The impact of diffusion on receptor binding during synaptic transmission.

Despite the importance of speed in synaptic transmission, in many synapses, neurotransmitters bind to their receptors at rates that appear to be slower than the diffusion limit. This assessment is generally based on a comparison with the Smoluchowski limit rather than an independent experimental analysis. In many synapses, miniature excitatory postsynaptic currents (mEPSCs) are controlled by the interplay between binding to receptors and diffusion of the neurotransmitter out of the synaptic cleft. A model for mEPSCs that incorporates these features was used to evaluate published data showing that elevated viscosity increases mEPSC amplitude. With diffusion-limited binding, the model predicts that raising the viscosity will decrease the amplitude rather than increase it. Diffusion-independent binding predicts an increase that is larger than that observed. To explore the intermediate behavior between the diffusion-limited and diffusion-independent extremes, a general expression for intermolecular rates was used that depends on both collision frequency and intrinsic reactivity. This analysis yielded an estimate for collision frequency that is about an order of magnitude above the measured rate of association and an order of magnitude below the Smoluchowski limit.

Somatostatin modulation of initial fusion pores in Ca2+-triggered exocytosis from mouse chromaffin cells.

Somatostatin, a peptide hormone that activates G-protein-coupled receptors, inhibits the secretion of many hormones. This study investigated the mechanisms of this inhibition using amperometry recording of Ca2+-triggered catecholamine secretion from mouse chromaffin cells. Two distinct stimulation protocols, high-KCl depolarization and caffeine, were used to trigger exocytosis, and confocal fluorescence imaging was used to monitor the rise in intracellular free Ca2+. Analysis of single-vesicle fusion events (spikes) resolved the action of somatostatin on fusion pores at different stages. Somatostatin reduced spike frequency, and this reduction was accompanied by prolongation of pre-spike feet and slowing of spike rise times. This indicates that somatostatin stabilizes initial fusion pores and slows their expansion. This action on the initial fusion pore impacted the release mode to favour kiss-and-run over full-fusion. During a spike the permeability of a fusion pore peaks, declines and then settles into a plateau. Somatostatin had no effect on the plateau, suggesting no influence on late-stage fusion pores. These actions of somatostatin were indistinguishable between exocytosis triggered by high-KCl and caffeine, and fluorescence imaging showed that somatostatin had no effect on stimulus-induced rises in cytosolic Ca2+. Our findings thus demonstrate that the signalling cascades activated by somatostatin target the exocytotic machinery that controls the initial and expanding stages of fusion pores, while having no effect on late-stage fusion pores. As a result of its stronger inhibition of full-fusion compared to kiss-and-run, somatostatin will preferentially inhibit the secretion of large peptides over the secretion of small catecholamines. KEY POINTS: Somatostatin inhibits the secretion of various hormones by activating G-protein-coupled receptors. In this study, we used amperometry to investigate the mechanism by which somatostatin inhibits catecholamine release from mouse chromaffin cells. Somatostatin increased pre-spike foot lifetime and slowed fusion pore expansion. Somatostatin inhibited full-fusion more strongly than kiss-and-run. Our results suggest that the initial fusion pore is the target of somatostatin-mediated regulation of hormone release. The stronger inhibition of full-fusion by somatostatin will result in preferential inhibition of peptide release.

Predicting Dental General Anesthesia Use among Children with Behavioral Health Conditions.

OBJECTIVES: To evaluate how different data sources affect the performance of machine learning algorithms that predict dental general anesthesia use among children with behavioral health conditions. STUDY DESIGN: Observational study using claims data. METHODS: Using Medicaid claims from Partners For Kids (2013-2019), electronic medical record data, and the Ohio Child Opportunity Index, we conducted a retrospective cohort study of 12,410 children with behavioral health diagnoses. Four lasso-regularized logistic regression models were developed to predict dental general anesthesia use, each incorporating different data sources. Lift scores, or the ratio of positive predictive value to base case prevalence, were used to compare models, and a lift score of 2.5 was considered minimally acceptable for risk prediction. RESULTS: Dental general anesthesia use ranged from 3.2% to 3.9% across models, which made it difficult for the machine learning models to achieve high positive predictive value. Model performance was best when either the electronic medical record (lift = 2.59) or Ohio Child Opportunity Index (lift = 2.56), but not both (lift = 2.34) or neither (lift = 1.87), was used. CONCLUSIONS: Incorporating additional data sources improved machine learning model performance, and 2 models achieved satisfactory performance. The model using electronic medical record data could be applied in hospital-based settings, and the model using the Ohio Child Opportunity Index could be more valuable in community-based settings. KNOWLEDGE TRANSFER STATEMENT: Machine learning was applied to satisfactorily predict which children with behavioral health diagnoses would require dental treatment under general anesthesia. Incorporating electronic medical record data or area-level social determinants of health data, but not both, improved the performance of the machine learning predictions. The 2 highest performing models could be applied by hospitals using medical record data or by organizations using area-level social determinants of health data to risk stratify the pediatric behavioral health population.

Inter and intralaminar excitation of parvalbumin interneurons in mouse barrel cortex.

Parvalbumin (PV) interneurons are inhibitory fast-spiking cells with essential roles in directing the flow of information through cortical circuits. These neurons set the balance between excitation and inhibition and control rhythmic activity. PV interneurons differ between cortical layers in their morphology, circuitry, and function, but how their electrophysiological properties vary has received little attention. Here we investigate responses of PV interneurons in different layers of primary somatosensory barrel cortex (BC) to different excitatory inputs. With the genetically-encoded hybrid voltage sensor, hVOS, we recorded voltage changes in many L2/3 and L4 PV interneurons simultaneously, with stimulation applied to either L2/3 or L4. A semi-automated procedure was developed to identify small regions of interest corresponding to single responsive PV interneurons. Amplitude, half-width, and rise-time were greater for PV interneurons residing in L2/3 compared to L4. Stimulation in L2/3 elicited responses in both L2/3 and L4 with longer latency compared to stimulation in L4. These differences in latency between layers could influence their windows for temporal integration. Thus, PV interneurons in different cortical layers of BC respond in a layer specific and input specific manner, and these differences have potential roles in cortical computations.

Fusion pore flux controls the rise-times of quantal synaptic responses.

The release of neurotransmitter from a single synaptic vesicle generates a quantal response, which at excitatory synapses in voltage-clamped neurons is referred to as a miniature excitatory postsynaptic current (mEPSC). We analyzed mEPSCs in cultured mouse hippocampal neurons and in HEK cells expressing postsynaptic proteins enabling them to receive synaptic inputs from cocultured neurons. mEPSC amplitudes and rise-times varied widely within and between cells. In neurons, mEPSCs with larger amplitudes had longer rise-times, and this correlation was stronger in neurons with longer mean rise-times. In HEK cells, this correlation was weak and unclear. Standard mechanisms thought to govern mEPSCs cannot account for these results. We therefore developed models to simulate mEPSCs and assess their dependence on different factors. Modeling indicated that longer diffusion times for transmitters released by larger vesicles to reach more distal receptors cannot account for the correlation between rise-time and amplitude. By contrast, incorporating the vesicle size dependence of fusion pore expulsion time recapitulated experimental results well. Larger vesicles produce mEPSCs with larger amplitudes and also take more time to lose their content. Thus, fusion pore flux directly contributes to mEPSC rise-time. Variations in fusion pores account for differences among neurons, between neurons and HEK cells, and the correlation between rise-time and the slope of rise-time versus amplitude plots. Plots of mEPSC amplitude versus rise-time are sensitive to otherwise inaccessible properties of a synapse and offer investigators a means of assessing the role of fusion pores in synaptic release.

Intrinsic and Synaptic Contributions to Repetitive Spiking in Dentate Granule Cells.

Repetitive firing of granule cells (GCs) in the dentate gyrus (DG) facilitates synaptic transmission to the CA3 region. This facilitation can gate and amplify the flow of information through the hippocampus. High-frequency bursts in the DG are linked to behavior and plasticity, but GCs do not readily burst. Under normal conditions, a single shock to the perforant path in a hippocampal slice typically drives a GC to fire a single spike, and only occasionally more than one spike is seen. Repetitive spiking in GCs is not robust, and the mechanisms are poorly understood. Here, we used a hybrid genetically encoded voltage sensor to image voltage changes evoked by cortical inputs in many mature GCs simultaneously in hippocampal slices from male and female mice. This enabled us to study relatively infrequent double and triple spikes. We found GCs are relatively homogeneous and their double spiking behavior is cell autonomous. Blockade of GABA type A receptors increased multiple spikes and prolonged the interspike interval, indicating inhibitory interneurons limit repetitive spiking and set the time window for successive spikes. Inhibiting synaptic glutamate release showed that recurrent excitation mediated by hilar mossy cells contributes to, but is not necessary for, multiple spiking. Blockade of T-type Ca2+ channels did not reduce multiple spiking but prolonged interspike intervals. Imaging voltage changes in different GC compartments revealed that second spikes can be initiated in either dendrites or somata. Thus, pharmacological and biophysical experiments reveal roles for both synaptic circuitry and intrinsic excitability in GC repetitive spiking.

Multi-omics for studying and understanding polar life.

Polar ecosystems are experiencing amongst the most rapid rates of regional warming on Earth. Here, we discuss 'omics' approaches to investigate polar biodiversity, including the current state of the art, future perspectives and recommendations. We propose a community road map to generate and more fully exploit multi-omics data from polar organisms. These data are needed for the comprehensive evaluation of polar biodiversity and to reveal how life evolved and adapted to permanently cold environments with extreme seasonality. We argue that concerted action is required to mitigate the impact of warming on polar ecosystems via conservation efforts, to sustainably manage these unique habitats and their ecosystem services, and for the sustainable bioprospecting of novel genes and compounds for societal gain.

Velocity of conduction between columns and layers in barrel cortex reported by parvalbumin interneurons.

Inhibitory interneurons expressing parvalbumin (PV) play critical roles throughout the brain. Their rapid spiking enables them to control circuit dynamics on a millisecond time scale, and the timing of their activation by different excitatory pathways is critical to these functions. We used a genetically encoded hybrid voltage sensor to image PV interneuron voltage changes with sub-millisecond precision in primary somatosensory barrel cortex (BC) of adult mice. Electrical stimulation evoked depolarizations with a latency that increased with distance from the stimulating electrode, allowing us to determine conduction velocity. Spread of responses between cortical layers yielded an interlaminar conduction velocity and spread within layers yielded intralaminar conduction velocities in different layers. Velocities ranged from 74 to 473 µm/ms depending on trajectory; interlaminar conduction was 71% faster than intralaminar conduction. Thus, computations within columns are more rapid than between columns. The BC integrates thalamic and intracortical input for functions such as texture discrimination and sensory tuning. Timing differences between intra- and interlaminar PV interneuron activation could impact these functions. Imaging of voltage in PV interneurons reveals differences in signaling dynamics within cortical circuitry. This approach offers a unique opportunity to investigate conduction in populations of axons based on their targeting specificity.

Inter and Intralaminar Excitation of Parvalbumin Interneurons in Mouse Barrel Cortex.

Parvalbumin (PV) interneurons are inhibitory fast-spiking cells with essential roles in directing the flow of information through cortical circuits. These neurons set the balance between excitation and inhibition, control rhythmic activity, and have been linked to disorders including autism spectrum and schizophrenia. PV interneurons differ between cortical layers in their morphology, circuitry, and function, but how their electrophysiological properties vary has received little attention. Here we investigate responses of PV interneurons in different layers of primary somatosensory barrel cortex (BC) to different excitatory inputs. With the genetically-encoded hybrid voltage sensor, hVOS, we recorded voltage changes simultaneously in many L2/3 and L4 PV interneurons to stimulation in either L2/3 or L4. Decay-times were consistent across L2/3 and L4. Amplitude, half-width, and rise-time were greater for PV interneurons residing in L2/3 compared to L4. Stimulation in L2/3 elicited responses in both L2/3 and L4 with longer latency compared to stimulation in L4. These differences in latency between layers could influence their windows for temporal integration. Thus PV interneurons in different cortical layers of BC show differences in response properties with potential roles in cortical computations.

