An approach to recognising and identifying metabolic presentations in the paediatric Irish Traveller population.

The Irish Traveller population are an endogamous, traditionally nomadic, Irish population. Irish Travellers practice consanguinity in the majority of marriages, thus resulting in a higher rate of rare autosomal recessive conditions within the population due to homozygous variants. Herein, we outline the clinical phenotypes associated with metabolic conditions seen in this population presenting in the neonatal period, infancy and childhood. Although Irish Travellers are traditionally based in Ireland and the UK, there are populations also living in mainland Europe and the USA. While there is generally an understanding amongst Irish paediatricians of the recessive conditions seen with this population in Ireland, they may be less commonly encountered abroad. It is important to consider a non-genetic aetiology alongside any consideration for a metabolic disorder. CONCLUSION: This paper acts as a comprehensive review of the metabolic conditions seen and provides a guide for the investigation of an Irish Traveller child with a suspected metabolic condition. WHAT IS KNOWN: • The Irish Traveller population are an endogenous population. • There are higher rates of inherited metabolic conditions in this population compared to the general population in Ireland. WHAT IS NEW: • This paper is a comprehensive review of all known inherited metabolic conditions encountered in the Irish Traveller population.

PGDIS position statement on the transfer of mosaic embryos 2021.

Chromosome testing strategies, such as preimplantation genetic testing for aneuploidy (PGT-A), improve initial IVF outcomes by avoiding unwitting transfer of aneuploid embryos in morphology-based selection practices. Newer technologies have revealed that some embryos may appear to have intermediate whole chromosome (or parts of a chromosome termed segmental) copy number results suggesting trophectoderm mosaicism. An embryo with a trophectoderm mosaic-range result may be the only option for transfer for some patients. Recent data suggest that such mosaic embryos can be transferred without added risk of abnormal birth outcomes but may be associated with increased implantation failure and miscarriage rates, with higher values of mosaicism appearing to be less favourable for producing good outcomes. In this Position Statement, we provide guidance to laboratories, clinics, clinicians and counsellors to assist in discussions on the utility and transfer of mosaic embryos.

Serious fungal disease incidence and prevalence in Indonesia.

BACKGROUND: Indonesia is a tropical country, warm and humid, with numerous environmental fungi. Data on fungal disease burden help policymakers and clinicians. OBJECTIVES: We have estimated the incidence and prevalence of serious fungal diseases. METHODS: We found all published and unpublished data and estimated the incidence and prevalence of fungal diseases based on populations at risk. HIV data were derived from UNAIDS (2017), pulmonary tuberculosis (PTB) data from 2013-2019, data on chronic pulmonary aspergillosis (CPA) were used to estimate CPA prevalence and likely deaths, COPD data from Hammond (2020), lung cancer incidence was from Globocan 2018, and fungal rhinosinusitis was estimated using community data from India. RESULTS: Overall ~7.7 million Indonesians (2.89%) have a serious fungal infection each year. The annual incidence of cryptococcosis in AIDS was 7,540. Pneumocystis pneumonia incidence was estimated at 15,400 in HIV and an equal number in non-HIV patients. An estimated 1% and 0.2% of new AIDS patients have disseminated histoplasmosis or Talaromyces marneffei infection. The incidence of candidaemia is 26,710. The annual incidence of invasive aspergillosis was estimated at 49,500 and the prevalence of CPA is at 378,700 cases. Allergic bronchopulmonary aspergillosis prevalence in adults is estimated at 336,200, severe asthma with fungal sensitisation at 443,800, and fungal rhinosinusitis at 294,000. Recurrent vulvovaginal candidiasis is estimated at 5 million/year (15-50 years old). The incidence of fungal keratitis around 40,050. Tinea capitis prevalence in schoolchildren about 729,000. CONCLUSIONS: Indonesia has a high burden of fungal infections.

Diagnostic Limitations in Congenital Zika Virus Infection.

This is the first documented case of an infant with congenital Zika virus infection (ZVI) born in Ireland. A term infant was delivered with an antenatal diagnosis of severe microcephaly. First trimester bloods confirmed maternal ZVI and although the infant did not have Zika virus RNA or Zika-specific IgM in her blood or urine, she had multiple clinical features of congenital ZVI and Zika virus RNA was present in the placenta.

A novel diagnosis scoring model to predict invasive pulmonary aspergillosis in the intensive care unit.

OBJECTIVES: To improve the quality of invasive pulmonary aspergillosis (IPA) management for intensive care unit (ICU) patients using a practical diagnostic scoring model. METHODS: This nested case-control study aimed to determine the incidence of IPA in 405 ICU patients, between July 2012 and June 2014, at 6 hospitals in Jakarta, Indonesia. Phenotypic identifications and galactomannan (GM) tests of sera and lung excreta were performed in mycology laboratory, Parasitology Department, Faculty of Medicine, Universitas Indonesia in Jakarta, Indonesia. RESULTS: The incidence of IPA in the ICUs was 7.7% (31 of 405 patients). A scoring model used for IPA diagnosis showed 4 variables as the most potential risk factors: lung excreta GM index (score 2), solid organ malignancy (score 2), pulmonary tuberculosis (score 2), and systemic corticosteroids (score 1). Patients were included in a high-risk group if their score was greater than 2, and in a low-risk group if their score was less than 2. CONCLUSION: This study provides a novel diagnosis scoring model to predict IPA in ICU patients. Using this model, a more rapid diagnosis and treatment of IPA may be possible. The application of the diagnosis scoring should be preceded by specified pre-requisites.

Production of Highly Polarized Positrons Using Polarized Electrons at MeV Energies.

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-Z target. Positron polarization up to 82% have been measured for an initial electron beam momentum of 8.19 MeV/c, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.

Neonatal Discharge Planning: Could Unscheduled Reviews be reduced in the First Six Weeks of Life?

The postnatal period offers an opportunity to provide information and education to new mothers. We analysed factors associated with unscheduled presentations of newborns to local primary care, maternity and paediatric services over a 3 week period to assess whether these could be targeted with discharge planning educational interventions. Data was collected prospectively from electronic databases and manually from patient records in the maternity hospital. Two hundred and seventy six patients under 6 weeks of age presented to the three services. Half of these visits were unscheduled 137 (49%). 40 (29%) of those that were unscheduled were felt to represent benign neonatal variants whilst 28 (20%) presented with feeding problems. Eighty one (59.3%) patients were discharged home, and this was unaffected by referrer patterns; GPs 19 (56%), Nurses 13 (57%) or parents77 (67%). At least 40 (29%) of reviews were felt to be inappropriate and could have been prevented. There is room for cost saving and quality improvement of the service through education.

Polar body based aneuploidy screening is poorly predictive of embryo ploidy and reproductive potential.

PURPOSE: Polar body (polar body) biopsy represents one possible solution to performing comprehensive chromosome screening (CCS). This study adds to what is known about the predictive value of polar body based testing for the genetic status of the resulting embryo, but more importantly, provides the first evaluation of the predictive value for actual clinical outcomes after embryo transfer. METHODS: SNP array was performed on first polar body, second polar body, and either a blastomere or trophectoderm biopsy, or the entire arrested embryo. Concordance of the polar body-based prediction with the observed diagnoses in the embryos was assessed. In addition, the predictive value of the polar body -based diagnosis for the specific clinical outcome of transferred embryos was evaluated through the use of DNA fingerprinting to track individual embryos. RESULTS: There were 459 embryos analyzed from 96 patients with a mean maternal age of 35.3. The polar body-based predictive value for the embryo based diagnosis was 70.3%. The blastocyst implantation predictive value of a euploid trophectoderm was higher than from euploid polar bodies (51% versus 40%). The cleavage stage embryo implantation predictive value of a euploid blastomere was also higher than from euploid polar bodies (31% versus 22%). CONCLUSION: Polar body based aneuploidy screening results were less predictive of actual clinical outcomes than direct embryo assessment and may not be adequate to improve sustained implantation rates. In nearly one-third of cases the polar body based analysis failed to predict the ploidy of the embryo. This imprecision may hinder efforts for polar body based CCS to improve IVF clinical outcomes.

The mind your health project: a randomized controlled trial of an innovative behavioral treatment for obesity.

OBJECTIVE: To determine whether acceptance-based behavioral treatment (ABT) would result in greater weight loss than standard behavioral treatment (SBT), and whether treatment effects were moderated by interventionist expertise or participants' susceptibility to eating cues. Recent research suggests that poor long-term weight-control outcomes are due to lapses in adherence to weight-control behaviors and that adherence might be improved by enhancing SBT with acceptance-based behavioral strategies. DESIGN AND METHODS: Overweight participants (n = 128) were randomly assigned to 40 weeks of SBT or ABT. RESULTS: Both groups produced significant weight loss, and when administered by experts, weight loss was significantly higher in ABT than SBT at post-treatment (13.17% vs. 7.54%) and 6-month follow-up (10.98% vs. 4.83%). Moreover, 64% of those receiving ABT from experts (vs. 46% for SBT) maintained at least a 10% weight loss by follow-up. Moderation analyses revealed a powerful advantage, at follow-up, of ABT over SBT in those potentially more susceptible to eating cues. For participants with greater baseline depression symptomology, weight loss at follow-up was 11.18% in ABT versus 4.63% in SBT; other comparisons were 10.51% versus 6.00% (emotional eating), 8.29% versus 6.35% (disinhibition), and 9.70% versus 4.46% (responsivity to food cues). Mediation analyses produced partial support for theorized food-related psychological acceptance as a mechanism of action. CONCLUSIONS: Results offer strong support for the incorporation of acceptance-based skills into behavioral weight loss treatments, particularly among those with greater levels of depression, responsivity to the food environment, disinhibition, and emotional eating, and especially when interventions are provided by weight-control experts.

Embryos whose polar bodies contain isolated reciprocal chromosome aneuploidy are almost always euploid.

STUDY QUESTION: When a chromosome aneuploidy is detected in the first polar body and a reciprocal loss or gain of the same chromosome is detected in the second polar body, is the resulting embryo usually aneuploid for that chromosome? SUMMARY ANSWER: When reciprocal aneuploidy occurs in polar bodies, the resulting embryo is usually normal for that chromosome, indicating that premature separation of sister chromatids (PSSC)-not non-disjunction-likely occurred in meiosis I. WHAT IS KNOWN ALREADY: Single-nucleotide polymorphism-based microarray analysis can be used to accurately determine the chromosomal status of polar bodies and embryos. Sometimes, the only abnormality found is a reciprocal gain or loss of one or two chromosomes in the two polar bodies. Prediction of the status of the resulting embryo in these cases is problematic. STUDY DESIGN, SIZE, DURATION: Blinded microarray analysis of previously diagnosed aneuploid embryos that had reciprocal polar body aneuploidy. MATERIALS, SETTING, METHODS: IVF cycles were performed between 2008 and 2011 in patients aged 40 ± 3 years (range 35-47 years) with an indication for polar body-based aneuploidy screening. Thirty-five aneuploid vitrified Day 3 embryos were warmed, cultured to Day 5 and biopsied for microarray analysis. Predictions were made for the ploidy status of the embryo if PSSC or non-disjunction had occurred. The signal intensity for the aneuploid chromosome in the first polar body was compared between those that resulted in euploid and aneuploid embryos. MAIN RESULTS AND THE ROLE OF CHANCE: Among 34 embryos with evaluable results, 31 were euploid on re-analysis. Of 43 chromosomes that had reciprocal aneuploidy in the polar bodies, 41 were disomic in the embryo, indicating that PSSC was likely to have occurred 95% (95% confidence interval 85-99%) of the time. The log 2 ratio signal intensity from the chromosomes that underwent non-disjunction, resulting in unbalanced embryos, were outliers when compared with those that underwent PSSC. LIMITATIONS, REASONS FOR CAUTION: Although most embryos with reciprocal aneuploid polar bodies were euploid, it is unknown whether they maintain equivalent reproductive potential when transferred. Further study is needed to determine whether these embryos should be re-biopsied and considered for transfer. WIDER IMPLICATIONS OF THE FINDINGS: This study is consistent with increasing evidence that PSSC is the primary cause of meiosis I errors in embryos from women of advanced reproductive age. Clinicians should be cautious in interpreting results from polar body aneuploidy screening, especially when only the first polar body is tested.

Recurring pulmonary hamartomas: cause for concern?

We report the case of a well-controlled female asthmatic who developed 'multiple pulmonary hamartomas' on three separate occasions over a period of 25 years that necessitated surgical resection. To our knowledge, this is the first report of recurrent hamartomas in a single individual necessitating multiple thoracotomies.

Single embryo transfer with comprehensive chromosome screening results in improved ongoing pregnancy rates and decreased miscarriage rates.

BACKGROUND: Single embryo transfer (SET) provides the most certain means to reduce the risk of multiple gestation. Regrettably, prospective trials of SET have demonstrated reductions in per-cycle delivery rates. A validated method of comprehensive chromosome screening (CCS) has the potential to optimize SET by transferring only euploid embryos. This retrospective study evaluates the efficacy of SET with CCS in an infertile population. METHODS: Overall and age-controlled ongoing pregnancy rates (OPR) were compared between women undergoing SET following CCS (CCS-SET, n= 140) and those undergoing SET without aneuploidy screening (control SET, n= 182). All transfers were at the blastocyst stage, with CCS performed after trophectoderm biopsy of expanded blastocysts and analysis with rapid PCR allowing for fresh transfer. RESULTS: In the CCS-SET and control SET groups, an OPR of 55.0 and 41.8%, respectively, was obtained. The OPR was lower for the control group (P< 0.01) despite a younger age than the CCS group (37.3 ± 3.4 versus 34.2 ± 3.9 years; P< 0.001). Birthweight and gestational age at delivery were equivalent. The proportion of clinical pregnancies resulting in miscarriage was higher in the control group (24.8 versus 10.5%, P< 0.01), with more patients requiring surgical interventions for aneuploid pregnancies. There was one monozygotic twin delivery in the CCS group and none in the control group. CONCLUSIONS: Compared with traditional blastocyst SET, SET after trophectoderm biopsy and rapid PCR-based CCS increases OPR and reduces the miscarriage rate. The enhanced selection empowered by CCS with SET may provide a practical way to eliminate multi-zygotic multiple gestation without compromising clinical outcomes per cycle.

Abnormal liver function tests in patients with Type 1 diabetes mellitus: prevalence, clinical correlations and underlying pathologies.

AIMS: To determine the prevalence of elevated alanine transaminase (ALT) in a large cohort of patients with Type 1 diabetes and to examine the clinical correlations and causes. Methods Patients with Type 1 diabetes mellitus were prospectively recruited and ALT, glycated haemoglobin and lipid profile were measured. Patients with Type 2 diabetes mellitus were recruited as a comparison group. PATIENTS: with abnormal ALT were investigated for underlying causes. Prevalence of abnormal ALT was analysed at three separate cut-offs and multivariable analysis used to identify independent risk factors. RESULTS: Nine hundred and eleven with Type 1 diabetes and 963 with Type 2 diabetes were included. The prevalence of elevated ALT was dependent on the cut-off value: > 30 IU/l in males and > 19 IU/l in females, > 50 and > 63 IU/l was 34.5, 4.3 and 1.9%, respectively, in Type 1 diabetes and 51.4, 8.2 and 3.7%, respectively, in Type 2 diabetes. In Type 1 diabetes an elevated ALT was associated with worse glycaemic control, age > 55 years and elevated triglycerides. Investigation of these patients revealed a cause in 43.6% of patients, predominantly non-alcoholic fatty liver disease (NAFLD). CONCLUSIONS: Elevated ALT is not uncommon in Type 1 diabetes and is associated with NAFLD-related risk factors. Patients with Type 1 diabetes and elevated ALT should be investigated as significant abnormalities may be found which are amenable to interventions.

Ehrlichiosis infection in a 5-year-old boy with neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly.

Ehrlichiosis should be considered in the differential diagnosis of any patient with recent fever, pancytopenia, hepatosplenomegaly, and history of tick exposure. We present a previously healthy 5-year-old boy who was referred to the Hematology-Oncology Clinic to consider a bone marrow etiologic process after his pediatrician discovered progressive neutropenia, anemia, thrombocytopenia, and hepatosplenomegaly accompanied by 2 days of fever. Bone marrow aspirate and biopsy were nonrevealing. Because of the history of a recent tick bite, a diagnosis of ehrlichiosis infection was considered and ultimately confirmed by IgG-specific serum testing. The patient's fever was treated symptomatically with acetaminophen, and symptoms resolved on their own without intervention. Ehrlichiosis is a tick-borne infection that occurs throughout the spring and summer, often causing findings that mimic a malignancy or serious hematologic disorder. The diagnosis should be considered in any person living in tick-infested areas and can be confirmed by polymerase chain reaction or serum antibody titers. Treatment with doxycycline can lead to rapid clinical improvement if the diagnosis is made early.

The role of preoperative chemotherapy in the treatment of infantile fibrosarcoma.

Infantile fibrosarcoma (IFS) is a rare tumor most often affecting the extremities of infants and young children. Unlike its adult counterpart, IFS has a low potential for metastatic spread, and surgical extirpation alone has therefore resulted in an excellent prognosis. The amputation rate, however, exceeds 50%. The dramatic response in 2 recent cases to preoperative chemotherapy, given in an attempt to avoid amputation, prompted this report and a review of the literature.

Chronic recurrent subluxation of the peroneal tendons in a pediatric patient. Surgical recommendations.

Numerous surgical and non-operative approaches have been used to treat chronic recurrent subluxation of the peroneal tendons in adult athletes. There have been no published reports of surgical repair in children. In this report on a skeletally immature patient a modification of the Chrisman-Snook procedure (previously described for lateral ligament reconstruction) is described to correct recurrent subluxation of the peroneal tendons, child.