Low-dose diazoxide is safe and effective in infants with transient hyperinsulinism.

OBJECTIVE: Transient hyperinsulinism (THI) is the most common form of recurrent hypoglycaemia in neonates beyond the first week of life. Although self-resolving, treatment can be required. Consensus guidelines recommend the lower end of the diazoxide 5-15 mg/kg/day range in THI to reduce the risk of adverse events. We sought to determine if doses <5 mg/kg/day of diazoxide can be effective in THI. DESIGN, PATIENTS, MEASURMENTS: Infants with THI (duration <6 months) were treated with low-dose diazoxide from October 2015 to February 2021. Dosing was based on weight at diazoxide start: 2 mg/kg/day in infants 1000-2000 g (cohort 1), 3 mg/kg/day in those 2000-3500 g (cohort 2) and 5 mg/kg/day in those >3500 g. RESULTS: A total of 73 infants with THI (77% male, 33% preterm, 52% small-for-gestational age) were commenced on diazoxide at a median age of 11 days (range 3-43) for a median duration of 4 months (0.3-6.8), with no difference between cohorts. The mean effective diazoxide dose was 3 mg/kg/day (range 1.5-10); 35% (26/73) required an increase from their starting dose, including 60% (9/15) of cohort 1. There was no association between perinatal stress risk factors or treatment-related characteristics and dose increase. Adverse events occurred in 13 patients (18%); oedema (12%) and hyponatraemia (5%) were the most common. Two infants developed suspected necrotising enterocolitis (NEC); none had pulmonary hypertension. CONCLUSION: Diazoxide doses <5 mg/kg/day are effective in THI. While the nature of the association between diazoxide and NEC was unclear, other adverse events were mild. We suggest considering starting doses as low as 2-3 mg/kg/day in THI to balance the side effect risk while maintaining euglycaemia.

Pubertal Status at the Time of Fertility Preservation in Transgender Girls.

BACKGROUND: Puberty blockade and gender-affirming hormone therapy can impair fertility. Counseling on fertility preservation is important before initiation of therapy. Our study aimed to assess Tanner staging and the presence of virilizing secondary sex characteristics at the time of sperm collection and correlate the viability of sperm with the Tanner staging and degree of virilization. METHODS: A retrospective chart review of 23 transgender girls referred to pediatric urology at our academic pediatric transgender clinic for fertility preservation counseling was performed. At the initial visit before treatment, pubertal staging along with the assessment of virilizing secondary characteristics was performed. The semen analyses were evaluated for volume, sperm concentration, total sperm count, motility, and total motile count. RESULTS: Of the first 23 transgender girls evaluated and counseled, 8 transgender females successfully produced a sperm sample for cryopreservation. The average testicular volume was 18.5 ml and ranged from 12 ml to 20 ml. The median semen parameters were at or above the 2021 World Health Organization threshold. The 8 transgender females who successfully underwent fertility preservation presented with at least 1 secondary sex characteristic. In 1 subject with Tanner stage 3 pubic hair development and a testicular volume of 12 ml, only voice change was reported. Facial hair and laryngeal prominence were not present on examination. CONCLUSION: More than a third of our patients who accepted a referral to pediatric urology agreed to produce a sperm sample for cryopreservation. All of these patients successfully preserved sperm. With counseling and early referral to pediatric urology, a high percentage of fertility preservation in transgender girls was achieved.

Fertility Preservation in Children and Adolescents: Where We Are and Where We Are Going.

PURPOSE OF REVIEW: This review will describe current pediatric and adolescent fertility preservation methodologies and the ethical concerns surrounding these procedures, as well as highlight recent research that may pave the way for the development of new fertility preservation options. RECENT FINDINGS: Research is ongoing to allow prepubertal patients, particularly those with testes, to be able to have biologic children in the future. Studies on sperm in vitro maturation highlight the importance of supporting the spermatogonial stem cell niche for the development of mature sperm. The live birth of a rhesus macaque from in vitro fertilization using prepubertal testicular tissue and in vivo matured sperm gives hope to future human births. For patients with ovaries, prior work has led to successful fertility but further research is underway to refine these techniques and optimize outcomes. Organoid scaffolds have shown promise when being used for in vitro oocyte maturation. For children and adolescents undergoing gonadotoxic treatment, such as chemotherapy, or hormonal treatment, such as gender-affirming hormone therapy, future fertility potential may be negatively impacted. It is recommended that fertility preservation (FP) be offered to these patients and families prior to undergoing treatment. Fertility preservation for postpubertal patients mimics that in adults. For prepubertal children, however, the options are limited and in some cases still experimental. It is essential that this work continues so that we may offer children and adolescents the right to an open future and preserve their fertility potential.

