The average three-dimensional face for different sex and age groups in a Dutch population.

The increasing use of three-dimensional imaging calls for reference models representing large parts of the population. The aim of this prospective study was to create templates depicting facial maturation in the younger age groups. Healthy Dutch volunteers were captured, without selection of inclusions. Three-dimensional average faces were created using MATLAB, for both genders in four age groups (4-8 years, 8-12 years, 12-16 years, and ≥16 years). Variation within the groups was calculated and depicted on an average face with a green to red colour scale, corresponding to standard deviations between 0 and ≥ 3 mm, respectively. Measurements of the distances of eight peri-oral landmarks were provided as ratios. The statistical analysis was performed using ANOVA and Tukey's test. Three-dimensional reconstructions of the average face and their first principal component were created for each gender and age group. The first principal component comprised the facial width for each group, and the variation of landmarks was low. All ratios showed an increasing trend with increasing age, except for the ratio of philtrum width to mouth width. This study is novel in comparing facial morphology by means of ratios and in creating average faces for the different young age groups. These data provide useful insights into facial maturation, which might be beneficial for facial surgeons.

Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19.

INTRODUCTION: Endothelial damage and thrombosis caused by COVID-19 may imperil cardiovascular health. More than a year since the WHO declared COVID-19 pandemic, information on its effects beyond the acute phase is lacking. We investigate endothelial dysfunction, coagulation and inflammation, 3 months post-COVID-19. MATERIALS AND METHODS: A cohort study was conducted including 203 patients with prior COVID-19. Macrovascular dysfunction was assessed by measuring the carotid artery diameter in response to hand immersion in ice-water. A historic cohort of 312 subjects served as controls. Propensity score matching corrected for baseline differences. Plasma concentrations of endothelin-1 were measured in patients post-COVID-19, during the acute phase, and in matched controls. Coagulation enzyme:inhibitor complexes and inflammatory cytokines were studied. RESULTS AND CONCLUSIONS: The prevalence of macrovascular dysfunction did not differ between the COVID-19 (18.6%) and the historic cohort (22.5%, RD -4%, 95%CI: -15-7, p = 0.49). Endothelin-1 levels were significantly higher in acute COVID-19 (1.67 ± 0.64 pg/mL) as compared to controls (1.24 ± 0.37, p < 0.001), and further elevated 3 months post-COVID-19 (2.74 ± 1.81, p < 0.001). Thrombin:antithrombin(AT) was high in 48.3%. Markers of contact activation were increased in 16-30%. FVIIa:AT (35%) and Von Willebrand Factor:antigen (80.8%) were elevated. Inflammatory cytokine levels were high in a majority: interleukin(IL)-18 (73.9%), IL-6 (47.7%), and IL-1ra (48.9%). At 3 months after acute COVID-19 there was no indication of macrovascular dysfunction; there was evidence, however, of sustained endothelial cell involvement, coagulation activity and inflammation. Our data highlight the importance of further studies on SARS-CoV-2 related vascular inflammation and thrombosis, as well as longer follow-up in recovered patients.

Coupling Charge and Topological Reconstructions at Polar Oxide Interfaces.

In oxide heterostructures, different materials are integrated into a single artificial crystal, resulting in a breaking of inversion symmetry across the heterointerfaces. A notable example is the interface between polar and nonpolar materials, where valence discontinuities lead to otherwise inaccessible charge and spin states. This approach paved the way for the discovery of numerous unconventional properties absent in the bulk constituents. However, control of the geometric structure of the electronic wave functions in correlated oxides remains an open challenge. Here, we create heterostructures consisting of ultrathin SrRuO_{3}, an itinerant ferromagnet hosting momentum-space sources of Berry curvature, and LaAlO_{3}, a polar wide-band-gap insulator. Transmission electron microscopy reveals an atomically sharp LaO/RuO_{2}/SrO interface configuration, leading to excess charge being pinned near the LaAlO_{3}/SrRuO_{3} interface. We demonstrate through magneto-optical characterization, theoretical calculations and transport measurements that the real-space charge reconstruction drives a reorganization of the topological charges in the band structure, thereby modifying the momentum-space Berry curvature in SrRuO_{3}. Our results illustrate how the topological and magnetic features of oxides can be manipulated by engineering charge discontinuities at oxide interfaces.

Psychosocial care in dementia in European higher education: Evidence from the SiDECar ("Skills in DEmentia Care") project.

In dementia care, psychosocial interventions can increase people's quality of life with dementia and their caregivers. Despite their effectiveness, their translation into practice lacks the desirable systematicity. Systematic educational programs on psychosocial interventions in dementia will improve this translation, as it prepares professionals to face the complexity of dementia care. This study aimed to systematically map out the extent to which higher education programs in Europe include teaching activities about psychosocial care of dementia. We collected quantitative and qualitative data about 303 higher education teaching activities on psychosocial care in dementia across Europe. The analysis revealed that the number of teaching activities focusing on psychosocial care in dementia was relative. Although the results reflected UNESCO indications, the teaching activities on psychosocial care in dementia appeared less systematized than optimal. As world health agencies recommend, international higher education systems should consider more psychosocial care topics because they can prepare professionals to respond timely and effectively to dementia patients and caregivers' needs.

Effects of short-term exposures to ultrafine particles near an airport in healthy subjects.

BACKGROUND: Recent studies reported elevated concentrations of ultrafine particles (UFP) near airports. Little is known about the health effects of UFP from aviation. Since UFP can deposit deep into the lungs and other organs, they may cause significant adverse health effects. OBJECTIVE: We investigated health effects of controlled short-term human exposure to UFP near a major airport. METHODS: In this study, 21 healthy non-smoking volunteers (age range: 18-35 years) were repeatedly (2-5 visits) exposed for 5 h to ambient air near Schiphol Airport, while performing intermittent moderate exercise (i.e. cycling). Pre- to post-exposure changes in cardiopulmonary outcomes (spirometry, forced exhaled nitric oxide, electrocardiography and blood pressure) were assessed and related to total- and size-specific particle number concentrations (PNC), using linear mixed effect models. RESULTS: The PNC was on average 53,500 particles/cm3 (range 10,500-173,200). A 5-95th percentile increase in exposure to UFP (i.e. 125,400 particles/cm3) was associated with a decrease in FVC of -73.8 mL (95% CI -138.8 - -0.4) and a prolongation of the corrected QT (QTc) interval by 9.9 ms (95% CI 2.0 - 19.1). These effects were associated with particles < 20 nm (mainly UFP from aviation), but not with particles > 50 nm (mainly UFP from road traffic). DISCUSSION: Short-term exposures to aviation-related UFP near a major airport, was associated with decreased lung function (mainly FVC) and a prolonged QTc interval in healthy volunteers. The effects were relatively small, however, they appeared after single exposures of 5 h in young healthy adults. As this study cannot make any inferences about long-term health impacts, appropriate studies investigating potential health effects of long-term exposure to airport-related UFP, are urgently needed.

Microstructured beta-tricalcium phosphate for alveolar cleft repair: a two-centre study.

The current standard of care in alveolar cleft repair is timing the procedure in the mixed dentition stage and making use of autologous bone to restore the maxillary defect. Using a synthetic bone substitute bypasses the risk of donor site morbidity and reduces the operation time. In this study, the outcome of alveolar cleft repair using microporous beta-tricalcium phosphate (ß-TCP) was investigated in patients with unilateral cleft lip and palate. Twenty patients were enrolled prospectively in this study, divided between two centres. Continuity of the alveolar process, recurrence of oronasal fistulas, and eruption of teeth into the repaired cleft were evaluated at 1year postoperative. Also, cone beam computed tomography scans were analyzed using a volume-based semi-automatic segmentation protocol. No adverse events were reported. The mean residual bone volume in the repaired cleft at 1year postoperative was 65%. There was no recurrence of oronasal fistula. Furthermore, 90% of the teeth adjacent to the cleft erupted spontaneously and all patients showed a continuous alveolar process. Secondary alveolar grafting using microporous ß-TCP can safely be used in the clinical situation. Residual calcified tissue, canine eruption, and complication rates at the recipient site are comparable to those with autologous grafts.

Breast conserving surgery for extensive DCIS using multiple radioactive seeds.

BACKGROUND AND OBJECTIVES: Breast conserving surgery (BCS) can be challenging for large regions of ductal carcinoma in situ (DCIS), resulting in high rates of positive resection margins. Radioactive seed localization (RSL) using multiple radioactive iodine (125I) seeds can be used to bracket extensive DCIS (eDCIS). The goal of this study was to retrospectively compare the use of a single or multiple 125I seeds in RSL to enable BCS in patients with eDCIS. METHODS: All patients with eDCIS (area of ≥3.0 cm) who underwent either single or multiple-seed RSL between January 2008 and December 2016 were included. Patient, tumor and surgery characteristics were compared between both groups. Primary outcome measures were positive resection margin and re-operation rates. RESULTS: Respectively 48 and 58 patients with eDCIS underwent single- and multiple-seed RSL and subsequent BCS. The rate of positive resection margin (focal and more than focal) with single-seed RSL was 47.9%, compared to 29.3% with multiple-seed RSL (p = 0.06). The re-operation rate was 39.6% with single-seed RSL and 20.7% in the multiple-seed RSL group (p = 0.05). CONCLUSION: Multiple-seed RSL enables bracketing of large areas of DCIS, with the potential to decrease the high rate of positive resection margins in this patient group.

The impact of ambient air pollution on the human blood metabolome.

BACKGROUND: Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution. METHODS: We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2h before and 2 and 18h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study. RESULTS: We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism. CONCLUSIONS: This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome.

[Nonretractable foreskin in boys without complaints : An indication for circumcision?] / Die nicht-retrahierbare Vorhaut bei beschwerdefreien Jungen : Eine Indikation zur Zirkumzision?

BACKGROUND: Removing boys' foreskins, even for medical reasons, is increasingly and critically discussed. The aim of this study is to retrospectively verify if the indication for the removal of boys' foreskins was justified. The study is based on the records of boys who underwent preputial operation in an outpatient medical office for pediatric surgery. METHODS: Preoperative clinical findings, complaints, applied conservative and/or surgical procedures and histological results of the resected foreskins of boys, who underwent preputial operation between 2013-2015, were retrospectively analyzed. RESULTS: A total of 176 boys (age 5 on average) underwent a preputial operation. In 85 % of the cases it was completely removed. Most frequent clinical findings (80 %) were that the prepuce was simply not retractable. 86 % of the boys were free of complaints. The most frequent histological findings were a discrete to moderately pronounced chronic fibrous posthitis (69 %) and subepithelial fibrosis (18 %), In the first case 78 % of the boys had been free of complaints, in the latter 72 %. CONCLUSION: The majority of the treated boys were free of complaints; however, most of them underwent a complete removal of their foreskin simply because it was nonretractable. The foreskin represents the most sensitive part of the male genital, preputiolysis is a natural process that can go on until early adolescence. Irreversible surgical procedures, such as a complete foreskin removal, should thus be restricted to a clear medical indication.

The impact of particle filtration on indoor air quality in a classroom near a highway.

A pilot study was performed to investigate whether the application of a new mechanical ventilation system with a fine F8 (MERV14) filter could improve indoor air quality in a high school near the Amsterdam ring road. PM10, PM2.5, and black carbon (BC) concentrations were measured continuously inside an occupied intervention classroom and outside the school during three sampling periods in the winter of 2013/2014. Initially, 3 weeks of baseline measurements were performed, with the existing ventilation system and normal ventilation habits. Next, an intervention study was performed. A new ventilation system was installed in the classroom, and measurements were performed during 8 school weeks, in alternating 2-week periods with and without the filter in the ventilation system under otherwise identical ventilation conditions. Indoor/outdoor ratios measured during the weeks with filter were compared with those measured without filter to evaluate the ability of the F8 filter to improve indoor air quality. During teaching hours, the filter reduced BC exposure by, on average, 36%. For PM10 and PM2.5, a reduction of 34% and 30% was found, respectively. This implies that application of a fine filter can reduce the exposure of schoolchildren to traffic exhaust at hot spot locations by about one-third.

Radioactive seed localization in breast cancer treatment.

BACKGROUND: Breast cancer screening, improved imaging and neoadjuvant systemic therapy (NST) have led to increased numbers of non-palpable tumours suitable for breast-conserving surgery (BCS). Accurate tumour localization is essential to achieve a complete resection in these patients. This study evaluated the role of radioactive seed localization (RSL) in improving breast- and axilla-conserving surgery in patients with breast cancer with or without NST. METHODS: Patients who underwent RSL between 2007 and 2014 were included. Learning curves were analysed by the rates of minimally involved (in situ/invasive tumour cells on a length of 0-4 mm on ink) and positive resection margins (over 4 mm on ink) after BCS, and the median resection volume over time. RESULTS: A total of 367 patients with in situ carcinomas and 199 with non-palpable invasive breast cancer underwent RSL before primary surgery. A further 697 patients had RSL before NST, of whom 206 also underwent RSL of a histologically verified axillary lymph node metastasis. BCS was performed in 93·2 and 87·9 per cent of patients undergoing primary surgery for in situ and invasive tumours respectively, and 57·5 per cent of those in the NST group. The rate of BCS with positive resection margins was low and stable over time in the three groups (9·1, 9·7 and 11·2 per cent respectively). The median resection volume decreased significantly with time in the invasive cancer and NST groups. CONCLUSION: In the present study of more than 1200 patients and 7 years of experience, RSL was shown to facilitate breast- and axilla-conserving surgery in a diverse patient population. There was a significant reduction in resection volume while maintaining low positive resection margin rates after BCS.

A comparison between four techniques to measure cardiac output.

Cardiac output is an important variable when monitoring hemodynamic status. In particular, changes in cardiac output represent the goal of several circulatory management therapies. Unfortunately, cardiac output is very difficult to estimate, either in experimental or clinical settings. The goal of this work is to compare four techniques to measure cardiac output: pressure-volume catheter, aortic flow probe, thermodilution, and the PiCCO monitor. These four techniques were simultaneously used during experiments of fluid and endotoxin administration on 7 pigs. Findings show that, first, each individual technique is precise, with a relative coefficient of repeatability lower than 7 %. Second, 1 cardiac output estimate provided by any technique relates poorly to the estimates from the other 3, even if there is only small bias between the techniques. Third, changes in cardiac output detected by one technique are only detected by the others in 62 to 100 % of cases. This study confirms the difficulty of obtaining a reliable clinical cardiac output measurement. Therefore, several measurements using different techniques should be performed, if possible, and all such should be treated with caution.

Subperiosteal abscess in a child. Trueta's osteomyelitis hypothesis undermined?

Subperiosteal abscess formation is almost exclusively seen secondary to underlying hematogenous infected osteomyelitis or secondary as a result of a contagious focus. We present an unusual case of a 9-year-old girl with progressive ankle pain due to an isolated subperiosteal abscess of the distal fibula without concomitant osteomyelitis. The subperiosteal abscess was most likely caused by hematogenous spread to the periosteal region of the distal fibula located above the highly vascularized metaphysis. Remarkably, there were no signs of osteomyelitis on either MRI or during surgical inspection. She was successfully treated with debridement and antibiotic therapy. We hypothesize that subperiosteal abscess formation near the metaphysis originates in the periosteal region and not from outward extension from the sinusoidal veins in the intrametaphyseal area to the cortex and subperiosteal region.

Veno-venous extracorporeal CO2 removal improves pulmonary hemodynamics in a porcine ARDS model.

BACKGROUND: Protective lung ventilation is recommended in patients with acute respiratory distress syndrome (ARDS) to minimize additional injuries to the lung. However, hypercapnic acidosis resulting from ventilation at lower tidal volume enhances pulmonary hypertension and might induce right ventricular (RV) failure. We investigated if extracorporeal veno-venous CO2 removal therapy could have beneficial effects on pulmonary circulation and RV function. METHODS: This study was performed on an experimental model of ARDS obtained in eight anaesthetized pigs connected to a volume-cycled ventilator. A micromanometer-tipped catheter was inserted into the main pulmonary artery and an admittance micromanometer-tipped catheter was inserted into the right ventricle. RV-arterial coupling was derived from RV pressure-volume loops. ARDS was obtained by repeated bronchoalveolar lavage. Protective ventilation was then achieved, and the pigs were connected to a pump-driven extracorporeal membrane oxygenator (PALP, Maquet, Germany) in order to achieve CO2 removal. RESULTS: ARDS induced severe hypercapnic acidosis. Systolic pulmonary artery pressure significantly increased from 29.6±1.8 to 43.9±2.0 mmHg (P<0.001). After the PALP was started, acidosis was corrected and normocarbia was maintained despite protective ventilation. Pulmonary artery pressure significantly decreased to 31.6±3.2 mmHg (P<0.001) and RV-arterial coupling significantly improved (RV-arterial coupling index=1.03±0.33 vs. 0.55±0.41, P<0.05). CONCLUSION: Veno-venous CO2 removal therapy enabled protective ventilation while maintaining normocarbia during ARDS. CO2 removal decreased pulmonary hypertension and improved RV function. This technique may be an effective lung- and RV-protective adjunct to mechanical ventilation.

[Stability of long-term professional objectives of young physicians during postgraduate training. Results of a multicenter cohort study]. / Stabilität der beruflichen Endziele im Verlauf der fachärztlichen Weiterbildung. Ergebnisse einer multizentrischen Kohortenstudie mit zweijährigem Intervall.

INTRODUCTION: We investigated persistences and changes of career preferences of medical residents in Germany after two years of postgraduate training with regard to future working place and position. The results are compared with those forwarded at graduation from medical school in a gender comparative perspective. METHODS: The study is based on a standardized postal survey among the participants in the "KarMed" study, originally based on 1012 graduates of the medical faculties of Erlangen, Giessen, Hamburg, Heidelberg, Cologne, Leipzig and Magdeburg in 2009. 2107 persons were contacted. The return rate at baseline was 48 %, and the two surveys after the baseline reached return rates of 87 % and 89 % respectively. In all samples 2/3 were women as in actual medical undergraduate education. Descriptive statistics and regression analysis were performed. RESULTS: After 2 years of residency, residents after 2 years of postgraduate training still preferred the hospital over private practice as their final workplace after postgraduate training. The attractiveness of leading positions in the hospital declined among men, whereas it was already low for women at graduation. A large proportion of those physicians preferring the ambulatory sector, especially women, wishes to work as employee instead of private practice. At the personal level, almost 60 % forwarded the same preferences as those at graduation. Gender, parenthood and region of study (East vs. West Germany) did not influence stability or change of preferences. CONCLUSION: The results demonstrate the persistence of professional preferences regarding future sector and position of medical work during postgraduate training. These preferences do neither match with principles of gender equality nor with future workforce needs (e. g. in primary care).

The effect of head movement on CT perfusion summary maps: simulations with CT hybrid phantom data.

