Aging alters signaling properties in the mouse spinal dorsal horn.

A well-recognized relationship exists between aging and increased susceptibility to chronic pain conditions, underpinning the view that pain signaling pathways differ in aged individuals. Yet despite the higher prevalence of altered pain states among the elderly, the majority of preclinical work studying mechanisms of aberrant sensory processing are conducted in juvenile or young adult animals. This mismatch is especially true for electrophysiological studies where patch clamp recordings from aged tissue are generally viewed as particularly challenging. In this study, we have undertaken an electrophysiological characterization of spinal dorsal horn neurons in young adult (3-4 months) and aged (28-32 months) mice. We show that patch clamp data can be routinely acquired in spinal cord slices prepared from aged animals and that the excitability properties of aged dorsal horn neurons differ from recordings in tissue prepared from young animals. Specifically, aged dorsal horn neurons more readily exhibit repetitive action potential discharge, indicative of a more excitable phenotype. This observation was accompanied by a decrease in the amplitude and charge of spontaneous excitatory synaptic input to dorsal horn neurons and an increase in the contribution of GABAergic signaling to spontaneous inhibitory synaptic input in aged recordings. While the functional significance of these altered circuit properties remains to be determined, future work should seek to assess whether such features may render the aged dorsal horn more susceptible to aberrant injury or disease-induced signaling and contribute to increased pain in the elderly.

Post-pandemic influenza A/H1N1pdm09 is associated with more severe outcomes than A/H3N2 and other respiratory viruses in adult hospitalisations.

This study compares the frequency and severity of influenza A/H1N1pdm09 (A/H1), influenza A/H3N2 (A/H3) and other respiratory virus infections in hospitalised patients. Data from 17 332 adult hospitalised patients admitted to Sir Charles Gairdner Hospital, Perth, Western Australia, with a respiratory illness between 2012 and 2015 were linked with data containing reverse transcription polymerase chain reaction results for respiratory viruses including A/H1, A/H3, influenza B, human metapneumovirus, respiratory syncytial virus and parainfluenza. Of these, 1753 (10.1%) had test results. Multivariable regression analyses were conducted to compare the viruses for clinical outcomes including ICU admission, ventilation, pneumonia, length of stay and death. Patients with A/H1 were more likely to experience severe outcomes such as ICU admission (OR 2.5, 95% CI 1.2-5.5, P = 0.016), pneumonia (OR 3.0, 95% CI 1.6-5.7, P < 0.001) and lower risk of discharge from hospital (indicating longer lengths of hospitalisation; HR 0.64 95% CI 0.47-0.88, P = 0.005), than patients with A/H3. Patients with a non-influenza respiratory virus were less likely to experience severe clinical outcomes than patients with A/H1, however, had similar likelihood when compared to patients with A/H3. Patients hospitalised with A/H1 had higher odds of severe outcomes than patients with A/H3 or other respiratory viruses. Knowledge of circulating influenza strains is important for healthcare preparedness.

High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus-induced exacerbations: A prospective cohort study.

BACKGROUND: The major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus-induced exacerbations is unknown. OBJECTIVE: To assess whether type 2 inflammation is associated with an increased risk of virus-induced exacerbations of asthma. METHODS: Stable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR. RESULTS: A total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow-up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus-induced exacerbation (HR 7.6 95% CI: 1.6-35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1-10.4, P=.033). CONCLUSION AND CLINICAL RELEVANCE: Established type 2 inflammation during stable disease is a risk factor for virus-induced exacerbations in a real-life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies.

Energetic costs of mange in wolves estimated from infrared thermography.

Parasites, by definition, extract energy from their hosts and thus affect trophic and food web dynamics even when the parasite may have limited effects on host population size. We studied the energetic costs of mange (Sarcoptes scabiei) in wolves (Canis lupus) using thermal cameras to estimate heat losses associated with compromised insulation during the winter. We combined the field data of known, naturally infected wolves with a data set on captive wolves with shaved patches of fur as a positive control to simulate mange-induced hair loss. We predict that during the winter in Montana, more severe mange infection increases heat loss by around 5.2-12 MJ per night (1,240-2,850 kcal, or a 65-78% increase) for small and large wolves, respectively, accounting for wind effects. To maintain body temperature would require a significant proportion of a healthy wolf's total daily energy demands (18-22 MJ/day). We also predict how these thermal costs may increase in colder climates by comparing our predictions in Bozeman, Montana to those from a place with lower ambient temperatures (Fairbanks, Alaska). Contrary to our expectations, the 14°C differential between these regions was not as important as the potential differences in wind speed. These large increases in energetic demands can be mitigated by either increasing consumption rates or decreasing other energy demands. Data from GPS-collared wolves indicated that healthy wolves move, on average, 17 km per day, which was reduced by 1.5, 1.8, and 6.5 km for light, medium, and severe hair loss. In addition, the wolf with the most hair loss was less active at night and more active during the day, which is the converse of the movement patterns of healthy wolves. At the individual level, mange infections create significant energy demands and altered behavioral patterns, this may have cascading effects on prey consumption rates, food web dynamics, predator-prey interactions, and scavenger communities.

Long-term outcomes of Murray Valley encephalitis cases in Western Australia: what have we learnt?

BACKGROUND: Murray Valley encephalitis virus (MVEV) is a mosquito-borne flavivirus that causes encephalitis in some cases of infection. It is endemic in Northern Australia and cases occasionally occur in South Eastern Australia. The long-term sequelae of MVEV infection have not previously been well described. AIM: To investigate the long-term sequelae of MVEV infection. METHODS: This was a descriptive case series of all clinical MVEV infections using data linkage and standard surveys. Hospital admissions, emergency department, psychiatric outpatients and mortality data were obtained. We attempted to follow-up all 53 cases of MVEV clinical infection that occurred in Western Australia from 1978 to 2011 inclusive. Two cases opted out of the study. RESULTS: We followed-up 39 surviving cases. Seven of the nine with paralysis or paresis were under 5 years and they fared worse than other patients, requiring lengthy hospitalisation (median duration 133 days). Two died due to complications of quadriplegia following a total of 691 days in hospital. Nine surviving patients, including two with non-encephalitic illness, required care for depression and other psychiatric conditions following MVEV infection. Two patients who were discharged with neurological sequelae had no further documented hospital occasions of service but reported ongoing challenges with cognitive dysfunction and inability to work. CONCLUSIONS: This is the first study of long-term outcomes of Murray Valley encephalitis that included cases with no obvious sequelae at discharge. In spite of the small numbers involved, the study demonstrated the significant medical and social burden due to MVEV in Australia.

Social living mitigates the costs of a chronic illness in a cooperative carnivore.

Infection risk is assumed to increase with social group size, and thus be a cost of group living. We assess infection risk and costs with respect to group size using data from an epidemic of sarcoptic mange (Sarcoptes scabiei) among grey wolves (Canis lupus). We demonstrate that group size does not predict infection risk and that individual costs of infection, in terms of reduced survival, can be entirely offset by having sufficient numbers of pack-mates. Infected individuals experience increased mortality hazards with increasing proportions of infected pack-mates, but healthy individuals remain unaffected. The social support of group hunting and territory defence are two possible mechanisms mediating infection costs. This is likely a common phenomenon among other social species and chronic infections, but difficult to detect in systems where infection status cannot be measured continuously over time.

Consensus guidelines for the investigation and management of encephalitis in adults and children in Australia and New Zealand.

Encephalitis is a complex neurological syndrome caused by inflammation of the brain parenchyma. The management of encephalitis is challenging because: the differential diagnosis of encephalopathy is broad; there is often rapid disease progression; it often requires intensive supportive management; and there are many aetiologic agents for which there is no definitive treatment. Patients with possible meningoencephalitis are often encountered in the emergency care environment where clinicians must consider differential diagnoses, perform appropriate investigations and initiate empiric antimicrobials. For patients who require admission to hospital and in whom encephalitis is likely, a staged approach to investigation and management is preferred with the potential involvement of multiple medical specialties. Key considerations in the investigation and management of patients with encephalitis addressed in this guideline include: Which first-line investigations should be performed?; Which aetiologies should be considered possible based on clinical features, risk factors and radiological features?; What tests should be arranged in order to diagnose the common causes of encephalitis?; When to consider empiric antimicrobials and immune modulatory therapies?; and What is the role of brain biopsy?

Human migration is important in the international spread of exotic Salmonella serovars in animal and human populations.

The exposure of indigenous humans and native fauna in Australia and the Wallacea zoogeographical region of Indonesia to exotic Salmonella serovars commenced during the colonial period and has accelerated with urbanization and international travel. In this study, the distribution and prevalence of exotic Salmonella serovars are mapped to assess the extent to which introduced infections are invading native wildlife in areas of high natural biodiversity under threat from expanding human activity. The major exotic Salmonella serovars, Bovismorbificans, Derby, Javiana, Newport, Panama, Saintpaul and Typhimurium, isolated from wildlife on populated coastal islands in southern temperate areas of Western Australia, were mostly absent from reptiles and native mammals in less populated tropical areas of the state. They were also not recorded on the uninhabited Mitchell Plateau or islands of the Bonaparte Archipelago, adjacent to south-eastern Indonesia. Exotic serovars were, however, isolated in wildlife on 14/17 islands sampled in the Wallacea region of Indonesia and several islands off the west coast of Perth. Increases in international tourism, involving islands such as Bali, have resulted in the isolation of a high proportion of exotic serovar infections suggesting that densely populated island resorts in the Asian region are acting as staging posts for the interchange of Salmonella infections between tropical and temperate regions.

Characteristics of a widespread community cluster of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza in Australia.

BACKGROUND: Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported. METHODS: Influenza specimens from the Asia-Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses. RESULTS: Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution. CONCLUSIONS: This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.

Key lessons from the COVID-19 public health response in Australia.

Australia avoided the worst effects of the COVID-19 pandemic, but still experienced many negative impacts. Reflecting on lessons from Australia's public health response, an Australian expert panel composed of relevant discipline experts identified the following key lessons: 1) movement restrictions were effective, but their implementation requires careful consideration of adverse impacts, 2) disease modelling was valuable, but its limitations should be acknowledged, 3) the absence of timely national data requires re-assessment of national surveillance structures, 4) the utility of advanced pathogen genomics and novel vaccine technology was clearly demonstrated, 5) decision-making that is evidence informed and consultative is essential to maintain trust, 6) major system weaknesses in the residential aged-care sector require fixing, 7) adequate infection prevention and control frameworks are critically important, 8) the interests and needs of young people should not be compromised, 9) epidemics should be recognised as a 'standing threat', 10) regional and global solidarity is important. It should be acknowledged that we were unable to capture all relevant nuances and context specific differences. However, the intent of this review of Australia's public health response is to critically reflect on key lessons learnt and to encourage constructive national discussion in countries across the Western Pacific Region.

Secondary attack rate of pandemic influenza A(H1N1) 2009 in Western Australian households, 29 May-7 August 2009.

Understanding household transmission of the pandemic influenza A(H1N1)2009 virus, including risk factors for transmission, is important for refining public health strategies to reduce the burden of the disease. During the influenza season of 2009 we investigated transmission of the emerging virus in 595 households in which the index case was the first symptomatic case of influenza A(H1N1)2009. Secondary cases were defined as household contacts with influenza-like illness (ILI) or laboratory-confirmed influenza A(H1N1)2009, occurring at least one day after but within seven days following symptom onset in the index case. ILI developed in 231 of the 1,589 household contacts, a secondary attack rate of 14.5% (95% confidence interval (CI): 12.9­16.4). At least one secondary case occurred in 166 of the 595 households (a household transmission rate of 27.9%; 95% CI: 24.5­31.6).Of these, 127 (76.5%) households reported one secondary case and 39 (23.5%) households reported two or more secondary cases. Secondary attack rates were highest in children younger than five years (p=0.001), and young children were also more efficient transmitters (p=0.01). Individual risk was not associated with household size. Prophylactic antiviral therapy was associated with reduced transmission (p=0.03). The secondary attack rate of ILI in households with a confirmed pandemic influenza A(H1N1)2009 index case was comparable to that described previously for seasonal influenza.

Association between 2009 seasonal influenza vaccine and influenza-like illness during the 2009 pandemic: preliminary results of a large household transmission study in Western Australia.

We conducted a prospective household transmission study to examine whether receipt of 2009 trivalent influenza vaccine (TIV) was associated with increased risk of influenza-like illness (ILI) among contacts of confirmed pandemic influenza A(H1N1) 2009 patients. In the week following onset of pandemic illness in a household member, 46 (15%) of 304 TIV-vaccinated contacts, and 174 (15%) of 1,162 unvaccinated contacts developed ILI (p=0.95). Receipt of 2009 TIV had no effect on one's risk of pandemic illness.

The impact of the pandemic influenza A(H1N1) 2009 virus on seasonal influenza A viruses in the southern hemisphere, 2009.

Data collected over winter 2009 by five World Health Organisation National Influenza Centres in the southern hemisphere were used to examine the circulation of pandemic and seasonal influenza A strains during the first pandemic wave in the southern hemisphere.There is compelling evidence that the pandemic influenza A(H1N1) 2009 virus significantly displaced seasonal influenza A(H1N1) and, to a lesser extent, A(H3N2) viruses circulating in the southern hemisphere. Complete replacement of seasonal influenza A strains, however, was not observed during the first pandemic wave.

Neural networks modelling of nitrogen export: model development and application to unmonitored boreal forest watersheds.

In remotely located boreal forest watersheds, monitoring nitrogen (N) export in stream discharge often is not feasible because of high costs and site inaccessibility. Therefore, modelling tools that can predict N export in unmonitored watersheds are urgently needed to support management decisions for these watersheds. The hydrological and biogeochemical processes that regulate N export in streams draining watersheds are complex and not fully understood, which makes artificial neural network (ANN) modelling suitable for such an application. This study developed ANN models to predict N export from watersheds relying only on easily accessible climate data and remote sensing (RS) data from the public domain. The models were able to predict the daily N export (g/km2/d) in five watersheds ranging in size from 5-130 km2 with reasonable accuracy. Similarity indices were developed between any two studied watersheds to quantify watershed similarity and guide the transferability of models from monitored watersheds to unmonitored ones. To demonstrate the applicability of the ANN models to unmonitored watersheds, the calibrated ANN models were used to predict N export in different watersheds (unmonitored watersheds in this perspective) without further calibration. The similarity index based upon a rainfall index, a peatland index and a RS normalized difference water index showed the best correlation with the transferability of the models. This study represents an important first step towards transferring ANN models developed for one watershed to unmonitored watersheds using similarity indices that rely on freely available climate and RS data.

Mutagenicity of cycasin aglycone (methylazoxymethanol), a naturally occurring carcinogen.

Methylazoxymethanol, a carcinogenic and hepatotoxic methylating agent prepared from cycad plants, has been found to be a good mutagen in Salmonella typhimurium.

Specialization of rabbit reticulocyte transfer RNA content for hemoglobin synthesis.

The amount of acceptance of each amino acid per absorbancy unit of rabbit reticulocyte transfer RNA was determined. The results were compared with the amino acid composition of rabbit hemoglobin and with a similar determination of the transfer RNA content of rabbit liver. The histidine and isoleucine transfer RNA content of reticulocytes is specialized for the synthesis of hemoglobin, in which histidine is unusually common and isoleucine unusually scarce compared to most proteins.

Teratogenic effects of alcohol in humans and laboratory animals.

The teratogenicity of alcohol has been demonstrated in humans through clinical studies, behavioral studies, and epidemiologic studies, and in animals through controlled laboratory experiments. In humans exposed to alcohol during gestation the effects can range from fetal alcohol syndrome in some offspring of chronic alcoholic women to reduced average birth weight in offspring of women reporting an average consumption of two to three drinks or more per day. The behavioral effects of such exposure may range from mental retardation in children with fetal alcohol syndrome to milder developmental and behavioral effects in infants born to social drinkers. In animals, exposure to alcohol in utero may result in death, malformation, and growth deficiency as well as behavioral and developmental abnormalities. The mechanisms of impairment and related risk factors are yet to be elucidated.

Petroleum refinery secondary effluent polishing using freezing processes--toxicity and organic contaminant removal.

A petroleum refinery secondary effluent was treated using two freezing techniques--spray freezing and unidirectional downward freezing (UDF). The freezing processes were effective to remove toxicity and total organic carbon (TOC)- and chemical oxygen demand (COD)-causing materials in the effluent. Agitation of the liquid during UDF significantly improved the impurity separation efficiency; 85 to 96% removal of TOC and COD was achieved without any pretreatment and freezing only 70% of the feed water. The treatment efficiency of the spray freezing was at the same level as that of UDF without mixing. The spray ice with longer storage time released more contaminants with early meltwater. The initial contaminant concentration of the feed water and the freezing temperatures (-10 degrees C and -25 degrees C) had no significant influence on the treatment efficiency. A small fluctuation in effluent TOC concentration caused a dramatic change in effluent toxicity (Microtox). The effective concentration (EC20) (Microtox) was effective in detecting effluent toxicity.

Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass.

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has important implications for prognosis. The aetiology of cardiac surgery-associated AKI is complex, but renal hypoxia, particularly in the medulla, is thought to play at least some role. There is strong evidence from studies in experimental animals, clinical observations and computational models that medullary ischaemia and hypoxia occur during CPB. There are no validated methods to monitor or improve renal oxygenation during CPB, and thus possibly decrease the risk of AKI. Attempts to reduce the incidence of AKI by early transfusion to ameliorate intra-operative anaemia, refinement of protocols for cooling and rewarming on bypass, optimization of pump flow and arterial pressure, or the use of pulsatile flow, have not been successful to date. This may in part reflect the complexity of renal oxygenation, which may limit the effectiveness of individual interventions. We propose a multi-disciplinary pathway for translation comprising three components. Firstly, large-animal models of CPB to continuously monitor both whole kidney and regional kidney perfusion and oxygenation. Secondly, computational models to obtain information that can be used to interpret the data and develop rational interventions. Thirdly, clinically feasible non-invasive methods to continuously monitor renal oxygenation in the operating theatre and to identify patients at risk of AKI. In this review, we outline the recent progress on each of these fronts.

Effects of freezing on the survival of Escherichia coli and Bacillus and response to UV and chlorine after freezing.

Escherichia coli (E. coli) and Bacillus megaterium bacteria were frozen at -15 degrees C using a freezer and a spray freezing method. The frozen Bacillus spores were also exposed to UV and free chlorine. An average of 4.7-log inactivation was obtained from the spray ice with 2-day storage time, while the freezer freezing only caused 0.84-log reduction with the same storage time. Significantly higher inactivation levels were observed for the E. coli cells with 2-day storage compared with those without storage. The spray freezing was found more effective in killing the E. coli cells, while more cells were sublethally injured by the freezer freezing. Freezing did not kill the Bacillus megaterium spores, but affected their response to UV and chlorine. Greater inactivation levels were observed at higher free chlorine doses or longer contact time, and the UV fluence-response curve showed initial rapid kill followed by tailing for the frozen spores.