International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients

Mistreatment of university students most common during medical studies

BACKGROUND: This study concerns the occurrence of various forms of mistreatment by staff and fellow students experienced by students in the Faculty of Medicine and the other four faculties of the University of Oulu, Finland. METHODS: A questionnaire with 51 questions on various forms of physical and psychological mistreatment was distributed to 665 students (451 females) after lectures or examinations and filled in and returned. The results were analysed by gender and faculty. The differences between the males and females were assessed statistically using a test for the equality of two proportions. An exact two-sided P value was calculated using a mid-P approach to Fisher's exact test (the null hypothesis being that there is no difference between the two proportions). RESULTS: About half of the students answering the questionnaire had experienced some form of mistreatment by staff during their university studies, most commonly humiliation and contempt (40%), negative or disparaging remarks (34%), yelling and shouting (23%), sexual harassment and other forms of gender-based mistreatment (17%) and tasks assigned as punishment (13%). The students in the Faculty of Medicine reported every form of mistreatment more commonly than those in the Faculties of Humanities, Education, Science and Technology. Experiences of mistreatment varied, but clear messages regarding its patterns were to be found in each faculty. Female students reported more instances of mistreatment than males and were more disturbed by them. Professors, lecturers and other staff in particular mistreated female students more than they mistreated males. About half of the respondents reported some form of mistreatment by their fellow students. CONCLUSION: Students in the Faculty of Medicine reported the greatest amount of mistreatment. If a faculty mistreats its students, its success in the main tasks of universities, research, teaching and learning, will be threatened. The results challenge university teachers, especially in faculties of medicine, to evaluate their ability to create a safe environment conducive to learning

Reef-building corals thrive within hot-acidified and deoxygenated waters

Coral reefs are deteriorating under climate change as oceans continue to warm and acidify and thermal anomalies grow in frequency and intensity. In vitro experiments are widely used to forecast reef-building coral health into the future, but often fail to account for the complex ecological and biogeochemical interactions that govern reefs. Consequently, observations from coral communities under naturally occurring extremes have become central for improved predictions of future reef form and function. Here, we present a semi-enclosed lagoon system in New Caledonia characterised by diel fluctuations of hot-deoxygenated water coupled with tidally driven persistently low pH, relative to neighbouring reefs. Coral communities within the lagoon system exhibited high richness (number of species = 20) and cover (24-35% across lagoon sites). Calcification rates for key species (Acropora formosa, Acropora pulchra, Coelastrea aspera and Porites lutea) for populations from the lagoon were equivalent to, or reduced by ca. 30-40% compared to those from the reef. Enhanced coral respiration, alongside high particulate organic content of the lagoon sediment, suggests acclimatisation to this trio of temperature, oxygen and pH changes through heterotrophic plasticity. This semi-enclosed lagoon therefore provides a novel system to understand coral acclimatisation to complex climatic scenarios and may serve as a reservoir of coral populations already resistant to extreme environmental conditions

A systematic review of rodent pest research in Afro-Malagasy small-holder farming systems: Are we asking the right questions?

Rodent pests are especially problematic in terms of agriculture and public health since they can inflict considerable economic damage associated with their abundance, diversity, generalist feeding habits and high reproductive rates. To quantify rodent pest impacts and identify trends in rodent pest research impacting on small-holder agriculture in the Afro-Malagasy region we did a systematic review of research outputs from 1910 to 2015, by developing an a priori defined set of criteria to allow for replication of the review process. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We reviewed 162 publications, and while rodent pest research was spatially distributed across Africa (32 countries, including Madagascar), there was a disparity in number of studies per country with research biased towards four countries (Tanzania [25%], Nigeria [9%], Ethiopia [9%], Kenya [8%]) accounting for 51% of all rodent pest research in the Afro-Malagasy region. There was a disparity in the research themes addressed by Tanzanian publications compared to publications from the rest of the Afro-Malagasy region where research in Tanzania had a much more applied focus (50%) compared to a more basic research approach (92%) in the rest of the Afro-Malagasy region. We found that pest rodents have a significant negative effect on the Afro-Malagasy small-holder farming communities. Crop losses varied between cropping stages, storage and crops and the highest losses occurred during early cropping stages (46% median loss during seedling stage) and the mature stage (15% median loss). There was a scarcity of studies investigating the effectiveness of various management actions on rodent pest damage and population abundance. Our analysis highlights that there are inadequate empirical studies focused on developing sustainable control methods for rodent pests and rodent pests in the Africa-Malagasy context is generally ignored as a research topic

Patterns of comorbidity in community-dwelling older people hospitalised for fall-related injury: A cluster analysis

<p>Abstract</p> <p>Background</p> <p>Community-dwelling older people aged 65+ years sustain falls frequently; these can result in physical injuries necessitating medical attention including emergency department care and hospitalisation. Certain health conditions and impairments have been shown to contribute independently to the risk of falling or experiencing a fall injury, suggesting that individuals with these conditions or impairments should be the focus of falls prevention. Since older people commonly have multiple conditions/impairments, knowledge about which conditions/impairments coexist in at-risk individuals would be valuable in the implementation of a targeted prevention approach. The objective of this study was therefore to examine the prevalence and patterns of comorbidity in this population group.</p> <p>Methods</p> <p>We analysed hospitalisation data from Victoria, Australia's second most populous state, to estimate the prevalence of comorbidity in patients hospitalised at least once between 2005-6 and 2007-8 for treatment of acute fall-related injuries. In patients with two or more comorbid conditions (multicomorbidity) we used an agglomerative hierarchical clustering method to cluster comorbidity variables and identify constellations of conditions.</p> <p>Results</p> <p>More than one in four patients had at least one comorbid condition and among patients with comorbidity one in three had multicomorbidity (range 2-7). The prevalence of comorbidity varied by gender, age group, ethnicity and injury type; it was also associated with a significant increase in the average cumulative length of stay per patient. The cluster analysis identified five distinct, biologically plausible clusters of comorbidity: cardiopulmonary/metabolic, neurological, sensory, stroke and cancer. The cardiopulmonary/metabolic cluster was the largest cluster among the clusters identified.</p> <p>Conclusions</p> <p>The consequences of comorbidity clustering in terms of falls and/or injury outcomes of hospitalised patients should be investigated by future studies. Our findings have particular relevance for falls prevention strategies, clinical practice and planning of follow-up services for these patients.</p

Rapid draft sequencing and real-time nanopore sequencing in a hospital outbreak of Salmonella

Background: Foodborne outbreaks of Salmonella remain a pressing public health concern. We recently detected a large outbreak of Salmonella enterica serovar Enteritidis phage type 14b affecting more than 30 patients in our hospital. This outbreak was linked to community, national and European-wide cases. Hospital patients with Salmonella are at high risk, and require a rapid response. We initially investigated this outbreak by whole-genome sequencing using a novel rapid protocol on the Illumina MiSeq; we then integrated these data with whole-genome data from surveillance sequencing, thereby placing the outbreak in a national context. Additionally, we investigated the potential of a newly released sequencing technology, the MinION from Oxford Nanopore Technologies, in the management of a hospital outbreak of Salmonella. Results: We demonstrate that rapid MiSeq sequencing can reduce the time to answer compared to the standard sequencing protocol with no impact on the results. We show, for the first time, that the MinION can acquire clinically relevant information in real time and within minutes of a DNA library being loaded. MinION sequencing permits confident assignment to species level within 20 min. Using a novel streaming phylogenetic placement method samples can be assigned to a serotype in 40 min and determined to be part of the outbreak in less than 2 h. Conclusions: Both approaches yielded reliable and actionable clinical information on the Salmonella outbreak in less than half a day. The rapid availability of such information may facilitate more informed epidemiological investigations and influence infection control practices

Type II and VI collagen in nasal and articular cartilage and the effect of IL-1α on the distribution of these collagens

The distribution of type II and VI collagen was immunocytochemically investigated in bovine articular and nasal cartilage. Cartilage explants were used either fresh or cultured for up to 4 weeks with or without interleukin 1α (IL-1α). Sections of the explants were incubated with antibodies for both types of collagen. Microscopic analyses revealed that type II collagen was preferentially localized in the interchondron matrix whereas type VI collagen was primarily found in the direct vicinity of the chondrocytes. Treatment of the sections with hyaluronidase greatly enhanced the signal for both types of collagen. Also in sections of explants cultured with IL-1α a higher level of labeling of the collagens was found. This was apparent without any pre-treatment with hyaluronidase. Under the influence of IL-1α the area positive for type VI collagen that surrounded the chondrocytes broadened. Although the two collagens in both types of cartilage were distributed similarly, a remarkable difference was the higher degree of staining of type VI collagen in articular cartilage. Concomitantly we noted that digestion of this type of cartilage hardly occurred in the presence of IL-1α whereas nasal cartilage was almost completely degraded within 18 days of culture. Since type VI collagen is known to be relatively resistant to proteolysis we speculate that the higher level of type VI collagen in articular cartilage is important in protecting cartilage from digestion

Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi

Depression affects 10-15% of pregnant women and has been associated with preterm delivery and later developmental, behavioural and learning disabilities. We tested the hypothesis that maternal depression is associated with DNA methylation alterations in maternal T lymphocytes, neonatal cord blood T lymphocytes and adult offspring hippocampi. Genome-wide DNA methylation of CD3+ T lymphocytes isolated from 38 antepartum maternal and 44 neonatal cord blood samples were analyzed using Illumina Methylation 450 K microarrays. Previously obtained methylation data sets using methylated DNA immunoprecipitation and array-hybridization of 62 postmortem hippocampal samples of adult males were re-analyzed to test associations with history of maternal depression. We found 145 (false discovery rate (FDR) q<0.05) and 2520 (FDR q<0.1) differentially methylated CG-sites in cord blood T lymphocytes of neonates from the maternal depression group as compared with the control group. However, no significant DNA methylation differences were detected in the antepartum maternal T lymphocytes of our preliminary data set. We also detected 294 differentially methylated probes (FDR q<0.1) in hippocampal samples associated with history of maternal depression. We observed a significant overlap (P=0.002) of 33 genes with changes in DNA methylation in T lymphocytes of neonates and brains of adult offspring. Many of these genes are involved in immune system functions. Our results show that DNA methylation changes in offspring associated with maternal depression are detectable at birth in the immune system and persist to adulthood in the brain. This is consistent with the hypothesis that system-wide epigenetic changes are involved in life-long responses to maternal depression in the offspring. © 2015 Translational Psychiatry