Cyclin A1 is essential for setting the pluripotent state and reducing tumorigenicity of induced pluripotent stem cells

The proper differentiation and threat of cancer rising from the application of induced pluripotent stem (iPS) cells are major bottlenecks in the field and are thought to be inherently linked to the pluripotent nature of iPS cells. To address this question, we have compared iPS cells to embryonic stem cells (ESCs), the gold standard of ground state pluripotency, in search for proteins that may improve pluripotency of iPS cells. We have found that when reprogramming somatic cells toward pluripotency, 1%-5% of proteins of 5 important cell functions are not set to the correct expression levels compared to ESCs, including mainly cell cycle proteins. We have shown that resetting cyclin A1 protein expression of early-passage iPS cells closer to the ground state pluripotent state of mouse ESCs improves the pluripotency and reduces the threat of cancer of iPS cells. This work is a proof of principle that reveals that setting expression of certain proteins correctly during reprogramming is essential for achieving ESC-state pluripotency. This finding would be of immediate help to those researchers in different fields of iPS cell work that specializes in cell cycle, apoptosis, cell adhesion, cell signaling, and cytoskeleton

Can an intervention based on a serious videogame prior to cognitive behavioral therapy be helpful in bulimia nervosa? A clinical case study

Background: Several studies have highlighted the implications of impulsivity and novelty seeking for both the maintenance and the process of recovery from bulimia nervosa (BN). Cognitive behavioral therapy (CBT) is the treatment of choice for BN, but for some cases, this treatment alone might not be sufficient for reducing the high levels of impulsivity. The paper presents a case report of a patient with BN, examining the effectiveness of using a videogame (VG; Playmancer) as an additional intervention designed to address impulsivity. Design: Psychometric and neuropsychological measures were collected at baseline. After this assessment, Playmancer was applied prior to CBT, following an 'A-B-A-C-A' single case experimental design. Impulsivity levels were assessed with the Conner's Continuous Performance Test II (CPT-II). After the Playmancer treatment, the patient started CBT, and the levels of impulsivity were recorded again. Finally, psychometric and neuropsychological measures were collected after treatment. Weekly frequency of binges and vomiting were also recorded during the entire procedure. Results: After the VG intervention, psychometric measures such as anxiety levels, impulsivity and novelty seeking decreased. Regarding the neuropsychological measures, impulsivity levels (measured with the CPT-II) progressively decreased throughout the intervention, and an improvement in decision making capacities was observed. Furthermore, the frequency of binges also decreased during and after the VG intervention. Discussion: This case report suggests that using the Playmancer VG to reduce impulsivity prior to CBT may enhance the final results of the treatment for BN

Plant hormones increase efficiency of reprogramming mouse somatic cells to induced pluripotent stem cells and reduce tumorigenicity

Reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined pluripotency and self-renewal factors has taken stem cell technology to the forefront of regenerative medicine. However, a number of challenges remain in the field including efficient protocols and the threat of cancer. Reprogramming of plant somatic cells to plant embryonic stem cells using a combination of two plant hormones was discovered in 1957 and has been a routine university laboratory practical for over 30 years. The plant hormones responsible for cell reprogramming to pluripotency, indole-3-acetic acid (IAA) and isopentenyl adenosine (IPA), are present in human cells, leading to the exciting possibility that plant hormones might reprogram mammalian cells without genetic factors. We found that plant hormones on their own could not reprogram mammalian cells but increase the efficiency of the early formation of iPS cells combined with three defined genetic factors during the first 3 weeks of reprogramming by accelerating the cell cycle and regulating pluripotency genes. Moreover, the cytokinin IPA, a known human anticancer agent, reduced the threat of cancer of iPS cell in vitro by regulating key cancer and stem cell-related genes, most notably c-Myc and Igf-1. In conclusion, the plant hormones, auxin and cytokinin, are new small chemicals useful for enhancing early reprogramming efficiency of mammalian cells and reducing the threat of cancer from iPS cells. These findings suggest a novel role for plant hormones in the biology of mammalian cell plasticit

Diagnosis of late-life depression using estructural equation modeling and dynamic effective connectivity during resting fMRI

