Induced pluripotent stem cells derived from patients carrying mitochondrial mutations exhibit altered bioenergetics and aberrant differentiation potential.

BACKGROUND: Human mitochondrial DNA mutations are associated with common to rare mitochondrial disorders, which are multisystemic with complex clinical pathologies. The pathologies of these diseases are poorly understood and have no FDA-approved treatments leading to symptom management. Leigh syndrome (LS) is a pediatric mitochondrial disorder that affects the central nervous system during early development and causes death in infancy. Since there are no adequate models for understanding the rapid fatality associated with LS, human-induced pluripotent stem cell (hiPSC) technology has been recognized as a useful approach to generate patient-specific stem cells for disease modeling and understanding the origins of the phenotype. METHODS: hiPSCs were generated from control BJ and four disease fibroblast lines using a cocktail of non-modified reprogramming and immune evasion mRNAs and microRNAs. Expression of hiPSC-associated intracellular and cell surface markers was identified by immunofluorescence and flow cytometry. Karyotyping of hiPSCs was performed with cytogenetic analysis. Sanger and next-generation sequencing were used to detect and quantify the mutation in all hiPSCs. The mitochondrial respiration ability and glycolytic function were measured by the Seahorse Bioscience XFe96 extracellular flux analyzer. RESULTS: Reprogrammed hiPSCs expressed pluripotent stem cell markers including transcription factors POU5F1, NANOG and SOX2 and cell surface markers SSEA4, TRA-1-60 and TRA-1-81 at the protein level. Sanger sequencing analysis confirmed the presence of mutations in all reprogrammed hiPSCs. Next-generation sequencing demonstrated the variable presence of mutant mtDNA in reprogrammed hiPSCs. Cytogenetic analyses confirmed the presence of normal karyotype in all reprogrammed hiPSCs. Patient-derived hiPSCs demonstrated decreased maximal mitochondrial respiration, while mitochondrial ATP production was not significantly different between the control and disease hiPSCs. In line with low maximal respiration, the spare respiratory capacity was lower in all the disease hiPSCs. The hiPSCs also demonstrated neural and cardiac differentiation potential. CONCLUSION: Overall, the hiPSCs exhibited variable mitochondrial dysfunction that may alter their differentiation potential and provide key insights into clinically relevant developmental perturbations.

Delivery of multiple ecosystem services in pasture by shelter created from the hybrid sterile bioenergy grass Miscanthus x giganteus.

The benefits of shelter in increasing crop yields and accelerating ripening has been well researched in fruit, arable and horticultural crops. Its benefits to pasture, despite its importance for livestock production, is less well researched. In this work, Miscanthus shelterbelts were established on an intensively irrigated dairy farm. Seven key ecosystem services associated with these belts were identified and quantified. Pasture yield and quality were recorded in Miscanthus-sheltered and control field boundaries with little shelter. Pasture yield increased by up to 14% in the sheltered areas downwind of Miscanthus. Pasture quality was equivalent in the sheltered and open areas. Miscanthus provided more favourable nesting sites for bumblebees and for New Zealand endemic lizards (skinks) compared to field boundaries. The sheltered areas also had higher mineralisation rates of organic matter and higher numbers of earthworms. Using a high-yielding sterile grass such as Miscanthus to deliver a wide range of ecosystem services also produced a bioenergy feedstock. In conclusion, full benefits of shelterbelts to the farming system cannot be fully assessed unless direct and indirect benefits are properly assessed, as in this work.

Nursing interventions for preventing alcohol-related harm.

Harrington-Dobinson and Blows recently provided a three-part series of articles on alcohol, its consequences for health and wellbeing, and the role of the nurse. Their third article outlined the health education and health promotion role of the nurse. They outlined basic principles for nursing practice in relation to the patient with alcohol dependence in the acute general hospital. The authors of this article believe that much more can, and must, be said in relation to the vital issue of nurses' clinical interventions for alcohol. This article builds on the third article from Harrington-Dobinson and Blows by outlining, in more concrete terms, how nurses in all settings can effectively intervene with patients. It introduces the current evidence-based guidelines in this area and use the 'consensus model' contained within them to describe the process of effective alcohol intervention. Using dialogue examples to illustrate the research, the authors introduce the literature on brief interventions and motivational interviewing to the nursing audience.

Does socio-economic status influence the acceptability of, attendance for, and outcome of, screening and brief interventions for alcohol misuse: a review.

AIMS: To determine whether socio-economic status (SES) influences (i) willingness to participate in brief intervention (BI) research, (ii) attendance to receive BI once allocated, and (iii) treatment outcome. METHODS: Systematic review of published, randomised controlled trials of BI for non-dependent alcohol misuse in primary health care settings. RESULTS: Eighteen papers met inclusion criteria. There is evidence that once recruited, and following attendance for intervention, participants' SES does not influence treatment outcome. However, the effect of choosing to participate remains unclear, and the generalizability of results to the whole primary care population remains equivocal. Socio-economic status may influence willingness to participate in BI treatment research, and may influence attendance to receive such interventions where allocated. CONCLUSION: Brief interventions should remain available to all non-dependent hazardous and harmful drinkers in primary care. However, fidelity to research design is suggested to allow for any participation effects to occur. Benefits of such an approach exist for both clinicians and patients. The characteristics of those who participate in BI trials, compared to those who do not, should be studied in detail. Socio-economic variables should be included as potentially important characteristics. The impact of BI on drinking style as well as consumption needs further attention.

Links between drug and alcohol misuse and psychiatric disorders.

Substance use is common in a wide range of psychiatric disorders. Psychiatric disorder can increase the risks of such use developing into a substance use disorder. Conversely, substance use disorders are frequently accompanied by psychiatric symptoms. In some people such symptoms indicate formal psychiatric disorder. Whatever the causes, comorbidity may complicate treatment and resolution of both disorders, often presenting as a vicious circle that is difficult to break.

Understanding the nurse's role in improving suicide prevention.

This article considers the role of non-specialist nursing staff in suicide prevention. It is not expected that such staff could or should undertake in-depth risk assessment or treatment intervention with suicidal individuals. Rather their importance is in identifying those at potential risk for suicide, and securing specialist assessment and intervention for them.

Management of intentional overdose in A&E departments.

This guided reflection article discusses the biological, psychological and social causes of intentional overdose and how the A&E nurse can treat the suicidal patient. The author shows how nurses in A&E can provide interventions that address patients' physical and psychosocial needs. The correct acute response to the medications commonly taken in an intentional overdose case are described. These interventions promote patient survival, improve concordance with mental health follow-up and reduce recidivism.

Comorbid chronic non-cancer pain and opioid use disorders.

Patients with chronic non-cancer pain and opioid dependence are difficult to treat effectively. This article reviews the common issues that arise in relation to assessment and treatment, and recommends the adoption of an integrated approach to this patient population.

Critical realism and psychiatric nursing: a philosophical inquiry.

BACKGROUND: There is a tension within contemporary psychiatric nursing between those who would embrace the knowledge and methods of psychiatry and psychology, and those who instead argue for the development of an autonomous nursing profession. This tension cannot be resolved by way of the underpinning philosophies of these positions, namely empiricism and idealism. Instead, critical realism, positioned between these philosophies offers a methodology through which to seek a new paradigm. AIM: This paper aims to determine whether psychiatric nursing has the potential to exist as an independent and autonomous profession, concerned with providing a helping response to those in mental distress. METHOD: The paper asks critical realism's transcendental question in order to identify the a priori requirements of an autonomous psychiatric nursing, independent of both psychiatry and psychology. Consideration of these a priori requirements includes selected information from contemporary texts in order to identify potentially helpful nursing responses to mental distress, as opposed to the theorising that surrounds these helping responses. FINDINGS: The theories of psychiatry and psychology are neither necessary nor sufficient in providing a foundation for an autonomous psychiatric nursing. While medications have an intrinsic helpfulness for some people, for some of their problems, for some of the time, this does not illuminate the causes of mental distress. There is an intrinsic helping response in human interpersonal communication, yet this is not specific to 'psychotherapy' and does not 'belong' solely to psychotherapists. CONCLUSION: Support is found for an autonomous and independent profession of psychiatric nursing, able to provide a helping response to those in mental distress independent of psychiatry and psychology.