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1.
Int J Parasitol Parasites Wildl ; 18: 292-299, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35934997

RESUMO

In the year 2012 a total of seven individuals (one bull and six cows) of European bison (Bison bonasus) were introduced to a fenced 200 ha area in a forest district (Almindingen, Island Bornholm, Denmark) in the Baltic Sea. In 2017 the herd was supplemented by introduction of another bull. The animals all originated from a population in the Polish Bialowieza forest. Faecal samples were recovered with intervals and subjected to a copro-parasitological investigation (applying egg flotation, sedimentation and Baermann technique). In addition, parasites were sampled during necropsy of animals euthanized or found dead three years after introduction. The animals carried a range of parasite types including trematodes (liver fluke Fasciola and rumen fluke), cestodes (Moniezia), nematodes (Dictyocaulus viviparus, trichurids, and other gastrointestinal nematodes (GIN) including Trichostrongylus axei and Haemonchus contortus). Egg and larval morphology also suggested presence of GIN genera Nematodirus, Ostertagia and Cooperia. The trematodes did not establish a life cycle in the recipient area, as judged by examination of calves born in the new area, but the cestode and several nematode species occurred in these animals. Especially Dictyocaulus viviparus was successfully spread and occurred together with GIN at moderate to high infection intensities at most sampling points. The reproduction among bison in the herd was high during the first few years. The exact birth rate is unknown but up to 24 calves are believed to be born during the ten year study period. Mortality among adults and calves occurred and in early June 2022 the total number of live animals was 11 (seven males, three females, one calf). The possible impact of the parasite infections on the bison health and future wildlife infection status is discussed.

2.
Water Sci Technol ; 85(6): 1981-1998, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35358083

RESUMO

Digital twins of urban drainage systems require simulation models that can adequately replicate the physical system. All models have their limitations, and it is important to investigate when and where simulation results are acceptable and to communicate the level of performance transparently to end users. This paper first defines a classification of four possible 'locations of uncertainty' in integrated urban drainage models. It then develops a structured framework for identifying and diagnosing various types of errors. This framework compares model outputs with in-sewer water level observations based on hydrologic and hydraulic signatures. The approach is applied on a real case study in Odense, Denmark, with examples from three different system sites: a typical manhole, a small flushing chamber, and an internal overflow structure. This allows diagnosing different model errors ranging from issues in the underlying asset database and missing hydrologic processes to limitations in the model software implementation. Structured use of signatures is promising for continuous, iterative improvements of integrated urban drainage models. It also provides a transparent way to communicate the level of model adequacy to end users.


Assuntos
Modelos Teóricos , Água , Hidrologia , Incerteza , Movimentos da Água
3.
J Phys Chem A ; 123(46): 10057-10064, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31670512

RESUMO

Superfluid helium nanodroplets comprised of thousands to millions of helium atoms can serve as a reactor for the synthesis of heterogeneous molecular clusters at cryogenic conditions. The cluster synthesis occurs via consecutive pick-up of the cluster building blocks by the helium droplet and their subsequent coalescence within the droplet. The effective collision cross section of the building blocks is determined by the helium droplet size and thus exceeds by orders of magnitude that of a reactive collision in the gas phase. Moreover, the cryogenic helium environment (at 0.38 K) as a host promotes the formation of metastable cluster configurations. The question arises as to the extent of the actual involvement of the helium environment in the cluster formation. The present study deals with clusters of single phthalocyanine (Pc) molecules with single water molecules. A large fluorophore such as Pc offers several sites where the water molecule can attach. The resulting isomeric variants of the Pc-H2O complex can be selectively identified by electronic spectroscopy. We compare the experimental electronic spectra of the Pc-H2O complex generated in superfluid helium nanodroplets with the results of quantum-chemical calculations on the same cluster but under gas-phase conditions. The number of isomeric variants observed in the helium droplet experiment comes out the same as that obtained from our gas-phase calculations.