Head movement is common during CT brain perfusion (CTP) acquisition of patients with acute ischemic stroke. The effects of this movement on the accuracy of CTP analysis has not been studied previously. The purpose of this study was to quantify the effects of head movement on CTP analysis summary maps using simulated phantom data. A dynamic digital CTP phantom dataset of 25 time frames with a simulated infarct volume was generated. Head movement was simulated by specific translations and rotations of the phantom data. Summary maps from this transformed phantom data were compared to the original data using the volumetric dice similarity coefficient (DSC). DSC for both penumbra and core strongly decreased for rotation angles larger than approximately 1°, 2°, and 7° for, respectively, pitch, roll, and yaw. The accuracy is also sensitive for small translations in the z-direction only. Sudden movements introduced larger errors than gradual movement. These results indicate that CTP summary maps are sensitive to head movement, even for small rotations and translations. CTP scans with head movement larger than the presented values should be interpreted with extra care.

Ultrasound diagnosis of supracondylar fractures in children.

PURPOSE: The objective of our study was to evaluate the safety and accuracy of ultrasound (US) compared to standard radiographs in diagnosing supracondylar fractures (SCFs) of the humerus in children. PATIENTS AND METHODS: A total of 106 children (aged between 1 and 13 years) with clinically suspected SCF of the humerus were primarily examined by US followed by standard two-plane radiographs of the elbow. US was conducted with a linear scanner viewing the distal humerus from seven standardized sectional planes. US fracture diagnosis was established either by a cortical bulging or cortical gap, or by a positive dorsal fat pad (dFP) sign. X-ray diagnosis was stated by an independent pediatric radiologist and, afterwards, compared to our US findings. Sonographic and radiographic findings were collected in a contingency table. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) for US fracture diagnosis were calculated according to the radiographs. In addition, by identifying significant angulation and/or disrupture, SCFs were classified as non-operative/stable and operative/instable SCFs according to the AO Pediatric Fracture Classification System. RESULTS: By US, a SCF could be excluded in 43 patients and in 63 patients, a fracture was diagnosed. In contrast, by radiographs, an SCF could be excluded in 46 patients and in 60 patients, a fracture was diagnosed. For US fracture diagnosis in comparison to radiographs, we calculated a sensitivity of 100 %, a specificity of 93.5 %, an NPV of 100 %, and a PPV of 95.2 %. Thirty-nine SCFs were sonographically classified as stable grades 1/2 SCFs and confirmed in 37 patients by X-rays. All four operative/instable SCFs were correctly identified by US. CONCLUSION: By identifying a positive dFP sign and/or cortical lesions of the distal humerus, SCFs can be detected very sensitively by US. Even the estimation of fracture displacement seems to be possible. We suggest US as an applicable alternative method in the primary evaluation of suspected SCF in children, guiding further diagnostics, where appropriate. After minor injuries, if clinical assessment for an elbow fracture is low and US examination is negative for fracture, additional radiographs are dispensable. Thereby, the amount of X-ray burden during childhood can be reduced, without loss of diagnostic safety.

Otocephaly-Dysgnathia Complex: Description of Four Cases and Confirmation of the Role of OTX2.

Otocephaly-dysgnathia complex is characterized by mandibular hypo- or aplasia, ear abnormalities, microstomia, and microglossia. Mutations in the orthodenticle homeobox 2 (OTX2) and paired related homeobox 1 (PRRX1) genes have recently been identified in some cases. We screened 4 otocephalic cases for these 2 genes and identified OTX2 mutations in 2 of them, thus confirming OTX2 is implicated in otocephaly. No PRRX1 mutation was identified. Interestingly, ocular involvement is not a constant feature in otocephalic cases with an OTX2 mutation. In one case, the mutation was inherited from a microphthalmic mother. The mechanism underlying this intrafamilial phenotypic variability remains unclear, but other genetic factors are likely to be necessary for the manifestation of the otocephalic phenotype.