Autonomic cardiac regulation during spontaneous nocturnal hypoglycemia in children with type 1 diabetes

Hypoglycemia is the most common complication in insulin treated diabetes. Though mostly mild, it can be fatal in rare cases: It is hypothesized that hypoglycemia related QTc prolongation contributes to cardiac arrhythmia.; To evaluate influence of nocturnal hypoglycemia on QTc and heart rate variability (HRV) in children with T1D.; Children and adolescents with T1D for at least 6 months participated in an observational study using continuous glucose monitoring (CGM) and Holter electrocardiogram for five consecutive nights. Mean QTc was calculated for episodes of nocturnal hypoglycemia (<3.7 mmol/L) and compared to periods of the same duration preceding hypoglycemia. HRV (RMSSD, low and high frequency power LF and HF) was analyzed for different 15 min intervals: before hypoglycemia, onset of hypoglycemia, before/after nadir, end of hypoglycemia and after hypoglycemia.; Mean QTc during hypoglycemia was significantly longer compared to euglycemia (412 ± 15 vs. 405 ± 18 ms, p = 0.005). HRV changed significantly: RMSSD (from 88 ± 57 to 73 ± 43 ms) and HF (from 54 ± 17 to 47 ± 17nu) decreased from before hypoglycemia to after nadir, while heart rate (from 69 ± 9 to 72 ± 12 bpm) and LF (from 44 ± 17 to 52 ± 21 nu) increased (p = 0.04).; A QTc lengthening effect of nocturnal hypoglycemia in children with T1D was documented. HRV changes occurred even before detection of nocturnal hypoglycemia by CGM, which may be useful for hypoglycemia prediction

Tubulopathy in nephrolithiasis: Consequence rather than cause

Tubulopathy in nephrolithiasis: Consequence rather than cause. To address whether a renal tubular dysfunction is encountered in a particular patient subgroup with urolithiasis, the following parameters of tubular function were measured in urine taken in the morning from 214 stone formers after fasting: pH, excretion of lysozyme and γ-glutamyl transferase (γ-GT); fractional excretion (FE) of glucose, insulin, Mg, K, and HCO3 after an alkali loading; and the renal threshold for phosphate (TmP/GFR). The following diagnoses were made in the patient group: primary hyperparathyroidism (N = 8), medullary sponge kidneys (N = 21), hyperuricemia (N = 10), cystinuria (N = 2), struvite stone disease (N = 6), idiopathic hypercalciuria of the absorptive (N = 25), dietary (N = 69) or renal (N = 7) type, and normocalciuric idiopathic urolithiasis (N = 66). In 31% of the patients TmP/GFR was below 0.80 mmole/liter and in 13% of the patients, FE HCO3 after alkali loading was above normal. Urinary excretion of lysozyme and that of γ-GT both were elevated in 17% of the patients. FE glucose, FE insulin, FE Mg, and FE K were elevated in 8, 9, 3, and 7% of the patients, respectively. This study demonstrates that a significant number of stone formers present with signs of renal tubular dysfunction, primarily involving the proximal tubule since apparent leaks of phosphate and of bicarbonate were most frequently encountered. The defects were not specific for a given etiologic group of patients; on the other hand, occurrence was related to the presence of large stones in the pyelocaliceal system at the time data were gathered. Taken together these data suggest that the tubulopathy in nephrolithiasis is the consequence rather than the cause of the stone

Fear of hypoglycemia and quality of life in young people with type 1 diabetes and their parents in the era of sensor glucose monitoring