4.
Transl Psychiatry ; 9(1): 214, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477683

RESUMO

Depression is a severe and debilitating mental disorder diagnosed by evaluation of affective, cognitive and physical depression symptoms. Severity of these symptoms strongly impacts individual's quality of life and is influenced by a combination of genetic and environmental factors. One of the molecular mechanisms allowing for an interplay between these factors is DNA methylation, an epigenetic modification playing a pivotal role in regulation of brain functioning across lifespan. The aim of this study was to investigate if there are DNA methylation signatures associated with depression symptomatology in order to identify molecular mechanisms contributing to pathophysiology of depression. We performed an epigenome-wide association study (EWAS) of continuous depression symptomatology score measured in a cohort of 724 monozygotic Danish twins (346 males, 378 females). Through EWAS analyses adjusted for sex, age, flow-cytometry based blood cell composition, and twin relatedness structure in the data we identified depression symptomatology score to be associated with blood DNA methylation levels in promoter regions of neuropsin (KLK8, p-value = 4.7 × 10-7) and DAZ associated protein 2 (DAZAP2, p-value = 3.13 × 10-8) genes. Other top associated probes were located in gene bodies of MAD1L1 (p-value = 5.16 × 10-6), SLC29A2 (p-value = 6.15 × 10-6) and AKT1 (p-value = 4.47 × 10-6), all genes associated before with development of depression. Additionally, the following three measures (a) DNAmAge (calculated with Horvath and Hannum epigenetic clock estimators) adjusted for chronological age, (b) difference between DNAmAge and chronological age, and (c) DNAmAge acceleration were not associated with depression symptomatology score in our cohort. In conclusion, our data suggests that depression symptomatology score is associated with DNA methylation levels of genes implicated in response to stress, depressive-like behaviors, and recurrent depression in patients, but not with global DNA methylation changes across the genome.


Assuntos
Depressão/genética , Epigênese Genética , Epigenoma , Gêmeos Monozigóticos/genética , Idoso , Metilação de DNA , Dinamarca , Feminino , Interação Gene-Ambiente , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
5.
Vet J ; 250: 36-43, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31383418

RESUMO

Higher concentrations of circulating serotonin have been reported in Cavalier King Charles spaniels (CKCS) compared to other dog breeds. The CKCS is also a breed highly predisposed to myxomatous mitral valve disease (MMVD). The aim of this study was to determine urine concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite and excretion product of serotonin, in a population of CKCS with preclinical MMVD, and to evaluate whether urine 5-HIAA concentrations were associated with MMVD severity, dog characteristics, setting for urine sampling, platelet count, and serotonin concentration in serum and platelet-poor plasma (PPP). The study population consisted of 40 privately-owned CKCS (23 females; 17 males) with and without preclinical MMVD as follows: American College of Veterinary Internal Medicine (ACVIM) group A (n = 11), ACVIM group B1 (n = 21) and ACVIM group B2 (n = 8). Urine 5-HIAA concentrations were not significantly associated with preclinical MMVD disease, platelet count or circulating concentrations of serotonin (in serum and PPP; P > 0.05). Females had higher 5-HIAA concentrations than males in morning urine collected at home (females, 3.1 [2.9-3.7] µmol/mmol creatinine [median and quartiles]; males, 1.7 [1.2-2.2] µmol/mmol creatinine; P = 0.0002) and urine collected at the clinic (females, 3.5 [3.1-3.9] µmol/mmol creatinine; males, 1.6 [1.3-2.1] µmol/mmol creatinine; P < 0.0001). Five-HIAA concentrations in urine collected at home and at the clinic were significantly associated (P = 0.0004; r = 0.73), and higher concentrations were found in urine collected at the clinic (P = 0.013). Urine 5-HIAA concentration was influenced by sex and setting of urine sampling. Urine 5-HIAA concentration was not associated with MMVD severity or circulating concentrations of serotonin in CKCS with preclinical disease.


Assuntos
Doenças do Cão/metabolismo , Doenças das Valvas Cardíacas/veterinária , Ácido Hidroxi-Indolacético/urina , Serotonina/sangue , Animais , Cães , Feminino , Doenças das Valvas Cardíacas/urina , Masculino , Valva Mitral/patologia , Contagem de Plaquetas/veterinária , Especificidade da Espécie
6.
Exp Brain Res ; 236(3): 665-677, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29299640

RESUMO

Sudden limb displacement evokes a complex sequence of compensatory muscle activity. Following the short-latency reflex and preceding voluntary reactions is an epoch termed the medium-latency reflex (MLR) that could reflect spinal processing of group II muscle afferents. One way to test this possibility is oral ingestion of tizanidine, an alpha-2 adrenergic agonist that inhibits the interneurons transmitting group II signals onto spinal motor neurons. We examined whether group II afferents contribute to MLR activity throughout the major muscles that span the elbow and shoulder. MLRs of ankle muscles were also tested during walking on the same day, in the same participants as well as during sitting in a different group of subjects. In contrast to previous reports, the ingestion of tizanidine had minimal impact on MLRs of arm or leg muscles during motor actions. A significant decrease in magnitude was observed for 2/16 contrasts in arm muscles and 0/4 contrasts in leg muscles. This discrepancy with previous studies could indicate that tizanidine's efficacy is altered by subtle changes in protocol or that group II afferents do not substantially contribute to MLRs.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Vias Aferentes/efeitos dos fármacos , Clonidina/análogos & derivados , Extremidade Inferior/fisiologia , Atividade Motora/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Reflexo/efeitos dos fármacos , Extremidade Superior/fisiologia , Adulto , Clonidina/farmacologia , Eletromiografia , Feminino , Humanos , Interneurônios/efeitos dos fármacos , Masculino , Neurônios Motores/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Robótica , Adulto Jovem
7.
Brain Stimul ; 11(2): 346-357, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29187320

RESUMO

BACKGROUND: A session of motor skill learning is accompanied by transient increases in corticospinal excitability(CSE), which are thought to reflect acute changes in neuronal connectivity associated with improvements in sensorimotor performance. Factors influencing changes in excitability and motor skill with continued practice remain however to be elucidated. OBJECTIVE/HYPOTHESIS: Here we investigate the hypothesis that progressive motor practice during consecutive days can induce repeated transient increases in corticospinal excitability and promote motor skill learning. METHODS: Changes in motor performance and CSE were assessed during 4 consecutive days of skill learning and 8 days after the last practice session. CSE was assessed as area under recruitment curves(RC) using transcranial magnetic stimulation(TMS). Two groups of participants(n = 12) practiced a visuomotor tracking-task with task difficulty progressively increased with individual proficiency(PPG) or with the same task level throughout all 4 days(NPPG). RESULTS: Progressive practice resulted in superior motor learning compared to NPPG(p < 0.001). Whereas NPPG displayed increased CSE following only the first day of practice(p < 0.001), progressive motor practice was accompanied by increases in CSE on both the first and the final session of motor practice(p = 0.006). Eight days after ended practice, the groups showed similar CSE, but PPG maintained superior performance at a skilled task level and transfer task performance(p < 0.005,p = 0.029). CONCLUSION: The results demonstrate that progressive practice promotes both motor learning and repeated increases in CSE across multiple days. While changes in CSE did not relate to learning our results suggest that they signify successful training. Progressive practice is thus important for optimizing neurorehabilitation and motor practice protocols in general.


Assuntos
Aprendizagem , Destreza Motora , Tratos Piramidais/fisiologia , Adulto , Potencial Evocado Motor , Humanos , Masculino , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana/métodos
8.
J Vet Intern Med ; 32(1): 57-63, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29230874

RESUMO

BACKGROUND: Symmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species. HYPOTHESIS: Hypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independently of CKD, are associated with changes in serum SDMA. ANIMALS: Ninety-four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls). METHODS: Case-control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed. Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log-transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA. RESULTS: Median (range) serum SDMA for the renal group (positive control) was 19 (10-93) µg/dL, whereas for the control group (negative control), it was 10 (5-15) µg/dL. For the cardiac and diabetic groups, serum SDMA was 9 (4-24) µg/dL and 7 (3-11) µg/dL, respectively. The renal group had significantly higher SDMA concentrations and the diabetic group significantly lower SDMA concentrations compared to all other groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum SDMA concentrations in cats with HCM were not significantly different from those of healthy control cats. Cats with DM, however, had significantly lower SDMA concentrations than controls, a finding that needs further investigation and should be kept in mind when evaluating renal function of cats with this endocrinopathy.


Assuntos
Arginina/análogos & derivados , Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/sangue , Diabetes Mellitus/veterinária , Insuficiência Renal Crônica/veterinária , Animais , Arginina/sangue , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Estudos de Casos e Controles , Gatos , Comorbidade , Diabetes Mellitus/sangue , Feminino , Masculino , Insuficiência Renal Crônica/sangue
9.
Epidemiol Infect ; 145(13): 2787-2796, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28768556

RESUMO

The spread of African swine fever virus (ASFV) threatens to reach further parts of Europe. In countries with a large swine production, an outbreak of ASF may result in devastating economic consequences for the swine industry. Simulation models can assist decision makers setting up contingency plans. This creates a need for estimation of parameters. This study presents a new analysis of a previously published study. A full likelihood framework is presented including the impact of model assumptions on the estimated transmission parameters. As animals were only tested every other day, an interpretation was introduced to cover the weighted infectiousness on unobserved days for the individual animals (WIU). Based on our model and the set of assumptions, the within- and between-pen transmission parameters were estimated to ß w = 1·05 (95% CI 0·62-1·72), ß b = 0·46 (95% CI 0·17-1·00), respectively, and the WIU = 1·00 (95% CI 0-1). Furthermore, we simulated the spread of ASFV within a pig house using a modified SEIR-model to establish the time from infection of one animal until ASFV is detected in the herd. Based on a chosen detection limit of 2·55% equivalent to 10 dead pigs out of 360, the disease would be detected 13-19 days after introduction.


Assuntos
Vírus da Febre Suína Africana/fisiologia , Febre Suína Africana/transmissão , Febre Suína Africana/diagnóstico , Febre Suína Africana/virologia , Animais , Abrigo para Animais , Modelos Teóricos , Suínos , Reino Unido
10.
Scand J Med Sci Sports ; 27(11): 1523-1532, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27790760

RESUMO

A single bout of high-intensity exercise can augment off-line gains in skills acquired during motor practice. It is currently unknown if the type of physical exercise influences the effect on motor skill consolidation. This study investigated the effect of three types of high-intensity exercise following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill were performed 1 (R1h) and 24 h (R1d) post acquisition. For all exercise groups, mean motor performance scores decreased at R1h compared to post acquisition (POST) level; STR (P = 0.018), CT (P = 0.02), HOC (P = 0.014) and performance scores decreased for CT compared to CON (P = 0.049). Mean performance scores increased from POST to R1d for all exercise groups; STR (P = 0.010), CT (P = 0.020), HOC (P = 0.007) while performance scores for CON decreased (P = 0.043). Changes in motor performance were thus greater for STR (P = 0.006), CT (P < 0.001) and HOC (P < 0.001) compared to CON from POST to R1d. The results demonstrate that high-intensity, acute exercise can lead to a decrease in motor performance assessed shortly after motor skill practice (R1h), but enhances offline effects promoting long-term retention (R1d). Given that different exercise modalities produced similar positive off-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed.


Assuntos
Exercício Físico , Consolidação da Memória , Destreza Motora/fisiologia , Adulto , Hóquei , Humanos , Aprendizagem , Masculino , Treinamento Resistido , Adulto Jovem
11.
Neurobiol Aging ; 50: 60-63, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27889677

RESUMO

The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic twins, we investigated the association of DNAmAge, difference between DNAmAge and chronological age and age acceleration with cognition. Despite using a powerful paired twin design, we found no evidence for association of blood DNAmAge with cognitive abilities. This observation was confirmed in unpaired analyses, where DNAmAge initially correlated with cognitive abilities, until adjusting for chronological age. Overall, our study shows that for middle-aged individuals DNAmAge calculated in blood does not correlate with cognitive abilities.


Assuntos
Envelhecimento/genética , Cognição/fisiologia , Metilação de DNA , Gêmeos Monozigóticos , Estudos Transversais , Epigênese Genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade
12.
Andrology ; 4(4): 735-44, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27230552

