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STUDY QUESTION What are the characteristics of patients with conceptions transplanted in childhood and adolescence? SUMMARY ANSWER Insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence was possible, even after myeloablative conditioning regimes, although some patients required reproductive medicine support. WHAT IS KNOWN ALREADY Preparative regimens of HCT are highly gonadotoxic, which leads to gonadal failure and pubertal development disorders. There are few population-based studies assessing the risk of future infertility in children after HCT. STUDY DESIGN, SIZE, DURATION We conducted a retrospective study to investigate natural or assisted conceptions and their outcomes in patients PARTICIPANTS/MATERIALS, SETTING, METHODS Detailed information concerning pregnancy occurrences and outcomes were obtained by a separate questionnaire. Quantitative variables were presented as medians with their interquartile range (IQR) or range, and categorical variables were presented as frequencies and percentages. MAIN RESULTS AND THE ROLE OF CHANCE In total, 62 988 pediatric patients received a first HCT in EBMT centers between 1995 and 2016. Pregnancy was reported in 406 patients in the database. The median age at transplantation was 15.7 (range: 0.7–18) years, and the median age at declared conception was 25.0 (range: 16.3–38.8) years. Details concerning the first pregnancy and pregnancy outcome were obtained from 99 patients (24%) from the returned questionnaires. The median age at delivery or pregnancy interruption of the females was 23.0 (IQR: 20.8–27) years, with a median time after transplant of 10.7 (IQR: 6.6–15.4) years. Compared with the mean age of healthy women at their first child’s birth (29 years old), the transplanted women delivered 5 years earlier (mean: 24.3 years). In terms of conception modality, 13/25 (52%) females conditioned with total body irradiation (TBI) and 50/52 (96%) of those conditioned without TBI conceived naturally. All seven male patients who had been conditioned with TBI achieved fatherhood but required assisted fertilization or used their cryopreserved sperm. In the females, 63/70 (90%) of all conceptions resulted in a live birth, 49/63 (84.5%) were at term and 43/46 (93%) had normal birthweight. Cesarean delivery was performed in 9/61 (15%) especially in women who had received a myeloablative regimen. LIMITATIONS, REASONS FOR CAUTION In the EBMT pediatric dataset, the age at last follow-up or death was WIDER IMPLICATIONS OF THE FINDINGS Reproductive health surveillance and fertility preservation counseling are important in younger transplanted patients. Our results showed that there is a window of opportunity to conceive naturally or with reproductive medicine support. STUDY FUNDING/COMPETING INTEREST(S) Funding was provided by the ‘Stiftung für krebskranke Kinder Regio Basiliensis’, Basel, Switzerland. All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

The current study examines neural responses to satiety- and fasting-related volatiles and their effect on the processing of body shapes. Axillary sweat was sampled with cotton pads from 10 individuals after 12 h of fasting, and after having consumed a standard breakfast. Pure cotton pads served as the control. The chemosensory stimuli were presented to 20 participants (via a constant-flow olfactometer) exclusively, and additionally as context to images of overweight and underweight avatars. EEG was recorded (61 electrodes), and chemosensory (CSERPs, P1, N1, P2, P3) and visual event-related potentials (VERPs, N1, P2, P3a, P3b) were analyzed. The amplitudes of all positive CSERP components differed more strongly from cotton in response to chemosensory satiety cues as compared to fasting cues (P1: p = 0.023, P2: p = 0.083, P3: p = 0.031), paralleled by activity within the middle frontal and temporal gyrus. Overweight compared to underweight body shapes tended to elicit larger VERP P2 amplitudes (p = 0.068), and chemosensory satiety cues amplified the VERP amplitudes in response to any body shape (P2, P3a, P3b, all ps ≤ 0.017) as compared to the cotton control. The results indicate that chemosensory satiety cues transmit complex social information, overriding the processing of analogous visual input.

Background Optoelectronic Plethysmography (OEP) is an effective method for evaluating thoracoabdominal kinematics. However, little is known about the viability and use the OEP in people with obesity. Objective Summarize information on the use and feasibility of OEP in the assessment of thoracoabdominal kinematics in people with obesity. Methods Studies were identified through PubMed, EMBASE, Science Direct, Web of Science and Scopus databases in the February 2021. Results Six studies met the inclusion criteria. The studies used the OEP to assess abdominal and thoracic mobility in obese people of different BMI, using the default setting. No study reported the impossibility of using OEP in people with obesity. Conclusion Has been shown that it is possible to use the OEP in people with obesity with a BMI of up to 50 kg/m2. More studies are needed to demonstrate the feasibility of the method in people with a BMI greater than this value.

The role of catheter ablation as an adjunct and alternative to ICD implantation is not known in patients at risk for recurrent ventricular tachycardia (VT) and sudden cardiac death (SCD) across Asia. Patients with nonischemic etiologies of cardiomyopathy, which are highly prevalent in Asia, have not been previously enrolled in randomized trials of VT ablation. To evaluate whether preemptive catheter ablation in patients with monomorphic VT and an indication for ICD implantation results in improved clinical outcomes compared to ICD implantation with standard medical therapy alone. To examine the natural history of ablation outcomes in the absence of background ICD therapy in patients that refuse randomization. The PAUSE-SCD study (NCT02848781) is a prospective, multi-center, randomized controlled trial enrolling patients with structural heart disease (EF

BackgroundChildhood cancer and its treatment may lead to many acute and chronic health complications. Related impairment in quality of life, excess in deaths, and accumulated health care costs are relevant. There is a wide inter-individual variability in the type and severity of health complications. Genetic variations are suggested to contribute to individual susceptibility. So far, only few genetic variants have been used to risk-stratify treatment and follow-up care. This study platform aims to identify germline genetic variants associated with acute and late complications of childhood cancer.MethodsThe Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study is a nationwide cohort study. It includes patients and survivors who were diagnosed with childhood cancers or Langerhans cell histiocytosis before age 21 years, were registered in the Swiss Childhood Cancer Registry (SCCR) since 1976 and have consented to the Pediatric Biobank for Research in Hematology and Oncology (BaHOP), Geneva, host of the Germline DNA Biobank Switzerland for Childhood Cancer and Blood Disorders (BISKIDS). BISKIDS is a national biobank for the collection of germline DNA in childhood cancer patients and survivors.GECCOS uses demographic and clinical data from the SCCR and the associated Swiss Childhood Cancer Survivor Study (SCCSS), which contains health-related data of survivors. Phenotypic data consist of objective measurements, health conditions diagnosed by physicians, second primary neoplasms, self-reported and health-related information from participants. Germline genetic samples and sequencing data have been collected in BISKIDS. We will perform gene panel sequencing, whole-exome sequencing, or whole-genome sequencing depending on the research questions. We will perform association analyses to identify genetic variants associated with specified health conditions. We will use clustering and machine-learning techniques and assess multiple health conditions in different models.DiscussionGECCOS will serve as an overarching platform to enable genotype-phenotype association analyses on complications associated with childhood cancer and its treatments. Knowledge of germline genetic variants associated with childhood cancer-associated health conditions will help to further individualize cancer treatment and follow-up care, potentially resulting in improved efficacy and reduced side effects, for personalized cancer care.Trial registrationClinicaltrials.gov: NCT04702321

Aim: Sperm cryopreservation (SCP) should be offered to every adolescent before gonadotoxic treatment, but experience in this age range is still relatively limited. The goal of this study is to assess how to optimize this procedure.Methods and Patients: One hundred thirty-three patients between 12 and 20 years old, who underwent SCP between 1980 and 2017, were included. Baseline data (age, indication for SCP, and semen parameters at freezing) and follow-up data (outcome of sperm straws and follow-up of sperm quality) were collected and analyzed.Results: SCP is feasible from the age of 12. Semen assessment parameters at this age were close to parameters of adults. However, we observed quantitative impairments in testicular tumors and qualitative impairments in leukemia and bone marrow failure. Four patients (3%) used their cryopreserved semen for medically assisted reproduction, 15 patients died (11.3%), 18 asked for destruction of their straws (13.5%), and nine samples were destroyed because of lack of news (6.8%). Very few patients underwent a sperm analysis after treatment.Conclusions: SCP is an efficient, still underused, procedure for adolescents and young adults. Cryopreserved sperm is rarely used and rarely destroyed, but studies with a longer follow-up are needed to better assess these observations. Follow-up with a specialist of reproductive medicine is valuable for better information of the patient.

Acute Graft versus Host Disease (aGvHD) grades 2–4 occurs in 15–60% of pediatric patients undergoing allogeneic haematopoietic stem-cell transplantation (allo-HSCT). The collateral damage to normal tissue by conditioning regimens administered prior to allo-HSCT serve as an initial trigger for aGvHD. DNA-repair mechanisms may play an important role in mitigating this initial damage, and so the variants in corresponding DNA-repair protein-coding genes via affecting their quantity and/or function. We explored 51 variants within 17 DNA-repair genes for their association with aGvHD grades 2–4 in 60 pediatric patients. The cumulative incidence of aGvHD 2–4 was 12% (n = 7) in the exploratory cohort. MGMT rs10764881 (G>A) and EXO rs9350 (c.2270C>T) variants were associated with aGvHD 2–4 [Odds ratios = 14.8 (0 events out of 40 in rs10764881 GG group) and 11.5 (95% CI: 2.3–191.8), respectively, multiple testing corrected p ≤ 0.001]. Upon evaluation in an extended cohort (n = 182) with an incidence of aGvHD 2–4 of 22% (n = 40), only MGMT rs10764881 (G>A) remained significant (adjusted HR = 2.05 [95% CI: 1.06–3.94]; p = 0.03) in the presence of other clinical risk factors. Higher MGMT expression was seen in GG carriers for rs10764881 and was associated with higher IC50 of Busulfan in lymphoblastoid cells. MGMT rs10764881 carrier status could predict aGvHD occurrence in pediatric patients undergoing allo-HSCT.

Ovarian failure is a major long-term adverse event following gonadotoxic treatment of malignant diseases. Ovarian tissue cryopreservation can be offered in some conditions to preserve fertility. We report the case of a 13-year-old female with a diagnosis of acute myeloid leukemia, who presented with hypergonadotropic hypogonadism after unilateral ovariectomy for fertility preservation and before highly gonadotoxic treatment. Even though damage seemed only partial, this case suggests that the remaining contralateral ovarian function may be compromised after ovarian tissue cryopreservation, leading per se to a hypergonadotropic hypogonadism. Although indication of ovarian cryopreservation is not called into question in situations of highly gonadotoxic therapy, this procedure should only be performed after evaluation by a specialized multidisciplinary team and provided a solid indication.

Introduction Pediatric neuroendocrine tumors (NETs) of the appendix are mostly detected incidentally after appendectomy for acute appendicitis. NET management is a matter of controversy. In this national, multicenter study, we aimed to establish guidelines based on our results and the literature. Materials and Methods Medical records of children (0–16 years) with NET of the appendix, treated in Switzerland (1991–2012), were reviewed. Results Forty cases (28 girls) were analyzed. Median age at diagnosis was 12.7 years (interquartile range [IQR]: 4.0). Tumor size was 0.1–24 mm (median: 0.6, IQR: 0.6). Four patients (10%) underwent additional surgery because of either tumor size > 15 mm (1/4), extension to the mesoappendix (1/4), or incomplete resection (2/4). Three patients with a tumor of ≥ 20 mm had no additional surgery. No patient had lymph node metastases. All patients were in complete remission at the last follow-up (median: 3.0 years, IQR: 10.9). Conclusion We conclude from this study and from an extensive review of the literature that two criteria may point to the need for additional surgery, i.e., the possibility of regional lymph node involvement: tumor size > 20 mm and incomplete surgical resection margins. Childhood NET of the appendix has an excellent prognosis.

indexation en cours; Chemosensory anxiety signals effectively prime motor responses related to withdrawal behavior, such as the startle reflex, in adult humans. As the reproductive status strongly affects the response to social chemosignals, the current study examined whether chemosensory anxiety signals would augment the startle response in prepubertal children as it does in adults. Using cotton pads, axillary sweat was collected from 28 men while waiting for an important oral examination (anxiety condition), and during ergometer training (sport control condition). Using a constant-flow olfactometer, sweat samples and pure cotton samples (cotton control) were presented to 10 prepubertal girls aged 9-13years (M=11.25, SD=1.25) for 3000ms during inhalation. White noise bursts of 102dB(A) served as startle probes, and startle responses were recorded via electromyography of the orbicularis oculi muscle. The girls showed larger startle amplitudes to probes presented in the context of chemosensory anxiety signals as compared to a context of sport control sweat (p

Reduction of mu activity within the EEG is an indicator of cognitive empathy and can be generated in response to visual depictions of others in pain. The current study tested whether this brain response can be modulated by an auditory and a chemosensory context. Participants observed pictures of painful and non-painful actions while pain associated and neutral exclamations were presented (Study 1, N = 30) or while chemosensory stimuli were presented via a constant flow olfactometer (Study 2, N = 22). Chemosensory stimuli were sampled on cotton pads while donors participated in a simulated job interview (stress condition) or cycled on a stationary bike (sport condition). Pure cotton was used as a control. The social chemosignals could not be detected as odors. Activity within the 8–13 Hz band at electrodes C3, C4 (mu activity) and electrodes O1, O2 (alpha-activity) was calculated using Fast-Fourier-Transformation (FFT). As expected, suppression of power in the 8–13 Hz band was stronger when painful as compared to non-painful actions were observed (Study 1, p = 0.020; Study 2, p = 0.005). In addition, as compared to the neutral auditory and chemosensory context, painful exclamations (Study 1, p = 0.039) and chemosensory stress signals (Study 2, p = 0.014) augmented mu-/alpha suppression also in response to non-painful pictures. The studies show that processing of social threat-related information is not dominated by visual information. Rather, cognitive appraisal related to empathy can be affected by painful exclamations and subthreshold chemosensory social information.

The tumor suppressor folliculin (FLCN) forms a repressor complex with AMP-activated protein kinase (AMPK). Given that AMPK is a master regulator of cellular energy homeostasis, we generated an adipose-specific Flcn (Adipoq-FLCN) knockout mouse model to investigate the role of FLCN in energy metabolism. We show that loss of FLCN results in a complete metabolic reprogramming of adipose tissues, resulting in enhanced oxidative metabolism. Adipoq-FLCN knockout mice exhibit increased energy expenditure and are protected from high-fat diet (HFD)-induced obesity. Importantly, FLCN ablation leads to chronic hyperactivation of AMPK, which in turns induces and activates two key transcriptional regulators of cellular metabolism, proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) and estrogen-related receptor α (ERRα). Together, the AMPK/PGC-1α/ERRα molecular axis positively modulates the expression of metabolic genes to promote mitochondrial biogenesis and activity. In addition, mitochondrial uncoupling proteins as well as other markers of brown fat are up-regulated in both white and brown FLCN-null adipose tissues, underlying the increased resistance of Adipoq-FLCN knockout mice to cold exposure. These findings identify a key role of FLCN as a negative regulator of mitochondrial function and identify a novel molecular pathway involved in the browning of white adipocytes and the activity of brown fat.

Background and objectives. Financial aid for the blind which is awarded based only on medical certificates and results of examinations has in the past resulted in too many false diagnoses;therefore, Bavaria seeks to pay financial aid to the blind only on the basis of a specific ophthalmological assessment according to the standards of the German pension medical ordinance (VersMedV, Versorgungsmedizinische Verordnung). Because these ophthalmological assessments initially contribute to a higher financial burden on the state, longer processing times and inconvenience to the patient, investigations should be undertaken to determine if ophthalmological findings, reports and medical certificates can be a suitable basis for an expert assessment and in how many cases blindness which had been certified by the original examination could be confirmed by a specific ophthalmological assessment. Methods. A total of 925 applications for financial assistance to the blind within the catchment area of the Bavarian Center for Family and Social Services (ZBFS, Zentrum Bayern Familie und Soziales) regional center in Upper Bavaria between 2003 and 2008, all of which had been subjected to an assessment by the same practitioner acting as external expert, were statistically analyzed. Results. Of the 357 applicants who had been classified as blind according to the medical certificate and findings, 283 (79 %) were confirmed as being blind after the assessment and in 73 (21 %) blindness could not be confirmed. Of the 262 applicants who were classified as not being blind during the first examination, the diagnosis was confirmed in 192 (73 %) while 70 cases (27 %) were classified as blind. Of the 304 applicants for whom an assessment was not possible by the medical certification, 165 were ultimately classified as blind and 139 as not blind. Out of 32 applicants who were explicitly classified as being blind in the medical certificate, 13 were confirmed as being blind while the remaining 18 were classified in the subsequent assessment as not blind. Conclusion. Apart from unambiguous cases, the awarding of financial aid to the blind should only be based on an ophthalmological assessment which follows the VersMedV guidelines. Only this approach can result in an equal treatment of all applicants before the law and the awarding of financial aid to the blind to assist those truly in need. In addition, fiscal budget results revealed that the falsely awarded financial aid to the blind reached well beyond millions of Euros.

The current study is the first to examine the central nervous processing of aggression chemosignals within men and women by means of chemosensory event-related potential (CSERP) analysis. Axillary sweat was collected from 17 men and 17 women participating in a competitive computer game (aggression condition) and playing a construction game (control condition). Sweat samples were pooled with reference to donor gender and condition, and presented to 23 men and 25 women via a constant flow olfactometer. Ongoing electroencephalogram was recorded from 61 scalp locations, CSERPs (P2, P3-1, P3-2) were analysed and neuronal sources calculated (low-resolution electromagnetic tomography, LORETA). Women, especially, showed larger P3-1 and P3-2 amplitudes in response to male as compared with female aggression signals (allpvalues < 0.01). The peak activation of this effect was related to activity within the dorsomedial prefrontal cortex (Brodmann area 8). As male aggression commonly targets physical harm, the competence of the human brain to sensitively detect male aggression signals is considered to be highly adaptive. The detection of male aggression signals seems to be of higher importance for women than for men. It is suggested that the processing of male aggression signals in women induces an immediate response selection.This article is part of the Theo Murphy meeting issue ‘Olfactory communication in humans’.

Sex-typed play behavior shows large sex differences and seems to be affected by prenatal sex hormones. For example, a smaller, more male-typical ratio between the second and fourth digit length (2D:4D), a proposed marker for prenatal testosterone exposure, has been shown to be related to sex-typed play preference in childhood. Nevertheless, it is still being debated whether 2D:4D displays a stable sex difference throughout childhood, as there are few longitudinal studies. In the present study, children’s 2D:4D was measured on both hands on four occasions from early infancy to early childhood (T1: 5 months, T2: 9 months, T3: 20 months, and T4: 40 months) providing the rare possibility to test the temporal stability of the sex difference. Parents completed the Preschool Activities Inventory at T4 and reported on the number of older brothers and sisters as a measure for socialization influences. Parents described boys as playing more masculine and less feminine than girls. Boys had smaller 2D:4D than girls at all measurements (T1–T4) and on both hands (right/left). Nevertheless, 2D:4D increased significantly from T3 to T4 in both sexes. Girls, but not boys, who were described as playing more masculine and less feminine had more masculine 2D:4D ratios at T1–T4 on both hands (except for right 2D:4D at T2 and T3) and had more older brothers and fewer older sisters. These data underline the stability of the sex difference in 2D:4D and show the importance of both biological and social influences on sex-typed play behavior.

Activation of AMPK has been associated with pro‐atrophic signaling in muscle. However, AMPK also has anti‐inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory‐driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα‐induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A‐769662, a specific AMPK activator. AICAR and A‐769662 co‐treatment was found to be synergistic, suggesting that the anti‐cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation‐driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.

Objective: Childhood cancer survivors are at high risk for late effects. Regular attendance to long-term follow-up care is recommended and helps monitoring survivors' health. Using the Theory of Planned Behavior (TPB) we aimed to 1) investigate the predictors of the intention to attend follow-up care, and 2) examine the associations between perceived control and behavioral intention with actual follow-up care attendance in Swiss childhood cancer survivors. Methods: We conducted a questionnaire survey in Swiss childhood cancer survivors (diagnosed with cancer aged

Isocitrate Dehydrogenase-1 (IDH1) is a driver gene in several cancers including brain tumors such as low-grade and high-grade gliomas. Mutations of SMARCB1 were described in atypical teratoid rhabdoid tumors and to date have not been associated with the pathogenesis of medulloblastoma. We report concurrent IDH1 and SMARCB1 mutations in a medulloblastoma patient. We searched the catalog of somatic mutations in cancer (COSMIC) database and other mutation databases and -to our knowledge- this is the first reported case of medulloblastoma harboring both mutations together. Our patient is a 13-year-old male presenting with headache and vomiting at diagnosis. MRI revealed left cerebellar expansive lesion with no evidence of metastasis. A histopathological diagnosis of desmoplastic/nodular medulloblastoma was made after complete resection of the tumor. Immunophenotypic characterization and methylation profiling suggested a medulloblastoma with SHH activation. Next generation sequencing of a panel of 400 genes revealed heterozygous somatic IDH1(p.R132C), SMARCB1(p.R201Q), and CDH11(p.L625T) mutations. The patient was treated according to the HIT-SIOP PNET 4 protocol. He is in complete remission more than 2 years after diagnosis. In conclusion, increasing use of high throughput sequencing will certainly increase the frequency with which rare mutations or mutation combinations are identified. The exact frequency of this mutation combination and whether it has any particular therapeutic implications or prognostic relevance requires further investigation.

In humans, stress can be contagiously transmitted via chemosignals on a subconscious level. This study investigates how pregnancy affects neural responses to anxiety chemosignals. Using cotton pads, 28 men donated axillary sweat immediately before an academic examination (anxiety sweat) and during ergometer training (control). Via a constant-flow olfactometer, samples were presented (oddball paradigm) to 12 non-pregnant (NP) women, 14 women in their first (T1), and 18 in their third (T3) trimester of pregnancy. Chemosensory event-related potentials and current source densities (CSD) were analysed (60 electrode setup). Compared to NP-women, pregnant women display diminished evaluative processing of the sweat samples (targets; P3-1/ P3-2 amplitudes) and delayed evaluative processing of the anxiety sweat (targets; P3-2 latency). T3-women show attenuated early processing (targets; N1 amplitude) compared to NP-women, and reduced evaluative processing compared to T1-women (standards; P3-2 amplitude). CSDs (P3-1/ P3-2 latency ranges) reveal that T1- and T3-women show an atypical activation distribution to anxiety sweat. Most participants were unable to detect the sweat samples (anxiety sweat: 79.5%, sport sweat 88.6%). The results demonstrate that the processing of anxiety chemosignals progressively vanishes during pregnancy. This effect is likely to occur without any cognitive control.

BACKGROUND Little is known about follow-up care attendance of adolescent survivors of childhood cancer, and which factors foster or hinder attendance. Attending follow-up care is especially important for adolescent survivors to allow for a successful transition into adult care. We aimed to (i) describe the proportion of adolescent survivors attending follow-up care; (ii) describe adolescents' health beliefs; and (iii) identify the association of health beliefs, demographic, and medical factors with follow-up care attendance. PROCEDURE Of 696 contacted adolescent survivors diagnosed with cancer at ≤16 years of age, ≥5 years after diagnosis, and aged 16-21 years at study, 465 (66.8%) completed the Swiss Childhood Cancer Survivor Study questionnaire. We assessed follow-up care attendance and health beliefs, and extracted demographic and medical information from the Swiss Childhood Cancer Registry. Cross-sectional data were analyzed using descriptive statistics and logistic regression models. RESULTS Overall, 56% of survivors reported attending follow-up care. Most survivors (80%) rated their susceptibility for late effects as low and believed that follow-up care may detect and prevent late effects (92%). Few (13%) believed that follow-up care is not necessary. Two health beliefs were associated with follow-up care attendance (perceived benefits: odds ratio [OR]: 1.56; 95% confidence interval [CI]: 1.07-2.27; perceived barriers: OR: 0.70; 95%CI: 0.50-1.00). CONCLUSIONS We show that health beliefs are associated with actual follow-up care attendance of adolescent survivors of childhood cancer. A successful model of health promotion in adolescent survivors should, therefore, highlight the benefits and address the barriers to keep adolescent survivors in follow-up care. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.

Introduction: In the last decade transplant activity increased constantly and consequently the number of long-term survivors. Most applied conditioning regimes are known to impair normal puberty development and can lead to infertility. Pregnancies in women who had undergone a HSCT as well as in partners of transplanted men have been documented. However, the true incidence of pregnancies and its related complications in patients transplanted during their childhood remains unknown. The Pediatric WP of the EBMT conducted a study aiming to analyze pregnancy rates and to evaluate pregnancy outcomes in survivors of childhood HSCT. Material and Methods: In this study, we first evaluate the available data on the EBMT registry. To collect additional data a survey was conducted between July 2017- June 2018. 203 centers with pediatric activity reported to the EBMT patients were asked to fill-out the survey with 36 items related to treatment plan, pregnancies and pregnancies outcome. Adoptions were not considered in the study. Results: Data obtained from the EBMT database "Promise" reported that 62'988 pediatric patients were transplanted in the EBMT centers from 1995 to end of 2016. In 484 (0.76%) patients a conception after HSCT has been reported. 341/484 patients (70%) had an allograft, 134 of them (40%) were males. 143/484 had an autologous, 53 of them (37%) were male. The median age of patients was 15.02 years (range 0.6 - 17.9 years), was similar for male and females regardless of whether they were auto or allogeneic transplanted. 283 patients (58%) had conditioning regimes containing alkylating agents, irradiation or both. Data obtained from the conducted survey provide precise information of 27 (13 %) EBMT centers from 16 countries about 114 pregnancies of 99 patients and their partners. Pregnancies were in 30/99 (30%) from partners of post HSCT male patients and 60/99 (70%) were of post HSCT females. Underlying diseases for HSCT were reported in 82 of all 99 patients. 47/82 (57%) had a malignant disease and35/82 (43%) had a non-malignant disease. 29/99 (29%) had a reduced conditioning regime, 70/99 (71%) a myeloablative conditioning regime. 25/82 (30%) received TBI as part of the conditioning regimes. Regarding conception in patients post TBI, 12/23 (52%) became naturally pregnant (2/12 had 2 Gy only), 9/23(39%) required assisted fertilization and 2 used cryopreserved sperms. In patients conditioned without TBI, 54/59 (92%) had a natural conception, 4/59 (7%) required assisted fertilization and 1 used cryopreserved sperms. In 90/99 (90%) patients pregnancy resulted in a livebirth. 13 of the 90 livebirths (14%) were preterm, with a higher proportion than in normal the population (5.5-11%) and 6 of the 90 livebirths (6%) presented a low birthweight which is comparable to the normal population (6.5%). Conclusion: This study confirms a low pregnancy rate in survivors of childhood HSCT. Natural conception was possible when patients are conditioned without TBI. After TBI, pregnancy assisted fertilization techniques may increase pregnancy rate. The number of live births and complications indicate the need to advise survivors of childhood HSCT about the potential risks and outcome of pregnancy and advise them appropiately. Disclosures Bader: Cellgene: Consultancy; Neovii: Research Funding; Medac: Patents & Royalties, Research Funding; Riemser: Research Funding; Novartis: Consultancy, Speakers Bureau.

INTRODUCTION: Acute fibrinous and organizing pneumonia (AFOP) is a recently described histologic pattern of diffuse pulmonary disease. In children, all cases reported to date have been fatal. In this study, we describe the first nonfatal AFOP in a child and review the literature. DESCRIPTION: A 10-year-old boy developed very severe aplastic anemia (VSAA) after being admitted to our hospital with a fulminant hepatic failure of unknown origin. A chest computed tomography scan revealed multiple lung nodules and a biopsy of a pulmonary lesion showed all the signs of AFOP. Infectious workup remained negative. We started immunosuppressive therapy with antithymocyte globulin and cyclosporine to treat VSAA. Subsequent chest computed tomography scans showed a considerable diminution of the lung lesions but the VSAA did not improve until we performed hematopoietic stem cell transplantation 5 months later. CONCLUSIONS: Aplastic anemia is associated with a variety of autoimmune syndromes. The sequence of events in our patient suggests that the hepatic failure, AFOP, and the VSAA may all have been part of an autoimmune syndrome. AFOP could be the result of immune dysregulation in this pediatric case with favorable outcome after immunosuppressive therapy and hematopoietic stem cell transplantation.

Background Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE). Its safety was established in a thorough clinical development program. Objective To characterize the safety profile of dapoxetine in PE treatment and to report the incidence, severity, and type of adverse events. Design, setting, and participants We conducted a 12-wk, open-label, observational study with a 4-wk, postobservational contact. A total of 10 028 patients were enrolled, with 6712 patients (67.6%) treated with dapoxetine 30–60mg (group A)and 3316 (32.4%) treated with alternative care/nondapoxetine (group B). Interventions Treatment with dapoxetine or alternative care/nondapoxetine. Outcome measurements and statistical analysis Treatment-emergent adverse events (TEAEs) and concomitant therapy use during the 12-wk observational and the postobservational period were reported. Results and limitations The mean age for all patients was 40.5 yr. In group A, 93.0% of the patients were initially prescribed dapoxetine 30mg. Treatment options for group B patients included clomipramine, paroxetine, fluoxetine, sertraline, topical drugs, condoms, and behavioral counseling. Both treatment regimens were well tolerated. TEAEs were reported by 12.0% and 8.9% of group A and group B, respectively, with the highest incidence observed in patients aged >65 yr for group A (21.4%) and 30–39 yr (9.8%) for group B. The most commonly reported TEAEs were nausea, headache, and vertigo, with a higher incidence in group A (3.1%, 2.6%, and 1.0%, respectively) than in group B (oral drugs: 2.3%, 1.3%, and 0.9%, respectively). There were no cases of syncope in group A and one case in group B. A major limitation is that this was a nonrandomized, open-label, short-term study lacking efficacy data. Conclusions The results of this postmarketing observational study demonstrated that dapoxetine for treatment of PE has a good safety profile and low prevalence of TEAEs. Syncope and major cardiovascular adverse events were not reported. The high level of adherence by healthcare providers to the contraindications, special warnings, and precautions for dapoxetine minimizes the risk for its use in routine clinical practice. The current risk minimization measures for its identified and potential risks are effective.

TA-TMA is a pathology that occurs after allogenic HSC transplantation with an incidence of 4-13%, and represents one of the most severe vascular damage related with this therapy. We report here the case of a nine-yr-old girl suffering from a severe refractory aplastic anemia who received an unrelated, 9/10 HLA-matched HSC. Soon after transplantation, the patient developed a graft-versus-host disease (GvHD), a TA-TMA, and renal insufficiency. These pathologies remained refractory to the various treatments undertaken and required several hospitalizations in the intensive care unit. On day 106 post-HSC transfusion, after several episodes of intensive care, the patient was infused with mismatched, third-party MSCs. Schizocyte levels rapidly decreased after MSC infusion, and two wk later, most biological parameters returned to normal. Erythrocyte and thrombocyte transfusions were discontinued, and the patient remained stable for 10 wk. Thereafter, TA-TMA symptoms, viral reactivation, pleural and cardiac effusions reappeared and lead to the death of the patient. Our observations suggest that allogenic MSC infusion may decrease the symptoms of TA-TMA, but further investigation is required to determine how and when MSC should be infused to develop a long-lasting protective effect.

Nach Abschluss der Akutversorgung bei schweren neurologischen Erkrankungen werden Patienten in Deutschland in der sog. Phase B fruhzeitig rehabilitiert. Uber den Langzeitverlauf dieser Patienten existieren bisher keine Studien. Patienten der Phase B aus 9 Zentren wurden im Jahr 2002 prospektiv erfasst und nach 5 und 6 Jahren nachuntersucht. Als Assessmentinstrumente dienten der Barthel-Index, die Rankin-Skala und der EQ-5D. Mittels multivariater logistischer Regressionen wurden Faktoren fur das Risiko fur schlechtes bzw. Chancen fur gutes Outcome ermittelt. Insgesamt 1280 Patienten wurden in die Studie eingeschlossen. Ein hohes Alter (Hazard-Quotient [HQ] 1,05; 95%-KI: 1,04–1,06) erhohte und eine hohe Punktzahl in der Komaremissionsskala (HQ 0,93; 95%-KI: 0,92–0,96) und im Barthel-Index (HQ 0,97; 95%-KI: 0,97–0,98) bei Entlassung verringerten das Sterberisiko nach 5 Jahren. Die Faktoren Schluckstorung (OR 3,1; 95%-KI: 1,7–5,5) und Uberwachungspflicht am Ende der Rehabilitation (OR 3,2; 95%-KI: 1,2–8,6) erhohten das Risiko fur ein schlechtes Ergebnis in der Rankin-Skala 2–4 und die Faktoren Verstandigungsstorung (OR 5,0; 95%-KI: 2,0–12,8) und perkutane endoskopische Gastrostomie (OR 19,7; 95%-KI: 2,7–144,4) bei Entlassung erhohten das Risiko fur eine reduzierte gesundheitsbezogene Lebensqualitat (definiert als EQ-5D-VAS

Although olfactory identification deficits in schizophrenia have been repeatedly demonstrated, some studies indicate that schizophrenia patients may also show an olfactory hypersensitivity. In addition, recent evidence points to impaired odor hedonics in schizophrenia. It was the aim of the present study to investigate olfactory information processing in schizophrenia patients with positive symptoms, by means of chemosensory event-related potential (CSERP) analysis. To control for modality-specific effects, these data were compared to visual event-related potentials (VERP), and in order to control for disorder-specific effects, the schizophrenia patients were compared to healthy controls as well as to patients with major depressive disorder (MDD). In each group, nine subjects were investigated. During EEG recording (32 scalp locations) two odors (positive valence: phenyl-ethylalcohol, negative valence: isobutyraldehyde) were presented using the constant flow method. Afterwards, two colors (red, yellow) were presented. The schizophrenia patients responded to both odors with shorter CSERP latencies than healthy controls and MDD-patients. This effect was most pronounced for the early processing (N1 component) of the emotionally negative odor. However, in response to colors, schizophrenia patients showed increased N1 latencies and a reduced P3 amplitude. It will be discussed whether schizophrenia patients with positive symptoms show a general processing advantage for emotionally negative (threat-related) information.

Die Laterodysgnathie ist eine Sonderform der skelettalen Dysgnathie, die sich durch eine Asymmetrie des Gesichtsschadels auszeichnet. Bei der chirurgischen Korrektur kommen die Verfahren der Umstellungsosteotomien zur Anwendung. Zusatzliche Masnahmen zur Verbesserung der auseren Kontur und der Okklusion sind moglich. Je nach Auspragung der Dysgnathie werden die Eingriffe in abgestufter Form durchgefuhrt. Insbesondere bei Defiziten im Weichgewebe konnen Restasymmetrien verbleiben. Vier klinische Falle werden hier vorgestellt.

Socioeconomic status (SES) discrepancies exist for child and adult cancer morbidity and are a major public health concern. In this Swiss population-based matched case-control study on the etiology of childhood leukemia, we selected the cases from the Swiss Childhood Cancer Registry diagnosed since 1991 and the controls randomly from census. We assigned eight controls per case from the 1990 and 2000 census and matched them by the year of birth and gender. SES information for both cases and controls was obtained from census records by probabilistic record linkage. We investigated the association of SES with childhood leukemia in Switzerland, and explored whether it varied with different definitions of socioeconomic status (parental education, living condition, area-based SES), time period, and age. In conditional logistic regression analyses of 565 leukemia cases and 4433 controls, we found no consistent evidence for an association between SES and childhood leukemia. The odds ratio comparing the highest with the lowest SES category ranged from 0.95 (95% CI: 0.71-1.26; P trend = 0.73) for paternal education to 1.37 (1.00-1.89; P trend = 0.064) for maternal education. No effect modification was found for time period and age at diagnosis. Based on this population-based study, which avoided participation and reporting bias, we assume the potential association of socioeconomic status and childhood leukemia if existing to be small. This study did not find evidence that socioeconomic status, of Switzerland or comparable countries, is a relevant risk factor or strong confounder in etiological investigations on childhood leukemia.

Delphine Arni, Fabienne Gumy-Pause, Marc Ansari, Johanna A. Kremer Hovinga, and Val erie A. McLin Division of Pediatric Surgery, Pediatric Onco-hematology unit, Geneva University Hospitals, Geneva, Switzerland; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, Switzerland; and Swiss Center of Liver Disease, Geneva University Hospitals, Geneva, Switzerland

The aim of the present study was to investigate whether chemosensory anxiety signals can activate behavioral withdrawal systems in humans. Twelve male university students donated their axillary sweat in two situations: right before an oral academic examination (anxiety condition) and during ergometric training (exercise condition). Subjective ratings revealed that the odor donors experienced significantly more anxiety and less pleasure during the anxiety condition than during the exercise condition. Seven subjects (three females) participated in the psychophysiological experiment. The chemosensory stimuli from pooled sweat samples of the donors, and from unused cotton pads (pad condition) were presented via a constant-flow olfactometer. Acoustic startle probes (100 dB (A)) were delivered during and between the presentations of the chemosensory stimuli. Only three subjects were able to discriminate the chemosensory stimuli of the human sweat samples from room air. However, the startle reflex amplitude (EMG of the eyeblink response) recorded in the context of chemosensory anxiety signals was increased, as compared to the amplitude recorded in the context of chemosensory stimuli from either exercise (p = 0.018) or cotton pad (p = 0.012). It is concluded that chemosensory anxiety signals may pre-attentively prime defensive behavior.