Comparing confocal and two-photon Ca2+ imaging of thin low-scattering preparations.

Ca2+ imaging provides insight into biological processes ranging from subcellular dynamics to neural network activity. Two-photon microscopy has assumed a dominant role in Ca2+ imaging. The longer wavelength infra-red illumination undergoes less scattering, and absorption is confined to the focal plane. Two-photon imaging can thus penetrate thick tissue ∼10-fold more deeply than single-photon visible imaging to make two-photon microscopy an exceptionally powerful method for probing function in intact brain. However, two-photon excitation produces photobleaching and photodamage that increase very steeply with light intensity, limiting how strongly one can illuminate. In thin samples, illumination intensity can assume a dominant role in determining signal quality, raising the possibility that single-photon microscopy may be preferable. We therefore tested laser scanning single-photon and two-photon microscopy side by side with Ca2+ imaging in neuronal compartments at the surface of a brain slice. We optimized illumination intensity for each light source to obtain the brightest signal without photobleaching. Intracellular Ca2+ rises elicited by one action potential had twice the signal/noise ratio with confocal as with two-photon imaging in axons, were 31% higher in dendrites, and about the same in cell bodies. The superior performance of confocal imaging in finer neuronal processes likely reflects the dominance of shot noise when fluorescence is dim. Thus, when out-of-focus absorption and scattering are not issues, single-photon confocal imaging can yield better quality signals than two-photon microscopy.

Imaging Voltage Globally and in Isofrequency Lamina in Slices of Mouse Ventral Cochlear Nucleus.

The cochlear nuclei (CNs) receive sensory information from the ear and perform fundamental computations before relaying this information to higher processing centers. These computations are performed by distinct types of neurons interconnected in circuits dedicated to the specialized roles of the auditory system. In the present study, we explored the use of voltage imaging to investigate CN circuitry. We tested two approaches based on fundamentally different voltage sensing technologies. Using a voltage-sensitive dye we recorded glutamate receptor-independent signals arising predominantly from axons. The mean conduction velocity of these fibers of 0.27 m/s was rapid but in range with other unmyelinated axons. We then used a genetically-encoded hybrid voltage sensor (hVOS) to image voltage from a specific population of neurons. Probe expression was controlled using Cre recombinase linked to c-fos activation. This activity-induced gene enabled targeting of neurons that are activated when a mouse hears a pure 15-kHz tone. In CN slices from these animals auditory nerve fiber stimulation elicited a glutamate receptor-dependent depolarization in hVOS probe-labeled neurons. These cells resided within a band corresponding to an isofrequency lamina, and responded with a high degree of synchrony. In contrast to the axonal origin of voltage-sensitive dye signals, hVOS signals represent predominantly postsynaptic responses. The introduction of voltage imaging to the CN creates the opportunity to investigate auditory processing circuitry in populations of neurons targeted on the basis of their genetic identity and their roles in sensory processing.

Synaptophysin transmembrane domain III controls fusion pore dynamics in Ca2+-triggered exocytosis.

Synaptophysin (syp) is a major protein of secretory vesicles with four transmembrane domains (TMDs) and a large cytoplasmic C-terminus. Syp has been shown to regulate exocytosis, vesicle cycling, and synaptic plasticity through its C-terminus. However, the roles of its TMDs remain unclear. The TMDs of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are thought to line initial fusion pores, and structural work together with sequence analysis suggest that TMD III of syp may play a similar role. To test this hypothesis, we performed tryptophan scanning experiments of TMD III in chromaffin cells and used amperometry to evaluate fusion pores. In contrast to SNARE TMDs, tryptophan substitutions in syp TMD III had no effect on the flux through initial fusion pores. However, a number of these mutants increased the fraction of kiss-and-run events and decreased the initial fusion pore lifetime. These results indicate that TMD III stabilizes the initial fusion pore and controls the initial choice between kiss and run and full fusion. Late-stage fusion pores were not impacted by TMD III mutations. These results indicate that syp TMD III does not line the initial fusion pore. However, its impact on pore dynamics suggests that it interacts with a SNARE protein implicated as a part of the fusion pore that forms at the onset of exocytosis.

Unitary synaptic responses of parvalbumin interneurons evoked by excitatory neurons in the mouse barrel cortex.

The mammalian cortex integrates and processes information to transform sensory inputs into perceptions and motor outputs. These operations are performed by networks of excitatory and inhibitory neurons distributed through the cortical layers. Parvalbumin interneurons (PVIs) are the most abundant type of inhibitory cortical neuron. With axons projecting within and between layers, PVIs supply feedforward and feedback inhibition to control and modulate circuit function. Distinct populations of excitatory neurons recruit different PVI populations, but the specializations of these synapses are poorly understood. Here, we targeted a genetically encoded hybrid voltage sensor to PVIs and used fluorescence imaging in mouse somatosensory cortex slices to record their voltage changes. Stimulating a single visually identified excitatory neuron with small-tipped theta-glass electrodes depolarized multiple PVIs, and a common threshold suggested that stimulation elicited unitary synaptic potentials in response to a single excitatory neuron. Excitatory neurons depolarized PVIs in multiple layers, with the most residing in the layer of the stimulated neuron. Spiny stellate cells depolarized PVIs more strongly than pyramidal cells by up to 77%, suggesting a greater role for stellate cells in recruiting PVI inhibition and controlling cortical computations. Response half-width also varied between different excitatory inputs. These results demonstrate functional differences between excitatory synapses on PVIs.

Viz.ai Implementation of Stroke Augmented Intelligence and Communications Platform to Improve Indicators and Outcomes for a Comprehensive Stroke Center and Network.

BACKGROUND AND PURPOSE: Comprehensive stroke centers continually strive to narrow neurointerventional time metrics. Although process improvements have been put in place to streamline workflows, complex pathways, disparate imaging locations, and fragmented communications all highlight the need for continued improvement. MATERIALS AND METHODS: This Quality Improvement Initiative (VISIION) was implemented to assess our transition to the Viz.ai platform for immediate image review and centralized communication and their effect on key performance indicators in our comprehensive stroke center. We compared periods before and following deployment. Sequential patients having undergone stroke thrombectomy were included. Both direct arriving large-vessel occlusion and Brain Emergency Management Initiative telemedicine transfer large-vessel occlusion cases were assessed as were subgroups of OnHours and OffHours. Text messaging thread counts were compared between time periods to assess communications. Mann-Whitney U and Student t tests were used. RESULTS: Eighty-two neurointerventional cases were analyzed pre vs. post time periods: (DALVO-OnHours 7 versus 7, DALVO-OffHours 10 versus 5, BEMI-OnHours 13 versus 6, BEMI-OffHours 17 versus 17). DALVO-OffHours had a 39% door-to-groin reduction (157 versus 95 minutes, P = .009). DALVO-All showed a 32% reduction (127 versus 86 minutes, P = .006). BEMI-All improved 33% (42 versus 28 minutes, P = .036). Text messaging thread counts improved 30% (39 versus 27, P = .04). CONCLUSIONS: There was an immediate improvement following Viz.ai implementation for both direct arriving and telemedicine transfer thrombectomy cases. In the greatest opportunity subset (direct arriving large-vessel occlusion-OffHours: direct arriving cases requiring team mobilization off-hours), we noted a 39% improvement. With Viz.ai, we noted that immediate access to images and streamlined communications improved door-to-groin time metrics for thrombectomy. These results have implications for future care processes and can be a model for centers striving to optimize workflow and improve thrombectomy timeliness.

Methylation subgroup and molecular heterogeneity is a hallmark of glioblastoma: implications for biopsy targeting, classification and therapy.

