Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre.

Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at baseline and during early treatment that are related to overall survival (OS). In addition, PSMA PET/CT-, PSA-response, and safety and tolerability (CTCAE adverse event reporting) were assessed. Efficacy endpoints were calculated using stratified Kaplan-Meier methods and Cox regression models. Mean applied dose was 17.7 GBq (mean 5.3 ± 1.1 GBq per cycle) with an average of 3.6 (range 1-8) therapy cycles. Patients were followed up for a mean of 12.4 months (range 1-39). The median OS was 15 months (95% CI 12.8-17.2). The best overall response rate in patients assessed with PSMA PET/CT and PSA response was 27.9%, and 50.0% had at least stable disease. Nine patients had a ≥grade 3 adverse event with anemia being the most frequent adverse event. Positive predictors for prolonged OS from baseline parameters were pre-treatment hemoglobin level of ≥10 g/dL and a lower PSA values at treatment start, while the presence of visceral or liver metastases were not significantly associated with worse prognoses in this cohort. With careful patient selection, an individualized Lu-PSMA treatment approach is feasible and patients with dose-limiting factors or visceral metastases should be included in prospective trials.

Supplementation of the maternal diet with Brazil nut (Bertholletia excelsa H.B.K.) prevents cognitive impairment in the offspring of obese mothers.

Maternal obesity may trigger long-term neurodevelopmental disorders in offspring. Considering the benefits of the Brazil nut (Bertholletia excelsa H.B.K.), a rich source of nutrients such as selenium, this study aimed to evaluate its effect on the behavior of obese rat offspring and its relationship with oxidative stress. From 60 days of age until weaning, female Wistar rats were fed a high-fat diet (mHF) or an HF diet supplemented with 5% Brazil nut (mHF/BN), while control mothers (mCTL) were fed a standard diet or a standard diet supplemented with 5% Brazil nut (mBN). Male pups received a standard diet throughout life and, at 30 and 90 days old, were subjected to behavioral tasks to evaluate anxiety and cognition. Biochemical evaluations were performed at 90 days of age. No alterations were observed in the anxiety behavior of the offspring. However, the offspring of the mHF group (oHF) exhibited impaired short-term memory at 30 and 90 days of age and impaired long-term memory at 30 days. Short-term memory impairment was prevented by Brazil nuts in young rats (30 days). While the serum selenium concentration was reduced in the oHF group, the serum catalase concentration was reduced in all groups, without changes in lipid peroxidation or protein carbonylation. Brazil nut maternal diet supplementation prevented short- and long-term cognitive impairment in the offspring, which may be related to the selenium levels.

Neurofeedback trains a superordinate system relevant for seemingly opposing behavioral control deficits depending on ADHD subtype.

ADHD is one of the most prevalent neuropsychiatric disorders of childhood, but symptoms vary considerably between individuals. Therefore, different ADHD subtypes can be distinguished. Yet, it is widely elusive whether the specific subtype is critical to consider when examining treatment effects. Based on theoretical considerations, this could be the case for EEG theta/beta neurofeedback. We examine the effects of such an intervention on rapid response execution and inhibition processes using a Go/Nogo task in the inattentive (ADD) and the combined (ADHD-C) subtype. We show that a single neurofeedback protocol affects opposing deficits depending on the ADHD subtype - namely the execution (in ADD) and inhibition of action (in ADHD-C). No changes occurred in the healthy controls. These findings are discussed in relation to overarching principles of neural oscillations, particularly in the beta frequency band. The data suggest that theta/beta neurofeedback trains a superordinate system strongly related to the function of neural beta frequency oscillations to tune neural networks important for the sampling of sensory information used for behavioral control.

The impact of stimulus modality on the processing of conflicting sensory information during response inhibition.

Response inhibition is a central aspect of cognitive control. Usually, response inhibition is examined using information from a single sensory modality. Yet, evidence suggests that conflicts between information from different modalities affect response inhibition. It is, however, crucial to consider that there are modality differences in the efficiency to trigger response inhibition that may also modulate the impact of conflicts between different sensory modalities. In the current study, we compared an auditory-tactile to an auditory-visual Go/NO-GO task. We recorded EEG data and performed signal decomposition and source localization. On the behavioral level, we show stronger interference effects in the visual than the tactile modality. Despite sensory processes were experimentally varied, temporally decomposed EEG data show that response selection mechanisms are associated with these effects and not the sensory processing stage. These modulations of response selection processes occur in the temporo-parietal junction (TPJ, BA40) and inferior frontal structures (IFG, BA47). The smaller activity in the TPJ during auditory-tactile, compared to auditory-visual conflicts suggests that task representations are less affected by interfering auditory information when the tactile modality informs response inhibition processes. This also explains why less intense braking processes (reflected by IFG activity) are still able to maintain a reasonable response inhibition performance level. It can be concluded that the tactile and visual domains do not only differ in regard to their efficiency to trigger response inhibition processes but also in their susceptibility to interference while informing inhibitory control. Clinical implications are discussed.

A comparative study on the neurophysiological mechanisms underlying effects of methylphenidate and neurofeedback on inhibitory control in attention deficit hyperactivity disorder.

In Attention Deficit Hyperactivity Disorder (AD(H)D), treatments using methylphenidate (MPH) and behavioral interventions like neurofeedback (NF) reflect major therapeutic options. These treatments also ameliorate executive dysfunctions in AD(H)D. However, the mechanisms underlying effects of MPH and NF on executive functions in AD(H)D (e.g. the ability to inhibit prepotent responses) are far from understood. It is particularly unclear whether these interventions affect similar or dissociable neural mechanisms and associated functional neuroanatomical structures. This, however, is important when aiming to further improve these treatments. We compared the neurophysiological mechanisms of MPH and theta/beta NF treatments on inhibitory control on the basis of EEG recordings and source localization analyses. The data show that MPH and theta/beta NF both increase the ability to inhibit pre-potent responses to a similar extent. However, the data suggest that MPH and NF target different neurophysiological mechanisms, especially when it comes to functional neuroanatomical structures associated with these effects. Both treatments seem to affect neurophysiological correlates of a 'braking function' in medial frontal areas. However, in case of the NF intervention, inferior parietal areas are also involved. This likely reflects the updating and stabilisation of efficient internal representations in order to initiate appropriate actions. No effects were seen in correlates of perceptual and attentional selection processes. Notably, reliable effects were only obtained after accounting for intra-individual variability in the neurophysiological data, which may also explain the diversity of findings in studies on treatment effects in AD(H)D, especially concerning neurofeedback.

Carbon and hydrogen stable isotope ratios of carotenoids and beta-carotene-based dietary supplements.

Considering the increasing nutritional and commercial importance of carotenoids, there is an interest in developing a reliable method for authenticity assessment of these compounds. Applying isotope ratio mass spectrometry using elemental analysis in the "combustion" (C) and "pyrolysis" (P) modes (EA-C/P-IRMS), the delta (13)C V-PDB and delta (2)H V-SMOW values of selected carotenoids and alpha/beta-carotene-based commercial dietary supplements were determined in comparison to those of synthetic and "natural" references. The delta (13)C V-PDB and delta (2)H V-SMOW values of synthetic beta-carotene samples ( n = 4), ranging from -25.3 per thousand to -26.4 per thousand and from -144 per thousand to -155 per thousand, respectively, differed clearly from the data determined for carotenoids from various natural sources, including C 3 plant material ( n = 9; delta (13)C V-PDB ranging from -28.5 per thousand to -32.8 per thousand and delta (2)H V-SMOW from -180 per thousand to -275 per thousand) and microalgae Dunaliella salina ( n = 1; delta (13)C V-PDB value of -15.6 per thousand and delta (2)H V-SMOW value of -191 per thousand). From five commercial dietary supplements under study, two revealed delta (13)C V-PDB and delta (2)H V-SMOW values in areas as found for synthetic references, and the other three had values near those of biotechnological beta-carotene produced by D. salina. The delta (13)C V-PDB and delta (2)H V-SMOW values recorded for natural lycopene ( n = 4) and lutein ( n = 5) ranged from -31.1 per thousand to -31.8 per thousand and from -180 to -201 per thousand, as well as from -28.8 per thousand to -32.2 per thousand and from -186 per thousand to -245 per thousand, respectively. Synthetic canthaxanthin ( n = 3) exhibited delta (13)C V-PDB and delta (2)H V-SMOW values ranging from -25.0 per thousand to -28.6 per thousand and from -133 per thousand to -153 per thousand, respectively. The EA-C/P-IRMS application of this study showed that the natural stable isotopic composition of carotenoids is a powerful tool for determining their origin.