Multiple Single-Unit Long-Term Tracking on Organotypic Hippocampal Slices Using High-Density Microelectrode Arrays

A novel system to cultivate and record from organotypic brain slices directly on high-density microelectrode arrays (HD-MEA) was developed. This system allows for continuous recording of electrical activity of specific individual neurons at high spatial resolution while monitoring at the same time, neuronal network activity. For the first time, the electrical activity patterns of single neurons and the corresponding neuronal network in an organotypic hippocampal slice culture were studied during several consecutive weeks at daily intervals. An unsupervised iterative spike-sorting algorithm, based on PCA and k-means clustering, was developed to assign the activities to the single units. Spike-triggered average extracellular waveforms of an action potential recorded across neighboring electrodes, termed ‘footprints’ of single-units were generated and tracked over weeks. The developed system offers the potential to study chronic impacts of drugs or genetic modifications on individual neurons in slice preparations over extended times

Dissipation of angular momentum in light heavy ion collision

The inclusive energy distributions of fragments (4$\leq$Z$\leq$7) emitted in the reactions $^{16}$O (116 MeV) + $^{27}$Al, $^{28}$Si, $^{20}$Ne (145 MeV) + $^{27}$Al, $^{59}$Co have been measured in the angular range $\theta_{lab}$= 10$^\circ$ - 65$^\circ$. Fusion-fission and deep inelastic components of the fragment emission have been extracted from the experimental data. The angular mometum dissipations in fully damped deep inelastic collisions have been estimated assming exit channel configuration similar to those for fusion-fission process. It has been found that, the angular momentum dissipations are more than those predicted by the empirical sticking limit in all cases. The deviation is found to increase with increasing charge transfer (lighter fragments). Qualitatively, this may be due to stronger friction in the exit channel. Moreover, for the heavier system $^{20}$Ne + $^{59}$Co, the overall magnitude of deviation is less as compared to those for the lighter systems, {\it i.e.}, $^{16}$O + $^{27}$Al, $^{28}$Si, $^{20}$Ne + $^{27}$Al. This may be due to lesser overlap in time scales of fusion and deep inelastic time scales for heavier systems.Comment: 15 pages, 9 figures, accepted for publication in Phys. Rev.

Searching for plasticity in dissociated cortical cultures on multi-electrode arrays

We attempted to induce functional plasticity in dense cultures of cortical cells using stimulation through extracellular electrodes embedded in the culture dish substrate (multi-electrode arrays, or MEAs). We looked for plasticity expressed in changes in spontaneous burst patterns, and in array-wide response patterns to electrical stimuli, following several induction protocols related to those used in the literature, as well as some novel ones. Experiments were performed with spontaneous culture-wide bursting suppressed by either distributed electrical stimulation or by elevated extracellular magnesium concentrations as well as with spontaneous bursting untreated. Changes concomitant with induction were no larger in magnitude than changes that occurred spontaneously, except in one novel protocol in which spontaneous bursts were quieted using distributed electrical stimulation

Targeted deep sequencing of mucinous ovarian tumors reveals multiple overlapping RAS-pathway activating mutations in borderline and cancerous neoplasms

Background: Mucinous ovarian tumors represent a distinct histotype of epithelial ovarian cancer. The rarest (2-4 % of ovarian carcinomas) of the five major histotypes, their genomic landscape remains poorly described. We undertook hotspot sequencing of 50 genes commonly mutated in human cancer across 69 mucinous ovarian tumors. Our goals were to establish the overall frequency of cancer-hotspot mutations across a large cohort, especially those tumors previously thought to be “RAS-pathway alteration negative”, using highly-sensitive next-generation sequencing as well as further explore a small number of cases with apparent heterogeneity in RAS-pathway activating alterations. Methods: Using the Ion Torrent PGM platform, we performed next generation sequencing analysis using the v2 Cancer Hotspot Panel. Regions of disparate ERBB2-amplification status were sequenced independently for two mucinous carcinoma (MC) cases, previously established as showing ERBB2 amplification/overexpression heterogeneity, to assess the hypothesis of subclonal populations containing either KRAS mutation or ERBB2 amplification independently or simultaneously. Results: We detected mutations in KRAS, TP53, CDKN2A, PIK3CA, PTEN, BRAF, FGFR2, STK11, CTNNB1, SRC, SMAD4, GNA11 and ERBB2. KRAS mutations remain the most frequently observed alteration among MC (64.9 %) and mucinous borderline tumors (MBOT) (92.3 %). TP53 mutation occurred more frequently in carcinomas than borderline tumors (56.8 % and 11.5 %, respectively), and combined IHC and mutation data suggest alterations occur in approximately 68 % of MC and as many as 20 % of MBOT. Proven and potential RAS-pathway activating changes were observed in all but one MC. Concurrent ERBB2 amplification and KRAS mutation were observed in a substantial number of cases (7/63 total), as was co-occurrence of KRAS and BRAF mutations (one case). Microdissection of ERBB2-amplified regions of tumors harboring KRAS mutation suggests these alterations are occurring in the same cell populations, while consistency of KRAS allelic frequency in both ERBB2 amplified and non-amplified regions suggests this mutation occurred in advance of the amplification event. Conclusions: Overall, the prevalence of RAS-alteration and striking co-occurrence of pathway “double-hits” supports a critical role for tumor progression in this ovarian malignancy. Given the spectrum of RAS-activating mutations, it is clear that targeting this pathway may be a viable therapeutic option for patients with recurrent or advanced stage mucinous ovarian carcinoma, however caution should be exercised in selecting one or more personalized therapeutics given the frequency of non-redundant RAS-activating alterations

Psychophysiological responses underlying unresolved loss and trauma in the Adult Attachment Interview

Unresolved loss/trauma in the context of the Adult Attachment Interview (AAI) has been theorised to result from dissociative processing of fear-related memories and ideas. To examine the plausibility of this model, this study tested hypothesised associations between unresolved loss/trauma and indicators of autonomic nervous system (ANS) reactivity. First-time pregnant women (N = 235) participated in the AAI while heart rate (interbeat interval; IBI) and indicators of parasympathetic reactivity (respiratory sinus arrhythmia; RSA) and sympathetic reactivity (pre-ejection period; PEP, skin conductance level; SCL) were recorded. Using multilevel modelling, ANS reactivity was examined in relation to topic (loss/trauma versus other questions); discussion of actual loss/trauma; classification of unresolved/disorganised; and unresolved responses during the interview. Responses to loss/trauma questions and discussion of loss were associated with respectively larger and smaller IBIs. There was no moderation by unresolved/disorganised status. Unresolved responses about loss were associated with smaller IBIs. Participants classified as unresolved/disorganised showed decreasing PEP and blunted SCL throughout the whole interview. The findings suggest that unresolved speech about loss co-occurs with physiological arousal, although the inconclusive findings regarding parasympathetic and sympathetic nervous system responses fail to clearly support the role of fear

Effect of long-term physical activity and acute exercise on markers of systemic inflammation in persons with chronic spinal cord injury: a systematic review

Objective: To evaluate the effect of long-term physical activity (PA) and acute exercise on markers of systemic inflammation in persons with chronic spinal cord injury (SCI)

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study

Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects