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Changes in the epidemiology and ecology of H5N1 highly pathogenic avian influenza are devastating wild bird and poultry populations, farms and communities, and wild mammals worldwide. Having originated in farmed poultry, H5N1 viruses are now spread globally by wild birds, with transmission to many mammal and avian species, resulting in 2024 in transmission among dairy cattle with associated human cases. These ecological changes pose challenges to mitigating the impacts of H5N1 highly pathogenic avian influenza on wildlife, ecosystems, domestic animals, food security, and humans. H5N1 highly pathogenic avian influenza highlights the need for One Health approaches to pandemic prevention and preparedness, emphasising multisectoral collaborations among animal, environmental, and public health sectors. Action is needed to reduce future pandemic risks by preventing transmission of highly pathogenic avian influenza among domestic and wild animals and people, focusing on upstream drivers of outbreaks, and ensuring rapid responses and risk assessments for zoonotic outbreaks. Political commitment and sustainable funding are crucial to implementing and maintaining prevention programmes, surveillance, and outbreak responses.
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Photoperiod insensitivity (auto-flowering) in drug-type Cannabis sativa circumvents the need for short day (SD) flowering requirements making outdoor cultivation in high latitudes possible. However, the benefits of photoperiod insensitivity are counterbalanced by low cannabinoid content and poor flower quality in auto-flowering genotypes. Despite recent studies in cannabis flowering, a mechanistic understanding of photoperiod insensitivity is still lacking. We used a combination of genome-wide association study and genetic fine-mapping to identify the genetic cause of auto-flowering in cannabis. We then used gene expression analyses and transient transformation assays to characterize flowering time control. Herein, we identify a splice site mutation within circadian clock gene PSEUDO-RESPONSE REGULATOR 37 (CsPRR37) in auto-flowering cannabis. We show that CsPRR37 represses FT expression and its circadian oscillations transition to a less repressive state during SD as compared to long days (LD). We identify several key circadian clock genes whose expression is altered in auto-flowering cannabis, particularly under non-inductive LD. Research into the pervasiveness of this mutation and others affecting flowering time will help elucidate cannabis domestication history and advance cannabis breeding toward a more sustainable outdoor cultivation system.
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Cannabis , Flores , Regulación de la Expresión Génica de las Plantas , Mutación , Fotoperiodo , Cannabis/genética , Cannabis/crecimiento & desarrollo , Cannabis/fisiología , Relojes Circadianos , Ritmo Circadiano , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Estudio de Asociación del Genoma Completo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sitios de Empalme de ARNRESUMEN
The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system.
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Animales Salvajes , Zoonosis , Animales , Humanos , Zoonosis/epidemiología , Zoonosis/prevención & controlRESUMEN
Introduction: There is clinical equipoise as to whether hyperoxia is injurious to the myocardium, both in the setting of acute ischaemic insults and on the stable myocardium. This study examined the effect of extreme hyperoxia - in the form of hyperbaric oxygen treatment - on the myocardium through measurement of high-sensitivity cardiac troponin. Methods: Forty-eight individuals were enrolled to undergo a series of 30 exposures to hyperbaric oxygen for treatment of non-cardiac pathologies. High-sensitivity troponin T was measured before and after each session. Results: There was no clinically significant difference in troponin measurements following acute or recurrent sequential exposures to extreme hyperoxia, despite the studied patient population having a high rate of previous ischaemic heart disease or cardiovascular risk factors. Conclusions: This study demonstrates that profound hyperoxaemia does not induce any measurable cardiac injury at a biochemical level. Neither is there a reduction in cardiac troponin to suggest a cardioprotective effect of hyperbaric hyperoxia. This provides some reassurance as to the cardiac safety of the routine use of hyperbaric oxygen treatment in management of non-cardiac pathology.
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Oxigenoterapia Hiperbárica , Hiperoxia , Humanos , Troponina T , Oxígeno , BiomarcadoresRESUMEN
Sindbis virus (SINV) is a widely dispersed mosquito-borne alphavirus. Reports of Sindbis disease are largely restricted to northern Europe and South Africa. SINV is frequently sampled in Australian mosquito-based arbovirus surveillance programs, but human disease has rarely been reported. Molecular epidemiological studies have characterized six SINV genotypes (G1-G6) based on E2 gene phylogenies, mostly comprising viruses derived from the African-European zoogeographical region and with limited representation of Australasian SINV. In this study, we conducted whole genome sequencing of 66 SINV isolates sampled between 1960 and 2014 from countries of the Australasian region: Australia, Malaysia, and Papua New Guinea. G2 viruses were the most frequently and widely sampled, with three distinct sub-lineages defined. No new G6 SINV were identified, confirming geographic restriction of these viruses to south-western Australia. Comparison with global SINV characterized large-scale nucleotide and amino acid sequence divergence between African-European G1 viruses and viruses that circulate in Australasia (G2 and G3) of up to 26.83% and 14.55%, respectively, divergence that is sufficient for G2/G3 species demarcation. We propose G2 and G3 are collectively a single distinct alphavirus species that we name Argyle virus, supported by the inapparent or mild disease phenotype and the higher evolutionary rate compared with G1. Similarly, we propose G6, with 24.7% and 12.61% nucleotide and amino acid sequence divergence, is a distinct alphavirus species that we name Thomson's Lake virus.
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Culicidae , Virus Sindbis , Animales , Humanos , Virus Sindbis/genética , Australia , Genómica , NucleótidosRESUMEN
BACKGROUND: A fatal case of Japanese encephalitis (JE) occurred in a resident of the Tiwi Islands, in the Northern Territory of Australia in February 2021, preceding the large JE outbreak in south-eastern Australia in 2022. This study reports the detection, whole genome sequencing and analysis of the virus responsible (designated JEV/Australia/NT_Tiwi Islands/2021). METHODS: Reverse transcription quantitative PCR (RT-qPCR) testing was performed on post-mortem brain specimens using a range of JE virus (JEV)-specific assays. Virus isolation from brain specimens was attempted by inoculation of mosquito and mammalian cells or embryonated chicken eggs. Whole genome sequencing was undertaken using a combination of Illumina next generation sequencing methodologies, including a tiling amplicon approach. Phylogenetic and selection analyses were performed using alignments of the Tiwi Islands JEV genome and envelope (E) protein gene sequences and publicly available JEV sequences. RESULTS: Virus isolation was unsuccessful and JEV RNA was detected only by RT-qPCR assays capable of detecting all JEV genotypes. Phylogenetic analysis revealed that the Tiwi Islands strain is a divergent member of genotype IV (GIV) and is closely related to the 2022 Australian outbreak virus (99.8% nucleotide identity). The Australian strains share highest levels of nucleotide identity with Indonesian viruses from 2017 and 2019 (96.7-96.8%). The most recent common ancestor of this Australian-Indonesian clade was estimated to have emerged in 2007 (95% HPD range: 1998-2014). Positive selection was detected using two methods (MEME and FEL) at several sites in the E and non-structural protein genes, including a single site in the E protein (S194N) unique to the Australian GIV strains. CONCLUSION: This case represents the first detection of GIV JEV acquired in Australia, and only the second confirmed fatal human infection with a GIV JEV strain. The close phylogenetic relationship between the Tiwi Islands strain and recent Indonesian viruses is indicative of the origin of this novel GIV lineage, which we estimate has circulated in the region for several years prior to the Tiwi Islands case.
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Virus de la Encefalitis Japonesa (Especie) , Virus de la Encefalitis Japonesa (Subgrupo) , Encefalitis Japonesa , Animales , Humanos , Filogenia , Encefalitis Japonesa/epidemiología , Genotipo , Nucleótidos , Northern Territory , MamíferosRESUMEN
A fatal case of Japanese encephalitis (JE) occurred in northern Australia in early 2021. Sequence studies showed that the virus belonged to genotype IV (GIV), a genotype previously believed to be restricted to the Indonesian archipelago. This was the first locally acquired case of Japanese encephalitis virus (JEV) GIV to occur outside Indonesia, and the second confirmed fatal human case caused by a GIV virus. A closely related GIV JEV strain subsequently caused a widespread outbreak in eastern Australia in 2022 that was first detected by fetal death and abnormalities in commercial piggeries. Forty-two human cases also occurred with seven fatalities. This has been the first major outbreak of JEV in mainland Australia, and geographically the largest virgin soil outbreak recorded for JEV. This outbreak provides an opportunity to discuss and document the factors involved in the virus' spread and its ecology in a novel ecological milieu in which other flaviviruses, including members of the JE serological complex, also occur. The probable vertebrate hosts and mosquito vectors are discussed with respect to virus spread and its possible endemicity in Australia, and the need to develop a One Health approach to develop improved surveillance methods to rapidly detect future outbreak activity across a large geographical area containing a sparse human population. Understanding the spread of JEV in a novel ecological environment is relevant to the possible threat that JEV may pose in the future to other receptive geographic areas, such as the west coast of the United States, southern Europe or Africa.
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Culex , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Humanos , Virus de la Encefalitis Japonesa (Especie)/genética , Genotipo , Mosquitos Vectores , VertebradosRESUMEN
AIM: This cluster-based randomised control trial examines the comparative efficacy of two eLearning programs that teach clinicians evidence-based bronchiolitis management for children less than 12 months of age. METHODS: Six hospitals, matched for size, were randomly allocated to either video-based (arm A) or slide-based (arm B) eLearning programs. To assess behavioural change, participants (doctors and nurses) were asked to declare how they would manage a video scenario of an infant with bronchiolitis, before and after either eLearning method. Measured outcomes included the number of investigations and treatments ordered, admissions to hospital and discharge planning. Confidence scores and change in understanding for bronchiolitis management were also measured. RESULTS: Both methods of eLearning instruction resulted in reductions in unnecessary investigations and treatments performed, as well as improved confidence and understanding of bronchiolitis management on the video scenario. Video-based eLearning instruction additionally demonstrated a significant reduction in unnecessary hospital admissions and better discharge planning, based on learners' declarations to the video scenario, relative to slide-based learning. CONCLUSION: Slide-based and video-based eLearning both demonstrate improvements in reported bronchiolitis management. However, video-based eLearning may yield more significant practice changes, improved clinician confidence in management, as well as improved patient experience.
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Bronquiolitis , Instrucción por Computador , Médicos , Lactante , Niño , Humanos , Instrucción por Computador/métodos , Bronquiolitis/terapiaRESUMEN
High temperature stress inhibits photosynthesis and threatens wheat production. One measure of photosynthetic heat tolerance is Tcrit - the critical temperature at which incipient damage to photosystem II (PSII) occurs. This trait could be improved in wheat by exploiting genetic variation and genotype-by-environment interactions (GEI). Flag leaf Tcrit of 54 wheat genotypes was evaluated in 12 thermal environments over 3 years in Australia, and analysed using linear mixed models to assess GEI effects. Nine of the 12 environments had significant genetic effects and highly variable broad-sense heritability (H2 ranged from 0.15 to 0.75). Tcrit GEI was variable, with 55.6% of the genetic variance across environments accounted for by the factor analytic model. Mean daily growth temperature in the month preceding anthesis was the most influential environmental driver of Tcrit GEI, suggesting biochemical, physiological and structural adjustments to temperature requiring different durations to manifest. These changes help protect or repair PSII upon exposure to heat stress, and may improve carbon assimilation under high temperature. To support breeding efforts to improve wheat performance under high temperature, we identified genotypes superior to commercial cultivars commonly grown by farmers, and demonstrated potential for developing genotypes with greater photosynthetic heat tolerance.
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Complejo de Proteína del Fotosistema II , Termotolerancia , Clorofila , Interacción Gen-Ambiente , Fotosíntesis/genética , Complejo de Proteína del Fotosistema II/genética , Complejo de Proteína del Fotosistema II/metabolismo , Fitomejoramiento , Triticum/fisiologíaRESUMEN
In early 2022, the Japanese encephalitis virus (JEV) was identified as the cause of stillborn and mummified piglets in pig farms in southeastern Australia. Human cases and additional pig farms with infected piglets were subsequently identified across a widespread area encompassing four states. To inform surveillance and control programs, we synthesized existing information on Australian vectors of JEV, much of which was generated in response to incursions of JEV into the northern state of Queensland between 1995 and 2005. Members of the Culex sitiens subgroup, particularly Culex annulirostris, should be considered the primary vectors of JEV in Australia, as they yielded >87% of field detections of JEV, were highly efficient laboratory vectors of the virus, readily fed on pigs and birds (the key amplifying hosts of the virus) when they were available, and are widespread and often occur in large populations. Three introduced species, Culex quinquefasciatus, Culex gelidus and Culex tritaeniorhynchus may also serve as vectors, but more information on their geographical distribution, abundance and bionomics in the Australian context is required. Mosquitoes from other genera, such as Aedes and Verrallina, whilst considered relatively poor vectors, could play a regional or supplemental role in transmission, especially facilitating vertical transmission as a virus overwintering mechanism. Additional factors that could impact JEV transmission, including mosquito survival, dispersal and genetics, are also discussed. Possible directions for investigation are provided, especially in the context of the virus emerging in a region with different mosquito fauna and environmental drivers than northern Australia.
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Aedes , Culex , Virus de la Encefalitis Japonesa (Especie) , Encefalitis Japonesa , Animales , Australia/epidemiología , Virus de la Encefalitis Japonesa (Especie)/genética , Mosquitos Vectores , PorcinosRESUMEN
Fast synaptic communication requires receptors that respond to the presence of neurotransmitter by opening an ion channel across the post-synaptic membrane. The muscle-type nicotinic acetylcholine receptor from the electric fish, Torpedo, is the prototypic ligand-gated ion channel, yet the structural changes underlying channel activation remain undefined. Here we use cryo-EM to solve apo and agonist-bound structures of the Torpedo nicotinic receptor embedded in a lipid nanodisc. Using both a direct biochemical assay to define the conformational landscape and molecular dynamics simulations to assay flux through the pore, we correlate structures with functional states and elucidate the motions that lead to pore activation of a heteromeric nicotinic receptor. We highlight an underappreciated role for the complementary subunit in channel gating, establish the structural basis for the differential agonist affinities of α/δ versus α /γ sites, and explain why nicotine is less potent at muscle nicotinic receptors compared to neuronal ones.
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Canales Iónicos Activados por Ligandos , Receptores Nicotínicos , Animales , Sitios de Unión , Canales Iónicos Activados por Ligandos/metabolismo , Ligandos , Músculos , Receptores Nicotínicos/metabolismo , Torpedo/metabolismoRESUMEN
INTRODUCTION: Medial epicondyle fracture displacement is notoriously difficult to determine on conventional radiography, and follow-up computed tomography (CT) is often obtained to measure precise displacement. Another option for fracture characterization is digital tomosynthesis (DT), a technology providing high in-plane resolution of bony anatomy by acquiring multiple low-dose images in a linear arc. Advantages of DT include lower radiation exposure and lower cost than CT, rapid image acquisition, and a similar patient experience to conventional radiography. The digital application of tomosynthesis is relatively new and is integrated as an add-on feature with modern radiography equipment. This study compares DT, CT and conventional radiography for measurement accuracy in medial epicondyle fractures with the goal of determining relative accuracy in measuring medial epicondyle fracture displacement. METHODS: Medial epicondyle fractures were created in 5 cadaveric elbow specimens. Each specimen was imaged with conventional radiography, DT, and CT. True displacement measured by digital calipers was compared with "measured" displacement for each image acquisition. CT images included axial, sagittal, and coronal reformats. DT images of the elbow included anteroposterior (AP) longitudinal and transverse, lateral longitudinal and transverse, and axial longitudinal and transverse. Conventional radiographs included AP, lateral, and axial distal humerus images. Four physicians reviewed all images 3 months later. Each reviewer independently measured maximum apparent fracture displacement to the nearest 0.1 mm. Measurement accuracy was calculated as percent difference [(measured displacement-actual displacement)/actual displacement] for each acquisition. Mean, median, and SD for measurement accuracy were calculated. Two-tailed paired t tests were performed on each acquisition to compare the measurement accuracy. RESULTS: Compared with conventional radiographs, accuracy of DT was superior in AP longitudinal (P=0.03), AP transverse (P=0.01), axial longitudinal (P=0.0001), and axial transverse projections (P=0.001). Accuracy of CT was superior to conventional radiography in the AP projection (P=0.03), but was equivalent in the axial projection (P=0.9). Accuracy of CT was similar to DT in AP longitudinal (P=0.6), AP transverse (P=0.5), and axial longitudinal projections (P=0.07). Accuracy of DT in the axial transverse projection was superior to CT (P=0.03). CONCLUSION: DT is more accurate than conventional radiography (both AP and axial views) and as accurate as CT in assessing millimeters of displacement of medial epicondyle fracture fragments. LEVEL OF EVIDENCE: Level IV-diagnostic study.