Interictal epileptiform discharges affect memory in an Alzheimer's disease mouse model.

Interictal epileptiform discharges (IEDs) are transient abnormal electrophysiological events commonly observed in epilepsy patients but are also present in other neurological diseases, such as Alzheimer's disease (AD). Understanding the role IEDs have on the hippocampal circuit is important for our understanding of the cognitive deficits seen in epilepsy and AD. We characterize and compare the IEDs of human epilepsy patients from microwire hippocampal recording with those of AD transgenic mice with implanted multilayer hippocampal silicon probes. Both the local field potential features and firing patterns of pyramidal cells and interneurons were similar in the mouse and human. We found that as IEDs emerged from the CA3-1 circuits, they recruited pyramidal cells and silenced interneurons, followed by post-IED suppression. IEDs suppressed the incidence and altered the properties of physiological sharp-wave ripples, altered their physiological properties, and interfered with the replay of place field sequences in a maze. In addition, IEDs in AD mice inversely correlated with daily memory performance. Together, our work implies that IEDs may present a common and epilepsy-independent phenomenon in neurodegenerative diseases that perturbs hippocampal-cortical communication and interferes with memory.

An update to Hippocampome.org by integrating single-cell phenotypes with circuit function in vivo.

Understanding brain operation demands linking basic behavioral traits to cell-type specific dynamics of different brain-wide subcircuits. This requires a system to classify the basic operational modes of neurons and circuits. Single-cell phenotyping of firing behavior during ongoing oscillations in vivo has provided a large body of evidence on entorhinal-hippocampal function, but data are dispersed and diverse. Here, we mined literature to search for information regarding the phase-timing dynamics of over 100 hippocampal/entorhinal neuron types defined in Hippocampome.org. We identified missing and unresolved pieces of knowledge (e.g., the preferred theta phase for a specific neuron type) and complemented the dataset with our own new data. By confronting the effect of brain state and recording methods, we highlight the equivalences and differences across conditions and offer a number of novel observations. We show how a heuristic approach based on oscillatory features of morphologically identified neurons can aid in classifying extracellular recordings of single cells and discuss future opportunities and challenges towards integrating single-cell phenotypes with circuit function.

Mechanisms and plasticity of chemogenically induced interneuronal suppression of principal cells.

How do firing patterns in a cortical circuit change when inhibitory neurons are excited? We virally expressed an excitatory designer receptor exclusively activated by a designer drug (Gq-DREADD) in all inhibitory interneuron types of the CA1 region of the hippocampus in the rat. While clozapine N-oxide (CNO) activation of interneurons suppressed firing of pyramidal cells, unexpectedly the majority of interneurons also decreased their activity. CNO-induced inhibition decreased over repeated sessions, which we attribute to long-term synaptic plasticity between interneurons and pyramidal cells. Individual interneurons did not display sustained firing but instead transiently enhanced their activity, interleaved with suppression of others. The power of the local fields in the theta band was unaffected, while power at higher frequencies was attenuated, likely reflecting reduced pyramidal neuron spiking. The incidence of sharp wave ripples decreased but the surviving ripples were associated with stronger population firing compared with the control condition. These findings demonstrate that DREADD activation of interneurons brings about both short-term and long-term circuit reorganization, which should be taken into account in the interpretation of chemogenic effects on behavior.

Measuring moral distress in health professionals using the MMD-HP-SPA scale.

BACKGROUND: Moral distress (MD) is the psychological damage caused when people are forced to witness or carry out actions which go against their fundamental moral values. The main objective was to evaluate the prevalence and predictive factors associated with MD among health professionals during the pandemic and to determine its causes. METHODS: A regional, observational and cross-sectional study in a sample of 566 professionals from the Public Health Service of Andalusia (68.7% female; 66.9% physicians) who completed the MMD-HP-SPA scale to determine the level of MD (0-432 points). Five dimensions were used: i) Health care; ii) Therapeutic obstinacy-futility, iii) Interpersonal relations of the Healthcare Team, iv) External pressure; v) Covering up of medical malpractice. RESULTS: The mean level of MD was 127.3 (SD=66.7; 95% CI 121.8-132.8), being higher in female (135 vs. 110.3; p<0.01), in nursing professionals (137.8 vs. 122; p<0.01) and in the community setting (136.2 vs. 118.3; p<0.001), with these variables showing statistical significance in the multiple linear regression model (p<0.001; r2=0.052). With similar results, the multiple logistic regression model showed being female was a higher risk factor (OR=2.27; 95% CI 1.5-3.4; p<0.001). 70% of the sources of MD belonged to the dimension "Health Care" and the cause "Having to attend to more patients than I can safely attend to" obtained the highest average value (Mean=9.8; SD=4.9). CONCLUSIONS: Female, nursing professionals, and those from the community setting presented a higher risk of MD. The healthcare model needs to implement an ethical approach to public health issues to alleviate MD among its professionals.

Preventing Mislabeling: A Comparative Chromatographic Analysis for Classifying Medical and Industrial Cannabis.

Gas chromatography (GC) techniques for analyzing and determining the cannabinoid profile in cannabis (Cannabis sativa L.) are widely used in standard laboratories; however, these methods may mislabel the profile when used under rapid conditions. Our study aimed to highlight this problem and optimize GC column conditions and mass spectrometry (MS) parameters to accurately identify cannabinoids in both standards and forensic samples. The method was validated for linearity, selectivity, and precision. It was observed that when tetrahydrocannabinol (Δ9-THC) and cannabidiolic acid (CBD-A) were examined using rapid GC conditions, the resulting derivatives generated identical retention times. Wider chromatographic conditions were applied. The linear range for each compound ranged from 0.02 µg/mL to 37.50 µg/mL. The R2 values ranged from 0.996 to 0.999. The LOQ values ranged from 0.33 µg/mL to 5.83 µg/mL, and the LOD values ranged from 0.11 µg/mL to 1.92 µg/mL. The precision values ranged from 0.20% to 8.10% RSD. In addition, forensic samples were analyzed using liquid chromatography (HPLC-DAD) in an interlaboratory comparison test, with higher CBD and THC content than GC-MS determination (p < 0.05) in samples. Overall, this study highlights the importance of optimizing GC techniques to avoid mislabeling cannabinoids in cannabis samples.

Status epilepticus induces chronic silencing of burster and dominance of regular firing neurons during sharp wave-ripples in the mouse subiculum.

Sharp wave-ripples (SWRs) are hippocampal oscillations associated with memory consolidation. The subiculum, as the hippocampal output structure, ensures that hippocampal memory representations are transferred correctly to the consolidating neocortical regions. Because patients with temporal lobe epilepsy often develop memory deficits, we hypothesized that epileptic networks may disrupt subicular SWRs. We therefore investigated the impact of experimentally induced status epilepticus (SE) on subicular SWRs and contributing pyramidal neurons using electrophysiological recordings in mouse hippocampal slices. Subicular SWRs expressed hyperexcitable features post-SE, including increased ripple and unit activity. While regular firing neurons normally remain silent during SWRs, selective disinhibition recruited more regular firing neurons for action potential generation during SWRs post-SE. By contrast, burster neurons generated fewer action potential bursts during SWRs post-SE. Furthermore, altered timing of postsynaptic and action potentials suggested distorted neuronal recruitment during SWRs. Distorted subicular SWRs may therefore impair information processing and memory consolidation in epilepsy.

Holm oak decline is determined by shifts in fine root phenotypic plasticity in response to belowground stress.

Climate change and pathogen outbreaks are the two major causes of decline in Mediterranean holm oak trees (Quercus ilex L. subsp. ballota (Desf.) Samp.). Crown-level changes in response to these stressful conditions have been widely documented but the responses of the root systems remain unexplored. The effects of environmental stress over roots and its potential role during the declining process need to be evaluated. We aimed to study how key morphological and architectural root parameters and nonstructural carbohydrates of roots are affected along a holm oak health gradient (i.e. within healthy, susceptible and declining trees). Holm oaks with different health statuses had different soil resource-uptake strategies. While healthy and susceptible trees showed a conservative resource-uptake strategy independently of soil nutrient availability, declining trees optimized soil resource acquisition by increasing the phenotypic plasticity of their fine root system. This increase in fine root phenotypic plasticity in declining holm oaks represents an energy-consuming strategy promoted to cope with the stress and at the expense of foliage maintenance. Our study describes a potential feedback loop resulting from strong unprecedented belowground stress that ultimately may lead to poor adaptation and tree death in the Spanish dehesa.

Freshwater-Derived Streptomyces: Prospective Polyvinyl Chloride (PVC) Biodegraders.

Polyvinyl chloride (PVC) is widely used in industrial applications, such as construction and clothing, owing to its chemical, physical, and environmental resistance. Owing to the previous characteristics, PVC is the third most consumed plastic worldwide and, consequently, an increasing waste accumulation-related problem. The current study evaluated an in-house collection of 61 Actinobacteria strains for PVC resin biodegradation. Weight loss percentage was measured after the completion of incubation. Thermo-gravimetric analysis was subsequently performed using the PVC incubated with the three strains exhibiting the highest weight loss. GC-MS and ionic exchange chromatography analyses were also performed using the culture media supernatant of these three strains. After incubation, 14 strains had a PVC weight loss percentage higher than 50% in ISP-2 broth. These 14 strains were identified as Streptomyces strains. Strains 208, 250, and 290 showed the highest weight loss percentages (57.6-61.5% range). The thermal stability of PVC after bacterial exposure using these three strains was evaluated, and a modification of the representative degradation stages of nonincubated PVC was observed. Additionally, GC-MS analysis revealed the presence of aromatic compounds in the inoculated culture media, and ionic exchange chromatography showed chloride release in the supernatant. A mathematical relation between culture conditions and PVC weight loss was also found for strains 208 and 290, showing an accuracy up to 97.99%. These results highlight the potential of the freshwater-derived Streptomyces strains as candidates for the PVC biodegradation strategy and constitute the first approach to a waste management control scale-up process.