BACKGROUND: Intratumoral heterogeneity at the cellular and molecular level is a hallmark of glioblastoma (GB) that contributes to treatment resistance and poor clinical outcome. Little is known regarding epigenetic heterogeneity and intratumoral phylogeny and their implication for molecular classification and targeted therapies. PATIENTS AND METHODS: Multiple tissue biopsies (238 in total) were sampled from 56 newly-diagnosed, treatment-naive GB patients from a prospective in-house cohort and publicly available data and profiled for DNA methylation using the Illumina MethylationEPIC array. Methylation-based classification using the glioma classifier developed by Ceccarelli et al. and estimation of the MGMT promoter methylation status via the MGMT-STP27 model were carried out. In addition, copy number variations (CNVs) and phylogeny were analyzed. RESULTS: Almost half of the patients (22/56, 39%) harbored tumors composed of heterogeneous methylation subtypes. We found two predominant subtype combinations: classic-/mesenchymal-like, and mesenchymal-/pilocytic astrocytoma-like. Nine patients (16%) had tumors composed of subvolumes with and without MGMT promoter methylation, whereas 20 patients (36%) were homogeneously methylated, and 27 patients (48%) were homogeneously unmethylated. CNV analysis revealed high variations in many genes, including CDKN2A/B, EGFR, and PTEN. Phylogenetic analysis correspondingly showed a general pattern of CDKN2A/B loss and gain of EGFR, PDGFRA, and CDK4 during early stages of tumor development. CONCLUSIONS: (Epi)genetic intratumoral heterogeneity is a hallmark of GB, both at DNA methylation and CNV level. This intratumoral heterogeneity is of utmost importance for molecular classification as well as for defining therapeutic targets in this disease, as single biopsies might underestimate the true molecular diversity in a tumor.

Obesity and perioperative adverse events in patients undergoing complex revision surgery for the thoracolumbar spine.

BACKGROUND: There are no previous studies that evaluate the effect of obesity on patients undergoing complex revision thoracolumbar spine surgery. The primary objective was to determine the relationship between obesity and perioperative adverse events (AEs) with patients undergoing complex revision thoracolumbar spine surgery while controlling for psoas muscle index (PMI) as a confounding variable. The secondary objective was to determine the relationship between obesity and 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, and post-operative length of stay (LOS). METHODS: Between May 2016 and February 2020, a retrospective analysis of individuals undergoing complex revision surgery of the thoracolumbar spine was performed at a single institution. Obesity was defined as BMI ≥ 30.0 kg/m2. PMI < 500 mm2/m2 for males and < 412 mm2/m2 for females were used to define low muscle mass. A Spine Surgical Invasiveness Index (SSII) > 10 was used to define complex revision surgery. A multivariable logistic regression model was used to ascertain the effects of low muscle mass, obesity, age, and gender on the likelihood of the occurrence of any AE. RESULTS: A total of 114 consecutive patients were included in the study. Fifty-four patients were in the obese cohort and 60 patients in the non-obese cohort. There was not a significant difference in perioperative outcomes of both the obese and non-obese patients. There were 22 obese patients (40.7%) and 33 non-obese patients (55.0%) that experienced any AE (p = 0.130). Multivariable analysis demonstrated that individuals with low muscle mass had a significantly higher likelihood for an AE than individuals with normal or high muscle mass (OR: 7.53, 95% CI: 3.05-18.60). Obesity did not have a significant effect in predicting AEs. CONCLUSIONS: Obesity is not associated with perioperative AEs, 30-day readmission rates, 30-day re-operation rates, rate of discharge to a facility, or post-operative length of stay (LOS) among patients undergoing complex revision thoracolumbar spine surgery. LEVEL OF EVIDENCE: III.

Full-fusion and kiss-and-run in chromaffin cells controlled by irreversible vesicle size-dependent fusion pore transitions.

Exocytosis operates through two distinct modes. Full-fusion leads to rapid expulsion of the entire content of a vesicle; kiss-and-run leads to slow and partial expulsion. These two modes have important biological consequences for endocrine regulation and synaptic transmission. Amperometry recordings of catecholamine release from chromaffin cells reveal single-vesicle fusion events corresponding to both of these modes, but classification is often difficult. This study introduces a new method of analyzing amperometry data to improve this classification. The ratio of the average amplitude to the peak amplitude differs between full-fusion and kiss-and-run, and the probability distribution of this ratio is well fitted by a double-Gaussian. Kiss-and-run events identified by this method have fusion pores with kinetic properties different from pores associated with full-fusion. They have slower transition rates and lifetime distributions indicative of irreversible transitions. The total-charge of an amperometric spike is expected to scale with vesicle volume during a full-fusion event. The cube root of this quantity should therefore scale with diameter, but the distribution of this quantity differs from the distribution of vesicle diameter seen in the electron microscope. Fusion pore lifetimes associated with full-fusion depend on vesicle size, and this makes the choice of mode size dependent. The fusion pore thus bifurcates after opening, and vesicle size influences this choice. The secretory vesicle protein synaptophysin influences the size dependence of fusion pore lifetime and the choice of release mode. Incorporating vesicle size into an analysis of release mode reconciled the kinetics of fusion pores, as well as the distributions of vesicle diameter and catecholamine content. Thus, the initial fusion pore emerges as a critical focus in endocrine regulation. By modulating the size-dependence of the mode of exocytosis, changes in the molecular makeup of the exocytotic apparatus can impact the shape and size of an amperometric event, and the speed and composition of secretion.

Percutaneous Transsplenic Balloon-Assisted Transjugular Intrahepatic Portosystemic Shunt Placement in Patients with Portal Vein Obliteration for Portal Vein Recanalization: Feasibility, Safety and Effectiveness.

PURPOSE: To assess the feasibility, safety and effectiveness of portal vein recanalization (PVR)-transjugular portosystemic shunt (TIPS) placement via splenic access using a balloon puncture technique. MATERIALS AND METHODS: In a single-center retrospective study from March 2017 to February 2021, 14 consecutive patients with portal hypertension, chronic liver disease and portal vein occlusion or near-complete (> 95%) occlusion were referred for PVR-TIPS placement. Feasibility, safety and effectiveness including procedural characteristics such as technical success, complication profile and splenic access time (SAT), balloon positioning time (BPT), conventional portal vein entry time (CPVET), overall procedure time (OPT), fluoroscopy time (FT), dose-area product (DAP) and air kerma (AK) were evaluated. RESULTS: Transsplenic PVR-TIPS using balloon puncture technique was technically feasible in 12 of 14 patients (8 men, 49 ± 13 years). In two patients without detectable intrahepatic portal vein branches, TIPS placement was not feasible and both patients were referred for further treatment with nonselective beta blockers and endoscopic variceal ligation. No complications grade > 3 of the Cardiovascular and Interventional Radiological Society of Europe classification system occurred. The SAT was 25 ± 21 min, CPVET was 33 ± 26 min, the OPT was 158 ± 54 min, the FT was 42 ± 22 min, the DAP was 167.84 ± 129.23 Gy*cm2 and the AK was 1150.70 ± 910.73 mGy. CONCLUSIONS: Transsplenic PVR-TIPS using a balloon puncture technique is feasible and appears to be safe in our series of patients with obliteration of the portal vein. It expands the interventional options in patients with chronic PVT.

Os 100 anos de “Além do Princípio do Prazer” e as novas concepções sobre a pulsão de morte / 100th year of the text “Beyond the Pleasure Principle” and the new conceptions on death drive

O interesse teórico e clínico acerca dos desdobramentos da noção freudiana de pulsão de morte ressurge com intensidade em razão do advento dos 100 anos do texto Além do Princípio do Prazer, sobretudo para aqueles que se dedicam à escuta de sofrimentos relacionados ao vazio psíquico, ao tédio e à apatia. No presente artigo, a autora dedica-se a apreciar as construções metapsicológicas derivadas desse texto freudiano, dando ênfase ao pensamento de Sándor Ferenczi, Donald Winnicott, André Green e Michael Balint, assim como aos aspectos clínicos referentes à posição do analista na escuta de tais casos em que predomina a circulação do mortífero.(AU)

The theoretical and clinical interest regarding the development of the Freudian notion of death drive reappears with intensity due to the advent of the 100th year of the text Beyond the Pleasure Principle, especially for those who work in psychoanalytical clinic with patients suffering from boredom, apathy and psychic void. In this article, the author appreciates the metapsychological constructions derived from this Freudian text, emphasizing the theories of Sándor Ferenczi, Donald Winnicott, André Green and Michael Balint, as well as the clinical aspects regarding the analyst’s position in listening to such cases in which predominates the circulation of the death drive.(AU)