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Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient’s needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics. Here we present a case series of 6 patients with classical A-T and variant A-T, which illustrates the phenotypic variability of A-T that can present in childhood with prominent extrapyramidal features, with or without cerebellar ataxia. We report the clinical data, together with a detailed genotype description, immunological analyses, and related expression of the ATM protein. We show that the presence of some residual ATM kinase activity leads to the clinical phenotype variant A-T that differs from the classical A-T. Our data illustrate that the diagnosis of the variant form of A-T can be delayed and difficult, while early recognition of the variant form as well as the classical A-T is a prerequisite for providing a correct prognosis and appropriate rehabilitation and support, including the avoidance of diagnostic X-ray procedures, given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment.

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.

Self-reported empathy differs with gender and sexual orientation. The current study investigated whether mu-suppression, reflecting brain activity especially related to state empathy, also is modulated by gender and sexual orientation. Pictures of painful and non-painful actions were presented to 20 lesbians, 20 gay men, 20 heterosexual men and 20 heterosexual women, while EEG was recorded. Individual peak frequencies of mu-activity (electrodes C3, C4) were detected within the 6–11 Hz band for each participant, and mu-suppression indices were calculated. Further, verbal indicators of state empathy (pain ratings) and compassion were assessed. Only heterosexual individuals showed the typical pattern of enhanced mu-suppression in response to painful relative to non-painful pictures. Lesbian women and gay men did not show a differential mu-response. Moreover, they felt less compassion compared to heterosexual individuals. In line with this finding, the more compassion the participants reported, the stronger the mu-suppression in response to painful relative to non-painful pictures was. Pain ratings did not vary with sexual orientation. The lesser compassion reported by lesbian women and gay men is discussed as a mediator of their non-differential mu-suppression response. It is hypothesized that this pattern might relate to gay men and lesbian women tending to perceive the anonymous depicted actors as outgroup members, hence showing less compassion and reduced mu-suppression. As empathy is often related to negative feelings (empathic stress), a clear distinction between individuals to empathize with versus individuals not to emphasize with may well be an adaptive feature in same-sex oriented individuals.

Mosaic somatic mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) genes have been identified in most enchondromas by targeted mutation analysis. Next-generation sequencing (NGS), that may detect even low-level mosaic mutation rates, has not previously been applied to enchondromas. Immunohistochemistry using the H09 clone is routinely used as a surrogate for the common R132H IDH1 mutation in gliomas. We compared immunohistochemistry and NGS results in a series of 13 enchondromas from 8 pediatric patients. NGS identified a heterozygous IDH mutation in all enchondromas, showing identical mutation status in patients with multiple tumors assessed, thereby confirming somatic mosaicism. A majority of the tumors harbored an IDH1 mutation (p.R132H in 3 tumors; p.R132C in 4 tumors from 2 patients; p.R132L and p.R132G in one tumor each). A p.R172S IDH2 mutation was identified in 4 enchondromas, but not in the ependymoma from one patient with Ollier disease, who further displayed a heterozygous STK11 missense mutation. IDH mutation rates varied between 14% (indicative of mutations in 28% of the cells and of intratumoral mosaicism) and 45% (tumor content was close to 100%). Cytoplasmic H09 reactivity was observed as expected in tumors with an IDH1 p.R132H mutation; cross-reactivity was seen with the p.R132L variant. This first NGS study of pediatric enchondromas confirms that IDH mutations may occur in a mosaic fashion. STK11 gene mutations may provide insights in the development of multiple cartilaginous tumors in enchondromatosis, this tumor suppressor gene having been shown in animal models to regulate both chondrocyte maturation and growth plate organization during development.

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

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.

Growing tumors exist in metabolically compromised environments that require activation of multiple pathways to scavenge nutrients to support accelerated rates of growth. The folliculin (FLCN) tumor suppressor complex (FLCN, FNIP1, FNIP2) is implicated in the regulation of energy homeostasis via 2 metabolic master kinases: AMPK and mTORC1. Loss-of-function mutations of the FLCN tumor suppressor complex have only been reported in renal tumors in patients with the rare Birt-Hogg-Dube syndrome. Here, we revealed that FLCN, FNIP1, and FNIP2 are downregulated in many human cancers, including poor-prognosis invasive basal-like breast carcinomas where AMPK and TFE3 targets are activated compared with the luminal, less aggressive subtypes. FLCN loss in luminal breast cancer promoted tumor growth through TFE3 activation and subsequent induction of several pathways, including autophagy, lysosomal biogenesis, aerobic glycolysis, and angiogenesis. Strikingly, induction of aerobic glycolysis and angiogenesis in FLCN-deficient cells was dictated by the activation of the PGC-1α/HIF-1α pathway, which we showed to be TFE3 dependent, directly linking TFE3 to Warburg metabolic reprogramming and angiogenesis. Conversely, FLCN overexpression in invasive basal-like breast cancer models attenuated TFE3 nuclear localization, TFE3-dependent transcriptional activity, and tumor growth. These findings support a general role of a deregulated FLCN/TFE3 tumor suppressor pathway in human cancers.

Reports of a female advantage in empathy-related measures suggest a role for sex hormones, although the data are inconsistent. Studies also report similar sex differences in human olfactory perception. In rodents, olfaction is involved in detecting and integrating socially relevant information and is modulated by the brain actions of estrogens. We hypothesized that olfaction may untangle the mixed evidence on the relationship between sex hormones and empathy-related measures (cognitive and affective) in humans. To test this, we examined 60 healthy participants in three sex-hormone-status groups: free-cycling women tested in cycle phases with higher 17-β estradiol and progesterone, oral-contraceptive users (low estradiol and progesterone), and men. We assessed empathy-related measures, facial mimicry (from zygomaticus and corrugator muscle activity), and odor discrimination ability. In the empathy-related measures and facial mimicry, we did not find overall group effects or meaningful associations with salivary levels of estradiol, progesterone, or testosterone. Free-cycling women only outperformed men in the recognition of emotions from pictures of the eye region, but sex hormones were unrelated to emotion recognition performance. Oral contraceptive users showed higher scores in the affective empathy-related measure when viewing negative emotions, with no relation to hormone levels. Free-cycling women exhibited the strongest facial mimicry (viewing female, but not male protagonists), positively associated with progesterone. Finally, the groups differed in odor discrimination, with free-cycling women outperforming men. However, odor discrimination ability and empathy-related performance were not correlated. Our results support a role of sex hormones in odor perception and in empathy-related measures, to a certain extent. However, no common underlying mechanism was found.

It is well documented how chemosensory anxiety signals affect the perceiver's physiology, however, much less is known about effects on overt social behavior. The aim of the present study was to investigate the effects of chemosensory anxiety signals on trust and risk behavior in men and women. Axillary sweat samples were collected from 22 men during the experience of social anxiety, and during a sport control condition. In a series of five studies, the chemosensory stimuli were presented via an olfactometer to 214 participants acting as investors in a bargaining task either in interaction with a fictitious human co-player (trust condition) or with a computer program (risk condition). It could be shown that chemosensory anxiety signals reduce trust and risk behavior in women. In men, no effects were observed. Chemosensory anxiety is discussed to be transmitted contagiously, preferentially in women.

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

Sex differences in self-control become apparent during preschool years. Girls are better able to delay their gratification and show less attention problems and overactive behavior than boys. In this context, organizational effects of gonadal steroids affecting the neural circuitry underlying self-control could be responsible for these early sex differences. In the present study testosterone levels measured in amniotic fluid (via ultra performance liquid chromatography and tandem mass spectrometry) were used to examine the role of organizational sex hormones on self-control. One hundred and twenty-two 40-month-old children participated in a delay of gratification task (DoG task) and their parents reported on their attention problems and overactive behavior. Girls waited significantly longer for their preferred reward than boys, and significantly more girls than boys waited the maximum period of time, providing evidence for sex differences in delay of gratification. Boys that were rated as suffering from more attention problems and overactive behavior waited significantly shorter in the DoG task. Amniotic testosterone measures were reliable in boys only. Most importantly, boys who waited shorter in the DoG task and boys who were reported to suffer from more attention problems and overactive behavior had higher prenatal testosterone levels. These findings extend our knowledge concerning organizational effects of testosterone on the brain circuitry underlying self-control in boys, and are of relevance for understanding how sex differences in behavioral disorders are connected with a lack of self-control.