Objective: To study the effects of augmented exercise therapy time for arm rehabilitation as either Bobath therapy or the impairment-oriented training (Arm BASIS training) in stroke patients with arm severe paresis. Design: Single blind, multicentre randomized control trial. Setting: Three inpatient neurorehabilitation centres. Subjects: Sixty-two anterior circulation ischaemic stroke patients. Interventions: Random assignment to three group: (A) no augmented exercise therapy time, (B) augmented exercise therapy time as Bobath therapy and (C) augmented exercise therapy time as Arm BASIS training. Main measures: Main outcome measure: Fugl-Meyer arm motor score. Secondary measure: Action Research Arm Test (ARA). Ancillary measures: Fugl-Meyer arm sensation and joint motion/pain scores and the Ashworth Scale (elbow flexors). Results: An overall effect of augmented exercise therapy time on Fugl-Meyer scores after four weeks was not corroborated (mean and 95% confidence interval (CI) of change scores: no augmented exercise therapy time ( n = 20) 8.8, 5.2–12.3; augmented exercise therapy time ( n = 40) 9.9, 6.8-13.9; p = 0.2657). The group who received the augmented exercise therapy time as Arm BASIS training ( n = 20) had, however, higher gains than the group receiving the augmented exercise therapy time as Bobath therapy ( n = 20) (mean and 95% CI of change scores: Bobath 7.2, 2.6-11.8; BASIS 12.6, 8.4 - 16.8; p = 0.0432). Passive joint motion/pain deteriorated less in the group who received BASIS training (mean and 95% CI of change scores: Bobath -3.2, -5.2 to -1.1; BASIS 0.1, -1.8-2.0; p = 0.0090). ARA, Fugl-Meyer arm sensation, and Ashworth Scale scores were not differentially affected. Conclusions: The augmented exercise therapy time as Arm BASIS training enhanced selective motor control. Type of training was more relevant for recovery of motor control than therapeutic time spent.

In this study, it is hypothesized that a planned increase in the dose of recombinant human erythropoietin (rh-EPO) can prevent transfusion in very low birth weight infants. Two different regimens of rh-EPO were administrated, one consisting in increasing dosage up to 5000 U/kg/wk, according to the individual reticulocytes response, and the second in a standard therapy of 1250 U/kg/wk. Fifty-one infants participated. Despite a significant higher reticulocytosis, the study was prematurely terminated due to the results of an interim analysis showing that transfusion was not avoided by increasing the rh-EPO. No significant differences were found between the two regimens concerning transfusion rate, volume transfused, gain in weight, and adverse effects. Progressive titration of rh-EPO to improve the biological response does not leave premature infants free of transfusion.

Pohl M, Ruckriem S, Strik H, Hortinger B, Meiβner D, Mehrholz J, Pause M. Treatment of pressure ulcers by serial casting in patients with severe spasticity of cerebral origin. Arch Phys Med Rehabil 2002;83:35-9. Objective: To assess the effectiveness of serial casting in the treatment of pressure ulcers caused by severe spasticity. Design: Case series. Setting: A clinic for the rehabilitation of persons with neurologic disorders. Patients: Nine patients with 11 pressure ulcers resulting from severe cerebral spasticity, the ulcers being intractable to conventional management because of repeated friction and/or inaccessibility. Intervention: Serial casting of the limb(s) with the pressure ulcer(s), with either fenestration or a cast arch providing access to the wound. Main Outcome Measures: Improved healing of pressure ulcers, as quantified with the National Pressure Ulcer Advisory Panel classification system. Results: Within a mean of 4.6 weeks, 7 ulcers healed completely and 4 improved markedly. The casting caused no complications. Moreover, extension deficits improved markedly in all patients (105° ± 27° to 17° ± 10°). Conclusion: Serial casting may be a valuable tool in the treatment of pressure ulcers at the extremities of patients with severe cerebral spasticity. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

In adult therapy, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are recognized as active treatment of relapsed acute promyelocytic leukemia (APL). The efficacy of this combination in pediatric APL has not yet been well established. We report the case of a 6-year-old girl with relapsed APL, with a PML-RARα mutation, treated with a combination of ATO and ATRA. Over a period of 5 months, she received in total, 75 doses of intravenous ATO and 40 doses of oral ATRA. Currently, 22 months after relapse, she is still in complete remission. Here, we describe treatment of a relapsed APL in a child with limited treatment of ATO and ATRA and review the literature.

The aim of the present study is to investigate olfactory sensitivity and odor evaluations in a homogenous sample of unipolar depressive patients using pure olfactory odors. Twenty-four in-patients with major depressive disorder (MDD) were investigated during their acute depressive phase. Eighteen of them participated a second time after successful treatment. A group of healthy subjects, matched by age, sex, and smoking behavior, served as a control. Olfactory sensitivity, as measured by threshold tests, was strongly reduced in patients with severe depression. Additional correlative analyses revealed that the lowered sensitivity could partly be predicted by high depression scores. After successful medical treatment, these sensitivity differences were reduced and did not reach the significance level. The subjective odor evaluations (valence and intensity ratings) were not markedly changed in general. The results reveal that olfactory performance in MDD patients is reduced at an early perceptional level of stimulus processing. It is discussed whether this effect can be attributed to the close functional connection between the main olfactory bulb and the amygdala.

Objective : The aim of the study was to determine how odor processing is altered in patients with unilateral supratentorial brain tumors. Methods : Olfactory event-related potentials (OERPs) were evaluated in 10 patients with unilateral brain tumors of the frontal or temporal lobe in response to linalool and allylcaproate. Both odors were presented monorhinally by a constant-flow olfactometer. In addition, 20 healthy subjects were examined. While sniffing, the subjects were asked to discriminate the two odors. EEG was recorded from 7 electrode positions (Fz, Cz, Pz, F3/4, P3/4). Amplitudes and latencies of 3 peaks (N1, P2, P3) were measured. To control for effects of modality-non-specific alterations on the olfactory components acoustic event-related potentials (AERPs) were registered by use of an oddball paradigm. Results : Patients with right-sided lesions showed distinct deficits in the discrimination task after stimulation of the right and left nostril. In contrast, patients with left-sided lesions only had an attenuation of correct reactions after left-sided stimulation. In the OERPs, patients with right-sided lesions showed P2- and P3-components with decreased amplitudes at parietal electrode positions. These alterations appeared after ipsi- and contralateral stimulation. Patients with left-sided lesions showed a significant effect of the side of stimulation. Their OERP-amplitudes were decreased after left-sided stimulation but not after right-sided stimulation. After right-sided olfactory stimulation a correlation between the olfactory and the acoustic ERP was seen in patients with right-sided lesions. Conclusions : Olfactory performance of the participating patients was markedly reduced. Patients with right-sided lesions showed bilateral impairment, which would support the importance of the right hemisphere in olfaction. The alteration of the topographic distribution of P2- and P3-amplitudes in patients with right-sided lesions might reflect an impairment of early and late olfactory processing steps.

Mutations of the VHL tumor suppressor gene occur in patients with VHL disease and in the majority of sporadic clear cell renal carcinomas (VHL(-/-) RCC). Loss of VHL protein function is associated with constitutive expression of mRNAs encoding hypoxia-inducible proteins, such as vascular endothelial growth factor. Overproduction of angiogenic factors might explain why VHL(-/-) RCC tumors are so highly vascularized, but whether this overproduction is sufficient for oncogenesis still remains unknown. In this report, we examined the activity of transforming growth factor-alpha (TGF-alpha), another VHL-regulated growth factor. We show that TGF-alpha mRNA and protein are hypoxia-inducible in VHL(-/-) RCC cells expressing reintroduced VHL. In addition to its overexpression by VHL(-/-) RCC cells, TGF-alpha can also act as a specific growth-stimulatory factor for VHL(-/-) RCC cells expressing reintroduced wild-type VHL, as well as primary renal proximal tubule epithelial cells, the likely site of origin of RCC. This role is in contrast to those of other growth factors overexpressed by VHL(-/-) RCC cells, such as vascular endothelial growth factor and TGF-beta1, which do not stimulate RCC cell proliferation. A TGF-alpha-specific antisense oligodeoxynucleotide blocked TGF-alpha production in VHL(-/-) RCC cells, which led to the dependence of those cells on exogenous growth factors to sustain growth in culture. Growth of VHL(-/-) RCC cells was also significantly reduced by a drug that specifically inhibits the epidermal growth factor receptor, the receptor through which TGF-alpha stimulates proliferation. These results suggest that the generation of a TGF-alpha autocrine loop as a consequence of VHL inactivation in renal proximal tubule epithelial cells may provide the uncontrolled growth stimulus necessary for the initiation of tumorigenesis.

Zusammenfassung. Die Untersuchung der affektiven Reaktion auf olfaktorische und visuelle Reize bei Patienten mit Major Depression (MD) hatte zum Ziel, aufzuklären, ob eine abweichende Reizbewertung bei MD-Patienten modalitätsspezifisch ist und/oder von der Reiz-Valenz abhängig ist. Es wurden 26 MD-Patienten untersucht und mit einer nach Alter und Geschlecht parallelisierten Kontroll- Stichprobe verglichen. Die Teilnehmer hatten zur Aufgabe, ihre emotionale Reaktion auf 10 Gerüche und 20 Bilder aus dem International Affective Picture System (IAPS) auf drei Dimensionen (Valenz, Arousal, Dominanz) zu beschreiben. Alle Reize wurden entsprechend ihrer Valenz in positive, neutrale und negative klassifiziert. Depressive Patienten reagierten mit stärkerer Erregung auf negative Reize als die nicht-depressiven Kontrollen. Dieser Effekt war unabhängig von der Reizmodalität. Außerdem fühlten sich MD-Patienten bei beiden Reizqualitäten und unabhängig von der Valenz-Klasse submissiver als die Kontrollen. Auf der Valenz-Dimension ergaben sich keine Gruppen-Unterschiede.

Androstenone is a boar pheromone. and has also been found within different human body fluids. However, it is still unclear whether it carries pheromonal information in humans and whether it contributes significantly to the complex human body odor at all. Some humans fail to perceive the odor of androstenone, but most of these anosmics can achieve sensitivity by daily sniffing. The following study was designed to investigate whether sensitivity to androstenone influences the perception of body odors. Four females osmic to and four females anosmic to androstenone attended two EEG sessions. Anosmics were successfully sensitized to androstenone between sessions. CSERPs (chemosensory event-related potentials) were obtained while subjects perceived their own body odor and a male body odor within an olfactory oddball paradigm. The CSERPs showed a general decrease in amplitude from the first to the second session except for the sensitized anosmics in response to male body odor. The results indicate that the sensitivity to androstenone in females is associated with a stronger brain response to male body odor.

This paper addresses two questions related to the inherent association between breathing and odor perception: Does central nervous processing of odors change when an artificial breathing technique (velopharyngeal closure) is introduced and secondly, does odor processing vary with the oral breathing phase (inhalation or exhalation)? Chemosensory event-related potentials (CSERP) were obtained from eight female subjects while they were smelling an odor mixture (citral, eugenol, linalool, menthol and isoamylacetate). Each subject was required to perform spontaneous mouth breathing (120 trials) as well as the velopharyngeal closure technique (120 trials). Simultaneously, a thermistor monitored the phase of the respiratory cycle. The results reveal that the central nervous correlates of odor processing change with the breathing technique but not with the oral breathing cycle. The findings that early stimulus processing is faster (N1 latency) and late stimulus processing more pronounced (P3 amplitudes) when the subjects are breathing spontaneously are discussed with regard to attentional effects. The reduction of the N1 amplitude during the spontaneous breathing condition may be caused by larger latency variations and longer stimulus rise-times. Furthermore, it is concluded that the oral breathing cycle is less important than the nasal breathing cycle for olfactory information transmission.

Abstract The mismatch negativity (MMN) is thought to indicate automatic stimulus discrimination in response to acoustic stimuli. In the present study six male subjects were presented with the odors linalool and eugenol within a passive oddball-paradigm. The subjects were instructed to ignore the odors and concentrate on an auditory distractor task. In two sessions each odor served once as the standard stimulus and once as the deviant stimulus. Both odors when presented as deviants led to a negative deflection of the olfactory event-related potential (OERP) between 500-600 ms. After 600 ms the waveforms in response to the deviants were differentially influenced by odor quality. Although the present study should be understood as exploratory, the results suggest the existence of an early mismatch detector in the olfactory modality independent of attention and odor quality.

Zusammenfassung. Bereits mehrfach sind in der Fachliteratur spezifische Anosmien - im Volksmund auch als Geruchsblindheit bezeichnet - für unterschiedliche Duftstoffe bei Menschen und Tieren beschrieben worden. Die durchgeführte Studie befaßt sich in der Hauptsache mit der Frage, ob bei Vorliegen einer spezifischen Anosmie olfaktorische Sensitivität induzierbar ist. Zu diesem Zweck wurden Frauen mit spezifischer Anosmie für den Duftstoff Androstenon auf Induzierbarkeit der Wahrnehmung geprüft, indem die absoluten Wahrnehmungsschwellen für diesen Duftstoff vor und nach wiederholter Duftexposition bestimmt wurde. Androstenon ist eine Komponente des menschlichen Körpergeruchs und findet sich im Achselschweiß von Männern in stärkerer Konzentration als bei Frauen. Die Resultate der vorliegenden Untersuchung zeigen, daß bei über 80 % der Duft-exponierten Teilnehmerinnen nach anfänglicher Anosmie Wahrnehmung induziert werden konnte.

A new method will be presented which allows the perception of body odors in humans to be studied objectively. The analysis of body odor‐evoked potentials was used to investigate if and how the human brain is able to differentiate self from non‐self body odor for the first time. Six subjects (three females) participated in two experimental sessions. In each session, two body odors (axillary hair) were presented within an olfactory oddball paradigm. One of the odors was collected from the subject and the other from an odor donor of the same sex. In the first session the subjects' attention was distracted to a secondary task (passive paradigm), in the second session the subjects were asked to actively differentiate the odors (active paradigm). For the EEG recordings the odors were presented within a constantly flowing airstream. The results show that the subjects could hardly differentiate the body odors subjectively. However, it could be demonstrated that the central nervous processing of one's own odor was faster than the processing of the chemosensory non‐self signal. Moreover, in the active paradigm, the potentials appeared to be larger when the subjects perceived their own body odor. The conclusion is reached that the measurement of chemosensory event‐related potentials (CSERP) is the method of choice for the investigation of HLA‐associated body odors.

Androstenone, a compound of human male body odor, might act as a chemosensory signal communicating dominance or aggressiveness. In order to clarify its communicative significance, the relationship between androstenone perception and the level of circulating steroid hormones was investigated in both men and women. Androstenone perception was assessed within n=26 men and n=25 women. Female participants were not currently using hormonal contraception and were in their follicular menstrual cycle phase. Androstenone perception was assessed in terms of olfactory sensitivity, quality judgments, and emotional self-ratings. The perception of isovaleric acid served as a control. Over the course of 2h five saliva samples were collected, aliquots were mixed and levels of estradiol and testosterone were analyzed via enzyme-linked immunosorbent assays. In men, higher testosterone levels were associated with lower olfactory sensitivity to androstenone (p=0.014) and negative feelings when exposed to it (p=0.047). In women, higher estradiol levels were related to judging androstenone as less pleasant (p=0.009) and more unpleasant (p=.0036). The perception of isovaleric acid was unrelated to sex-hormone levels. The current results support the notion of androstenone communicating dominance, aggression or competition. Men with higher testosterone levels are more sensitive to androstenone and dislike its odor, possibly indicating that androstenone signals the readiness for competition in men. Similarly, the fact that women with higher estradiol levels dislike androstenone may be due to androstenone being a signal of reduced willingness for social cooperation and an increased likelihood to engage in extramarital sex.

Background: Cerebral injury can render meaningless an otherwise successful cardiac operation. As carbon dioxide management during hypothermic cardiopulmonary bypass has a major impact on cerebral blood flow during bypass, it may also influence postoperative cerebral function. The objective of this prospective, controlled, double-blind study was to compare the effect of pH-stat (temperature correction of blood gas analyses) or α-stat (no temperature correction) on brain function. Methods: Cerebral function was assessed non-invasively using neurological examination, a neuropsychological test battery, quantitative electroencephalogram and the cognitive evoked potential P300 preoperatively and on postoperative day 7 or 8. Forty-five patients undergoing elective aortocoro-nary bypass grafting in barbiturate/opiate anesthesia were randomised into a pH-stat- (n=23) and an α-stat-group (n=22). Membrane oxygenators with arterial line filtration and non-pulsatile flow at a perfussion pressure of 50–60 mmHg were used throughout. Results: One patient in each group developed a new paresis. Among 49 comparisons of cerebral function parameters, only 3 showed significant differences at the 5%-level, i.e. exactly what is expected purely by chance. These differences were too small to be clinically relevant and favored either pH-stat (theta-amplitude) or α-stat (subtest 3 of syndrome-short-test, number of mistakes in aiming). Conclusion: Under the bypass conditions of this study there was no difference in early cerebral functional outcome between pH- or α-stat carbon dioxide management during hypothermic cardiopulmonary bypass.

Objective parameters are needed to quantify cerebral dysfunction following cardiac surgery in outcome and comparative studies. In this investigation we assessed the value of the late auditory evoked potentials N100 and P300 to measure the neuropsychological deficit after coronary artery bypass grafting (CABG). N100, an exogenous potential is influenced by the stimulus pattern (frequency, intensity and stimulus presentation rate). P300, an endogenous potential, depends on the cognitive processing invoked by the stimulus. With approval of the Human Investigation Committee and the patients' consents, 52 subjects undergoing elective CABG were enrolled. Operation, extracorporal circulation, anesthesia and postoperative intensive care were standardized. Twenty-channel recordings of N100 and P300 were obtained for off-line analysis. P300 was elicited using an oddball paradigm with rare target tones interspersed among frequent non-target tones. Additionally, neuropsychological tests (syndrome short test SKT and letter cancellation test) were carried out. Neurological examination and all tests were compared preoperatively and one week postoperatively. A significant deterioration in cerebral function was documented by the SKT score (P = 0.04), an increase in P300 latency (P = 0.004) and an increase of mistake rate in counting the P300 target tone (P = 0.02). No differences between preoperative and postoperative testing were found for letter cancellation, P300 amplitude and any N100 parameter. No correlation was found between the preoperative/postoperative changes in SKT score and P300 latency. P300 was proved to be an objective neurophysiological parameter that allows for the quantification of cerebral function after CABG.

A key function of the olfactory system is the detection of differences in odour quality. Therefore, a test was developed to assess odour discrimination ability in normosmic humans. Out of six monomolecular substances (capric acid, coumarin, eugenol, geraniol, phenylethyl alcohol, and vanillin) quaternary mixtures were prepared. Within one item, three odour mixtures were presented (triangle forced-choice procedure). The deviant odour contained the same substances as the two remaining odours; however, the proportions were changed. Study 1 (120 participants) aimed to select items that contribute to a high internal consistency. Study 2 (104 participants) assessed test–retest reliability, parallel test reliability and test validity. Out of 45 items, a 15-item test (Düsseldorf Odour Discrimination Test, DODT) with an internal consistency of 0.61 and medium item difficulties was prepared. The test–retest reliability of the DODT was 0.66 (test interval = 4 weeks) and the parallel test reliability 0.42. The DODT correlated significantly with the University of Pennsylvania Smell Identification Test and to a lesser extent with the phenylethyl alcohol odour threshold test. As the DODT did not correlate with the odour discrimination test of the Sniffin' Sticks, the two tests seem to measure different performances of the olfactory system.

HISTORY AND ADMISSION FINDINGS A 70 year old woman had suffered from diabetes mellitus type 2 since she was 52. Three years before the surgery she had begun to experience weakness together with altered sensitivity in the right leg, which was regarded as having been caused by diabetic polyneuropathy. During the admission examination the level for algesia on the right-hand side was at about D 11, a distal paraparesis of the leg (3-4 degrees, Janda's classification), more intense on the right, hyperactive deep tendon reflexes, Babinski's reflex on both sides, and depressed abdominal cutaneous reflexes. The sensitivity to vibrations on the Malleolus medialis on both sides was 0/8. The patient could walk only with the help of a Rollator. INVESTIGATIONS Over the three-year period following onset of symptoms the following tests were carried out: motor nerve conduction speeds of the N. tibialis and N. peronaeus, electromyogram of the N. tibialis anterior and the M. gastrocnemius, somatosensory evoked potentials (SSEP) of the N. tibialis, which indicated a lesion in the peripheral nerves or nerve roots. Cranial computed tomography (CCT), CT scan of the lumbar spine (L3-S1) and angiological investigation elicited no significant pathological findings. An MRI of the thoracal spine showed a vertebra-sized dorsal tumor pressing on the spinal cord from left to right. TREATMENT AND COURSE By means of microsurgery the spinal tumor was completely removed. Suspected meningeoma was confirmed by histological analysis. During the post-surgical period, the incomplete paraplegia quickly regressed, and 7 weeks after the removal of the spinal meningeoma the patient was able to climb stairs. CONCLUSION In case of slowly-developing paresis of the legs in diabetic patients, diabetic polyneuropathy should not be diagnosed without careful consideration, and rare spinal tumors should be considered as part of the differential diagnosis, especially if the blood glucose level is normal, and intensive physiotherapy brings no improvement in the patient's condition.

We describe a case of fatal acute disseminated breakthrough toxoplasmosis in a 19-year-old adolescent after haploidentical hematopoietic stem cell transplantation for acute lymphoblastic leukemia despite continued atovaquone prophylaxis. Diagnosis was at necropsy, and confirmed by postmortem polymerase chain reaction analysis in plasma. This report illustrates the need for protozoal monitoring despite atovaquone prophylaxis, in severely immunocompromised patients with intolerance to standard treatment.