Revisiting the Santa Barbara sense of direction scale, mental rotations, and gender differences in spatial orientation

Angular direction estimation to landmarks of varying distance in the physical environment was utilised to investigate the ecological validity of the Santa Barbara sense of direction scale (SBSOD). Two- and three-dimensional MR measures were included to enable further the scale applicability. Results showed a moderate correlation between SBSOD and angular deviation from landmarks in the immediate landscape, but not with local or distant landmarks. Moreover, the findings suggest that skills which underlie three-dimensional MR better relate to pointing accuracy (PA) of distant landmarks and the cardinal direction, North. Results also showed a gender-related systematic biases in landmark estimation

Analysis of gut microbiota in rheumatoid arthritis patients. Disease-related dysbiosis and modifications induced by etanercept

A certain number of studies were carried out to address the question of how dysbiosis could affect the onset and development of rheumatoid arthritis (RA), but little is known about the reciprocal influence between microbiota composition and immunosuppressive drugs, and how this interaction may have an impact on the clinical outcome. The aim of this study was to characterize the intestinal microbiota in a groups of RA patients treatment-naïve, under methotrexate, and/or etanercept (ETN). Correlations between the gut microbiota composition and validated immunological and clinical parameters of disease activity were also evaluated. In the current study, a 16S analysis was employed to explore the gut microbiota of 42 patients affected by RA and 10 healthy controls. Disease activity score on 28 joints (DAS-28), erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptides, and dietary and smoking habits were assessed. The composition of the gut microbiota in RA patients free of therapy is characterized by several abnormalities compared to healthy controls. Gut dysbiosis in RA patients is associated with different serological and clinical parameters; in particular, the phylum of Euryarchaeota was directly correlated to DAS and emerged as an independent risk factor. Patients under treatment with ETN present a partial restoration of a beneficial microbiota. The results of our study confirm that gut dysbiosis is a hallmark of the disease, and shows, for the first time, that the anti-tumor necrosis factor alpha (TNF-α) ETN is able to modify microbial communities, at least partially restoring a beneficial microbiota

Alterations in Event Related Potentials (ERP) associated with tinnitus distress and attention

Tinnitus related distress corresponds to different degrees of attention paid to the tinnitus. Shifting attention to a signal other than the tinnitus is therefore particularly difficult for patients with high tinnitus related distress. As attention effects on Event Related Potentials (ERP) have been shown this should be reflected in ERP measurements (N100, phase locking). In order to prove this hypothesis single sweep ERP recordings were obtained in 41 tinnitus patients as well as 10 control subjects during a period of time when attention was shifted to a tone (attended) and during a second phase (unattended) when they did not focus attention to the tone. Whereas tinnitus patients with low distress showed a significant reduction in both N100 amplitude and phase locking when comparing the attended and unattended measurement condition a group of patients with high tinnitus related distress did not show such ERP alterations. Using single sweep ERP measurements the results of our study show, that attention in high tinnitus related distress patients is captured by their tinnitus significantly more than in low distress patients. Furthermore our results provide the basis for future neurofeedback based tinnitus therapies aiming at maximizing the ability to shift attention away from the tinnitus. © 2008 The Author(s)

SSCP-based identification of members within the Pseudoterranova decipiens complex (Nematoda : Ascaridoidea : Anisakidae) using genetic markers in the internal transcribed spacers of ribosomal DNA

The anisakid nematodes morphologically corresponding with Pseudoterranova decipiens sensu lato (s.l.) (Krabbe, 1878) from different seal or sea lion hosts and geographical origins, previously identified as Pseudoterranova krabbei, P. decipiens (s.s.), P. bulbosa, P. azarasi and P. cattani by multilocus enzyme electrophoresis, were characterized using a DNA approach. Also a population of P. decipiens (s.l.) from Chaenocephalus aceratus, the blackfin icefish, from Antarctica and another from Osmerus eperlanus, the European smelt, from Germany were included in the study. The first (ITS-1) and second (ITS-2) internal transcribed spacers (ITS) of ribosomal DNA (rDNA) were amplified by PCR from individual nematodes and analysed by single-strand conformation polymorphism (SSCP), followed by selective sequencing. While no variation in single-stranded ITS-1 and ITS-2 profiles was detected among samples representing each of the species or populations (with the exception of slight microheterogeneity), SSCP analysis of the ITS-2 amplicons allowed the unequivocal differentiation of all of the 5 sibling species of P. decipiens (s.l.) examined, which was supported by sequence differences in ITS rDNA. Samples representing the P. decipiens (s.l.) population from O. eperlanus had the same SSCP profile as those of P. decipiens (s.s.), which was supported by a lack of nucleotide difference in the ITS between them, suggesting that the former represented P. decipiens (s.s.). Based on SSCP results and ITS sequence data, P. decipiens (s.l.) from C. aceratus was genetically most distinct with respect to all other members of Pseudoterranova examined, which indicated that it may represent P. decipiens E (based on geographical origin) or a distinct species. These findings and the molecular approach taken should have important implications for studying the life-cycles, transmission patterns, epidemiology and population genetics of these anisakid nematodes, and the diagnosis of their infections

Salivary cortisol and α-amylase production at awakening is associated with positivity (POS) levels in healthy young subjects

A large variety of positive outcomes including social adjustment, psychological well-being and health, have been recently closely associated with positivity (POS). On the assumption that differences in the POS degree might be associated with different individual neuroendocrine assets that enables people to cope effectively with stress, the present study examined the association between POS, salivary cortisol and α-Amylase (α-Amy) production in a group of healthy male volunteers university students, respectively scoring high (POS-H, N = 10) and low (POS-L, N = 10) in POS. Participants were selected from a larger sample of 300 students of the Medical School at Sapienza University of Rome on the basis of their positivity level: POS was analysed and the upper and lower 25% were invited to participate in this new study. The findings report a distinct salivary cortisol and α-Amy production in the study population: in comparison to the POS-H group, the POS-L subjects presented a lower salivary cortisol awake response (CAR) and a flattened α-Amy production at 30 and 60 min after awakening. In addition, salivary cortisol and α-Amy areas under the curve (AUCs), which were calculated as indicators of the two subclinical biomarkers production during the first hour after awakening, resulted significantly lower in the POS-L group in comparison to the POS-H group. Further studies on larger and different populations are needed to definitively confirm that the different cortisol and α-Amy secretion patterns between POS-H and POS-L individuals is associated with a potentially better capacity to preserving an adequate quality of life in individuals being equipped with a system apparently able to better respond to external and/or internal stimuli. Lastly, a better understanding of the biological correlates of POS is crucial to design psychological interventions able to take advantage of individuals’ assets and thus to integrate and strengthen the efficacy of traditional medications

Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease

Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer’s disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing

Begging and feeding responses vary with relatedness and sex of provisioners in a cooperative breeder

Begging behaviour can provide information on offspring hunger levels and be used by parents to adjust food provisioning efforts. In cooperative breeders, helpers also provide care by feeding the young. However, how helpers of different sex and relatedness to the offspring respond to begging behaviour has rarely been studied in cooperatively breeding species, which limits our understanding of the indirect and/or direct benefits that helpers may obtain by responding to offspring demand. Here, we used a cooperatively breeding bird, the sociable weaver, Philetairus socius, to investigate how nest intervisit intervals of breeders and different types of helpers, distinguished by sex and relatedness, varied with acoustic begging. Moreover, we tested whether these different classes of provisioners experienced distinct levels of begging. Our results show that only breeding males, but not breeding females or helpers of any sex and relatedness to the nestlings, returned faster to the nest to feed after experiencing more begging calls. When contrasted directly, we confirmed a statistically supported difference in responses to begging between male and female breeders. Surprisingly, second-order relatives experienced more begging calls than the other classes of more related helpers and breeders. These results show that we might find differences in how provisioners respond to begging levels when classifying group members according to their potential fitness gains. In sociable weavers, the benefits and costs of adjusting feeding efforts to begging seem to differ with sex and life history stage. Experimental and more detailed investigations on begging-feeding interactions are necessary to understand the origin and prevalence of these differences across cooperatively breeding systems. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour. This is an open access article under the CC BY license (http://creativecommons.org/licenses/ by/4.0/)

Phase I dose-escalation trial of the oral AKT inhibitor uprosertib in combination with the oral MEK1/MEK2 inhibitor trametinib in patients with solid tumors.

PurposeThis study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition.MethodsThis was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD.ResultsAdverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses).ConclusionsContinuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested