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.

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.

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.

The clinical presentation, treatment and outcome of serologically confirmed paediatric Lyme disease in the Republic of Ireland over a 5-year period: a retrospective cohort study.

Lyme disease (LD) is the most common tick-borne illness in Europe. Population-based studies in European children are few. This study aimed to assess the incidence, clinical presentation, treatment and outcome of serologically confirmed paediatric LD in the Republic of Ireland over a 5-year period. A retrospective review of records from accredited laboratories performing Borrelia burgdorferi serological testing was undertaken. Proformas were distributed to clinicians of children and adolescents with positive Lyme serology. Data were requested regarding clinical presentation, treatment and outcome. Updated NICE guidelines were used to classify clinical cases. Serology testing for B. burgdorferi was performed on 2908 samples. Sixty-three (2.2%) children were two-tier positive, generating a crude annual incidence rate of 1.15/100,000. Proformas were returned for 55 (87%) and 47 met clinical and laboratory criteria for LD. Twenty-seven (57%) presented with non-focal symptoms (erythema migrans and/or influenza-like symptoms), and 20 (43%) with focal symptoms (cranial nerve involvement, 11; CNS involvement, 8; arthritis, 1). Median age at presentation was 8.2 (2.5-17.9) years. Seventeen (36%) acquired LD overseas. Twenty-five (83%) of the remaining 30 children acquired infection in the West/Northwest of Ireland. Full resolution of symptoms was reported in 97% of those with available data. Serologically confirmed LD in children is relatively rare in the Republic of Ireland. Ninety-eight percent of children tested were seronegative. Of the seropositive cases, 40% could have been diagnosed based on clinical findings alone. Neurological presentations (40%) were common. Full resolution of symptoms occurred in almost all (97%) where data were available.

The incidence of transient infantile pseudohypoaldosteronism in Ireland: A prospective study.

AIM: To review the clinical course, outcome and incidence of infantile salt wasting associated with urinary tract infection (UTI) and/or urinary tract malformation (UTM) over a two-year surveillance period on the island of Ireland. METHODS: A two-year (2013-14) prospective surveillance undertaken via the Irish and Ulster Paediatric Surveillance Units. Monthly prepaid postcards were circulated to consultant paediatricians (n = 260) at all paediatric units on the island of Ireland. Infants under one year of age presenting for the first time with hyponatraemia (Na < 130 mmol/L) and/or hyperkalaemia (K > 5.0 mmol/L) associated with urosepsis/UTM were reported. RESULTS: All 7 reported patients (6 male) had culture-proven UTI, and 5 (71%) also had an underlying UTM (one diagnosed antenatally). Four (57%) patients had a documented elevated serum aldosterone supporting secondary pseudohypoaldosteronism (PHA) as the underlying diagnosis. Data on aldosterone were not reported in the other 3 patients, but clinical features were suggestive of secondary PHA. The estimated incidence for the Irish population of transient PHA is 1 per 13,200 total live births per year. CONCLUSIONS: Salt wasting is a rare complication of UTI, especially if associated with underlying UTM. Boys appear to be at particular risk.

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.

Food and temperature stressors have opposing effects in determining flexible migration decisions in brown trout (Salmo trutta).

With rapid global change, organisms in natural systems are exposed to a multitude of stressors that likely co-occur, with uncertain impacts. We explored individual and cumulative effects of co-occurring environmental stressors on the striking, yet poorly understood, phenomenon of facultative migration. We reared offspring of a brown trout population that naturally demonstrates facultative anadromy (sea migration), under different environmental stressor treatments and measured life history responses in terms of migratory tactics and freshwater maturation rates. Juvenile fish were exposed to reduced food availability, temperatures elevated to 1.8°C above natural conditions or both treatments in combination over 18 months of experimental tank rearing. When considered in isolation, reduced food had negative effects on the size, mass and condition of fish across the experiment. We detected variable effects of warm temperatures (negative effects on size and mass, but positive effect on lipids). When combined with food restriction, temperature effects on these traits were less pronounced, implying antagonistic stressor effects on morphological traits. Stressors combined additively, but had opposing effects on life history tactics: migration increased and maturation rates decreased under low food conditions, whereas the opposite occurred in the warm temperature treatment. Not all fish had expressed maturation or migration tactics by the end of the study, and the frequency of these 'unassigned' fish was higher in food deprivation treatments, but lower in warm treatments. Fish showing migration tactics were smaller and in poorer condition than fish showing maturation tactics, but were similar in size to unassigned fish. We further detected effects of food restriction on hypo-osmoregulatory function of migrants that may influence the fitness benefits of the migratory tactic at sea. We also highlight that responses to multiple stressors may vary depending on the response considered. Collectively, our results indicate contrasting effects of environmental stressors on life history trajectories in a facultatively migratory species.

Sensor Technology for Smart Homes.

As advances in technology continue relentlessly, intriguing possibilities for smart home services have emerged [...].

Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: Report of seven new cases.

Alpha-mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi-systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha-mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha-mannosidase in leucocytes and screening for abnormal urinary excretion of mannose-rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER ) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3-23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two-sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management.

Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance.

Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration. CONCLUSION: Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.

Aromatase inhibitors for short stature in male children and adolescents.

BACKGROUND: As a result of the essential role of oestrogens in epiphyseal closure, aromatase inhibitors have been trialled as an intervention to improve height outcomes in male children and adolescents by inhibiting the conversion of testosterone to oestradiol. OBJECTIVES: To assess the effects of aromatase inhibitors in male children and adolescents with short stature. SEARCH METHODS: To identify relevant trials, we searched the Cochrane Library (2014, Issue 7), MEDLINE, EMBASE, and the World Health Organization (WHO) ICTRP trial register from their inception until August 2014. In addition, we conducted citation searches and screened reference lists of included trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) if they compared use of an aromatase inhibitor with placebo in male children and adolescents with short stature. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles and abstracts for relevance. Both authors carried out screening for inclusion, data extraction, and risk of bias assessment, with any disagreements resolved following discussion. We assessed trials for quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument. We contacted study authors regarding missing information. Primary outcomes were final or near-final height, adverse events, and health-related quality of life. Secondary outcomes included all-cause mortality, cognitive outcomes, socioeconomic effects, laboratory measures, short-term growth parameters, and assessment of effects on bone health. Meta-analysis was not appropriate due to the substantial clinical heterogeneity between trials; we presented the findings of the review in narrative format. MAIN RESULTS: We included four RCTs involving 207 participants (84 on interventions) in the review. Trials included males with constitutional delay of growth and puberty (CDGP), idiopathic short stature (ISS), and growth hormone (GH) deficiency. Three of the trials had an overall low or unclear risk of bias for primary outcomes. Short-term growth outcomes, such as predicted adult height, improved in all trials. Just one trial reported the primary outcome of final and near-final height as an extension under non-randomised conditions. None of the trials assessed health-related quality of life. One publication provided detailed information regarding the incidence of adverse events. A significant proportion (45%) of prepubertal boys with ISS treated with letrozole developed mild morphological abnormalities of their vertebrae, compared with none in the placebo group. AUTHORS' CONCLUSIONS: Available evidence suggested that aromatase inhibitors improved short-term growth outcomes. There was no evidence to support an increase in final adult height, based on limited data, with only one of four trials publishing final height data under non-randomised conditions.

Seaweed polysaccharides (laminarin and fucoidan) as functional ingredients in pork meat: an evaluation of anti-oxidative potential, thermal stability and bioaccessibility.

The anti-oxidative potential of laminarin (L), fucoidan (F) and an L/F seaweed extract was measured using the DPPH free radical scavenging assay, in 25% pork (longissimus thoracis et lumborum (LTL)) homogenates (TBARS) (3 and 6 mg/mL) and in horse heart oxymyoglobin (OxyMb) (0.1 and 1 mg/mL). The DPPH activity of fresh and cooked minced LTL containing L (100 mg/g; L100), F100 and L/F100,300, and bioaccessibility post in vitro digestion (L/F300), was assessed. Theoretical cellular uptake of antioxidant compounds was measured in a transwell Caco-2 cell model. Laminarin displayed no activity and fucoidan reduced lipid oxidation but catalysed OxyMb oxidation. Fucoidan activity was lowered by cooking while the L/F extract displayed moderate thermal stability. A decrease in DPPH antioxidant activity of 44.15% and 36.63%, after 4 and 20 h respectively, indicated theoretical uptake of L/F antioxidant compounds. Results highlight the potential use of seaweed extracts as functional ingredients in pork.

Detecting type 2 diabetes and prediabetes among asymptomatic adults in the United States: modeling American Diabetes Association versus US Preventive Services Task Force diabetes screening guidelines.

BACKGROUND: Screening to detect prediabetes and diabetes enables early prevention and intervention. This study describes the number and characteristics of asymptomatic, undiagnosed adults in the United States who could be detected with prediabetes and type 2 diabetes using the American Diabetes Association (ADA) guidelines compared to the United States Preventive Services Task Force (USPSTF) guidelines. METHODS: We developed predictive models for undiagnosed diabetes and prediabetes using polytomous logistic regression from data on risk factors in the 2003-2010 National Health and Nutrition Examination Survey (n = 19,056). We applied these predictive models to the 2010 Medical Expenditure Panel Survey, which contains health care use data, to generate probabilities of undiagnosed diabetes and undetected prediabetes for each adult. We summed individual probabilities to estimate the number of adults who would be detected with prediabetes and/or type 2 diabetes if screened under ADA or USPSTF guidelines. We analyzed health care use patterns of people at high risk for diabetes. RESULTS: In 2010, 59.1 million adults met the USPSTF screening criteria including 24.4 million people with undetected prediabetes and 3.7 million people with undiagnosed diabetes. In comparison, among the 86.3 million people who met the ADA screening criteria, there were 33.9 million with undetected prediabetes and 4.6 million with undiagnosed type 2 diabetes. The ADA guidelines detected 38.9% more cases of prediabetes and 24.3% more cases of type 2 diabetes compared to the USPSTF guidelines. Subgroup analysis showed that ADA guidelines would detect 78% more cases of diabetes among the age 54 and younger population, in 40% more blacks, and in more than twice as many Hispanics than USPSTF guidelines. Only 58% of adults meeting ADA guidelines and 70% meeting USPSTF guidelines had ≥ 1 primary care office visit in 2010. CONCLUSIONS: Compared to USPSTF guidelines, ADA guidelines would screen more people and detect more cases of both prediabetes and type 2 diabetes, though a substantial percentage of patients with undetected cases had no contact with a primary care provider in 2010. Addressing the problem of large numbers of undetected prediabetes and type 2 diabetes cases will require new strategies for screening.

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.

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.

Economic model of a birth cohort screening program for hepatitis C virus.

UNLABELLED: Recent research has identified high hepatitis C virus (HCV) prevalence among older U.S. residents who contracted HCV decades ago and may no longer be recognized as high risk. We assessed the cost-effectiveness of screening 100% of U.S. residents born 1946-1970 over 5 years (birth-cohort screening), compared with current risk-based screening, by projecting costs and outcomes of screening over the remaining lifetime of this birth cohort. A Markov model of the natural history of HCV was developed using data synthesized from surveillance data, published literature, expert opinion, and other secondary sources. We assumed eligible patients were treated with pegylated interferon plus ribavirin, with genotype 1 patients receiving a direct-acting antiviral in combination. The target population is U.S. residents born 1946-1970 with no previous HCV diagnosis. Among the estimated 102 million (1.6 million chronically HCV infected) eligible for screening, birth-cohort screening leads to 84,000 fewer cases of decompensated cirrhosis, 46,000 fewer cases of hepatocellular carcinoma, 10,000 fewer liver transplants, and 78,000 fewer HCV-related deaths. Birth-cohort screening leads to higher overall costs than risk-based screening ($80.4 billion versus $53.7 billion), but yields lower costs related to advanced liver disease ($31.2 billion versus $39.8 billion); birth-cohort screening produces an incremental cost-effectiveness ratio (ICER) of $37,700 per quality-adjusted life year gained versus risk-based screening. Sensitivity analyses showed that reducing the time horizon during which health and economic consequences are evaluated increases the ICER; similarly, decreasing the treatment rates and efficacy increases the ICER. Model results were relatively insensitive to other inputs. CONCLUSION: Birth-cohort screening for HCV is likely to provide important health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths and is cost-effective at conventional willingness-to-pay thresholds.

Lack of sensitivity of the 1-µg low-dose ACTH stimulation test in a paediatric population with suboptimal cortisol responses to insulin-induced hypoglycaemia.

CONTEXT: The insulin-tolerance test (ITT) is the gold standard for evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. The low-dose ACTH stimulation test is increasingly used for evaluation of secondary adrenal insufficiency as several studies performed in adults have demonstrated high sensitivity and specificity when compared to the ITT. Whether the ACTH stimulation test demonstrates similar sensitivity in a paediatric and adolescent population compared with the gold standard is unclear. OBJECTIVE: To compare the sensitivity of the low-dose (1-µg) Synacthen(™) test (LDSST) and the gold-standard ITT in a paediatric and adolescent population. DESIGN AND PATIENTS: A retrospective review of 42 consecutive LDSSTs in children and adolescents with suboptimal cortisol responses (peak <500 nm) on ITT. RESULTS: Thirty-one patients (74%) had an adequate cortisol response to low-dose Synacthen(™) (sensitivity 26%). Patients had a higher cortisol increment with the LDSST than ITT (median Δ cortisol 294 vs 168 nm, P < 0.0001) and correspondingly a higher cortisol peak (median peak cortisol 572 vs 396 nm, P < 0.0001). Patients who had a suboptimal peak cortisol both on ITT and on LDSST had a lower baseline cortisol on ITT (median 178 vs 227 nm, P = 0.04). Peak cortisol on ITT was significantly higher in patients who had a subsequent normal LDSST than those that did not (median 417 vs 300 nm, P = 0.0005). CONCLUSIONS: The 1-µg LDSST lacks sensitivity in detection of secondary adrenal insufficiency in children when compared to the gold-standard ITT.