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1.
Phys Rev Lett ; 132(13): 131004, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38613261

RESUMO

We present first results from a dark photon dark matter search in the mass range from 44 to 52 µeV (10.7-12.5 GHz) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area 0.5 m^{2} and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon photon mixing parameters χ≳10^{-12} in this range at 90% confidence level. This surpasses existing constraints by about 2 orders of magnitude and is the most stringent bound on dark photons in this range below 49 µeV.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38498029

RESUMO

Background and purpose: Little is known about the applicability, utilization, and effectiveness of mind-body interventions (MBIs) for conditions that are not predominantly pain, neoplastic, or psychiatric, particularly in pediatric patients. This scoping review describes research pertaining to such interventions in youth with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Methods: Searches of EBSCO CINAHL, Elsevier Scopus, Ovid for MEDLINE, and Ovid PsycInfo were conducted to investigate MBIs in youth under 18 years of age with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Articles published between 2010 and 2020 were included. Abstracts were screened by three authors for inclusion, and disagreements were resolved by a designated author. Selected full-text articles were divided among all authors for review of study quality, intervention feasibility and acceptability, and effectiveness. Results: The search yielded 1010 titles with 15 meeting the final inclusion criteria, studying a total of 641 youth. Participants ranged in age from 6 to 19 years (included studies had data on participants <18 years reported separately); 61.5% were female (n = 394) and 38.5% were male (n = 247). The two most common conditions studied were asthma and irritable bowel syndrome, with yoga being the most popular intervention. Overall, MBIs showed promising preliminary evidence for improving symptoms and quality of life in youth with chronic medical conditions. Conclusion: MBIs have been successfully delivered and show promise in symptom palliation and quality of life improvement for youth with a variety of chronic medical conditions. More data from high-quality randomized controlled trials are needed to further characterize the effectiveness of specific modalities for specific conditions.

3.
J Comput Aided Mol Des ; 38(1): 14, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38499823

RESUMO

Computer-aided drug design has advanced rapidly in recent years, and multiple instances of in silico designed molecules advancing to the clinic have demonstrated the contribution of this field to medicine. Properly designed and implemented platforms can drastically reduce drug development timelines and costs. While such efforts were initially focused primarily on target affinity/activity, it is now appreciated that other parameters are equally important in the successful development of a drug and its progression to the clinic, including pharmacokinetic properties as well as absorption, distribution, metabolic, excretion and toxicological (ADMET) properties. In the last decade, several programs have been developed that incorporate these properties into the drug design and optimization process and to varying degrees, allowing for multi-parameter optimization. Here, we introduce the Artificial Intelligence-driven Drug Design (AIDD) platform, which automates the drug design process by integrating high-throughput physiologically-based pharmacokinetic simulations (powered by GastroPlus) and ADMET predictions (powered by ADMET Predictor) with an advanced evolutionary algorithm that is quite different than current generative models. AIDD uses these and other estimates in iteratively performing multi-objective optimizations to produce novel molecules that are active and lead-like. Here we describe the AIDD workflow and details of the methodologies involved therein. We use a dataset of triazolopyrimidine inhibitors of the dihydroorotate dehydrogenase from Plasmodium falciparum to illustrate how AIDD generates novel sets of molecules.


Assuntos
Inteligência Artificial , Desenho de Fármacos , Algoritmos , Evolução Molecular
4.
Pediatr Res ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287106

RESUMO

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

5.
Pediatr Blood Cancer ; 70(4): e30243, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36726036

RESUMO

BACKGROUND: Children, adolescents, and young adults with hematologic and/or oncologic conditions experience multiple, significant symptoms (e.g., pain, stress, and anxiety), which may be addressed by nonpharmacologic approaches such as massage therapy (MT). The purpose of this study was to describe the clinical delivery of MT provided by a certified pediatric massage therapist and assess effectiveness in two patient groups: those with sickle cell disease (SCD) or hematologic and/or oncologic conditions excluding SCD (HemOnc). METHODS: Investigators conducted a retrospective review of MT sessions provided to patients 0-39 years with hematologic and/or oncologic conditions at a large pediatric academic medical center. RESULTS: Between October 2019 and December 2021, 3015 MT sessions were provided to 243 patients (171 HemOnc; 72 SCD) and documented in the electronic health record. Patients (mean age: 12.21 ± 7.19 years) were generally White (49.4%) or Black/African American (43.2%), non-Hispanic (94.2%), and 52.3% female. Patients in the SCD group (vs. patients in the HemOnc group) reported significantly higher (p < .05) pretreatment pain (6.95 vs. 4.46), stress (6.47 vs. 4.58), and anxiety (6.67 vs. 4.59). All patients reported clinically and statistically significant (p < .001) mean reductions in pain (-2.25 ± 1.87), stress (-2.50 ± 1.73), and anxiety (-2.52 ± 1.69), with patients in the HemOnc group reporting greater mean pain change (-2.54 vs. -1.87) than patients in the SCD group. CONCLUSIONS: This study supports the clinical effectiveness of MT for addressing acute pain, stress, and anxiety among youth with hematologic and/or oncologic conditions. Future research is needed to identify optimal MT utilization.


Assuntos
Dor Aguda , Anemia Falciforme , Hematologia , Humanos , Adolescente , Criança , Feminino , Adulto Jovem , Pré-Escolar , Adulto , Masculino , Manejo da Dor , Ansiedade/terapia , Anemia Falciforme/terapia , Massagem
6.
Phys Rev Lett ; 128(13): 131801, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426699

RESUMO

We introduce the Broadband Reflector Experiment for Axion Detection (BREAD) conceptual design and science program. This haloscope plans to search for bosonic dark matter across the [10^{-3},1] eV ([0.24, 240] THz) mass range. BREAD proposes a cylindrical metal barrel to convert dark matter into photons, which a novel parabolic reflector design focuses onto a photosensor. This unique geometry enables enclosure in standard cryostats and high-field solenoids, overcoming limitations of current dish antennas. A pilot 0.7 m^{2} barrel experiment planned at Fermilab is projected to surpass existing dark photon coupling constraints by over a decade with one-day runtime. Axion sensitivity requires <10^{-20} W/sqrt[Hz] sensor noise equivalent power with a 10 T solenoid and 10 m^{2} barrel. We project BREAD sensitivity for various sensor technologies and discuss future prospects.

7.
Vet Anaesth Analg ; 49(4): 344-353, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35490089

RESUMO

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.


Assuntos
Injúria Renal Aguda , Doenças do Cão , Hipotensão , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/veterinária , Animais , Biomarcadores , Creatinina/urina , Doenças do Cão/diagnóstico , Doenças do Cão/etiologia , Cães , Diagnóstico Precoce , Hemorragia/veterinária , Hipotensão/diagnóstico , Hipotensão/etiologia , Hipotensão/veterinária , Lipocalina-2/urina , Masculino , Estudos Prospectivos
8.
J Anim Physiol Anim Nutr (Berl) ; 106(5): 1009-1016, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34528730

RESUMO

Serum creatinine (SCr) in humans has proven to be a reliable biomarker of body protein breakdown and/or muscle mass change. This study set out to investigate the potential of SCr to indicate a loss in sow muscle mass over lactation, validated against 3 methyl histidine (3MH) and blood urea nitrogen (BUN), markers of dietary and/or body protein breakdown. A total of 40 sows were allocated to four treatment groups aimed to induce body weight changes by restrictively feeding sows using a stepwise percentage reduction model. Data were pooled and reallocated into three groups representing the 25th , 50th and 75th percentiles based on body weight change over lactation in the range -22.3 to -4.1% (treatment 25), -4.0 to 6.2% (Treatment 50), and 6.3-15.2% (Treatment 75). Indirect measures for the prediction of protein (3MH, BUN) or fat change (caliper, P2) were taken on entry into the farrowing house, day 5 of lactation, and at weaning. Serum was collected on these days, and SCr, 3MH and BUN were analysed. Piglet weaning weight and average daily feed intake did not differ between treatments (p > .05). There were no changes (p > .05) in indirect measures of body composition (sow caliper score, P2) and analytes (SCr, 3MH, BUN) over lactation. By day 20, those sows in treatment 25 had higher (p < .05) 3MH concentrations whilst changes from day 5 to 20 were not different (p > .05) and did not correlate with SCr change (p > .05) but were highly correlated to BUN change (R2 = 0.691, p < .001). The data suggested that concentrations of SCr and BUN may have been the result of dietary and/or body protein breakdown and/or changes in muscle mass. In the current testing conditions, SCr was not a reliable marker of changes in muscle mass.


Assuntos
Dieta , Lactação , Ração Animal/análise , Animais , Biomarcadores , Peso Corporal , Creatinina , Dieta/veterinária , Feminino , Humanos , Músculos , Suínos , Desmame
9.
Prev Vet Med ; 196: 105478, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34487918

RESUMO

Dystocia contributes to lamb and ewe mortality in the periparturient period but impacts for extensive sheep production systems remain poorly understood. Here we show that lamb and ewe mortality associated with dystocia has important impacts on sheep production in Australia and New Zealand, and quantify financial impacts for the Australian sheep industry. A systematic review of the literature identified 11 publications published since 1990 that reported sheep mortality due to dystocia in Australia or New Zealand. Assumptions for ewe breeding flock structure and reproductive performance were based on Australian sheep industry data. The proportion of lamb mortality attributable to dystocia (including stillbirths and perinatal deaths with evidence of hypoxic injury) pooled across all studies (pooled proportional mortality ratio) was 47 % (95 % Confidence Interval (CI): 38, 55). Pooled proportional mortality ratio for Australian studies was 53 % (95 %CI: 47, 60), and for New Zealand studies was 35 % (95 %CI: 19, 51). Pooled proportional mortality ratio was similar for lambs born to Merino and non-Merino ewes, although more data are needed to determine effects of ewe breed independent of other factors. Pooled proportional mortality ratio was higher for single lambs (59 %; 95 % CI: 55, 63) than twin (47 %; 41, 54) or triplet (49 %; 46, 52) lambs. However, the number of dystocia-associated mortalities is higher for twin-born lambs than for singles because total mortality is higher for twin-born lambs. It is estimated that approximately 7.7 million lamb deaths and 297,500 ewe deaths per year are attributable to dystocia in Australia for the national flock of 38 million breeding ewes. The whole-farm bio-economic Model of an Integrated Dryland Agricultural System (MIDAS) was used to determine the impacts of dystocia-associated ewe and lamb mortality on Australian farm profit. Dystocia is estimated to reduce Australian national farm profit by AU$780 million or $23.00 per ewe mated based on an assumed lamb sale price of AU$6.50 per kg carcass weight. These estimates do not include the costs of reduced productivity for surviving ewes and lambs, intervention, post-farmgate impacts, delayed genetic progress, or impacts on animal welfare and access into sheep meat and wool markets. Reducing dystocia through improved genetics and sheep management will improve animal welfare and farm profit.


Assuntos
Distocia , Doenças dos Ovinos , Animais , Austrália/epidemiologia , Distocia/mortalidade , Distocia/veterinária , Fazendas/economia , Feminino , Modelos Econômicos , Nova Zelândia/epidemiologia , Gravidez , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/mortalidade , Carneiro Doméstico
10.
Glob Adv Health Med ; 10: 21649561211042574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471570

RESUMO

INTRODUCTION: The field of implementation science is the study of methods that promote the uptake of evidence-based interventions into healthcare policy and practice. While acupuncture has gained significant traction in the American healthcare landscape, its journey has been somewhat haphazard and non-linear. METHODS: In June 2019, a group of thirty diverse stakeholders was convened by the Society for Acupuncture Research with the support of a Patient Centered Outcomes Research Institute, Eugene Washington Engagement Award. This group of stakeholders represented a diverse mix of patients, providers, academicians, researchers, funders, allied health professionals, insurers, association leaders, certification experts, and military program developers. The collective engaged in discussion that explored acupuncture's status in healthcare, including reflections on its safety, effectiveness, best practices, and the actual implementation of acupuncture as seen from diverse stakeholder viewpoints. OBJECTIVES: A primary goal was to consider how to utilize knowledge from the field of implementation science more systematically and intentionally to disseminate information about acupuncture and its research base, through application of methods known to implementation science. The group also considered novel challenges that acupuncture may present to known implementation processes. FINDINGS: This article summarizes the initial findings of this in-person meeting of stakeholders and the ongoing discussion among the subject matter experts who authored this report. The goal of this report is to catalyze greater conversation about how the field of implementation science might intersect with practice, access, research, and policymaking pertaining to acupuncture. Core concepts of implementation science and its relationship to acupuncture are introduced, and the case for acupuncture as an Evidence Based Practice (EBP) is established. The status of the field and current environment of acupuncture is examined, and the perspectives of four stakeholder groups--patients, two types of professional practitioners, and researchers--are explored in more detail.

11.
Res Vet Sci ; 139: 78-86, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34261014

RESUMO

Novel urinary biomarkers are increasingly utilized for the diagnosis of acute kidney injury (AKI) in dogs. Magnetic-bead based immunoassays for the simultaneous measurement of multiple biomarkers represent a potentially efficient and cost effective tool for investigators; however there is limited data to support their reliable use in dogs. Analytical validation of a commercial multiplex assay for the measurement of five AKI biomarkers: clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 and neutrophil gelatinase-associated lipocalin (NGAL) in canine urine was performed. The effect of pre-analytical factors including potential interfering substances and sample storage methods were investigated. Urine from 110 healthy dogs was used to determine reference intervals for each biomarker measured, according to American Society of Veterinary Clinical Pathology guidelines. Additionally, urine from 21 dogs with pyuria was used to evaluate the impact of pyuria on biomarker concentration. The assay performed with acceptable accuracy and precision for the measurement of NGAL only. Clinically relevant urine concentrations of bilirubin, haemoglobin, and synthetic colloid solutions led to interference (mean percentage difference > +/- 15% compared to control) with measurement of all or some of the biomarkers. All biomarkers were stable in urine stored at 20-22 °C for 2 h, 4 °C for 12 h, or -20 °C for 6 months. Reference intervals could not be established for KIM-1 due to unacceptable measurement imprecision (intra- and inter assay coefficient of variation 45% and 20% respectively). Urine NGAL concentration was significantly elevated in pyuria (P < 0.001).


Assuntos
Injúria Renal Aguda , Doenças do Cão , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/veterinária , Animais , Biomarcadores , Doenças do Cão/diagnóstico , Cães , Imunoensaio/veterinária
12.
Glob Adv Health Med ; 10: 2164956120980694, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104573

RESUMO

Dissemination research is the study of distributing information and intervention materials to a specific clinical practice or public health audience. Acupuncture, a healthcare practice involving the stimulation of certain body points, often with thin needles, is considered an evidence-based treatment for low back pain (LBP), but is underutilized in the United States. Body: We will use the example of acupuncture for LBP to identify opportunities to leverage dissemination research to increase utilization of acupuncture. Deficits in the awareness or knowledge of acupuncture may limit its adoption by patients and other stakeholders. Thus, we summarize methods to gather data on stakeholder awareness and knowledge of acupuncture for LBP, i.e., audience research. Engaging multiple stakeholder audiences (e.g., health system leaders, primary care providers, patients), is needed to generate knowledge on promising dissemination strategies for each audience. Audience segmentation is important for identifying population subgroups for whom adoption of acupuncture may require a more intensive or tailored dissemination strategy. To illustrate potential audience 'segments', our research discussion focused on developing dissemination strategies by age (i.e., older adults - those age 65 years or older, and younger adults - those under age 65 ). This decision was prompted by Medicare's recent policy covering acupuncture for chronic LBP. We leverage current knowledge of barriers and facilitators of acupuncture use to discuss how further tailoring of dissemination strategies might optimize adoption of acupuncture in both groups of adults. Experimental study designs could then be used to compare the effectiveness of such strategies to increase awareness, knowledge, or adoption of acupuncture. Conclusions: Conducting dissemination research may improve awareness and knowledge of acupuncture, and ultimately the adoption of acupuncture in biomedical settings. We anticipate that the concepts highlighted in this manuscript will also be helpful for those disseminating information about other complementary and integrative health approaches.

13.
Res Vet Sci ; 135: 547-554, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33223120

RESUMO

Several protein biomarkers have been shown to be useful for the early diagnosis of acute kidney injury (AKI) in animals and people. Multiplex assays for measurement of a panel of renal biomarkers in canine samples have recently become available. This study compared the use of two such assays, versus previously validated ELISAs, to measure five biomarkers in canine samples during ischaemia-reperfusion (IR) AKI. Blood and urine was collected from six male anaesthetised greyhounds that underwent 1-h of renal ischaemia (severe hypotension induced by acute haemorrhage) and 2-h of reperfusion (intravenous fluid resuscitation). Histology confirmed presence of acute tubular injury at 2 h of reperfusion. Concentrations of clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1, and neutrophil gelatinase-associated lipocalin (NGAL) at baseline and following IR, measured by two different multiplex assays and previously-validated single analyte immunoassays, were compared. Only NGAL was significantly elevated following IR with all assays investigated. Whether concentrations of the other four biomarkers were significantly increased following IR depended on the assay used. Concentrations of cystatin C and KIM-1 measured with the multiplex assays were of a vast magnitude lower than those measured with the corresponding single analyte ELISAs. We conclude that further validation is required before these assays can reliably be used to measure AKI biomarkers in canine samples.


Assuntos
Injúria Renal Aguda/veterinária , Biomarcadores/metabolismo , Doenças do Cão/metabolismo , Imunoensaio/veterinária , Rim/metabolismo , Traumatismo por Reperfusão/veterinária , Injúria Renal Aguda/metabolismo , Animais , Biomarcadores/sangue , Doenças do Cão/patologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Imunoensaio/métodos , Isquemia/veterinária , Rim/patologia , Lipocalina-2/metabolismo , Lipocalina-2/urina , Masculino , Reperfusão/veterinária , Traumatismo por Reperfusão/metabolismo
14.
Animals (Basel) ; 10(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066189

RESUMO

There is significant public interest in the Australian live animal export industry and a need to develop a program that can measure and monitor animal welfare throughout the supply chain. An online survey of stakeholder opinions of this industry and animal welfare measures was carried out in 2015 with 921 respondents: 30% from the public who identified as animal welfare advocates (AWAs); 44% from the public who did not identify as AWAs (general public; GP); 26% live export industry (LEI) workers. AWA and GP respondents expressed greater concern than LEI respondents for animal welfare throughout the supply chain but had less concern for animals at Australian feedlots than in other parts of the supply chain. The majority of AWA and GP respondents believed data collected on animal welfare should be made public and should be collected by independent welfare officers and used to regulate the industry and impose penalties for poor welfare. LEI workers believed that data should be confidential, collected by LEI workers and used by the industry to self-regulate. AWA and GP respondents rated the importance and practicality of a number of welfare indicators greater than LEI workers, while respondents shared an analogous view of the importance and practicality of these indicators. Results can be used to develop welfare assessments that ensure a better understanding between industry members and those not in the industry, while facilitating welfare improvements and promoting greater transparency for the live export industry.

15.
Toxins (Basel) ; 12(9)2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32825482

RESUMO

Dihydrodinophysistoxin-1 (dihydro-DTX1, (M-H)-m/z 819.5), described previously from a marine sponge but never identified as to its biological source or described in shellfish, was detected in multiple species of commercial shellfish collected from the central coast of the Gulf of Maine, USA in 2016 and in 2018 during blooms of the dinoflagellate Dinophysis norvegica. Toxin screening by protein phosphatase inhibition (PPIA) first detected the presence of diarrhetic shellfish poisoning-like bioactivity; however, confirmatory analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS) failed to detect okadaic acid (OA, (M-H)-m/z 803.5), dinophysistoxin-1 (DTX1, (M-H)-m/z 817.5), or dinophysistoxin-2 (DTX2, (M-H)-m/z 803.5) in samples collected during the bloom. Bioactivity-guided fractionation followed by liquid chromatography-high resolution mass spectrometry (LC-HRMS) tentatively identified dihydro-DTX1 in the PPIA active fraction. LC-MS/MS measurements showed an absence of OA, DTX1, and DTX2, but confirmed the presence of dihydro-DTX1 in shellfish during blooms of D. norvegica in both years, with results correlating well with PPIA testing. Two laboratory cultures of D. norvegica isolated from the 2018 bloom were found to produce dihydro-DTX1 as the sole DSP toxin, confirming the source of this compound in shellfish. Estimated concentrations of dihydro-DTX1 were >0.16 ppm in multiple shellfish species (max. 1.1 ppm) during the blooms in 2016 and 2018. Assuming an equivalent potency and molar response to DTX1, the authority initiated precautionary shellfish harvesting closures in both years. To date, no illnesses have been associated with the presence of dihydro-DTX1 in shellfish in the Gulf of Maine region and studies are underway to determine the potency of this new toxin relative to the currently regulated DSP toxins in order to develop appropriate management guidance.


Assuntos
Dinoflagellida/isolamento & purificação , Toxinas Marinhas/análise , Ácido Okadáico/análogos & derivados , Frutos do Mar/análise , Animais , Dinoflagellida/química , Maine , Toxinas Marinhas/toxicidade , Ácido Okadáico/análise , Ácido Okadáico/toxicidade , Fitoplâncton/química , Fitoplâncton/isolamento & purificação , Frutos do Mar/toxicidade , Intoxicação por Frutos do Mar/diagnóstico , Intoxicação por Frutos do Mar/etiologia , Espectrometria de Massas em Tandem/métodos
16.
Animals (Basel) ; 10(7)2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32645863

RESUMO

The identification and assessment of pain in sheep under field conditions are important, but, due to their stoic nature, are fraught with many challenges. In Australia, various husbandry procedures that are documented to cause pain are routinely performed at lamb marking, including ear tagging, castration, mulesing, and tail docking. This study evaluated the validity of a novel methodology to assess pain in lambs: qualitative behavioural assessment (QBA) was used to compare the behavioural expression of control lambs (CONTROL) with that of lambs subject to these procedures that received either a saline placebo 15 min before procedures (PLACEBO), or were administered meloxicam 15 min before procedures in addition to the standard analgesic Tri-Solfen at the time of procedures, as per the manufacturer's recommendations (ANALGESIC TREATMENT; AT). In terms of behavioural expression, it was expected that: CONTROL ≠ PLACEBO, AT = CONTROL, and PLACEBO ≠ AT. Video footage of the 6-8-week-old lambs (n = 10 for each treatment) was captured approximately 1.5 h postprocedure and was presented, in a random order, to 19 observers for assessment using the Free-Choice Profiling (FCP) approach to QBA. There was significant consensus (p < 0.001) among the observers in their assessment of the lambs, with two main dimensions of behavioural expression explaining 69.2% of the variation. As expected, observers perceived differences in the demeanour of lambs in the first dimension, scoring all lambs subject to the routine husbandry procedures as significantly more 'dull' and 'uneasy' compared to the control lambs (p < 0.05). Contrary to expectations, the results also suggested that analgesic treatment did not provide relief at the time of observation. Further investigations to validate the relationship between behavioural expression scores and pain are necessary, but these results suggest that painful husbandry procedures alter the behavioural expression of lambs and these differences can be captured using QBA methodology.

17.
Animals (Basel) ; 10(7)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708293

RESUMO

Animal welfare is an important issue for the live export industry (LEI), in terms of economic returns, community attitudes and international socio-political relations. Mortality has traditionally been the main welfare measure recorded within the LEI; however, high mortality incidents are usually acted upon after adverse events occur, reducing the scope for proactive welfare enhancement. We reviewed 71 potential animal welfare measures, identifying those measures that would be appropriate for use throughout the LEI for feeder and slaughter livestock species, and categorised these as animal-, environment- and resource-based. We divided the live export supply chain into three sectors: (1) Australian facilities, (2) vessel and (3) destination country facilities. After reviewing the relevant regulations for each sector of the industry, we identified 38 (sector 1), 35 (sector 2) and 26 (sector 3) measures already being collected under current practice. These could be used to form a 'welfare information dashboard': a LEI-specific online interface for collecting data that could contribute towards standardised industry reporting. We identified another 20, 25 and 28 measures that are relevant to each LEI sector (sectors 1, 2, 3, respectively), and that could be developed and integrated into a benchmarking system in the future.

18.
J Vet Diagn Invest ; 32(5): 656-663, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32627718

RESUMO

Interest is growing in measurement of novel biomarkers for the diagnosis of acute kidney injury. Multiplex assays may provide a rapid and cost-effective way of measurement; however, sparse information is published regarding their use in dogs. We aimed to validate a commercial magnetic bead-based assay for 5 biomarkers: clusterin (Clus), cystatin C (CysC), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Intra- and inter-assay imprecision, linearity under dilution (LUD), spike recovery (S-R), and hemoglobin interference were evaluated using serum from healthy and diseased dogs. Additionally, the effect of sample type (serum vs. plasma) was investigated. All values for Clus and MCP-1 were outside the assay's measurable range. Intra- and inter-assay precision were acceptable for NGAL (CVs 8.8% and 13.2%, respectively). Regression analysis of LUD and S-R indicated good linearity for CysC and NGAL. Hemolysis did not affect measurement of any biomarker. Measured concentrations of CysC (p = 0.018) and NGAL (p = 0.015) were significantly lower in sodium citrate plasma compared to serum. We conclude that this magnetic bead-based assay is precise and accurate for NGAL measurement in canine serum. Inappropriate standards for MCP-1 and Clus, and poor accuracy for KIM-1 measurement, suggest that this assay cannot reliably quantify those biomarkers in canine blood. Measurements of CysC in canine blood using this assay must be interpreted with caution given inter-assay imprecision.


Assuntos
Injúria Renal Aguda/veterinária , Biomarcadores/sangue , Doenças do Cão/diagnóstico , Imunoensaio/veterinária , Injúria Renal Aguda/diagnóstico , Animais , Cães , Feminino , Imunoensaio/métodos , Masculino
19.
J Anim Sci ; 98(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32583856

RESUMO

Dietary tryptophan (Trp) is a precursor for serotonin, a neuromediator involved in stress responses. Tryptophan competes with other large neutral amino acids (LNAA: tyrosine, isoleucine, leucine, valine, and phenylalanine) to cross the blood-brain barrier; therefore, the regulation of circulating LNAA can influence Trp availability in the cortex and serotonin biosynthesis. The hypothesis examined in this study was that increased supplementation of dietary Trp and a reduction in LNAA for weaned pigs experimentally infected with enterotoxigenic Escherichia coli (ETEC; F4) will increase Trp availability in plasma and reduce indices of the stress response, which will translate to reduced production losses. At 21 ± 3 d of age (mean ± SEM), 96 male pigs (Large White × Landrace) weighing 6.3 ± 0.98 kg (mean ± SEM) were individually penned and allocated to a 4 × 2 factorial arrangement of treatments, with respective factors being 1) four dietary standardized ileal digestible (SID) Trp and LNAA contents, being HTrpHLNAA (Low Trp-High LNAA; 0.24% SID Trp: 5.4% SID LNAA), HTrpHLNAA (Low Trp-Low LNAA; 0.24% SID Trp: 4.6% SID LNAA), HTrpHLNAA (High Trp-High LNAA; 0.34% SID Trp: 5.4% SID LNAA), and HTrpHLNAA (High Trp-Low LNAA; 0.34% SID Trp: 4.6% SID LNAA), and 2) without/with ETEC infection. Pigs were orally infected with 0.8 mL (3.6 × 109 CFU/mL) ETEC at days 7 and 8 after weaning. Pigs fed diets high in Trp irrespective of the level of LNAA (HTrpHLNAA and HTrpLLNAA) had higher plasma Trp concentrations (P < 0.001) and a Trp:LNAA ratio (P < 0.001) before infection and 6 d after infection. Following infection, noninfected pigs had higher plasma Trp (P = 0.03) and a Trp:LNAA ratio (P = 0.004) compared with pigs infected with ETEC. Plasma cortisol levels after infection were higher in ETEC-infected pigs (P = 0.05) and altering dietary Trp and LNAA concentrations did not influence (P > 0.05) plasma cortisol. Pigs fed diet HTrpLLNAA had higher serum serotonin levels 24 h after infection (P = 0.02) compared with pigs fed diets LTrpLLNAA and HTrpHLNAA. Similarly, pigs fed diet HTrpLLNAA had a higher (P = 0.02) average daily gain during the 3-wk study. Overall, average daily feed intake tended to be higher in pigs fed an HTrpLLNAA diet compared with the other diets (P = 0.08). These results suggest that the increased supplementation of dietary Trp with reduced LNAA increased circulating Trp levels that, in turn, likely caused higher serum serotonin levels, irrespective of infection with ETEC, and improved aspects of post-weaning performance.


Assuntos
Aminoácidos Neutros/administração & dosagem , Dieta/veterinária , Escherichia coli Enterotoxigênica , Infecções por Escherichia coli/veterinária , Doenças dos Suínos/microbiologia , Triptofano/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Infecções/veterinária , Masculino , Serotonina , Suínos , Doenças dos Suínos/terapia , Triptofano/administração & dosagem , Triptofano/sangue , Aumento de Peso/efeitos dos fármacos
20.
Animals (Basel) ; 10(4)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316532

RESUMO

Australian livestock industries face increased scrutiny from animal welfare groups and society, and the long-distance transport of livestock by sea has recently gained particular attention. Other than non-compliance with broad regulatory standards and voyage mortality rates, there is minimal information to ascertain the welfare of exported livestock. There is currently no standardised, validated animal welfare assessment protocol for livestock on-farm prior to live export or when undergoing transport. This study describes a novel assessment protocol suitable for use on live feeder and slaughter animals exported by sea from Australia. Health and welfare indicators for use in the livestock export supply chain were identified by reviewing three internationally recognised animal welfare assessment protocols for livestock; Welfare Quality®, AWIN and AssureWel, as well as consulting with industry compliance standards and guidelines. This paper proposes a welfare protocol designed to assess sheep and beef cattle exported by sea from Australia, and incorporates environmental-, resource-, management- and animal-based measures. In collaboration with industry, this welfare protocol can be tested on commercial livestock consignments, and be used for ongoing management, for increased transparency and to provide feedback to operators for continuous improvement.

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