Renal Outcomes in Neonates and Infants with Transposition Physiology Undergoing Arterial Switch Procedure.

Acute kidney injury (AKI) in children with Transposition of Great arteries (TGA) undergoing Arterial Switch operation (ASO) is an important complication in the post-operative period associated with worse outcomes. AKI in children post open cardiac surgery has been well studied, with lesser data in literature pertaining to TGA and its sub-types specifically. This was a prospective, observational study enrolling infants with TGA undergoing ASO at a single center over a span of a decade from January 2010 to December 2020. The infants were followed during the duration of ICU and hospital stay, with documentation of baseline and intraoperative parameters as well as post-operative course. Out of 145 infants enrolled in the study, 83.1% developed AKI with majority (83.9%) having stage 1 AKI. Higher odds of AKI were seen in infants requiring Norepinephrine [odds ratio - 16.76 (95% CI 2.19-128.2), p < 0.001] and those who developed gram-negative infections [2.81 (1.04-7.56), p - 0.036]. Infants with AKI had significantly higher vasoactive-inotropic support at day 1 than those without AKI [16 (12.5-21.50 vs 13 (10.25-15.75), p - 0.014]. Seventeen infants in the AKI group (14%) died as opposed to none in the non-AKI group (p = 0.076). Median hours of ventilator support required were significantly higher in those with AKI than those who did not develop AKI (48 vs 45.5 p = 0.015). The infants with ASO + ASD + PDA (53% of neonates who died) were younger, had less weight at admission, more gram-negative sepsis and need for dopamine, as compared to ASO + VSD + ASD (23.5% of mortality) and ASO + ASD + VSD + aortic arch repair (23.5% of mortality). AKI in infants with TGA undergoing ASO is common and associated with poorer outcomes. In this subpopulation, AKI development is associated most commonly with hemodynamic instability and infections. This is the first study, looking at outcomes of TGA depending on the sub-types of ASO surgeries done in the infants [ASO with ASD + PDA or ASD + VSD or ASD + VSD + Arch Repair].

Artificial intelligence for good health: a scoping review of the ethics literature.

BACKGROUND: Artificial intelligence (AI) has been described as the "fourth industrial revolution" with transformative and global implications, including in healthcare, public health, and global health. AI approaches hold promise for improving health systems worldwide, as well as individual and population health outcomes. While AI may have potential for advancing health equity within and between countries, we must consider the ethical implications of its deployment in order to mitigate its potential harms, particularly for the most vulnerable. This scoping review addresses the following question: What ethical issues have been identified in relation to AI in the field of health, including from a global health perspective? METHODS: Eight electronic databases were searched for peer reviewed and grey literature published before April 2018 using the concepts of health, ethics, and AI, and their related terms. Records were independently screened by two reviewers and were included if they reported on AI in relation to health and ethics and were written in the English language. Data was charted on a piloted data charting form, and a descriptive and thematic analysis was performed. RESULTS: Upon reviewing 12,722 articles, 103 met the predetermined inclusion criteria. The literature was primarily focused on the ethics of AI in health care, particularly on carer robots, diagnostics, and precision medicine, but was largely silent on ethics of AI in public and population health. The literature highlighted a number of common ethical concerns related to privacy, trust, accountability and responsibility, and bias. Largely missing from the literature was the ethics of AI in global health, particularly in the context of low- and middle-income countries (LMICs). CONCLUSIONS: The ethical issues surrounding AI in the field of health are both vast and complex. While AI holds the potential to improve health and health systems, our analysis suggests that its introduction should be approached with cautious optimism. The dearth of literature on the ethics of AI within LMICs, as well as in public health, also points to a critical need for further research into the ethical implications of AI within both global and public health, to ensure that its development and implementation is ethical for everyone, everywhere.

Post-hypospadias urethrocutaneous fistulae: no difference in repair success between proximal and distal fistulae.

INTRODUCTION Urethrocutaneous fistulae are the most common complication after hypospadias repair. We sought to compare outcomes of proximal versus distal urethrocutaneous fistula repair and hypothesized that patients with proximal fistulae would have lower rates of success than those with distal fistulae. We also aimed to evaluate factors that affected these outcomes. MATERIAL AND METHODS: Current procedural terminology codes were used to identify patients undergoing urethrocutaneous fistula repair after hypospadias surgery between 2014 and 2017 at an academic, pediatric urology referral center. Characteristics for each initial hypospadias repair and each fistula repair were noted, including location of meatus, location of fistula, type of magnification, suture type, interposition layer and post-operative stenting. The primary outcome was successful fistula repair. Univariate and multivariate analysis was performed. RESULTS: During the study period, 416 hypospadias repairs were performed. Thirty-one of these later presented with a fistula (8% fistula rate). Sixty-eight percent of fistulae were successfully closed with a single repair. There were 17 distal fistulae and 14 proximal fistulae. There was no difference in success between distal (71%) and proximal (64%) fistulae (p = 0.73). There was no statistically significant association between the primary outcome (successful fistula repair) and fistula location (p = 0.71), magnification (p = 0.38), suture type (p = 0.49), interposition coverage layer (0.43), or postoperative stenting (p = 0.92) on univariate or multivariate analysis. CONCLUSION: There is no difference in success when repairing distal versus proximal urethrocutaneous fistulae. Neither fistula location, type of magnification, suture type, interposition layer nor stenting affected outcomes.

Phosphorylation of mycobacterial phosphodiesterase by eukaryotic-type Ser/Thr kinase controls its two distinct and mutually exclusive functionalities.

Phosphorylation-mediated negative feedback regulation of cAMP levels by phosphodiesterase is well-established in eukaryotic cells. However, such a mechanism remains unexplored in prokaryotes. We report here the involvement of eukaryotic-type Ser/Thr kinases, particularly PknA in trans-phosphorylating phosphodiesterase from Mycobacterium tuberculosis (mPDE), that resulted in decreased enzyme turnover rate compared with its unphosphorylated counterpart. To elucidate the role of mPDE phosphorylation in hydrolyzing cellular cAMP, we utilized a phosphodiesterase knock-out Escherichia coli strain, ΔcpdA, where interference of endogenous eukaryotic-type Ser/Thr kinases could be excluded. Interestingly, the mPDE-complemented ΔcpdA strain showed enhanced cAMP levels in the presence of PknA, and this effect was antagonized by PknA-K42N, a kinase-dead variant. Structural analysis of mPDE revealed that four Ser/Thr residues (Ser-20, Thr-22, Thr-182, and Thr-240) were close to the active site, indicating their possible role in phosphorylation-mediated alteration in enzymatic activity. Mutation of these residues one at a time to alanine or a combination of all four (mPDE-4A) affected catalytic activity of mPDE. Moreover, mPDE-4A protein in kinase assays exhibited reduction in its phosphorylation compared with mPDE. In consonance, phosphoproteins obtained after co-expression of PknA with mPDE/S20A/T240A/4A displayed decreased phospho-signal intensities in immunoblotting with anti-phosphoserine/phosphothreonine antibodies. Furthermore, unlike mPDE, phospho-ablated mPDE-T309A protein exhibited impaired cell wall localization in Mycobacterium smegmatis, whereas mPDE-4A behaved similarly as wild type. Taken together, our findings establish mutually exclusive dual functionality of mPDE upon PknA-mediated phosphorylation, where Ser-20/Thr-240 influence enzyme activity and Thr-309 endorses its cell wall localization.

Determinants of Clinic Absenteeism: A Novel Method of Examining Distance from Clinic and Transportation.

Delayed treatment and non-adherence are associated with inferior prostate cancer (CaP) outcomes. Missed clinic appointments (MA) are one form of non-adherence that may be preventable. We conducted a retrospective cohort study of 1341 scheduled clinic encounters for men referred to an academic urology clinic for evaluation of known or suspected CaP. Driving distance and public transit times were calculated using a Google Distance Matrix API algorithm. Zip code level data regarding socioeconomic status was obtained from the 2013 American Community Survey. Logistic regression multivariate analysis was used to identify MA predictors. Of scheduled clinic encounters, 14% were missed. Public health insurance was associated with MA (Private insurance 10%, Public insurance 19%), (p < 0.01) Calendar month was associated with MA with December showing the highest rate (21.2%) and June the lowest (5.3%) rates. (p = 0.02) Appointments for suspected CaP were more likely to be missed (19.3%) than those for known CaP (10.5%), p < 0.01. Driving distance was inversely associated with rate of MA (CA median 11.8 miles, MA median 10.4 miles, p = 0.04) while public transit times were not (66.7 min for CA, 65.3 min for MA, p = 0.36). Men that missed appointments were from areas with lower household incomes and educational attainment. Patient encounter type, insurance status, and reason for referral remained significantly associated with MA after multivariable adjusted analysis. By computing public transit time to the clinic using a mapping engine, we present a novel way to measure this parameter for studies of urban health care.

Investigating an errorless learning approach for developing dental operative technique skills: A pilot study.

INTRODUCTION: Explicit instruction (conscious knowledge/rules) is generally used for learning dental operative skills; however, recent work has demonstrated advantages of learning skills implicitly with minimal accrual of conscious knowledge and reduced attentional demands. Therefore, this study examined the effects of learning handpiece manipulation skills explicitly (errorful) and implicitly (errorless: limited error detection/correction) under conditions of increased attentional demands (ie multitasking and additional instructions). MATERIALS AND METHODS: Non-dental university students were randomly assigned to errorless (n = 11) or errorful (n = 8) groups. They used pencil lead instead of a bur, with errorless learners shading shapes from simple (small circle) to complex (cross), while errorful learners shaded the shapes in reverse. During testing, they completed simulated cavities in baseline, additional instructions and multitask conditions. Learning performance was calculated as per cent of the shape shaded successfully. Test performance was computed as error in cavity length/depth and was compared with dental students who had completed their operative technique course (n = 14). RESULTS: Errorless learners were more accurate than errorful learners especially when shading difficult shapes (P = 0.042). With additional instructions, errorless and errorful learners did not differ in cavity depth (P = 0.057) or length (P = 0.540). When multitasking, errorless learners prepared the cavity length (P = 0.048) but not depth (P = 0.920) more accurately than errorful learners. Overall, performance of errorless learners was comparable to dental students. CONCLUSIONS: These preliminary findings suggest handpiece skills can be acquired implicitly via errorless learning, and it is less attentionally demanding than errorful learning, as evident by maintenance of preparation performance when processing additional relevant instructions and multitasking.

The Development of Prostate Adenocarcinoma in a Transgender Male to Female Patient: Could Estrogen Therapy Have Played a Role?

BACKGROUND: Prostate adenocarcinoma (PCa) is a rare diagnosis in the male to female transgender (MtFT) population with only a few case reports published in the current medical literature. Long standing beliefs of androgen suppression conferring a protective effect against prostate cancer development have been challenged by the literature citing adenocarcinoma development in the prostate of rodent models following combined estrogen and testosterone treatment. MATERIALS AND METHODS: We herein present a MtFT patient who presented with high grade PCa following 20 years of exogenous estrogen therapy. RESULTS: Immunohistochemical (IHC) localization of estrogen receptor alpha (ER-α) and progesterone receptor (PR) demonstrated positive staining in stromal cells; while, androgen receptor (AR) demonstrated positive staining in malignant glands and weak scattered staining in adjacent stroma. CONCLUSION: This pattern of staining raises concern for a possible contributing role of exogenous estrogen therapy in tumorigenesis. As awareness of gender dysphoria and acceptance of gender reassignment surgery has seen a recent increase, the unique needs of this population must be recognized. Prostate 77:824-828, 2017. © 2017 Wiley Periodicals, Inc.

Effort and trust: the underpinnings of active learning.

Three undergraduate students and their teacher discuss two crucial issues that form the implicit basis of active learning: effort and trust. They use a single course in a Health Sciences Program to anchor their comments.

Multitask training promotes automaticity of a fundamental laparoscopic skill without compromising the rate of skill learning.

