A Role Beyond Learning for NMDA Receptors in Reward-Based Decision-Making—a Pharmacological Study Using d-Cycloserine

N-methyl-D-aspartate (NMDA) receptors are known to fulfill crucial functions in many forms of learning and plasticity. More recently, biophysical models, however, have suggested an additional role of NMDA receptors in evidence integration for decision-making, going beyond their role in learning. We designed a task to study the role of NMDA receptors in human reward-guided learning and decision-making. Human participants were assigned to receive either 250 mg of the partial NMDA agonist d-cycloserine (n=20) or matching placebo capsules (n=27). Reward-guided learning and decision-making were assessed using a task in which participants had to integrate learnt and explicitly shown value information to maximize their monetary wins and minimize their losses. To tease apart the effects of NMDA on learning and decision-making we used simple learning models. D-cycloserine shifted decision-making towards a more optimal integration of the learnt and the explicitly shown information, in the absence of a direct learning effect. In conclusion, our results reveal a distinct role for NMDA receptors in reward-guided decision-making. We discuss these findings in the context of NMDA''s roles in neuronal super-additivity and as crucial for evidence integration for decisions.     

Dissolution of cholesterol ductal stones in the biliary tree with medium-chain glycerides

In vitro andin vivo experiments were carried out with medium-chain glycerides.In vitro, cholesterol gallstones were rapidly dissolved by medium-chain glycerides; control experiments with saline solution failed to modify the size of the stones.In vivo, medium-chain glycerides were instilled through an, intraductal tube in 12 patients with retained bile duct stones. Perfusions lasted 2–10 days. After perfusion, stones disappeared in six cases, were reduced in size in one case, and remained unchanged in five cases. In five cases, nausea, vomiting, diarrhea, or pain were observed. Medium-chain glyceride infusion rapidly dissolves cholesterol gallstones, but is commonly associated with mild to servre side effects.     

Understanding the implications of the “vaping epidemic” among adolescents and young adults: A call for action

In the past 5 years, the use of nicotine delivered through electronic cigarettes (“e-cigarettes”) has sky-rocketed among adolescents and young adults. E-cigarettes, with their high nicotine content, appealing flavors, low costs, wide availability, and discreet designs threaten 5 decades of progress in the fight against tobacco use. Aside from the increased risk of subsequent use of traditional cigarettes, marijuana, opioids, and other illicit drugs, building evidence indicates that e-cigarette use also exposes youth to several acute and long-term health risks that greatly outweigh the as-yet unfounded potential benefits from the use of e-cigarettes as a smoking reduction or cessation tool in this age group. We discuss some of the latest research on e-cigarettes, highlighting risks and harms associated with their use in adolescents and young adults, and suggest opportunities for action, including the enforcement of age, sales and marketing limitations, and concerted research and public health efforts to help curb what has become a new nicotine epidemic among youth.     

The study protocol of: ‘Initiating end of life care in stroke: clinical decision-making around prognosis’

Background

The initiation of end of life care in an acute stroke context should be focused on those patients and families with greatest need. This requires clinicians to synthesise information on prognosis, patterns (trajectories) of dying and patient and family preferences. Within acute stroke, prognostic models are available to identify risks of dying, but variability in dying trajectories makes it difficult for clinicians to know when to commence palliative interventions. This study aims to investigate clinicians’ use of different types of evidence in decisions to initiate end of life care within trajectories typical of the acute stroke population.

Methods/design

This two-phase, mixed methods study comprises investigation of dying trajectories in acute stroke (Phase 1), and the use of clinical scenarios to investigate clinical decision-making in the initiation of palliative care (Phase 2). It will be conducted in four acute stroke services in North Wales and North West England. Patient and public involvement is integral to this research, with service users involved at each stage.

Discussion

This study will be the first to examine whether patterns of dying reported in other diagnostic groups are transferable to acute stroke care. The strengths and limitations of the study will be considered. This research will produce comprehensive understanding of the nature of clinical decision-making around end of life care in an acute stroke context, which in turn will inform the development of interventions to further build staff knowledge, skills and confidence in this challenging aspect of acute stroke care.

     

Moderate acute exercise (70% VO2 peak) induces TGF‐β, α‐amylase and IgA in saliva during recovery

Strenuous exercise promotes changes in salivary IgA and can be associated with a high incidence of upper respiratory tract Infections. However, moderate exercise enhances immune function. The effect of exercise on salivary IgA has been well studied, but its effect on other immunological parameters is poorly studied. Thus, this study determined the effect of moderate acute exercise on immunological salivary parameters, such as the levels of cytokines (TGF‐β and IL‐5), IgA, α‐amylase and total protein, over 24 h. Ten male adult subjects exercised for 60 min at an intensity of 70% VO₂ peak. Saliva samples were collected before (‘basal’) and 0, 12 and 24 h after an exercise session. The total salivary protein was lower after 12 and 24 h than immediately after exercise, whereas α‐amylase increased at 12 and 24 h after exercise compared with basal levels. The IgA concentration was increased at 24 h after exercise relative to immediately after exercise, and there was no difference in the IL‐5 while TGF‐β concentration increased in recovery. In conclusion, 70% VO₂ peak exercise does not induce changes immediately after exercise, but after 24 h, it produces an increase in salivary TGF‐β without changing IL‐5.     

Resting-state connectivity and network parameter analysis in alcohol-dependent males. A simultaneous EEG-MEG study

There is supporting evidence of alcohol negative effects on the brain: neuroimaging and psychophysiological studies finding anatomical and functional connectivity (FC) changes associated with the dependence process. Thus, the aim of this work was to evaluate brain FC and network characteristics of alcohol-dependent individuals in resting state. For this study, we included males diagnosed with alcohol dependence (N = 25) and a group of healthy individuals (N = 23). Simultaneous EEG-MEG (electroencephalographic and magnetoencephalographic) activity was recorded in 5 min of eyes-closed resting state. EEG-MEG activity was preprocessed and FC was computed through the leakage-corrected version of phase locking value (ciPLV). Additionally, local (degree, efficiency, clustering) and global (efficiency, characteristic path length) network parameters were computed. Connectivity analysis showed an increase in phase-lagged synchronization, mainly between frontal and frontotemporal regions, in high beta band, and a decrease in interhemispheric gamma, for alcohol-dependent individuals. Network analysis revealed intergroup differences at the local level for high beta, indicating higher degree, clustering, and efficiency, mostly at frontal nodes, together with a decrease in these measures at more posterior sites for patients’ group. The hyper-synchronization in beta, next to the hypo-synchronization in gamma, could indicate an alteration in communication between hemispheres, but also a possible functional compensation mechanism in neural circuits. This could be also supported by network characteristic data, where local alterations in communication are observed.     

Endovascular treatment of a Superior Mesenteric Artery Syndrome variant secondary to traumatic pseudoaneurysm

Pseudoaneurysms related to the superior mesenteric artery (SMA) are a recognised complication of trauma to the vessel, and successful treatment with stenting has been previously described. We report the case of a patient who presented with obstruction of the fourth part of the duodenum secondary to a traumatic pseudoaneurysm, a hitherto unreported variant of superior mesenteric artery syndrome. Exclusion of the pseudoaneurysm and relief of the duodenal obstruction were simultaneously achieved by placement of a covered stent.     

Factors predictive of response and survival in patients with metastatic colorectal cancer in Taiwan

5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.