Depolarization of sperm membrane potential is a common feature of men with subfertility and is associated with low fertilization rate at IVF

STUDY QUESTION. Are significant abnormalities in outward (K+) conductance and resting membrane potential (Vm) present in the spermatozoa of patients undertaking IVF and ICSI and if so, what is their functional effect on fertilization success? SUMMARY ANSWER. Negligible outward conductance (≈5% of patients) or an enhanced inward conductance (≈4% of patients), both of which caused depolarization of Vm, were associated with a low rate of fertilization following IVF. WHAT IS KNOWN ALREADY. Sperm-specific potassium channel knockout mice are infertile with defects in sperm function, suggesting that these channels are essential for fertility. These observations suggest that malfunction of K+ channels in human spermatozoa might contribute significantly to the occurrence of subfertility in men. However, remarkably little is known of the nature of K+ channels in human spermatozoa or the incidence and functional consequences of K+ channel defects. STUDY DESIGN, SIZE AND DURATION. Spermatozoa were obtained from healthy volunteer research donors and subfertile IVF and ICSI patients attending a hospital assisted reproductive techniques clinic between May 2013 and December 2015. In total, 40 IVF patients, 41 ICSI patients and 26 normozoospermic donors took part in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS. Samples were examined using electrophysiology (whole-cell patch clamping). Where abnormal electrophysiological characteristics were identified, spermatozoa were further examined for Ca2+ influx induced by progesterone and penetration into viscous media if sufficient sample was available. Full exome sequencing was performed to specifically evaluate potassium calcium-activated channel subfamily M α 1 (KCNMA1), potassium calcium-activated channel subfamily U member 1 (KCNU1) and leucine-rich repeat containing 52 (LRRC52) genes and others associated with K+ signalling. In IVF patients, comparison with fertilization rates was done to assess the functional significance of the electrophysiological abnormalities. MAIN RESULTS AND THE ROLE OF CHANCE. Patch clamp electrophysiology was used to assess outward (K+) conductance and resting membrane potential (Vm) and signalling/motility assays were used to assess functional characteristics of sperm from IVF and ICSI patient samples. The mean Vm and outward membrane conductance in sperm from IVF and ICSI patients were not significantly different from those of control (donor) sperm prepared under the same conditions, but variation between individuals was significantly greater (P< 0.02) with a large number of outliers (>25%). In particular, in ≈10% of patients (7/81), we observed either a negligible outward conductance (4 patients) or an enhanced inward current (3 patients), both of which caused depolarization of Vm. Analysis of clinical data from the IVF patients showed significant association of depolarized Vm (≥0 mV) with low fertilization rate (P= 0.012). Spermatozoa with electrophysiological abnormities (conductance and Vm) responded normally to progesterone with elevation of [Ca2+]i and penetration of viscous medium, indicating retention of cation channel of sperm (CatSper) channel function. LIMITATIONS, REASONS FOR CAUTION. For practical, technical, ethical and logistical reasons, we could not obtain sufficient additional semen samples from men with conductance abnormalities to establish the cause of the conductance defects. Full exome sequencing was only available in two men with conductance defects. WIDER IMPLICATIONS OF THE FINDINGS. These data add significantly to the understanding of the role of ion channels in human sperm function and its impact on male fertility. Impaired potassium channel conductance (Gm) and/or Vm regulation is both common and complex in human spermatozoa and importantly is associated with impaired fertilization capacity when the Vm of cells is completely depolarized.

Growing up in a mainstream world: a retrospective enquiry into the childhood experiences of young adults with a physical disability.

Children with disabilities are at greater risk of developing mental health problems than their peers, yet the emotional well-being of this group is largely overlooked and there is scant literature about children with a mobility disability. This study examined the retrospective experiences of growing up with mobility disability. The sample comprised of 16-25 year olds with mobility disability. A thematic analysis, informed by grounded theory was used. Themes identified included a common socio educational journey, conflict between care and independence in school and the impact of being singled out because of disability out side school. The result was a range of psycho-social issues that affected participants view of themselves and the world around them. The study also looked at what the participants found helpful in dealing with the emotional impact of their disability. Whilst some sought help through talking therapies, others found involvement in disability sport was helpful.

Mental health nurses’ attitudes, behaviour, experience and knowledge regarding adults with a diagnosis of borderline personality disorder: systematic, integrative literature review

Aims and objectives To establish whether mental health nurses responses to people with borderline personality disorder are problematic and, if so, to inform solutions to support change. Background There is some evidence that people diagnosed with borderline personality disorder are unpopular among mental health nurses who respond to them in ways which could be counter-therapeutic. Interventions to improve nurses’ attitudes have had limited success. Design Systematic, integrative literature review. Methods Computerised databases were searched from inception to April 2015 for papers describing primary research focused on mental health nurses’ attitudes, behaviour, experience, and knowledge regarding adults diagnosed with borderline personality disorder. Analysis of qualitative studies employed metasynthesis; analysis of quantitative studies was informed by the theory of planned behaviour. Results Forty studies were included. Only one used direct observation of clinical practice. Nurses’ knowledge and experiences vary widely. They find the group very challenging to work with, report having many training needs, and, objectively, their attitudes are poorer than other professionals’ and poorer than towards other diagnostic groups. Nurses say they need a coherent therapeutic framework to guide their practice, and their experience of caregiving seems improved where this exists. Conclusions Mental health nurses’ responses to people with borderline personality disorder are sometimes counter-therapeutic. As interventions to change them have had limited success there is a need for fresh thinking. Observational research to better understand the link between attitudes and clinical practice is required. Evidence-based education about borderline personality disorder is necessary, but developing nurses to lead in the design, implementation and teaching of coherent therapeutic frameworks may have greater benefits. Relevance to clinical practice There should be greater focus on development and implementation of a team-wide approach, with nurses as equal partners, when working with patients with borderline personality disorder.