Sexual health and fertility in Duchenne muscular dystrophy—An exploratory study

Introduction/Aims Recent clinical guidelines recommend that adolescents with Duchenne muscular dystrophy (DMD) who are on daily glucocorticoid treatment should be offered pubertal induction in order to ensure adult levels of sex hormones as they reach adulthood. However, it remains unclear how gonadal status, including androgen concentrations, impacts physical function and future fertility. The aim of this study was to give a voice to adults with DMD, exploring their perspectives around sexual health, hormone treatment, and fertility. Methods Qualitative data was collected from six adults with DMD through two online focus groups. Participants were recruited through Pathfinders Neuromuscular Alliance and Duchenne UK and invited to take part if they had DMD and were 18 years of age or older. Conversations were transcribed verbatim and an interpretivist paradigm was used with thematic analysis. Results The main themes identified were (1) the need for communication and information about sexual health, (2) dealing with the potential fear of rejection, (3) physical barriers to relationships including sex, (4) testosterone supplementation in DMD, and (5) parenthood and fertility. Discussion We recommend that clinicians work with young people with DMD individually, to explore the benefits of testosterone treatment for them and their personal sexual health needs. If they are offered treatment, this should always be accompanied by the opportunity for psychological support. This work highlights the need for further research to establish the role of testosterone supplementation in adults with DMD and its effects on fertility and the value of specific emotional and practical support for sexual health

NNT pseudoexon activation as a novel mechanism for disease in two siblings with familial glucocorticoid deficiency

CONTEXT: Intronic DNA frequently encodes potential exonic sequences called pseudoexons. In recent years, mutations resulting in aberrant pseudoexon inclusion have been increasingly recognized to cause disease. OBJECTIVES: To find the genetic cause of familial glucocorticoid deficiency (FGD) in two siblings. PATIENTS: The proband and his affected sibling, from nonconsanguineous parents of East Asian and South African origin, were diagnosed with FGD at the ages of 21 and 8 months, respectively. DESIGN: Whole exome sequencing was performed on genomic DNA (gDNA) of the siblings. Variants in genes known to cause FGD were assessed for causality. Further analysis of gDNA and cDNA was performed by PCR/RT-PCR followed by automated Sanger sequencing. RESULTS: Whole exome sequencing identified a single, novel heterozygous variant (p.Arg71*) in nicotinamide nucleotide transhydrogenase (NNT) in both affected individuals. Follow-up cDNA analysis in the proband identified a 69-bp pseudoexon inclusion event, and Sanger sequencing of his gDNA identified a 4-bp duplication responsible for its activation. The variants segregated with the disease: p.Arg71* was inherited from the mother, the pseudoexon change was inherited from the father, and an unaffected sibling had inherited only the p.Arg71* variant. CONCLUSIONS: FGD in these siblings is caused by compound heterozygous mutations in NNT; one causing pseudoexon inclusion in combination with another leading to Arg71*. Discovery of this pseudoexon activation mutation highlights the importance of identifying sequence changes in introns by cDNA analysis. The clinical implications of these findings include: facilitation of antenatal genetic diagnosis, early institution of potentially lifesaving therapy, and the possibility of preventative or curative interventio

An investigation into unusual access sites for arterial endovascular interventions

The endovascular revolution has transformed clinical practice with significant benefits to patients, in particular, as minimally invasive treatment options for those who would have previously been deemed inoperable by conventional ‘open’ surgical techniques. However, it is impossible to perform arterial endovascular interventions without accessing the arterial system first. Despite close to 100 years of technological and procedural improvement, the femoral artery remains the gold standard arterial access site. In those patients where femoral arterial access is contraindicated, alternative access sites have been described. The majority of these access sites are standard alternatives and are already used in routine clinical practice. However, other arterial access sites are more unusual, and their use is potentially more harmful to patients than standard access. As a vascular, endovascular and aortic surgeon, I have a varied practice that ranges from traditional open surgery to arterial endovascular interventions, creating alternative vascular access for other specialties who may require it and also repairing the complications arising from vascular access as well. I remain keen to maximise the benefits of endovascular surgery for all my patients, even if femoral arterial access is contraindicated. This led me to investigate unusual arterial access sites for arterial endovascular interventions. Some of the early descriptions in the literature of unusual access sites for arterial endovascular interventions were not just radical but potentially significantly harmful to patients. A lack of pooled contemporary evidence was sorely lacking, and I embarked on this body of work to fill that evidence gap. My ultimate aim was to educate myself and my colleagues who may also require unusual access sites in their clinical practice, whilst keeping patient safety at the forefront and of paramount importance

Sexual health and fertility in Duchenne muscular dystrophy - an exploratory study

