Early Onset Horizontal Gaze Palsy and Progressive Scoliosis Due to a Noncanonical Splicing-Site Variant and a Missense Variant in the ROBO3 Gene

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene. RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10 CONCLUSION: This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy

Epidemiology of birth defects based on a birth defects surveillance system in southwestern China and the associated risk factors

BackgroundBirth defects (BDs) are associated with many potential risk factors, and its causes are complex.ObjectivesThis study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs.MethodsBDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs.ResultsBetween 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58–122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108–1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283–1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age (R = 0.732, P < 0.01) and education level (R = 0.586, P < 0.05) and having pre-gestational diabetes mellitus (PGDM)/gestational diabetes mellitus (GDM) (R = 0.711, P < 0.01), while when the pregnant women had a family history of a dead fetus (R = −0.536, P < 0.05) and a birth of a fetus with BDs (R = −0.528, P < 0.05) were negatively correlated with BDs.ConclusionA significant increase in the prevalence of BDs was detected between 2016 and 2020 in Guangxi, especially the prevalence of CHDs that most significantly increased. Older maternal age, higher maternal education level, and having PGDM before pregnancy or GDM in early pregnancy were the risk factors for BDs

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Modeling of 2DEG characteristics of In_xAl_1−xN/AlN/GaN-Based HEMT Considering Polarization and Quantum Mechanical Effect

A comprehensive model for 2DEG characteristics of InxAl1−xN/AlN/GaN heterostructure has been presented, taking both polarization and bulk ionized charge into account. Investigations on the 2DEG density and electron distribution across the heterostructure have been carried out using solutions of coupled 1-D Schrödinger-Poisson equations solved by an improved iterative scheme. The proposed model extends a previous approach allowing for estimating the quantum mechanical effect for a generic InAlN/GaN-based HEMT within the range of the Hartree approximation. A critical AlN thickness (~2.28 nm) is predicted when considering the 2DEG density in dependence on a lattice matched In0.17Al0.83N thickness. The obtained results present in this work provide a guideline for the experimental observation of the subband structure of InAlN/GaN heterostructure and may be used as a design tool for the optimization of that epilayer structure

Simulation of AlGaN/GaN HEMTs’ Breakdown Voltage Enhancement Using Gate Field-Plate, Source Field-Plate and Drain Field Plate

A 2-D simulation of off-state breakdown voltage (VBD) for AlGaN/GaN high electron mobility transistors (HEMTs) with multi field-plates (FPs) is presented in this paper. The effect of geometrical variables of FP and insulator layer on electric field distribution and VBD are investigated systematically. The FPs can modulate the potential lines and distribution of an electric field, and the insulator layer would influence the modulation effect of FPs. In addition, we designed a structure of HEMT which simultaneously contains gate FP, source FP and drain FP. It is found that the VBD of AlGaN/GaN HEMTs can be improved greatly with the corporation of gate FP, source FP and drain FP. We achieved the highest VBD in the HEMT contained with three FPs by optimizing the structural parameters including length of FPs, thickness of FPs, and insulator layer. For HEMT with three FPs, FP-S alleviates the concentration of the electric field more effectively. When the length of the source FP is 24 μm and the insulator thickness between the FP-S and the AlGaN surface is 1950 nm, corresponding to the average electric field of about 3 MV/cm at the channel, VBD reaches 2200 V. More importantly, the 2D simulation model is based on a real HMET device and will provide guidance for the design of a practical device

Early onset horizontal gaze palsy and progressive scoliosis due to a noncanonical splicing‐site variant and a missense variant in the ROBO3 gene

Abstract Background Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. Methods We described an HGPPS patient and performed whole‐exome sequencing (WES) to identify the causative gene. Results We identified a missense variant and a splice‐site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10−4, by a review of our in‐house database. Conclusion This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy