Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

"Sometimes we can't fix things": A qualitative study of health care professionals' perceptions of end of life care for patients with heart failure

Background Although heart failure has a worse prognosis than some cancers, patients often have restricted access to well-developed end of life (EoL) models of care. Studies show that patients with advanced heart failure may have a poor understanding of their condition and its outcome and, therefore, miss opportunities to discuss their wishes for EoL care and preferred place of death. We aimed to explore the perceptions and experiences of health care professionals (HCPs) working with patients with heart failure around EoL care. Design A qualitative in-depth interview study nested in a wider ethnographic study of unplanned admissions in patients with heart failure (HoldFAST). We interviewed 24 HCPs across primary, secondary and community care in three locations in England, UK – the Midlands, South Central and South West. Results The study revealed three issues impacting on EoL care for heart failure patients. Firstly, HCPs discussed approaches to communicating with patients about death and highlighted the challenges involved. HCPs would like to have conversations with patients and families about death and dying but are aware that patient preferences are not easy to predict. Secondly, professionals acknowledged difficulties recognising when patients have reached the end of their life. Lack of communication between patients and professionals can result in situations where inappropriate treatment takes place at the end of patients’ lives. Thirdly, HCPs discussed the struggle to find alternatives to hospital admission for patients at the end of their life. Patients may be hospitalised because of a lack of planning which would enable them to die at home, if they so wished. Conclusions The HCPs regarded opportunities for patients with heart failure to have ongoing discussions about their EoL care with clinicians they know as essential. These key professionals can help co-ordinate care and support in the terminal phase of the condition. Links between heart failure teams and specialist palliative care services appear to benefit patients, and further sharing of expertise between teams is recommended. Further research is needed to develop prognostic models to indicate when a transition to palliation is required and to evaluate specialist palliative care services where heart failure patients are included

Compositional and Functional Considerations for Bovine-, Caprine- and Plant-Based Infant Formulas

Breastmilk is the optimal source of nutrition for infants. However, in circumstances where breastfeeding is not possible or feasible, infant formula provides an essential alternative to fulfil the nutritional requirements of the developing infant. Traditionally, the manufacture of infant formula has involved utilisation of bovine milk as a base ingredient, formulated with other nutrients and bioactive ingredients to closely match the composition of human breastmilk. While it is the most widely available type of formula on the market, bovine-based infant formula is not suitable for all infants, and therefore alternatives such as those based on caprine milk, soy and rice protein are becoming increasingly available. This review provides a detailed examination of the composition of infant formula prepared from bovine milk, caprine milk, soy, and rice protein sources. Available literature on nutrient bio-accessibility and aspects of protein functionality relevant to infant formula is discussed

Religious leaders’ perceptions of advance care planning: a secondary analysis of interviews with Buddhist, Christian, Hindu, Islamic, Jewish, Sikh and Bahá’í leaders

Abstract Background International guidance for advance care planning (ACP) supports the integration of spiritual and religious aspects of care within the planning process. Religious leaders’ perspectives could improve how ACP programs respect patients’ faith backgrounds. This study aimed to examine: (i) how religious leaders understand and consider ACP and its implications, including (ii) how religion affects followers’ approaches to end-of-life care and ACP, and (iii) their implications for healthcare. Methods Interview transcripts from a primary qualitative study conducted with religious leaders to inform an ACP website, ACPTalk, were used as data in this study. ACPTalk aims to assist health professionals conduct sensitive conversations with people from different religious backgrounds. A qualitative secondary analysis conducted on the interview transcripts focussed on religious leaders’ statements related to this study’s aims. Interview transcripts were thematically analysed using an inductive, comparative, and cyclical procedure informed by grounded theory. Results Thirty-five religious leaders (26 male; mean 58.6-years-old), from eight Christian and six non-Christian (Jewish, Buddhist, Islamic, Hindu, Sikh, Bahá’í) backgrounds were included. Three themes emerged which focussed on: religious leaders’ ACP understanding and experiences; explanations for religious followers’ approaches towards end-of-life care; and health professionals’ need to enquire about how religion matters. Most leaders had some understanding of ACP and, once fully comprehended, most held ACP in positive regard. Religious followers’ preferences for end-of-life care reflected family and geographical origins, cultural traditions, personal attitudes, and religiosity and faith interpretations. Implications for healthcare included the importance of avoiding generalisations and openness to individualised and/ or standardised religious expressions of one’s religion. Conclusions Knowledge of religious beliefs and values around death and dying could be useful in preparing health professionals for ACP with patients from different religions but equally important is avoidance of assumptions. Community-based initiatives, programs and faith settings are an avenue that could be used to increase awareness of ACP among religious followers’ communities

Extending awareness of Catholic healthcare ethics among junior clinicians : A qualitative study

As Catholic healthcare organizations form a substantive part of healthcare delivery in the USA and Australia, ethical standards for Catholic health care were developed to guide practice. This study examined junior staff’s understanding of Catholic ethics. Using a qualitative descriptive design, we recruited 22 medical and nursing staff to interviews/focus groups. Though Catholic ethics seldom informed ethical approaches, the principles were acknowledged as being useful to support development of confident and respectful care approaches. Findings provide early insights into challenges faced in considering implementation of ethical codes across both secular and religious healthcare organizations, suggesting that a more creative and pastoral approach to dialoguing and implementing Catholic ethics is required

Adenylate kinase 9 is essential for sperm function and male fertility in mammals

Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (AK9) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.ISSN:0027-8424ISSN:1091-649