NEUROTRANSMITTERS AND RESTING STATE NETWORKS: CLINICAL IMPLICATION FOR MAJOR PSYCHIATRIC DISORDER

Alterations in brain intrinsic activity \u2013 as organized in resting-state networks (RSNs) such as sensorimotor network (SMN), salience network (SN) and default-mode network (DMN) \u2013 and in neurotransmitters signaling \u2013 such as dopamine (DA) and serotonin (5-HT) \u2013 have been independently detected in psychiatric disorders like bipolar disorder and schizophrenia. Thus, the aim of this work was to investigate the relationship between such neurotransmitters and RSNs in healthy, by reviewing the relevant work on this topic and performing complementary analyses, in order to better understand their physiological link as well as their alterations in psychiatric disorders. According to the reviewed data, neurotransmitters nuclei diffusively project to subcortical and cortical regions of RSNs. In particular, the dopaminergic substantia nigra (SNc)-related nigrostriatal pathway is structurally and functionally connected with core regions of the SMN, while the ventral tegmental area (VTA)-related mesocorticolimbic pathway with core regions of the SN. The serotonergic raphe nuclei (RNi) connections involve regions of the SMN and DMN. Coherently, changes in neurotransmitters activity impact the functional configuration and level of activity of RSNs, as measured by functional connectivity (FC) and amplitude of low-frequency fluctuations/temporal variability of BOLD signal. Specifically, DA signaling is associated with increase in FC and activity in the SMN (hypothetically via the SNc-related nigrostriatal pathway) and SN (hypothetically via the VTA-related mesocorticolimbic pathway), as well as concurrent decrease in FC and activity in the DMN. By contrast, 5-HT signaling (via the RNi-related pathways) is associated with decrease in SMN activity along with increase in DMN activity. Complementally, our empirical data showed a positive correlation between SNc-related FC and SMN activity, while a negative correlation between RNi-related FC and SMN activity (along with tilting of networks balance toward the DMN). According to these data, we hypothesize that the activity of neurotransmitters-related neurons synchronize the low-frequency oscillations within different RSNs regions, thus affecting the baseline level of RSNs activity and their balancing. In our model, DA signaling favors the predominance of SMN-SN activity, while 5-HT signaling favors the predominance of DMN activity, manifesting in distinct behavioral patterns. In turn, alterations in neurotransmitters signaling (or its disconnection) may favor a correspondent functional reorganization of RSNs, manifesting in distinct psychopathological states. The here suggested model carries important implications for psychiatric disorders, providing novel and well testable hypotheses especially on bipolar disorder and schizophrenia

Occupy: A People Yet To Come

The term Occupy represents a belief in the transformation of the capitalist system through a new heterogenic world of protest and activism that cannot be conceived in terms of liberal democracy, parliamentary systems, class war or vanguard politics. These conceptualisations do not articulate where power is held, nor from where transformation may issue. This collection of essays by world-leading scholars of Deleuze and Guattari examines how capitalism can be understood as a global abstract machine whose effects pervade all of life and how Occupy can be framed as a response to this as a heterogenic movement based on new tactics, revitalised democratic processes and nomadic systems of organisation. Seeing the question as a political tactic aimed at delegitimizing their protest, Occupiers refused to answer the question ‘what do you want?’, produce manifestos, elect leaders or act as a vanguard. Occupy: A People Yet to Come goes some considerable way towards providing the terms upon which this refusal can be understood within a changed landscape of political activism and the rewriting of the conventions of political protest. Including essays by Claire Colebrook, Giuseppina Mecchia, John Protevi, Rodrigo Nunes, Verena Andermatt Conley, Nicholas Thoburn, Ian Buchanan, David Burrows, Eugene Holland and Andrew Conio, the volume examines the economic predicates of capitalist economics: liberal democracy and its alternatives, the conjugation of protest and aesthetics, how occupy experiments with different types of leadership and how power, hierarchies and resistance might be understood using Deleuze and Guattari’s radical conceptualizations of debt; subjectivity, the minor and the molecular, occupation, dispersed leadership, territory, smooth space and the war machine

Temporary placement of a fully covered self-expanding metal stent to allow therapeutic ERCP

n/

Przekład

bra

Palliative radiotherapy in addition to self-expanding metal stent for improving dysphagia and survival in advanced oesophageal cancer (ROCS: Radiotherapy after Oesophageal Cancer Stenting):study protocol for a randomized controlled trial

Background: The single most distressing symptom for patients with advanced esophageal cancer is dysphagia. Amongst the more effective treatments for relief of dysphagia is insertion of a self-expanding metal stent (SEMS). It is possible that the addition of a palliative dose of external beam radiotherapy may prolong the relief of dysphagia and provide additional survival benefit. The ROCS trial will assess the effect of adding palliative radiotherapy after esophageal stent insertion. Methods/Design: The study is a randomized multicenter phase III trial, with an internal pilot phase, comparing stent alone versus stent plus palliative radiotherapy in patients with incurable esophageal cancer. Eligible participants are those with advanced esophageal cancer who are in need of stent insertion for primary management of dysphagia. Radiotherapy will be administered as 20 Gray (Gy) in five fractions over one week or 30 Gy in 10 fractions over two weeks, within four weeks of stent insertion. The internal pilot will assess rates and methods of recruitment; pre-agreed criteria will determine progression to the main trial. In total, 496 patients will be randomized in a 1:1 ratio with follow up until death. The primary outcome is time to progression of patient-reported dysphagia. Secondary outcomes include survival, toxicity, health resource utilization, and quality of life. An embedded qualitative study will explore the feasibility of patient recruitment by examining patients’ motivations for involvement and their experiences of consent and recruitment, including reasons for not consenting. It will also explore patients’ experiences of each trial arm. Discussion: The ROCS study will be a challenging trial studying palliation in patients with a poor prognosis. The internal pilot design will optimize methods for recruitment and data collection to ensure that the main trial is completed on time. As a pragmatic trial, study strengths include collection of all follow-up data in the usual place of care, and a focus on patient-reported, rather than disease-orientated, outcomes. Exploration of patient experience and health economic analyses will be integral to the assessment of benefit for patients and the NHS

Risk of Malignant Progression in Barrett’s Esophagus Patients: Results from a Large Population-Based Study

BACKGROUND: Barrett’s esophagus (BE) is a premalignant lesion that predisposes to esophageal adenocarcinoma. However, the reported incidence of esophageal adenocarcinoma in patients with BE varies widely. We examined the risk of malignant progression in patients with BE using data from the Northern Ireland Barrett’s esophagus Register (NIBR), one of the largest population-based registries of BE worldwide, which includes every adult diagnosed with BE in Northern Ireland between 1993 and 2005. SUBJECTS AND METHODS: We followed 8522 patients with BE, defined as columnar lined epithelium of the esophagus with or without specialized intestinal metaplasia (SIM), until the end of 2008. Patients with incident adenocarcinomas of the esophagus or gastric cardia or with high-grade dysplasia of the esophagus were identified by matching the NIBR with the Northern Ireland Cancer Registry, and deaths were identified by matching with records from the Registrar General’s Office. Incidence of cancer outcomes or high-grade dysplasia was calculated as events per 100 person-years (% per year) of follow-up, and Cox proportional hazard models were used to determine incidence by age, sex, length of BE segment, presence of SIM, macroscopic BE, or low-grade dysplasia. All P values were from two-sided tests. RESULTS: After a mean of 7.0 years of follow-up, 79 patients were diagnosed with esophageal cancer, 16 with cancer of the gastric cardia, and 36 with high-grade dysplasia. In the entire cohort, incidence of esophageal or gastric cardia cancer or high-grade dysplasia combined was 0.22% per year (95% confidence interval [CI] = 0.19% to 0.26%). SIM was found in 46.0% of patients. In patients with SIM, the combined incidence was 0.38% per year (95% CI = 0.31 to 0.46%). The risk of cancer was statistically significantly elevated in patients with vs without SIM at index biopsy (0.38% per year vs 0.07% per year; hazard ratio [HR] = 3.54, 95% CI = 2.09 to 6.00, P < .001), in men compared with women (0.28% per year vs 0.13% per year; HR = 2.11, 95% CI = 1.41 to 3.16, P < .001), and in patients with low-grade dysplasia compared with no dysplasia (1.40% per year vs 0.17% per year; HR = 5.67, 95% CI = 3.77 to 8.53, P < .001). CONCLUSION: We found the risk of malignant progression among patients with BE to be lower than previously reported, suggesting that currently recommended surveillance strategies may not be cost-effective

Asthma-like symptoms: is it always a pulmonary issue?

Background Double aortic arch is a rare congenital and complete vascular ring around trachea and esophagus. It is usually diagnosed during infancy. The symptoms are generally related to respiratory and gastroesophageal tracts. Case presentation A 20-year-old female patient was referred to our outpatient clinic for persistent dry cough. She had a history of an episode of inhalation of food bolus as an infant and recurrent bronchitis, anorexia and allergic bronchial asthma since the childhood. Since the beginning, an intrathoracic obstruction was suspected at pulmonary function tests. After 1 month of complete asthma treatment, the cough was unchanged and the spirometry confirmed the presence of an intrathoracic obstruction. Then, she underwent a chest CT with contrast medium, a contrast transthoracic echocardiography, a fiberbronchoscopy and an esophageal radiography with contrast medium. The final diagnosis was made and a double aortic arch was found. Conclusion A careful observation of the flow/volume curve should always be guaranteed and the presence of congenital vascular anomalies should be suspected in case of difficult-to-treat asthma