Trends in Management of Fetuses with Suspected Lower Urinary Tract Obstruction (LUTO): A High-Risk Fetal and Pediatric Center Experience in a Universal-Access-to-Care System.

INTRODUCTION: Neonates with lower urinary tract obstruction (LUTO) experience high morbidity and mortality associated with the development of chronic kidney disease. The prenatal detection rate for LUTO is less than 50%, with late or missed diagnosis leading to delayed management and long-term sequelae in the remainder. We aimed to explore the trends in prenatal detection and management at a high-risk fetal center and determine if similar trends of postnatal presentations were noted for the same period. METHODS: Prenatal and postnatal LUTO databases from a tertiary fetal center and its associated pediatric center between 2009 and 2021 were reviewed, capturing maternal age, gestational age (GA) at diagnosis, and rates of termination of pregnancy (TOP). Time series analysis using autocorrelation was performed to investigate time trend changes for prenatally suspected and postnatally confirmed LUTO cases. RESULTS: A total of 161 fetuses with prenatally suspected LUTO were identified, including 78 terminations. No significant time trend was found when evaluating the correlation between time periods, prenatal suspicion, and postnatal confirmation of LUTO cases (Durbin-Watson [DW] = 1.99, p = 0.3641 and DW = 2.86, p = 0.9113, respectively). GA at referral was 20.0 weeks (interquartile range [IQR] 12, 35) and 22.0 weeks (IQR 13, 37) for TOP and continued pregnancies (p < 0.0001). GA at initial ultrasound was earlier in terminated fetuses compared to continued (20.0 [IQR 12, 35] weeks vs. 22.5 [IQR 13, 39] weeks, p < 0.0001). While prenatal LUTO suspicion remained consistently higher than postnatal presentations, the rates of postnatal presentations and terminations remained stable during the study years (p = 0.7913 and 0.2338), as were GA at TOP and maternal age at diagnosis (p = 0.1710 and 0.1921). CONCLUSION: This study demonstrated that more severe cases of LUTO are referred earlier and are more likely to undergo TOP. No significant trend was detected between time and prenatally suspected or postnatally confirmed LUTO, highlighting the need for further studies to better delineate factors that can increase prenatal detection.

Kidney function and transplants in prune belly syndrome: a scoping review.

BACKGROUND: Children with prune belly syndrome (PBS) are at higher risk of developing kidney dysfunction and requiring kidney replacement therapy (KRT). While studies have described surgical and survival outcomes in these populations, there has yet to be a focused synthesis of evidence regarding kidney outcomes in this population. Here, the focus of this scoping review was to highlight knowledge gaps and report standards on kidney outcomes in PBS of all ages. METHODS: Following scoping review methodology, EMBASE, MEDLINE, and Scopus were searched for peer-reviewed literature that describe kidney outcomes in PBS. All studies with a broad set of kidney outcomes (such as kidney function measures, chronic kidney disease (CKD), KRT and associated outcomes) were included. Findings were summarized and qualitatively synthesized. RESULTS: Of the 436 unique records identified, 25 were included for synthesis. A total of 17 studies (441 patients) reported on kidney insufficiency outcomes, with an estimated prevalence of CKD ranging from 8 to 66%. A total of 15 studies (314 patients) described KRT, primary kidney transplant, and outcomes. Of these, the age for KRT ranged from 4 to 21 years, and graft survival ranged from 22 to 87% by last follow-up (range 1.3-27 years). CONCLUSIONS: There is significant variability in studies reporting kidney outcomes in PBS which limits meaningful synthesis. There is a need for future studies with comprehensive reporting of confounders and drivers for kidney insufficiency in PBS.

Pathological Findings in Fetuses Terminated for Suspected Lower Urinary Tract Obstruction: Experience From a High-Risk Fetal Center in Canada.

PURPOSE: Pregnancies complicated by prenatally suspected lower urinary tract obstruction (LUTO) can be associated with high rates of terminations due to potentially poor outcomes. Herein, we assessed autopsy findings of fetuses terminated for suspected LUTO to evaluate the prenatal diagnostic accuracy and spectrum of underlying pathologies. MATERIALS AND METHODS: We performed a retrospective review of all pregnancies referred to a high-risk fetal center in a universal access to care health care system for suspected LUTO that opted for termination of pregnancy between 2009 and 2022. Ultrasound features, genetic investigations, placental findings, and distribution of postmortem diagnoses were assessed. RESULTS: Of a total of 190 pregnancies with suspected LUTO evaluated during the study period, 79 (42%) were terminated. We excluded 35 fetuses with incomplete data, resulting in 44 available for analysis. Pregnancies were terminated at a mean gestation of 22 ± 5 weeks. A LUTO diagnosis was confirmed in 37 (84.1%) fetuses (35 males, 2 females), and the remaining 7 showed other pathologies. Pulmonary hypoplasia was found in 62.2% (n = 23) and placental pathologies in 56.8% of confirmed LUTO compared to 33.4% and 71.4% in non-LUTO cases, respectively. Overall, a total of 31 fetuses underwent additional prenatal investigations with genetic anomalies detected only in fetuses with a confirmed LUTO diagnosis (13.6%). CONCLUSIONS: In our health care system, almost half of prenatally suspected LUTO pregnancies are terminated. The sonographic diagnostic accuracy for LUTO is reasonable at 84%. However, the remaining 16% still had significant pathologies. Genetic abnormalities are uncommon and rarely the trigger for pregnancy terminations.

External validation and reliability assessment of posterior urethral morphology on initial voiding cystourethrogram as a predictor for infants with posterior urethral valves.

INTRODUCTION: The morphology of the bladder and posterior urethra on initial voiding cystourethrogram (VCUG) in posterior urethral valve (PUV) has been proposed as a meaningful early metric for short- and long-term kidney outcomes. Here, we seek to externally validate the proposed association and assess the reliability of PUV morphology characteristics. MATERIALS AND METHODS: We reviewed our institutional database for patients managed for PUV between 2000 and 2022 and included those treated with primary ablation with at least 1 year of follow-up for kidney function. Each VCUG was evaluated by three independent raters for the height-width ratio of the bladder (HW-B), height-width ratio of the posterior urethra (HW-PU), and posterior-anterior urethral ratio (PA-UR), and trabeculation (none, fine, or coarse). We assessed the reliability in these with intra-class coefficient and Fleiss kappa for continuous and categorical data, respectively. We performed univariate analysis with nadir creatinine and five-year follow-up glomerular filtration rate (GFR). RESULTS: In total, 98 patients met inclusion criteria. The median age at diagnosis and ablation was 10 and 21 days, respectively. Patients with nadir creatinine <0.8 mg/dL had higher follow-up GFR (101 vs. 20 ml/min/1.73 m2, p = 0.04), and lower risk of CKD (odds ratio 14.7, p = 0.002). The median value for HW-B was 1.4, median HW-PU was 2.1, and median PA-U was 4.7, There was significant inter-class agreement between all three measures of 0.80, 0.51, and 0.70 (p < 0.001). The inter-rater agreement for bladder trabeculation was fair (Fleiss K = 0.40, p < 0.001). There was no statistically significant correlation between HW-B, HW-PU, PU-A with nadir creatinine (p = 0.07, 0.33, 0.91) or 5-year GFR (0.27, 0.45, 0.62), respectively. DISCUSSION: There is significant interest in determining prognostic factors and metrics in PUV. The morphological characteristics on VCUG are reliable and is available information for all boys diagnosed with PUV, resulting in an attractive metric. While we do not demonstrate correlation with kidney outcomes, VCUG features warrant further attention as prognostic factors in PUV. CONCLUSIONS: PUV morphology on initial VCUG is a reliable metric of lower urinary tract deformity but is not associated with 5-year kidney outcomes.

The role of circumcision in preventing urinary tract infections in children with antenatal hydronephrosis: Systematic review and meta-analysis.

INTRODUCTION: Circumcision has been reported to reduce the risk of urinary tract infections (UTIs) in boys with antenatal hydronephrosis (HN). Our aim was to compare the incidence of UTIs in circumcised vs. uncircumcised boys with antenatal HN by conducting a systematic review and meta-analysis. STUDY DESIGN: A comprehensive search was performed until December 2022. Comparative studies were evaluated according to Cochrane collaboration recommendations. Assessed measures included: UTIs, continuous antibiotic prophylaxis (CAP) use, renal outcomes, and circumcision complications. Odds ratios (OR) and mean difference with 95% confidence interval (CI) were extrapolated from available data. Random-effects meta-analysis were performed. RESULTS: Twenty-three studies describing 9093 boys with antenatal HN were identified, including 4677 uncircumcised and 4416 circumcised boys. Overall effect estimates demonstrate that circumcised boys have significantly reduced odds of developing any UTI [OR 0.26, 95%CI 0.21, 0.32; p < 0.001]]. In addition, there a significantly reduced odds of developing UTI when circumcised and on CAP [OR 0.19, 95% CI 0.13, 0.30; p < 0.001]. When stratifying by etiology, circumcision reduced the odds of UTI in boys with isolated HN [OR 0.33, 95% CI 0.16, 0.68; p = 0.003], vesicoureteral reflux [OR 0.23, 95% CI 0.13, 0.42; P < 0.00001], or with posterior urethral valves [OR 0.29, 95% CI 0.13, 0.64; p = 0.002]. DISCUSSION: Circumcision reduces the incidence of UTIs in boys with antenatal HN. This review is limited by the varied definitions of UTIs and inconsistent reporting on HN etiology, renal outcomes, and circumcision complications. CONCLUSIONS: Circumcision should be considered in boys with antenatal HN to prevent the risk of developing UTI. Further research is warranted to individualize the prophylactic role of circumcision for patients with HN.

A time slice analysis of dentistry students' visual search strategies and pupil dilation during diagnosing radiographs.

Diagnosing orthopantomograms (OPTs: panoramic radiographs) is an essential skill dentistry students acquire during university training. While prior research described experts' visual search behavior in radiology as global-to-focal for chest radiographs and mammography, generalizability to a hybrid search task in OPTs (i.e., searching for multiple, diverse anomalies) remains unclear. Addressing this gap, this study investigated visual search of N = 107 dentistry students while they were diagnosing anomalies in OPTs. Following a global-to-focal expert model, we hypothesized that students would use many, short fixations representing global search in earlier stages, and few, long fixations representing focal search in later stages. Furthermore, pupil dilation and mean fixation duration served as cognitive load measures. We hypothesized that later stages would be characterized by elaboration and a reflective search strategy, leading to higher cognitive load being associated with higher diagnostic performance in late compared to earlier stages. In line with the first hypothesis, students' visual search comprised of a three-stage process that grew increasingly focal in terms of the number of fixations and anomalies fixated. Contrary to the second hypothesis, mean fixation duration during anomaly fixations was positively associated with diagnostic performance across all stages. As OPTs greatly varied in how difficult it was to identify the anomalies contained therein, OPTs with above-average difficulty were sampled for exploratory analysis. Pupil dilation predicted diagnostic performance for difficult OPTs, possibly capturing elaborative cognitive processes and cognitive load compared to mean fixation duration. A visual analysis of fine-grained time slices indicated large cognitive load differences towards the end of trials, showcasing a richness-resolution-trade-off in data sampling crucial for future studies using time-slicing of eye tracking data.

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Posterior urethral valves, pressure pop-offs, and kidney function: systematic review and meta-analysis.

PURPOSE: To determine the role of pressure pop-off mechanisms, including vesicoureteral reflux and renal dysplasia (VURD) syndrome, in determining long-term kidney outcomes in boys with posterior urethral valves (PUV). METHODS: A systematic search was performed in December 2022. Descriptive and comparative studies with a defined pressure pop-off group were included. Assessed outcomes included end-stage renal disease (ESRD), kidney insufficiency (defined as chronic kidney disease [CKD] stage 3 + or SCr > 1.5 mg/dL), and kidney function. Pooled proportions and relative risks (RR) with 95% confidence intervals (CI) were extrapolated from available data for quantitative synthesis. Random-effects meta-analyses were performed according to the study design and techniques. The risk of bias was assessed with the QUIPS tool and GRADE quality of evidence. The systematic review was prospectively registered on PROSPERO (CRD42022372352). RESULTS: A total of 15 studies describing 185 patients with a median follow-up of 6.8 years were included. By the last follow-up, overall effect estimates demonstrate the prevalence of CKD and ESRD to be 15.2% and 4.1%, respectively. There was no significant difference in the risk of ESRD in patients with pop-off compared to no pop-off patients [RR 0.34, 95%CI 0.12, 1.10; p = 0.07]. There was a significantly reduced risk for kidney insufficiency in boys with pop-off [RR 0.57, 95%CI 0.34, 0.97; p = 0.04], but this protective effect was not re-demonstrated after excluding studies with inadequate reporting of CKD outcomes [RR 0.63, 95%CI 0.36, 1.10; p = 0.10]. Included study quality was low, with 6 studies having moderate risk and 9 having a high risk of bias. CONCLUSIONS: Pop-off mechanisms may be associated with reducing the risk of kidney insufficiency, but current certainty in the evidence is low. Further research is warranted to investigate sources of heterogeneity and long-term sequelae in pressure pop-offs.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

OBJECTIVE: To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. METHODS: We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. RESULTS: A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P < .001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P = .021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P = .025). CONCLUSION: While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

Does VURD syndrome impact voiding efficiency in posterior urethral valves?

INTRODUCTION: There is debate regarding the effect of VURD syndrome, consisting of vesicoureteral reflux (VUR) and ipsilateral kidney dysplasia, on long-term outcomes in boys with posterior urethral valve (PUV). Here, we assessed whether VURD syndrome played a "protective" role on long-term bladder outcomes and voiding efficiency in boys with PUV. MATERIALS AND METHOD: A retrospective chart review was conducted for toilet-trained children with PUV managed at our institution between 2000 and 2022, only excluding cases without recorded uroflowmetry studies. Patients were stratified by VUR status and by the presence of VURD syndrome (high-grade VUR + ipsilateral kidney dysplasia). Outcomes included initial and final uroflowmetry parameters, and initiation of clean-intermittent catheterization (CIC). RESULTS: We identified a total of 101 patients who met study inclusion criteria, with an overall median follow-up of 114 months (IQR 67, 169). The median age of first and last uroflowmetry was 57 months (IQR 48, 82) and 120 months (IQR 89, 160), respectively. Patients with VURD syndrome had similar flow velocity, post-void residuals, and bladder voiding efficiency to other PUV patients at last follow-up uroflowmetry. On survival analysis, patients with VURD syndrome had no significant difference in risk of requiring CIC compared to patients without pop-offs (p = 0.06). DISCUSSION: Like more contemporary studies on pressure pop-offs, we show that this population is not at higher risk of poorer voiding and intermittent catheterization than others. VURD syndrome does not confer protection against poorer bladder function. Instead, our study suggests an independent association between kidney dysplasia and bladder outcomes which requires further attention. CONCLUSIONS: Among boys with PUV, VURD syndrome was not associated with significantly different uroflowmetry findings or rates of CIC by last follow-up.

The effect of primary urinary diversion on kidney function in posterior urethral valve: A matched comparison.

OBJECTIVE: To determine long-term kidney outcomes in boys with posterior urethral valve (PUV) undergoing either primary valve ablation or urinary diversion with matched baseline kidney function. METHODS: After retrospective review of patients managed for PUV at our institution, propensity score matched analysis was conducted using nadir serum creatinine with logistic regression analysis. Nearest neighbor matching was used to allocate boys to primary urinary diversion and primary ablation groups. Primary outcomes included kidney function by creatinine or estimated glomerular filtration rate, chronic kidney disease, and end-stage renal disease. Comparative statistics by odds ratio (OR) and hazard ratios on survival analysis were calculated. RESULTS: A total of 21 boys undergoing primary diversion were matched with 42 boys undergoing ablation using nadir serum creatinine and follow-up time with a median follow-up of 4.8 years. After matching, there was no significant difference in last follow-up kidney function by creatinine (P = .99) or estimated glomerular filtration rate (P = .98). Primary diversion was not associated with increased likelihood of developing chronic kidney disease stage 3 (OR 1.33; P = .31) or end-stage renal disease (OR 1.88; P = .35 and hazard ratios 1.85; P = .30) compared to primary ablation. CONCLUSIONS: Our propensity matched study suggests that long-term kidney function and kidney outcomes are similar between primary ablation and primary diversion after adjusting for baseline kidney function in boys with PUV.

Comparison of outcomes of prenatal versus postnatal presentation of posterior urethral valves: a systematic review and meta-analysis.

OBJECTIVE: To determine through a comprehensive systematic review and meta-analysis the differences in the outcomes of prenatally versus postnatally diagnosed posterior urethral valves (PUV) to ascertain if prenatal detection of PUV has superior outcomes. METHODS: We conducted a systematic review and meta-analysis in March 2022 (PROSPERO ID - CRD42021243546) and included all studies that reported outcomes of prenatally and postnatally diagnosed PUV. However, for meta-analysis, only those studies that described both groups were included. The main outcomes of interest included progression of chronic kidney disease (CKD), need for renal replacement therapy (RRT) and renal transplant, and bladder dysfunction as determined by initiation of clean intermittent catheterization (CIC). Time to event analyses were completed when possible. RESULTS: The systematic review included 49 studies (3820 patients). The pooled effect estimates for progression to CKD (OR 0.75 [95% CI 0.43, 1.31]), need for RRT (OR 1.39 [95% CI 0.64, 2.99]) and need for renal transplant (OR 1.64 [95% CI 0.61, 4.42]) between prenatal and postnatal groups was not different. CICs rates were as high as 32% in the prenatal group and 22% in the postnatal group. Most studies had a moderate or serious risk of bias. CONCLUSION: The existing comparative literature on prenatal versus postnatal presentation of PUV is very heterogeneous. The diagnostic and treatment protocols have not been reported in majority of the studies. The outcome variables are also reported inconsistently. Based on the current evidence, prenatal diagnosis of PUV does not appear to improve the long-term outcomes of these patients.

Target insertion depth of nasopharyngeal temperature probes in children: A prospective observational study analyzing magnetic resonance images.

BACKGROUND: Core temperature monitoring is indispensable to prevent children from perioperative thermal perturbations. Although nasopharyngeal measurements are commonly used in anesthesia and considered to reflect core temperature accurately, standardized target depths for probe insertion are unknown in children. AIMS: Our primary goal was to determine a target depth of nasopharyngeal temperature probe insertion in children by measuring distances on magnetic resonance imaging (MRI). Secondary aims were to correlate these measurements with biometric variables and facial landmark-distances to derive formulas estimating target depth. METHODS: We conducted a prospective observational study in children ≤12 years undergoing cranial MRI with anesthesia. We documented patient characteristics and measured the landmark-distances nostril-mandible, nostril-tragus, and philtrum-tragus on patient's faces. On MRI, the target point for the probe tip was considered to be the site of the nasopharyngeal mucosa with the closest proximity to the internal carotid artery. After its determination in the transverse axis and triangulation to the sagittal axis, we measured the distance to the nostril. This distance, defined as target insertion depth, was correlated with the patient characteristics and used for univariate and multiple linear regression analysis. RESULTS: One hundred twenty children with a mean age of 4.5 years were included. The target insertion depth ranged from 61.8 mm in infants to 89.8 mm in 12-year-old children. Height correlated best (ρ = 0.685, 95%-CI: [0.57-0.77]). The best-fit estimation in millimeters, "40.8 + height [cm] × 0.32,″ would lead to a placement in the target position in 67% of cases. A simplified approach by categories of 50-80, 80-110, 110-130, and >130 cm height with target insertion depths of 60, 70, 80, and 85 mm, respectively, achieved similar probabilities. CONCLUSIONS: Height-based formulas could be a valuable proxy for the insertion depth of nasopharyngeal temperature probes. Further clinical trials are necessary to investigate their measurement accuracy.

Working with estimation-formulas to predict nasopharyngeal airway insertion depth in children: Looking at magnetic resonance images - A prospective observational study (WEND:LI-Study).

OBJECTIVE: To determine the accuracy of the recently proposed landmark-method 'nostril-to-tragus minus 10 mm' and compare with ERC-recommended distances for nasopharyngeal airway length sizing in children. METHOD: We conducted a prospective observational study in sedated children < 12 years. Nasopharyngeal airways were inserted following 'nostril-to-tragus minus 10 mm'. Primary outcome was the rate of nasopharyngeal airway tips between soft palate and epiglottis on magnetic resonance imaging (MRI) indicated for medical reasons. An optimal placement was defined when the tip lied within 25-75% of the total soft palate-to-epiglottis distance. Between 0-100% of this distance, placement was still considered acceptable, below 0% too proximal or above 100% too distal. Secondary outcomes were the rate of adverse events, the qualitative positions of airway tips, and the comparison of ́nostril-to-tragus minus 10 mm with the ERC-recommended distances 'nostril-to-angle of the mandible' and 'nostril-to-tragus' with objective MRI measurements. RESULTS: We analysed 92 patients with a mean age of 4.3 years. Nasopharyngeal airways were optimally placed in 37.0% (8.7% too proximal-77.2% acceptable-14.1% too distal). Three qualitative malpositions, but no airway-associated adverse event occurred. Objective measurements on MRI revealed the probability of 40.2% optimally placed nasopharyngeal airways (5.4%-67.4%-27.2%) for 'nostril-to-tragus minus 10 mm', 38.0% (17.4%-58.7%-23.9%) for 'nostril-to-mandible' and 13.0% (0%-28.3%-71.7%) for 'nostril-to-tragus', respectively. CONCLUSION: No landmark-method predicted nasopharyngeal airway position reliably. 'Nostril-to-tragus minus 10 mm' seems the least inaccurate one and could be a valuable approximation until another estimation-formula proves more accurate. During insertion, careful clinical evaluation of airway patency is crucial. REGISTERED CLINICAL TRIAL: German Clinical Trials Register; DRKS00021007.

Impact of glgA1, glgA2 or glgC overexpression on growth and glycogen production in Synechocystis sp. PCC 6803.

Low production rates are still one limiting factor for the industrial climate-neutral production of biovaluable compounds in cyanobacteria. Next to optimized cultivation conditions, new production strategies are required. Hence, the use of established molecular tools could lead to increased product yields in the cyanobacterial model organism Synechocystis sp. PCC6803. Its main storage compound glycogen was chosen to be increased by the use of these tools. In this study, the three genes glgC, glgA1 and glgA2, which are part of the glycogen synthesis pathway, were combined with the Pcpc560 promoter and the neutral cloning site NSC1. The complete genome integration, protein formation, biomass production and glycogen accumulation were determined to select the most productive transformants. The overexpression of glgA2 did not increase the biomass or glycogen production in short-term trials compared to the other two genes but caused transformants death in long-term trials. The transformants glgA1_11 and glgC_2 showed significantly increased biomass (1.6-fold - 1.7-fold) and glycogen production (3.5-fold - 4-fold) compared to the wild type after 96 h making them a promising energy source for further applications. Those could include for example a two-stage production process, with first energy production (glycogen) and second increased product formation (e.g. ethanol).

Exiguous premeal saccharide intake reduces subsequent food intake in men.

PURPOSE: Satiety is a crucial factor in the attempt to reduce food intake for long-term body weight loss. Since there is evidence for a negative correlation between cerebral energy levels and food intake, the provision of the primary energy substrate glucose to the brain through oral ingestion of carbohydrates could trigger feelings of satiety. Therefore, we hypothesized that a low-calorie saccharide preload would increase satiety, reduce subsequent food intake, and thereby decrease overall calorie consumption. METHODS: In a randomized single-blind crossover study, 17 healthy young normal-weight men received saccharide (26 kcal in total) or placebo capsules 30 min before a standardized breakfast buffet. We analysed food intake from the test buffet as well as plasma glucose and serum insulin levels. RESULTS: The saccharide preload reduced food intake from the buffet by 168 (± 34) kcal (p < 0.001) compared to control. This corresponds to a net reduction in total calorie consumption by 142 (± 34) kcal (p < 0.001) or 9.3% due to saccharide capsules. CONCLUSION: A very low-calorie saccharide preload considerably reduces subsequent food intake leading to decreased overall calorie consumption. A saccharide preload before meals could, therefore, be a promising support for reducing caloric intake. GERMAN CLINICAL TRIALS REGISTER: DRKS00010281 (date of registration: 11.04.2016).

How to support dental students in reading radiographs: effects of a gaze-based compare-and-contrast intervention.

In dental medicine, interpreting radiographs (i.e., orthopantomograms, OPTs) is an error-prone process, even in experts. Effective intervention methods are therefore needed to support students in improving their image reading skills for OPTs. To this end, we developed a compare-and-contrast intervention, which aimed at supporting students in achieving full coverage when visually inspecting OPTs and, consequently, obtaining a better diagnostic performance. The comparison entailed a static eye movement visualization (heat map) on an OPT showing full gaze coverage from a peer-model (other student) and another heat map showing a student's own gaze behavior. The intervention group (N = 38) compared five such heat map combinations, whereas the control group (N = 23) diagnosed five OPTs. Prior to the experimental variation (pre-test) and after it (post-test), students in both conditions searched for anomalies in OPTs while their gaze was recorded. Results showed that students in the intervention group covered more areas of the OPTs and looked less often and for a shorter amount of time at anomalies after the intervention. Furthermore, they fixated on low-prevalence anomalies earlier and high-prevalence anomalies later during the inspection. However, the students in the intervention group did not show any meaningful improvement in detection rate and made more false positive errors compared to the control group. Thus, the intervention guided visual attention but did not improve diagnostic performance substantially. Exploratory analyses indicated that further interventions should teach knowledge about anomalies rather than focusing on full coverage of radiographs.

How massed practice improves visual expertise in reading panoramic radiographs in dental students: An eye tracking study.

The interpretation of medical images is an error-prone process that may yield severe consequences for patients. In dental medicine panoramic radiography (OPT) is a frequently used diagnostic procedure. OPTs typically contain multiple, diverse anomalies within one image making the diagnostic process very demanding, rendering students' development of visual expertise a complex task. Radiograph interpretation is typically taught through massed practice; however, it is not known how effective this approach is nor how it changes students' visual inspection of radiographs. Therefore, this study investigated how massed practice-an instructional method that entails massed learning of one type of material-affects processing of OPTs and the development of diagnostic performance. From 2017 to 2018, 47 dental students in their first clinical semester diagnosed 10 OPTs before and after their regular massed practice training, which is embedded in their curriculum. The OPTs contained between 3 to 26 to-be-identified anomalies. During massed practice they diagnosed 100 dental radiographs without receiving corrective feedback. The authors recorded students' eye movements and assessed the number of correctly identified and falsely marked low- and high prevalence anomalies before and after massed practice. Massed practice had a positive effect on detecting anomalies especially with low prevalence (p < .001). After massed practice students covered a larger proportion of the OPTs (p < .001), which was positively related to the detection of low-prevalence anomalies (p = .04). Students also focused longer, more frequently, and earlier on low-prevalence anomalies after massed practice (ps < .001). While massed practice improved visual expertise in dental students with limited prior knowledge, there is still substantial room for improvement. The results suggest integrating massed practice with more deliberate practice, where, for example, corrective feedback is provided, and support is adapted to students' needs.

Correction: Pupil diameter differentiates expertise in dental radiography visual search.

[This corrects the article DOI: 10.1371/journal.pone.0223941.].