Stem cell therapy for the treatment of early stage avascular necrosis of the femoral head: a systematic review

BACKGROUND: Avascular necrosis (AVN) of the femoral head (FH) is believed to be caused by a multitude of etiologic factors and is associated with significant morbidity in younger populations. Eventually, the disease progresses and results in FH collapse. Thus, a focus on early disease management aimed at joint preservation by preventing or delaying progression is key. The use of stem cells (SC) for the treatment of AVN of the FH has been proposed. We undertook a systematic review of the medical literature examining the use of SC for the treatment of early stage (precollapse) AVN of the FH, in both pre-clinical and clinical studies. METHODS: Data collected included: Pre-clinical studies – model of AVN, variety and dosage of SC, histologic and imaging analyses. Clinical studies – study design, classification and etiology of AVN, SC dosage and treatment protocol, incidence of disease progression, patient reported outcomes, volume of necrotic lesion and hip survivorship. RESULTS: In pre-clinical studies, the use of SC uniformly demonstrated improvements in osteogenesis and angiogenesis, yet source of implanted SC was variable. In clinical studies, groups treated with SC showed significant improvements in patient reported outcomes; however hip survivorship was not affected. Discrepancies regarding dose of SC, AVN etiology and disease severity were present. CONCLUSIONS: Routine use of this treatment method will first require further research into dose and quality optimization as well as confirmed improvements in hip survivorship

A Novel Mitigation Mechanism for Photo-Induced Trapping in an Anthradithiophene Derivative Using Additives

© 2020 Wiley-VCH GmbH A novel trap mitigation mechanism using molecular additives, which relieves a characteristic early turn-on voltage in a high-mobility p-type acene-based small-molecule organic semiconductor, when processed from hydrous solvents, is reported. The early turn-on voltage is attributed to photo-induced trapping, and additive incorporation is found to be very effective in suppressing this effect. Remarkably, the molecular additive does not disturb the charge transport properties of the small-molecule semiconductor, but rather intercalates in the crystal structure. This novel technique allows for the solution-processing of small molecular semiconductors from hydrous solvents, greatly simplifying manufacturing processes for large-area electronics. Along with various electric and spectroscopic characterization techniques, simulations have given a deeper insight into the trap mitigation effect induced by the additive

A perspective on using experiment and theory to identify design principles in dye-sensitized solar cells

Dye-sensitized solar cells (DSCs) have been the subject of wide-ranging studies for many years because of their potential for large-scale manufacturing using roll-to-roll processing allied to their use of earth abundant raw materials. Two main challenges exist for DSC devices to achieve this goal; uplifting device efficiency from the 12 to 14% currently achieved for laboratory-scale ‘hero’ cells and replacement of the widely-used liquid electrolytes which can limit device lifetimes. To increase device efficiency requires optimized dye injection and regeneration, most likely from multiple dyes while replacement of liquid electrolytes requires solid charge transporters (most likely hole transport materials – HTMs). While theoretical and experimental work have both been widely applied to different aspects of DSC research, these approaches are most effective when working in tandem. In this context, this perspective paper considers the key parameters which influence electron transfer processes in DSC devices using one or more dye molecules and how modelling and experimental approaches can work together to optimize electron injection and dye regeneration. This paper provides a perspective that theory and experiment are best used in tandem to study DSC device

Development of mental health first aid guidelines for deliberate non-suicidal self-injury: A Delphi study

<p>Abstract</p> <p>Background</p> <p>It is estimated that around 4% of the population engages, or has engaged, in deliberate non-suicidal self-injury. In clinical samples, the figures rise as high as 21%. There is also evidence to suggest that these figures may be increasing. A family member or friend may suspect that a person is injuring themselves, but very few people know how to respond if this is the case. Simple first aid guidelines may help members of the public assist people to seek and receive the professional help they require to overcome self-injury.</p> <p>Methods</p> <p>This research was conducted using the Delphi methodology, a method of reaching consensus in a panel of experts. Experts recruited to the panels included 26 professionals, 16 people who had engaged in self-injurious behaviour in the past and 3 carers of people who had engaged in self-injurious behaviour in the past. Statements about providing first aid to a person engaged in self-injurious behaviour were sought from the medical and lay literature, but little was found. Panel members were asked to respond to general questions about first aid for NSSI in a variety of domains and statements were extracted from their responses. The guidelines were written using the items most consistently endorsed by the consumer and professional panels.</p> <p>Results</p> <p>Of 79 statements rated by the panels, 18 were accepted. These statements were used to develop the guidelines appended to this paper.</p> <p>Conclusion</p> <p>There are a number of actions which are considered to be useful for members of the public when they encounter someone who is engaging in deliberate, non-suicidal self-injury. These guidelines will be useful in revising curricula for mental health first aid and NSSI first aid training programs. They can also be used by members of the public who want immediate information about how to assist a person who is engaging in such behaviour.</p