Background: Late-life depression (LLD) is characterized by cognitive and social impairments. Determining neurobiological alterations in connectivity in LLD by means of fMRI may lead to a better understanding of the neural basis underlying this disorder and more precise diagnostic markers. The primary objective of this paper is to identify a structural model that best explains the dynamic effective connectivity (EC) of the default mode network (DMN) in LLD patients compared to controls. Methods: Twenty-seven patients and 29 healthy controls underwent resting-state fMRI during a period of eight minutes. In both groups, jackknife correlation matrices were generated with six ROIs of the DMN that constitute the posterior DMN (pDMN). The different correlation matrices were used as input to estimate each structural equation model (SEM) for each subject in both groups incorporating dynamic effects. Results: The results show that the proposed LLD diagnosis algorithm achieves perfect accuracy in classifying LLD patients and controls. This differentiation is based on three aspects: the importance of ROIs 4 and 6, which seem to be the most distinctive among the subnetworks; the shape that the specific connections adopt in their networks, or in other words, the directed connections that are established among the ROIs in the pDMN for each group; and the number of dynamic effects that seem to be greater throughout the six ROIs studied [t = 54.346; df = 54; p < .001; 95 % CI difference = 5.486-5.906]. Limitations: The sample size was moderate, and the participants continued their current medications. Conclusions: The network models that we developed describe a pattern of dynamic activation in the pDMN that may be considered a possible biomarker for LLD, which may allow early diagnosis of this disorder

Lifetime Weight course as a phenotypic marker of severity and therapeutic response in patients with eating disorders

The association between lifetime weight fluctuations and clinical characteristics has been widely studied in populations with eating disorders (ED). However, there is a lack of literature examining the potential role of weight course as a transdiagnostic factor in ED so far. Therefore, the aim of this study is to compare ED severity and treatment outcomes among four specific BMI profiles based on BMI-trajectories across the lifespan: (a) persistent obesity (OB-OB; (n = 74)), (b) obesity in the past but currently in a normal weight range (OB-NW; n = 156), (c) normal weight throughout the lifespan (NW-NW; n = 756), and (d) current obesity but previously at normal weight (NW-OB; n = 314). Lifetime obesity is associated with greater general psychopathology and personality traits such as low persistence and self-directedness, and high reward dependence. Additionally, greater extreme weight changes (NW-OB and OB-NW) were associated with higher psychopathology but not with greater ED severity. Higher dropout rates were found in the OB-OB group. These results shed new light on the BMI trajectory as a transdiagnostic feature playing a pivotal role in the severity and treatment outcome in patients with ED

Emotion regulation as a transdiagnostic factor in eating disorders and gambling disorder: Treatment outcome implications

Background: A first approach addressed to ascertain whether emotion regulation (ER) could be a transdiagnostic construct between eating disorders (EDs) and gambling disorder (GD) (through a joint clinical clustering analysis of both disorders) was performed by Munguia et al. (2021). Both conditions were represented by a severe, moderate, and low ER profile subgroups, according to the degree of ER difficulties. Results showed a linear relationship between the severity of ER difficulties and the severity of the disorder and the psychopathological state. Aims: Based on the aforementioned cross-sectional study, the objective of this longitudinal research was to explore the treatment response of the different ER subgroups. Methods: 459 adult patients (n = 277 ED; n =182 GD) were included. Several clinical variables, as well as outcome indicators (after completing 16 weeks of cognitive-behavioral therapy), were evaluated. Results: The three subgroups found in the previous cross-sectional study were taken for the performance of the present research. ED and GD distribution in each subgroup replicates the one exposed by Mungula et al. (2021), as well as their characterization, considering psychopathology, disorder severity and personality traits. The low ER subgroup reported a better response to treatment, whereas the severe group had the highest rates of non-remission and dropouts. Conclusions: Our results suggest that greater difficulties in ER lead to poorer treatment outcomes. Therefore, tailored treatments for patients with poor ER abilities would be recommended to improve adherence and treatment outcomes

Suicidal ideation and history of suicide attempts in treatment-seeking patients with gambling disorder: The role of emotion dysregulation and high trait impulsivity

Background and aims: Gambling disorder (GD) presents high rates of suicidality. The combined influences of emotion dysregulation and trait impulsivity are crucially important (albeit understudied) for developing strategies to treat GD and prevent suicide attempts. The aim of this study is to investigate the association between trait impulsivity, emotion dysregulation, and the dispositional use of emotion regulation (ER) strategies with suicidal ideation and psychopathological symptom severity in GD. Methods: The sample composed of 249 patients with GD (166 with suicidal ideation) who underwent face-to-face clinical interviews and completed questionnaires to assess psychopathological symptoms, impulsive traits, and ER. Results: Patients with GD who presented suicidal ideation were older and had a later age of GD onset and higher GD severity. Analyses of variance showed higher comorbid symptoms, emotion dysregulation, and trait impulsivity in patients with suicidal ideation. Still, no significant differences were found in the use of ER strategies. SEM analysis revealed that a worse psychopathological state directly predicted suicidal ideation and that both emotion dysregulation and GD severity indirectly increased the risk of suicidal ideation through this state. High trait impulsivity predicted GD severity. Finally, a history of suicide attempts was directly predicted by suicidal ideation. Conclusions: Patients with GD are at risk of presenting suicidal behaviors. The results of this study revealed the importance of comorbid psychopathology in the occurrence of suicidal ideation and the indirect effect of trait impulsivity and emotion dysregulation on suicidality. Thus, suicidal rates in GD could possibly be reduced by specifically targeting these domains during treatment

