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International Forum of Allergy &... Jul 2024Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant...
Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes.
PubMed: 38958881
DOI: 10.1002/alr.23403 -
Current Diabetes Reports Jul 2024This review explores the emerging evidence regarding pathogenesis, future trajectories, treatment options, and phenotypes of youth-onset type 2 diabetes (T2D). (Review)
Review
PURPOSE OF REVIEW
This review explores the emerging evidence regarding pathogenesis, future trajectories, treatment options, and phenotypes of youth-onset type 2 diabetes (T2D).
RECENT FINDINGS
Youth-onset T2D is increasing in incidence and prevalence worldwide, disproportionately affecting First Nations communities, socioeconomically disadvantaged youth, and people of colour. Youth-onset T2D differs in pathogenesis to later-onset T2D and progresses more rapidly. It is associated with more complications, and these occur earlier. While there are limited licensed treatment options available, the available medications also appear to have a poorer response in youth with T2D. Multiple interacting factors likely contribute to this rising prevalence, as well as the increased severity of the condition, including structural inequities, increasing obesity and sedentary lifestyles, and intergenerational transmission from in-utero exposure to maternal hyperglycemia and obesity. Youth-onset T2D is also associated with stigma and poorer mental health, and these impact clinical management. There is an urgent need to develop effective interventions to prevent youth-onset T2D and enhance engagement of affected youth. It is also critical to better understand the differing phenotypes of youth-onset T2D, to effectively target treatments, and to address intergenerational transmission in high-risk populations.
PubMed: 38958831
DOI: 10.1007/s11892-024-01546-2 -
Odontology Jul 2024Hyaluronic acid (HA), known for diverse properties, was investigated for its potential in dental pulp therapy. This study investigated the potential of HA in dental pulp...
Hyaluronic acid (HA), known for diverse properties, was investigated for its potential in dental pulp therapy. This study investigated the potential of HA in dental pulp therapy by examining the physical properties and effects of zinc oxide eugenol (ZOE) pulpotomy materials containing varying HA concentrations on rat molar teeth. In vitro tests assessed compressive strength and hardness of ZOE materials blended with HA (0.5%, 1%, 3%) and HA gels (0.54%, 0.8%). 120 samples, encompassing the control group, underwent compressive strength testing, while 60 samples were designated for hardness assessment. In vivo experiments on rat molars studied histological effects of HA-containing ZOE on dental pulp over 1 week and 1 month. Gels with HA concentrations of 0.5%, 1%, and 0.54% were used in pulpotomy on 22 rats. Each rat underwent the procedure on four teeth, with one tooth serving as a control, totaling 88 teeth subjected to the intervention. In the analyses, SPSS 22.0 was used and the significance level was set at P = 0.05. Findings showed that HA at 0.5% maintained compressive strength, but higher concentrations decreased mechanical properties significantly (P = 0.001). Histological assessments indicated better outcomes with lower HA concentrations in terms of odontoblast layer continuity (P = 0.005 at 1 month) and pulp vitality (P = 0.001 at 1 week and P = 0.018 at 1 month). The study suggests HA holds promise for pulpotomy and regenerative endodontic treatments, but further research is needed to understand long-term clinical implications.
PubMed: 38958828
DOI: 10.1007/s10266-024-00973-7 -
Pediatric Surgery International Jul 2024Split abdominal wall muscle flap (SAWMF) is a technique to repair large defects in congenital diaphragmatic hernia (CDH). A possible objection to this intervention could...
PURPOSE
Split abdominal wall muscle flap (SAWMF) is a technique to repair large defects in congenital diaphragmatic hernia (CDH). A possible objection to this intervention could be any associated abdominal muscle weakness. Our aim is to analyze the evolution of this abdominal muscle wall weakness.
METHODS
Retrospective review of CDH repair by SAWMF (internal oblique muscle and transverse) from 2004 to 2023 focusing on the evolution of muscle wall weakness.
RESULTS
Eighteen neonates of 148 CDH patients (12,1%) were repaired using SAWMF. Mean gestational age and birth weight were 35.7 ± 3.5 weeks and 2587 ± 816 g. Mean lung-to-head ratio was 1.49 ± 0.28 and 78% liver-up. Seven patients (38%) were prenatally treated by tracheal occlusion. Ninety-four percent of the flaps were used for primary repair and one to repair a recurrence. One patient (5.6%) experienced recurrence. Abdominal muscle wall weakness was present in the form of a bulge. Resolution of weakness at 1, 2 and 3 years was 67%, 89% and 94%, respectively. No patient required treatment for weakness or died.
CONCLUSIONS
Abdominal muscular weakness after a split abdominal wall muscle flap repair is not a limitation for its realization since it is asymptomatic and presents a prompt spontaneous resolution.
LEVEL OF EVIDENCE
IV.
Topics: Humans; Hernias, Diaphragmatic, Congenital; Infant, Newborn; Retrospective Studies; Male; Surgical Flaps; Female; Abdominal Wall; Muscle Weakness; Abdominal Muscles; Herniorrhaphy; Postoperative Complications; Treatment Outcome
PubMed: 38958763
DOI: 10.1007/s00383-024-05751-8 -
Journal of Neurology Jul 2024Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have... (Review)
Review
BACKGROUND
Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data.
METHODS
A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases.
RESULTS
A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78-10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01-8.03) and for late-onset cases, it was 5.48 (95% CI 4.10-7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder.
CONCLUSIONS
The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy.
PubMed: 38958756
DOI: 10.1007/s00415-024-12452-8 -
Child's Nervous System : ChNS :... Jul 2024Cervicothoracic ventral-dorsal rhizotomy (VDR) is a potential treatment of medically refractory hypertonia in patients who are not candidates for intrathecal baclofen,...
PURPOSE
Cervicothoracic ventral-dorsal rhizotomy (VDR) is a potential treatment of medically refractory hypertonia in patients who are not candidates for intrathecal baclofen, particularly in cases of severe upper limb hypertonia with limited to no function. A longitudinal cohort was identified to highlight our institutional safety and efficacy using cervicothoracic VDR for the treatment of hypertonia.
METHODS
Retrospective data analysis was performed for patients that underwent non-selective cervicothoracic VDR between 2022 and 2023. Non-modifiable risk factors, clinical variables, and operative characteristics were collected.
RESULTS
Six patients (three female) were included. Four patients underwent a bilateral C6-T1 VDR, one patient underwent a left C7-T1 VDR, and another underwent a left C6-T1 VDR. Three patients had quadriplegic mixed hypertonia, one patient had quadriplegic spasticity, one patient had triplegic mixed hypertonia, and one patient had mixed hemiplegic hypertonia. The mean difference of proximal upper extremity modified Ashworth scale (mAS) was - 1.4 ± 0.55 (p = 0.002), and - 2.2 ± 0.45 (p < 0.001) for the distal upper extremity. Both patients with independence noted quality of life improvements as well as increased ease with dressing and orthotics fits. Caregivers for the remaining four patients noted improvements in caregiving provision, mainly in dressing, orthotics fit, and ease when transferring.
CONCLUSION
Cervicothoracic VDR is safe and provides tone control and quality of life improvements in short-term follow-up. It can be considered for the treatment of refractory hypertonia. Larger multicenter studies with longer follow-up are necessary to further determine safety along with long-term functional benefits in these patients.
PubMed: 38958730
DOI: 10.1007/s00381-024-06479-5 -
Neuroradiology Jul 2024Infants undergoing CSF shunting procedures face a rare complication which we propose to rename "Widespread Haemorrhages in Infants Post-Shunting" (WHIPS) to better...
PURPOSE
Infants undergoing CSF shunting procedures face a rare complication which we propose to rename "Widespread Haemorrhages in Infants Post-Shunting" (WHIPS) to better capture this unique phenomenon specific to infants undergoing CSF diversion. Our objective is to analyse the risk factors for WHIPS development and provide a detailed neuroradiological description of these haemorrhages.
MATERIALS AND METHODS
A radiology information system (RIS) was searched using the search terms "shunt" and/or "catheter" and/or "drain" and/or "ventriculoperitoneal" and/or "VP" between September 2008 to January 2021 for patients < 12 months of age. Clinical data was compiled for each patient meeting the inclusion criteria. Included cases were reviewed by three radiologists for the presence of WHIPS with calculation of the bifrontal ratio and documenting haemorrhage number, morphology, location and lobar distribution.
RESULTS
51 patients met inclusion criteria, 8 WHIPS patients and 43 controls. There was a statistically significant correlation between a larger post-op head circumference and WHIPS (p = 0.04). WHIPS was associated with post-haemorrhagic hydrocephalus and post-infectious hydrocephalus (p = 0.009). WHIPS were identified in the cortico-subcortical regions, periventricular white matter, and deep white matter. Haemorrhages were either punctate, ovoid or confluent. Haemorrhages ranged from single to innumerable.
CONCLUSIONS
WHIPS represent a rare and under-recognised complication of CSF shunting unique to the infantile population. We postulate deep and superficial medullary venous haemorrhage as an underlying mechanism related to disordered intracranial hydrodynamics which are exacerbated in the infantile population due to underdeveloped arachnoid granulations and a compliant skull.
PubMed: 38958705
DOI: 10.1007/s00234-024-03418-8 -
Diabetologia Jul 2024Strategies to augment functional beta cell mass include directed differentiation of stem cells towards a beta cell fate, which requires extensive knowledge of...
AIMS/HYPOTHESIS
Strategies to augment functional beta cell mass include directed differentiation of stem cells towards a beta cell fate, which requires extensive knowledge of transcriptional programs governing endocrine progenitor cell differentiation in vivo. We aimed to study the contributions of the Brahma-related gene-1 (BRG1) and Brahma (BRM) ATPase subunits of the SWI/SNF chromatin remodelling complex to endocrine cell development.
METHODS
We generated mice with endocrine progenitor-specific Neurog3-Cre BRG1 removal in the presence of heterozygous (Brg1;Brm) or homozygous (double knockout: DKO) BRM deficiency. Whole-body metabolic phenotyping, islet function characterisation, islet quantitative PCR and histological characterisation were performed on animals and tissues postnatally. To test the mechanistic actions of SWI/SNF in controlling gene expression during endocrine cell development, single-cell RNA-seq was performed on flow-sorted endocrine-committed cells from embryonic day 15.5 control and mutant embryos.
RESULTS
Brg1;Brm mice exhibit severe glucose intolerance, hyperglycaemia and hypoinsulinaemia, resulting, in part, from reduced islet number; diminished alpha, beta and delta cell mass; compromised islet insulin secretion; and altered islet gene expression programs, including reductions in MAFA and urocortin 3 (UCN3). DKO mice were not recovered at weaning; however, postnatal day 6 DKO mice were severely hyperglycaemic with reduced serum insulin levels and beta cell area. Single-cell RNA-seq of embryonic day 15.5 lineage-labelled cells revealed endocrine progenitor, alpha and beta cell populations from SWI/SNF mutants have reduced expression of Mafa, Gcg, Ins1 and Ins2, suggesting limited differentiation capacity. Reduced Neurog3 transcripts were discovered in DKO endocrine progenitor clusters, and the proliferative capacity of neurogenin 3 (NEUROG3) cells was reduced in Brg1;Brm and DKO mutants.
CONCLUSIONS/INTERPRETATION
Loss of BRG1 from developing endocrine progenitor cells has a severe postnatal impact on glucose homeostasis, and loss of both subunits impedes animal survival, with both groups exhibiting alterations in hormone transcripts embryonically. Taken together, these data highlight the critical role SWI/SNF plays in governing gene expression programs essential for endocrine cell development and expansion.
DATA AVAILABILITY
Raw and processed data for scRNA-seq have been deposited into the NCBI Gene Expression Omnibus (GEO) database under the accession number GSE248369.
PubMed: 38958700
DOI: 10.1007/s00125-024-06211-7 -
European Journal of Pediatrics Jul 2024Although sleep is essential for (recovery of) health, it is adversely affected by hospitalization, due to disease discomfort, environmental noise, and care routines,...
Although sleep is essential for (recovery of) health, it is adversely affected by hospitalization, due to disease discomfort, environmental noise, and care routines, causing reduced sleep and increased disturbances. This study evaluates factors affecting sleep quality and quantity in hospitalized children and compares inpatient sleep with sleep at home. Using an observational, prospective study design, we assessed sleep in hospitalized children aged 1-12 years, admitted to a tertiary center, and compared this with home 6-8 weeks after discharge. We measured total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency, awakenings, and subjective sleep quality, using actigraphy, sleep diaries, and PROMIS questionnaires. We explored an array of sleep-disturbing factors. Regression analyses identified key determinants affecting sleep patterns, while mixed linear models compared sleep in hospital to sleep at home. Out of 621 eligible patients, 467 were invited, and 272 (58%) consented to participate. Key determinants of sleep included pain, number of previous admissions, (underlying) chronic illness, and environment-, staff-, and disease-related factors. Parents reported lower perceived sleep quality in the hospital compared to at home, 97-min (SE 9) lower TST, 100-min (5) longer WASO, more difficulties with falling asleep, lower sleep satisfaction, and more awakenings. Actigraphy outcomes revealed shorter TST (20 min (6)), but better sleep efficiency and fewer awakenings in the hospital. Conclusion: Sleep in hospital was compromised in comparison to sleep at home, primarily due to disturbances related to treatment, environment, and staff. These findings underscore the necessity and potential of relative simple interventions to improve sleep quality and minimize sleep disturbances in hospitalized children.
PubMed: 38958694
DOI: 10.1007/s00431-024-05660-x -
European Journal of Nuclear Medicine... Jul 2024While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's...
PURPOSE
While sedation is routinely used in pediatric PET examinations to preserve diagnostic quality, it may result in side effects and may affect the radiotracer's biodistribution. This study aims to investigate the feasibility of sedation-free pediatric PET imaging using ultra-fast total-body (TB) PET scanners and deep learning (DL)-based attenuation and scatter correction (ASC).
METHODS
This retrospective study included TB PET (uExplorer) imaging of 35 sedated pediatric patients under four years old to determine the minimum effective scanning time. A DL-based ASC method was applied to enhance PET quantification. Both quantitative and qualitative assessments were conducted to evaluate the image quality of ultra-fast DL-ASC PET. Five non-sedated pediatric patients were subsequently used to validate the proposed approach.
RESULTS
Comparisons between standard 300-second and ultra-fast 15-second imaging, CT-ASC and DL-ASC ultra-fast 15-second images, as well as DL-ASC ultra-fast 15-second images in non-sedated and sedated patients, showed no significant differences in qualitative scoring, lesion detectability, and quantitative Standard Uptake Value (SUV) (P = ns).
CONCLUSIONS
This study demonstrates that pediatric PET imaging can be effectively performed without sedation by combining ultra-fast imaging techniques with a DL-based ASC. This advancement in sedation-free ultra-fast PET imaging holds potential for broader clinical adoption.
PubMed: 38958680
DOI: 10.1007/s00259-024-06818-3