Mental health first aid training of the public in a rural area: a cluster randomized trial [ISRCTN53887541]

BACKGROUND: A Mental Health First Aid course has been developed which trains members of the public in how to give initial help in mental health crisis situations and to support people developing mental health problems. This course has previously been evaluated in a randomized controlled trial in a workplace setting and found to produce a number of positive effects. However, this was an efficacy trial under relatively ideal conditions. Here we report the results of an effectiveness trial in which the course is given under more typical conditions. METHODS: The course was taught to members of the public in a large rural area in Australia by staff of an area health service. The 16 Local Government Areas that made up the area were grouped into pairs matched for size, geography and socio-economic level. One of each Local Government Area pair was randomised to receive immediate training while one served as a wait-list control. There were 753 participants in the trial: 416 in the 8 trained areas and 337 in the 8 control areas. Outcomes measured before the course started and 4 months after it ended were knowledge of mental disorders, confidence in providing help, actual help provided, and social distance towards people with mental disorders. The data were analysed taking account of the clustered design and using an intention-to-treat approach. RESULTS: Training was found to produce significantly greater recognition of the disorders, increased agreement with health professionals about which interventions are likely to be helpful, decreased social distance, increased confidence in providing help to others, and an increase in help actually provided. There was no change in the number of people with mental health problems that trainees had contact with nor in the percentage advising someone to seek professional help. CONCLUSIONS: Mental Health First Aid training produces positive changes in knowledge, attitudes and behaviour when the course is given to members of the public by instructors from the local health service

Assessing knowledge of human papillomavirus and collecting data on sexual behavior: computer assisted telephone versus face to face interviews

<p>Abstract</p> <p>Background</p> <p>Education campaigns seeking to raise awareness of human papillomavirus (HPV) and promoting HPV vaccination depend on accurate surveys of public awareness and knowledge of HPV and related sexual behavior. However, the most recent population-based studies have relied largely on computer-assisted telephone interviews (CATI) as opposed to face to face interviews (FTFI). It is currently unknown how these survey modes differ, and in particular whether they attract similar demographics and therefore lead to similar overall findings.</p> <p>Methods</p> <p>A comprehensive survey of HPV awareness and knowledge, including sexual behavior, was conducted among 3,045 Singaporean men and women, half of whom participated via CATI, the other half via FTFI.</p> <p>Results</p> <p>Overall levels of awareness and knowledge of HPV differed between CATI and FTFI, attributable in part to demographic variations between these survey modes. Although disclosure of sexual behavior was greater when using CATI, few differences between survey modes were found in the actual information disclosed.</p> <p>Conclusion</p> <p>Although CATI is a cheaper, faster alternative to FTFI and people appear more willing to provide information about sexual behavior when surveyed using CATI, thorough assessments of HPV awareness and knowledge depend on multiple survey modes.</p

Binding to serine 65-phosphorylated ubiquitin primes Parkin for optimal PINK1-dependent phosphorylation and activation

This is the author accepted manuscript. The final version is available from EMBO Press via the DOI in this recordMutations in the mitochondrial protein kinase PINK1 are associated with autosomal recessive Parkinson disease (PD). We and other groups have reported that PINK1 activates Parkin E3 ligase activity both directly via phosphorylation of Parkin serine 65 (Ser(65))--which lies within its ubiquitin-like domain (Ubl)--and indirectly through phosphorylation of ubiquitin at Ser(65). How Ser(65)-phosphorylated ubiquitin (ubiquitin(Phospho-Ser65)) contributes to Parkin activation is currently unknown. Here, we demonstrate that ubiquitin(Phospho-Ser65) binding to Parkin dramatically increases the rate and stoichiometry of Parkin phosphorylation at Ser(65) by PINK1 in vitro. Analysis of the Parkin structure, corroborated by site-directed mutagenesis, shows that the conserved His302 and Lys151 residues play a critical role in binding of ubiquitin(Phospho-Ser65), thereby promoting Parkin Ser(65) phosphorylation and activation of its E3 ligase activity in vitro. Mutation of His302 markedly inhibits Parkin Ser(65) phosphorylation at the mitochondria, which is associated with a marked reduction in its E3 ligase activity following mitochondrial depolarisation. We show that the binding of ubiquitin(Phospho-Ser65) to Parkin disrupts the interaction between the Ubl domain and C-terminal region, thereby increasing the accessibility of Parkin Ser(65). Finally, purified Parkin maximally phosphorylated at Ser(65) in vitro cannot be further activated by the addition of ubiquitin(Phospho-Ser65). Our results thus suggest that a major role of ubiquitin(Phospho-Ser65) is to promote PINK1-mediated phosphorylation of Parkin at Ser(65), leading to maximal activation of Parkin E3 ligase activity. His302 and Lys151 are likely to line a phospho-Ser(65)-binding pocket on the surface of Parkin that is critical for the ubiquitin(Phospho-Ser65) interaction. This study provides new mechanistic insights into Parkin activation by ubiquitin(Phospho-Ser65), which could aid in the development of Parkin activators that mimic the effect of ubiquitin(Phospho-Ser65).Wellcome Trust Senior Research Fellowship in Clinical Science101022/Z/13/Z; Medical Research Council; Wellcome Trust; Parkinson's UK; Michael J. Fox Foundation for Parkinson's Disease Research; Tenovus Scotland; Wellcome/MRC; UCL Institute of Neurology; University of Sheffield; MRC‐PPU of University of Dundee; Division of Signal Transduction Therapy Unit (AstraZeneca, Boehringer‐Ingelheim, GlaxoSmithKline, Merck KGaA, Janssen Pharmaceutica and Pfizer

Expression and trans-specific polymorphism of self-incompatibility RNases in Coffea (Rubiaceae)

Self-incompatibility (SI) is widespread in the angiosperms, but identifying the biochemical components of SI mechanisms has proven to be difficult in most lineages. Coffea (coffee; Rubiaceae) is a genus of old-world tropical understory trees in which the vast majority of diploid species utilize a mechanism of gametophytic self-incompatibility (GSI). The S-RNase GSI system was one of the first SI mechanisms to be biochemically characterized, and likely represents the ancestral Eudicot condition as evidenced by its functional characterization in both asterid (Solanaceae, Plantaginaceae) and rosid (Rosaceae) lineages. The S-RNase GSI mechanism employs the activity of class III RNase T2 proteins to terminate the growth of "self" pollen tubes. Here, we investigate the mechanism of Coffea GSI and specifically examine the potential for homology to S-RNase GSI by sequencing class III RNase T2 genes in populations of 14 African and Madagascan Coffea species and the closely related self-compatible species Psilanthus ebracteolatus. Phylogenetic analyses of these sequences aligned to a diverse sample of plant RNase T2 genes show that the Coffea genome contains at least three class III RNase T2 genes. Patterns of tissue-specific gene expression identify one of these RNase T2 genes as the putative Coffea S-RNase gene. We show that populations of SI Coffea are remarkably polymorphic for putative S-RNase alleles, and exhibit a persistent pattern of trans-specific polymorphism characteristic of all S-RNase genes previously isolated from GSI Eudicot lineages. We thus conclude that Coffea GSI is most likely homologous to the classic Eudicot S-RNase system, which was retained since the divergence of the Rubiaceae lineage from an ancient SI Eudicot ancestor, nearly 90 million years ago.United States National Science Foundation [0849186]; Society of Systematic Biologists; American Society of Plant Taxonomists; Duke University Graduate Schoolinfo:eu-repo/semantics/publishedVersio

Assessment of human resources management practices in Lebanese hospitals

© 2009 El-Jardali et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens