANCE: Veterinarians should be aware of the high prevalence of subclinical HCM when treating cats. ABBREVIATIONS: CAM: Systolic anterior motion of the chordae tendineae; CFN: Centre for Feline Nutrition; HCM: Hypertrophic cardiomyopathy; LA/Ao: Left atrial to aortic ratio; LV FS: Left ventricular fractional shortening; LVIDd: Left ventricular internal diameters in end-diastole; LVIDs: Left ventricular internal diameter in end-systole; LVWT: Max Maximum left ventricular wall thickness; SAM: Systolic anterior motion of the mitral valve; 2D: Two-dimensional.
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The leukodystrophies (LD) and leukoencephalopathies (LE) are a diverse group of conditions involving the cerebral white and grey matter. There is heterogeneity in the clinical presentations, imaging features, and biochemical dysfunction. Given the number of conditions and varied imaging appearances, this topic can be difficult for non-specialist radiologists who do not routinely work in dedicated paediatric neuroradiology centres. This article will aim to provide a simplified and step-wise approach to assessing suspected LD/LE, focussing on the more common diagnoses you may encounter in the UK. Additionally, it will highlight important non-LD/LE differentials, which if considered early, may significantly alter treatment and prognosis. By the end of this review, we hope the reader will begin to develop an awareness of physiological paediatric brain development in terms of normal myelination; the ability to recognise and categorise the distribution of abnormal signal based on the established diagnostic framework outlined by Schiffmann & Van der Knapp; and be aware of potential non-LD/LE radiological mimics.
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Leucoencefalopatias , Humanos , Criança , Leucoencefalopatias/diagnóstico , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: DNA methylation patterning is cell-type-specific and altered DNA methylation is well established to occur early in breast carcinogenesis, affecting non-cancerous, histopathologically normal breast tissue. Previous work assessing risk factor-associated alterations to DNA methylation in breast tissue has been limited, with even less published research in breast milk, a noninvasively obtained biospecimen containing sloughed mammary epithelial cells that may identify early alterations indicative of cancer risk. METHODS: Here, we present a novel library for the estimation of the cellular composition of breast tissue and milk and subsequent assessment of cell-type-independent alterations to DNA methylation associated with established breast cancer-risk factors in solid breast tissue (n = 95) and breast milk (n = 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array. RESULTS: We identified 772 hypermethylated CpGs (P < 0.01) associated with age consistent between breast tissue and breast milk samples. Age-associated hypermethylated CpG loci were significantly enriched for CpG island shore regions known to be important for regulating gene expression. Among the overlapping hypermethylated loci mapping to genes, a differentially methylated region was identified in the promoter region of SFRP2, a gene observed to undergo promoter hypermethylation in breast cancer. CONCLUSIONS: Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens. IMPACT: This work demonstrates the potential of using breast milk as a noninvasive biomarker of breast cancer risk, improving our ability to detect early-stage disease and lowering the overall disease burden.
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Neoplasias da Mama , Metilação de DNA , Feminino , Humanos , Animais , Leite , Neoplasias da Mama/genética , Epigênese Genética , Ilhas de CpG/genética , Fatores de Risco , Regulação Neoplásica da Expressão GênicaRESUMO
OBJECTIVES: To determine the causative organisms, clinical features and outcome of canine infective endocarditis in the UK. MATERIALS AND METHODS: Medical records of three veterinary referral hospitals were searched for dogs with infective endocarditis between December 2009 and December 2019. Signalment, clinical signs, causative organism, valve affected, treatment and survival data were recorded. RESULTS: Seventy-seven cases with possible or definite infective endocarditis (according to the modified Duke criteria) were included. The majority were large breed (40/77 - 51.9%). There were 47 of 77 (61%) male dogs and the mean age was 7.3 ±3 years. A causative organism was identified in 26 of 77 (33.8%) cases. The most common organisms were Escherichia coli (7/27 - 25.9%), Pasteurella spp. (5/27 - 18.5%), Staphylococcus spp. (4/27 - 14.8%) and Corynebacterium spp. (4/27 - 14.8%). Bartonella spp. were not detected in any patients. The mitral valve was most commonly affected (48/77 - 62.3%). Clinical features were non-specific, with lethargy being the most common clinical sign observed (53/77 - 68.8%). Fifty-three dogs (68.8%) survived to discharge. The median survival time post discharge was 425 days (2 to 3650 days). The development of congestive heart failure was associated with a poorer outcome. Cardiac troponin concentration, antithrombotic use and the development of thromboembolism or arrhythmias were not significantly associated with outcome. CLINICAL SIGNIFICANCE: Some dogs with infective endocarditis that survive to discharge can have a long lifespan. The inability to detect an underlying organism is common and Bartonella spp. may be a less prevalent cause of canine infective endocarditis in the UK than in the USA.
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Bartonella , Doenças do Cão , Endocardite Bacteriana , Endocardite , Cães , Masculino , Animais , Feminino , Assistência ao Convalescente , Alta do Paciente , Endocardite Bacteriana/epidemiologia , Endocardite Bacteriana/veterinária , Endocardite Bacteriana/diagnóstico , Endocardite/epidemiologia , Endocardite/veterinária , Endocardite/diagnóstico , Reino Unido/epidemiologia , Estudos Retrospectivos , Doenças do Cão/diagnósticoRESUMO
We have performed the first direct measurement of two resonances of the ^{7}Be(α,γ)^{11}C reaction with unknown strengths using an intense radioactive ^{7}Be beam and the DRAGON recoil separator. We report on the first measurement of the 1155 and 1110 keV resonance strengths of 1.73±0.25(stat)±0.40(syst) eV and 125_{-25}^{+27}(stat)±15(syst) meV, respectively. The present results have reduced the uncertainty in the ^{7}Be(α,γ)^{11}C reaction rate to â¼9.4%-10.7% over T=1.5-3 GK, which is relevant for nucleosynthesis in the neutrino-driven outflows of core-collapse supernovae (νp process). We find no effect of the new, constrained reaction rate on νp-process nucleosynthesis.
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Hypoxic-ischemic injury is the most common cause of neonatal encephalopathy. T1-weighted punctate white matter lesions have been described in hypoxic-ischemic injury. We have reviewed a healthy volunteer neonatal population to assess the prevalence of punctate white matter lesions in neonates with no clinical signs of hypoxic-ischemic injury. Fifty-two subjects were scanned on a neonatal-specific 3T MR imaging scanner. Twelve patients were excluded due to the lack of T1-weighted imaging, leaving a total of 40 patients (35 term, 5 preterm) assessed in the study. One had a solitary T1-punctate white matter lesion. We concluded that solitary punctate white matter lesions have a low prevalence in healthy neonates.
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Encefalopatias , Hipóxia-Isquemia Encefálica , Substância Branca , Recém-Nascido , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Prevalência , Voluntários Saudáveis , Imageamento por Ressonância Magnética/métodos , Encefalopatias/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Hipóxia-Isquemia Encefálica/patologiaRESUMO
INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in ß-oxidation of fatty acids and an increased dependence upon glycolysis. OBJECTIVES: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease. METHODS: Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases. RESULTS: Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased. CONCLUSIONS: The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced ß-oxidation. This proposed explanation warrants further research.
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Doenças do Cão , Insuficiência Cardíaca , Doenças das Valvas Cardíacas , Animais , Cães , Ácidos Graxos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/veterinária , Doenças das Valvas Cardíacas/veterinária , Humanos , Lipídeos , MetabolômicaRESUMO
Introduction: Screening for atrial fibrillation and timely initiation of oral anticoagulation, rhythm management, and treatment of concomitant cardiovascular conditions can improve outcomes in high-risk populations. Whether wearables can facilitate screening in older adults is not known. Methods and Analyses: The multicenter, international, investigator-initiated, single-arm case-finding Smartphone and wearable detected atrial arrhythmia in older adults case finding study (Smart in OAC - AFNET 9) evaluates the diagnostic yield of a validated, cloud-based analysis algorithm detecting atrial arrhythmias via a signal acquired by a smartphone-coupled wristband monitoring system in older adults. Unselected participants aged ≥65 years without known atrial fibrillation and not receiving oral anticoagulation are enrolled in three European countries. Participants undergo continuous pulse monitoring using a wristband with a photo plethysmography (PPG) sensor and a telecare analytic service. Participants with PPG-detected atrial arrhythmias will be offered ECG loop monitoring. The study has a virtual design with digital consent and teleconsultations, whilst including hybrid solutions. Primary outcome is the proportion of older adults with newly detected atrial arrhythmias (NCT04579159). Discussion: Smart in OAC - AFNET 9 will provide information on wearable-based screening for PPG-detected atrial arrhythmias in Europe and provide an estimate of the prevalence of atrial arrhythmias in an unselected population of older adults.
