关键词： adolescence   amygdala   chronic pain   hippocampus   mRNA   prefrontal cortex   telomere length  

摘要： All children experience pain, and although many recover quickly, some go on to develop chronic pain. Adolescent chronic pain is a growing epidemic. It is unknown why some adolescents recover without incident and others experience persistent pain. Although unexplored, early life adversity may contribute to the development and maintenance of chronic pain. This study investigated the effects and underlying neurobiological mechanisms of an early life stressor on nociceptive (pain) sensitivity and emotional function in male and female Sprague-Dawley rats. Using maternal separation (MS) as an established model of early life stress, we addressed two aims: investigation of the effects of MS on behavior (anxiety and pain sensitivity), and investigation of the effects of MS on mRNA and pathophysiological changes associated with an acutely painful stimulus. Our results indicate that MS increased anxiety-like behavior and altered nociceptive responsivity in adolescent rats, with decreased mechanical withdrawal thresholds indicative of heightened and prolonged pain-related behavior. The MS groups also demonstrated increased expression of genes involved in regulating the stress and fight-or-flight response, mood, and neuroplasticity;as well as increased levels of inflammatory markers. We conclude that nociception, both at the behavioral and molecular level, is altered in response to the MS stressor.

关键词： Perfusion   Early neurological deterioration   Reperfusion therapy   Imaging  

摘要： Early neurological deterioration (END) after thrombolysis occurs in 10% acute ischemic stroke (AIS) patients, and its mechanism remains unclear in majority of cases, named as unexplained END. We tested the hypothesis that penumbra/infarct growth beyond the initial penumbra might be the cause of unexplained END. We reviewed the database of AIS patients who received reperfusion therapy. Unexplained END was defined as >= 2-point increase of NIHSS from baseline to 24 h, without straightforward causes. For each unexplained END patient, we extracted 2 matched controls based on 4 clinical and radiological characteristics which were strongly associated with unexplained END. We defined extra-penumbra and extra-infarct as penumbra and infarct growth at 24 h beyond baseline penumbral tissue and then investigated the relationship between extra-penumbra and extra-infarct and the presence of unexplained END. Finally, 44 unexplained END patients and 88 matched controls were included. The volume of both extra-infarct (OR, 1.032 per 1-mL increase;p = 0.018) and extra-penumbra (OR, 1.070 per 1-mL increase;p < 0.001) were associated with the presence of unexplained END, while the absence of recanalization was associated with the presence of either extra-infarct or extra-penumbra (OR, 3.291;p = 0.001). Moreover, 51.4% cases with extra-penumbra at 24 h finally progressed to infarct at 7 days, and they underwent higher increase of NIHSS from 24 h to 7 days than those that did not progress to infarct at 7 days (4.0 vs 1.0;p = 0.017). Penumbra/infarct growth beyond the initial penumbra is involved in the unexplained END in AIS patients receiving reperfusion therapy.

关键词： Schizophrenia   First-degree unaffected relatives   Remission   Neurological soft signs   Cognitive function   Composite endophenotype  

摘要： Neurological soft signs (NSS) and neurocognitive deficits (ND) are highly prevalent in schizophrenia, and have been separately proposed as candidate endophenotypes of schizophrenia. However, few relevant studies focus on remitted patients with schizophrenia (RP) and integrate NSS and ND as a composite endophenotype. This study aimed to explore the NSS and ND and examine the comparative relationship between them in RP, their first-degree unaffected relatives (FDR), and healthy controls, furthermore, to seek potential endophenotypes subitems of NSS and ND and create a composite endophenotype. 86 RP, 86 FDR, and 86 healthy controls were included. NSS and ND were independently assessed with Cambridge Neurological Inventory and MATRICS (TM) Consensus Cognitive Battery. RP had more NSS and ND than FDR in all subitems except disinhibition, information processing speed, working memory, and visual memory. Similarly, FDR presented poorer performance than controls in all subscales except disinhibition, sensory integration, working memory, and visual memory. Six subitems of NSS and ND met the criteria of endophenotype and the three groups were most accurately classified (71.2%) with these subitems working as a composite endophenotype. Moreover, information processing speed, attention, and social cognition were associated with sensory integration in RP and FDR. These findings add evidences that certain subitems of NSS and ND might be the endophenotypes of schizophrenia and integrating these endophenotypes may prove useful in identifying schizophrenia and high-risk individuals. Furthermore, sensory integration and specific cognitive domains covary, hence suggesting an overlap of compromised underlying neural systems.

关键词： Out of hospital cardiac arrest   Intraosseous access   Registry   Outcome   Practices assessment   Medical device  

摘要： Purpose To compare intraosseous access with peripheral venous access on adults out-of-hospital cardiac arrest (OHCA) patients' clinical outcomes. Methods A national retrospective multicentre study was conducted based on the French National Cardiac Arrest Registry. Comparison of patients (intraosseous vs. peripheral venous access) was conducted before and after a matching using a propensity score. The propensity score included confounding factors: age, time between the call (T0) to epinephrine (to take account of how quickly vascular access was achieved), the aetiology of OHCA, the shock and the patient initial rhythm at MMT arrival. Results A total of 1576 patients received intraosseous access, and 27,280 received peripheral intravenous access. Before matching, OHCA patients with intraosseous access were less likely to survive at all stages (return of spontaneous circulation (ROSC), 0-day survival and 30-day survival). No significant difference in neurological outcome was observed. After propensity score matching, no significant differences in 30-day survival rates (OR = 0.763 [0.473;1.231]) and neurological outcome (OR = 1.296 [0.973;1.726]) were observed. However, intraosseous patients still showed lower likelihood of short-term survival (ROSC and 0-day survival) even after propensity score matching was implemented. Conclusion The populations we investigated were similar to those of other studies suggesting that intraosseous access is associated with reduced survival and poorer neurological outcome. Our findings suggest that intraosseous access is a comparably effective alternative to peripheral intravenous access for treating OHCA patients on matched populations.

关键词： Major depressive disorder   Insomnia   Neurobiological   Heart rate variability   Sleep stage  

摘要： It remains unclear whether neurobiological dysfunction observed in major depressive disorder (MDD) and insomnia is an expression of common or independent bases. The present investigation sought to explore differences in heart rate variability (HRV)-a widely utilized biomarker of neurobiological functioning-among individuals with MDD, insomnia, and healthy controls, while awake and during distinct sleep stages (REM, N2), with the goal of improving our understanding of shared neurobiological factors in depression and insomnia. Participants were 73 adults who underwent home polysomnography. All N2 and REM sleep epochs with a duration greater than or equal to 5 min were identified for HRV analysis. Additionally, a single waking epoch was defined for each participant. From waking to N2 sleep, and waking to REM sleep, changes in HRV indices indicated participants experienced reductions in sympathetic arousal and increases in parasympathetic arousal. Contrary to hypotheses, however, no between group differences were observed in HRV. Though the present findings do not support the hypotheses of a shard neurobiological pathway between MDD and insomnia, more work is warranted to advance our understanding of the neurobiological bases of these common, debilitating, and frequently co-occurring psychiatric conditions, to improve early detection and identify novel intervention targets for these disorders.

关键词： Brain metastasis   Neurological death   Radiosurgery   Non-small cell lung cancer  

摘要： The role of radiosurgery has become further accentuated in the era of targeted agents (TA). Thus, the neurologic outcome of radiosurgery in brain metastasis (BM) of non-small cell lung cancer (NSCLC) was reviewed. We analyzed 135 patients with BM of NSCLC who were administered Cyberknife radiosurgery (CKRS) as either initial or salvage therapy. We evaluated local failure (LF), intracranial failure (IF), and neurological death (ND) due to BM. Primary outcome was neurological death-free survival (NDFS). Median follow-up was 16.2 months. Median CKRS dose of 22 Gy was administered to median 2 targets per patient. Among 99 deaths, 14 (14%) were ND. Upfront treatment for BM included CKRS alone in 85 patients (63%), CKRS + TA in 26 patients (19%), and WBRT in 24 patients (18%). No patients or tumor related factors were associated with ND. However, the type of upfront treatment for BM was significantly associated with ND [HR 0.07 (95% CI 0.01-0.57) for CKRS + TA, HR 0.56 (95% CI 0.19-1.68) for CKRS alone] compared with the WBRT group (P = 0.01). The 2-year NDFS rates for the CKRS + TA, CRKS alone, and WBRT groups were 94%, 87%, and 78%, respectively (P = 0.03). Upfront CKRS showed significantly higher 2-year LF-free survival rate (P < 0.01). IF rate was insignificantly lower in the WBRT group compared with CKRS group (P = 0.38). Upfront CKRS + TA was associated with the best neurological outcome with high NDFS. Active brain control by early delivery of radiosurgery could achieve better neurological outcome in NSCLC with BM.

关键词： Paroxysmal neurological disorder   Migraine   Ataxia   Kinesigenic  

摘要： Emerging data have established links between paroxysmal neurological disorders or psychiatric disorder, such as migraine, ataxia, movement disorders and epilepsy. Common gene signatures such as expression, protein interaction and the associated signalling pathways link genes in these associated disorders, with the object to predict unknown disease or risk genes. In this study, we used gene interaction networks to investigate common gene signatures associated with the above phenotypes. In total, 19 candidate genes were used for making an interaction network which further revealed 39 associated genes (including KCNA1, SCN2A, CACNA1A, KCNM4, KCNO3, SCN1B and CACNB4) implicated in paroxysmal neurological disorders development and progression. The meta-regression analysis showed the strongest association of SCN2A with genes involved in schizophrenia and neurodevelopmental disorders. Importantly, our analysis showed KCNMA1 as a common gene signature with a link to epilepsy, movement disorders and wide paroxysmal neurological presentations-with the greatest potential risk of being a disease gene in a paroxysmal or psychiatric disorder. Further gene interaction analysis is required to identify unidentified gene interactions which may be targets for future drugs development.

摘要： Brain Awareness Week is the global campaign to foster public enthusiasm and support for brain science. Every March, “partners host imaginative activities in their communities that share the wonders of the brain and the impact brain science has on our everyday lives”.