7T functional MRI finds no evidence for distinct functional subregions in the subthalamic nucleus during a speeded decision-making task

The subthalamic nucleus (STN) is a small, subcortical brain structure. It is a target for deep brain stimulation, an invasive treatment that reduces motor symptoms of Parkinson’s disease. Side effects of DBS are commonly explained using the tripartite model of STN organization, which proposes three functionally distinct subregions in the STN specialized in cognitive, limbic, and motor processing. However, evidence for the tripartite model exclusively comes from anatomical studies and functional studies using clinical patients. Here, we provide the first experimental tests of the tripartite model in healthy volunteers using ultra-high field 7 Tesla (T) functional magnetic resonance imaging (fMRI). Thirty-four participants performed a random-dot motion decision-making task with a difficulty manipulation and a choice payoff manipulation aimed to differentially affect cognitive and limbic networks. Moreover, participants responded with their left and right index finger, differentially affecting motor networks. We analysed BOLD signal in three subregions of the STN along the dorsolateral-ventromedial axis, identified using manually delineated high resolution anatomical images and based on a previously published atlas. Using these paradigms, all segments responded equally to the experimental manipulations, and the tasks did not provide evidence for the tripartite model

Induction of morphological aberrations by enzyme inhibition in Drosophila melanogaster

Zusatz zum Futter vonDrosophila melanogaster von 5-Fluoro-2-deoxyuridin oder Aminopterin induziert überzählige Skutellar- und Dorsozentralborsten sowie gekerbte Flügel. Diese Modifikationen wurden als Konsequenz von Enzymhemmung interpretiert

Functional Analysis of Cladosponum fulvum Effector Catalog

Onlangs is de DNA-sequentie van het genoom van Cladosporium fulvum bepaald. Het voornaamste doel daarvan is de identificatie en karakterisering van nieuwe effectors

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

Experiences of Dutch maternity care professionals during the first wave of COVID-19 in a community based maternity care system

Background and objective During the COVID-19 pandemic the organization of maternity care changed drastically; this study into the experiences of maternity care professionals with these changes provides suggestions for the organization of care during and after pandemics. Design An online survey among Dutch midwives, obstetricians and obstetric residents. Multinomial logistic regression analyses were used to investigate associations between the respondents' characteristics and answers. Results Reported advantages of the changes were fewer prenatal and postpartum consultations (50.1%). The necessity and safety of medical interventions and ultrasounds were considered more critically (75.9%); 14.8% of community midwives stated they referred fewer women to the hospital for decreased fetal movements, whereas 64.2% of the respondents working in hospital-based care experienced fewer consultations for this indication. Respondents felt that women had more confidence in giving birth at home (57.5%). Homebirths seemed to have increased according to 38.5% of the community midwives and 65.3% of the respondents working in hospital-based care. Respondents appreciated the shift to more digital consultations rather than face-to-face consultations. Mentioned disadvantages were that women had appointments alone, (71.1%) and that the community midwife was not allowed to join a woman to obstetric-led care during labour and subsequently stay with her (56.8%). Fewer postpartum visits by family and friends led to more tranquility (59.8%). Overall, however, 48.0% of the respondents felt that the safety of maternity care was compromised due to policy changes. Conclusions Maternity care professionals were positive about the decrease in routine care and the increased confidence of women in home birth, but also felt that safety in maternity care was sometimes compromised. According to the respondents in a future crisis situation it should be possible for community midwives to continue to deliver a personal handover after the referral of women to the hospital, and to stay with them

Decreased exposure to sunitinib due to concomitant administration of ifosfamide: results of a phase I and pharmacokinetic study on the combination of sunitinib and ifosfamide in patients with advanced solid malignancies

Background:This study aimed to define the maximally tolerated dose (MTD) of sunitinib combined with two different infusion schedules of ifosfamide. Methods:Patients with advanced solid tumours, good performance score, good organ function, and no standard therapy available were eligible. Continuous once daily sunitinib, in escalating doses per cohort, was combined with ifosfamide, 9 g m-2 for 3 days or 6 g m-2 for 5 days, administered every 3 weeks. Pharmacokinetic (PK) and pharmacodynamic (PD) assessments were performed. Results:With growth-factor support, the MTD of sunitinib combined with either ifosfamide schedule was 12.5 mg in 32 patients enrolled. Neutropenia-related adverse events were dose-limiting toxicities. Sunitinib did not affect ifosfamide PK. Ifosfamide significantly decreased exposure to sunitinib and increased exposure to its metabolite, SU12662. No consistent changes in PD parameters were observed. Conclusion:With growth-factor support, the MTD of sunitinib with both ifosfamide schedules was 12.5 mg. Ifosfamide produced decreased sunitinib blood levels because of CYP3A induction. As PK interactions cannot explain the relatively low sunitinib doses that can be combined with ifosfamide, synergy in toxicity is likely. Whether this also holds true for anti-tumour activity needs to be further explored.British Journal of Cancer advance online publication, 18 May 2010; doi:10.1038/sj.bjc.6605696 www.bjcancer.com