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Duchenne muscular dystrophy (DMD) is one of the most prevalent X-linked inherited neuromuscular disorders, with an estimated incidence between 1 in 3500 and 5000 live male births. The median life expectancy at birth is around 30 years due to a rapid and severe disease progression. Currently, there is no cure for DMD, and the standard of care is mainly palliative therapy and glucocorticoids to mitigate symptoms and improve quality of life. Recent advances in phosphorodiamidate morpholino antisense oligonucleotide (PMO) technology has proven optimistic in providing a disease-modifying therapy rather than a palliative treatment option through correcting the primary genetic defect of DMD by exon skipping. However, as a result of the high variance in mutations of the dystrophin gene causing DMD, it has been challenging to tailor an effective therapy in most patients. Viltolarsen is effective in 8% of patients and accurately skips exon 53, reestablishing the reading frame and producing a functional form of dystrophin and milder disease phenotype. Results of recently concluded preclinical and clinical trials show significantly increased dystrophin protein expression, no severe adverse effects, and stabilization of motor function. In summary, viltolarsen has provided hope for those working toward giving patients a safe and viable treatment option for managing DMD. This review summarizes an overview of the presentation, pathophysiology, genetics, and current treatment guidelines of DMD, pharmacological profile of viltolarsen, and a summary of the safety and efficacy with additional insights using recent clinical trial data. [ABSTRACT FROM AUTHOR]

This article describes the outcomes of five years of the face-to-face, group-based carbohydrate counting education programme Cook and Eat, described previously in this journal. Ninety-four attendees aged 16 years or under were compared with ninety-four non-attendees matched for age and diabetes duration. There was no significant difference in HbA1c between attendees and non-attendees, or for those who attended more than one session. Sixty children and young people (63.8%) attended the programme more than once. Children and young people who attended their first session at primary school age tended to have lower HbA1c than those first attending at secondary school age, and were less likely to increase HbA1c over time. Repeated attendance suggests the Cook and Eat groups were perceived as valuable. The authors advocate caution on the over-reliance of HbA1c as the only marker of group value or success. [ABSTRACT FROM AUTHOR]

The saccade duration increases with an increase in the time-on-task (TOT) during a two-hour air traffic control stimulating task. The saccade amplitude decreases during the beginning of the two-hour period, increases in the middle, and then decreases again at the end of the task. The increase in the duration decreases the regression line slope, which connects saccade amplitude to duration. A decrease in the slope due to TOT reflects a rise in the number of low velocity saccades occurring with high fatigue. The saccades occurring during an eye blink are slower than those occurring without it.

ABSTRACT With organizations seeking faster, cheaper, and smarter ways of delivering higher quality software, many are looking towards generative artificial intelligence (AI) to drive efficiencies and innovation throughout the software development lifecycle. However, generative AI can suffer from several fundamental issues, including a lack of traceability in concept generation and decision‐making, the potential for making incorrect inferences (hallucinations), shortcomings in response quality, and bias. Quality engineering (QE) has long been utilized to enable more efficient and effective delivery of higher quality software. A core aspect of QE is adopting quality models to support various lifecycle practices, including requirements definition, quality risk assessments, and testing. In this position paper, we introduce the application of QE to AI systems, consider shortcomings in existing AI quality models from the International Organization for Standardization (ISO), and propose extensions to ISO models based on the results of a survey. We also reflect on skills that IT graduates may need in the future, to support delivery of better‐quality AI. [ABSTRACT FROM AUTHOR]

The use of ultraviolet absorption and a charge-coupled camera allows real time monitoring of DNA migration in pulsed-field gel electrophoresis. The 254-nm UV makes sampling simpler and safer as there is no need for stains or isotope labels and the DNA is analyzed in its natural state. Real time monitoring makes on-the-spot background and program corrections possible. By setting buffer, agarose and electric field strengths as well as temperature and pulse time at their optimum, total run time can be reduced by as much as a tenth of a constant field program run.

Abstract Background Since betaine is an osmolyte and methyl donor, and abnormal betaine loss is common in diabetes mellitus (>20% patients), we investigated the relationship between betaine and the post-methionine load rise in homocysteine, in diabetes and control subjects. The post-methionine load test is reported to be both an independent vascular risk factor and a measure of betaine sufficiency. Methods Patients with type 2 diabetes (n = 34) and control subjects (n = 17) were recruited. We measured baseline fasting plasma and 4-hour post-methionine load (L-methionine, 0.1 mg/kg body weight) concentrations of homocysteine, betaine, and the betaine metabolite N,N-dimethylglycine. Baseline urine excretions of betaine, dimethylglycine and glucose were measured on morning urine samples as the ratio to urine creatinine. Statistical determinants of the post-methionine load increase in homocysteine were identified in multiple linear regression models. Results Plasma betaine concentrations and urinary betaine excretions were significantly (p p = 0.00014) and plasma dimethylglycine concentrations (p = 0.039) were also more variable. In diabetes, plasma betaine was a significant negative determinant (p Conclusions Both high and low plasma betaine concentrations, and high and low urinary betaine excretions, are more prevalent in diabetes. The availability of betaine affects the response in the methionine load test. The benefits of increasing betaine intake should be investigated.

Good quality diabetes education is essential for all children and young people (CYP) with diabetes. Cook and Eat is an annual educational session for CYP to actively learn about carbohydrate counting developed and run by the team at Exeter Children and Young People's Diabetes Service. Cook and Eat allows CYP and their families or carers to explore food, learning basic cooking skills and basic maths skills related to carbohydrate counting. During the COVID-19 pandemic, the team were unable to deliver this face to face and so moved to online sessions. This article describes how these sessions were delivered and the initial feedback from the CYP, and their families and carers. [ABSTRACT FROM AUTHOR]

Objectives: Prader-Willi Syndrome (PWS) is characterised by hyperphagia often leading to obesity; a known risk factor for insulin resistance and type 2 (T2) diabetes. We present a prepubertal girl with PWS who developed diabetes. Case presentation: Our case was diagnosed with PWS in infancy following investigation for profound central hypotonia and feeding difficulties. She commenced growth hormone (GH) aged 8 years for short stature and treatment improved linear growth. At age 12 years, she presented with polydipsia, polyuria and vulvovaginitis. She was overweight (BMI SDS +1.43). Diabetes was diagnosed (Blood glucose = 24.2 mmol/L, HbA1c = 121 mmol/mol or 13.2%). She was not acidotic and had negative blood ketones. Autoantibodies typical of type 1 diabetes were negative. She was initially treated with basal bolus insulin regime. GH was discontinued 3 months later due to concerns regarding GH-induced insulin resistance. Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy. However off GH, she reported significant lethargy with static growth and increased weight. Combinations of Metformin with differing insulin regimes did not improve glucose levels. Liraglutide (GLP-1 agonist) and Metformin did not improve glucose levels nor her weight. Liraglutide and Empaglifozin (SGLT-2 inhibitor) therapy used in combination were well tolerated and demonstrated rapid normalisation of blood glucose and improvement in her HbA1c to within target (48 mmol/mol) which was sustained after 6 months of treatment. Conclusions: Newer treatments for type 2 diabetes (e. g. GLP-1 agonists or SGLT-2 inhibitors) offer potential treatment options for those with diabetes and PWS when conventional treatments are ineffective. – DM (Diabetes mellitus) is a rare complication of Prader-Willi Syndrome (PWS) before puberty. – This case demonstrates the challenges of managing PWS and DM including negotiating growth hormone therapy and pubertal induction/augmentation. – Conventional therapies (e. g. oral hypoglycaemic agents and insulin) failed to achieve adequate glycaemic parameters. – Recently developed therapies of Liraglutide (GLP-1) and Empaglifozin (SGLT-2 inhibitor) used combination were well tolerated, led to rapid normalisation of blood glucose and a sustained improvement in HbA1c within target. – This is the first case report describing the use of a GLP-1 agonist and a SGLT-2 inhibitor used in combination in a child with PWS and DM. [ABSTRACT FROM AUTHOR]

Aims. To examine the outcome of potential live kidney donors (PLKD) assessment program at Christchurch Hospital and, also, to review findings of Computed Tomographic (CT) renal angiograms that led to exclusion in the surgical assessment. Methods. Clinical data was obtained from the database of kidney transplants, Proton. Radiological investigations were reviewed using the hospital database, Éclair. The transplant coordinator was interviewed to clarify information about PLKD who did not proceed to surgery, and a consultant radiologist was interviewed to explain unfavorable findings on CT renal angiograms. Results. 162 PLKD were identified during the period January 04-June 08. Of those, 65 (40%) proceeded to have nephrectomy, 15 were accepted and planned to proceed to surgery, 13 were awaiting further assessment, and 69 (42.5%) did not proceed to nephrectomy. Of the 162 PLKD, 142 (88%) were directed donors. The proportion of altruistic PLKD who opted out was significantly higher than that of directed PLKD (45% versus 7%, P = 0.00004). Conclusions. This audit demonstrated a positive experience of live kidney donation at Christchurch Hospital. CT renal angiogram can potentially detect incidental or controversial pathologies in the kidney and the surrounding structures. Altruistic donation remains controversial with higher rates of opting out. [ABSTRACT FROM AUTHOR]

Addresses solution nonmetal determinations on a fundamental level. Characterizes research in this area of chemical instrumentation. Discusses the fundamental limitations of nonmetal atomic spectrometry, the status of nonmetals and atomic spectroscopic techniques, and current directions in solution nonmetal determinations. (CW)

Background: The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi-center, prospective, randomised, single-blind (assessor), controlled, parallel assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD) patients from 7 centers in New Zealand. The trial will evaluate the hypothesis that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass. Since it’s inception, observational evidence has suggested increased mortality risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i) increased levels of high-sensitivity Troponin T (hsTnT), a well-established marker of intra-dialytic myocardial micro-injury in HD populations, and (ii) increased fixed LV segmental wall motion abnormalities, a marker of recurrent myocardial stunning and micro-injury, and (iii) detrimental changes in LV geometry due to maladaptive homeostatic mechanisms. Methods/design: The SoLID trial and the Mac-SoLID study are funded by the Health Research Council of New Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre-dialysis serum sodium <135 mM, and maintenance haemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials that contraindicate the study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will receive dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure for the Mac-SOLID study is repeated measures of [hsTnT] at 0, 3, 6, 9, and 12 months. The secondary outcomes will be assessed using cardiac magnetic resonance imaging (MRI), and comprise LV segmental wall motion abnormality scores, LV mass to volume ratio and patterns of LV remodeling at 0 and 12 months. Discussion: The Mac-SoLID study enhances and complements the SoLID trial. It tests whether potential gains in cardiovascular health (reduced LV mass) which low dialysate [Na+] is expected to deliver, are counteracted by deterioration in cardiovascular health through alternative mechanisms, namely repeated LV stunning and micro-injury. [ABSTRACT FROM AUTHOR]

Background: The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients. Methods/design: The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials, which contraindicate the SoLID study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will be dialysed using dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure is left ventricular mass index, as measured by cardiac magnetic resonance imaging, after 12 months of intervention. Eleven or more secondary outcomes will be studied in an attempt to better understand the physiologic and clinical mechanisms by which lower dialysate sodium alters the primary end point. Discussion: The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients. Trial registration: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998 [ABSTRACT FROM AUTHOR]

Abstract: Cryptococcus neoformans is an encapsulated yeast that can cause primary pulmonary infections or disseminate and cause infections of the central nervous system, meninges, skin, and bone in the immunocompromised host. We present here an unusual case of an immunocompetent patient who had laryngitis due to C. neoformans that mimicked a laryngeal carcinoma on clinical examination and imaging studies. [ABSTRACT FROM AUTHOR]

Elevated plasma homocysteine (Hcy), dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease (ESRD) and are recognized risk factors for arteriosclerosis. To study the effect of folate supplementation on these factors we conducted a randomized controlled trial. Thirteen hemodialysis (HD) and 8 continuous ambulatory peritoneal dialysis (CAPD) patients received either 5 mg folic acid daily or placebo for 3 months. After 1 and 3 months, fasting blood samples were taken for Hcy, lipid profile, blood and plasma viscosity, red blood cell (RBC) osmotic fragility, plasma fibrinogen concentration and in vivo platelet aggregability. At baseline, the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity. Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33%. Mean total cholesterol, LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate. Folate had no significant effect on hemorheology. In conclusion, folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles. In our patients, hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Good blood pressure (BP) control has been reported previously in haemodialysis (HD) patients receiving 8-h dialysis sessions. Home HD allows patients to dialyse for long periods, but there are few data on the BP control achieved by these patients. We studied BP control, using ambulatory blood pressure monitoring (ABPM), in our home-HD patients who were receiving long-hours dialysis. [ABSTRACT FROM PUBLISHER]

Henoch–Schönlein purpura (HSP) is a systemic small-vessel leucocytoclastic vasculitis with deposition of immune complexes containing Immunoglobulin A (IgA). IgA Nephropathy (IgAN) is a glomerulonephritis caused by mesangial deposition of IgA. The onset of HSP, but not IgAN, has been linked to influenza vaccination.We report the first case of HSP with glomerular involvement, in a renal transplant recipient following influenza vaccination. The patient had prior end-stage renal failure (ESRF) secondary to IgAN, without clinical evidence of IgAN recurrence after transplantation. This is of clinical relevance as influenza vaccination is regarded safe, effective, and recommended after renal transplantation.Nephrologists should be aware of the potential for influenza vaccination to have adverse effects in renal transplant recipients, especially if the primary renal disease is HSP or IgAN. [ABSTRACT FROM PUBLISHER]

After the publication of our paper Dunlop et al. "Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass", we became aware of further data correlating left ventricular (LV) mass index at baseline and their correpsonding mass at 12 months, using cardiac margnetic resonanace imaging (MRI) in patients on hemodialysis. The original published sample size for the SoLID trial of 118 was a conservative estimate, calculated using analysis of covariance and a within person Pearson's correlation for LV mass index of 0.75. New data communicated to the SoLID trial group has resulted in re-calcuation of the sample size, based upon a within person Pearson's correlation of 0.8 but otherwise unchanged assumptions. As a result, the SoLID trial will now recruit 96 participants. [ABSTRACT FROM AUTHOR]

Background: The current literature recognises that left ventricular hypertrophy makes a key contribution to the high rate of premature cardiovascular mortality in dialysis patients. Determining how we might intervene to ameliorate left ventricular hypertrophy in dialysis populations has become a research priority. Reducing sodium exposure through lower dialysate sodium may be a promising intervention in this regard. However there is clinical equipoise around this intervention because the benefit has not yet been demonstrated in a robust prospective clinical trial, and several observational studies have suggested sodium lowering interventions may be deleterious in some dialysis patients.Methods/design: The Sodium Lowering in Dialysate (SoLID) study is funded by the Health Research Council of New Zealand. It is a multi-centre, prospective, randomised, single-blind (outcomes assessor), controlled parallel assignment 3-year clinical trial. The SoLID study is designed to study what impact low dialysate sodium has upon cardiovascular risk in dialysis patients. The study intends to enrol 118 home hemodialysis patients from 6 sites in New Zealand over 24 months and follow up each participant over 12 months. Key exclusion criteria are: patients who dialyse more frequently than 3.5 times per week, pre-dialysis serum sodium of <135 mM, and maintenance hemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials, which contraindicate the SoLID study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will be dialysed using dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure is left ventricular mass index, as measured by cardiac magnetic resonance imaging, after 12 months of intervention. Eleven or more secondary outcomes will be studied in an attempt to better understand the physiologic and clinical mechanisms by which lower dialysate sodium alters the primary end point.Discussion: The SoLID study is designed to clarify the effect of low dialysate sodium upon the cardiovascular outcomes of dialysis patients. The study results will provide much needed information about the efficacy of a cost effective, economically sustainable solution to a condition which is curtailing the lives of so many dialysis patients.Trial Registration: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998. [ABSTRACT FROM AUTHOR]