Enhancing genomics-based outbreak detection of endemic Salmonella enterica serovar Typhimurium using dynamic thresholds.

Salmonella enterica serovar Typhimurium is the leading cause of salmonellosis in Australia, and the ability to identify outbreaks and their sources is vital to public health. Here, we examined the utility of whole-genome sequencing (WGS), including complete genome sequencing with Oxford Nanopore technologies, in examining 105 isolates from an endemic multi-locus variable number tandem repeat analysis (MLVA) type over 5 years. The MLVA type was very homogeneous, with 90 % of the isolates falling into groups with a five SNP cut-off. We developed a new two-step approach for outbreak detection using WGS. The first clustering at a zero single nucleotide polymorphism (SNP) cut-off was used to detect outbreak clusters that each occurred within a 4 week window and then a second clustering with dynamically increased SNP cut-offs were used to generate outbreak investigation clusters capable of identifying all outbreak cases. This approach offered optimal specificity and sensitivity for outbreak detection and investigation, in particular of those caused by endemic MLVA types or clones with low genetic diversity. We further showed that inclusion of complete genome sequences detected no additional mutational events for genomic outbreak surveillance. Phylogenetic analysis found that the MLVA type was likely to have been derived recently from a single source that persisted over 5 years, and seeded numerous sporadic infections and outbreaks. Our findings suggest that SNP cut-offs for outbreak cluster detection and public-health surveillance should be based on the local diversity of the relevant strains over time. These findings have general applicability to outbreak detection of bacterial pathogens

Evaluation of a Diagnostic Decision Support System for the Triage of Patients in a Hospital Emergency Department

One of the biggest challenges for the management of the emergency department (ED) is to expedite the management of patients since their arrival for those with low priority pathologies selected by the classification systems, generating unnecessary saturation of the ED. Diagnostic decision support systems (DDSS) can be a powerful tool to guide diagnosis, facilitate correct classification and improve patient safety. Patients who attended the ED of a tertiary hospital with the preconditions of Manchester Triage system level of low priority (levels 3, 4 and 5), and with one of the five most frequent causes for consultation: dyspnea, chest pain, gastrointestinal bleeding, general discomfort and abdominal pain, were interviewed by an independent researcher with a DDSS, the Mediktor system. After the interview, we compare the Manchester triage and the final diagnoses made by the ED with the triage and diagnostic possibilities ordered by probability obtained by the Mediktor system, respectively. In a final sample of 214 patients, the urgency assignment made by both systems does not match exactly, which could indicate a different classification model, but there were no statistically significant differences between the assigned levels (S = 0.059, p = 0.442). The diagnostic accuracy between the final diagnosis and any of the first 10 Mediktor diagnoses was of 76.5%, for the first five diagnoses was 65.4%, for the first three diagnoses was 58%, and the exact match with the first diagnosis was 37.9%. The classification of Mediktor in this segment of patients shows that a higher level of severity corresponds to a greater number of hospital admissions, hospital readmissions and emergency screenings at 30 days, although without statistical significance. It is expected that this type of applications may be useful as a complement to the triage, to accelerate the diagnostic approach, to improve the request for appropriate complementary tests in a protocolized action model and to reduce waiting times in the ED

Transient peak-strain matching partially recovers the age-impaired mechanoadaptive cortical bone response

Mechanoadaptation maintains bone mass and architecture; its failure underlies age-related decline in bone strength. It is unclear whether this is due to failure of osteocytes to sense strain, osteoblasts to form bone or insufficient mechanical stimulus. Mechanoadaptation can be restored to aged bone by surgical neurectomy, suggesting that changes in loading history can rescue mechanoadaptation. We use non-biased, whole-bone tibial analyses, along with characterisation of surface strains and ensuing mechanoadaptive responses in mice at a range of ages, to explore whether sufficient load magnitude can activate mechanoadaptation in aged bone. We find that younger mice adapt when imposed strains are lower than in mature and aged bone. Intriguingly, imposition of short-term, high magnitude loading effectively primes cortical but not trabecular bone of aged mice to respond. This response was regionally-matched to highest strains measured by digital image correlation and to osteocytic mechanoactivation. These data indicate that aged bone’s loading response can be partially recovered, non-invasively by transient, focal high strain regions. Our results indicate that old murine bone does respond to load when the loading is of sufficient magnitude, and bones’ age-related adaptation failure may be due to insufficient mechanical stimulus to trigger mechanoadaptation

Neurogenesis Drives Stimulus Decorrelation in a Model of the Olfactory Bulb

The reshaping and decorrelation of similar activity patterns by neuronal networks can enhance their discriminability, storage, and retrieval. How can such networks learn to decorrelate new complex patterns, as they arise in the olfactory system? Using a computational network model for the dominant neural populations of the olfactory bulb we show that fundamental aspects of the adult neurogenesis observed in the olfactory bulb -- the persistent addition of new inhibitory granule cells to the network, their activity-dependent survival, and the reciprocal character of their synapses with the principal mitral cells -- are sufficient to restructure the network and to alter its encoding of odor stimuli adaptively so as to reduce the correlations between the bulbar representations of similar stimuli. The decorrelation is quite robust with respect to various types of perturbations of the reciprocity. The model parsimoniously captures the experimentally observed role of neurogenesis in perceptual learning and the enhanced response of young granule cells to novel stimuli. Moreover, it makes specific predictions for the type of odor enrichment that should be effective in enhancing the ability of animals to discriminate similar odor mixtures

Knowledge of dental academics about the COVID-19 pandemic: a multi-country online survey.

BACKGROUND: COVID-19 is a global pandemic affecting all aspects of life in all countries. We assessed COVID-19 knowledge and associated factors among dental academics in 26 countries. METHODS: We invited dental academics to participate in a cross-sectional, multi-country, online survey from March to April 2020. The survey collected data on knowledge of COVID-19 regarding the mode of transmission, symptoms, diagnosis, treatment, protection, and dental treatment precautions as well as participants' background variables. Multilevel linear models were used to assess the association between dental academics' knowledge of COVID-19 and individual level (personal and professional) and country-level (number of COVID-19 cases/ million population) factors accounting for random variation among countries. RESULTS: Two thousand forty-five academics participated in the survey (response rate 14.3%, with 54.7% female and 67% younger than 46 years of age). The mean (SD) knowledge percent score was 73.2 (11.2) %, and the score of knowledge of symptoms was significantly lower than the score of knowledge of diagnostic methods (53.1 and 85.4%, P <  0.0001). Knowledge score was significantly higher among those living with a partner/spouse than among those living alone (regression coefficient (B) = 0.48); higher among those with PhD degrees than among those with Bachelor of Dental Science degrees (B = 0.48); higher among those seeing 21 to 30 patients daily than among those seeing no patients (B = 0.65); and higher among those from countries with a higher number of COVID-19 cases/million population (B = 0.0007). CONCLUSIONS: Dental academics had poorer knowledge of COVID-19 symptoms than of COVID-19 diagnostic methods. Living arrangements, academic degrees, patient load, and magnitude of the epidemic in the country were associated with COVD-19 knowledge among dental academics. Training of dental academics on COVID-19 can be designed using these findings to recruit those with the greatest need

Assessment of risk factors related to healthcare-associated methicillin-resistant Staphylococcus aureus infection at patient admission to an intensive care unit in Japan

<p>Abstract</p> <p>Background</p> <p>Healthcare-associated methicillin-resistant <it>Staphylococcus aureus </it>(HA-MRSA) infection in intensive care unit (ICU) patients prolongs ICU stay and causes high mortality. Predicting HA-MRSA infection on admission can strengthen precautions against MRSA transmission. This study aimed to clarify the risk factors for HA-MRSA infection in an ICU from data obtained within 24 hours of patient ICU admission.</p> <p>Methods</p> <p>We prospectively studied HA-MRSA infection in 474 consecutive patients admitted for more than 2 days to our medical, surgical, and trauma ICU in a tertiary referral hospital in Japan. Data obtained from patients within 24 hours of ICU admission on 11 prognostic variables possibly related to outcome were evaluated to predict infection risk in the early phase of ICU stay. Stepwise multivariate logistic regression analysis was used to identify independent risk factors for HA-MRSA infection.</p> <p>Results</p> <p>Thirty patients (6.3%) had MRSA infection, and 444 patients (93.7%) were infection-free. Intubation, existence of open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission, were detected as independent prognostic indicators. Patients with intubation or open wound comprised 96.7% of MRSA-infected patients but only 57.4% of all patients admitted.</p> <p>Conclusions</p> <p>Four prognostic variables were found to be risk factors for HA-MRSA infection in ICU: intubation, open wound, treatment with antibiotics, and steroid administration, all occurring within 24 hours of ICU admission. Preemptive infection control in patients with these risk factors might effectively decrease HA-MRSA infection.</p

PISA. The effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute stroke: Protocol for a phase II double-blind randomised placebo-controlled trial [ISRCTN98608690]

BACKGROUND: During the first days after stroke, one to two fifths of the patients develop fever or subfebrile temperatures. Body temperature is a strong prognostic factor after stroke. Pharmacological reduction of temperature in patients with acute ischaemic stroke may improve their functional outcome. Previously, we studied the effect of high dose (6 g daily) and low dose (3 g daily) paracetamol (acetaminophen) in a randomised placebo-controlled trial of 75 patients with acute ischemic stroke. In the high-dose paracetamol group, mean body temperature at 12 and 24 hours after start of treatment was 0.4°C lower than in the placebo group. The effect of ibuprofen, another potent antipyretic drug, on body-core temperature in normothermic patients has not been studied. AIM: The aim of the present trial is to study the effects of high-dose paracetamol and ibuprofen on body temperature in patients with acute ischaemic stroke, and to study the safety of these treatments. DESIGN: Seventy-five (3 × 25) patients with acute ischaemic stroke confined to the anterior circulation will be randomised to treatment with either: 400 mg ibuprofen, 1000 mg acetaminophen, or with placebo 6 times daily during 5 days. Body-temperatures will be measured with a rectal electronic thermometer at the start of treatment and after 24 hours. An infrared tympanic thermometer will be used to monitor body temperature at 2-hour intervals during the first 24 hours and at 12-hour intervals thereafter. The primary outcome measure will be rectal temperature at 24 hours after the start of treatment. The study results will be analysed on an intent-to-treat basis, but an on-treatment analysis will also be performed. No formal interim analysis will be carried out

Complement Activity in the Egg Cytosol of Zebrafish Danio rerio: Evidence for the Defense Role of Maternal Complement Components

Most fish embryos that develop externally are exposed to an environment full of microbes. How they survive microbial attacks are not understood to date. Here we demonstrated that the egg cytosol prepared from the newly fertilized eggs of zebrafish Danio rerio is capable of killing the Gram-negative bacterium Escherichia coli, via in vitro assay system of the complement activity established. All findings indicate that it is the complement system operating via the alternative pathway that is attributable to the bacteriolytic activity. This is the first report providing the evidence for the functional role of the maternal complement components in fish eggs, paving the way for study of maternal immunity in other organisms whose eggs are fertilized in vitro