- Carbamazepine-induced suppression of repetitive firing in CA1 pyramidal neurons is greater in the dorsal hippocampus than the ventral hippocampus. [Journal Article]
- EREpilepsy Res 2018 Jun 09; 145:63-72
- Medial temporal lobe epilepsy (mTLE)-the most common form of focal epilepsy-is defined by recurrent partial seizures originating within the medial temporal lobe. Such seizures are commonly associated...
Medial temporal lobe epilepsy (mTLE)-the most common form of focal epilepsy-is defined by recurrent partial seizures originating within the medial temporal lobe. Such seizures are commonly associated with the anterior hippocampus (as opposed to the posterior hippocampus), and refractory to the currently available anti-epileptic drugs (AED) for about one third of patients. Unfortunately, the mechanisms driving seizure generation and AED efficacy along the longitudinal hippocampal axis remain poorly understood. Recently, several groups investigating differences in excitability along the rodent longitudinal hippocampal axis have demonstrated that CA1 pyramidal neurons from the rodent ventral hippocampus (the rodent homolog of the human anterior hippocampus) are intrinsically more excitable than their dorsal counterparts (the rodent homolog of the human posterior hippocampus). This phenotypic difference is accompanied by significant differences in gene expression along the longitudinal hippocampal axis, which include gene products-such as voltage-gated sodium channel β-subunits-known to influence AED efficacy. Given this phenotypic heterogeneity, and the differential expression of gene products known to influence anti-epileptic drug efficacy, we sought to investigate the efficacy of the classical use-dependent sodium channel blocker, carbamazepine, in CA1 pyramidal neurons across the longitudinal hippocampal axis. Accordingly, we performed whole-cell current-clamp recordings on CA1 pyramidal neurons from acute hippocampal slices prepared from the dorsal and ventral hippocampus, and found that acute exposure to 100 μM carbamazepine induced a significantly greater suppression of repetitive firing for dorsal neurons relative to ventral neurons by inducing profound spike frequency adaptation (SFA). Moreover, we observed a small, but significant depolarization of resting membrane potential (RMP) for dorsal neurons (but not ventral neurons), following exposure to carbamazepine. Together, these observations demonstrate that carbamazepine's effect is concentrated in the dorsal hippocampus, which could provide meaningful insight into the side effect profile of carbamazepine (and related anti-epileptic drugs) in non-epileptic tissue, and inform future work investigating the mechanisms of carbamazepine resistance in epileptic tissue.
- Shedding light on the association between repetitive negative thinking and deficits in cognitive control - A meta-analysis. [Review]
- CPClin Psychol Rev 2018 Jun 11; 63:56-65
- Individuals who experience recurrent negative thoughts are at elevated risk for mood and anxiety disorders. It is thus essential to understand why some individuals get stuck in recurrent negative thi...
Individuals who experience recurrent negative thoughts are at elevated risk for mood and anxiety disorders. It is thus essential to understand why some individuals get stuck in recurrent negative thinking (RNT), whereas others are able to disengage eventually. Theoretical models propose that individuals high in recurrent negative thinking suffer from deficits in controlling the contents of working memory. Empirical findings, however, are inconclusive. In this meta-analysis, we synthesize findings from 94 studies to examine the proposed association between RNT and deficits in cognitive control. We included numerous effect sizes not reported in the primary publications. Moderator analyses tested the influence of variables, such as stimuli valence, cognitive control function (e.g., shifting, discarding), or type of RNT (i.e., rumination or worry). Results demonstrated an association between repetitive negative thinking and deficits in only one specific cognitive control function, namely difficulty discarding no longer relevant material from working memory (r = -0.20). This association remained significant after controlling for level of psychopathology. There was no substantial association between RNT and deficits in any other cognitive control function. All other moderators were not significant. We discuss limitations (e.g., primary sample sizes, reliability of paradigms) and highlight implications for future research and clinical interventions.
- Spontaneous and iatrogenic preterm birth rates among unselected women in three consecutive pregnancies. [Journal Article]
- EJEur J Obstet Gynecol Reprod Biol 2018 Jun 11; 228:92-97
- CONCLUSIONS: We studied a population with three subsequent singleton deliveries within 10 year. The incidence of PTB decreased with 50% from the 1st to the 2nd pregnancy, to then stay relative stable in the 3rd pregnancy. Compared to PTB in the 1st pregnancy, PTB in the 2nd pregnancy is more predictive for the occurrence of PTB in the 3rd pregnancy.
- Deficiency of adenosine deaminase 2; special focus on central nervous system imaging. [Journal Article]
- JNJ Neuroradiol 2018 Jun 15
- CONCLUSIONS: DADA2 should be included in the differential diagnosis of young patients presenting with ischemic and/or hemorrhagic lesions located in the brain stem and deep gray matter, especially if they have a family history or additional systemic abnormalities.
- Risk factors for recurrent neurotrauma: a population-based study in Southeastern Michigan. [Journal Article]
- BIBrain Inj 2018 Jun 18; :1-4
- CONCLUSIONS: This study validated the hypothesis that comorbid psychiatric conditions are a significant risk factor for recurrent neurotrauma and validate prior studies showing gender and race as significant risk factors.
- Human demographic history has amplified the effects of background selection across the genome. [Journal Article]
- PGPLoS Genet 2018 Jun 18; 14(6):e1007387
- Natural populations often grow, shrink, and migrate over time. Such demographic processes can affect genome-wide levels of genetic diversity. Additionally, genetic variation in functional regions of ...
Natural populations often grow, shrink, and migrate over time. Such demographic processes can affect genome-wide levels of genetic diversity. Additionally, genetic variation in functional regions of the genome can be altered by natural selection, which drives adaptive mutations to higher frequencies or purges deleterious ones. Such selective processes affect not only the sites directly under selection but also nearby neutral variation through genetic linkage via processes referred to as genetic hitchhiking in the context of positive selection and background selection (BGS) in the context of purifying selection. While there is extensive literature examining the consequences of selection at linked sites at demographic equilibrium, less is known about how non-equilibrium demographic processes influence the effects of hitchhiking and BGS. Utilizing a global sample of human whole-genome sequences from the Thousand Genomes Project and extensive simulations, we investigate how non-equilibrium demographic processes magnify and dampen the consequences of selection at linked sites across the human genome. When binning the genome by inferred strength of BGS, we observe that, compared to Africans, non-African populations have experienced larger proportional decreases in neutral genetic diversity in strong BGS regions. We replicate these findings in admixed populations by showing that non-African ancestral components of the genome have also been affected more severely in these regions. We attribute these differences to the strong, sustained/recurrent population bottlenecks that non-Africans experienced as they migrated out of Africa and throughout the globe. Furthermore, we observe a strong correlation between FST and the inferred strength of BGS, suggesting a stronger rate of genetic drift. Forward simulations of human demographic history with a model of BGS support these observations. Our results show that non-equilibrium demography significantly alters the consequences of selection at linked sites and support the need for more work investigating the dynamic process of multiple evolutionary forces operating in concert.
- Birth Month and Course of Recurrent Depressive Disorders in a Polish Population. [Journal Article]
- MSMed Sci Monit 2018 Jun 18; 24:4169-4174
- CONCLUSIONS: The results obtained indicate that birth month may be significantly associated with the course of recurrent depressive disorders. In patients from Central Europe, the first trimester of pregnancy falling in autumn and winter seems to be significant. These results need to be interpreted with caution due to the small size of the examined group.
- Adverse Events and Reinterventions Following Pancreatic Endoscopic Sphincterotomy. [Journal Article]
- PPancreas 2018 Jun 16
- CONCLUSIONS: The likelihood of reintervention after PES is high, particularly when the primary indication is suspected sphincter pathology such as idiopathic recurrent acute pancreatitis. Further prospective studies are needed to clarify if and when this maneuver confers significant benefit to patients.
- Impact of serum lipoprotein(a) on endothelium-dependent coronary vasomotor response assessed by intracoronary acetylcholine provocation. [Journal Article]
- CACoron Artery Dis 2018 Jun 16
- CONCLUSIONS: In our study, there was no relationship between the elevated Lp(a) level and the vasospastic response to the intracoronary ACh provocation test; however, higher Lp(a) levels were associated with poor clinical outcomes up to 5 years.
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- Role of Cholecystectomy After Endoscopic Sphincterotomy in the Management of Choledocholithiasis in High-risk Patients: A Systematic Review and Meta-Analysis. [Journal Article]
- JCJ Clin Gastroenterol 2018 Jun 16
- CONCLUSIONS: Although we found no difference in mortality between the 2 strategies after ES, laparoscopic cholecystectomy should be recommended as it is associated with lower rates of subsequent recurrent cholecystitis, cholangitis, and biliary colic down the road even in high-risk surgical patients.