IntroductionIt is crucial to understand psychosocial outcomes in children and adolescents with type 1 diabetes (T1D) and their families to provide optimal family-centered care. Hence, the aim of this study was to explore psychosocial outcomes in young people with T1D and their parents using currently available glucose monitoring devices in a real-life clinic setting.MethodsChildren and adolescents aged 2-18 years with T1D for more than 6 months and their parents were recruited into a cross-sectional study to complete the Hypoglycemia Fear Survey (HFS) and the Pediatric Quality of Life Inventory (PedsQL) Generic Score Scales, Diabetes Module and Family Impact Module. Demographics and diabetes-specific parameters were obtained from medicals records.ResultsFifty-nine children and adolescents (mean age 15.1 ± 3.0 years) and 49 parents of children (mean age of children 12.5± 3.3 years) of which 44 were child-parent dyads completed the questionnaires. Parents had a higher mean (SD) FOH total and worry subscore than children, total score was 37.9 (14.6) vs. 32.2 (11.9), p = 0.047 and worry subscore was 17.8 (10.4) vs. 12.8 (9.0), p = 0.01. Furthermore, lower parental diabetes-specific QoL score was observed in parents, 78.8 (12.2) vs. 82.7 (10.3), p=0.02. No difference in FOH and QoL between real-time continuous glucose monitoring (rtCGM) and intermittently scanned glucose monitoring (isCGM) users and users of devices with and without alerts was observed. In isCGM users (n=36 completing the child questionnaires, n=33 completing parent questionnaires), higher parental FOH and lower parental diabetes-specific QoL correlated with higher scanning frequency, r = 0.399, p = 0.021, and r = -0.464, p = 0.007 respectively. No significant correlation was documented between scanning frequency and child questionnaire scores.ConclusionsParents are more likely to perceive higher levels of psychosocial burden related to their child’s diabetes than children and adolescents with T1D, especially parents of younger children. This highlights the need for family-based education and treatment resources to support parents in diabetes management in addition to rapidly advancing diabetes technology. In isCGM users, higher parental FOH and lower parent-perceived QoL correlated with a higher scanning frequency, indicating the potential impact of glucose monitoring modality on psychosocial outcomes or vice versa

Metabolic trajectories of diabetic ketoacidosis onset described by breath analysis

PurposeThis feasibility study aimed to investigate the use of exhaled breath analysis to capture and quantify relative changes of metabolites during resolution of acute diabetic ketoacidosis under insulin and rehydration therapy.MethodsBreath analysis was conducted on 30 patients of which 5 with DKA. They inflated Nalophan bags, and their metabolic content was subsequently interrogated by secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS).ResultsSESI-HRMS analysis showed that acetone, pyruvate, and acetoacetate, which are well known to be altered in DKA, were readily detectable in breath of participants with DKA. In addition, a total of 665 mass spectral features were found to significantly correlate with base excess and prompt metabolic trajectories toward an in-control state as they progress toward homeostasis.ConclusionThis study provides proof-of-principle for using exhaled breath analysis in a real ICU setting for DKA monitoring. This non-invasive new technology provides new insights and a more comprehensive overview of the effect of insulin and rehydration during DKA treatment

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others

Bordetella pertussis and concomitant viral respiratory tract infections are rare in children with cough illness

BACKGROUND: Case reports, case series, and retrospective and prospective studies have reported concomitant Bordetella pertussis and viral respiratory tract pathogen infections in children with cough illness with conflicting results regarding their frequency. METHOD: A prospective 1-year study was performed in ambulatory and hospitalized patients aged 0 to 17 years with a cough illness. Polymerase chain reaction for viral (influenza A and B, parainfluenza 1 and 3, respiratory syncytial, metapneumovirus, and adenovirus) and bacterial pathogens including B. pertussis and B. parapertussis was applied to nasopharyngeal aspirate (NPA) specimens. The primary goal of the study was to assess the frequency of unsuspected Bordetella infections in patients thought to have a viral respiratory tract infection. The secondary goal was to determine the frequency of concomitant viral respiratory tract and Bordetella infections. RESULTS: B. pertussis and B. parapertussis DNA was amplified in 21 (2.0%) and 5 (0.5%) cases, respectively, of 1059 NPA specimens. Of the 1059 NPA specimens, 877 were tested in parallel for respiratory viruses, B. pertussis, and B. parapertussis; <1 virus was identified in 427 (48.7%) and Bordetella species was identified in 10 (1.1%) of these 877 NPA specimens but only 2 (0.2%) concomitant virus/Bordetella infections were identified. Specifically, of 268 NPAs positive for RSV, 1 (0.37%) was concomitant with B. pertussis infection as was 1 (3.7%) of 27 NPAs positive for hMPV. CONCLUSIONS:: B. pertussis and B. parapertussis infections were rare in patients with cough illness and so were concomitant virus/Bordetella infections. We propose that virus/Bordetella coinfections primarily occur by chance

Symptomatic Congenital Cytomegalovirus Infection in Children of Seropositive Women

Cytomegalovirus (CMV) is the most frequent congenital virus infection worldwide. The risk of congenital CMV (cCMV) transmission is highest in seronegative women who acquire primary CMV infection during pregnancy. A growing body of evidence indicates that secondary CMV infections in pregnant women with preconceptual immunity (either through reactivation of latent virus or re-infection with a new strain of CMV) contribute to a much greater proportion of symptomatic cCMV than was previously thought. Here, we describe a case of symptomatic cCMV infection in the newborn of a woman with proven immunity prior to pregnancy. Diagnosis was confirmed by CMV PCR from amniotic fluid and fetal MR imaging. The newborn presented with typical cCMV symptoms including jaundice, hepatosplenomegaly, cholestasis, petechiae, small head circumference, and sensorineural hearing loss, the most common neurologic sequela. CMV was detected in infant blood and urine by PCR, and intravenous ganciclovir was initiated and continued orally for 6 weeks totally. Apart from persisting right-sided deafness, the child exhibited normal neurological development up through the last follow-up at 4.5 years. To date, the most effective strategy to prevent vertical CMV transmission is hygiene counseling for women of childbearing age, which, in our case, and in concordance with recent literature, applies to seronegative, as well as seropositive, women. Once an expecting mother shows seroconversion or signs of an active CMV infection, there are no established procedures to reduce the risk of transmission, or therapeutic options for the fetus with signs of infection. After birth, symptomatic infants can be treated with ganciclovir to inhibit viral replication and improve hearing ability and neurodevelopmental outcome. A comprehensive review of the literature, including our case study, reveals the most current and significant diagnostic and treatment options available. In conclusion, the triad of maternal hygiene counseling, postnatal hearing screening of all newborns, followed by CMV PCR in symptomatic infants, and antiviral therapy of infants with symptomatic cCMV provides an outline of best practice to reduce the burden of CMV transmission sequelae

Tumor-associated FGF-23-induced hypophosphatemic rickets in children: a case report and review of the literature

Background: Tumor-associated fibroblast growth factor 23 (FGF-23)-induced hypophosphatemic rickets is a rare but known pediatric entity first described in 1959. It results from local production of phosphatonins by benign and malignant mesenchymal tumors. Case-Diagnosis/Treatment: We report an 8-year-old boy with tumor-associated hypophosphatemic rickets due to paraneoplastic FGF-23 secretion from a benign mesenchymal pelvic-bone tumor. Excessive FGF-23 production was visualized by immunohistochemistry in the resected tumor. Phosphate wasting stopped immediately after tumor resection. We reviewed 26 reports of pediatric patients with tumor-induced hypophosphatemic rickets; paraneoplastic FGF-23 secretion was documented in only three of them. All tumors developed inside bone, were benign in 21/26 cases, and were localized in femur/tibia (13/26), radius/ulna/humerus (7/26), pelvis (4/26), rib (1/26), and craniofacial (1/26) bones. Mean interval between onset of signs and/or symptoms and diagnosis was 34months. Conclusions: In patients with hypophosphatemic rickets acquired beyond infancy, radiologic investigations for bone tumors need to be performed rapidly. In contrast to biochemical screening for increased circulating FGF-23 levels, immunohistochemical confirmation of FGF-23 production in resected tumor tissue can be regarded as being well established

Simulation-Based Evaluation of Treatment Adjustment to Exercise in Type 1 Diabetes

Regular exercise is beneficial and recommended for people with type 1 diabetes, but increased glucose demand and changes in insulin sensitivity require treatment adjustments to prevent exercise-induced hypoglycemia. Several different adjustment strategies based on insulin bolus reductions and additional carbohydrate intake have been proposed, but large inter- and intraindividual variability and studies using different exercise duration, intensity, and timing impede a direct comparison of their effects. In this study, we use a mathematical model of the glucoregulatory system and implement published guidelines and strategies in-silico to provide a direct comparison on a single ‘typical’ person on a standard day with three meals. We augment this day by a broad range of exercise scenarios combining different intensity and duration of the exercise session, and different timing with respect to adjacent meals. We compare the resulting blood glucose trajectories and use summary measures to evaluate the time-in-range and risk scores for hypo- and hyperglycemic events for each simulation scenario, and to determine factors that impede prevention of hypoglycemia events. Our simulations suggest that the considered strategies and guidelines successfully minimize the risk for acute hypoglycemia. At the same time, all adjustments substantially increase the risk of late-onset hypoglycemia compared to no adjustment in many cases. We also find that timing between exercise and meals and additional carbohydrate intake during exercise can lead to non-intuitive behavior due to superposition of meal- and exercise-related glucose dynamics. Increased insulin sensitivity appears as a major driver of non-acute hypoglycemic events. Overall, our results indicate that further treatment adjustment might be required both immediately following exercise and up to several hours later, but that the intricate interplay between different dynamics makes it difficult to provide generic recommendations. However, our simulation scenarios extend substantially beyond the original scope of each model component and proper model validation is warranted before applying our in-silico results in a clinical setting.ISSN:1664-239