Pathological gambling is an impulse control disorder reported in association with dopamine agonists used to treat Parkinson's disease. Although impulse control disorders are conceptualized as lying ...within the spectrum of addictions, little neurobiological evidence exists to support this belief. Functional imaging studies have consistently demonstrated abnormalities of dopaminergic function in patients with drug addictions, but to date no study has specifically evaluated dopaminergic function in Parkinson's disease patients with impulse control disorders. We describe results of a 11C raclopride positron emission tomography (PET) study comparing dopaminergic function during gambling in Parkinson's disease patients, with and without pathological gambling, following dopamine agonists. Patients with pathological gambling demonstrated greater decreases in binding potential in the ventral striatum during gambling (13.9%) than control patients (8.1%), likely reflecting greater dopaminergic release. Ventral striatal bindings at baseline during control task were also lower in patients with pathological gambling. Although prior imaging studies suggest that abnormality in dopaminergic binding and dopamine release may be markers of vulnerability to addiction, this study presents the first evidence of these phenomena in pathological gambling. The emergence of pathological gambling in a number of Parkinson's disease patients may provide a model into the pathophysiology of this disorder.
Some patients with Parkinson disease (PD) develop pathological gambling when treated with dopamine agonists (DAs). However, little is known about DA-induced changes in neuronal networks that may ...underpin this drug-induced change in behavior in vulnerable individuals. In this case-control study, we aimed to investigate DA-induced changes in brain activity that may differentiate patients with PD with DA-induced pathological gambling (gamblers) from patients with PD without such a history (controls).
Following overnight withdrawal of antiparkinsonian medication, patients were studied with H₂(15)O PET before and after administration of DA (3 mg apomorphine) to measure changes in regional cerebral blood flow as an index of regional brain activity during a card selection game with probabilistic feedback.
We observed that the direction of DA-related activity change in brain areas that are implicated in impulse control and response inhibition (lateral orbitofrontal cortex, rostral cingulate zone, amygdala, external pallidum) distinguished gamblers from controls. DA significantly increased activity in these areas in controls, while gamblers showed a significant DA-induced reduction of activity.
We propose that in vulnerable patients with PD, DAs produce an abnormal neuronal pattern that resembles those found in nonparkinsonian pathological gambling and drug addiction. DA-induced disruption of inhibitory key functions--outcome monitoring (rostral cingulate zone), acquisition and retention of negative action-outcome associations (amygdala and lateral orbitofrontal cortex)--together with restricted access of those areas to executive control (external pallidum)--may well explain loss of impulse control and response inhibition in vulnerable patients with PD, thereby fostering the development of pathological gambling.
This systematic review (SR) and meta-analysis aims to compare the surgery-related results and oncological outcomes between SH and RH in patients with early-stage cervical cancer.
We systematically ...searched databases including PubMed, Embase and Cochrane to collect studies that compared oncological and surgery-related outcomes between SH and RH groups in patients with stage IA2 and IB1 cervical cancer. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4.
Seven studies comprising 6977 patients were included into our study. For oncological outcomes, we found no statistical difference in recurrence rate OR = 0.88; 95% CI (0.50, 1.57); P = 0.68 and Overall Survival (OS) OR = 1.23; 95% CI (0.69, 2.19), P = 0.48. No difference was detected in the prevalence of positive LVSI and lymph nodes metastasis between the two groups. Concerning surgery-related outcomes, the comprehensive effects revealed that the bladder injury OR = 0.28; 95% CI (0.08, 0.94), P = 0.04 and bladder disfunction OR = 0.10; 95% CI (0.02, 0.53), P = 0.007 of the RH group were higher compared to the SH group.
This meta-analysis suggested there are no significant differences in terms of both recurrence rate and overall survival among patients with stage IA2-IB1 cervical cancer undergoing SH or RH, while the SH group has better surgery-related outcomes. These data confirm the need to narrow the indication for RH in early-stage cervical cancer.
Postural sway increases when a cognitive task is performed concurrently with a postural task. The author examined the hypothesis that following dual-task training, a concurrent cognitive task would ...not amplify postural sway. Participants (N = 18) were assigned to no-training, single-task training, or dual-task training groups. Single-task training consisted of 3 sessions in which the postural task, quiet standing on a compliant surface, and the cognitive task, counting backward by 3s, were practiced separately. Dual-task training consisted of 3 sessions of concurrent practice of the cognitive and postural tasks. After training, performance of a concurrent cognitive task increased postural sway in the no-training and single-task training groups but not in the dual-task training group. Results suggest that dual-task practice improves dual-task performance.
A universal challenge in genetic studies of autism spectrum disorders (ASDs) is determining whether a given DNA sequence alteration will manifest as disease. Among different population controls, we ...observed, for specific exons, an inverse correlation between exon expression level in brain and burden of rare missense mutations. For genes that harbor de novo mutations predicted to be deleterious, we found that specific critical exons were significantly enriched in individuals with ASD relative to their siblings without ASD (P < 1.13 × 10(-38); odds ratio (OR) = 2.40). Furthermore, our analysis of genes with high exonic expression in brain and low burden of rare mutations demonstrated enrichment for known ASD-associated genes (P < 3.40 × 10(-11); OR = 6.08) and ASD-relevant fragile-X protein targets (P < 2.91 × 10(-157); OR = 9.52). Our results suggest that brain-expressed exons under purifying selection should be prioritized in genotype-phenotype studies for ASD and related neurodevelopmental conditions.
Tandem repeat expansions (TREs) are associated with over 60 monogenic disorders and have recently been implicated in complex disorders such as cancer and autism spectrum disorder. The role of TREs in ...schizophrenia is now emerging. In this study, we have performed a genome-wide investigation of TREs in schizophrenia. Using genome sequence data from 1154 Swedish schizophrenia cases and 934 ancestry-matched population controls, we have detected genome-wide rare (<0.1% population frequency) TREs that have motifs with a length of 2-20 base pairs. We find that the proportion of individuals carrying rare TREs is significantly higher in the schizophrenia group. There is a significantly higher burden of rare TREs in schizophrenia cases than in controls in genic regions, particularly in postsynaptic genes, in genes overlapping brain expression quantitative trait loci, and in brain-expressed genes that are differentially expressed between schizophrenia cases and controls. We demonstrate that TRE-associated genes are more constrained and primarily impact synaptic and neuronal signaling functions. These results have been replicated in an independent Canadian sample that consisted of 252 schizophrenia cases of European ancestry and 222 ancestry-matched controls. Our results support the involvement of rare TREs in schizophrenia etiology.
Port-site hernia (PSH) of less than 10 mm is an exceptionally rare complication of minimally invasive surgery (MIS). To date, there have been no cases in the literature reporting recurrence of PSH ...from a 5 mm incision. We present the first case of PSH recurrence in a woman who underwent surgery for benign gynaecological pathology via a MIS approach. Her post-operative course was complicated by an episode of symptomatic hernia arising from a 5 mm accessory trocar which was surgically managed. A few months later she re-presented with the same symptoms and had a PSH recurrence of the same port-site. Two corrective surgeries employing different techniques were performed. The first episode was managed laparoscopically using interrupted stitches. On the other hand, the PSH recurrence was managed by placement of a mesh. Ultrasound played a crucial role in diagnostics, especially in the recurrent setting. Due to the complete absence of similar cases in the literature, the decision making around the management of a PSH recurrence from a 5 mm trocar site proved to be challenging. As MIS is the current standard of care, more cases are likely to occur, however despite the increasing number of surgical procedures performed via MIS, no established guidelines for managing such complications have been proposed. Trying to bridge this gap, we present the case report of the first case of PSH recurrence from a 5 mm accessory port and a review of the most significant literature available to date. We finally summarise the reported cases of PSH and the types of surgical repair conducted to highlight the absence of a standard of care.
The purpose of the present project was to determine whether postural sway varied with the difficulty of a concurrent unrelated cognitive task. Participants stood on a compliant surface under four ...conditions of varied attentional demand. Information reduction tasks (digit reversal, digit classification, counting backward by 3s) were used to quantify the attentional demands of the cognitive activity. Results showed attentional demands of the cognitive task impacted postural sway, with the most difficult cognitive task having the greatest influence.