Classification of facial periâ implant soft tissue dehiscence/deficiencies at single implant sites in the esthetic zone

BackgroundThe incidence of a periâ implant soft tissue dehiscence/deficiency (PSTD) is not a rare finding. Despite multiple previous attempts aimed at correcting the PSTDs, a classification of these conditions has not yet been proposed. This lack in the literature may also lead to discrepancies in the reported treatment outcomes and thus misinform the clinician or the readers. The aim of the present article was therefore to present a classification of periâ implant PSTD at a single implant site.MethodsFour classes of PSTDs were discussed based on the position of the gingival margin of the implantâ supported crown in relation to the homologous natural tooth. In addition, the buccoâ lingual position of the implant head was also taken into consideration. Each class was further subdivided based on the height of the anatomical papillae.ResultsSubsequently, for each respective category a surgical approach (including bilaminar techniques, the combined prostheticâ surgical approach or soft tissue augmentation with a submerged healing) was also suggested.ConclusionThis paper provides a new classification system for describing PSTDs at single implant sites, with the appropriate recommended treatment protocol.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151905/1/jper10351_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151905/2/jper10351.pd

Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus

Autosomal dominant North Carolina macular dystrophy (NCMD) is believed to represent a failure of macular development. The disorder has been linked to two loci, MCDR1 (chromosome 6q16) and MCDR3 (chromosome 5p15-p13). Recently, non-coding variants upstream of PRDM13 (MCDR1) and a duplication including IRX1 (MCDR3) have been identified. However, the underlying disease-causing mechanism remains uncertain. Through a combination of sequencing studies on eighteen NCMD families, we report two novel overlapping duplications at the MCDR3 locus, in a gene desert downstream of IRX1 and upstream of ADAMTS16. One duplication of 43 kb was identified in nine families (with evidence for a shared ancestral haplotype), and another one of 45 kb was found in a single family. Three families carry the previously reported V2 variant (MCDR1), while five remain unsolved. The MCDR3 locus is thus refined to a shared region of 39 kb that contains DNAse hypersensitive sites active at a restricted time window during retinal development. Publicly available data confirmed expression of IRX1 and ADAMTS16 in human fetal retina, with IRX1 preferentially expressed in fetal macula. These findings represent a major advance in our understanding of the molecular genetics of NCMD and provide insights into the genetic pathways involved in human macular development

Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring.

BACKGROUND: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established. METHODOLOGY/PRINCIPAL FINDING: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone. CONCLUSIONS/SIGNIFICANCE: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies

PRISM (Program of Resources, Information and Support for Mothers) Protocol for a community-randomised trial [ISRCTN03464021]

BACKGROUND: In the year after birth one in six women has a depressive illness, and 30% are still depressed, or depressed again, when their child is 2 years old, 94% experience at least one major health problem (e.g. back pain, perineal pain, mastitis, urinary or faecal incontinence), 26% experience sexual problems and almost 20% have relationship problems with partners. Women with depression report less practical and emotional support from partners, less social support overall, more negative life events, and poorer physical health. Their perceptions of factors contributing to depression are lack of support, isolation, exhaustion and physical health problems. Fewer than one in three affected women seek help in primary care despite frequent contacts. METHODS/DESIGN: PRISM aims to reduce depression and physical health problems of recent mothers through primary care strategies to increase practitioners' response to these issues, and through community-based strategies to develop broader family and community supports for recent mothers. Eligible local governments will be recruited and randomised to intervention or comparison arms, after stratification (urban/rural, size, birth numbers, extent of community activity), avoiding contiguous boundaries. Maternal depression and physical health will be measured six months after birth, in a one year cohort of mothers, in intervention and comparison communities. The sample size to detect a 20% relative reduction in depression, adjusting for cluster sampling, and estimating a population response fraction of 67% is 5740 × 2. Analysis of the physical and mental health outcomes, by intention to treat, will adjust for the correlated structure of the data

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Stuttered swallowing: Electric stimulation of the right insula interferes with water swallowing. A case report

<p>Abstract</p> <p>Background</p> <p>Various functional resonance imaging, magnetoencephalographic and lesion studies suggest the involvement of the insular cortex in the control of swallowing. However, the exact location of insular activation during swallowing and its functional significance remain unclear.</p> <p>Case presentation</p> <p>Invasive electroencephalographic monitoring was performed in a 24-year-old man with medically intractable stereotyped nocturnal hypermotor seizures due to a ganglioglioma. During stimulation of the right inferior posterior insular cortex with depth electrodes the patient spontaneously reported a perception of a "stutter in swallowing". Stimulation of the inferior posterior insular cortex at highest intensity (4 mA) was also associated with irregular and delayed swallows. Swallowing was not impaired during stimulation of the superior posterior insular cortex, regardless of stimulation intensity.</p> <p>Conclusions</p> <p>These results indicate that the right inferior posterior insular cortex is involved in the neural circuitry underlying the control of swallowing.</p

Avoiding the danger that stop smoking services may exacerbate health inequalities: building equity into performance assessment

<p>Abstract</p> <p>Background</p> <p>The UK is the only developed country to have established a nation-wide stop smoking treatment service. Apart from addressing tobacco dependence, which is the leading preventable cause of ill health and premature death, smoking cessation has been identified by the UK department of health as a service priority for reducing gaps in health between disadvantaged groups and the country as a whole. However smoking cessation tends to be more successful among affluent than disadvantaged groups. This means that for stop smoking services there is a trade-off to be had in terms of maximising the number of quitters and reducing socioeconomic inequalities in smoking prevalence. Current performance targets for the national stop smoking services in the UK are set only in terms of numbers of quitters, which does not encourage the adoption of strategies to reduce socioeconomic inequalities in smoking prevalence.</p> <p>Discussion</p> <p>This paper proposes an assessment framework, which allows the two dimensions of overall reduction in smoking prevalence and reductions of inequalities in smoking prevalence to be assessed together. The framework is used to assess the performance over time of a stop smoking service in Derwentside, a former Primary Care Trust in the North East of England, both in terms of meeting targets for the overall number of quitters and in terms of reducing socioeconomic inequalities in smoking prevalence.</p> <p>The example demonstrates how the proposed assessment framework can be applied in practice given existing records kept by stop smoking services in England and the available information on smoking prevalence at small area level. For Derwentside it is shown that although service expansion was successful in increasing the overall number of quitters, the service continued to exacerbate inequality in smoking prevalence between deprived and affluent wards.</p> <p>Summary</p> <p>The Secretary of State for Health in the UK has warned about the dangers of health promotion services and messages being taken up more readily by the better-off, thus exacerbating health inequalities. Because smokers from affluent backgrounds are more successful at quitting than those living in deprived circumstances, it is important to build an equity element into the monitoring of individual stop smoking services. Otherwise the danger highlighted by the Secretary of State for Health will go undetected and unaddressed.</p

How to achieve synergy between medical education and cognitive neuroscience? An exercise on prior knowledge in understanding

A major challenge in contemporary research is how to connect medical education and cognitive neuroscience and achieve synergy between these domains. Based on this starting point we discuss how this may result in a common language about learning, more educationally focused scientific inquiry, and multidisciplinary research projects. As the topic of prior knowledge in understanding plays a strategic role in both medical education and cognitive neuroscience it is used as a central element in our discussion. A critical condition for the acquisition of new knowledge is the existence of prior knowledge, which can be built in a mental model or schema. Formation of schemas is a central event in student-centered active learning, by which mental models are constructed and reconstructed. These theoretical considerations from cognitive psychology foster scientific discussions that may lead to salient issues and questions for research with cognitive neuroscience. Cognitive neuroscience attempts to understand how knowledge, insight and experience are established in the brain and to clarify their neural correlates. Recently, evidence has been obtained that new information processed by the hippocampus can be consolidated into a stable, neocortical network more rapidly if this new information fits readily into a schema. Opportunities for medical education and medical education research can be created in a fruitful dialogue within an educational multidisciplinary platform. In this synergetic setting many questions can be raised by educational scholars interested in evidence-based education that may be highly relevant for integrative research and the further development of medical education

Antibody Targeting of Cathepsin S Inhibits Angiogenesis and Synergistically Enhances Anti-VEGF

Angiogenesis is a key hallmark of tumourigenesis and its inhibition is a proven strategy for the development of novel anti-cancer therapeutics. An important aspect of early angiogenesis is the co-ordinated migration and invasion of endothelial cells through the hypoxic tumour tissue. Cathepsin S has been shown to play an important role in angiogenesis as has vascular endothelial growth factor (VEGF). We sought to assess the anti-angiogenic effect of Fsn0503, a novel cathepsin S inhibitory antibody, when combined with anti-VEGF on vascular development. where it significantly retarded the development of vasculature in human xenograft models. Furthermore, when Fsn0503 was combined with an anti-VEGF antibody, a synergistic inhibition of microvascular development was observed.Taken together, this data demonstrates that the antibody-mediated targeting of cathepsin S represents a novel method of inhibiting angiogenesis. Furthermore, when used in combination with anti-VEGF therapies, Fsn0503 has the potential to significantly enhance current treatments of tumour neovascularisation and may also be of use in the treatment of other conditions associated with inappropriate angiogenesis