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.

BACKGROUND Smoking harms health, particularly that of childhood cancer survivors, who face risk of pulmonary and cardiovascular diseases because of chemotherapy and radiotherapy to the chest. This nationwide study assessed smoking habits and reasons for smoking in adolescent survivors and healthy peers. METHODS As part of the Swiss Childhood Cancer Survivor Study, we sent a questionnaire to all Swiss resident survivors, who were aged 16-19 years. We compared smoking status and reasons for smoking between 511 survivors, 141 of their siblings, and 1,727 adolescents in a representative population-based study, the Tobacco Monitoring Switzerland (TMS). RESULTS Current smoking was less prevalent in survivors (17%) and their siblings (17%) compared with TMS (32%). Survivors and TMS adolescents gave similar reasons for smoking. Stress control, smoking being a habit, and good taste were the reasons for smoking cited most often in both groups. Peer smoking was more important in survivors (49%) than in TMS (34%, P = 0.004). Most important reasons for not smoking in both groups were smoking being unhealthy and not wanting to be addicted. CONCLUSIONS In Switzerland, survivors smoke as often as their siblings but less than the general population. Peer smoking was a more important reason for smoking in survivors than in the general population, suggesting that reducing smoking in peers could result in a reduction of smoking in survivors. Overall, reasons for smoking were very similar, thus interventions to reduce smoking in survivors could be the same as those used in the general population.

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

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.

Theories of neuroaesthetics assume, that looking at traces of actions used in creating artwork (e.g. brush marks) is associated with a simulation of these actions in the observer’s sensorimotor-cortex. The aim of the current study is to dissociate the activation of the sensorimotor-cortex by the observation of action traces from associated visual processes. Twenty-eight participants observed handmade graphics (acrylic paint on paper) of different complexity (line, triangle, shape of a house) and computer-generated counterparts. Central mu-activity, as an index of sensorimotor-cortex activity, and occipital alpha-activity, as an index of visual cortex activity were recorded in the 8–13 Hz EEG-band. In line with the hypothesis, mu-activity at electrode C4 is sensitive for the complexity of handmade (p = 0.001), but not computer-generated graphics (p > 0.500). In contrast, occipital alpha-activity is sensitive for the complexity of both handmade and computer-generated graphics (p

The present study assessed emotion regulation in response to chemosensory and visual stimuli. Using cognitive reappraisal, 40 female participants regulated their emotions in response to disgusting pictures and odors, while the startle reflex was elicited and emotion ratings were assessed. Participants reported feeling less negative, and less aroused, while down-regulating their emotions towards both odors and pictures. Although being rated as equally negative and arousing, odor presentations were accompanied by larger startle responses than picture presentations. Furthermore, as compared to pictures emotion regulation towards odors followed a strikingly different time course suggesting less effective emotion regulation in response to disgusting odors. Questionnaire data show that differences between emotion regulation outcome towards odors was not attributable to different regulation strategies used. Thus, the current data suggest a unique role of olfaction in emotion perception, and show that cognitive emotion regulation – although being generally effective – may also be limited.

On an individual level, human body odors carry information about whether a person is an eligible mate. The current studies investigate if body odors also transmit information about individuals being potential partners in more general terms, namely in regards to gender and sexual orientation. In study 1, 14 gay and 14 heterosexual men were presented with body odors obtained from potential partners (gay male and heterosexual female body odors, respectively) and heterosexual male body odor as a control. In study 2, 14 lesbian and 14 heterosexual women were presented with lesbian female and heterosexual male body odors representing body odors of potential partners, and heterosexual female body odor as a control. Central nervous processing was analyzed using chemosensory event-related potentials and current source density analysis (64-channel EEG recording). Gay and heterosexual men responded with shorter P2 latencies to the body odors of their preferred sexual partners, and lesbian women responded with shorter P2 latencies to body odors of their preferred gender. In response to heterosexual male body odors, lesbian women displayed the most pronounced P3 amplitude, and distinct neuronal activation in medial frontal and parietal neocortical areas. A similar pattern of neuronal activation was observed in gay men when presented with heterosexual male body odor. Both the early processing advantage (P2) for desirable partners' body odors as well as the enhanced evaluative processing (P3, CSD) of undesirable partners' body odors suggest that human body odors indeed carry information about individuals being potential partners in terms of gender and sexual orientation.

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.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.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.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.

In accordance with simulation theories of empathy, the somatosensory cortex is involved in the perception of pain of others. Cognitive processes, like perspective taking, can alter empathy-related activity within the somatosensory cortex. The current study investigates whether this modulation is caused by the imagined sensation of pain or by the cognitive load of a perspective-taking task. Applying a within-subject design, participants (N = 30) watched pictures of painful and nonpainful actions, while imagining reduced, normal, or increased pain perception of the observed individual. Mu activity (8-13 Hz), which is inversely correlated with sensorimotor-cortex activity, was measured via EEG. To calculate mu activity (central electrodes) and alpha activity (occipital electrodes), which served as a control for effects of cognitive load, a fast Fourier transform was applied. Mu suppression linearly increased from reduced to normal to increased imagined pain (p .05), while alpha activity was unaffected by the imagined pain (p .80). Suppression of the 8-13 Hz band at central and occipital electrodes was stronger in response to painful actions compared to nonpainful actions (p .01). These results indicate that modulation of mu activity through perspective taking reflects the imagined pain intensity and not the cognitive load induced by the task.

Reactive oxygen species (ROS) are key modulators of apoptosis and carcinogenesis. One of the important sources of ROS is NADPH oxidases (NOXs). The isoform NOX5 is highly expressed in lymphoid tissues, but it has not been detected in any common Hodgkin or non-Hodgkin lymphoma cell lines. In diverse, nonlymphoid malignant cells NOX5 exerts an antiapoptotic effect. Apoptosis suppression is the hallmark feature of a rare type of lymphoma, termed anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large-cell lymphoma (ALCL), and a major factor in the therapy resistance and relapse of ALK(+) ALCL tumors. We applied RT-PCR and Western blot analysis to detect NOX5 expression in three ALK(+) ALCL cell lines (Karpas-299, SR-786, SUP-M2). We investigated the role of NOX5 in apoptosis by small-interfering RNA (siRNA)-mediated gene silencing and chemical inhibition of NOX5 using FACS analysis and examining caspase 3 cleavage in Karpas-299 cells. We used immunohistochemistry to detect NOX5 in ALK(+) ALCL pediatric tumors. NOX5 mRNA was uniquely detected in ALK(+) ALCL cells, whereas cell lines of other lymphoma classes were devoid of NOX5. Transfection of NOX5-specific siRNA and chemical inhibition of NOX5 abrogated calcium-induced superoxide production and increased caspase 3-mediated apoptosis in Karpas-299 cells. Immunohistochemistry revealed focal NOX5 reactivity in pediatric ALK(+) ALCL tumor cells. These results indicate that NOX5-derived ROS contribute to apoptosis blockage in ALK(+) ALCL cell lines and suggest NOX5 as a potential pharmaceutical target to enhance apoptosis and thus to suppress tumor progression and prevent relapse in pediatric ALK(+) ALCL patients that resist classical therapeutic approaches.

The scent of blood is potentially one of the most fundamental and survival-relevant olfactory cues in humans. This experiment tests the first human parameters of perceptual threshold and emotional ratings in men and women of an artificially simulated smell of fresh blood in contact with the skin. We hypothesize that this scent of blood, with its association with injury, danger, death, and nutrition will be a critical cue activating fundamental motivational systems relating to either predatory approach behavior or prey-like withdrawal behavior, or both. The results show that perceptual thresholds are unimodally distributed for both sexes, with women being more sensitive. Furthermore, both women and men's emotional responses to simulated blood scent divide strongly into positive and negative valence ratings, with negative ratings in women having a strong arousal component. For women, this split is related to the phase of their menstrual cycle and oral contraception (OC). Future research will investigate whether this split in both genders is context-dependent or trait-like. published

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.

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using clinical scales such as the Modified Ashworth Scale (MAS). In the literature, the time and period of maximum effect of a bolus dose of intrathecally administered baclofen in patients with cerebral spasticity is variously reported. The aim of the study was, therefore, to reveal the time course of the effect of a BBT on severe cerebral spasticity by the use of a recently described spasticity measurement method. Spasticity in knee joints of 13 patients with severe cerebral spasticity was repeatedly assessed using the MAS and also continuously recorded by the measurement of force under circular fibreglass casts. Force was recorded as nettorque by multiplying the force by the distance between sensor and joint axis, thus allowing inter-individual comparison. Half-hour time integrals (TI) of net-torque were determined 9 hours before and 22 hours after intrathecal baclofen administration. Post-BBT half-hour time integrals (TI+0, TI+0.5, to TI+22) were compared with the mean of 17 pre-BBT half-hour time integrals % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn % hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D % aebbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaaeaaakeaada % qadaqaamaanaaabaGaaeivaiaabMeaaaWaaSbaaSqaaiabgkHiTiaa % iMdacaaMe8UaaeiDaiaab+gacaaMe8UaeyOeI0IaaGymaaqabaaaki % aawIcacaGLPaaaaaa!4430! $$ {\left( {\overline{{{\text{TI}}}} _{{ - 9\;{\text{to}}\; - 1}} } \right)} $$ . Significantly lower post-BBT half-hour time integrals compared with % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn % hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D % aebbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaaeaaakeaada % qadaqaamaanaaabaGaaeivaiaabMeaaaWaaSbaaSqaaiabgkHiTiaa % iMdacaaMe8UaaeiDaiaab+gacaaMe8UaeyOeI0IaaGymaaqabaaaki % aawIcacaGLPaaaaaa!4430! $$ {\left( {\overline{{{\text{TI}}}} _{{ - 9\;{\text{to}}\; - 1}} } \right)} $$ were found between TI+2 and TI+8 (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients was TI+4. The lowest mean MAS scores were found 4 hours after BBT. The findings suggest that the greatest effect of BBT on cerebral spasticity occurs between 2 and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen injection. Clinical scales used to determine the effect of BBT should thus be carried out during this period—ideally at 4 hours after baclofen injection.

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using the modified Ashworth Scale (MAS) and Penn Spasm Frequency Scales (SFS). The result of a BBT may be difficult to interpret in patients with reduced joint mobility caused by contractures. The aim of this study was to apply a new spasticity measurement which would quantify and visualise the effect of a BBT in 10 patients with severe cerebral spasticity and contractures. Spasticity was recorded continuously by the measurement of force under circular fibreglass casts in 10 knee joint contractures. Force was recorded as net-torque by multiplying the force and distance between sensor and joint axis, thus allowing inter-individual comparison. MAS, SFS, and two three-hour time integrals of net-torque were determined before and after intrathecally administered baclofen. No significant changes in MAS (p = 0.1) and SFS (p = 0.07) were observed; however, a significant reduction of time integrals of net-torque after baclofen administration (p = 0.005) was found. The present study shows that the antispastic effect of intrathecally administered BBT can be quantitatively assessed and visualised using the described method. It also suggests that this method can be helpful in the assessment of the effectiveness of the BBT in patients with severe spasticity of cerebral origin and contractures.

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.

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.

The recording of chemosensory event-related potentials (CSERPs) has been established as an objective method in the assessment of central odor processing in humans. In the present study CSERPs were used to investigate whether human body odor is genetically determined by the major histocompatibility complex (MHC), referred to in humans as the human leukocyte antigen (HLA). The immunological function of the MHC is the discrimination of self/nonself within the immune system. In rodents it has been shown that body odor is significantly influenced by the MHC and that it can be discriminated by members of different species. To create a sufficiently large subject pool, 144 subjects were screened for their HLA class I loci A and B. During the electroencephalography (EEG) session the subjects (n= 40/20 women) were confronted with the body odor (axillary hair) of three different donors. Two donors (d1 and d2) were HLA-similar but had a different HLA type than the third donor (d3) and the perceiving subject. The third donor and the perceiver shared a similar HLA type. Half of the perceivers received odors from donors of the same sex, the other half smelt odors from donors of the opposite sex. In the EEG session subjects were presented with 200 trials. The odors were delivered through a constant flow olfactometer nonsynchronously to breathing. The odor of d1 appeared frequently (p= 0.6) whereas the odors of d2 and d3 appeared each at a rate of p= 0.2. During half the trials the subjects were instructed to respond to the odor of d2, during the other half to the odor of d3. The EEG was recorded from Fz, Cz, Pz, F3, P3, F4 and P4 in reference to linked mastoids. First results show that male perceivers show enhanced potentials in response to male donors of a similar HLA type (d3). The CSERP results of the other groups as well as valence and attractiveness ratings will be discussed.

Two studies were conducted to investigate the influence of attention on the components of the chemosensory event-related potential (CSERP). In the first study the odors linalool and eugenol were delivered to six male subjects, in the second study three male and two female subjects were presented with their own body odor (axillary hair) and the body odor of a same sex donor. In both studies the odors were presented in an oddball paradigm under ignore and attend conditions via a constant-flow olfactometer. In the ignore condition attention was diverted from the odors with a distractor task, while in the attend condition the subjects were asked to respond to the infrequently occurring odor. In both studies the allocation of attention led to a decrease in the latency of the early components (N1, P2, N2) and to an increase in the amplitude of the late positivities. The modulation of the early components suggests that attentional gating in olfaction might already be effective at an early processing level.

ATM promoter hypermethylation has been recently reported in adult carcinomas, but no information is available concerning the methylation status of ATM gene promoter in childhood B-precursor acute lymphoblastic leukaemia (ALL). Furthermore, involvement of somatic ATM promoter mutations in cancer is not known. We report a complete ATM gene promoter analysis in 74 childhood lymphoid malignancies.

Chemosensory event-related potentials (CSERP) can be used to examine central nervous odor processing. An important question for understanding odor perception is how different concentrations are processed. In the present study two odors were chosen which activate either the olfactory (linalool) or the trigeminal (menthol) system. Both odors were presented to 11 subjects in four different concentrations. Four subjects had to attend actively to the odors while the others perceived the odors under passive attention. The results showed that increased concentrations of the olfactory stimulus resulted in shorter latencies of the N1 component but did not affect the amplitudes of the CSERP. However, the amplitudes of the stimulus dependent, exogenous components (N1, P2) increased with higher concentrations of the trigeminal stimulus. The amplitude of the late positive complex, which reflects endogenous processes, was usually larger when the odorous stimuli had to be attended to actively. It is concluded that olfactory intensity coding results in a qualitatively different but not in a stronger neuronal response of the human brain.

Across a wide variety of domains, experts differ from novices in their response to stimuli linked to their respective field of expertise. It is currently unknown whether similar patterns can be observed with regard to social expertise. The current study therefore focuses on social openness, a central social skill necessary to initiate social contact. Human body odors were used as social cues, as they inherently signal the presence of another human being. Using functional MRI, hemodynamic brain responses to body odors of women reporting a high (n = 14) or a low (n = 12) level of social openness were compared. Greater activation within the inferior frontal gyrus and the caudate nucleus was observed in high socially open individuals compared to individuals low in social openness. With the inferior frontal gyrus being a crucial part of the human mirror neuron system, and the caudate nucleus being implicated in social reward, it is discussed whether human body odor might constitute more of a significant and rewarding social signal to individuals high in social openness compared to individuals low in social openness process.

