Mice integrate conspecific and contextual information in forming social episodic-like memories under spontaneous recognition task conditions.

The ability to remember unique past events (episodic memory) may be an evolutionarily conserved function, with accumulating evidence of episodic-(like) memory processing in rodents. In humans, it likely contributes to successful complex social networking. Rodents, arguably the most used laboratory models, are also rather social animals. However, many behavioural paradigms are devoid of sociality, and commonly-used social spontaneous recognition tasks (SRTs) are open to non-episodic strategies based upon familiarity. We address this gap by developing new SRT variants. Here, in object-in-context SRTs, we asked if context could be specified by the presence/absence of either a conspecific (experiment 1) or an additional local object (experiment 2). We show that mice readily used the conspecific as contextual information to distinguish unique episodes in memory. In contrast, no coherent behavioural response emerged when an additional object was used as a potential context specifier. Further, in a new social conspecific-in-context SRT (experiment 3) where environment-based change was the context specifier, mice preferably explored a more recently-seen familiar conspecific associated with contextual mismatch, over a less recently-seen familiar conspecific presented in the same context. The results argue that, in incidental SRT conditions, mice readily incorporate conspecific cue information into episodic-like memory. Thus, the tasks offer different ways to assess and further understand the mechanisms at work in social episodic-like memory processing.

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Rats use strategies to make object choices in spontaneous object recognition tasks.

Rodent spontaneous object recognition (SOR) paradigms are widely used to study the mechanisms of complex memory in many laboratories. Due to the absence of explicit reinforcement in these tasks, there is an underlying assumption that object exploratory behaviour is 'spontaneous'. However, rodents can strategise, readily adapting their behaviour depending on the current information available and prior predications formed from learning and memory. Here, using the object-place-context (episodic-like) recognition task and novel analytic methods relying on multiple trials within a single session, we demonstrate that rats use a context-based or recency-based object recognition strategy for the same types of trials, depending on task conditions. Exposure to occasional ambiguous conditions changed animals' responses towards a recency-based preference. However, more salient and predictable conditions led to animals exploring objects on the basis of episodic novelty reliant on contextual information. The results have important implications for future research using SOR tasks, especially in the way experimenters design, analyse and interpret object recognition experiments in non-human animals.

The Hippocampal Horizon: Constructing and Segmenting Experience for Episodic Memory.

How do we recollect specific events that have occurred during continuous ongoing experience? There is converging evidence from non-human animals that spatially modulated cellular activity of the hippocampal formation supports the construction of ongoing events. On the other hand, recent human oriented event cognition models have outlined that our experience is segmented into discrete units, and that such segmentation can operate on shorter or longer timescales. Here, we describe a unification of how these dynamic physiological mechanisms of the hippocampus relate to ongoing externally and internally driven event segmentation, facilitating the demarcation of specific moments during experience. Our cross-species interdisciplinary approach offers a novel perspective in the way we construct and remember specific events, leading to the generation of many new hypotheses for future research.

Cholinergic input to the hippocampus is not required for a model of episodic memory in the rat, even with multiple consecutive events.

Previous work has shown that depletion of the cholinergic input to the hippocampus produces no impairment in an episodic (what-where-which) memory task in rats. However, in contrast a where-which task was significantly impaired. Models of acetylcholine function related to pattern separation were used to explain this result. Recent development of spontaneous recognition tasks to assess multiple trials consecutively in the same testing session allow an opportunity to assess whether an increase in interference produces an impairment in the episodic memory task using the same cholinergic lesion. By increasing the number of trials happening consecutively the proactive interference between events being remembered increases, with the prediction that a reduction in pattern separation as a result of reduced acetylcholine in the hippocampus would now produce an impairment in this task. We show that a continual trials approach to the episodic memory task has no impact on the effects of cholinergic depletion of the hippocampus, with effects mirroring those from using just one trial a day approaches to these tasks. We suggest that pattern separation models of acetylcholine function can still explain our findings, but with an apparent emphasis on context-specific locations rather than all types of memory.

ImmunoglobuliN in the Treatment of Encephalitis (IgNiTE): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirical evidence of a beneficial response following its use in the treatment of viral and autoimmune encephalitis. In immune-mediated encephalitis, IVIG is often used after a delay (by weeks in some cases), while diagnosis is confirmed. Wider use of IVIG in infectious encephalitis and earlier use in immune-mediated encephalitis could improve outcomes for these conditions. We describe the protocol for the first ever randomised control trial of IVIG treatment for children with all-cause encephalitis. METHODS AND ANALYSIS: 308 children (6 months to 16 years) with a diagnosis of acute/subacute encephalitis will be recruited in ∼30 UK hospitals and randomised to receive 2 doses (1 g/kg/dose) of either IVIG or matching placebo, in addition to standard treatment. Recruitment will be over a 42-month period and follow-up of each participant will be for 12 months post randomisation. The primary outcome is 'good recovery' (score of 2 or lower on the Glasgow Outcome Score Extended-paediatric version), at 12 months after randomisation. Additional secondary neurological measures will be collected at 4-6 weeks after discharge from acute care and at 6 and 12 months after randomisation. Safety, radiological, other autoimmune and tertiary outcomes will also be assessed. ETHICS AND DISSEMINATION: This trial has been approved by the UK National Research Ethics committee (South Central-Oxford A; REC 14/SC/1416). Current protocol: V4.0 (10/03/2016). The findings will be presented at national and international meetings and conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT02308982, EudraCT201400299735 and ISRCTN15791925; Pre-results.

