Search

Klinefelter syndrome is the most prevalent chromosome disorder in infertile men, characterized by one or more additional X chromosomes. This manuscript reviews the spectrum of phenotypic variability, testicular histopathology and hormonal imbalances associated with Klinefelter syndrome across different developmental stages from infancy through adulthood. Klinefelter syndrome typically manifests with small firm testes, azoospermia, hypergonadotrophic hypogonadism and a tall feminine stature. Testicular biopsies reveal progressive germ cell depletion, seminiferous tubule hyalinization, testicular fibrosis and Leydig cell hyperplasia, contributing to elevated luteinizing hormone and follicle stimulating hormone levels alongside decreased inhibin B and anti-Müllerian hormone levels from mid-puberty onwards. Despite extensive research, the exact mechanisms underlying these changes remain unclear, highlighting the need for further investigation to enhance diagnostic accuracy and therapeutic outcomes for Klinefelter individuals, especially in fertility preservation and restoration strategies. [ABSTRACT FROM AUTHOR]

This study calls for the meaningful inclusion of disabled children within Physical Education (PE), by exploring the experiences of a triad of key stakeholders: (a) Disabled children and their families; (b) PE teachers; and (c) Initial Teacher Training (ITT) Providers. Semi-structured interviews were conducted between September 2017 and September 2019 with a total of 34 participants from across these three groups. Thematic analysis of the interviews revealed the following: (i) disabled children still face many barriers to participation in PE lessons in 'mainstream' schools in England; (ii) teaching professionals remain unprepared for including disabled children in PE; and, (iii) both parents and teaching professionals (teachers and ITT providers) cited recommendations to enhance the inclusion of disabled children in PE. It is concluded that disabled children are still outsiders to PE in mainstream schools in England and an intervention into PE teacher training is needed to promote strategies for inclusion. Disabled children across the world have traditionally experienced exclusion from Physical Education lessons in mainstream schools. Disabled children still face many barriers to participation in Physical Education lessons in mainstream schools in England. Teaching professionals remain unprepared for including disabled children in Physical Education settings. Both parents and teaching professionals cited recommendations to enhance the inclusion of disabled children in Physical Education. The authors suggest that changes to the structure and content of the initial teacher training for Physical Education teachers is needed to promote strategies for the meaningful inclusion of disabled children. [ABSTRACT FROM AUTHOR]

Which early-diagnosed Klinefelter syndrome patients have been offered cryopreservation of testicular tissue as part of fertility preservation before spermatogonial stem cell (SSC) loss? Do these Klinefelter syndrome patients present with behavioural, cognitive and/or psychological problems? Does a testicular biopsy procedure have long-term effects on the gonadal development of Klinefelter syndrome patients? Early-diagnosed Klinefelter syndrome patients followed between 2009 and 2020 and offered testicular tissue banking in an experimental context at the Universitair Ziekenhuis Brussel were included. The prevalence of behavioural, cognitive and/or psychological problems was determined. Changes in testicular volume and in gonadal function (LH, FSH, testosterone and inhibin B [INHB]) were studied. Of the 48 Klinefelter syndrome patients included, 22 had testicular tissue removed (biopsy group) and 26 had no surgical intervention (control group). The need for specialized education was significantly higher in prenatally (P = 0.0159) and prepubertally (P = 0.0002) diagnosed Klinefelter syndrome patients. Psychological problems were significantly more prevalent in Klinefelter syndrome patients who did not opt for fertility preservation (P = 0.0447). In the first 4.2 (1.9–9.1) years after testicular biopsy, no difference in testicular volume was observed between the biopsied and the contralateral non-biopsied testes (P > 0.9999). After pubertal onset, no differences in LH, FSH, testosterone and INHB were found between the biopsy and the control groups (P = 0.1324 for LH, P > 0.9999 for FSH, P = 0.5433 for testosterone, P > 0.9999 for INHB). Early-diagnosed Klinefelter syndrome patients presented with behavioural, cognitive and/or psychological problems. Only psychological problems seemed to influence the decision towards fertility preservation. Follow-up data confirm that harvesting testicular tissue does not have a long-term impact on the gonadal development of Klinefelter syndrome patients. [ABSTRACT FROM AUTHOR]

Background: In high income countries, ~30% of pregnant women are provided with intrapartum antibiotic prophylaxis (IAP) for early‐onset group B streptococcal infection (EOGBSI). The infection rate is low, 0.2/1000 livebirths in our jurisdiction, and others. We hypothesised factors, other than IAP alone, were reasons for the low rate of EOGBSI. Aims: Compliance with our local guideline, referred to here as 'the guideline'. Method: Compliance was defined as an initial dose of benzylpenicillin IAP followed by four‐hourly doses until birth. The study population was drawn from 4098 women who had 4100 pregnancies resulting in 4200 babies in an Australian birth setting from 1/1/2016 to 31/12/2016. Most, 93%, were eligible for universal GBS screening, 67% were reported as screened and 90% of these had a result documented; 23% were positive for GBS. A random sample (n = 223) was taken for further analysis. Results: The adjusted odds of receiving benzylpenicillin IAP in accord with the guideline were three times higher among primiparous compared to multiparous women (P < 0.001, odds ratio (OR) = 3.4, 95% CI 1.7–6.7) and three times higher among women experiencing induction of labour compared to women who commenced labour spontaneously (P < 0.001, OR = 3.4, 95% CI 1.8–6.3). Of the 223 women, 188 received IAP: 176 received benzylpenicillin IAP, 31% (or 24% of the total sample) received this intervention in accord with the guideline, 24% received benzylpenicillin ≥4 h before birth but not in accord with the guideline and 44% received benzylpenicillin <4 h before birth. Conclusion: We conclude that sub‐optimal compliance was largely a consequence of an unrealistic guideline. [ABSTRACT FROM AUTHOR]

Cutaneous wound healing in adult mammals is a complex multi-step process involving overlapping stages of blood clot formation, inflammation, re-epithelialization, granulation tissue formation, neovascularization, and remodelling. Re-epithelialization describes the resurfacing of a wound with new epithelium. The cellular and molecular processes involved in the initiation, maintenance, and completion of epithelialization are essential for successful wound closure. A variety of modulators are involved, including growth factors, cytokines, matrix metalloproteinases, cellular receptors, and extracellular matrix components. Here, we focus on cellular mechanisms underlying keratinocyte migration and proliferation during epidermal closure. Inability to re-epithelialize is a clear indicator of chronic non-healing wounds, which fail to proceed through the normal phases of wound healing in an orderly and timely manner. This review summarizes the current knowledge regarding the management and treatment of acute and chronic wounds, with a focus on re-epithelialization, offering some insights into novel future therapies. Unlabelled Image [ABSTRACT FROM AUTHOR]

Aim: To describe the epidemiology of EOS including blood culture utilisation, across a large and geographically diverse Australian health district. Background: Sepsis in the first three days of life remains a leading cause of death and morbidity. In high-income countries, group B Streptococcus (GBS) and Escherichia coli (E. coli) have dominated as causes of EOS for five decades. Method: An 11-year retrospective cohort study to determine the epidemiology of EOS. Incidence rates were calculated per 1000 live births. Logistic regression with linear temporal trend and covariates for potential effect modifiers were employed. Blood culture utilisation was determined by examining the rate of babies undergoing blood culture within 72 hours of birth. Results: Among 93,584 live born babies, 65 had confirmed EOS (0.69/1000 live births); 22 term, 43 preterm. Across the 4 largest birth units, the proportion of babies having blood culture within 72 hours of birth varied from 1.9–5.1% for term and 21–35% for preterm babies. The annual change in the EOS rate was significant, OR 0.91 (95% CI, 0.84 to 0.99, p = 0.03). Group B Streptococcus was the most common cause of EOS in term neonates at 0.35/1000 live births (95% CI, 0.07–0.63) in 2006 and 0.1/1000 live births (95% CI, 0–0.2) in 2016. Escherichia coli was the most common cause in preterm babies at 3.4/1000 (95% CI, 0.11–6.76) in 2006 reducing significantly to 1.35/1000 live births (95% CI, -0.07–2.78) by 2016. Conclusions: Escherichia coli and GBS were the most common causes of EOS in preterm and term babies respectively. Rates of all cause term and preterm EOS declined significantly as did preterm sepsis due to E. coli. While rate of sepsis due to early-onset GBS declined, this did not reach significance. Given the high proportion of preterm babies undergoing blood culture, it is unlikely that any EOS events were missed. [ABSTRACT FROM AUTHOR]

Background: Intrapartum antibiotic prophylaxis (IAP) to reduce the likelihood of neonatal early-onset group B streptococcal infection (EOGBS) has coincided with major reductions in incidence. While the decline has been largely ascribed to IAP following either universal screening or a risk-based approach to identify mothers whose babies may most benefit from IAP, there is lack of high quality evidence to support this view. Aims: To describe management of maternal GBS colonisation in one local health district using universal screening and assess rates of EOGBS over time. Methods: A retrospective cohort study was undertaken to describe compliance with GBS management, to determine the incidence of EOGBS and association between rates and maternal screening. Linking routinely collected maternity and pathology data, we explored temporal trends using logistic regression and covariates for potential effect modifiers. Results: Our cohort included 62,281 women who had 92,055 pregnancies resulting in 93,584 live born babies. Screening occurred in 76% of pregnancies; 69% had a result recorded, 21.5% of those were positive for GBS. Prophylaxis was used by 79% of this group. Eighteen babies developed EOGBS, estimated incidence/1000 live births in 2006 and 2016 was 0.35 (95% CI, 0.07 to 0.63) and 0.1 (95% CI, 0 to 0.2) respectively. Seven of 10 term babies with EOGBS were born to mothers who screened negative. Data were unable to provide evidence of difference in rates of EOGBS between screened and unscreened pregnancies. We estimated the difference in EOGBS incidence from crude and weighted models to be 0 (95% CI, -0. 2 to 0.17) and -0.01 (95% CI, -0.13 to 0.10) /1000 live births respectively. Conclusion: No change was detected in rates of EOGBS over time and no difference in EOGBS in babies of screened and unscreened populations. Screening and prophylaxis rates were modest. Limitations of universal screening suggest alternatives be considered. [ABSTRACT FROM AUTHOR]

We discuss two electrochemical plating approaches for nanotwinned copper (ECP nt-Cu)--Gen 1 and Gen 2. These two approaches allow control over columnar width and transition layer thickness on Cu substrates, enabling the filling of nanotwinned Cu for bonding applications. Both approaches produce stable nt-Cu structures with minimal transition layers when electroplated on (111) Cu substrate. However, grain size, transition layer thickness on polycrystalline substrates, and feature-filling behavior differ. The researchers suggest that the choice between Gen 1 and Gen 2 depends on the feature size, aspect ratio, and applications. In addition, further exploration into other additives improves bottom-up filling capabilities, enabling more versatility for applications. Both approaches enable the filling of nanotwinned Cu inside bottom-seeded and complete-seeded features, with 100% nanotwin growth parallel to the substrate for bottomseeded features. However, nanotwin growth percentage and direction depend on feature size and aspect ratio for complete-seeded features. Gen 2 tends to have less sidewall growth due to its smaller grain size and is more compatible with other additives, making it promising for high aspect ratio small features. [ABSTRACT FROM AUTHOR]

One claim of the UK Government’s Department for Culture, Media and Sport is that the London 2012 Paralympic Games ‘improved attitudes to disability and provided new opportunities for disabled people to participate in society’. In addition, the International Paralympic Committee’s strategic plan suggests that the Paralympic Games is a vehicle for achieving ‘a more equitable society’. The aim of this study was to examine the reflections of a group of retired British Paralympic athletes on the relationship between the Paralympic Games and disability equality in the United Kingdom. Narrative interviews were conducted with five male retired British Paralympians and one female retired British Paralympian who had participated in a total of 22 Summer Paralympic Games events. I will argue that some Paralympic athletes who are not obvious ‘activists’ can still contribute to equality for disabled people. [ABSTRACT FROM PUBLISHER]

