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This study connects to an ongoing discussion about the limits and affordances of simulators as realistic and relevant contexts for professional learning, in this case in the development of visual expertise. Earlier studies of simulator-based maritime pilot training conclude that there are risks associated with so-called negative skills transfer due to a lack of photorealism in simulator environments. The aim of this study is to carefully examine how visual expertise develops in and through training in a simulated environment. Through a practice-based approach to the development of visual expertise, and by using qualitative interaction analysis of video recorded training sessions, the analytical focus is directed towards maritime pilot trainees' talk about imperfections and inconsistencies in the virtual environment during exercises in a high-fidelity bridge simulator. Considering the multi-layered nature of the maritime pilot's visual expertise, findings show that the maritime pilots in training noticed and adapted to the specific methodological and technological challenges when manoeuvring a simulated vessel. During such reflection-in-action, they also commented on and explored the differences between, navigating in a simulator, on the one hand, and, on the other hand, navigating on board a ship. Instead of concluding that there is a risk for negative skills transfer that follows from the differences between the two contexts of navigating, we argue that the challenges introduced by representations encountered when training in a virtual environment may add to the expertise of the trainees and lead to enriched conceptual, methodological, and technical knowledge regarding the specificities of visually demanding and ambiguous navigation situations. In this way, this study contributes to advance our understanding of learning in virtual environments to the frontline of learning research.

Abstract Introduction Fine-needle aspiration cytology (FNAC) is an effective tool in the diagnostic work-up of patients with thyroid nodules. The aim of our study was to assess the diagnostic sensitivity of FNAC in thyroid cancer (TC) in Sweden by correlating the findings of preoperative FNAC with those obtained through final histology of the surgical specimen. Methods A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing patient FNAC and histology reports. Results Among the 2519 cases operated with a final diagnosis of TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%), included in the present study. Among these, 1679 patients (72%) were female and the median age at TC diagnosis was 52.3 years (range 18-94.6). In 353 cases (15.1%) FNAC was not performed at all; whereas in the remaining 1965 cases, the diagnostic sensitivity of FNAC was 81.6%. In lesions > 1 cm, FNAC diagnostic sensitivity reached 86.5%, whereas in lesions 1 cm, the diagnostic sensitivity of US-guided FNAC (n = 1504) was 86.9% as compared to 76.9% in clinically applied FNAC without US utilization (n = 118). Conclusions FNAC is performed in most patients operated for TC in Sweden (85%) and retains its value as a tool in TC diagnostic work-up with an overall sensitivity of 82%, reaching 87% in lesions > 1 cm, that harbor clinically relevant TC.

Abstract Many applications are suggested for Ti‐MXene motivating strong interest in studies of Ti3C2Tx synthesis by solution‐based methods. However, so far only ex situ studies of the synthesis are performed, mostly due to the difficulty of handling HF‐based solutions. Here the first time‐resolved in situ synchrotron radiation X‐ray Diffraction study of MXene synthesis performed using a plastic capillary‐size reaction cell directly in HF solution is reported. This study provides the first report on the structure of “pristine MXene” formed by Ti3AlC2 etching with LiF+HCl. The term “pristine” refers to the MXene structure found directly in HF solution. By comparing the interlayer distances of pristine MXene (≈13.5 Å), solvent‐free Li‐intercalated MXene (≈12.2 Å), and Li‐free MXene (≈10.7 Å), it can be concluded that the width of “slit pores” formed by terminated MX layers during the Al etching does not exceed ≈3 Å. The width of these slit pores is a key factor for HF etching of Al within the interlayers. This space constraint explains the slow kinetics of MXene formation in HF‐based synthesis methods. No intermediate phases are observed, suggesting that the crystalline MXene phase is formed by the simultaneous etching of Al and termination of Ti3C2 layers.

Abstract Swelling is the most fundamental property of graphite oxides (GO). Here, a structural study of Brodie graphite oxide (BGO) swelling in a set of long chain 1‐alcohols (named C11 to C22 according to the number of carbons) performed using synchrotron radiation X‐ray diffraction at elevated temperatures is reported. Even the longest of tested alcohols (C22) is found to intercalate BGO with enormous expansion of the interlayer distance from ≈6Å up to ≈63Å, the highest expansion of GO lattice ever reported. Swelling transitions from low temperature α‐phase to high temperature β‐phase are found for BGO in all alcohols in the C11–C22 set. The transitions correspond to decrease of inter‐layer distance correlating with the length of alcohol molecules, and change in their orientation from perpendicular to GO planes to layered parallel to GO (Type II transitions). These transitions are very different compared to BGO swelling transitions (Type I) found in smaller alcohols and related to insertion/de‐insertion of additional layer of alcohol parallel to GO. Analysis of general trends in the whole set of 1‐alcohols (C1 to C22) shows that the 1‐alcohol chain length defines the type of swelling transition with Type I found for alcohols with C10.

Background Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their occurrence.Methods Data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development (I-DSD) Registry. Logistic regressions, fisher’s exact tests and spearman’s correlation tests were performed on the data to assess associations between clinical factors and complication rates.Results Of the 551 eligible boys, data were available on 160 (29%). Within the cohort, the median (range) External Masculinization Score (EMS) was 6 (2, 9). All presented with one or more additional genital malformation and 61 (38%) presented with additional extragenital malformations. Disorders of androgen action, androgen synthesis and gonadal development were diagnosed in 28 (18%), 22 (14%) and 9 (6%) boys, respectively. The remaining 101 (62%) patients were diagnosed as having non-specific 46,XY Disorders of Sex Development. Eighty (50%) boys had evidence of abnormal biochemistry, and gene variants were identified in 42 (26%). Median age at first hypospadias surgery was 2 years (0, 9), and median length of follow-up was 5 years (0, 17). Postsurgical complications were noted in 102 (64%) boys. There were no significant associations with postsurgical complications.Conclusions Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative complications. No clinical factors were significantly associated with complication rates. High complication rates with no observable cause suggest the involvement of other factors which need investigation.

Patient journeys are instruments developed by EURORDIS, The Voice of Rare Disease Patients in Europe, to collect patients’ experiences; they may identify gaps and areas deserving improvement, as well as elements positively considere d by affected persons. As with other patient-reported experiences, they can complete the clinical evaluation and management of a specific disease, improving the often long diagn ostic delay, therapy, patient education and access to knowledgeable multidisciplinary teams. This review discusses the utility of such patient-reported experience measures and summarises the experiences of patients with acromegaly, Addison’s disease and congenital adrenal hyperplasia from different European countries. Despite rare endo crine diseases being varied and presenting differently, feelings of not having been t aken seriously by health professionals, family and friends was a common patient complaint. Empathy and a positive patient-centred environment tend to improve clinical practice by creating a trustworthy and understanding atmosphere, where individual patient needs ar e considered. Offering access to adequate patient information on their disease, treatments and outcome helps to adapt to living with a chronic disease and what to expect in the future, contemplating the impact of a disease on patients’ everyday life, not only clinical outcome but also social, financial, educational, family and leisure issues is des irable; this facilitates more realistic expectancies for patients and can even lead to a reduction in health costs. Patient empowerment with patient-centred approaches to these complex or chronic diseases should be contemplated more and more, not only for the benefit o f those affected but also for the entire health system.

A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition that results in cortisol deficiency and excess production of adrenal androgens. While the introduction of newborn screening for CAH has reduced morbidity and mortality, management of CAH remains challenging. Lifelong treatment with glucocorticoids is required to replace the endogenous cortisol deficiency and reduce excess adrenal androgens. Undertreatment or overtreatment with glucocorticoids can lead to multiple disease- and treatment-related comorbidities, including impaired growth and compromised final height, menstrual irregularities and reduced fertility in females, and long-term cardiometabolic complications. In addition to avoiding adrenal crisis and sudden death, treatment goals in adolescent females with CAH are to obtain normal growth and bone maturation and normal timing of puberty. Management of adolescents is particularly challenging due to changes in growth and sex hormone levels that can lead to inadequate suppression of adrenal androgens and increasing independence that can affect treatment adherence. During the transition to adult care, treatment goals focus on preventing symptoms of hyperandrogenism, preserving menstrual regularity and fertility, and providing education and support for issues related to sexuality, atypical genitalia, and/or complications from previous surgical treatment. In addition, patients must be monitored continuously to prevent long-term complications such as decreased bone mineral density, obesity, diabetes, and hypertension. In this review, we discuss the challenges faced by adolescent and adult females with CAH and provide guidance to health-care professionals to help patients to navigate these challenges. [ABSTRACT FROM AUTHOR]

Abstract Very long‐chain acyl‐CoA dehydrogenase deficiency (VLCADD) is a recessive disorder of fatty acid beta‐oxidation with variable phenotype. Patients may present during the neonatal period with lethal multi‐organ failure or during adulthood with a myopathic phenotype. VLCADD is included in the Swedish newborn screening (NBS) program since 2010. The study describes the phenotype and biochemical findings in relation to the genotype, enzyme activity, and screening data in a Swedish cohort of pediatric patients with VLCADD. A total of 22 patients (20 diagnosed via NBS between 2010 and 2019, two diagnosed pre NBS) were included. Parameters analyzed were enzyme activity (palmitoyl CoA oxidation rate); ACADVL genotype; NBS results including Collaborative Laboratory Integrated Reports (CLIR) score; biochemical findings; treatment; clinical outcome. A clinical severity score (CSS) was compiled using treatment interventions and clinical symptoms. A possible correlation between CSS and VLCAD residual enzyme activity and NBS CLIR score was analyzed. The most common ACADVL variant (c.848T>C) was identified in 24/44 alleles. Five novel variants were detected. Clinical manifestations varied from asymptomatic to severe. There was a correlation between CSS, residual enzyme activity, and CLIR scores. Most patients diagnosed via NBS had less severe disease compared to those clinically diagnosed. In conclusion, the identified correlation between the NBS CLIR score, residual enzyme activity, and clinical outcome suggests that information available neonatally may aid in treatment decisions.

Abstract Inborn errors of mitochondrial fatty acid oxidation (FAO), such as medium‐chain acyl‐CoA dehydrogenase deficiency (MCAD) and very long‐chain acyl‐CoA dehydrogenase deficiency (VLCAD) affects cellular function and whole‐body metabolism. Carnitine uptake deficiency (CUD) disturbs the transportation of fatty acids into the mitochondria, but when treated is a mild disease without significant effects on FAO. For improved clinical care of VLCAD in particular, estimation of FAO severity could be important. We have investigated whether the oxygen consumption rate (OCR) of peripheral blood mononuclear cells (PBMCs) obtained from patients with MCAD, VLCAD, and CUD can be used to study cellular metabolism in patients with FAO defects and to determine the severity of FAO impairment. PBMCs were isolated from patients with VLCAD (n = 9), MCAD (n = 5–7), and CUD (n = 5). OCR was measured within 6‐hours of venous puncture using the Seahorse XFe96. The PBMCs were exposed to glucose alone or with caprylic acid (C8:0) or palmitic acid (C16:0). OCR was significantly lower in cells from patients with β‐oxidation deficiencies (MCAD and VLCAD) compared to CUD at basal conditions. When exposed to C16:0, OCR in VLCAD cells was unchanged, whereas OCR in MCAD cells increased but not to the levels observed in CUD. However, C8:0 did not increase OCR, as would be expected, in VLCAD cells. There was no clear relationship between clinical severity level and OCR. In patients with β‐oxidation deficiencies, changes of mitochondrial respiration in PBMCs are detectable, which indicate that PBMCs have translational potential for studies of β‐oxidation defects. However, further studies are warranted.

Abstract Background Turner syndrome is the result of the partial or complete absence of an X chromosome in phenotypic girls. This can cause an array of medical and developmental difficulties. The intelligence quotient in females with Turner syndrome has previously been described as uneven, but considered within normal range. Although their social, intellectual, and psychiatric profile is described, it is unclear to what extent these females meet the clinical criteria for neurodevelopmental or psychiatric diagnoses. The aim of this study was to examine the prevalence of neurodevelopmental and psychiatric disorders in females with Turner syndrome. Methods A retrospective cohort study was performed with a total of 1392 females with Turner syndrome identified through the Swedish National Patient Register and compared with 1:100 age- and sex-matched controls from the general population. The associations between Turner syndrome and diagnoses of neurodevelopmental and/or psychiatric disorders were calculated using conditional logistic regression and is presented as estimated risk (odds ratio, OR, 95% confidence interval, CI) in females with Turner syndrome compared with matched controls. Results Females with Turner syndrome had a higher risk of neurodevelopmental or psychiatric disorder (OR 1.37, 95% CI 1.20–1.57), an eightfold increased risk of intellectual disability (OR 8.59, 95% CI 6.58–11.20), and a fourfold increased risk of autism spectrum disorder (OR 4.26, 95% CI 2.94‑6.18) compared with the controls. In addition, females with Turner syndrome had twice the risk of a diagnosis of schizophrenia and related disorders (OR 1.98, 95% CI 1.36–2.88), eating disorders (OR 2.03, 95% CI 1.42–2.91), and behavioral and emotional disorders with onset in childhood (OR 2.01, 95% CI 1.35–2.99). Conclusions Females with Turner syndrome have an increased risk of receiving a diagnosis of neurodevelopmental or psychiatric disorder. This warrants extensive assessment of intellectual and cognitive functions from early age, and increased psychiatric vigilance should be a part of lifelong healthcare for females with Turner syndrome.

Deep Brain Stimulation (DBS) is an effective treatment for advanced Parkinson’s disease. However, identifying stimulation parameters, such as contact and current amplitudes, is time-consuming based on trial and error. Directional leads add more stimulation options and render this process more challenging with a higher workload for neurologists and more discomfort for patients. In this study, a sweet spot-guided algorithm was developed that automatically suggested stimulation parameters. These suggestions were retrospectively compared to clinical monopolar reviews. A cohort of 24 Parkinson’s disease patients underwent bilateral DBS implantation in the subthalamic nucleus at our center. First, the DBS’ leads were reconstructed with the open-source toolbox Lead-DBS. Second, a sweet spot for rigidity reduction was set as the desired stimulation target for programming. This sweet spot and estimations of the volume of tissue activated were used to suggest (i) the best lead level, (ii) the best contact, and (iii) the effect thresholds for full therapeutic effect for each contact. To assess these sweet spot-guided suggestions, the clinical monopolar reviews were considered as ground truth. In addition, the sweet spot-guided suggestions for best lead level and best contact were compared against reconstruction-guided suggestions, which considered the lead location with respect to the subthalamic nucleus. Finally, a graphical user interface was developed as an add-on to Lead-DBS and is publicly available. With the interface, suggestions for all contacts of a lead can be generated in a few seconds. The accuracy for suggesting the best out of four lead levels was 56%. These sweet spot-guided suggestions were not significantly better than reconstruction-guided suggestions (p = 0.3). The accuracy for suggesting the best out of eight contacts was 41%. These sweet spot-guided suggestions were significantly better than reconstruction-guided suggestions (p < 0.001). The sweet spot-guided suggestions of each contact’s effect threshold had a mean error of 1.2 mA. On an individual lead level, the suggestions can vary more with mean errors ranging from 0.3 to 4.8 mA. Further analysis is warranted to improve the sweet spot-guided suggestions and to account for more symptoms and stimulation-induced side effects.

Many applications are suggested for Ti‐MXene motivating strong interest in studies of Ti3C2Tx synthesis by solution‐based methods. However, so far only ex situ studies of the synthesis are performed, mostly due to the difficulty of handling HF‐based solutions. Here the first time‐resolved in situ synchrotron radiation X‐ray Diffraction study of MXene synthesis performed using a plastic capillary‐size reaction cell directly in HF solution is reported. This study provides the first report on the structure of "pristine MXene" formed by Ti3AlC2 etching with LiF+HCl. The term "pristine" refers to the MXene structure found directly in HF solution. By comparing the interlayer distances of pristine MXene (≈13.5 Å), solvent‐free Li‐intercalated MXene (≈12.2 Å), and Li‐free MXene (≈10.7 Å), it can be concluded that the width of "slit pores" formed by terminated MX layers during the Al etching does not exceed ≈3 Å. The width of these slit pores is a key factor for HF etching of Al within the interlayers. This space constraint explains the slow kinetics of MXene formation in HF‐based synthesis methods. No intermediate phases are observed, suggesting that the crystalline MXene phase is formed by the simultaneous etching of Al and termination of Ti3C2 layers. [ABSTRACT FROM AUTHOR]

Context Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with an impact on fracture incidence and bone mineral density after surgery have not been firmly established. Objective To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT). Design Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register. Setting Tertiary referral center. Patients or other participants Seven hundred nine patients with successful parathyroidectomy for pHPT and 2112 controls matched on sex, age, and municipality were included in the study. Main outcome measures Fracture incidence, absolute change, and ≥2.77% increase in bone mineral density of femoral neck, L2–L4, and distal third of radius at 1-year follow-up. Results Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (incidence rate ratio for the highest tertile 220– mg/d 0.29, 95% confidence interval 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin, and adenoma weight were all associated with bone mineral density recovery after surgery. Conclusion Twenty-four-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT. [ABSTRACT FROM AUTHOR]

Introduction Fine-needle aspiration cytology (FNAC) is an effective tool in the diagnostic work-up of patients with thyroid nodules. The aim of our study was to assess the diagnostic sensitivity of FNAC in thyroid cancer (TC) in Sweden by correlating the findings of preoperative FNAC with those obtained through final histology of the surgical specimen. Methods A Swedish nationwide cohort of patients having surgery for TC (n = 2519) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal surgery between 2004 and 2013 was obtained. Data was validated through scrutinizing patient FNAC and histology reports. Results Among the 2519 cases operated with a final diagnosis of TC, the diagnosis was substantiated and validated through the histology report in 2332 cases (92.6%), included in the present study. Among these, 1679 patients (72%) were female and the median age at TC diagnosis was 52.3 years (range 18-94.6). In 353 cases (15.1%) FNAC was not performed at all; whereas in the remaining 1965 cases, the diagnostic sensitivity of FNAC was 81.6%. In lesions > 1 cm, FNAC diagnostic sensitivity reached 86.5%, whereas in lesions < 1 cm, FNAC yielded a sensitivity of 61.5%. Approximately 85% of FNACs (n = 1981/2332) were performed using ultra-sonographic (US) guidance. In TC lesions > 1 cm, the diagnostic sensitivity of US-guided FNAC (n = 1504) was 86.9% as compared to 76.9% in clinically applied FNAC without US utilization (n = 118). Conclusions FNAC is performed in most patients operated for TC in Sweden (85%) and retains its value as a tool in TC diagnostic work-up with an overall sensitivity of 82%, reaching 87% in lesions > 1 cm, that harbor clinically relevant TC. [ABSTRACT FROM AUTHOR]

Countless papers have been published regarding the management and clinical outcome of vesicoureteral reflux (VUR), still no active treatment has been proven superior to another, regarding preserving renal function. When considering comparable treatment alternatives, qualitative research is needed to understand the parents' perspectives and preferences. This study aims to describe the parents' experiences of infant high-grade VUR (hVUR) regarding continuous antibiotic prophylaxis (CAP), surgical intervention (SI), urinary tract infection (UTI) and renal damage. We performed four randomized, semi-structured focus groups (FG) with 19 parents to 15 children (aged 1,5–6 years). All children had been diagnosed with hVUR at <8 months of age and treated with CAP (all groups) and SI (two groups). Discussions were recorded, transcribed and analysed to content. The sample size for the FGs was based on category saturation, which was confirmed through comparison analysis in multiple FGs. The FGs generated 2,897 parent-reported experiences, of which this study reports on 1,123, sorted into the abovementioned four themes and underlying categories. Negative experiences regarding CAP, such as stress regarding the daily intake and worries about long-term use and side effects, were abundant, whereas positive experiences were few. The experiences regarding SI were negatively affected by inadequate information and postoperative difficulties and positively by empathy, accurate information and adequate preparations. The increased risk of UTIs were described as a constant emotional stress causing restricted social activities, frequent visits to the hospital and challenges regarding urine-sampling. There was a common awareness of renal damage, but few experiences reflected any actual worry. The daily struggle with medications and monitoring for symptoms, concerns of future antibiotic resistance and a parental preference of SI have been documented in previous studies. FG methodology effectively collects data from several participants during the same occasion, the goal being to generate discussions that enable researchers to see the world from the participants' perspective. Since the management of infants with hVUR is still under debate, qualitative research can remind of valuable patient and parent perspectives. This study shows that CAP and the risk of UTI have non-negligible, everyday impact on family life, while renal damage seems of secondary importance. The concerns of surgical treatment are related to an isolated occasion, which can be optimized with proper care and improved preoperative preparations. Awareness of parents' experiences and preferences is helpful when managing children with hVUR. Summary table Summary table Themes and categories n = 1123 statements Parents' experiences of continuous antibiotic prophylaxis, CAP n=320 Emotional impact n = 140 (44%) Concerns about the effect of CAP n = 96 (30%) Influence of CAP intake n = 84 (26%) Parents' experiences of surgical intervention, SI n=182 Difficulties in surgical care n = 94 (52%) Qualities in surgical care n = 88 (48%) Parents' experiences of urinary tract infection (UTI) n=535 Family impact due to the child's UTI n = 273 (51%) Emergency care at suspected UTI of the child n = 131 (24%) Obstacles and facilitators of sampling and testing of urine n = 131 (24%) Parents' experiences of renal damage n=86 Risk of renal damage n = 86 (100%) [ABSTRACT FROM AUTHOR]

Introduction: Congenital adrenal hyperplasia (CAH) due to 21α-hydroxylase deficiency results in inadequate cortisol and aldosterone synthesis and concomitant overproduction of adrenal androgens. Despite adequate replacement, impaired growth and overweight remain a clinical challenge. The main objective was to investigate the differences in growth, final height (FH), and body mass index (BMI) between different CYP21A2 genotype groups and glucocorticoid treatment strategies during the different phases of growth. Methods: This is a population-based observational cohort study from diagnosis to FH. A total of 86 subjects were diagnosed with CAH in Sweden during 1989–1994. Eighty subjects were followed until FH. There were no interventions apart from the clinical standard of care treatment for CAH. The main outcome measure was the corrected FH standard deviation score (cFH SDS) and its correlation with genotype, accumulated total glucocorticoid dose, and treatment strategy. In addition, BMI and growth trajectories during infancy, childhood, and adolescence were studied. Results: FH was shorter in patients with the more severe CYP21A2 genotypes. Treatment doses of glucocorticoid were within the international treatment recommendations (10–15 mg/m2). Patients with the null and I2 splice genotypes lost approximately 1 SD in FH, whereas patients with the milder genotypes (I172N, P30L, and V281L) were within 0.5 to 0 SDS from target height. cFH SDS was negatively affected by the use of prednisolone but did not correlate with overall glucocorticoid treatment dose calculated as hydrocortisone equivalents. BMI at 18 years was higher in patients treated with prednisolone but did not correlate with genotype. Conclusions: Corrected FH was more affected in patients with severe CYP21A2 genotypes. The addition of a low dose of prednisolone to the hydrocortisone treatment, despite an equivalent total dose of glucocorticoids, was associated with shorter FH and higher BMI in growing subjects with CAH. [ABSTRACT FROM AUTHOR]

There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second—termed "mini-puberty"—in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroid biosynthesis, leading to hypocortisolism, hypoaldosteronism, and hyperandrogenism. Impaired quality of life (QoL) has been demonstrated in women with CAH, but data on men with CAH are scarce. We hypothesized that disease severity and poor treatment control are inversely associated with QoL. In this study, 109 men (16-68 years) with 21OHD were included. The WHOQOL-BREF questionnaire was used to measure self-reported QoL domain scores on a 0-100 scale, where higher scores reflect better QoL. QoL domain scores were compared to published data on healthy and chronically ill reference populations from France, Germany, the Netherlands, and the United Kingdom. Differences in QoL scores among groups of disease severity and treatment control were tested within the study population. Overall, the men with CAH in this study appeared to rate their QoL as good. Median domain scores were 78.6 (IQR: 67.9-85.7) for physical health, 79.2 (IQR: 66.7-87.5) for psychological health, 75.0 (IQR: 58.3-83.3) for social relationships, and 81.3 (IQR: 71.9-90.6) for environment. In general, these scores were similar to WHOQOL-BREF domain scores in healthy references and higher compared to chronically ill reference populations. The domain scores did not differ among genotype groups, but patients with undertreatment or increased 17-hydroxyprogestrone concentrations scored higher on several QoL domains (p

Context: Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective: To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design, patients, interventions, main outcome measures: 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results: In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion: In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.

Abstract Background Previous studies in quality of life (QOL) in individuals with disorders/differences of sex development (DSD) have been restricted to subpopulations of the condition. We describe QOL in adult persons with DSD compared to country specific references and assess the impact of diagnosis. Methods The multicentre cross-sectional clinical evaluation (dsd-LIFE) took place in 14 specialized clinics in six European countries. Adolescents (≥16 years) and adults having a DSD condition were included from 02/2014 to 09/2015. The main outcome QOL was measured by the WHOQOL-BREF (domains of physical health, psychological, social relationships, and environment). QOL was compared to country specific reference populations by using unpaired t-tests. Linear regression models explained the additional variance of the diagnosis on QOL. Results Three hundred one individuals with Turner Syndrome, 219 with Klinefelter Syndrome (including XYY), 226 with 46,XX CAH and 294 with rare DSD conditions (gonadal dysgenesis, androgen insensitivity syndrome, severe hypospadias, and androgen synthesis errors or other diagnosis) took part. Compared to healthy European populations, QOL was similar in psychological, slightly worse in physical health, and slightly better in environment. In social relationships, QOL was significantly poorer compared to healthy and non-healthy reference populations. In linear regression models health status was the most important predictor of QOL; additional variance was explained by feelings about household’s income in all domains, and the relationship status in social relationships. Diagnosis explained nearly no additional variance. Conclusions Except for social relationships, most people with DSD adapt well to their life circumstances and report a good QOL. Not diagnosis, but the individual’s health status is much more important than previously thought. Therefore care for people with DSD should focus more on chronic physical or mental health problems both related and unrelated to the diagnosis itself. Trial registration German Clinical Trials Register DRKS00006072.

Neutron reflectivity (NR) was used to study the sorption of Eu(III) by graphene oxide (GO) films exposed to ethanol solution of EuCl3. Most of the earlier sorption studies have been performed using GO dispersed in solution. In contrast, layered structure of GO films imposes limitations for penetration of ions between individual sheets. The analysis of NR data recorded before and after sorption under vacuum demonstrates an increase of GO film thickness due to sorption by 35–40%. The characterization of chemical state of Eu(III) sorbed by GO films by X‐ray absorption near‐edge structure (XANES) in high‐energy resolution fluorescence detection (HERFD) method at the Eu L3 edge reveals that it remains the same as in anhydrous EuCl3. Analysis of all collected data including reference experiments with bulk GO samples allows to conclude that EuCl3 penetrates into GO interlayers with ethanol solution and remains trapped in interlayers after evaporation of ethanol. Sorption of EuCl3 results in nearly complete amorphization of film and likely formation of voids, thus making NR models based on specific volume of unit cell not valid for quantitative evaluation of Eu sorption. Limitations of NR method must be taken into account in future studies of sorption by thin films. [ABSTRACT FROM AUTHOR]

The management of Differences of Sex Development (DSD) has evolved considerably in recent years. The questioning of systematic early childhood treatment of DSD requires a better understanding of the outcomes of such treatments and long-term studies are therefore essential to better evaluate the prognosis of DSD. Unfortunately, limitations are numerous including the limited size of the series, the absence of standardized methodology, the evaluation of managements that no longer take place today and the absence of prospective and comparative studies. Despite these difficulties, the purpose of this paper is to present the current data on the long-term follow-up of patients with DSD from the urological, sexual and fertility points of view. Even if it remains difficult at present to establish precise recommendations, we recapitulate the most important points that should drive follow-up of these patients especially the constitution of a multidisciplinary team with a holistic approach, the organization of the transition between adolescence and adulthood, a particular attention to psychological care, a careful communication with the patients and his/her family and the use of standardized data collection systems. [ABSTRACT FROM AUTHOR]

Background Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism. Methods Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up. Results A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5–93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries. Conclusion This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Small bowel neuroendocrine tumours often present with locally advanced or metastatic disease. The aim of this paper is to provide evidence-based recommendations regarding (controversial) topics in the surgical management of advanced small bowel neuroendocrine tumours. Methods: A working group of experts was formed by the European Society of Endocrine Surgeons. The group addressed 11 clinically relevant questions regarding surgery for advanced disease, including the benefit of primary tumour resection, the role of cytoreduction, the extent of lymph node clearance, and the management of an unknown primary tumour. A systematic literature search was performed in MEDLINE to identify papers addressing the research questions. Final recommendations were presented and voted upon by European Society of Endocrine Surgeons members at the European Society of Endocrine Surgeons Conference in Mainz in 2023. Results: The literature review yielded 1223 papers, of which 84 were included. There were no randomized controlled trials to address any of the research questions and therefore conclusions were based on the available case series, cohort studies, and systematic reviews/meta-analyses of the available non-randomized studies. The proposed recommendations were scored by 38–51 members and rated 'strongly agree' or 'agree' by 64–96% of participants. Conclusion: This paper provides recommendations based on the best available evidence and expert opinion on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours. This paper provides evidence-based recommendations on the surgical management of locally advanced and metastatic small bowel neuroendocrine tumours, primary tumour resections in the setting of metastatic disease, and surgical indications for grade 3 small bowel neuroendocrine tumours and small bowel neuroendocrine carcinomas. The recommendations are the result of a working group of experts, created by the European Society of Endocrine Surgeons. The group addressed 11 relevant clinical questions regarding surgery for advanced disease, emphasizing and confirming the key role of the surgeon for advanced small bowel neuroendocrine tumours. [ABSTRACT FROM AUTHOR]

Objective: The knowledge about health status in adults with disorder of sex development (DSD) is scarce. Design and methods: A cross-sectional observational study in 14 European tertiary centers recruited 1040 participants (717 females, 311 males, 12 others) with DSD. Mean age was 32.4 ± 13.6 year (range 16–75). The cohort was divided into: Turner (n = 301), Klinefelter (n = 224), XY-DSD (n = 222), XX-DSD (excluding congenital adrenal hyperplasia (CAH) and 46,XX males) (n = 21), 46,XX-CAH (n = 226) and 45,X/46,XY (n = 45). Perceived and objective health statuses were measured and compared to European control data. Results: In DSD, fair to very good general health was reported by 91.4% and only 8.6% reported (very) bad general health (controls 94.0% and 6.0%, P < 0.0001). Longstanding health issues other than DSD and feeling limited in daily life were reported in 51.0% and 38.6%, respectively (controls 24.5% and 13.8%, P < 0.0001 both). Any disorder except DSD was present in 84.3% (controls 24.6%, P < 0.0001). Males reported worse health than females. In the subgroup analysis, Klinefelter and 46, XX-DSD patients reported bad general health in 15.7% and 16.7%, respectively (Turner 3.2% and CAH 7.4%). Comorbidities were prevalent in all DSD subgroups but Klinefelter and Turner were most affected. Early diagnosis of DSD and a healthy lifestyle were associated with less comorbidities. Conclusions: Overall, general health appeared to be good but a number of medical problems were reported, especially in Klinefelter and Turner. Early diagnosis of DSD and a healthy lifestyle seemed to be important. Lifelong follow-up at specialized centers is necessary.

Abstract Microcapsules with specific functional properties, related to the capsule wall and core, are highly desired in a number of applications. In this study, hybrid cellulose microcapsules (1.2 ± 0.4 µm in diameter) were prepared by nanoengineering the outer walls of precursor capsules. Depending on the preparation route, capsules with different surface roughness (raspberry or broccoli-like), and thereby different wetting properties, could be obtained. The tunable surface roughness was achieved as a result of the chemical and structural properties of the outer wall of a precursor capsule, which combined with a new processing route allowed in-situ formation of silica nanoparticles (30–40 nm or 70 nm in diameter). By coating glass slides with “broccoli-like” microcapsules (30–40 nm silica nanoparticles), static contact angles above 150° and roll-off angles below 6° were obtained for both water and low surface-tension oil (hexadecane), rendering the substrate superamphiphobic. As a comparison, coatings from raspberry-like capsules were only strongly oleophobic and hydrophobic. The liquid-core of the capsules opens great opportunities to incorporate different functionalities and here hydrophobic superparamagnetic nanoparticles (SPIONs) were encapsulated. As a result, magnetic broccoli-like microcapsules formed an excellent superamphiphobic coating-layer on a curved geometry by simply applying an external magnetic field.