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1.
Pediatr Res ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982166

RESUMO

BACKGROUND: Early intervention for post-hemorrhagic ventricular dilatation (PHVD), guided by ventricular size measurements from cranial ultrasound (cUS), is associated with improved neurodevelopmental outcomes in preterm infants but benefits must be balanced against intervention risks. METHODS: Anterior horn width (AHW) and ventricular index (VI) were measured from cUS for preterm infants (<29 weeks) with intraventricular hemorrhage admitted from 2010-2018. PHVD was defined as AHW > 6 mm or VI >97th percentile for postmenstrual age. Individual ventricular size trajectories were plotted, and a growth mixture model (GMM) used to identify latent trajectory classes and compare these to predetermined outcome of neurosurgical intervention. RESULTS: Measurements were obtained from 1543 cUS in 249 infants, of whom 39 had PHVD without and 17 PHVD with neurosurgical intervention based on signs of raised intracranial pressure. The GMM predicted trajectory identified: 93.3% of infants without PHVD, 88.2% and 30.8% of infants with PHVD with and without intervention using AHW; 100% of infants without PHVD, 52.9% and 59.0% of infants with PHVD with and without intervention using VI. CONCLUSIONS: The AHW GMM identified a significant proportion of infants with severe PHVD. Model refinement offers a promising approach for identifying differences in PHVD trajectory at an early stage to guide management. IMPACT: It is difficult to distinguish the trajectory of PHVD in the early stage of development, in particular PHVD that spontaneously arrests from slowly progressive PHVD which eventually requires intervention. We report the first modeling-based evaluation of PHVD trajectory for the prediction of short-term outcome of PHVD progression and neurosurgical intervention. With additional clinical validation and optimization to increase accuracy, predictive modeling has the potential to identify important differences in PHVD trajectory at an early stage in the clinical course, allowing for more individualized data-driven risk-benefit assessments to guide decisions on early intervention.

2.
Can Vet J ; 64(6): 571-578, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37265816

RESUMO

Objective: To measure associations between self-care activities and depression, anxiety, and stress of preclinical veterinary students during a semester. Procedure: Preclinical veterinary students at the University of Calgary Faculty of Veterinary Medicine were recruited voluntarily. Depression, anxiety, and stress scores (DASS-21) were measured, and a self-care questionnaire was administered at the beginning and end of the semester. Results: Depression, anxiety, and stress scores did not change during the fall semester (P = 1.000). At the beginning of the semester, students who spent 15 to 30 min (P = 0.042) or 30 to 60 min (P = 0.013) outside daily had lower anxiety scores compared to those who spent < 15 min outside daily; students who spent > 2 h daily on social media had higher stress scores than students who spent < 60 min (P = 0.024); and students who slept for 6 to 8 h daily had lower stress scores than students who slept < 6 h (P = 0.015). At the end of the semester, students who "often" felt that self-care techniques managed their stress had lower depression (P = 0.003) and anxiety (P = 0.011) scores than those who "rarely" did; students who spent 30 to 60 min outside daily had lower depression scores than those who spent < 15 min (P = 0.031); students who spent 15 to 30 min (P = 0.002) or 30 to 60 min (P = 0.009) outside daily had lower stress scores than those who spent < 15 min; and students who exercised 30 to 60 min daily had lower stress scores than those who exercised < 15 min (P = 0.047). Conclusion: Self-care activities that were associated with lower depression, anxiety, or stress scores at the beginning or end of the semester included spending at least 15 min daily outside or exercising; spending < 30 min on social media daily; and sleeping 6 to 8 h daily. These practices warrant further investigation. Clinical relevance: Encouraging certain self-care practices among preclinical veterinary students has the potential to enhance their mental health and should be considered part of a veterinary school curriculum.