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We present the first direct measurement of an astrophysical reaction using a radioactive beam of isomeric nuclei. In particular, we have measured the strength of the key 447-keV resonance in the ^{26m}Al(p,γ)^{27}Si reaction to be 432_{-226}^{+146} meV and find that this resonance dominates the thermally averaged reaction rate for temperatures between 0.3 and 2.5 GK. This work represents a critical development in resolving one of the longest standing issues in nuclear astrophysics research, relating to the measurement of proton capture reactions on excited quantum levels, and offers unique insight into the destruction of isomeric ^{26}Al in astrophysical plasmas.
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Aims: Simplified detection of atrial arrhythmias via consumer-electronics would enable earlier therapy in at-risk populations. Whether this is feasible and effective in older populations is not known. Methods and results: The fully remote, investigator-initiated Smartphone and wearable detected atrial arrhythmia in Older Adults Case finding study (Smart in OAC-AFNET 9) digitally enrolled participants ≥65 years without known atrial fibrillation, not receiving oral anticoagulation in Germany, Poland, and Spain for 8 weeks. Participants were invited by media communications and direct contacts. Study procedures adhered to European data protection. Consenting participants received a wristband with a photoplethysmography sensor to be coupled to their smartphone. The primary outcome was the detection of atrial arrhythmias lasting 6â min or longer in the first 4 weeks of monitoring. Eight hundred and eighty-two older persons (age 71 ± 5 years, range 65-90, 500 (57%) women, 414 (47%) hypertension, and 97 (11%) diabetes) recorded signals. Most participants (72%) responded to adverts or word of mouth, leaflets (11%) or general practitioners (9%). Participation was completely remote in 469/882 persons (53%). During the first 4 weeks, participants transmitted PPG signals for 533/696â h (77% of the maximum possible time). Atrial arrhythmias were detected in 44 participants (5%) within 28 days, and in 53 (6%) within 8 weeks. Detection was highest in the first monitoring week [incidence rates: 1st week: 3.4% (95% confidence interval 2.4-4.9); 2nd-4th week: 0.55% (0.33-0.93)]. Conclusion: Remote, digitally supported consumer-electronics-based screening is feasible in older European adults and identifies atrial arrhythmias in 5% of participants within 4 weeks of monitoring (NCT04579159).
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INTRODUCTION: Anterior mitral valve leaflet (AMVL) elongation is a recognised feature of hypertrophic cardiomyopathy (HCM). However, whether AMVL elongation precedes left ventricular hypertrophy in cats is currently unknown. The aim of this study was to explore the risk of developing an HCM phenotype in cats with an elongated AMVL. ANIMALS: FIFTY-FIVE APPARENTLY HEALTHY CATS WITH A NORMAL BASELINE ECHOCARDIOGRAM AND A FOLLOW-UP ECHOCARDIOGRAM AT >ONE YEAR. MATERIALS AND METHODS: This was a retrospective longitudinal study. Cats at the baseline were grouped based on whether or not they developed an HCM phenotype at follow-up. AMVL length and left atrial and left ventricular dimensions were measured from two-dimensional images. RESULTS: The median follow-up period of the study population was 5.4 years (25th and 75th quartile, 2.7-6.7 years). During this time, 17 cats (30.9%) developed an HCM phenotype. At the baseline, cats that subsequently developed an HCM phenotype had greater AMVL length (9.4 mm [25th and 75th quartile, 9.0-10.6 mm] vs. 8.5 mm [25th and 75th quartile, 7.6-9.1 mm], P < 0.0001) and maximal left ventricular wall thickness (4.5 mm [25th and 75th quartile, 4.1-4.7 mm] vs. 4.0 mm [25th and 75th quartile, 3.7-4.6 mm], P = 0.007) than those that did not. Multiple logistic regression analysis confirmed that both baseline variables were independent predictors for development of an HCM phenotype. CONCLUSIONS: The AMVL length was greater in cats that subsequently developed left ventricular hypertrophy. Further studies investigating the clinical application of AMVL in the natural history of feline HCM are warranted.
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Cardiomiopatia Hipertrófica , Doenças do Gato , Animais , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/diagnóstico por imagem , Gatos , Ecocardiografia/veterinária , Estudos Longitudinais , Valva Mitral/diagnóstico por imagem , Estudos RetrospectivosRESUMO
AIM: To investigate whether computed tomography (CT)/magnetic resonance imaging (MRI) brain imaging is associated with detection of structural causes of a first episode of psychosis (FEP) or first episode of behavioural abnormality (FEB) in the paediatric population, as this has not been previously documented in the literature. MATERIALS AND METHODS: Individuals with FEP/FEB but no neurological signs referred to a tertiary children's centre for cerebral MRI or CT were reviewed retrospectively. Individuals were evaluated independently with one technique (CT or MRI) only. RESULTS: Thirty-four consecutive cerebral MRI and six consecutive CT examinations were identified between 2017 and 2020. No patients were identified as having an organic cause for the psychosis at MRI or CT. Four patients (9%) had incidental findings on MRI, unrelated to the psychosis, such as prominent perivascular spaces, hypoplastic transverse sinus, and sinonasal mucosal wall thickening. No abnormal findings were seen on CT. There was therefore no obvious difference between MRI and CT imaging in detecting organic disease potentially responsible for FEP. CONCLUSION: Routine structural MRI or CT of the brain is unlikely to reveal disease leading to a significant change in management. MRI demonstrated only a few incidental findings, unrelated to the child's clinical history. Therefore, routine brain structural imaging of FEP/FEB in paediatric patients without focal neurology may not be routinely required. If imaging is requested, then there is no significant difference between CT and MRI in detecting clinically significant lesions.
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Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imageamento por Ressonância Magnética/métodos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/patologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Neuroimagem/métodos , Estudos Retrospectivos , Reino UnidoRESUMO
INTRODUCTION: Both paroxysmal high-grade second-degree and persistent third-degree atrioventricular block (AVB) are recognised in cats. Our aim was to document the presentation, echocardiographic data, comorbidities and outcome in affected cats from a single referral hospital, including those that underwent epicardial pacemaker implantation (EPI). ANIMALS, MATERIALS AND METHODS: This retrospective study included 64 cats diagnosed with persistent third-degree or paroxysmal high-grade AVB, for which detailed patient history was available. Non-parametric testing, Kaplan-Meier curves and Cox proportional hazard testing were performed. RESULTS: Atrioventricular block was persistent in 43 cats (67%) and paroxysmal in 21 (33%). Forty-seven cats (74%) were referred for cardiac complaints (e.g. collapse, arrhythmia, tachypnea), 6 (9%) had non-specific complaints and AVB was an incidental finding in 11 cats (17%). Median duration of clinical signs prior to presentation was 21 days (1-1138 days). Thirty-nine (63%) cats had echocardiographic abnormalities; 13 (20%) presented with congestive heart failure. Forty-five (70%) cats had one or more comorbidities. Fifteen cats underwent EPI with immediate resolution of signs in 12 cats. Following EPI, two and four cats experienced major and minor complications, respectively. Forty-seven cats died; median survival time was 799 days (all-cause mortality). Cardiac-related death occurred in 17 cats (36%); median survival in these cats was 132 days. Heart failure on presentation was the only independent risk factor for cardiac death (p=0.002). CONCLUSIONS: Outcome in cats with AVB was variable, although most had good medium- to long-term survival. Cardiac death occurred in a minority of cats. Pacemaker implantation was effective in relieving clinical signs.
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Bloqueio Atrioventricular , Doenças do Gato , Animais , Arritmias Cardíacas/veterinária , Bloqueio Atrioventricular/terapia , Bloqueio Atrioventricular/veterinária , Doenças do Gato/terapia , Gatos , Insuficiência Cardíaca/veterinária , Marca-Passo Artificial/veterinária , Estudos RetrospectivosRESUMO
BACKGROUND: Despite the widespread and increasing use of NOACs in Saudi Arabia, there is a lack of contemporary guidance specific to the region. In particular, guidance on NOAC use in high-risk patients who are more likely to experience bleeding with oral anticoagulant therapy is needed. There is an unmet need for a review of contemporary evidence coupled with expert insights on safe and effective NOAC use in high-risk patients with AF in Saudi Arabia. RESEARCH DESIGN AND METHODS: This article provides a detailed review of contemporary literature on NOAC use in high-risk patients with AF. Additionally, key gaps in the literature are identified and expert insights are shared to guide effective management of patients and the significance of local data is evaluated with respect to challenges in optimizing the use of NOACs. CONCLUSIONS: This article provides information that complements and expands on existing reviews and guidelines on NOAC use in patients with AF, with a focus on challenges specific to the Saudi Arabian context with the potential to make a positive contribution to the medical community in Saudi Arabia and in other nations.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Administração Oral , Humanos , Assistência ao Paciente , Arábia Saudita , Acidente Vascular Cerebral/prevenção & controleRESUMO
AIM: To report the magnetic resonance imaging (MRI) findings from a retrospective case analysis of children with septo-optic dysplasia (SOD), a rare congenital disorder characterised by any combination of midline brain defects, optic nerve hypoplasia (ONH), and hypothalamic-pituitary dysfunction. MATERIALS AND METHODS: SOD was defined radiologically as complete or partial septum pellucidum (SP) absence with hypoplasia of at least one of the optic nerves and/or chiasm. Local MRI databases were searched for SOD cases in children over an 18-year period, and studies reviewed by two consultant paediatric neuroradiologists. The extent of structural SP, optic nerve, chiasm, and hypothalamic-pituitary involvement was recorded, along with coexisting brain abnormalities. RESULTS: Forty-eight cases of SOD were found; 44/48 (92%) demonstrated complete SP absence whereas 4/48 (8%) had partial absence. Eight of 48 cases (17%) exhibited unilateral ONH. Fifty-one percent of cases, where the pituitary was identified on MRI, demonstrated a structural pituitary abnormality, which included an ectopic posterior bright spot in 6%. The olfactory nerves were hypoplastic in 5/48 cases (10%). Twenty-seven of the 48 cases (56%) had another brain abnormality, resulting from some form of cortical formation abnormality/schizencephaly in 21/48 (44%). CONCLUSION: A high rate of associated brain abnormalities was found in the present cohort, including structural pituitary abnormalities in 51% and cortical formation abnormalities/schizencephaly in 44%. This suggests there is not a single cause for SOD, rather SOD is the phenotypic end point from multiple aetiological events. Individual children with SOD may have coexisting intracranial abnormalities, and, hence, high-quality MRI is required in all.
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Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Displasia Septo-Óptica/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Inglaterra , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
Neural development requires the orchestration of dynamic changes in gene expression to regulate cell fate decisions. This regulation is heavily influenced by epigenetics, heritable changes in gene expression not directly explained by genomic information alone. An understanding of the complexity of epigenetic regulation is rapidly emerging through the development of novel technologies that can assay various features of epigenetics and gene regulation. Here, we provide a broad overview of several commonly investigated modes of epigenetic regulation, including DNA methylation, histone modifications, noncoding RNAs, as well as epitranscriptomics that describe modifications of RNA, in neurodevelopment and diseases. Rather than functioning in isolation, it is being increasingly appreciated that these various modes of gene regulation are dynamically interactive and coordinate the complex nature of neurodevelopment along multiple axes. Future work investigating these interactions will likely utilize 'multi-omic' strategies that assay cell fate dynamics in a high-dimensional and high-throughput fashion. Novel human neurodevelopmental models including iPSC and cerebral organoid systems may provide further insight into human-specific features of neurodevelopment and diseases.
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Encéfalo/crescimento & desenvolvimento , Montagem e Desmontagem da Cromatina/fisiologia , Metilação de DNA/fisiologia , Epigênese Genética/fisiologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Neurogênese/fisiologia , Animais , HumanosRESUMO
In this work we evaluated a novel microreactor prepared using a surface modified, high surface-to-volume ratio multi-lumen fused silica capillary (MLC). The MLC investigated contained 126 parallel channels, each of 4 µm internal diameter. The MLC, along with conventional fused silica capillaries of 25 µm and 50 µm internal diameter, were treated by (3-aminopropyl)triethoxysilane (APTES) and then modified with gold nanoparticles, of â¼20 nm in diameter, to ultimately provide immobilisation sites for the proteolytic enzyme, trypsin. The modified capillaries and MLCs were characterised and profiled using non-invasive scanning capacitively coupled contactless conductivity detection (sC4D). The sC4D profiles confirmed a significantly higher amount of enzyme was immobilised to the MLC when compared to the fused silica capillaries, attributable to the increased surface to volume ratio. The MLC was used for dynamic protein digestion, where peptide fragments were collected and subjected to off-line chromatographic evaluation. The digestion was achieved with the MLC reactor, using a residence time of just 1.26 min, following which the HPLC peak associated with the intact protein decreased by >70%. The MLC reactors behaved similarly to the classical in vitro or in-solution approach, but provided a reduction in digestion time, and fewer peaks associated with trypsin auto-digestion, which is common using in-solution digestion. The digestion of cytochrome C using both the MLC-IMER and the in-solution approach, resulted in a sequence coverage of â¼80%. The preparation of the MLC microreactor was reproducible with <2.5% RSD between reactors (n = 3) as determined by sC4D.