Purpose - The purpose of this paper is to analyse in detail the findings from 40 serious case reviews (SCRs) involving adults who self-neglect, and to consider the commissioning and reporting of such inquiries in the context of accountability that also involves the Coroner and the Local Government Ombudsman. Design/methodology/approach - This study comprised a cross-case analysis of 32 SCRs, using a four-layer design of the adult and their living context, the team around the adult, the organisations around the team, and the Local Safeguarding Board around the organisations. Findings - Available reports tend towards description of events rather than appraisal of what influenced practice. They highlight the challenges in cases of self-neglect practice, including person-centred approaches, capacity assessment and securing engagement. Familiar themes emerge when the spotlight turns to professional and organisational networks, namely information-sharing, supervision, recording and compliance with procedures and legal rules. Some Local Safeguarding Adults Boards found the process of conducting and then using serious case reviews for service improvement challenging. Research limitations/implications - The cross-case approach to thematic analysis focuses on reports into situations where outcomes of professional and organisational intervention had been disappointing. Nonetheless, the themes derived from this analysis are similar to other research findings on what represents best practice when working with cases involving self-neglect. Practical implications - The paper identifies learning for the effective commissioning and conduct of SCRs, and for service improvement with respect to practice with adults who self-neglect. Originality/value - The paper offers further detailed analysis of a large sample of SCRs that builds the evidence-base for effective practice with adults who self-neglect and for efficient management of process of commissioning and conducting SCRs. [ABSTRACT FROM AUTHOR]

Purpose -- The purpose of this paper is to report the findings from research into 40 serious case reviews (SCRs) involving adults who self-neglect. Design/methodology/approach -- The study comprised analysis of 40 SCRs where self-neglect featured. The reviews were found through detailed searching of Local Safeguarding Adult Board (LSAB) web sites and through contacts with Board managers and independent chairs. A four layer analysis is presented of the characteristics of each case and SCR, of the recommendations and of the emerging themes. Learning for service improvement is presented thematically, focusing on the adult and their immediate context, the team around the adult, the organisations around the team and the Local Safeguarding Board around the organisations. Findings -- There is no one typical presentation of self-neglect; cases vary in terms of age, household composition, lack of self-care, lack of care of one's environment and/or refusal to engage. Recommendations foreground LSABs, adult social care and unspecified agencies, and focus on staff support, procedures and the components of best practice and effective SCRs. Reports emphasise the importance of a person-centred approach, within the context of ongoing assessment of mental capacity and risk, with agencies sharing information and working closely together, supported by management and supervision, and practising within detailed procedural guidance. Research limitations/implications -- There is no national database of SCRs commissioned by LSABs and currently there is no requirement to publish the outcomes of such inquiries. It may be that there are further SCRs, or other forms of inquiry, that have been commissioned by Boards but not publicised. This limits the learning that has been available for service improvement. Practical implications -- The paper identifies practice, management and organisational issues that should be considered when working with adults who self-neglect. These cases are often complex and stressful for those involved. The thematic analysis adds to the evidence-base of how best to approach engagement with adults who self-neglect and to engage the multi-agency network in assessing and managing risk and mental capacity. Originality/value -- The paper offers the first formal evaluation of SCRs that focus on adults who self-neglect. The analysis of the findings and the recommendations fromthe investigations into the 40 cases adds to the evidence-base for effective practice with adults who self-neglect. [ABSTRACT FROM AUTHOR]

This article reports on a learning set designed to support educators teaching law to social work students in England to build their capacity, first, for engaging with e-learning resources and, second, for evaluating the outcomes of their use in teaching. A mixed methods approach was used, including recording and transcription of the content of seven learning set meetings with eight participants over 2½ years, repeat measures questionnaires to capture changes in attitudes and orientation to the use of e-learning, reflective diaries, and individual interviews with learning set members. The findings demonstrate increased self-perceived capacity in blending e-learning into teaching and in researching the outcomes. The learning set enabled e-learning to become embedded in the curriculum progressively over two years. Participation was experienced as a constructive and empowering experience. There were positive changes in attitudes, motivators and barriers to the use of e-learning, and in orientation to the use of IT resulting in improved confidence. Similarly, understanding of, and the ability to apply, evaluation techniques to track changes in student learning improved throughout the project, confirming the collaborative capacity building value of the learning set approach. The findings have broad relevance for social work education beyond the teaching of law. [ABSTRACT FROM PUBLISHER]

Background: Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype. Methods: We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed. Results: We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size. Conclusions: In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC. [ABSTRACT FROM AUTHOR]

In a Christian context, the eternal change of identity from death to life through Jesus Christ becomes all-encompassing. Yet, other ephemeral identities also shape individuals. Using a range of theoretical ideas evident within disability studies and sports discourse, this essay attempts to contextualize and reflect upon the life of a disabled person who became a "born again" Christian in the aftermath (and amidst the tensions) of physical impairment. Reflections are provided on the interactions between the following identities: ex-solider (including Special Forces); ex-lorry driver; ex-nondisabled person; ex-Paralympic athlete (1992 Olympics in Barcelona, Spain); ex-sports development officer (for disabled people); disability activist; Christian; and academic. It is argued that the constructs of disability studies and disability sport need to be considered in terms of their relationship to the Christian faith. This area requires further research because within disability studies Christianity is largely ignored or placed in a historical context rather than explained as a current subjective experience (see Barnes & Mercer, 2011). In turn, disability sport discourse often either dismisses Christianity or contextualizes it historically rather than addressing its impact on the personal and the present (see Thomas, 2003). [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype. Methods: We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semiquantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed. Results: We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size. Conclusions: In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC. [ABSTRACT FROM AUTHOR]

Background Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent an important subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for molecular biomarkers and treatment targets in breast cancer, but their role in the progression of triple negative breast cancer remains largely unexplored. Methods This study has investigated miRNA expression profiles in 31 primary triple negative breast cancer cases and in 13 matched lymph node metastases compared with 23 matched normal breast tissues to determine miRNAs associated with the initiation of this disease subtype and those associated with its metastasis. Results 71 miRNAs were differentially expressed in triple negative breast cancer, the majority of which have previously been associated with breast cancer, including members of the miR- 200 family and the miR-17-92 oncogenic cluster, suggesting that the majority of miRNAs involved in the initiation of triple negative breast cancer are not subtype specific. However, the repertoire of miRNAs expressed in lymph node negative and lymph node positive triple negative breast cancers were largely distinct from one another. In particular, miRNA profiles associated with lymph node negative disease tended to be up-regulated, while those associated with lymph node positive disease were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. From this, 27 miRNAs were identified that are associated with metastatic capability in the triple negative breast cancer subtype. Conclusions These results provide novel insight into the repertoire of miRNAs that contribute to the initiation of and progression to lymph node metastasis in triple negative breast cancer and have important implications for the treatment of this breast cancer subtype. [ABSTRACT FROM AUTHOR]

This article offers an exploratory analysis of the opinions of disabled activists towards the Paralympic Games. With the use of a qualitative online survey, the work focuses on the perceptions of disabled individuals (n= 32) who are not Paralympic athletes but are affiliated to the disability rights group, the United Kingdom Disabled People’s Council. Working on the premise that the views of disabled activists have been excluded from Paralympic sports discourse to date, the results illustrate a nuanced yet negative view of the Games to contrast with an existing, yet overly positive, academic narrative. Participants were particularly cynical of the portrayal and production of the Games and its Paralympic athletes as they perceived that the wider population of disabled people is misrepresented. The overwhelming perception in this preliminary analysis suggests that the Paralympic Games can be counterproductive to disability rights beyond sport. [ABSTRACT FROM AUTHOR]

This article offers an exploratory analysis of the opinions of disabled activists towards the Paralympic Games. With the use of a qualitative online survey, the work focuses on the perceptions of disabled individuals (n= 32) who are not Paralympic athletes but are affiliated to the disability rights group, the United Kingdom Disabled People’s Council. Working on the premise that the views of disabled activists have been excluded from Paralympic sports discourse to date, the results illustrate a nuanced yet negative view of the Games to contrast with an existing, yet overly positive, academic narrative. Participants were particularly cynical of the portrayal and production of the Games and its Paralympic athletes as they perceived that the wider population of disabled people is misrepresented. The overwhelming perception in this preliminary analysis suggests that the Paralympic Games can be counterproductive to disability rights beyond sport. [ABSTRACT FROM PUBLISHER]

•Summary: This article reviews evidence on how social workers incorporate legal rules in their decision-making. It draws on a small empirical study in which practitioners shared with each other, in peer interviews, examples of their own casework, followed by individual interviews with a researcher. Taken together, the conversations cast light on the extent to which legal knowledge is foregrounded in practitioners’ accounts of their work.•Findings: The findings show that references to law are more likely to be implicit than explicit, particularly in adult social care, and that absence of legal references is a striking feature of the social workers’ narratives. The article draws on related literature to interrogate the potential reasons for the relatively low profile of ‘law talk’ and identifies four factors – lack of legal knowledge and confidence, reliance on organizational and procedural approaches, assumptions about the role of law in different service contexts, and individual orientations to practice – as significant factors in determining whether and how legal rules are relied upon. Thus it presents a more nuanced analysis of the relationship between law and practice than has hitherto been available.• Applications: The findings are significant in casting light on the complex range of factors that present barriers to the robust and consistent implementation of legal rules in social work. They have implications – in particular for the role of organizational management in the audit, development and supervision of practice – that are particularly topical in the context of the work in England of the Social Work Reform Board. [ABSTRACT FROM PUBLISHER]

Purpose -- The purpose of this article is to report the findings from research into the governance of adult safeguarding policy and practice in England, with particular focus on interagency partnership arrangements expressed through Safeguarding Adults Boards. Design/methodology/approach -- The study comprised a systematic search and thematic analysis of English-language literature on adult safeguarding governance, a survey of Safeguarding Adults Board documentation, and key informant interviews and workshops with professionals involved in adult protection. Findings -- The effectiveness of adult safeguarding governance arrangements has not been subject to prior formal evaluation and thus the literature provided little research-led evidence of good practice. The survey and workshops, however , revealed a rich and complex pattern of arrangements spanning a number of dimensions -- the goals and purpose of interagency working, the structures of boards, their membership, chairing and rules of engagement, their functions, and their accountabilities. Research limitations/implications -- The research focus here is England, and thus does not incorporate learning from other jurisdictions. Whilst the research scrutinises the extent to which Boards practise empowerment, service users and carers are not directly involved in the fieldwork aspects of this study. In view of the absence of outcomes evidence identified, there remains a need to investigate the impacts of different forms of governance. Practical implications -- Drawing on this research and on governance frameworks in the context of related interagency fields, the article identifies standards to benchmark the approach to governance taken by Safeguarding Adult Boards. Originality/value -- The benchmarking framework will enable Safeguarding Adults Boards to audit, evaluate, and further develop a range of robust governance arrangements. [ABSTRACT FROM AUTHOR]

Purpose - The research reported here aims to scope the concept of self-neglect as it is explored in the literature and interpreted in practice by professionals involved in adult safeguarding.Design/methodology/approach - The approach taken included a systematic search and thematic analysis of English-language literature on self-neglect, workshops with UK-based adult safeguarding leads and practitioners from social services, police and health services, and scrutiny of Safeguarding Adults Boards' documentation.Findings - The concept of self-neglect is complex with contrasting definitions and aetiology, accompanied by debates on the principles that guide intervention. Decision-making capacity is a key pivot upon which professional responses to self-neglect turn. Intervention in self-neglect requires careful exploration in the context of principles of personalisation, choice, control, and empowerment that underpin policy in adult social care and safeguarding.Research limitations/implications - As a conceptual scoping review, this study seeks to establish broad themes of use to practitioners working with self-neglect. It thus does not carry out a full quality review of the literature identified and discussed, but serves as a base for this to be done in future.Practical implications - Assessment in self-neglect should consider the influence of a number of possible causative factors, and intervention must balance respect for autonomy on the one hand and a perceived duty to preserve health and wellbeing on the other.Originality/value - This article summarises and critically analyses the emerging key features of evidence-informed practice in the challenging field of self-neglect. [ABSTRACT FROM AUTHOR]

• Summary: This article draws on the findings of two research studies: the first a systematic research review and survey of current education practice in teaching law to social workers; the second a 'user review' involving focus groups with a range of stakeholders in practice learning for social work students. • Findings: Although law is recognized as an important component of social work practice, much of the focus on how social workers learn about law has, to date, been upon classroom-based learning. Law often has a low profile in practice, despite the rich opportunities it offers. • Applications: Building from evidence of poor alignment between classroom learning and practice, the authors present an analysis of the barriers and opportunities that exist for enhancing the profile of law in the practice arena and conclude with indicators for the development of good pedagogic practice and improved practitioner confidence. [ABSTRACT FROM AUTHOR]