Pratiques d'autosoins et scores de dépression, d'anxiété et de stress chez les étudiants vétérinaires au cours d'un semestre. Objectif: Mesurer les associations entre les activités d'autosoins et la dépression, l'anxiété et le stress des étudiants vétérinaires au cours d'un semestre. Procédure: Les étudiants vétérinaires de la faculté de médecine vétérinaire de l'University of Calgary ont été recrutés sur une base volontaire. Des scores de dépression, d'anxiété et de stress (DASS-21) ont été mesurés et un questionnaire d'autosoins a été administré au début et à la fin du semestre. Résultats: Les scores de dépression, d'anxiété et de stress n'ont pas changé au cours du semestre d'automne (P = 1,000). Au début du semestre, les étudiants qui passaient 15 à 30 min (P = 0,042) ou 30 à 60 min (P = 0,013) à l'extérieur par jour présentaient des scores d'anxiété inférieurs à ceux qui passaient < 15 min à l'extérieur par jour; les étudiants qui passaient > 2 h par jour sur les réseaux sociaux avaient des scores de stress plus élevés que les étudiants qui passaient < 60 min (P = 0,024); et les étudiants qui dormaient de 6 à 8 h par jour avaient des scores de stress inférieurs à ceux qui dormaient < 6 h (P = 0,015). À la fin du semestre, les étudiants qui estimaient « souvent ¼ que les techniques d'autosoins géraient leur stress avaient des scores de dépression (P = 0,003) et d'anxiété (P = 0,011) inférieurs à ceux qui l'étaient « rarement ¼; les étudiants qui passaient 30 à 60 min à l'extérieur quotidiennement avaient des scores de dépression inférieurs à ceux qui passaient moins de 15 min (P = 0,031); les étudiants qui passaient 15 à 30 min (P = 0,002) ou 30 à 60 min (P = 0,009) à l'extérieur quotidiennement avaient des scores de stress inférieurs à ceux qui passaient < 15 min; et les étudiants qui faisaient de l'exercice de 30 à 60 min par jour avaient des scores de stress inférieurs à ceux qui faisaient de l'exercice < 15 min (P = 0,047). Conclusion: Les activités d'autosoins associées à des scores de dépression, d'anxiété ou de stress plus faibles au début ou à la fin du semestre comprenaient le fait de passer au moins 15 minutes par jour à l'extérieur ou de faire de l'exercice; passer < 30 minutes sur les réseaux sociaux quotidiennement; et dormir 6 à 8 h par jour. Ces pratiques méritent une enquête plus approfondie. Pertinence clinique: Encourager certaines pratiques d'autosoins chez les étudiants vétérinaires a le potentiel d'améliorer leur santé mentale et devrait être considéré comme faisant partie du programme d'études d'une école vétérinaire.(Traduit par Dr Serge Messier).


Assuntos
Depressão , Estudantes de Medicina , Animais , Humanos , Autocuidado/veterinária , Ansiedade , Inquéritos e Questionários , Estresse Psicológico
3.
J Vet Med Educ ; 48(4): 485-491, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32758091

RESUMO

The Objective Structured Clinical Examination (OSCE) is a valid, reliable assessment of veterinary students' clinical skills that requires significant examiner training and scoring time. This article seeks to investigate the utility of implementing video recording by scoring OSCEs in real-time using live examiners, and afterwards using video examiners from within and outside the learners' home institution. Using checklists, learners (n=33) were assessed by one live examiner and five video examiners on three OSCE stations: suturing, arthrocentesis, and thoracocentesis. When stations were considered collectively, there was no difference between pass/fail outcome between live and video examiners (χ2 = 0.37, p = .55). However, when considered individually, stations (χ2 = 16.64, p < .001) and interaction between station and type of examiner (χ2 = 7.13, p = .03) demonstrated a significant effect on pass/fail outcome. Specifically, learners being assessed on suturing with a video examiner had increased odds of passing the station as compared with their arthrocentesis or thoracocentesis stations. Internal consistency was fair to moderate (0.34-0.45). Inter-rater reliability measures varied but were mostly moderate to strong (0.56-0.82). Video examiners spent longer assessing learners than live raters (mean of 21 min/learner vs. 13 min/learner). Station-specific differences among video examiners may be due to intermittent visibility issues during video capture. Overall, video recording learner performances appears reliable and feasible, although there were time, cost, and technical issues that may limit its routine use.


Assuntos
Educação em Veterinária , Avaliação Educacional , Animais , Competência Clínica , Estudos de Viabilidade , Reprodutibilidade dos Testes , Gravação em Vídeo
4.
Can Vet J ; 60(8): 855-858, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31391602

RESUMO

Horses are long-day breeders and commence ovarian follicular activity during the spring. Evidence suggests that there is an endogenous circannual rhythm in mares, and it is uncertain whether hormonal manipulation during or immediately following the fall transition induces follicular development. The current study was designed to test the hypothesis that both deslorelin and naltrexone induce follicular development in late fall transitioning or anestrous mares. Five of six mares treated with deslorelin, and 4 of 6 mares treated with naltrexone, developed a pre-ovulatory-sized follicle and were inseminated. Zero of three deslorelin-control mares and 1 of 3 naltrexone-control mares were inseminated. The number of mares bred in the deslorelin treatment group was significantly higher than in the corresponding control group (P < 0.05). Six of nine mares inseminated were pregnant 14 days after insemination. In conclusion, we were able to induce follicular development resulting in fertile ovulations during and shortly after the fall transition.


Stimulation du développement folliculaire par le deslorelin et le naltrexone chez des juments durant la transition automnale et le début de l'anoestrus. Les chevaux sont des reproducteurs saisonniers influencés par la lumière du jour et l'activité folliculaire ovarienne débute au printemps. Les évidences suggèrent que chez les juments il y a un rythme circannuel endogène, et il est incertain si une manipulation hormonale durant ou immédiatement après la transition automnale induit le développement folliculaire. La présente étude a été conçue afin de vérifier l'hypothèse que le deslorelin et le naltrexone induisent le développement folliculaire tard à l'automne lors de la période de transition ou chez des juments en anoestrus. Cinq des six juments traitées avec du deslorin et quatre des six juments traitées avec du naltrexone ont développé un follicule de taille pré-ovulatoire et ont été inséminées. Aucune des trois juments témoins pour le deslorin et une des trois juments témoins pour le naltrexone furent inséminées. Le nombre de juments saillies dans le groupe de traitement deslorin était significativement supérieur à celui du groupe témoin correspondant (P < 0,05). Six des neuf juments inséminées étaient gestantes 14 jours après l'insémination. En conclusion, nous avons été en mesure d'induire le développement folliculaire résultant en des ovulations fertiles durant et tôt après la transition automnale.(Traduit par Dr Serge Messier).


Assuntos
Anestro , Naltrexona , Animais , Feminino , Cavalos , Ovulação , Gravidez , Pamoato de Triptorrelina/análogos & derivados
5.
BMC Vet Res ; 13(1): 360, 2017 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-29179766

RESUMO

BACKGROUND: Despite the use of water treadmills (WT) in conditioning horses, the intensity of WT exercise has not been well documented. The workload on a WT is a function of water height and treadmill speed. Therefore, the purpose of this study was to determine the effects of these factors on workload during WT exercise. Fifteen client-owned Quarter Horses were used in a randomized, controlled study. Three belt speeds and three water heights (mid cannon, carpus and stifle), along with the control condition (dry treadmill, all three speeds), were tested. Measured outcomes were oxygen consumption (V̇O2), ventilation (respiratory frequency, tidal volume (VT)), heart rate (HR), and blood lactate. An ergospirometry system was used to measure V̇O2 and ventilation. Linear mixed effects models were used to examine the effects of presence or absence of water, water height and speed (as fixed effects) on measured outcomes. RESULTS: Water height and its interaction with speed had a significant effect on V̇O2, VT and HR, all peaking at the highest water level and speed (stifle at 1.39 m/s, median V̇O2 = 16.70 ml/(kg.min), VT = 6 L, HR = 69 bpm). Respiratory frequency peaked with water at the carpus at 1.39 m/s (median 49 breaths/min). For a given water height, the small increments in speed did not affect the measured outcomes. Post-exercise blood lactate concentration did not change. CONCLUSIONS: Varying water height and speed affects the workload associated with WT exercise. The conditions utilized in this study were associated with low intensity exercise. Water height had a greater impact on exercise intensity than speed.


Assuntos
Coração/fisiologia , Cavalos/fisiologia , Consumo de Oxigênio/fisiologia , Esforço Físico/fisiologia , Fenômenos Fisiológicos Respiratórios , Animais , Teste de Esforço/veterinária , Frequência Cardíaca/fisiologia , Imersão , Ácido Láctico/sangue , Respiração , Volume de Ventilação Pulmonar/fisiologia
6.
Can Vet J ; 57(11): 1161-1165, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27807379

RESUMO

New technology allows noninvasive measurement of total hemoglobin (Hb) in humans through use of multiple wavelength co-oximetry. This monitor is now available to the veterinary market but no studies have been performed to validate its use in animals. This study investigated the use of co-oximetry to measure Hb in anesthetized dogs by comparing "gold standard" Hb measurements from a laboratory (LabHb) with those measured by the co-oximeter (SpHb). Bland-Altman analysis showed that the monitor had a bias of -3.01 (SpHb values were lower than LabHb values) and that 64.5% of measured SpHb values were greater than 20 g/L different from their associated LabHb values. Based on the results of this study, use of co-oximetry to measure Hb in anesthetized dogs is not accurate enough to direct treatment. Further studies are warranted in other animal species and under other clinical conditions.


Validation des mesures non invasives de l'hémoglobine à l'aide de la co-oximétrie chez les chiens anesthésiés. La nouvelle technologie permet la mesure non invasive de l'hémoglobine totale (Hb) chez les humains à l'aide d'une co-oximétrie à longueurs d'onde multiples. Ce moniteur est maintenant disponible pour le marché vétérinaire, mais aucune étude n'a été réalisée pour valider son utilisation chez les animaux. Cette étude a évalué l'utilisation de la co-oximétrie pour mesurer Hb chez des chiens anesthésiés en comparant les mesures Hb d'un laboratoire (LabHb) considérées comme les mesures étalons aux mesures effectuées par le co-oximètre (SpHb). L'analyse Bland-Altman a montré que le moniteur avait un biais de −3,01 (les valeurs SpHb étaient inférieures aux valeurs LabHb) et que 64,5 % des valeurs SpHb mesurées présentaient une différence supérieure à 20 g/L par rapport aux valeurs LabHb correspondantes. En se fondant sur les résultats de cette étude, on constate que l'utilisation de co-oximétrie pour mesurer Hb chez les chiens anesthésiés n'est pas suffisamment exacte pour orienter le traitement. De nouvelles études sont justifiées chez d'autres espèces animales et dans d'autres conditions cliniques.(Traduit par Isabelle Vallières).


Assuntos
Hemoglobinas/análise , Oximetria/veterinária , Anestesia/veterinária , Animais , Cães , Feminino , Masculino , Monitorização Fisiológica/veterinária , Reprodutibilidade dos Testes
7.
Epilepsia ; 56(1): 77-81, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25385396

RESUMO

OBJECTIVE: Hypsarrhythmia is the classic interictal electroencephalographic pattern associated with infantile spasms, and characterized by high voltage, disorganization, and multifocal independent epileptiform discharges. Given this seemingly simple definition, one might expect excellent interrater reliability (IRR) in the identification of this pattern. Alternatively, it may be argued that assessments of voltage and disorganization are fairly subjective, and thus quite challenging in borderline cases. We sought to test the IRR of hypsarrhythmia assessment in a systematic fashion. METHODS: Six blinded pediatric electroencephalographers from four centers reviewed 22 electroencephalography (EEG) samples from patients with infantile spasms. Each sample was 5 min in duration and included only wakefulness. Raters determined if each EEG was abnormal and if hypsarrhythmia was present/absent, and characterized relevant features: voltage, organization, epileptiform discharges, slowing, interictal attenuations, symmetry, and synchrony. In addition, raters indicated their level of confidence for each assessment. Multirater kappa statistics (κ) were calculated for the assessment of hypsarrhythmia and each feature. RESULTS: Although IRR was favorable in determining whether a study was normal or abnormal (κ=0.89), reliability was unfavorable for assessment of hypsarrhythmia (κ=0.40), modified hypsarrhythmia (κ=0.47), high voltage (κ=0.37), disorganization (κ=0.22), multifocal epileptiform discharges (κ=0.68), interictal voltage attenuations (κ=0.21), slowing (κ=0.20), asymmetry (κ=0.26), and asynchrony (κ=0.08). Despite generally unsatisfactory interrater agreement, raters consistently reported high confidence in assessments. SIGNIFICANCE: This study contradicts the view that hypsarrhythmia assessment is straightforward. Even small variability in the identification of hypsarrhythmia has potentially deleterious consequences for clinical care, as its presence or absence impacts decisions to pursue high-risk and high-cost therapies. These inconsistencies may similarly confound studies in which abolition of hypsarrhythmia is an outcome measure. There is a great need for practical, reliable, and unbiased measures of hypsarrhythmia.


Assuntos
Eletroencefalografia/estatística & dados numéricos , Neurologia/normas , Espasmos Infantis/diagnóstico , Pré-Escolar , Ensaios Clínicos como Assunto/normas , Humanos , Lactente , Variações Dependentes do Observador , Reprodutibilidade dos Testes
8.
Epilepsia ; 55(1): 103-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24446954

RESUMO

PURPOSE: This study investigated the short-term response to a standardized hormonal therapy protocol for treatment of infantile spasms. METHODS: Twenty-seven children with video electroencephalography (EEG)-confirmed infantile spasms received very high dose (8 mg/kg/day, max 60 mg/day) oral prednisolone for 2 weeks. Response (absence of both hypsarrhythmia and spasms) to prednisolone was ascertained by repeat overnight video-EEG. Responders were tapered over 2 weeks and nonresponders were immediately transitioned to high dose (150 IU/m(2)/day) intramuscular adrenocorticotropic hormone (ACTH) for two additional weeks. Response was again determined by overnight video-EEG after ACTH therapy. KEY FINDINGS: Sixty-three percent (17/27) of patients responded completely to prednisolone. Subsequently, 40% (4/10) of prednisolone nonresponders exhibited a complete response after an additional 2-week course with ACTH. Among 27 subjects with median follow-up of 13.5 months (interquartile range [IQR] 4.8-25.9), 12% (2/17) of prednisolone responders and 50% (2/4) of ACTH responders experienced a relapse between 2 and 9 months after initial response. SIGNIFICANCE: Very high dose prednisolone demonstrated significantly higher efficacy than previously reported for lower doses in prior studies. High dose ACTH may be superior to very high dose prednisolone, and in lieu of a definitive clinical trial, the choice between prednisolone and ACTH for initial treatment of infantile spasms remains controversial.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Anticonvulsivantes/uso terapêutico , Prednisolona/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Adolescente , Hormônio Adrenocorticotrópico/administração & dosagem , Anticonvulsivantes/administração & dosagem , Criança , Pré-Escolar , Esquema de Medicação , Quimioterapia Combinada , Eletroencefalografia , Feminino , Humanos , Lactente , Masculino , Monitorização Fisiológica , Prednisolona/administração & dosagem , Resultado do Tratamento
9.
J Clin Transl Endocrinol ; 37: 100363, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39161664

RESUMO

Objective: To assess change in total daily dose (TDD) of insulin following a switch from subcutaneous (SC) injections to continuous subcutaneous insulin infusion (CSII) in pediatric patients with type 1 diabetes (T1D). Secondary objectives were to determine the change in %basal insulin, insulin to carbohydrate (I:C) ratios, insulin sensitivity factor (ISF), and HbA1c/IDAA1c. Methods: A retrospective chart review of patients < 18 years of age who transitioned from SC to CSII at the Alberta Children's Hospital (Calgary, Alberta, Canada) between January 2019 and March 2022. Results: There was an increase of 0.04 units/kg/day in TDD from baseline vs 1-3 months later (p = 0.04, 95 % confidence interval (CI) [0.002, 0.072]). When stratified by age, a similar increase in TDD was observed in age 5-12 years only (p = 0.05, 95 % CI [0.0006, 0.8236]). There was a decrease in overall %basal insulin by 3 (44 % of TDD at baseline vs 41 % of TDD on CSII). (p = 0.02, 95 % CI [-5.5, -0.4]). No strengthening was seen in I:C ratios from baseline vs 1-3 months later. There was a significant strengthening of I:C ratios at all meals in the basal bolus group from 1-3 weeks to 1-3 months post-CSII; overall strengthening of ISF at both time points; and an overall HbA1c decrease -0.30 (p < 0.0001, CI [-0.45, -0.15]). Each extra year with diabetes was associated with a decrease in HbA1c by 0.07 % (p = 0.006). Conclusions: TDD of insulin was not found to be decreased post CSII initiation and patient characteristics should be considered when changing from SC to CSII. HbA1c was significantly improved post CSII.

10.
J Vet Diagn Invest ; : 10406387241269043, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39152694

RESUMO

Postmortem examination of deceased production animals with appropriate ancillary testing is fundamental to determining causes of morbidity and mortality. Reaching a definitive diagnosis is crucial to evidence-based herd management and treatment decisions that safeguard animal health and welfare, food safety, and human health. However, for a range of reasons, carcasses sometimes cannot be examined in a veterinary diagnostic laboratory. As a result, postmortem examinations of farmed animals, including cattle, are often performed on-farm by the referring veterinarian (rVet) with tissue samples submitted to a veterinary diagnostic laboratory for ancillary testing. For various reasons, field postmortems can be associated with lower diagnostic rates. We investigated real-time pathologist-assisted field postmortem examination (rtPAP) assistance to beef cattle rVets to gauge any improvement in attaining a final diagnosis. We found that rtPAPs improved the success of reaching a final diagnosis compared to unassisted field postmortem examinations. Both the participating bovine rVets and the pathologists saw benefits to the rtPAPs, with bovine rVets indicating that they would utilize this service in the future if available. Our proof-of-concept study demonstrated the positive role of rtPAPs in diagnosing beef cattle disease and speaks to the need for telepathology services supporting food animal rVets and producers.

11.
J Vet Med Sci ; 86(9): 979-985, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39034151

RESUMO

No study has determined the minimal effective dose of trazodone required to induce behavioral changes and its safety profile in rabbits. Therefore, this study aimed to determine the minimal effective dose of trazodone to improve compliance to handling, and to evaluate associated changes in motor activity, physiological and arterial blood gas parameters. Eight intact female New Zealand White rabbits (2-month-old; 1.66 ± 0.12 kg) were included in this prospective, blinded, randomized cross-over study. After a 10-day acclimation, rabbits randomly received placebo or trazodone 10, 20 or 30 mg/kg orally (PLAC, TRAZ10, TRAZ20, TRAZ30) with a 1-week wash-out period. Compliance scoring (dynamic interactive visual analog scale; DIVAS), activity levels measured with accelerometry (T0-T600), physiological parameters (temperature, heart, and respiratory rates), and arterial blood gas parameters (up to T240) were evaluated. Compliance scores, accelerometry, physiological and arterial blood gas parameters and hypoxemia prevalence (PaO2 <60 mmHg) were analyzed using linear mixed models and Chi-squared tests, respectively (P<0.05). When compared with PLAC, DIVAS scores were significantly higher at T80-120, T40-120 and T120-200 in TRAZ10, TRAZ20 and TRAZ30 post-administration, respectively. When compared with baseline, DIVAS scores were significantly higher from T80-160, T40-240 and T80-200 in TRAZ10, TRAZ20 and TRAZ30, respectively. All other parameters were not significantly different. In TRAZ30, hypoxemia was observed in 2/8 rabbits (P=0.104). In conclusion, oral trazodone improved rabbit compliance at all studied dosages, especially 20 mg/kg improved rabbit compliance without decreasing motor activity or causing hypoxemia.


Assuntos
Estudos Cross-Over , Trazodona , Animais , Coelhos , Feminino , Trazodona/administração & dosagem , Trazodona/farmacologia , Administração Oral , Estudos Prospectivos , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Gasometria/veterinária , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Inibidores Seletivos de Recaptação de Serotonina/farmacologia
12.
Bioorg Med Chem Lett ; 23(7): 1974-7, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23453068

RESUMO

Mutations in leucine-rich repeat kinase 2 (LRRK2) are associated with familial Parkinson's disease (PD). The kinase activity of this complex protein is increased by pathogenic mutations. Inhibition of LRRK2 kinase activity has therefore emerged as a promising approach for the treatment of PD. Herein we report our findings on a series of 4-alkylamino-7-aryl-3-cyanoquinolines that exhibit kinase inhibitory activity against both wild type and G2019S mutant LRRK2. Activity was determined in both biochemical and cellular assays. Compound 14 was further evaluated in an in vivo pharmacodynamic study and found to significantly inhibit Ser935 phosphorylation after oral dosing.


Assuntos
Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Quinolinas/farmacologia , Animais , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Modelos Moleculares , Estrutura Molecular , Mutação , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Quinolinas/síntese química , Quinolinas/química , Relação Estrutura-Atividade
14.
Bull Math Biol ; 74(8): 1912-37, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22718395

RESUMO

Individual-level models (ILMs) for infectious diseases, fitted in a Bayesian MCMC framework, are an intuitive and flexible class of models that can take into account population heterogeneity via various individual-level covariates. ILMs containing a geometric distance kernel to account for geographic heterogeneity provide a natural way to model the spatial spread of many diseases. However, in even only moderately large populations, the likelihood calculations required can be prohibitively time consuming. It is possible to speed up the computation via a technique which makes use a linearized distance kernel. Here we examine some methods of carrying out this linearization and compare the performances of these methods.


Assuntos
Teorema de Bayes , Doenças Transmissíveis/imunologia , Modelos Imunológicos , Modelos Estatísticos , Doenças Transmissíveis/epidemiologia , Simulação por Computador , Humanos , Cadeias de Markov , Método de Monte Carlo
15.
Front Vet Sci ; 9: 1020710, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387393

RESUMO

Background: Pupillometry, the measurement of pupil size and reactivity to a stimulus, has various uses in both human and veterinary medicine. These reflect autonomic tone, with the potential to assess nociception and emotion. Infrared pupillometry reduces inaccuracies that may occur when the pupillary light reflex is determined subjectively by the examiner. To our knowledge, there are no published studies outlining normal reference intervals for automated pupillometry in dogs. Objective: The objective of this study was to develop de novo automated pupillometry reference intervals from 126 healthy canine eyes. Methods: The pupillary light reflex (PLR) was measured with a handheld pupillometer (NeurOptics™ PLR-200™ Pupillometer). Parameters recorded included maximum pupil diameter (MAX), minimum pupil diameter (MIN), percent constriction (CON), latency (LAT), average constriction velocity (ACV), maximum constriction velocity (MCV), average dilation velocity (ADV) and time to 75% pupil diameter recovery (T75). One measurement was obtained for each eye. Results: The following reference intervals were developed: MAX (6.05-11.30 mm), MIN (3.76-9.44 mm), CON (-37.89 to -9.64 %), LAT (0.11-0.30 s), ACV (-6.39 to -2.63 mm/ s), MCV (-8.45 to -3.75 mm/s), ADV (-0.21-1.77 mm/s), and T75 (0.49-3.20 s). Clinical significance: The reference intervals developed in this study are an essential first step to facilitate future research exploring pupillometry as a pain assessment method in dogs.

16.
Eur J Clin Nutr ; 76(5): 772-774, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34675401

RESUMO

Chronic arsenic exposure is associated with a number of systemic diseases, including cardiovascular disease. Selenium has been shown to promote arsenic excretion from the body. We investigated if a high-selenium lentil diet has an effect on blood pressure and plasma lipid levels in an arsenic-exposed population by conducting a 6-month randomized controlled dietary intervention trial with 405 participants.


Assuntos
Arsênio , Doenças Cardiovasculares , Lens (Planta) , Selênio , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Dieta , Fatores de Risco de Doenças Cardíacas , Humanos , Fatores de Risco
17.
Conserv Physiol ; 10(1): coab103, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35492408

