A reusable 3D printed brain-like phantom for benchmarking electrical properties tomography reconstructions.

PURPOSE: In MR electrical properties tomography (MR-EPT), electrical properties (EPs, conductivity and permittivity) are reconstructed from MR measurements. Phantom measurements are important to characterize the performance of MR-EPT reconstruction methods, since they allow knowledge of reference EPs values. To assess reconstruction methods in a more realistic scenario, it is important to test the methods using phantoms with realistic shapes, internal structures, and dielectric properties. In this work, we present a 3D printing procedure for the creation of realistic brain-like phantoms to benchmark MR-EPT reconstructions. METHODS: We created two brain-like geometries with three different compartments using 3D printing. The first geometry was filled once, while the second geometry was filled three times with different saline-gelatin solutions, resulting in a total of four phantoms with different EPs. The saline solutions were characterized using a probe. 3D MR-EPT reconstructions were performed from MR measurements at 3T. The reconstructed conductivity values were compared to reference values of the saline-gelatin solutions. The measured fields were also compared to simulated fields using the same phantom geometry and electrical properties. RESULTS: The measured fields were consistent with simulated fields. Reconstructed conductivity values were consistent with the reference (probe) conductivity values. This indicated the suitability of such phantoms for benchmarking MR-EPT reconstructions. CONCLUSION: We presented a new workflow to 3D print realistic brain-like phantoms in an easy and affordable way. These phantoms are suitable to benchmark MR-EPT reconstructions, but can also be used for benchmarking other quantitative MR methods.

Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

OBJECTIVE: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood. METHODS: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing. RESULTS: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months). CONCLUSION: Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Racial/ethnic disparities in exposure to e-cigarette advertising among U.S. youth.

OBJECTIVES: This study aims to assess exposure to e-cigarette advertising across multiple marketing channels among U.S. youth and to examine whether racial/ethnic disparities exist in exposure to e-cigarette advertisements. STUDY DESIGN: This is a cross-sectional study. METHODS: Cross-sectional data were drawn from a longitudinal survey of participants recruited from two nationally representative panels (NORC's AmeriSpeak® and GfK's KnowledgePanel). A total of 2043 youth aged 13-17 completed the initial 2018 survey, and 2013 youth completed the follow-up survey in 2019 (including a replenishment sample of 690 youth). Outcome variables were self-reported e-cigarette advertisement exposure in the past three months through various sources, such as television, point of sale, and online/social media. Generalized estimating equation models were used to estimate the adjusted odds ratios (AOR) of the association between racial/ethnic identity and e-cigarette advertisement exposure. RESULTS: The prevalence of reported exposure to e-cigarette advertisements through any channel was 79.8% (95% CI: 77.1-82.2) in 2018 and 74.9% (95% CI: 72.5-77.1) in 2019, respectively. Point of sale was the most common source of e-cigarette advertisement exposure in both years. Non-Hispanic Black and non-Hispanic Asian youth were more likely to report exposure to e-cigarette advertisements through television (AOR = 2.07, 95% CI: 1.44-2.99 and AOR = 2.11, 95% CI: 1.17-3.82, respectively) and online/social media (AOR = 1.61; 95% CI: 1.11-2.33 and AOR = 1.99, 95% CI: 1.10-3.59, respectively) channels compared with non-Hispanic White youth. CONCLUSIONS: A substantial proportion of U.S. youth reported exposure to e-cigarette advertising through a variety of marketing channels. Significant racial/ethnic disparities existed, with non-Hispanic Black and Asian youth reporting more marketing exposure than their non-Hispanic White counterparts.

[Effects of a smoke-free policy on healthcare staff attitudes and aggression in psychiatry]. / Effecten van een rookvrijbeleid op attitudes zorgpersoneel en agressie in de psychiatrie.

Background The prevalence of smoking among patients with psychiatric disorders is 3-4 times higher than the general population. However, smoking is still permitted in many psychiatric clinics. The National Prevention Agreement (2018) mandates that all psychiatric wards be smoke-free by 2025. The UMC Utrecht clinics have been smoke-free since November 2020. Aim To examine healthcare workers’ attitudes before and after implementing the smoke-free policy. Method In an observational study with quantitative data analysis, data were collected in one center from healthcare workers in psychiatry departments with surveys. We collected demographic information, smoking status, attitudes towards the smoke-free policy, and its impact on patients and care. Incidents of aggression were prospectively recorded and reported in the MAP (aggression incidents in patient care). Results Out of 172 healthcare workers invited to participate, 30% (n = 52) completed the pre-implementation survey, and 20% (n = 34) completed the post-implementation survey. Prior to implementation, 62% (n = 32/52) of healthcare workers had a positive attitude towards the smoke-free policy, which increased to 77% (n = 26/34) post-implementation. Expectations of increased aggression incidents were reported by 62% (n = 32/52) during the pre-implementation phase. The number of aggression incidents was 46 in the one-year period before implementation (November 2019 – February 2020) and 45 incidents after implementation (November 2020 – February 2021). Conclusion This study supports the implementation of a smoke-free policy in psychiatric clinics due to the lack of a significant increase in aggression incidents. Healthcare workers perceived this outcome and observed quicker granting of ‘green’ freedoms.

Hyoid bone morphology in patients with isolated robin sequence - A case-control study utilizing 3D morphable models.

Background: Abnormalities of the hyoid bone are associated with impairment of oropharyngeal functions including feeding, swallowing, and breathing. Few studies have characterized anatomic abnormalities of the hyoid in patients with Robin sequence (RS), e.g. a less mineralized and voluminous hyoid. The purpose of this study was to compare normal hyoid bone morphology and hyoid bone morphology in children with isolated RS. Methods: Three-dimensional (3D) reconstructions of the hyoid bone were obtained from CT-imaging of children with RS and unaffected controls. A 3D morphable model was constructed using Principal Component Analysis (PCA). Partial least squares - Discriminant Analysis (PLS-DA) and multivariate analysis of variance (MANOVA) were used to characterize and compare hyoid shape differences between patients with RS and an age-matched control group. Results: The study included 23 subjects with RS (mean age 9.8 ± 10.3 months) and 46 age-matched control samples. A less voluminous hyoid was observed for the RS group with a larger lateral divergence of the greater horns compared to controls (MANOVA, p-value<0.001). The first shape variable from the PLS-DA model showed a significant correlation for the observed variance between the two groups (Spearman R = -0.56, p-value<0.001). The control samples and 151 CT-scans of subjects up to age 4 years were used to create a 3D morphable model of normal hyoid shape variation (n = 197, mean age 22.1 ± 13.1 months). For the normal 3D morphable model, a high degree of allometric shape variation was observed along the first principal component. Conclusions: The 3D morphable models provide a comprehensive and quantitative description of variation in normal hyoid bone morphology, and allow detection of distinct differences between patients with isolated RS and controls.

Single-center outcome analysis of 46 fetuses with megacystis after intrauterine vesico-amniotic shunting with the Somatex®intrauterine shunt.

OBJECTIVES: To assess the spectrum of underlying pathologies, the intrauterine course and postnatal outcome of 46 fetuses with megacystis that underwent intrauterine vesico-amniotic shunting (VAS) with the Somatex® shunt in a single center. METHODS: Retrospective analysis of 46 fetuses with megacystis that underwent VAS either up to 14 + 0 weeks (early VAS), between 14 + 1 and 17 + 0 weeks (intermediate VAS) or after 17 + 0 weeks of gestation (late VAS) in a single tertiary referral center. Intrauterine course, underlying pathology and postnatal outcome were assessed and correlated with the underlying pathology and gestational age at first VAS. RESULTS: 46 fetuses underwent VAS, 41 (89%) were male and 5 (11%) were female. 28 (61%) fetuses had isolated and 18 (39%) had complex megacystis with either aneuploidy (n = 1), anorectal malformations (n = 6), cloacal malformations (n = 3), congenital anomalies overlapping with VACTER association (n = 6) or Megacystis-Microcolon Intestinal-Hypoperistalsis Syndrome (MMIHS) (n = 2). The sonographic 'keyhole sign' significantly predicted isolated megacystis (p < 0.001). 7 pregnancies were terminated, 4 babies died in the neonatal period, 1 baby died at the age of 2.5 months and 34 (74%) infants survived until last follow-up. After exclusion of the terminated pregnancies, intention-to-treat survival rate was 87%. Mean follow-up period was 24 months (range 1-72). The underlying pathology was highly variable and included posterior urethral valve (46%), hypoplastic or atretic urethra (35%), MMIHS or prune belly syndrome (10%) and primary vesico-ureteral reflux (2%). In 7% no pathology could be detected postnatally. No sonographic marker was identified to predict the underlying pathology prenatally. 14 fetuses underwent early, 24 intermediate and 8 late VAS. In the early VAS subgroup, amnion infusion prior to VAS was significantly less often necessary (7%), shunt complications were significantly less common (29%) and immediate kidney replacement therapy postnatally became less often necessary (0%). In contrast, preterm delivery ≤ 32 + 0 weeks was more common (30%) and survival rate was lower (70%) after early VAS compared to intermediate or late VAS. Overall, 90% of liveborn babies had sufficient kidney function without need for kidney replacement therapy until last follow-up, and 95% had sufficient pulmonary function without need for mechanical respiratory support. 18% of babies with complex megacystis suffered from additional health restrictions due to their major concomitant malformations. CONCLUSIONS: Our data suggest that VAS is feasible from the first trimester onward. Early intervention has the potential to preserve neonatal kidney function in the majority of cases and enables neonatal survival in up to 87% of cases. Despite successful fetal intervention, parents should be aware of the potential of mid- or long-term kidney failure and of additional health impairments due to concomitant extra-renal anomalies that cannot be excluded at time of intervention.

D-Transposition of the great arteries with restrictive foramen ovale in the fetus: the dilemma of predicting the need for postnatal urgent balloon atrial septostomy.

OBJECTIVE: Restrictive foramen ovale (FO) in dextro-transposition of the great arteries (d-TGA) with intact ventricular septum may lead to severe life-threatening hypoxia within the first hours of life, making urgent balloon atrial septostomy (BAS) inevitable. Reliable prenatal prediction of restrictive FO is crucial in these cases. However, current prenatal echocardiographic markers show low predictive value, and prenatal prediction often fails with fatal consequences for a subset of newborns. In this study, we described our experience and aimed to identify reliable predictive markers for BAS. METHODS: We included 45 fetuses with isolated d-TGA that were diagnosed and delivered between 2010 and 2022 in two large German tertiary referral centers. Inclusion criteria were the availability of former prenatal ultrasound reports, of stored echocardiographic videos and still images, which had to be obtained within the last 14 days prior to delivery and that were of sufficient quality for retrospective re-analysis. Cardiac parameters were retrospectively assessed and their predictive value was evaluated. RESULTS: Among the 45 included fetuses with d-TGA, 22 neonates had restrictive FO postnatally and required urgent BAS within the first 24 h of life. In contrast, 23 neonates had normal FO anatomy, but 4 of them unexpectedly showed inadequate interatrial mixing despite their normal FO anatomy, rapidly developed hypoxia and also required urgent BAS ('bad mixer'). Overall, 26 (58%) neonates required urgent BAS, whereas 19 (42%) achieved good O2 saturation and did not undergo urgent BAS. In the former prenatal ultrasound reports, restrictive FO with subsequent urgent BAS was correctly predicted in 11 of 22 cases (50% sensitivity), whereas a normal FO anatomy was correctly predicted in 19 of 23 cases (83% specificity). After current re-analysis of the stored videos and images, we identified three highly significant markers for restrictive FO: a FO diameter < 7 mm (p < 0.01), a fixed (p = 0.035) and a hypermobile (p = 0.014) FO flap. The maximum systolic flow velocities in the pulmonary veins were also significantly increased in restrictive FO (p = 0.021), but no cut-off value to reliably predict restrictive FO could be identified. If the above markers are applied, all 22 cases with restrictive FO and all 23 cases with normal FO anatomy could correctly be predicted (100% positive predictive value). Correct prediction of urgent BAS also succeeded in all 22 cases with restrictive FO (100% PPV), but naturally failed in 4 of the 23 cases with correctly predicted normal FO ('bad mixer') (82.6% negative predictive value). CONCLUSION: Precise assessment of FO size and FO flap motility allows a reliable prenatal prediction of both restrictive and normal FO anatomy postnatally. Prediction of likelihood of urgent BAS also succeeds reliably in all fetuses with restrictive FO, but identification of the small subset of fetuses that also requires urgent BAS despite their normal FO anatomy fails, because the ability of sufficient postnatal interatrial mixing cannot be predicted prenatally. Therefore, all fetuses with prenatally diagnosed d-TGA should always be delivered in a tertiary center with cardiac catheter stand-by, allowing BAS within the first 24 h after birth, regardless of their predicted FO anatomy.

Ultrastructural characterization of maturing iPSC-derived nephron structures upon transplantation.

Pluripotent stem cell-derived kidney organoids hold great promise as a potential auxiliary transplant tissue for individuals with end-stage renal disease and as a platform for studying kidney diseases and drug discovery. To establish accurate models, it is crucial to thoroughly characterize the morphological features and maturation stages of the cellular components within these organoids. Nephrons, the functional units of the kidney, possess distinct morphological structures that directly correlate with their specific functions. High spatial resolution imaging emerges as a powerful technique for capturing ultrastructural details that may go unnoticed with other methods such as immunofluorescent imaging and scRNA sequencing. In our study, we have applied software capable of seamlessly stitching virtual slides generated from electron microscopy, resulting in high-definition overviews of tissue slides. With this technology, we can comprehensively characterize the development and maturation of kidney organoids when transplanted under the renal capsule of mice. These organoids exhibit advanced ultrastructural developments upon transplantation, including the formation of the filtration barrier in the renal corpuscle, the presence of microvilli in the proximal tubule, and various types of cell sub-segmentation in the connecting tubule similarly to those seen in the adult kidney. Such ultrastructural characterization provides invaluable insights into the structural development and functional morphology of nephron segments within kidney organoids and how to advance them by interventions such as a transplantation. Research Highlights High-resolution imaging is crucial to determine morphological maturation of hiPSC-derived kidney organoids. Upon transplantation, refined ultrastructural development of nephron segments was observed, such as the development of the glomerular filtration barrier.

A database for MR-based electrical properties tomography with in silico brain data-ADEPT.

PURPOSE: Several reconstruction methods for MR-based electrical properties tomography (EPT) have been developed. However, the lack of common data makes it difficult to objectively compare their performances. This is, however, a necessary precursor for standardizing and introducing this technique in the clinical setting. To enable objective comparison of the performances of reconstruction methods and provide common data for their training and testing, we created ADEPT, a database of simulated data for brain MR-EPT reconstructions. METHODS: ADEPT is a database containing in silico data for brain EPT reconstructions. This database was created from 25 different brain models, with and without tumors. Rigid geometric augmentations were applied, and different electrical properties were assigned to white matter, gray matter, CSF, and tumors to generate 120 different brain models. These models were used as input for finite-difference time-domain simulations in Sim4Life, used to compute the electromagnetic fields needed for MR-EPT reconstructions. RESULTS: Electromagnetic fields from 84 healthy and 36 tumor brain models were simulated. The simulated fields relevant for MR-EPT reconstructions (transmit and receive RF fields and transceive phase) and their ground-truth electrical properties are made publicly available through ADEPT. Additionally, nonattainable fields such as the total magnetic field and the electric field are available upon request. CONCLUSION: ADEPT will serve as reference database for objective comparisons of reconstruction methods and will be a first step toward standardization of MR-EPT reconstructions. Furthermore, it provides a large amount of data that can be exploited to train data-driven methods. It can be accessed from  https://doi.org/10.34894/V0HBJ8.

Listening for rain: Principal component analysis and linear discriminant analysis for broadband acoustic rainfall detection.

Rain falling on the ocean creates acoustic signals. Ma and Nystuen [(2005). J. Atmos. Oceanic Technol. 22, 1225-1248] described an algorithm that compares three narrowband "discriminant" frequencies to detect rain. In 2022, Trucco, Bozzano, Fava, Pensieri, Verri, and Barla [(2022). IEEE J. Oceanic Eng. 47(1), 213-225] investigated rain detection algorithms that use broadband spectral data averaged over 1 h. This paper implements a rainfall detector that uses broadband acoustic data at 3-min time resolution. Principal Component Analysis (PCA) reduces the dimensionality of the broadband data. Rainfall is then detected via a Linear Discriminant Analysis (LDA) on the data's principal component projections. This PCA/LDA algorithm was trained and tested on 5 months of data recorded by hydrophones in a shallow noisy cove, where it was not feasible to average spectral data over 1 h. The PCA/LDA algorithm successfully detected 78 ± 5% of all rain events over 1 mm/h, and 73 ± 5% of all rain events over 0.1 mm/h, for a false alarm rate of ≈ 1% in both cases. By contrast, the Ma and Nystuen algorithm detected 32 ± 5% of the rain events over 1.0 mm/h when run on the same data, for a comparable false alarm rate.

Postnatal surgical treatment and complications following intrauterine vesicoamniotic shunting with the SOMATEX® intrauterine shunt. A single center experience.

INTRODUCTION: Intrauterine vesicoamniotic shunting (VAS) using a Somatex® shunt was shown to significantly affect survival of male fetuses with megacystis in suspected lower urinary tract obstruction (LUTO) [Figure 1]. Data on postnatal surgical management and complications are largely lacking. OBJECTIVE: To describe the postnatal management of patients with prenatal VAS for megacystitis in suspected severe LUTO. STUDY DESIGN: All male newborns with previous intrauterine VAS using a Somatex® shunt treated in our institution were retrospectively analyzed. We evaluated the spectrum of urethral pathologies and postnatal surgical management, especially focusing on shunt removal. RESULTS: Between 2016 and 2022, 17 patients (all male) were treated postnatally in our institution after VAS for suspected severe LUTO. Five fetuses with dislocated shunts underwent re-implantation in utero. Overall, premature birth before the 38th week of gestation was observed in eight patients (8/17). Seven shunts could be removed without further anesthesia as a bedside procedure. Ten patients required surgical shunt removal under general anesthesia due to migration (59%). Laparoscopic shunt extraction was performed in 8/10 cases. Most frequently, dislocated shunts were located incorporated in the detrusor in eight cases and the removal required a bladder suture in 2/8 patients. In one case, the shunt was removed from the abdominal wall and in one case from the intestine wall [Figure 2]. Posterior urethral valves were found in 8/17 patients, 6/17 patients showed a urethral atresia and one patient had urethral duplication. In two patients, we identified a high grade bilateral vesicoureteral reflux without LUTO. CONCLUSION: In our observation, more than half of the newborns with megacystis in suspected LUTO require a shunt removal surgery after early VAS using a Somatex® shunt. Urethral atresia may be found more frequently in these patients. These data should be taken into consideration for prenatal counselling of parents and planning of postnatal management.

A qualitative study on the influence of COVID-19 on smoking behaviors through changing social and physical contexts.

Globally, COVID-19 has been a major societal stressor and disrupted social and physical environments for many. Elucidating mechanisms through which societal disruptions influence smoking behavior has implications for future tobacco control efforts. Qualitative interviews were conducted among 38 adults who smoked combustible cigarettes in 2020 and 2021. The majority were women (75.7%), identified as Black (56.8%), were employed (61.3%), had a smoke-free home (66.7%) and lived in a small metro or rural (79.0%) county, primarily in rural southwest Georgia. Participants reported more time at home, increased isolation and less socializing, changed work and financial situations and altered household and family contexts. The vast majority of participants smoked more at some point during the pandemic with about half of these continuing to smoke more at the time of the interview. More time at home, multiple sources of stress and boredom were the main reasons for increased smoking. Decreases in smoking were attributed to financial strain, smoke-free home rules and nonsmoking family members, concerns about COVID-19 and less socializing with friends who smoke. Future tobacco control efforts during societal stressors such as pandemics should take into account specific psychosocial and environmental influences in attempts to minimize negative changes to smoking patterns.

Frequency and associated symptoms of isthmoceles in women 6 months after caesarean section: a prospective cohort study.

PURPOSE: The purpose of this study was to determine the frequency of detection of isthmoceles by ultrasound 6 months after caesarean section (CS) and which symptoms associated with isthmocele formation occur after CS. Subsequently, it was determined how often the ultrasound finding "isthmocele" coincided with the presence of complaints. METHODS: A prospective multicentre cohort study was conducted with 546 patients from four obstetric centres in Berlin, who gave birth by primary or secondary CS from October 2019 to June 2020. 461 participants were questioned on symptoms 3 months after CS; 329 participants were included in the final follow-up 6 months after CS. The presence of isthmoceles was determined by transvaginal sonography (TVS) 6 months after CS, while symptoms were identified by questionnaire. RESULTS: Of the 329 women, 146 (44.4%) displayed an isthmocele in the TVS. There was no statistically significant difference in the manifestation of symptoms between the two groups of women with and without isthmocele; however, when expressed on a scale from 1 to 10 the intensity of both scar pain and lower abdominal pain was significantly higher in the set of women that had shown to have developed an isthmocele (p = 0.014 and p = 0.031, respectively). CONCLUSION: The prevalence of isthmoceles 6 months after CS was 44.4%. Additionally, scar pain and lower abdominal pain were more pronounced when an isthmocele was also observed in the TVS. TRIAL REGISTRATION: Trial registration number DRKS00024977. Date of registration 17.06.2021, retrospectively registered.

Physiological and radiological parameters predicting outcome from penetrating traumatic brain injury treated in the deployed military setting.

INTRODUCTION: Penetrating traumatic brain injury (TBI) is the most common cause of death in current military conflicts, and results in significant morbidity in survivors. Identifying those physiological and radiological parameters associated with worse clinical outcomes following penetrating TBI in the austere setting may assist military clinicians to provide optimal care. METHOD: All emergency neurosurgical procedures performed at a Role 3 Medical Treatment Facility in Afghanistan for penetrating TBI between 01 January 2016 and 18 December 2020 were analysed. The odds of certain clinical outcomes (death and functional dependence post-discharge) occurring following surgery were matched to existing agreed preoperative variables described in current US and UK military guidelines. Additional physiological and radiological variables including those comprising the Rotterdam criteria of TBI used in civilian settings were additionally analysed to determine their potential utility in a military austere setting. RESULTS: 55 casualties with penetrating TBI underwent surgery, all either by decompressive craniectomy (n=42) or craniotomy±elevation of skull fragments (n=13). The odds of dying in hospital attributable to TBI were greater with casualties with increased glucose on arrival (OR=70.014, CI=3.0399 to 1612.528, OR=70.014, p=0.008) or a mean arterial pressure <90 mm Hg (OR=4.721, CI=0.969 to 22.979, p=0.049). Preoperative hyperglycaemia was also associated with increased odds of being functionally dependent on others on discharge (OR=11.165, CI=1.905 to 65.427, p=0.007). Bihemispheric injury had greater odds of being functionally dependent on others at discharge (OR=5.275, CI=1.094 to 25.433, p=0.038). CONCLUSIONS: We would recommend that consideration of these three additional preoperative clinical parameters (hyperglycaemia, hypotension and bihemispheric injury on CT) when managing penetrating TBI be considered in future updates of guidelines for deployed neurosurgical care.

An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review.

Introduction: Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding. Method: A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: "protein binding," "beta-lactam antibiotic," and "body fluid." Only studies were included where protein binding was measured in humans in vivo. Results: The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding. Discussion/Conclusion: Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients. Systematic Review Registration: PROSPERO, identifier (CRD42021252776).

[Are conspiracy theorists psychotic? A comparison between conspiracy theories and paranoid delusions]. / Zijn complotdenkers psychotisch? Een vergelijking tussen complottheorieën en paranoïde wanen.

BACKGROUND: Conspiracy theories are popular during the COVID-19 pandemic. Conspiratorial thinking is characterised by the strong conviction that a certain situation that one sees as unjust is the result of a deliberate conspiracy of a group of people with bad intentions. Conspiratorial thinking appears to have many similarities with paranoid delusions. AIM: To explore the nature, consequences, and social-psychological dimensions of conspiratorial thinking, and describe similarities and differences with paranoid delusions. METHOD: Critically assessing relevant literature about conspiratorial thinking and paranoid delusions. RESULTS: Conspiratorial thinking meets epistemic, existential, and social needs. It provides clarity in uncertain times and connection with an in-group of like-minded people. Both conspiratorial thinking and paranoid delusions involve an unjust, persistent, and sometimes bizarre conviction. Unlike conspiracy theorists, people with a paranoid delusion are almost always the only target of the presumed conspiracy, and they usually stand alone in their conviction. Furthermore, conspiracy theories are not based as much on unusual experiences of their inner self, reality, or interpersonal contacts. CONCLUSIONS Conspirational thinking is common in uncertain circumstances. It gives grip, certainty, moral superiority and social support. Extreme conspirational thinking seems to fit current psychiatric definitions of paranoid delusions, but there are also important differences. To make a distinction with regard to conspiratorial thinking, deepening of conventional definitions of delusions is required. Instead of the strong focus on the erroneous content of delusions, more attention should be given to the underlying idiosyncratic, changed way of experiencing reality.

[Green tooth discoloration in a two-year-old boy]. / Groene tandverkleuring bij een peuter.

Green tooth discoloration can have several causes. From the patient history of the two-year-old with green tooth discoloration clear causal relationships can be identified. The pathological cause is an increase in bilirubin levels for an extended period of time. Determining the extent of tooth development in combination with the increase in bilirubin levels makes it possible to estimate the degree and pattern of green tooth discoloration. If the increase in bilirubin levels is short-lived, it is possible the permanent dentition will not be affected.

Risk factors of violent offending in mentally ill prisoners with autism spectrum disorders.

BACKGROUND: Results of research regarding a possible causal relation between autism spectrum disorders (ASDs) and violence are mixed. Several explanations have been proposed. AIMS: To assess prevalence rates of comorbid disorders in a large sample of mentally ill offenders diagnosed with ASD. Offenders with and without comorbid mental disorders were compared on several characteristics. To better understand the relationship between ASD and violent criminal behavior, the predictive value of several proposed risk factors (comorbidity, negative social network/influenceability, and childhood trauma/victimization) on violent offending was investigated. METHOD: Data of 394 male offenders with a diagnosis of ASD were included. Prevalence rates of comorbid mental disorders next to ASD were calculated, and characteristics were compared using chi-square or t-tests. The predictive value of the risk factors was assessed using a binary logistic regression (n = 357). RESULTS: High rates of comorbidity were found (78.9%), specifically for substance use disorders (39.8%), schizophrenia spectrum disorders (31.7%), and neurodevelopmental disorder other than ASD (24.1%). Offenders with and without comorbidity differed significantly in their criminal and mental health care history. Both comorbidity (OR = 1.68; 95% CI 1.27-2.18) and a negative social network/influenceability (OR = 1.49; 95% CI 1.11-1.99) showed to be significant predictors of violent offending within this sample. CONCLUSIONS: The highest rates of comorbid disorders found were disorders that have been previously linked to violent offending, and the risk of violent offending could be unrelated to ASD. However, the role of social functioning indicates a risk specific to the symptoms of ASD.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with truncus arteriosus communis (TAC).

PURPOSE: To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with truncus arteriosus communis (TAC) METHODS: All cases of TAC diagnosed prenatally over a period of 8 years were retrospectively collected in two tertiary referral centers. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. RESULTS: 39 cases of TAC were diagnosed prenatally. Mean gestational age at first diagnosis was 22 weeks (range, 13-38). Two cases were lost follow-up. Correct prenatal diagnosis of TAC was made in 21 of 24 (87.5%) cases and of TAC subtype in 19 of 21 (90.5%) cases. Prenatal diagnosis of TAC was incorrect in three cases: one newborn had aortic atresia with ventricular septal defect postnatally, one had hypoplastic right ventricle with dextro Transposition of the Great Arteries with coartation of the aorta and a third newborn had Tetralogy of Fallot with abnormal origin of the left pulmonary artery arising from the ascending aorta postnatally. These three cases were excluded from further analysis. In 9 of 34 (26.5%) cases, TAC was an isolated finding. 13 (38.2%) fetuses had additional chromosomal anomalies. Among them, microdeletion 22q11.2 was most common with a prevalence of 17.6% in our cohort. Another 3 fetuses were highly suspicious for non-chromosomal genetic syndromes due to their additional extra-cardiac anomalies, but molecular diagnosis could not be provided. Major cardiac and extra-cardiac anomalies occurred in 3 (8.8%) and in 20 (58.8%) cases, respectively. Predominantly, extra-cardiac anomalies occurred in association with chromosomal anomalies. Additionally, severe IUGR occurred in 6 (17.6%) cases. There were 14 terminations of pregnancy (41.2%), 1 (2.9%) intrauterine fetal death, 5 postnatal deaths (14.7%) and 14 (41.2%) infants were alive at last follow-up. Intention-to-treat survival rate was 70%. Mean follow-up among survivors was 42 months (range, 6-104). Postoperative health status among survivors was excellent in 11 (78.6%) infants, but 5 (46.2%) of them needed repeated re-interventions due to recurrent pulmonary artery or conduit stenosis. The other 3 (21.4%) survivors were significantly impaired due to non-cardiac problems. CONCLUSION: TAC is a rare and complex cardiac anomaly that can be diagnosed prenatally with high precision. TAC is frequently associated with chromosomal and extra-cardiac anomalies, leading to a high intrauterine and postnatal loss rate due to terminations and perioperative mortality. Without severe extra-cardiac anomalies, postoperative short- and medium-term health status is excellent, independent of the subtype of TAC, but the prevalence of repeated interventions due to recurrent stenosis is high.