Impact of informational feedback to clinicians on antibiotic-prescribing rates in a tertiary care hospital in Delhi.

CONTEXT: Antimicrobial use has been associated with increasing antimicrobial resistance. There is an urgent need for judicious use of antimicrobials. Informational feedback has been shown to result in changes in behavioural practices of physicians in certain healthcare settings. We conducted this study to see if the passive informational feedback can reduce in antimicrobial usage in a tertiary care centre. AIMS: The study was undertaken to evaluate if the feedback to clinicians on their own antibiotic prescription results in any change in their antibiotic prescription habits. SETTINGS AND DESIGN: The study was conducted at a tertiary care setting involving 33 units of different specialties. These units were split into 10 groups based on specialty and were allocated randomly to the control (16 units) and intervention (17 units) arms of the study. This study was a prospective intervention to assess the effect of prescribing feedback on clinical prescribing practices. MATERIALS AND METHODS: In the intervention arm, information on resistance rates and antibiotic-prescribing patterns was provided to all doctors. Behavioural change was assessed by comparing baseline prescribing rates of each unit with prescribing rates after the intervention. In the control arm, only information on monthly resistance rates was provided. STATISTICAL ANALYSIS: Change in the antimicrobial prescribing rates in the treatment group was assessed by using a Student's t-test. RESULTS: The mean antibiotic use for all the specialties was 189 DDDs/100BDs. The prospective intervention did not elicit any effect on the antibiotic prescribing practices of the physicians. Low prescribers continued to prescribe antibiotics at a low rate, and high prescribers continued to prescribe at a high rate. CONCLUSIONS: In view of unfavourable results of passive intervention in the above study, active intervention may be more effective.

Moving beyond standard procedures to assess spontaneous recognition memory.

This review will consider how spontaneous tasks have been applied alongside neuroscientific techniques to test complex forms of recognition memory for objects and their environmental features, e.g. the spatial location of an object or the context in which it is presented. We discuss studies that investigate the roles of the perirhinal cortex and the hippocampus in recognition memory using standard testing paradigms, and consider how these findings contribute to the ongoing debate about whether recognition memory is a single unitary process or multiple processes that can be dissociated anatomically and functionally. Due to the wide use of spontaneous tasks, the need for improved procedures that reduce animal use is acknowledged, with multiple trial paradigms discussed as a novel way of reducing variability and animal numbers in these tasks. The importance of improving translation of animal models to humans is highlighted, with emphasis on a shift away from relying on the phenomenological experience of human subjects.

Putting memory in context: dissociating memories by distinguishing the nature of context.

In recent years, spontaneous recognition tasks have become commonplace methods of assessing memory in animals. Adaptations of these tasks allow us to look at the role of objects, contexts and spatial locations in memory. Recent findings have highlighted that not all types of contexts in these tasks rely on the same neural systems. Similarly, asking different questions about the same types of context can allow the dissociation of neural systems underlying these memories. Here we review the current position in how context is used in such tasks, and we consider the fundamental importance of clearly defining both the nature of the context being used, and the questions asked of it in order to fully appreciate the neural and cognitive mechanisms being studied in such tasks.

αCaMKII controls the establishment of cocaine's reinforcing effects in mice and humans.

Although addiction develops in a considerable number of regular cocaine users, molecular risk factors for cocaine dependence are still unknown. It was proposed that establishing drug use and memory formation might share molecular and anatomical pathways. Alpha-Ca(2+)/calmodulin-dependent protein kinase-II (αCaMKII) is a key mediator of learning and memory also involved in drug-related plasticity. The autophosphorylation of αCaMKII was shown to accelerate learning. Thus, we investigated the role of αCaMKII autophosphorylation in the time course of establishing cocaine use-related behavior in mice. We found that αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice show delayed establishment of conditioned place preference, but no changes in acute behavioral activation, sensitization or conditioned hyperlocomotion to cocaine (20 mg kg(-1), intraperitoneal). In vivo microdialysis revealed that αCaMKII(T286A) mice have blunted dopamine (DA) and blocked serotonin (5-HT) responses in the nucleus accumbens (NAcc) and prefrontal cortex after acute cocaine administration (20 mg kg(-1), intraperitoneal), whereas noradrenaline responses were preserved. Under cocaine, the attenuated DA and 5-HT activation in αCaMKII(T286A) mice was followed by impaired c-Fos activation in the NAcc. To translate the rodent findings to human conditions, several CAMK2A gene polymorphisms were tested regarding their risk for a fast establishment of cocaine dependence in two independent samples of regular cocaine users from Brazil (n=688) and Switzerland (n=141). A meta-analysis across both samples confirmed that CAMK2A rs3776823 TT-allele carriers display a faster transition to severe cocaine use than C-allele carriers. Together, these data suggest that αCaMKII controls the speed for the establishment of cocaine's reinforcing effects.

The association of alcohol drinking pattern and self-inflicted intentional injury in Korea: a cross-sectional WHO collaborative emergency room study.

OBJECTIVES: Self-inflicted intentional injuries are increasing at an alarming rate in the Republic of Korea, yet few reports describe their relationship with alcohol consumption. The aim of this study was to characterise the association of alcohol drinking patterns and self-inflicted intentional injury in Korean emergency departments (EDs) using WHO collaborative study protocol. DESIGN: Cross-sectional study. SETTING: Data were collected from four general hospital EDs in four geographically diverse regions of Korea: Seoul, Suwon, Chuncheon and Gwangju. PARTICIPANTS: Information was collected on 1989 patients aged 18 and above. A representative probability sample was drawn from patients admitted to each ED for the first time within 6 h of injury. PRIMARY AND SECONDARY OUTCOME MEASURES: Alcohol-related non-fatal injuries. RESULTS: Among 467 persons with alcohol-related injuries, 33 (7.1%), were self-inflicted intentional injuries and 137 (29.3%) were intentional injuries caused by someone else. The adjusted odds of self-inflicted intentional injury verses unintentional injury were calculated for heavy (OR 1.764; 95% CI 0.783 to 3.976), binge (OR 2.125; 95% CI 0.930 to 4.858) and moderate drinking (OR 3.039; 95% CI 1.129 to 8.178) after controlling for demographic variables. Similar odds were reported for pooled intentional injury data (self-inflicted and caused by someone else) and drinking patterns. CONCLUSIONS: These data show a strong association between all patterns of acute alcohol consumption and self-inflicted intentional injury in the Republic of Korea.

Metabolic syndrome component combinations and chronic kidney disease: the severance cohort study.

OBJECTIVES: The effects of ethnicity and gender can produce varying results when evaluating risk of chronic kidney disease (CKD) development and metabolic syndrome (MetS) components. The risks of specific MetS component combinations and incident CKD are unclear. The aim of this study was to investigate the relationship between the combination of MetS components and CKD. METHODS: This prospective cohort study included 15,401 participants. Koreans 20-84 years of age were followed for 5.2 years. The NCEP-ATP III definition of MetS was used. CKD was defined as an estimated glomerular filtration rate of <60ml/min/1.73m(2) by the simplified Modification of Diet in Renal Disease equation. RESULTS: The incidence rate per 1000 person-years of CKD was determined in men (13.8) and women (14.1) with MetS. In a multivariate Cox proportional hazard model controlling for age and lifestyle variables, increased CKD risk in men (hazard ratio 1.45, 95% confidence interval 1.20-1.76) and women (1.52, 1.19-1.93) with Mets was found compared to those without MetS. Incidence and HRs for CKD elevated with increasing numbers of MetS components in men and women (P for trend <0.0001). The risks associated with MetS varied by combination of causative factors. High blood pressure (BP) and low high-density lipoprotein (HDL) were more likely to be associated with risk of CKD development. CONCLUSIONS: BP and HDL were the leading risk factors for CKD development in healthy Koreans. The association between MetS and kidney dysfunction were significantly independent of traditional cardiovascular risk factors.

Addiction research centres and the nurturing of creativity. The Korean Institute on Alcohol Problems (KIAP).

The aim of this paper is to provide an account of the history, current status and vision of the Korean Institute on Alcohol Problems (KIAP). In the context of increasing alcohol consumption, rising second-hand effects and industry-friendly government policy, the Korean College Alcohol Study (KCAS) was established in the Republic of Korea in 1999, and changed its name to the Korean Institute on Alcohol Problems (KIAP) in 2005. KIAP's mission is to decrease alcohol consumption and its related harms by promoting research, advocating policy, developing intervention programmes and preparing media communications. Since 1999, KIAP has published scientific papers and books in alcohol research and used the internet and other media for dissemination of specialized information to the general population. In the last decade, KIAP has trained front-line alcohol researchers, and advanced domestic and international networks to promote evidence-based alcohol control policy in Korea. The light of hope shines brightly as KIAP grows and establishes critical linkages to move forward in its mission.

A new behavioural apparatus to reduce animal numbers in multiple types of spontaneous object recognition paradigms in rats.

Standard object recognition procedures assess animals' memory through their spontaneous exploration of novel objects or novel configurations of objects with other aspects of their environment. Such tasks are widely used in memory research, but also in pharmaceutical companies screening new drug treatments. However, behaviour in these tasks may be driven by influences other than novelty such as stress from handling which can subsequently influence performance. This extra-experimental variance means that large numbers of animals are required to maintain power. In addition, accumulation of data is time consuming as animals typically perform only one trial per day. The present study aimed to explore how effectively recognition memory could be tested with a new continual trials apparatus which allows for multiple trials within a session and reduced handling stress through combining features of delayed nonmatching-to-sample and spontaneous object recognition tasks. In this apparatus Lister hooded rats displayed performance significantly above chance levels in object recognition tasks (Experiments 1 and 2) and in tasks of object-location (Experiment 3) and object-in-context memory (Experiment 4) with data from only five animals or fewer per experimental group. The findings indicated that the results were comparable to those of previous reports in the literature and maintained statistical power whilst using less than a third of the number of animals typically used in spontaneous recognition paradigms. Overall, the results highlight the potential benefit of the continual trials apparatus to reduce the number of animals used in recognition memory tasks.

Adolescent optimistic bias toward HIV/AIDS in Seoul, South Korea.

The reported rates of HIV/AIDS cases and risky sexual behaviors have increased among adolescents in South Korea. This study reports the presence, impact, and development of optimistic bias toward HIV/AIDS in Korean adolescents. Survey data from 2996 participants were randomly collected from 8 high school and 8 middle school students in Seoul, South Korea. This study found that Korean high and middle school students had greater optimistic bias toward HIV/AIDS compared with their peers (P = .000). Involvement (r = -0.19; P < .01) decreased optimistic bias, whereas self-esteem (r = 0.13; P < .01) and self-control (r = 0.22; P < .01) increased it. Univariate analysis results indicated that gender and academic performance significantly influenced optimistic bias. However, according to hierarchical multiple regression, this significance was lost, and involvement, self-esteem, and self-control exerted a greater effect. Equipping Korean adolescents with involvement, awareness, and tailored interventions will reduce optimistic bias and yield greater protection against HIV/AIDS.

Management of suspected viral encephalitis in children - Association of British Neurologists and British Paediatric Allergy, Immunology and Infection Group national guidelines.

In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramatically improved with aciclovir treatment. Delays in starting treatment, particularly beyond 48 h after hospital admission, are associated with a worse prognosis. Several comprehensive reviews of the investigation and management of encephalitis have been published. However, their impact on day-to-day clinical practice appears to be limited. The emergency management of meningitis in children and adults was revolutionised by the introduction of a simple algorithm as part of management guidelines. In February 2008 a group of clinicians met in Liverpool to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.

Management of suspected viral encephalitis in adults--Association of British Neurologists and British Infection Association National Guidelines.

In the 1980s the outcome of patients with herpes simplex encephalitis was shown to be dramatically improved with aciclovir treatment. Delays in starting treatment, particularly beyond 48 h after hospital admission, are associated with a worse prognosis. Several comprehensive reviews of the investigation and management of encephalitis have been published. However, their impact on day-to day clinical practice appears to be limited. The emergency management of meningitis in children and adults was revolutionised by the introduction of a simple algorithm as part of management guidelines. In February 2008 a group of clinicians met in Liverpool to begin the development process for clinical care guidelines based around a similar simple algorithm, supported by an evidence base, whose implementation is hoped would improve the management of patients with suspected encephalitis.

The genetic architecture of embryonic developmental rate and genetic covariation with age at maturation in rainbow trout Oncorhynchus mykiss.

The genetic architecture underlying variation in embryonic developmental rate (DR) and genetic covariation with age of maturation (MAT) was investigated in rainbow trout Oncorhynchus mykiss. Highly significant additive parental effects and more limited evidence of epistatic effects on progeny hatching time were detected in three diallel sets of families. Genome scans with an average of 142 microsatellite loci from all 29 linkage groups in two families detected significant quantitative trait loci (QTL) for developmental rate on RT-8 and RT-30 with genome-wide and chromosome-wide effects, respectively. The QTL on linkage group RT-8 explained 23·7% of the phenotypic variation and supports results from previous studies. The co-localization of QTL for both DR and MAT to several linkage groups and the observation that alleles associated with faster developmental rate were found significantly more often in early maturing rather than typical and later maturing male ancestors supports the hypothesis of genetic covariation between DR and MAT. The maturation background and schedule of additional sires, however, did not have a consistent association with their progeny hatching times, suggesting that other genetic, environmental and physiological effects contribute to variation in these life-history traits.