BACKGROUND: A defining characteristic of expertise is automated performance of skills, which frees attentional capacity to better cope with some common intraoperative stressors. There is a paucity of research on how best to foster automated performance by surgical trainees. This study examined the use of a multitask training approach to promote automated, robust laparoscopic skills. METHODS: Eighty-one medical students completed training of a fundamental laparoscopic task in either a traditional single-task training condition or a novel multitask training condition. Following training, participants' laparoscopic performance was tested in a retention test, two stress transfer tests (distraction and time pressure) and a secondary task test, which was included to evaluate automaticity of performance. The laparoscopic task was also performed as part of a formal clinical examination (OSCE). RESULTS: The training groups did not differ in the number of trials required to reach task proficiency (p = .72), retention of skill (ps > .45), or performance in the clinical examination (p = .14); however, the groups did differ with respect to the secondary task (p = .016). The movement efficiency (number of hand movements) of single-task trainees, but not multitask trainees, was negatively affected during the secondary task test. The two stress transfer tests had no discernable impact on the performance of either training group. CONCLUSION: Multitask training was not detrimental to the rate of learning of a fundamental laparoscopic skill and added value by providing resilience in the face of a secondary task load, indicative of skill automaticity. Further work is needed to determine the extent of the clinical utility afforded by multitask training.

Examining Movement-Specific Reinvestment and Performance in Demanding Contexts.

Two experiments examined the roles of the dimensions of movement-specific reinvestment (movement self-consciousness and conscious motor processing) on performance under demanding conditions. In Experiment 1, novice golfers practiced a golf putting task and were tested under low- and high-anxiety conditions. Conscious motor processing was not associated with putting proficiency or movement variability; however, movement self-consciousness was positively associated with putting proficiency and appeared to be negatively associated with variability of impact velocity in low-anxiety conditions, but not in high-anxiety conditions. Increased anxiety and effort possibly left few attention resources for movement self-consciousness under high anxiety. In Experiment 2, participants performed a quiet standing task in single- and dual-task conditions. Movement self-consciousness was positively associated with performance when attention demands were low (single task) but not when attention demands were high (dual task). The findings provide insight into the differential influence of the two dimensions of movement-specific reinvestment under demanding conditions.

Paratesticular Fibrous Pseudotumor in 8-Year-Old Male Following Scrotal Trauma.

Fibrous pseudotumors are a rare type of benign paratesticular mass that normally present to patients in their 30s secondary to local trauma. Here, we describe an 8-year-old male patient that presented with several right testicular masses following an injury 2 years prior. The masses were successfully resected in a testicle-sparing operation. This report describes the unique finding of a reactive fibroinflammatory mass in a pediatric patient, and also highlights the uncertainty of pseudotumor diagnostic criteria that need to be recognized in order to avoid unnecessary orchiectomy.

The Antitubercular Activities of Natural Products with Fused-Nitrogen-Containing Heterocycles.

Tuberculosis (TB) is notorious as the leading cause of death worldwide due to a single infectious entity and its causative agent, Mycobacterium tuberculosis (Mtb), has been able to evolve resistance to all existing drugs in the treatment arsenal complicating disease management programs. In drug discovery efforts, natural products are important starting points in generating novel scaffolds that have evolved to specifically bind to vulnerable targets not only in pathogens such as Mtb, but also in mammalian targets associated with human diseases. Structural diversity is one of the most attractive features of natural products. This review provides a summary of fused-nitrogen-containing heterocycles found in the natural products reported in the literature that are known to have antitubercular activities. The structurally targeted natural products discussed in this review could provide a revealing insight into novel chemical aspects with novel biological functions for TB drug discovery efforts.

Contemporary disparities in progression to orchiopexy for cryptorchidism as reported in the Pediatric Health Information System (PHIS) database.

INTRODUCTION: When evaluating the timeliness of orchiopexy for cryptorchidism, health disparities are apparent among Hispanic and African American males and those with public insurance. Since the publication of these data, the COVID-19 pandemic has stressed our healthcare system and significantly affected the provision of pediatric urology care. OBJECTIVE: We sought to assess if certain groups were disproportionately affected in progression to orchiopexy after the diagnosis of cryptorchidism during and after the pandemic in US freestanding children's hospitals. STUDY DESIGN: Using the PHIS database, pediatric patients ≤5 years who underwent orchiopexy between January 2018 and December 2022 were retrospectively analyzed. Exclusion criteria included prematurity, retractile testes, and testicular torsion. Primary outcomes were age at orchiopexy and the proportion of individuals undergoing timely orchiopexy for cryptorchidism. RESULTS: Over the study period 3140 patients ≤5 years old underwent orchiopexy for cryptorchidism. Non-Hispanic Blacks and Hispanics were significantly less likely to have timely orchiopexy and underwent orchiopexy 2.13 and 3.60 months later compared to whites (p < 0.01). As compared to pre-COVID-19, during the pandemic the proportion of patients who had timely surgery was higher and the median age was significantly lower (p = 0.01 and p < 0.01, respectively) in white patients only. Over the study period, patients with public insurance were less likely to have timely orchiopexy and underwent orchiopexy 2.94 months later (p < 0.01) than patients with private insurance. Compared to during the pandemic, post-pandemic a significantly lower proportion of publicly insured patients have since undergone timely orchiopexy (p = 0.04). Patients in the West were less likely to have timely orchiopexy and had a higher age at time of orchiopexy (p < 0.01) than other regions. However, in the West during the pandemic, the proportion of children who had timely surgery was higher compared to pre-and post-COVID-19 (p < 0.01). DISCUSSION: Overall, regardless of insurance status, race, or location, a significant proportion of patients did not undergo timely orchiopexy. During the pandemic white patients had a lower median age and an increased proportion underwent timely orchiopexy, despite the number of orchiopexies remaining constant. Disparities in the post-COVID-19 era have been further exacerbated for publicly insured patients, who a significantly lower proportion of have since undergone timely orchiopexy. Specific efforts are required across the United States to increase timely orchiopexy for all boys. CONCLUSIONS: Progression to timely orchiopexy remains low for all boys in the era surrounding COVID-19; certain groups appear to be more adversely affected.

Inter-disciplinary provider development of an online, interactive adolescent varicocele decision aid prototype.

BACKGROUND: Decision-making regarding varicocele management can be a complex process for patients and families. However, to date, no studies have presented ways to mitigate the decisional conflict surrounding varicoceles. OBJECTIVE: To facilitate a discussion among physicians in order to develop a framework of the decision-making process regarding adolescent varicocele management, which will inform the development of the first online, interactive decision aid. MATERIALS AND METHODS: Semi-structured interviews with pediatric urologists and interventional radiologists were conducted to discuss their rationale for varicocele decision-making. Interviews were audio recorded, transcribed, and coded. Key themes were identified, grouped, and then qualitatively analyzed using thematic analysis. Utilizing the common themes identified and the Ottawa Decision Support Framework, a decision aid prototype was developed and transformed into a user-friendly website: varicoceledecisionaid.com. RESULTS: Pediatric urologists (n = 10) and interventional radiologists (n = 2) were interviewed. Key themes identified included: (1) definition/epidemiology; (2) observation as an appropriate management choice; (3) reasons to recommend repair; (4) types of repair; (5) reasons to recommend one repair over another; (6) shared decision-making; and (7) appropriate counseling. With this insight, a varicocele decision aid prototype was developed that engages patients and parents in the decision-making process. DISCUSSION AND CONCLUSIONS: This is the first interactive and easily accessible varicocele decision aid prototype developed by inter-disciplinary physicians for patients. This tool aids in decision-making surrounding varicocele surgery. It can be used before or after consultation to help families understand more about varicoceles and their repair, and why intervention may or may not be offered. It also considers a patient and family's personal values. Future studies will incorporate the patient and family perspective into the decision-making aid as well as implement and test the usability of this decision aid prototype in practice and in the wider urologic community.

Does KUB play a role in the diagnosis of bladder bowel dysfunction?

INTRODUCTION: Kidney ureter bladder radiography (KUB) is widely used for the evaluation of constipation in children with bladder and bowel dysfunction (BBD); however, there is varying evidence to support its routine diagnostic use. One drawback to KUB is radiation exposure. The dangers of radiation in children are well-documented, and per As Low As Reasonably Achievable, non-beneficial radiation should be avoided. This risk is especially high in children who undergo repeated imaging in the follow up of constipation treatment. OBJECTIVE: We sought to assess the utility of KUB in diagnosing children with BBD by comparing it to four diagnostic tests and/or validated instruments: the Dysfunctional Voiding Symptom Score (DVSS), Rome IV criteria, rectal diameter on ultrasound (RD), and the Bristol Stool Form Score (BSFS). STUDY DESIGN: We prospectively enrolled a cohort of patients presenting to an academic pediatric urology practice with symptoms of BBD. Severity of stool burden on KUB (mild, moderate, or severe), RD on ultrasound (≥3.4 cm), DVSS, Rome IV, and BSFS were obtained for each patient. All imaging was interpreted by a pediatric radiologist and pediatric urologist. Primary outcomes were the association between the four diagnostic tests and KUB stool burden. Bivariate analysis of all individual variables versus KUB was performed, as well as multivariate regressions to determine if multiple measures were predictive of KUB stool burden when combined. RESULTS: Between October 2020 and May 2022, 50 patients were enrolled. All children were under the age of 18, with a median age of 8 years (IQR 3-13). 38 % were male. Median BMI-for-age-percentile was 80.8 (IQR 50.3-98.3). When comparing individual variables to KUB in bivariate analyses, it was found that RD on ultrasound is predictive of significant stool burden on KUB (p = 0.03). No other individual variables were predictive. In the multivariate analyses, no combination of tests was found to be predictive of KUB. DISCUSSION: We compared the effectiveness of four commonly used diagnostic tests in children with BBD to validate the use of KUB. In conclusion, our results support the use of RD on ultrasound as a non-radiating alternative to KUB to assess stool burden. Data also suggest that KUB for fecal load does not correlate with urinary (DVSS) or bowel (Rome IV, BSFS) symptoms in BBD, and that symptoms scores should still be used independently for diagnosis and monitoring of treatment response. CONCLUSION: In conclusion, KUB has a limited role in the diagnosis of BBD.

Environmental sphagnum-associated fungi target thiol homeostasis to compete with Mycobacterium tuberculosis.

Mycobacterial species in nature are found in abundance in sphagnum peat bogs where they compete for nutrients with a variety of microorganisms including fungi. We screened a collection of fungi isolated from sphagnum bogs by co-culture with Mycobacterium tuberculosis (Mtb) to look for inducible expression of antitubercular agents and identified five fungi that produced cidal antitubercular agents upon exposure to live Mtb. Whole genome sequencing of these fungi followed by fungal RNAseq after Mtb exposure allowed us to identify biosynthetic gene clusters induced by co-culture. Three of these fungi induced expression of patulin, one induced citrinin expression and one induced the production of nidulalin A. The biosynthetic gene clusters for patulin and citrinin have been previously described but the genes involved in nidulalin A production have not been described before. All three of these potent electrophiles react with thiols and treatment of Mtb cells with these agents followed by Mtb RNAseq showed that these natural products all induce profound thiol stress suggesting a rapid depletion of mycothiol. The induction of thiol-reactive mycotoxins through three different systems in response to exposure to Mtb suggests that fungi have identified this as a highly vulnerable target in a similar microenvironment to that of the caseous human lesion.

Recognition of Hyperinsulinaemic Hypoglycaemia in Infants with Congenital Central Hypoventilation Syndrome.

INTRODUCTION: Congenital central hypoventilation syndrome [CCHS] is a rare autosomal dominant condition due to mutations in the transcription factor PHOX2B. It is characterized by alveolar hypoventilation with symptoms of autonomic nervous system dysfunction. Hyperinsulinaemic hypoglycaemia [HH] due to glucose dysregulation caused by anomalous insulin secretion has been reported as a feature of CCHS. However, HH and glycaemic outcomes in the context of CCHS have not been characterised in longitudinal follow-up. We describe the variable phenotype of glucose dysregulation and glycaemic outcomes in children with CCHS. Case presenatation: : We report 6 children with PHOX2B mutation-positive CCHS diagnosed with HH in a national cohort from two UK Congenital Hyperinsulinism specialist centres. We describe the initial presentation, the challenges in management and glycaemic outcomes in longitudinal follow-up. All patients were term infants diagnosed with CCHS in the neonatal period, due to PHOX2B mutations and required long-term ventilation by tracheostomy. HH was diagnosed at a median age 222 days [range 36-594] with post-prandial hypoglycaemia [4/6 patients] or fasting hypoglycaemia [2/6 patients]. Two patients were treated with diazoxide monotherapy; one with diazoxide and overnight continuous gastrostomy feeds; one with acarbose and two with dietary manifestations and use of continuous glucose monitoring sensor [CGMS]. Three patients who presented earlier in the observation period demonstrated a reduction in the severity of HH over time, leading to hypoglycaemia resolution at a median age of 4.8 years [range 4.45-5.5 years]. CONCLUSION: Patients with CCHS, due to PHOX2B mutations, may experience both fasting and postprandial hypoglycemia, necessitating treatment for HH. Clinicians should screen children with CCHS for hypoglycemia symptoms to quickly identify those affected by HH, initiate prompt treatment, and prevent potential brain injury from severe hypoglycemia. The severity of hypoglycemia due to HH tends to decrease over time, with glycemic resolution potentially being achieved over several years.