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Citocromos c/química , Enzimas Imobilizadas/química , Insulina/química , Proteólise , Tripsina/química , Sequência de Aminoácidos , Cromatografia Líquida , Ouro/química , Espectrometria de Massas , Nanopartículas Metálicas/química , Fragmentos de Peptídeos/química , Propilaminas/química , Reprodutibilidade dos Testes , Silanos/química , Dióxido de Silício/químicaRESUMO
PURPOSE: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. METHODS: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. CONCLUSIONS: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery.
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Terapia por Exercício/métodos , Modalidades de Fisioterapia/psicologia , Neoplasias Gástricas/reabilitação , Sobreviventes/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Cats with hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) can have resolution of both left ventricular hypertrophy and CHF. OBJECTIVES: To describe the clinical characteristics of cats with transient myocardial thickening (TMT) and CHF compared with a control population of cats without resolution of HCM. ANIMALS: A total of 21 cats with TMT, 21 cats with HCM. METHODS: Retrospective study. Clinical records at 4 veterinary centers were searched for TMT cases and a control group of cats with HCM and CHF. TMT was defined as initial maximal left ventricular wall thickness (LVWT) ≥6 mm with left-sided CHF, with subsequent resolution of CHF, reduction in left atrium/aorta (LA/Ao), and LVWT<5.5 mm. HCM was defined as persistent LVWT ≥6 mm. RESULTS: Cats with TMT were younger (2 [0.4-11.4] years) than cats with HCM (8 [1.6-14] years) (P < 0.0001), and antecedent events were more common (15/21 versus 6/21, respectively) (P = 0.01). In cats with TMT, LVWT normalized from 6.8 [6.0-9.7] mm to 4.8 [2.8-5.3] mm and LA/Ao decreased from 1.8 [1.6-2.3] to 1.45 [1.2-1.7] after a mean interval of 3.3 (95% CI: 1.8-4.7) months. CHF recurred in 1 of 21 TMT and 15 of 21 cats with HCM. Cardiac treatment was discontinued in 20 of 21 cats with TMT and 0 of 21 HCM cats. All cats with TMT survived, whereas 8 of 19 cats with HCM died during the study period. CONCLUSIONS AND CLINICAL IMPORTANCE: TMT occurs in younger cats, and antecedent events are common. The prognosis is better in cats with CHF associated with TMT than HCM.
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Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/patologia , Insuficiência Cardíaca/veterinária , Hipertrofia Ventricular Esquerda/veterinária , Fatores Etários , Animais , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/patologia , Gatos , Ecocardiografia/veterinária , Feminino , Insuficiência Cardíaca/patologia , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/patologia , Masculino , Estudos RetrospectivosRESUMO
We have performed a direct measurement of the ^{19}Ne(p,γ)^{20}Na reaction in inverse kinematics using a beam of radioactive ^{19}Ne. The key astrophysical resonance in the ^{19}Ne+p system has been definitely measured for the first time at E_{c.m.}=456_{-2}^{+5} keV with an associated strength of 17_{-5}^{+7} meV. The present results are in agreement with resonance strength upper limits set by previous direct measurements, as well as resonance energies inferred from precision (^{3}He, t) charge exchange reactions. However, both the energy and strength of the 456 keV resonance disagree with a recent indirect study of the ^{19}Ne(d, n)^{20}Na reaction. In particular, the new ^{19}Ne(p,γ)^{20}Na reaction rate is found to be factors of â¼8 and â¼5 lower than the most recent evaluation over the temperature range of oxygen-neon novae and astrophysical x-ray bursts, respectively. Nevertheless, we find that the ^{19}Ne(p,γ)^{20}Na reaction is likely to proceed fast enough to significantly reduce the flux of ^{19}F in nova ejecta and does not create a bottleneck in the breakout from the hot CNO cycles into the rp process.