Simulation theories argue that humans simulate motor processes of others to gain information about intentions and emotional states of others. Mu-suppression is a valid electrophysiological correlate of these processes. Mu-activity can be measured via electroencephalography (EEG) in the alpha-band (8-13 Hz) above the sensorimotor cortex and is suppressed when actions are executed or observed. Based on a within-subject design, including 28 participants, it was tested whether the processes measured by mu-suppression could be modulated by empathic top-down-processes. Participants were asked to take the perspective of two actors, telling a story about a sad or neutral life event (video sequences). Afterwards, EEG was measured at central (C3, Cz, C4) and occipital (O1, Oz, O2) electrodes, while participants observed the actors drinking water (standardized video sequences, 8 s duration). Fast fourier transformation showed stronger suppression of power in the alpha-range (relative to baseline) at central and occipital electrodes while the actor with the sad story was observed relative to the actor with the neutral story. Furthermore, measures of state empathy correlated positively with the difference of mu-suppression between executed and observed movements, an indicator of self-other discrimination. Thus, mirror neuron activity measured by mu-suppression is modulated by empathic processes.

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.

Preformed anti-HLA antibodies (AHA) are known to be associated with delayed engraftment and reduced overall survival after adult hematopoietic stem cell transplantation. However, limited data is available in pediatric patients. In this study, we explored the role of AHA on clinical outcomes in 70 pediatric patients who received a single unit of HLA mismatch cord blood for hematologic malignancies, immunodeficiencies or metabolic diseases. The presence of AHA was detected in 44% (31/70) of the patients. Preformed class I AHA was associated with an increased occurrence of grade 1–4 acute graft-versus host disease (p

In the present study we examined whether olfactory information processing depends on the phase of the menstrual cycle. Five female subjects were investigated during three phases (follicular, ovulatory, luteal) of their menstrual cycle. In each session chemosensory (olfactory) event-related potentials (CSERP) were recorded and olfactory thresholds and the hedonic tone of the test stimulus (citral) were determined. Threshold values were correlated with the salivary cortisol level. The results show that olfactory perception changes during the menstrual cycle. After the first stimulus presentations in a recording session, odors were perceived as more complex or novel during the ovulatory period (enhanced amplitude of P3-1). With continued stimulation, odor processing became faster (reduced latency of NI, P2 and P3-2) around ovulation and slower during the follicular phase. Moreover, odors were described more differentially during the ovulatory period. Olfactory sensitivity was correlated positively with the peripheral cortisol level.

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.

The role of busulfan (Bu) metabolites in the adverse events seen during hematopoietic stem cell transplantation and in drug interactions is not explored. Lack of availability of established analytical methods limits our understanding in this area. The present work describes a novel gas chromatography-tandem mass spectrometric assay for the analysis of sulfolane (Su) in plasma of patients receiving high-dose Bu. Su and Bu were extracted from a single 100 μL plasma sample by liquid-liquid extraction. Bu was separately derivatized with 2,3,5,6-tetrafluorothiophenolfluorinated agent. Mass spectrometric detection of the analytes was performed in the selected reaction monitoring mode on a triple quadrupole instrument after electronic impact ionization. Bu and Su were analyzed with separate chromatographic programs, lasting 5min each. The assay for Su was found to be linear in the concentration range of 20-400ng/mL. The method has satisfactory sensitivity (lower limit of quantification, 20ng/mL) and precision (relative standard deviation less than 15%) for all the concentrations tested with a good trueness (100 ± 5%). This method was applied to measure Su from pediatric patients with samples collected 4h after dose 1 (n = 46), before dose 7 (n = 56), and after dose 9 (n = 54) infusions of Bu. Su (mean ± SD) was detectable in plasma of patients 4h after dose 1, and higher levels were observed after dose 9 (249.9 ± 123.4ng/mL). This method may be used in clinical studies investigating the role of Su on adverse events and drug interactions associated with Bu therapy. Figure Overall sample preparation procedure for quantification of sulfolane and busulfan in plasma from patients receiving higher doses of busulfan

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.

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.