The opium poppy Papaver somniferum contains an array of opiates. There is a variety of methods of preparation that can be used by people with opiate dependence, with patterns of use determined by numerous factors including cost, safety, potency and legal status. The objective of this study was to determine the frequency and nature of poppy seed tea (PST) use by opiate-dependent patients in the form of a written questionnaire. The study took place at the Community Alcohol and Drug Clinic, Wellington, New Zealand, and comprised 24 opiate-dependent patients attending the clinic. A total of 11 of 24 (46%) patients reported having used PST. In five patients currently using PST it represented the major source of opiates, and two had managed to withdraw from use of other opiates with regular PST use. Patients reported a median onset of action of 15 minures and an effect lasting a median of 24 hours. The major limitation of PST use was the foul taste. PST is used commonly by opiate-dependent patients attending an alcohol and drug clinic in New Zealand. The use of PST as the major source of opiates could be considered favourably within ‘harm reduction’ philosophies, because of its low cost, legal availability and oral route of administration. Conversely, there is the potential for PST to act as a ‘gateway drug’ by inducing opioid dependence and introducing people to the culture of drug abuse. [Braye K, Harwood T, Inder R, Beasley R, Robinson G. Poppy seed tea and opiate abuse in New Zealand. Drug Alcohol Rev 2007;26:215 – 219] [ABSTRACT FROM AUTHOR]

Volatile substance abuse (the deliberate inhalation of substances such as gas fuels, glues, aerosols or other solvent‐based products) by young people does not attract high level attention within the broader arena of drugs education and prevention programmes. Given the prevalence of volatile substances in the lives of vulnerable groups of young people, however, and the risks associated with their misuse, social work education and training might justifiably give a higher profile to the associated needs of young people in need and/or in public care. This paper reports on the findings from a study in England of the training needs of social workers, residential and foster carers in relation to volatile substance abuse by young people, and identifies the implications for further development of training materials and resources. [ABSTRACT FROM AUTHOR]

Significant developments have taken place over recent years in the legal and policy framework for children's participation in decision-making and the role of advocacy within this context. Whilst there is much here to be welcomed, there are also emerging concerns about the nature and direction of advocacy for children and young people in public care. This paper draws on evidence from an empirical study of children's participation in statutory reviews - one of the key arenas for decision-making relating to looked after children - in order to consider critical themes identifiable within the developing field of child advocacy. [ABSTRACT FROM AUTHOR]

In the context of debates about social work's relationship with individuals, the state and civil society, educators face a challenge. How best to ensure that professional education prepares practitioners to engage with the task of promoting social justice and human rights? This article draws on a systematic knowledge review of learning, teaching and assessment of one key subject area in social work education - that of law - to explore the contribution legal knowledge and skills can make to social work's engagement with its vision of empowerment and liberation. [ABSTRACT FROM AUTHOR]

In the context of debates about social work's relationship with individuals, the state and civil society, educators face a challenge. How best to ensure that professional education prepares practitioners to engage with the task of promoting social justice and human rights? This article draws on a systematic knowledge review of learning, teaching and assessment of one key subject area in social work education — that of law — to explore the contribution legal knowledge and skills can make to social work's engagement with its vision of empowerment and liberation. [ABSTRACT FROM AUTHOR]

This article considers the complex relationships between law, welfare policy and social work practice, in order to address the question of what role legal frameworks might play in achieving welfare policy and professional practice goals. It traces how law has developed as a core component of professional practice, and challenges some of the false expectations placed upon it. It then draws on findings from an international knowledge review of law teaching in social work education to propose a model for understanding how professional practice incorporates legal perspectives, and proposes ways in which legal frameworks can provide positive and constructive vehicles for accountable practice. [ABSTRACT FROM AUTHOR]

Abstract: The development of skin substitutes started 25 years ago with the cultivation of keratinocytes to replace the epidermis of extensively burned patients. It is now possible to reproduce in vitro the two layers of skin, epidermis and dermis. Cultured epidermises are now usually used in burn centers dealing with the more severe patients. They are provided by hospital or private laboratories. Dermal substrates are some collagen matrices, which act in vivo as a guide for the reconstruction of a neodermis. Living dermis include living fibroblasts. Different models are now available for clinical use. Living skin equivalent is obtained by coculturing fibroblast and keratinocytes on a collagen support. Clinical essays are going on for chronic wounds. We present the different skin equivalent models and their clinical applications. [Copyright &y& Elsevier]

This paper presents the findings from a systemic review of knowledge relating to current practice in the teaching, learning and assessment of law in social work education. The research comprised an internationally conducted systematic review of the literature, together with a survey of current education practice in the four countries of the UK. Two consultation events sought the views of a range of stakeholders, including the perspectives of service users and carers. Set in the context of debates about the relationship between law and social work practice, this paper identifies the common themes emerging from the review and offers an analysis of key findings, together with priorities for future directions in education practice. [ABSTRACT FROM AUTHOR]

Calls for greater collaboration between professionals in health and social care have led to pressures to move towards interprofessional education at both pre- and postregistration levels. Whilst this move has evolved out of‘common sense’ demands, such a multiple systems approach to education does not fit easily into existing traditional disciplinary frameworks and there is, as yet, no proven theoretical framework to guide its development. What is more, it lacks a clear causality and predictability and therefore does not fit easily into traditional scientific frameworks with their focus on analysis, prediction and control. This article considers how complexity theory, with its focus on connectivity, diversity, self-organization, and emergence, can provide interprofessional education with a coherent theoretical foundation, freeing it from the constraints of a traditional linear framework, enabling it to be better understood, questioned and challenged as a new paradigm of learning. [ABSTRACT FROM AUTHOR]

This paper, written jointly by tutors and students, discusses an enquiry-based approach to learning and assessing law as part of social work qualifying training in England. It is argued that social work law is an area of learning particularly suited to an approach in which enquiry and analysis skills are promoted through practical problem solving. The paper considers the theoretical rationale for this approach and identifies how this conceptual frame informs the learning and assessment structure. It identifies how students present evidence for assessment of their skill and knowledge development, through both written and verbal submission, and considers the learning outcomes achieved. The paper concludes with an evaluation of the approach as an example of knowledge and skill development through problem solving and reflection. [ABSTRACT FROM AUTHOR]

Background: Understanding the resistance mechanisms of tumor is crucial for advancing cancer therapies. The prospective MATCH-R trial (NCT02517892), led by Gustave Roussy, aimed to characterize resistance mechanisms to cancer treatments through molecular analysis of fresh tumor biopsies. This report presents the genomic data analysis of the MATCH-R study conducted from 2015 to 2022 and focuses on targeted therapies. Methods: The study included resistant metastatic patients (pts) who accepted an image-guided tumor biopsy. After evaluation of tumor content (TC) in frozen tissue biopsies, targeted NGS (10 < TC < 30%) or Whole Exome Sequencing and RNA sequencing (TC > 30%) were performed before and/or after the anticancer therapy. Patient-derived xenografts (PDX) were established by implanting tumor fragments into NOD scid gamma mice and amplified up to five passages. Results: A total of 1,120 biopsies were collected from 857 pts with the most frequent tumor types being lung (38.8%), digestive (16.3%) and prostate (14.1%) cancer. Molecular targetable driver were identified in 30.9% (n = 265/857) of the patients, with EGFR (41.5%), FGFR2/3 (15.5%), ALK (11.7%), BRAF (6.8%), and KRAS (5.7%) being the most common altered genes. Furthermore, 66.0% (n = 175/265) had a biopsy at progression on targeted therapy. Among resistant cases, 41.1% (n = 72/175) had no identified molecular mechanism, 32.0% (n = 56/175) showed on-target resistance, and 25.1% (n = 44/175) exhibited a by-pass resistance mechanism. Molecular profiling of the 44 patients with by-pass resistance identified 51 variants, with KRAS (13.7%), PIK3CA (11.8%), PTEN (11.8%), NF2 (7.8%), AKT1 (5.9%), and NF1 (5.9%) being the most altered genes. Treatment was tailored for 45% of the patients with a resistance mechanism identified leading to an 11 months median extension of clinical benefit. A total of 341 biopsies were implanted in mice, successfully establishing 136 PDX models achieving a 39.9% success rate. PDX models are available for EGFR (n = 31), FGFR2/3 (n = 26), KRAS (n = 18), ALK (n = 16), BRAF (n = 6) and NTRK (n = 2) driven cancers. These models closely recapitulate the biology of the original tumors in term of molecular alterations and pharmacological status, and served as valuable models to validate overcoming treatment strategies. Conclusion: The MATCH-R study highlights the feasibility of on purpose image guided tumor biopsies and PDX establishment to characterize resistance mechanisms and guide personalized therapies to improve outcomes in pre-treated metastatic patients. [ABSTRACT FROM AUTHOR]

Discusses accountability in social care services. Role of administrative law in ensuring accountability; Accountability to service users and to professional codes; Mechanisms to ensure accountability.

The development of targeted agents, such as osimertinib for EGFR -mutated non-small-cell lung cancer (NSCLC), has drastically improved patient outcome, but tumor resistance eventually always occurs. In osimertinib-resistant NSCLC, the emergence of a second molecular driver alteration (such as ALK, RET, FGFR3 fusions or BRAF , KRAS mutations) has been described. Whether those alterations and the activating EGFR mutations occur within a single cancer cell or in distinct cell populations is largely debated. Tumor sequencing was used to identify the acquired resistance mechanisms to osimertinib in the MATCH-R trial (NCT0251782). We implemented single-cell next-generation sequencing to investigate tumor heterogeneity on patient's frozen tissues in which multiple alterations have been identified. Patient-derived models, cell lines, and patient-derived xenografts were exposed to specific inhibitors to investigate combination treatment strategies. Among the 45 patients included in MATCH-R who progressed on osimertinib, 9 developed a second targetable alteration (n = 2 FGFR3-TACC3 , n = 1 KIF5B-RET , n = 1 STRN-ALK fusions; n = 2 BRAF V600E , n = 1 KRAS G12V , n = 1 KRAS G12R , n = 1 KRAS G12D mutations). Single-cell analysis revealed that the two driver alterations coexist within one single cancer cell in the four patients whose frozen samples were fully contributive. A high degree of heterogeneity within samples and sequential acquisitions of molecular events were highlighted. A combination treatment concomitantly targeting the two driver alterations was required on the corresponding patient-derived models to restore cell sensitivity, which was consistent with clinical data showing efficacy of brigatinib in the patient with ALK fusion after progression to osimertinib and crizotinib administered sequentially. Distinct molecular driver alterations at osimertinib resistance coexist with initial EGFR mutations in single cancer cells. The clonal evolution of cancer cell populations emphasized their heterogeneity leading to osimertinib relapse. Combining two targeted treatments is effective to achieve clinical benefit. • Clonal architecture of molecular alterations at the cellular level depicts cancer cell adaptation during targeted therapy. • Single-cell sequencing from patient biopsies revealed the coexistence of two driver alterations within single cancer cells. • Pharmacological evaluation in patient-derived models asserts the need for simultaneous inhibition of each driver. [ABSTRACT FROM AUTHOR]

Young boys undergoing gonadotoxic treatments are at high risk of spermatogonial stem cell (SSC) loss and fertility problems later in life. Stem cell loss can also occur in specific genetic conditions, eg, Klinefelter syndrome (KS). Before puberty, these boys do not yet produce sperm. Hence, they cannot benefit from sperm banking. An emerging alternative is the freezing of testicular tissue aiming to preserve the SSCs for eventual autologous transplantation or in vitro maturation at adult age. Many fertility preservation programmes include cryopreservation of immature testicular tissue, although the restoration procedures are still under development. Until the end of 2018, the Universitair Ziekenhuis Brussel has frozen testicular tissues of 112 patients between 8 months and 18 years of age. Testicular tissue was removed in view of gonadotoxic cancer treatment (35%), gonadotoxic conditioning therapy for bone marrow transplantation (35%) or in boys diagnosed with KS (30%). So far, none of these boys had their testicular tissue transplanted back. This article summarizes our experience with cryopreservation of immature testicular tissue over the past 16 years (2002-2018) and describes the key issues for setting up a cryopreservation programme for immature testicular tissue as a means to safeguard the future fertility of boys at high risk of SSC loss. [ABSTRACT FROM AUTHOR]

Young boys undergoing gonadotoxic treatments are at high risk of spermatogonial stem cell (SSC) loss and fertility problems later in life. Stem cell loss can also occur in specific genetic conditions, eg, Klinefelter syndrome (KS). Before puberty, these boys do not yet produce sperm. Hence, they cannot benefit from sperm banking. An emerging alternative is the freezing of testicular tissue aiming to preserve the SSCs for eventual autologous transplantation or in vitro maturation at adult age. Many fertility preservation programmes include cryopreservation of immature testicular tissue, although the restoration procedures are still under development. Until the end of 2018, the Universitair Ziekenhuis Brussel has frozen testicular tissues of 112 patients between 8 months and 18 years of age. Testicular tissue was removed in view of gonadotoxic cancer treatment (35%), gonadotoxic conditioning therapy for bone marrow transplantation (35%) or in boys diagnosed with KS (30%). So far, none of these boys had their testicular tissue transplanted back. This article summarizes our experience with cryopreservation of immature testicular tissue over the past 16 years (2002-2018) and describes the key issues for setting up a cryopreservation programme for immature testicular tissue as a means to safeguard the future fertility of boys at high risk of SSC loss. [ABSTRACT FROM AUTHOR]

Dans le cadre de la reconstruction mammaire par lambeau libre autologue, le lambeau de l'artère fémorale profonde (PAP) prend une place dans les options thérapeutiques de reconstruction microchirurgicales actuelles. Son prélèvement laissant une rançon cicatricielle discrète en fait un choix intéressant. Cette étude anatomique a pour objectif d'analyser la localisation de la perforante du PAP en rapport à des repères fiables et reproductibles, sa surface de vascularisation, la longueur du pédicule ainsi que le rendu volumique de cette vascularisation. Seize lambeaux sont prélevés sur des sujets frais, basés sur la première perforante de l'artère fémorale profonde. Les mesures anatomiques du pédicule (localisation de la perforante, longueur du pédicule ainsi que la localisation de la grande veine saphène interne [VSI]) sont notées. Le trajet du pédicule (musculocutané ou septocutané) est également décrit. Huit lambeaux sont scannés et radiographiés permettant une analyse tomodensitométrique trois dimension et angiographique deux dimension. Les surfaces radiologiques perfusées et les rendus volumiques sont notés. Sur les seize lambeaux analysés, la disposition du pédicule se trouve en moyenne à 7,6 cm du tubercule pubien et à 3,7 cm en arrière d'une ligne reliant ce dernier au condyle fémoral interne. La longueur du pédicule est en moyenne de 11,7 cm et la surface colorée au bleu de méthylène de 94,68 cm2. Le trajet de cette perforante est essentiellement musculocutané. Sur les images radiologiques des huit lambeaux, l'analyse montre une surface de perfusion moyenne de 111,25 cm2 et un rendu volumique moyen de 325,3 cm3. Le lambeau PAP est un choix thérapeutique intéressant dans le cadre d'une reconstruction mammaire. Sa surface et son volume associé à une cicatrice discrète en font une indication valable dans le cadre de cette chirurgie. Within the framework of mammary reconstruction, since 2012 when Allen first described it, the profunda femoral artery perforator flap (PAP) takes an important place in the current therapeutic options. This anatomical study aims to analyze the anatomy and morphologic consideration of the PAP : position of the perforating artery; length of the pedicle, area and volume of vascularization. Sixteen flaps were harvested on fresh subjects at the University Department of Anatomy of Rockfeller, Lyon. The first direct cutaneous branch from the deep femoral vessels was located between or through the adductor magnus and gracilis muscles. Pedicle location, diameter, length and position regard to the great saphenous vein were recorded. A flap based on this vessel was designed. Height, width, and surface of the skin paddle were recorded. Three-dimensional computed tomographic angiography was used to analyze the area and volume of cutaneous territory supplied by the studied perforator. On the 16 analyzed flaps, localization of the perforating artery is on average to 8.2 cm of the pubic tuber and 3.7 cm behind a line connecting the pubic tuber to the internal femoral condyle. The length of the pedicle is on average of 11.7 cm and the average area of skin perfused was 94,68 cm2. The way of this perforating arterty is primarily through the adductor magnus. On the radiological images of the 8 flaps, the analysis shows an average surface of 111,25 cm2 and a mean volume of 325.3 cm3. PAP is an interesting therapeutic choice within the framework of a mammary reconstruction. Its surface and its volume associated with a discrete scar make a valid indication within the framework of this surgery. [ABSTRACT FROM AUTHOR]

Hoarding has become increasingly prominent in clinical practice and popular culture in recent years, giving rise to extensive research and commentary. Critical responses in the social sciences have criticised the cultural assumptions built in to the construct of 'hoarding disorder' and expressed fears that it may generate stigma outweighing its benefits; however, few of these studies have engaged directly with 'hoarders' themselves. This paper reports on in-depth, semi-structured interviews with 10 individuals living in England, who received assessment and intervention for hoarding from Social Services. Their narratives drew on the cultural repertoire of values and discourses around waste and worth, the mediation of sociality and relationships through material objects, physical constraints on keeping order and the role played by mental health. Analysing these perspectives anthropologically shows how dominant models of hoarding, such as the DSM-5 paradigm, potentially lend themselves to reductionist understandings that efface the meaning 'hoarding' may have and thereby deny agency to the person labelled as 'hoarder'. More culturally informed analysis, by contrast, affords insights into the complex landscape of value, waste, social critique, emotion, interpersonal relationships and practical difficulties that may underlie hoarding cases, and points the way to more person-centred practice and analysis. [ABSTRACT FROM AUTHOR]

Objective: To assess whether testicular cell dynamics are altered during long-term culture after testicular tissue cryopreservation.Design: Experimental basic science study.Setting: Reproductive biology laboratory.Patient(s): Testicular tissue with normal spermatogenesis was obtained from six donors.Intervention(s): None.Main Outcome Measure(s): Detection and comparison of testicular cells from fresh and frozen tissues during long-term culture.Result(s): Human testicular cells derived from fresh (n = 3) and cryopreserved (n = 3) tissues were cultured for 2 months and analyzed with quantitative reverse-transcription polymerase chain reaction and immunofluorescence. Spermatogonia including spermatogonial stem cells (SSCs) were reliably detected by combining VASA, a germ cell marker, with UCHL1, a marker expressed by spermatogonia. The established markers STAR, ACTA2, and SOX9 were used to analyze the presence of Leydig cells, peritubular myoid cells, and Sertoli cells, respectively. No obvious differences were found between the cultures initiated from fresh or cryopreserved tissues. Single or small groups of SSCs (VASA(+)/UCHL1(+)) were detected in considerable amounts up to 1 month of culture, but infrequently after 2 months. SSCs were found attached to the feeder monolayer, which expressed markers for Sertoli cells, Leydig cells, and peritubular myoid cells. In addition, VASA(-)/UCHL1(+) cells, most likely originating from the interstitium, also contributed to this monolayer. Apart from Sertoli cells, all somatic cell types could be detected throughout the culture period.Conclusion(s): Testicular tissue can be cryopreserved before long-term culture without modifying its outcome, which encourages implementation of testicular tissue banking for fertility preservation. However, because of the limited numbers of SSCs available after 2 months, further exploration and optimization of the culture system is needed. [ABSTRACT FROM AUTHOR]

The article deals with issues concerning mental health and mental health services in Great Britain. Mental health law is the subject of review following high profile tragedies and inspection reports as a result of mental illness. These have highlighted fragmentary provision, doubts about inter-agency coordination and concerns about whether people are receiving appropriate treatment, assessment, support and reviews. The introduction of supervision registers and, through the Mental Health Act 1995, of supervised discharge orders, has raised concerns about the possible erosion of service users' rights in the name of public protection. Concerns about patchy implementation of services for people with mental health needs have also resulted in proposals to modernize social services. Health and local authorities will be required to set standards of care and treatment, to assess the mental health and social care needs of their population and to evaluate service performance and prepare plans to address gaps and pressures in services. Mental health law, policy and practice remain a highly contested area. Social workers have not always recognized and responded to mental health needs. Education and training must prepare then with the values, knowledge and skills for effective work with service users and their carers and with the confidence for intervening in the policy context.

Objective: The aim of this project was to assess the interobserver and intraobserver variability when identifying cytological criteria, which were found to have a statistically significant association with C3 within a workplace environment. Methods: Sixty C3 cases with known endpoints of malignant, benign proliferative or benign non‐proliferative diagnoses were blindly and independently screened by seven experienced cytologists to identify previously reported statistically significant criteria associated with the C3 category. The criteria included the presence of myoepithelial cells or bare bipolar nuclei, cohesiveness, cystic background, papillary fragments with fibrovascular cores and tubular structures. Kappa statistics were used to measure interobserver variability. Two cytologists repeated the process 6 months later to obtain intraobserver data. Results: The interobserver agreement was poor for all criteria except tubules which performed badly. The intraobserver variability for the two cytologists showed that one cytologist achieved moderate intraobserver agreement for all the criteria except cohesion which was poor, whilst the second cytologist showed poor agreement for all criteria. The reasons for the variability are multifactorial and include threshold effects where criteria lack good definition or error in identifying the criteria. Conclusion: Interobserver and intraobserver variability remains a significant challenge for cytologists. Despite attempts to define significant criteria associated with C3, good reproducibility could not be achieved. The C3 category is imprecise and highlights the inadequacy of the current classification reporting categories for breast FNA. The impending review of reporting breast cytology by the International Academy of Cytology is timely and appropriate. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-associated death rates. Triple negative breast cancers represent an important subtype that have an aggressive clinical phenotype, are associated with a higher likelihood of metastasis and are not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for molecular biomarkers and treatment targets in breast cancer, but their role in the progression of triple negative breast cancer remains largely unexplored.Methods: This study has investigated miRNA expression profiles in 31 primary triple negative breast cancer cases and in 13 matched lymph node metastases compared with 23 matched normal breast tissues to determine miRNAs associated with the initiation of this disease subtype and those associated with its metastasis.Results: 71 miRNAs were differentially expressed in triple negative breast cancer, the majority of which have previously been associated with breast cancer, including members of the miR-200 family and the miR-17-92 oncogenic cluster, suggesting that the majority of miRNAs involved in the initiation of triple negative breast cancer are not subtype specific. However, the repertoire of miRNAs expressed in lymph node negative and lymph node positive triple negative breast cancers were largely distinct from one another. In particular, miRNA profiles associated with lymph node negative disease tended to be up-regulated, while those associated with lymph node positive disease were down-regulated and largely overlapped with the profiles of their matched lymph node metastases. From this, 27 miRNAs were identified that are associated with metastatic capability in the triple negative breast cancer subtype.Conclusions: These results provide novel insight into the repertoire of miRNAs that contribute to the initiation of and progression to lymph node metastasis in triple negative breast cancer and have important implications for the treatment of this breast cancer subtype. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignancy in women world-wide. Triple negative breast cancer (TNBC) is a highly aggressive subtype that lacks expression of hormone receptors for estrogen, progesterone and human epidermal growth factor 2; and is associated with a high propensity for metastatic spread. Several studies have identified critical roles for microRNAs in breast cancer, but the role of two critical enzymes involved in microRNA biogenesis, Dicer and Drosha, is not well understood, particularly with respect to metastatic progression in this subtype.Methods: We examined the expression of Dicer and Drosha in a series of invasive 35 TNBCs with matched normal adjacent tissues (n = 18) and lymph node metastases (n = 15) using semi-quantitative real time RT-PCR. The relationship of their expression with clinical features including age at diagnosis, lymph node positivity and tumour size was analysed.Results: We report that Dicer was significantly decreased while Drosha was significantly increased in tumours when compared to normal adjacent tissues. While there was no difference in Drosha expression in lymph node metastases when compared to the primary tumour, Dicer was significantly increased. There was no correlation between the expression of either Dicer or Drosha to age at diagnosis, lymph node positivity and tumour size.Conclusions: In conclusion, Dicer and Drosha are dysregulated in TNBC and matched lymph node metastases however, the clinical relevance of this is still not known. The altered expression of Dicer and Drosha may serve as markers for disrupted miRNA biogenesis in TNBC. [ABSTRACT FROM AUTHOR]