RESUMO

Many modern pesticides have endocrine disrupting abilities and early-life exposure may affect growth and disease risk later in life. Previously, we reported associations between prenatal pesticide exposure and higher childhood body fat content measured by anthropometry. The associations were affected by child PON1 Q192R genotype. We aimed to study whether prenatal pesticide exposure was still associated with body fat content and distribution in the children at puberty and the potential impact of both maternal and child PON1 Q192R genotype. In this prospective cohort study of 247 children born by occupationally exposed or unexposed women (greenhouse workers and controls) two follow-up examinations (age 10-15 and 11-16 years) including simple anthropometry, skinfold measurements, pubertal staging and blood sampling were performed. Total and regional fat% was determined by dual X-ray absorptiometry (DXA) at age 10-15. Prenatal pesticide exposure was associated with increased total, android, and gynoid fat percentage (DXA) at age 10-15 years after adjustment for sex, socioeconomic status, and puberty (all ß = 0.5 standard deviation score (SDS) p < 0.05). Stratified by sex, the associations were significant in girls (total fat: ß = 0.7 SDS, android-gynoid ratio: ß = 0.1, both p < 0.05), but not in boys. Carrying the R-allele (child or mother, separately, or both) augmented the differences between exposed and unexposed children (total fat: ß = 1.0 SDS, ß = 0.8 SDS, p < 0.05, respectively, and ß = 1.2 SDS, p < 0.01). No exposure-related differences were found if either the child or mother had the QQ wild-type. At age 11-16, exposed children tended to have a higher total fat% estimated by skinfolds than unexposed children (p = 0.06). No significant associations between prenatal exposure and body mass index or waist circumference were found. Prenatal pesticide exposure was associated with higher adolescent body fat content, including android fat deposition, independent of puberty. Girls appeared more susceptible than boys. Furthermore, the association depended on maternal and child PON1 Q192R genotype.


Assuntos
Adiposidade/efeitos dos fármacos , Arildialquilfosfatase/genética , Distribuição da Gordura Corporal , Praguicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagem , Absorciometria de Fóton , Adolescente , Índice de Massa Corporal , Criança , Feminino , Genótipo , Humanos , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Estudos Prospectivos , Puberdade , Fatores Sexuais , Fatores Socioeconômicos
13.
Transbound Emerg Dis ; 63(2): 215-23, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25056842

RESUMO

In 2007, bluetongue virus (BTV) was introduced to both Denmark (DK) and the United Kingdom (UK). For this reason, simulation models were built to predict scenarios for future incursions. The DK and UK models have a common description of within-herd dynamics, but differ greatly in their descriptions of between-herd spread, one using an explicit representation of vector dispersal, the other a transmission kernel. Here, we compare model predictions for the dynamics of bluetongue in the UK, based on the 2007 incursion and vaccination rollout in 2008. We demonstrate how an agent-based model shows greater sensitivity to the level of vaccine uptake and has lower variability compared with a kernel-based model. However, a model using a transmission kernel requires less detailed data and is often faster.


Assuntos
Vírus Bluetongue/isolamento & purificação , Bluetongue/epidemiologia , Modelos Teóricos , Animais , Bluetongue/prevenção & controle , Bluetongue/transmissão , Vírus Bluetongue/imunologia , Bovinos , Ceratopogonidae/virologia , Dinamarca/epidemiologia , Insetos Vetores/virologia , Ovinos , Reino Unido/epidemiologia , Vacinação/veterinária
14.
Rev Sci Instrum ; 86(7): 073101, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26233350

RESUMO

We present a method for inverting charged particle velocity map images which incorporates a non-uniform detection function. This method is applied to the specific case of extracting molecular axis alignment from Coulomb explosion imaging probes in which the probe itself has a dependence on molecular orientation which often removes cylindrical symmetry from the experiment and prevents the use of standard inversion techniques for the recovery of the molecular axis distribution. By incorporating the known detection function, it is possible to remove the angular bias of the Coulomb explosion probe process and invert the image to allow quantitative measurement of the degree of molecular axis alignment.

15.
Obes Rev ; 16(4): 327-340, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25752329

RESUMO

Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P < 1 × 10(-32) ), WC (n = 152,631; 0.76 cm; 0.68-0.84, P < 1 × 10(-32) ) and FMI (n = 48,192; 0.17 kg m(-2) ; 0.13-0.22, P = 1.0 × 10(-13) ). Cox proportional hazard regression analyses for mortality showed that the hazards ratio (HR) for the minor allele of the FTO SNPs was 1.02 (1.00-1.04, P = 0.097), but the apparent excess risk was eliminated after adjustment for BMI and WC (HR: 1.00; 0.98-1.03, P = 0.662) and for FMI (HR: 1.00; 0.96-1.04, P = 0.932). In conclusion, this study does not support that the FTO SNP is associated with all-cause mortality independently of the adiposity phenotypes.


Assuntos
Adiposidade/genética , Obesidade/mortalidade , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato , Índice de Massa Corporal , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Obesidade/genética , Estudos Observacionais como Assunto , Circunferência da Cintura
16.
Cancer Gene Ther ; 22(3): 130-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25613481

RESUMO

Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in comparison with controls in mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly increased compared with control mice (*P<0.05) but not as compared with HSV-TK/GCV-treated mice. No significant differences were observed in clinical chemistry safety analyses. We conclude that both treatments showed a beneficial treatment response in comparison to controls on tumor growth and ToTK/AZT also on survival. There were no significant differences between these treatments. Therefore ToTK/AZT could be considered as an alternative treatment option for MG because of its favorable therapeutic characteristics.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Proteínas de Plantas/genética , Solanum lycopersicum/enzimologia , Timidina Quinase/genética , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Genes Transgênicos Suicidas , Terapia Genética , Glioma/patologia , Herpesvirus Humano 1/enzimologia , Humanos , Masculino , Camundongos Nus , Ratos , Carga Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Zidovudina/farmacocinética , Zidovudina/uso terapêutico
17.
J Vet Cardiol ; 17 Suppl 1: S220-32, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26776581

RESUMO

OBJECTIVES: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats and shares clinical and pathological characteristics with human HCM. Little is known about the pathogenic mechanisms underlying development of spontaneous feline HCM. ANIMALS: The study population consisted of seven cats diagnosed with HCM and eight age-matched cats with no evidence of cardiac disease. METHODS: Fresh myocardial biopsies taken from the middle of the left ventricular posterior free wall were obtained and examined with transmission electron microscopy. RESULTS: Electron microscopic examination showed ultrastructural aberrations of the myocardial cytoarchitecture and of the interstitium in the seven cats with HCM. In the most severely affected cats the myofibrils were disorganized and subsarcolemmal mitochondria were depleted. In control cats, contraction band artifacts were commonly seen. CONCLUSIONS: In this preliminary study we show that ultrastructural changes of the myocardium in seven cats with HCM involve the cytoskeleton and mitochondria. We suggest that our findings are important for future research aiming at elucidating the pathogenic mechanisms underlying the phenotypic expression of feline HCM. The results of this study prompt for a larger scale study, including quantitative measurements of mitochondrial distribution and cytoskeletal derangements in feline HCM.


Assuntos
Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/patologia , Miocárdio/ultraestrutura , Animais , Cardiomiopatia Hipertrófica/patologia , Estudos de Casos e Controles , Gatos , Feminino , Masculino , Retículo Sarcoplasmático/ultraestrutura
18.
Exp Gerontol ; 52: 23-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24462499

RESUMO

Preservation of functional ability is a well-recognized marker of longevity. At a molecular level, a major determinant of the physiological decline occurring with aging is the imbalance between production and accumulation of oxidative damage to macromolecules, together with a decreased efficiency of stress response to avoid or repair such damage. In this paper we investigated the association of 38 genes (311 SNPs) belonging to the pro-antioxidant pathways with physical and cognitive performances, by analyzing single SNP and gene-based associations with Hand Grip strength (HG), Activities of Daily Living (ADL), Walking Speed (WS), Mini Mental State Examination (MMSE) and Composite Cognitive Score (CCS) in a Cohort of 1089 Danish nonagenarians. Moreover, for each gene analyzed in the pro-antioxidant pathway, we tested the influence on longitudinal survival. In the whole sample, nominal associations were found for TXNRD1 variability with ADL and WS, NDUFS1 and UCP3 with HG and WS, GCLC and UCP2 with WS (p<0.05). Stronger associations although not holding the multiple comparison correction, were observed between MMSE and NDUFV1, MT1A and GSTP1 variability (p<0.009). Moreover, we found that association between genetic variability in the pro-antioxidant pathway and functional status at old age is influenced by sex. In particular, most significant associations were observed in nonagenarian females, between HG scores and GLRX and UCP3 variability, between ADL levels and TXNRD1, MMSE and MT1A genetic variability. In males, a borderline statistically significant association with ADL level was found for UQCRFS1 gene. Nominally significant associations in relation to survival were found in the female sample only with SOD2, NDUFS1, UCP3 and TXNRD1 variability, the latter two confirming previous observations reported in the same cohort. Overall, our work supports the evidence that genes belonging to the pro-anti-oxidant pathway are able to modulate physical and cognitive performance after the ninth decade of life, finally influencing extreme survival.


Assuntos
Atividades Cotidianas , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Cognição , Feminino , Humanos , Masculino
19.
Prev Vet Med ; 112(3-4): 194-202, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24080392

RESUMO

The decision on whether or not to change the control strategy, such as introducing emergency vaccination, is perhaps one of the most difficult decisions faced by the veterinary authorities during a foot-and-mouth disease (FMD) epidemic. A simple tool that may predict the epidemic outcome and consequences would be useful to assist the veterinary authorities in the decision-making process. A previously proposed simple quantitative tool based on the first 14 days outbreaks (FFO) of FMD was used with results from an FMD simulation exercise. Epidemic outcomes included the number of affected herds, epidemic duration, geographical size and costs. The first 14 days spatial spread (FFS) was also included to further support the prediction. The epidemic data was obtained from a Danish version (DTU-DADS) of a pre-existing FMD simulation model (Davis Animal Disease Spread - DADS) adapted to model the spread of FMD in Denmark. The European Union (EU) and Danish regulations for FMD control were used in the simulation. The correlations between FFO and FFS and the additional number of affected herds after day 14 following detection of the first infected herd were 0.66 and 0.82, respectively. The variation explained by the FFO at day 14 following detection was high (P-value<0.001). This indicates that the FFO may take a part in the decision of whether or not to intensify FMD control, for instance by introducing emergency vaccination and/or pre-emptive depopulation, which might prevent a "catastrophic situation". A significant part of the variation was explained by supplementing the model with the FFS (P-value<0.001). Furthermore, the type of the index-herd was also a significant predictor of the epidemic outcomes (P-value<0.05). The results of the current study suggest that national veterinary authorities should consider to model their national situation and to use FFO and FFS to help planning and updating their contingency plans and FMD emergency control strategies.


Assuntos
Epidemias/veterinária , Vírus da Febre Aftosa/fisiologia , Febre Aftosa/epidemiologia , Animais , Simulação por Computador , Dinamarca/epidemiologia , Febre Aftosa/economia , Febre Aftosa/transmissão , Gado , Modelos Biológicos , Estações do Ano , Fatores de Tempo
20.
Scand J Med Sci Sports ; 23(6): e381-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23730899

RESUMO

The aim of this study was to evaluate the effect of an intervention targeting the physical and organizational school environment for noncurricular physical activity (SPACE) on adiposity, aerobic fitness, and musculo-skeletal strength in Danish adolescents. The study used a cluster randomized controlled design. Fourteen schools and 1348 adolescents aged 11-14 years were included at baseline. Seven schools were randomized to the intervention, which was designed to change the organizational and physical environment of the school. The analysis revealed no significant differences between the adolescents in the intervention group compared to the comparison group after a 2-year follow-up. Adjusted for baseline, sex, age, and clustering within schools, the difference between the intervention schools compared to the comparison schools was 6 m in the shuttle run test [95% confidence interval (CI): -21; 33], 0.2 cm in waist circumference (95% CI: -2.6; 3.1), and -1.1 kg in handgrip strength (95% CI: -2.2; -0.1). The results did not provide evidence for the effect of the intervention on adiposity, aerobic fitness, or musculo-skeletal strength in adolescents. Reasons for not finding an effect could be related to both the design and the implementation of the intervention.


Assuntos
Planejamento Ambiental , Força da Mão , Promoção da Saúde/métodos , Atividade Motora , Sobrepeso/terapia , Aptidão Física , Instituições Acadêmicas , Gordura Abdominal , Acelerometria , Adiposidade , Adolescente , Índice de Massa Corporal , Criança , Dinamarca , Teste de Esforço , Feminino , Humanos , Masculino , Força Muscular , Músculo Esquelético , Serviços de Saúde Escolar , Instituições Acadêmicas/organização & administração , Circunferência da Cintura
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