Food addiction in eating disorders and obesity: Analysis of clusters and implications for treatment

Food addiction (FA) has been associated with greater psychopathology in individuals with eating disorders (ED) and obesity (OBE). The current study aims to provide a better phenotypic characterization of the FA construct by conducting a clustering analysis of FA in both conditions (ED and OBE). The total sample was comprised of 234 participants that scored positive on the Yale Food Addiction Scale 2.0. (YFAS-2) (119 bulimia nervosa (BN), 50 binge eating disorder (BED), 49 other specified feeding or eating disorder (OSFED) and 16 OBE). All participants completed a comprehensive battery of questionnaires. Three clusters of FA participants were identified. Cluster 1 (dysfunctional) was characterized by the highest prevalence of OSFED and BN, the highest ED severity and psychopathology, and more dysfunctional personality traits. Cluster 2 (moderate) showed a high prevalence of BN and BED and moderate levels of ED psychopathology. Finally, cluster 3 (adaptive) was characterized by a high prevalence of OBE and BED, low levels of ED psychopathology, and more functional personality traits. In conclusion, this study identified three distinct clusters of ED-OBE patients with FA and provides some insight into a better phenotypic characterization of the FA construct when considering psychopathology, personality and ED pathology. Future studies should address whether these three food addiction categories are indicative of therapy outcome

Modulation of higher-order olfaction components on executive functions in humans

The prefrontal (PFC) and orbitofrontal cortex (OFC) appear to be associated with both exec- utive functions and olfaction. However, there is little data relating olfactory processing and executive functions in humans. The present study aimed at exploring the role of olfaction on executive functioning, making a distinction between primary and more cognitive aspects of olfaction. Three executive tasks of similar difficulty were used. One was used to assess hot executive functions (Iowa Gambling Task-IGT), and two as a measure of cold executive functioning (Stroop Colour and Word Test-SCWT and Wisconsin Card Sorting Test- WCST). Sixty two healthy participants were included: 31 with normosmia and 31 with hyposmia. Olfactory abilities were assessed using the '' Sniffin ' Sticks '' test and the olfactory threshold, odour discrimination and odour identification measures were obtained. All partici- pants were female, aged between 18 and 60. Results showed that participants with hypos- mia displayed worse performance in decision making (IGT; Cohen ' s- d = 0.91) and cognitive flexibility (WCST; Cohen ' s- d between 0.54 and 0.68) compared to those with normosmia. Multiple regression adjusted by the covariates participants ' age and education level showed a positive association between odour identification and the cognitive inhibition response (SCWT-interference; Beta = 0.29; p = .034). The odour discrimination capacity was not a predictor of the cognitive executive performance. Our results suggest that both hot and cold executive functions seem to be associated with higher-order olfactory functioning in humans. These results robustly support the hypothesis that olfaction and executive mea- sures have a common neural substrate in PFC and OFC, and suggest that olfaction might be a reliable cognitive marker in psychiatric and neurologic disorders

Developmental trajectories of gambling severity after cognitive-behavioral therapy

Aims: To estimate trajectories of the gambling disorder (GD) severity for 12 months following a manualized cognitive-behavior-therapy (CBT) program, and to identify the main variables associated with each trajectory. Methods: Latent Class Growth Analysis examined the longitudinal changes of n = 603 treatment-seeking patients with GD. Results: Five separate empirical trajectories were identified: T1 (n = 383, 63.5%) was characterized by the most highest baseline gambling severity levels and positive progress to recovery during the follow-up period; T2 (n = 154, 25.5%) featured participants with high baseline gambling severity and good progress to recovery; T3 (n = 30, 5.0%) was made up of patients with high gambling baseline severity and slow progress to recovery; T4 (n = 13, 2.2%) and T5 (n = 23, 3.8%) contained participants with high baseline gambling severity and moderate (T4) and poor (T5) progress in GD severity during the follow-up. Psychopathological state and personality traits discriminated between trajectories. Poor compliance with the therapy guidelines and the presence of relapses also differed between the trajectories. Conclusions: Our findings show that patients seeking treatment for GD are heterogeneous and that trends in progress following treatment can be identified considering sociodemographic features, psychopatho- logical state and personality traits. These results could be useful in developing more efficient interventions for GD patients