Variant ataxia telangiectasia identified during evaluation for short stature.

Ataxia telangiectasia (A-T) (OMIM 208900) is an autosomal recessive multisystem disorder characterised by progressive cerebellar ataxia, telangiectasias, immunodeficiency and a predisposition to malignancy. 'Variant' A-T has later onset of neurological symptoms and slower progression compared with the 'classic' form. A woman presented with short stature in late childhood. Karyotype revealed rearrangements involving chromosomes 7 and 14. A chromosomal breakage disorder gene panel demonstrated compound heterozygote mutations in her ATM gene including one mutation c.7271T>G with residual ATM function, confirming the diagnosis of variant A-T. Since diagnosis, she has developed progressive cerebellar ataxia and telangiectasias. Long-standing restrictive and aversive feeding behaviours presented challenges for her management and necessitated gastrostomy.

Current management of neonatal abstinence syndrome: a survey of practice in the UK and Ireland.

OBJECTIVE: To study the current management practices of neonatal abstinence syndrome (NAS) throughout the UK and Ireland and identify changes in practice from the most recent survey in 2008. DESIGN: Postal questionnaire to a consultant paediatrician or neonatologist in all 215 neonatal units in the UK and Ireland in January 2020. RESULTS: Response rate was 62%. An objective scoring tool was used in 97% of units and the Finnegan score was favoured by 70%. Morphine sulfate use as first line for the treatment of opiate withdrawal was almost universal and 70% used a dose of 40 µg/kg every 4 hours (240 µg/kg/day). Phenobarbitone administration as a second-line agent for opiate withdrawal increased to 61% of units with significant reductions in chloral hydrate and chlorpromazine use compared with the previous survey. Morphine sulfate and phenobarbitone remain the preferred first-line and second-line agents, respectively, for polysubstance withdrawal. There was a significant increase in chlorpromazine use as first line for polydrug withdrawal (1.5-14.2%). The practice of units discharging infants' home on medication increased to 46% from 29%. All units now permit breastfeeding in mothers taking methadone, compared with 81% previously. CONCLUSION AND RELEVANCE: Compared with the previous survey, improvements in evidence-based practices were noted, highlighting the benefits of this type of research. Nonetheless, significant variation still exists in some aspects of the management of NAS. Post-discharge follow-up varies widely, with particular deficits in ophthalmology follow-up.

Spontaneous remission of pendulum swinging thyroid disease in Down syndrome.

Summary: Rare patients who have both thyroid-stimulating hormone (TSH) receptor-stimulating and -blocking antibodies can develop 'pendulum swinging' thyroid dysfunction. A 9-year-old girl with Down syndrome was treated with carbimazole for Graves' disease. After 2 years of treatment, she became profoundly biochemically hypothyroid, and this persisted after carbimazole was discontinued. Low-dose L-thyroxine was commenced. This was subsequently also discontinued as biochemical hyperthyroidism developed. TSH receptor antibody bioassay identified both TSH receptor-stimulating and -blocking antibodies. Mild hyperthyroidism persisted and while consultations regarding definitive treatment were ongoing, medication was not recommenced. Thyroid function normalised spontaneously and she has remained euthyroid for the past 3 years. Previous reports have advised definitive treatment; however, our patient developed spontaneous remission which has been prolonged and definitive therapies have been avoided. It is not yet known how commonly this particular phenomenon occurs. Learning points: Rare patients who have both TSH receptor-stimulating and -blocking antibodies can switch between hyperthyroidism and hypothyroidism or vice versa during treatment with antithyroid drugs or thyroxine. Metamorphic thyroid autoimmunity is more common in Down syndrome. Switching between hyperthyroidism and hypothyroidism and back again is less commonly reported. Definitive treatment such as radioactive iodine or thyroidectomy are usually recommended. Prolonged remission was achieved off all medication, without recourse to definitive treatments.

School-based management of type 1 diabetes in the Republic of Ireland: a cross-sectional mixed-methods analysis.

BACKGROUND: Qualitative research regarding the experience of diabetes self-care management in schools is underrepresented in published literature. In addition, there are methodologic limitations in some of the existing studies. AIMS: To investigate experiences of school-based diabetes self-care management in children and adolescents with type 1 diabetes. METHODS: Cross-sectional mixed-methods questionnaire survey. Sentiment analysis was undertaken of free-text responses by primary caregivers of young children and adolescents or adolescents themselves in relation to experiences regarding school-based support for self-care. Statements were rated on a 5-point Likert scale from strongly negative (1) to strongly positive (5). Responses were also grouped using thematic analysis. A quantitative analysis of the similarities and differences in responses between primary and secondary school students was undertaken. RESULTS: Text responses for analysis were present in 273 (65%) primary and 226 (56%) secondary school questionnaires. Sentiment analysis yielded mean scores of 3.5 and 2.8 for primary and secondary students, respectively. Three major themes were identified in the statements, namely attitude, education/knowledge, and resources. Scores within each theme were significantly higher for primary compared to secondary students. Attitude scored highest and education/knowledge scored lowest in both groups. Comments in relation to resources were significantly more frequent in primary school questionnaires, and comments regarding education and knowledge were more commonplace in secondary school responses. CONCLUSION: Our findings suggest that experiences regarding self-care management of type 1 diabetes are generally more positive among primary school students. Education and knowledge of school staff should be a particular area of focus in both cohorts.

Isolated splenic hydatid disease: a rare case in rural New Zealand.

Nil.

Whole exome sequencing based identification of a case of cardiofaciocutaneous syndrome type 3: the benefits of new sequencing technology in children with neurodevelopmental delay.

We report the case of a boy with a prolonged diagnostic workup for global developmental delay alongside feeding difficulties, failure to thrive, pulmonary stenosis and macrocephaly. Following a series of diagnostic tests over the first 25 months of life, whole-exome sequencing was performed which diagnosed cardiofaciocutaenous syndrome type 3.Global developmental delay is a common presentation to general paediatric and community paediatric clinics. This prompts the search for an aetiology to describe the child's constellation of symptoms which often consists of a chromosomal microarray, neuroimaging and investigations for an inborn error of metabolism. With developments in genetic testing such as the reducing cost of clinical exome sequencing or whole-exome sequencing, could these testing strategies offer a more comprehensive first line test?This case not only demonstrates the features of cardiofaciocutaneous syndrome type 3 but the added value of modern genetic technologies in the diagnosis of children with global developmental delay.

Modification and Validation of an mHealth App Quality Assessment Methodology for International Use: Cross-sectional and eDelphi Studies.

BACKGROUND: Over 325,000 mobile health (mHealth) apps are available to download across various app stores. However, quality assurance in this field of medicine remains relatively undefined. Globally, around 84% of the population have access to mobile broadband networks. Given the potential for mHealth app use in health promotion and disease prevention, their role in patient care worldwide is ever apparent. Quality assurance regulations both nationally and internationally will take time to develop. Frameworks such as the Mobile App Rating Scale and Enlight Suite have demonstrated potential for use in the interim. However, these frameworks require adaptation to be suitable for international use. OBJECTIVE: This study aims to modify the Enlight Suite, a comprehensive app quality assessment methodology, to improve its applicability internationally and to assess the preliminary validity and reliability of this modified tool in practice. METHODS: A two-round Delphi study involving 7 international mHealth experts with varied backgrounds in health, technology, and clinical psychology was conducted to modify the Enlight Suite for international use and to improve its content validity. The Modified Enlight Suite (MES) was then used by 800 health care professionals and health care students in Ireland to assess a COVID-19 tracker app in an online survey. The reliability of the MES was assessed using Cronbach alpha, while the construct validity was evaluated using confirmatory factor analysis. RESULTS: The final version of the MES has 7 sections with 32 evaluating items. Of these items, 5 were novel and based on consensus for inclusion by Delphi panel members. The MES has satisfactory reliability with a Cronbach alpha score of .925. The subscales also demonstrated acceptable internal consistency. Similarly, the confirmatory factor analysis demonstrated a positive and significant factor loading for all 32 items in the MES with a modestly acceptable model fit, thus indicating the construct validity of the MES. CONCLUSIONS: The Enlight Suite was modified to improve its international relevance to app quality assessment by introducing new items relating to cultural appropriateness, accessibility, and readability of mHealth app content. This study indicates both the reliability and validity of the MES for assessing the quality of mHealth apps in a high-income country, with further studies being planned to extrapolate these findings to low- and middle-income countries.

Prepubertal onset of type 2 diabetes in Shashi-Pena syndrome due to ASXL2 mutation.

Type 2 diabetes remains rare in the pediatric population and the majority of cases occur during puberty. A combination of genetic and environmental factors leads to the development of insulin resistance and ß-cell failure. An increased prevalence is recognized in a number of rare genetic disorders such as Alström and Bardet-Biedl syndromes. Recently, a rare neurodevelopmental disorder, Shashi-Pena syndrome due to the dominant negative effect of heterozygous mutations in additional Sex-Combs-Like Genes 2 (ASXL2) has been reported. ASXL2 null mice exhibit glucose intolerance, insulin resistance and lipodystrophy. The regulatory role of ASXL2 in glucose and lipid homeostasis occurs through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ), a gene implicated in the pathogenesis of type 2 diabetes on genome-wide association studies. Thiazolidinediones, used for the treatment of type 2 diabetes, exert their effects as direct agonists of PPARγ. We report the first case of type 2 diabetes in Shashi-Pena syndrome, occurring in an 8-year-old prepubertal boy with no family history. In addition, the proband had dyslipidemia, and fatty infiltration of the liver with elevated transaminases. Mutation of ASXL2 in humans, through its interaction with PPARγ appears to cause a phenotype of insulin resistance, type 2 diabetes, and dyslipidemia. Further reported cases will assist in confirming this association.

Acceptable Inclusion Levels for Selected Brown and Red Irish Seaweed Species in Pork Sausages.

Commercially available Irish edible brown (Himanthalia elongata­sea spaghetti (SS), Alaria esculenta­Irish wakame (IW)) and red (Palmaria palmata­dulse (PP), Porphyra umbilicalis­nori) seaweeds were incorporated into pork sausages at 1%, 2.5%, and 5%. Proximate composition, salt, water-holding (WHC), cook loss, instrumental colour analysis, texture profile analysis (TPA), and sensory analysis were examined. Protein (13.14−15.60%), moisture (52.81−55.71%), and fat (18.79−20.02%) contents of fresh pork sausages were not influenced (p > 0.05) by seaweed type or addition level. The ash content of pork sausages containing PP, SS, and IW at 2.5% and 5%, and nori at 5%, were higher (p < 0.05) than the control sample. In comparison to the control, sausages containing nori, SS, and IW at 5% displayed higher (p < 0.05) WHC. Cook loss was unaffected (p > 0.05) by the addition of seaweeds into sausage formulations, compared to the control and within each seaweed. The addition of seaweeds into sausages had an impact on the surface colour (L* a* b*) and texture profile analysis (TPA) at different inclusion levels. Overall, hedonic sensory acceptability decreased (p < 0.05) in cooked sausages containing PP at 2.5% and 5%, and SS and IW at 5%.

Adolescent onset of autoimmune polyglandular syndrome type 2.

An adolescent female was evaluated for fatigue, anorexia and unintentional weight loss of 7 kg. Initial investigations revealed subclinical autoimmune thyroid dysfunction, which progressed to overt hypothyroidism necessitating thyroxine replacement. She had entered early puberty, but this did not appear to be progressing. A high index of suspicion for coexisting endocrinopathies resulted in a diagnosis of Addison's disease and consequently autoimmune polyglandular syndrome type 2 (Schmidt syndrome). While basal gonadotropins were normal, anti-Mullerian hormone was low and ovarian autoantibodies were positive, consistent with preclinical premature ovarian failure. Glucocorticoid and mineralocorticoid replacement were instituted. Puberty progressed and menarche was subsequently attained. Screening for other autoantibodies was undertaken; however, none are positive to date.

Defining an optimal surveillance strategy for patients following choledochal cyst resection: results of a systematic review.

BACKGROUND: Choledochal cysts should be treated with complete surgical resection, or, rarely liver transplantation. Treated patients can remain at risk of developing metachronous cholangiocarcinomas and lifelong follow up is indicated. However, there is no agreement on what constitutes an acceptable follow up strategy. This review was undertaken to develop an evidenced based surveillance strategy. METHODS: A systematic review of MEDLINE, EMBASE, PubMed, Web of Science, and Google Scholar was undertaken for reports (published up to 10 September 2021) describing late biliary complications and development of metachronous cholangiocarcinoma following choledochal cyst resection. RESULTS: Twenty-five publications described 74 metachronous cholangiocarcinomas occurring in 3911 patients (overall incidence 2%). Cancers developed commonly at the hepatic hilus and were diagnosed after a median interval of 92 months (range 9-249 months) after the initial resection. While reporting is incomplete, the majority of cholangiocarcinomas developed following resection of type I and type IV cysts with few metachronous cancers recorded after treatment of type II or III cysts. Peak age range for presentation with metachronous cholangiocarcinoma is in the twenties following cyst resection in childhood suggesting that patients are at greatest risk for metachronous tumour development for up to 20 years (240 months). CONCLUSION: A surveillance strategy is proposed for patients treated primarily for cyst types I and IV and unresected type V using annual liver function tests, Ca 19-9 measurement and biannual ultrasound assessment for 20 years post cyst resection, with biannual liver function testing, Ca 19-9 measurement and three yearly ultrasound assessment thereafter.

Rectal swabs are a reliable method of assessing the colonic microbiome.

BACKGROUND: Advances in genome sequencing have enabled detailed microbiome analysis; however, the ideal specimen type for sequencing is yet to be determined. Rectal swabs may offer a rapid and convenient modality for colonic microbiome analysis. The aim of this study is to evaluate the use of rectal swabs compared to faecal specimens. METHODS AND RESULTS: Twenty health professionals participated in this study and provided a faecal specimen, a self-collected rectal swab and a rectal swab taken by a clinician. DNA was extracted and 16S rRNA gene sequencing was carried out for microbiome analysis. Alpha diversity was higher in swabs compared to faecal specimens; however, the difference was only significant when comparing clinician-obtained swabs to faeces. Analysis of beta diversity consistently showed that few taxa were affected by sample type. We found sample type accounted for only 6.8% of community variation (R2 = 0.067, p < 0.001, permanova). Notably, there were only six genera identified in clinician-obtained swabs that were not also found in the self-taken swabs. CONCLUSIONS: Both self-collected and clinician obtained rectal swabs are a reliable method of analysing the colonic microbiome. Obtaining specimens for microbiome analysis is often time-critical due to therapy, such as antibiotics, influencing the microbiome. Rectal swabs are shown to be a valid and convenient modality for microbiome analysis.

Acute Diverticulitis in Young Patients: A Review of the Changing Epidemiology and Etiology.

Acute diverticulitis is one of the leading gastrointestinal causes for hospitalization. The incidence of acute diverticulitis has been increasing in recent years, especially in patients under 50 years old. Historically, acute diverticulitis in younger patients was felt to represent a separate entity, being more virulent and associated with a higher rate of recurrence. Accordingly, young patients were often managed differently to older counterparts. Our understanding of the natural history of this condition has evolved, and current clinical practice guidelines suggest age should not alter management. The purpose of this review is to evaluate the changing epidemiology of acute diverticulitis, consider potential explanations for the observed increased incidence in younger patients, as well as review the natural history of acute diverticulitis in the younger population.

An Assessment of Selected Nutritional, Bioactive, Thermal and Technological Properties of Brown and Red Irish Seaweed Species.

Irish edible brown (Himanthalia elongata-sea spaghetti, Alaria esculenta-Irish wakame) and red seaweeds (Palmaria palmata-dulse, Porphyra umbilicalis-nori) were assessed for nutritional (proximate composition; salt; pH; amino acid; mineral and dietary fibre contents); bioactive (total phenolic content (TPC) and in vitro antioxidant activity (DPPH and FRAP)); thermal (thermogravimetric analysis (TGA)); and technological (water holding capacity (WHC), oil holding capacity (OHC) and swelling capacity (SC)) properties. Red seaweeds had higher (p < 0.05) protein levels, whereas brown seaweeds possessed higher (p < 0.05) moisture, ash, insoluble and total dietary fibre contents. Nori had the lowest (p < 0.05) salt level. Seaweed fat levels ranged from 1 to 2% DW. Aspartic and glutamic acids were the most abundant amino acids. The total amino acid (TAA) content ranged from 4.44 to 31.80%. Seaweeds contained numerous macro (e.g., Na) and trace minerals. The TPC, DPPH and FRAP activities followed the order: sea spaghetti ≥ nori > Irish wakame > dulse (p < 0.05). TGA indicated maximum weight loss at 250 °C. Dulse had the lowest (p < 0.05) WHC and SC properties. Dulse and nori had higher (p < 0.05) OHC than the brown seaweeds. Results demonstrate the potential of seaweeds as functional food product ingredients.

Dietary cardoon meal modulates rumen biohydrogenation and bacterial community in lambs.

Cardoon meal is a by-product of oil extraction from the seeds of Cynara cardunculus and can serve as a novel alternative feedstuff for ruminants. This study examined the rumen fermentation, biohydrogenation of fatty acids (FA) and microbial community in lambs fed a concentrate diet containing 15% dehydrated lucerne (CON, n = 8) or cardoon meal (CMD, n = 7) for 75 days pre-slaughter. Diets did not influence rumen fermentation characteristics and the abundance of bacteria, methanogens, fungi, or protozoa. Rumen digesta in CMD-fed lambs displayed a higher concentration of total saturated FA and lower total odd- and branched-chain FA and monounsaturated FA. Feeding CMD decreased total trans-18:1 isomer and the ratio of trans-10 to trans-11 C18:1, known as the "trans-10 shift". Amplicon sequencing indicated that the rumen bacterial community in CMD-fed lambs had lower diversity and a higher relative phyla abundance of Proteobacteria at the expense of Bacteroidetes and Fibrobacteres. At the genus level, CMD mediated specific shifts from Prevotella, Alloprevotella, Solobacterium and Fibrobacter to Ruminobacter, suggesting that these genera may play important roles in biohydrogenation. Overall, these results demonstrate that cardoon meal can be used as a feedstuff for ruminants without negatively affecting rumen fermentation and microbiota but its impact on biohydrogenation may influence the FA composition in meat or milk.

The Epidemiology and Etiology of Right-Sided Colonic Diverticulosis: A Review.

Diverticulosis of the colon is a common condition in Western countries and most patients will remain asymptomatic, but some will present with symptoms of acute diverticulitis or bleeding. Our understanding of diverticulosis is evolving but is mostly derived from diverticulosis affecting the left-sided colon. In contrast, right-sided colonic diverticulosis (RCD) is more commonly seen in Asian countries but is much less common overall. Based on the marked differences in epidemiology, it is commonly thought that these are 2 distinct disease processes. A review of the literature describing the epidemiology and etiology of RCD was performed, with a comparison to the current understanding of left-sided diverticulosis. RCD is becoming increasingly common. The epidemiology of RCD shows it to be a mostly acquired condition, and not congenital as previously thought. Many factors in the etiology of RCD are similar to that seen in left-sided diverticulosis, with a few variations. It is therefore likely that most cases of RCD represent the same disease process that is seen in the left colon.

The prevalence of right-sided colonic diverticulosis in a New Zealand population.

BACKGROUND: Once considered to be a congenital condition, the epidemiology of right-sided colonic diverticulosis (RCD) is evolving. Acute diverticulitis (AD) is a complication of RCD which is frequently misdiagnosed as appendicitis, resulting in unnecessary surgery, as there is strong evidence supporting medical management for right-sided AD. In general, the incidence of AD correlates with the prevalence of RCD, which shows marked geographic variation. Few data reporting RCD prevalence come from Western countries, so the aim of this study is to define the prevalence of RCD in a New Zealand population. METHODS: Independent review of the imaging from 1000 consecutive patients undergoing a computed tomography Kidney/Ureter/Bladder scan for suspected urolithiasis at Christchurch Hospital between January and November 2017 was undertaken, to determine the presence or absence, and distribution of colonic diverticulosis. Patients were excluded if they had a history of colonic resection, known IBD, or were less than 18-years old. RESULTS: Thirty-one patients were excluded, leaving 969 eligible patients. Overall, 95 patients (9.8%) had RCD identified. The prevalence of RCD increased significantly with advancing age, being present in 2.3% of those aged 18-29, increasing to 20.3% in those greater than 70-years old (p < 0.001). CONCLUSION: The prevalence of RCD in a New Zealand population is relatively high and increases significantly with age. This adds support to the role of cross-sectional imaging in the evaluation of suspected appendicitis, to exclude right-sided AD. The association with advancing age supports RCD being an acquired condition rather than a congenital condition as was previously thought.

Concentrate supplementation with dried corn gluten feed improves the fatty acid profile of longissimus thoracis muscle from steers offered grass silage.

BACKGROUND: Concentrate supplementation of a grass silage-based ration is a typical practice employed for indoor winter finishing of beef cattle in many temperate countries. Plant by-products, such as dried corn gluten feed (CGF), can be used to replace conventional feedstuffs in a concentrate supplement to enhance the sustainability of ruminant production systems and to improve meat quality. This study examined the chemical composition, fatty acid profile, oxidative stability and sensory attributes of beef (longissimus thoracis muscle) from steers offered grass silage and concentrate supplements containing varying levels (0%, 25%, 50%, 75%) of CGF substituted for barley / soybean meal. RESULTS: Feeding 50%CGF decreased the protein content and increased intramuscular fat in comparison with 25%CGF. Total phenol content and iron-reducing antioxidant power followed the order: 0%CGF > 50%CGF and 25%CGF > 0%CGF = 50%CGF, respectively. Compared to 0%CGF, 25%CGF and 75%CGF decreased C14:0 and increased C22:2n-6, C20:5n-3 and total n-3 polyunsaturated fatty acids whereas 75%CGF increased conjugated linoleic acids and C18:3n-3. Diet did not affect the oxidative stability and sensory attributes of beef patties. CONCLUSION: The inclusion of up to 75%CGF in a supplementary concentrate for steers increased the proportion of health-promoting unsaturated fatty acids without negatively influencing the shelf-life and eating quality of longissimus thoracis muscle. © 2021 Society of Chemical Industry.