Introduction/AimsRecent clinical guidelines recommend that adolescents with Duchenne muscular dystrophy (DMD) who are on daily glucocorticoid treatment should be offered pubertal induction in order to ensure adult levels of sex hormones as they reach adulthood. However, it remains unclear how gonadal status, including androgen concentrations, impacts physical function and future fertility. The aim of this study was to give a voice to adults with DMD, exploring their perspectives around sexual health, hormone treatment, and fertility.MethodsQualitative data was collected from six adults with DMD through two online focus groups. Participants were recruited through Pathfinders Neuromuscular Alliance and Duchenne UK and invited to take part if they had DMD and were 18 years of age or older. Conversations were transcribed verbatim and an interpretivist paradigm was used with thematic analysis.ResultsThe main themes identified were (1) the need for communication and information about sexual health, (2) dealing with the potential fear of rejection, (3) physical barriers to relationships including sex, (4) testosterone supplementation in DMD, and (5) parenthood and fertility.DiscussionWe recommend that clinicians work with young people with DMD individually, to explore the benefits of testosterone treatment for them and their personal sexual health needs. If they are offered treatment, this should always be accompanied by the opportunity for psychological support. This work highlights the need for further research to establish the role of testosterone supplementation in adults with DMD and its effects on fertility and the value of specific emotional and practical support for sexual health

D0−Dˉ0D^0 - \bar D^0 Mixing in the Presence of Isosinglet Quarks

We analyse $\Delta C=2$ transitions in the framework of a minimal extension of the Standard Model where either a $Q=2/3$ or a $Q=-1/3$ isosinglet quark is added to the standard quark spectrum. In the case of a $Q=2/3$ isosinglet quark, it is shown that there is a significant region of parameter space where $D^0 - \bar D^0$ mixing is sufficiently enhanced to be observed at the next round of experiments. On the contrary, in the case of a $Q=-1/3$ isosinglet quark, it is pointed out that obtaining a substancial enhancement of $D^0 - \bar D^0$ mixing, while complying with the experimental constraints on rare kaon decays, requires a contrived choice of parameters.Comment: 10 pages plus four figures. The figures are not included but are available upon reques

Lanczos exact diagonalization study of field-induced phase transition for Ising and Heisenberg antiferromagnets

Using an exact diagonalization treatment of Ising and Heisenberg model Hamiltonians, we study field-induced phase transition for two-dimensional antiferromagnets. For the system of Ising antiferromagnet the predicted field-induced phase transition is of first order, while for the system of Heisenberg antiferromagnet it is the second-order transition. We find from the exact diagonalization calculations that the second-order phase transition (metamagnetism) occurs through a spin-flop process as an intermediate step.Comment: 4 pages, 4 figure

Peripheral primitive neuroectodermal tumour - A rare cause of a popliteal fossa mass: A case report and review of the literature

A literature review of peripheral primitive neuroectodermal tumours, illustrated with an index case report describing an 80-year-old woman who presented with a mass in the left popliteal fossa, is reported. An excision biopsy was performed, revealing a possible peripheral primitive neuroectodermal tumour as the primary pathology. Normally confined to the chest wall and axial soft tissues of children and young adults, reports of this tumour existing in other areas and in the elderly population are scarce

A spin-dependent local moment approach to the Anderson impurity model

We present an extension of the local moment approach to the Anderson impurity model with spin-dependent hybridization. By employing the two-self-energy description, as originally proposed by Logan and co-workers, we applied the symmetry restoration condition for the case with spin-dependent hybridization. Self-consistent ground states were determined through variational minimization of the ground state energy. The results obtained with our spin-dependent local moment approach applied to a quantum dot system coupled to ferromagnetic leads are in good agreement with those obtained from previous work using numerical renormalization group calculations

The Full Range of Predictions for B Physics From Iso-singlet Down Quark Mixing

We extend the range of predictions of the isosinglet (or vector) down quark model to the fully allowed physical ranges, and also update this with the effect of new physics constraints. We constrain the present allowed ranges of sin(2*beta) and sin(2*alpha), gamma, x_s, and A_{B_s}. In models allowing mixing to a new isosinglet down quark (as in E_6) flavor changing neutral currents are induced that allow a Z^0 mediated contribution to B-Bbar mixing and which bring in new phases. In (rho, eta), (x_s, sin(gamma)), and (x_s, A_{B_s}) plots for the extra isosinglet down quark model which are herein extended to the full physical range, we find new allowed regions that will require experiments on sin(gamma) and/or x_s to verify or to rule out an extra down quark contribution.Comment: 13 pages in RevTeX, 7 postscript figure