Four genomic islands that mark post-1995 pandemic Vibrio parahaemolyticus isolates

BACKGROUND: Vibrio parahaemolyticus is an aquatic, halophilic, Gram-negative bacterium, first discovered in 1950 in Japan during a food-poisoning outbreak. Infections resulting from consumption of V. parahaemolyticus have increased globally in the last 10 years leading to the bacterium's classification as a newly emerging pathogen. In 1996 the first appearance of a pandemic V. parahaemolyticus clone occurred, a new O3:K6 serotype strain that has now been identified worldwide as a major cause of seafood-borne gastroenteritis. RESULTS: We examined the sequenced genome of V. parahaemolyticus RIMD2210633, an O3:K6 serotype strain isolated in Japan in 1996, by bioinformatic analyses to uncover genomic islands (GIs) that may play a role in the emergence and pathogenesis of pandemic strains. We identified 7 regions ranging in size from 10 kb to 81 kb that had the characteristics of GIs such as aberrant base composition compared to the core genome, presence of phage-like integrases, flanked by direct repeats and the absence of these regions from closely related species. Molecular analysis of worldwide clinical isolates of V. parahaemolyticus recovered over the last 33 years demonstrated that a 24 kb region named V. parahaemolyticus island-1 (VPaI-1) encompassing ORFs VP0380 to VP0403 is only present in new O3:K6 and related strains recovered after 1995. We investigated the presence of 3 additional regions, VPaI-4 (VP2131 to VP2144), VPaI-5 (VP2900 to VP2910) and VPaI-6 (VPA1254 to VPA1270) by PCR assays and Southern blot analyses among the same set of V. parahaemolyticus isolates. These 3 VPaI regions also gave similar distribution patterns amongst the 41 strains examined. CONCLUSION: The 4 VPaI regions examined may represent DNA acquired by the pandemic group of V. parahaemolyticus isolates that increased their fitness either in the aquatic environment or in their ability to infect humans

Comparison of the salivary and dentinal microbiome of children with severe-early childhood caries to the salivary microbiome of caries-free children

peer-reviewedBackground The main objectives of this study were to describe and compare the microbiota of 1) deep dentinal lesions of deciduous teeth of children affected with severe early childhood caries (S-ECC) and 2) the unstimulated saliva of these children and 3) the unstimulated saliva of caries-free children, and to compare microbiota compositional differences and diversity of taxa in these sampled sites. Methods Children with S-ECC and without S-ECC were recruited. The saliva of all children with and without S-ECC was sampled along with the deep dentinal microbiota from children affected by S-ECC. The salivary microbiota of children affected by S-ECC (n = 68) was compared to that of caries-free children (n = 70), by Illumina MiSeq sequencing of 16S rRNA amplicons. Finally, the caries microbiota of deep dentinal lesions of those children with S-ECC was investigated. Results Using two beta diversity metrics (Bray Curtis dissimilarity and UniFrac distance), the caries microbiota was found to be distinct from that of either of the saliva groups (caries-free & caries-active) when bacterial abundance was taken into account. However, when the comparison was made by measuring only presence and absence of bacterial taxa, all three microbiota types separated. While the alpha diversity of the caries microbiota was lowest, the diversity difference between the caries samples and saliva samples was statistically significant (p < 0.001). The major phyla of the caries active dentinal microbiota were Firmicutes (median abundance value 33.5%) and Bacteroidetes (23.2%), with Neisseria (10.3%) being the most abundant genus, followed by Prevotella (10%). The caries-active salivary microbiota was dominated by Proteobacteria (median abundance value 38.2%) and Bacteroidetes (27.8%) with the most abundant genus being Neisseria (16.3%), followed by Porphyromonas (9.5%). Caries microbiota samples were characterized by high relative abundance of Streptococcus mutans, Prevotella spp., Bifidobacterium and Scardovia spp. Conclusions Distinct differences between the caries microbiota and saliva microbiota were identified, with separation of both salivary groups (caries-active and caries-free) whereby rare taxa were highlighted. While the caries microbiota was less diverse than the salivary microbiota, the presence of these rare taxa could be the difference between health and disease in these children

Oral Care Practices in Stroke: Findings from the UK and Australia

Aims: To examine current practice, perceptions of healthcare professionals and factors affecting provision for oral care post-stroke in the UK and Australia. Background: Poor oral care has negative health consequences for people post-stroke. Little is known about oral care practice in hospital for people post-stroke and factors affecting provision in different countries. Design: A cross-sectional survey. Methods: Questionnaires were mailed to stroke specialist nurses in UK and Australian hospitals providing inpatient acute or rehabilitation care post-stroke. The survey was conducted between April and November 2019. Non-respondents were contacted up to five times. Results: Completed questionnaires were received from 150/174 (86%) hospitals in the UK, and 120/162 (74%) in Australia. A total of 52% of UK hospitals and 30% of Australian hospitals reported having a general oral care protocol, with 53% of UK and only 13% of Australian hospitals reporting using oral care assessment tools. Of those using oral care assessment tools, 50% of UK and 38% of Australian hospitals used local hospital-specific tools. Oral care assessments were undertaken on admission in 73% of UK and 57% of Australian hospitals. Staff had received oral care training in the last year in 55% of UK and 30% of Australian hospitals. Inadequate training and education on oral care for pre-registration nurses were reported by 63% of UK and 53% of Australian respondents. Conclusion: Unacceptable variability exists in oral care practices in hospital stroke care settings. Oral care could be improved by increasing training, performing individual assessments on admission, and using standardised assessment tools and protocols to guide high quality care. The study highlights the need for incorporating staff training and the use of oral care standardised assessments and protocols in stroke care in order to improve patient outcomes

Returning Individual Research Results from Digital Phenotyping in Psychiatry

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas

Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine

in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers.. Two volunteers mounted antibodies that were able to neutralize clade-matched viruses.ADMVA was well-tolerated and elicited durable humoral and cellular immune responses

Being Ready to Treat Ebola Virus Disease Patients

As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD

Covert observation in practice: lessons from the evaluation of the prohibition of smoking in public places in Scotland

Background: A ban on smoking in wholly or substantially enclosed public places has been in place in Scotland since 26th March 2006. The impact of this legislation is currently being evaluated in seven studies, three of which involve direct observation of smoking in bars and other enclosed public places. While the ethical issues around covert observation have been widely discussed there is little practical guidance on the conduct of such research. A workshop was therefore convened to identify practical lessons learned so far from the Scottish evaluation. Methods: We convened a workshop involving researchers from the three studies which used direct observation. In addition, one of the fieldwork managers collected written feedback on the fieldwork, identifying problems that arose in the field and some solutions. Results: There were four main themes identified: (i) the difficulty of achieving and maintaining concealment; (ii) the experience of being an observer; (iii) the risk of bias in the observations and (iv) issues around training and recruitment. These are discussed. Conclusion: Collecting covert observational data poses unique practical challenges, in particular in relation to the health and safety of the researcher. The findings and solutions presented in this paper will be of value to researchers designing similar studies

XIAP Protection of Photoreceptors in Animal Models of Retinitis Pigmentosa

BACKGROUND: Retinitis pigmentosa (RP) is a blinding genetic disorder that is caused by the death of photoreceptors in the outer nuclear layer of the retina. To date, 39 different genetic loci have been associated with the disease, and 28 mutated genes have been identified. Despite the complexity of the underlying genetic basis for RP, the final common pathway is photoreceptor cell death via apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, P23H and S334ter rhodopsin transgenic rat models of RP were used to test the neuroprotective effects of anti-apoptotic gene therapy. Adeno-associated viruses (AAV) carrying the X-linked inhibitor of apoptosis (XIAP) or green fluorescent protein (GFP) were delivered subretinally into the eye of transgenic rat pups. Histological and functional measures were used to assess neuroprotection. XIAP is known to block apoptosis by inhibiting the action of caspases-3, -7 and -9. The results show that XIAP gene therapy provides long-term neuroprotection of photoreceptors at both structural and functional levels. CONCLUSIONS/SIGNIFICANCE: Our gene therapy strategy targets the apoptotic cascade, which is the final common pathway in all forms of retinitis pigmentosa. This strategy holds great promise for the treatment of RP, as it allows for the broad protection of photoreceptors, regardless of the initial disease causing mutation

Loss of the Synaptic Vesicle Protein SV2B Results in Reduced Neurotransmission and Altered Synaptic Vesicle Protein Expression in the Retina

The Synaptic Vesicle Protein 2 (SV2) family of transporter-like proteins is expressed exclusively in vesicles that undergo calcium-regulated exocytosis. Of the three isoforms expressed in mammals, SV2B is the most divergent. Here we report studies of SV2B location and function in the retina. Immunolabeling studies revealed that SV2B is detected in rod photoreceptor synaptic terminals where it is the primary isoform. In mice lacking SV2B, synaptic transmission at the synapse between photoreceptors and bipolar neurons was decreased, as evidenced by a significant reduction in the amplitude of the b-wave in electroretinogram recordings. Quantitative immunoblot analyses of whole eyes revealed that loss of SV2B was associated with reduced levels of synaptic vesicle proteins including synaptotagmin, VAMP, synaptophysin and the vesicular glutamate transporter V-GLUT1. Immunolabeling studies revealed that SV2B is detected in rod photoreceptor synaptic terminals where it is the primary isoform. Thus, SV2B contributes to the modulation of synaptic vesicle exocytosis and plays a significant role in regulating synaptic protein content