RESUMO

Glucocorticoid (GC) levels are increasingly and widely used as biomarkers of hypothalamic-pituitary-adrenal (HPA) axis activity to study the effects of environmental changes and other perturbations on wildlife individuals and populations. However, identifying the intrinsic and extrinsic factors that influence GC levels is a key step in endocrinology studies to ensure accurate interpretation of GC responses. In muskoxen, qiviut (fine woolly undercoat hair) cortisol concentration is an integrative biomarker of HPA axis activity over the course of the hair's growth. We gathered data from 219 wild muskoxen harvested in the Canadian Arctic between October 2015 and May 2019. We examined the relationship between qiviut cortisol and various intrinsic (sex, age, body condition and incisor breakage) and extrinsic biotic factors (lungworm and gastrointestinal parasite infections and exposure to bacteria), as well as broader non-specific landscape and temporal features (geographical location, season and year). A Bayesian approach, which allows for the joint estimation of missing values in the data and model parameters estimates, was applied for the statistical analyses. The main findings include the following: (i) higher qiviut cortisol levels in males than in females; (ii) inter-annual variations; (iii) higher qiviut cortisol levels in a declining population compared to a stable population; (iv) a negative association between qiviut cortisol and marrow fat percentage; (v) a relationship between qiviut cortisol and the infection intensity of the lungworm Umingmakstrongylus pallikuukensis, which varied depending on the geographical location; and (vi) no association between qiviut cortisol and other pathogen exposure/infection intensity metrics. This study confirmed and further identified important sources of variability in qiviut cortisol levels, while providing important insights on the relationship between GC levels and pathogen exposure/infection intensity. Results support the use of qiviut cortisol as a tool to monitor temporal changes in HPA axis activity at a population level and to inform management and conservation actions.

18.
NPJ Sci Food ; 6(1): 46, 2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36175443

RESUMO

Cell culture media design is perhaps the most significant hurdle currently facing the commercialization of cultivated meat as an alternative source of dietary protein. Since media optimization for a specific culture system requires a significant amount of effort and investment, a major question remaining is whether media formulations can be easily shared across multiple production schemes for cells of different species and lineages. Here, we perform spent medium analysis to compare the specific nutrient utilization of primary embryonic chicken muscle precursor cells and fibroblasts to the murine C2C12 myoblast cell line. We demonstrate that these related cell types have significantly different nutrient utilization patterns collectively and on a per-cell basis, and that many components of conventional media do not appear to be depleted by the cells. Namely, glucose was not consumed as rapidly nor as completely by the chicken muscle precursors compared to other cells overall, and there were significant differences in specific consumption rates for several other key nutrients over the first day of culture. Ultimately, our results indicate that no one medium is likely ideal and cost effective to culture multiple cell types and that novel methods to streamline media optimization efforts will be important for the industry to develop.

20.
Front Vet Sci ; 6: 441, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31921902

RESUMO

Objective: This study aimed to determine the most appropriate suture bite and stitch interval (SBSI) size for closing feline linea alba. Study design: Randomized ex vivo mechanical testing. Sample population: Ventral abdominal walls from 35 male feline cadavers were harvested and separated into 125 segments. Methods: Segments were incised along midline then sutured back together using 3-0 polydioxanone using one of the following SBSI: 3, 5, 7.5, or 10 mm whereby the distance represents the distance both between the suture bites, and from the bite to incision line. The location of segments as well as the weight of the cadaver were recorded. A single linear distraction mechanical breaking test was performed. Statistical analyses (logistic and linear regression) were performed to determine which factors were associated with visual and mechanical failure, as well as load at failure or maximum displacement. Results: SBSI was significantly associated with load at failure or maximum displacement (p < 0.001). In particular, 5 mm SBSI had the highest load at failure amongst all the bite sizes (LSmeans = 27.55N, 95% Confidence Interval (CI): 23.65-31.44); this was significantly higher than 7.5 mm (LSmeans = 19.15N, 95% CI: 15.26-23.05, p = 0.016) and 10 mm (LSmeans = 16.55N, 95%CI:12.39-20.70, p = 0.0012) but not significantly higher than 3 mm (LSmeans = 23.78N, 95% CI: 19.69-27.86, p = 0.2). Increased SBSI increased the odds of visual failure (p < 0.001) whereas increased weight of the cadaver reduced the odds of visual failure (OR = 0.52, 95%CI: 0.30-0.88, p = 0.016). Conclusion: The 5 mm SBSI had the highest load at failure and was not significantly different from the 3 mm SBSI when apposing feline linea alba using 3-0 polydioxanone. Clinical significance: Using 5 mm SBSI is the preferred bite size compared to 7.5 or 10 mm SBSI when apposing feline linea alba with 3-0 polydioxanone.

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