Endoscopic ultrasonography-guided deployment of embolization coils and cyanoacrylate injection in gastric varices versus coiling alone: a randomized trial.

BACKGROUND: Gastric variceal bleeding is a life-threating condition with challenging management. We aimed to compare the efficacy and safety of endoscopic ultrasonography (EUS)-guided coil embolization and cyanoacrylate injection versus EUS-guided coil embolization alone in the management of gastric varices. METHODS: A single-center, parallel-randomized controlled trial involving 60 participants with gastric varices (GOV II and IGV I) who were randomly allocated to EUS-guided coil embolization and cyanoacrylate injection (n = 30) or EUS-guided coil embolization alone (n = 30). The primary end points were the technical and clinical success rates of both procedures. The secondary end points were the reappearance of gastric varices during follow-up, along with rebleeding, the need for reintervention, and complication and survival rates. RESULTS: The technical success rate was 100 % in both groups. Immediate disappearance of varices was observed in 86.7 % of patients treated with coils and cyanoacrylate, versus 13.3 % of patients treated with coils alone (P < 0.001). Median survival time was 16.4 months with coils and cyanoacrylate versus 14.2 months with coils alone (P = 0.90). Rebleeding occurred in 3.3 % of patients treated with combined treatment and 20 % of those treated with coils alone (P = 0.04). With combined treatment, 83.3 % of patients were free from reintervention versus 60 % with coils alone (hazard ratio 0.27; 95 % confidence interval 0.095 - 0.797; P = 0.01). CONCLUSIONS: EUS-guided coil embolization with cyanoacrylate injection achieved excellent clinical success, with lower rates of rebleeding and reintervention than coil treatment alone. Multicenter studies are required to define the most appropriate technique for gastric variceal obliteration.

MUSIC Speciation of γ-Al2O3 at the Solid Liquid Interface: How DFT Calculations Can Help with Amorphous and Poorly Crystalline Materials.

Transition aluminum oxides, such as γ-Al2O3 or alumina, are widely used in many different technical applications that rely on the surface reactivity of this material at the solid liquid interface. The speciation of surface sites of this material confronts several obstacles. On the one hand, alumina is a poorly crystalline oxide, thus allowing for a limited amount of empirical structural information for an important number of surface sites with different trends in reactivity and, on the other hand, it is a metastable material. In this work, we show several ways in which the multisite complexation model, combined with atomistic information from density functional theory and ab initio molecular dynamics (AIMD), can manage to perform speciation calculations of γ-Al2O3 surface sites at the solid liquid interface. Although the results are in good qualitative agreement with experimental titration curves, and they can serve as a guide for the interpretation of the reactivity of this material at the initial stages of an impregnation experiment and chemical weathering phenomena, this work highlights the need of more complex AIMD simulations to accurately model these phenomena in γ-Al2O3 surface/liquid interfaces.

Greater phylogenetic distance from native oaks predicts escape from insect leaf herbivores by non-native oak saplings.

PREMISE: Non-native plant species have been hypothesized to experience lower herbivory in novel environments as a function of their phylogenetic distance from native plant species. Although recent work has found support for this prediction, the plant traits responsible for such patterns have been largely overlooked. METHODS: In a common garden experiment in northwestern Spain, we tested whether oak species (Quercus spp.) not native to this region that are phylogenetically more distantly related to native species exhibit less insect leaf herbivory. In addition, we also investigated plant traits potentially correlated with any such effect of phylogenetic distance. RESULTS: As expected, phylogenetic distance from native species negatively predicted insect leaf herbivory on non-native oaks. In addition, we found that the leaf traits, namely phosphorus and condensed tannins, were significantly associated with herbivory, suggesting that they are associated with the effect of phylogenetic distance on leaf herbivory on non-native oak species. CONCLUSIONS: This study contributes to a better understanding of how evolutionary relationships (relatedness) between native and non-native plant species determine the latter's success in novel environments via locally shared enemies, and encourages more work investigating the plant traits that mediate the effects of phylogenetic distance on enemy escape.

Endoscopic-ultrasound-guided coil and cyanoacrylate embolization for gastric varices and the roles of endoscopic Doppler and endosonographic varicealography in vascular targeting.

OBJECTIVE: To report the results of endoscopic ultrasound-guided injection of coils with cyanoacrylate (CYA) using a less-expensive coil with an emphasis on the roles of Doppler and endosonographic varicealography (EV) in identifying the feeder vessel in gastric varix treatment. METHODS: An observational, descriptive study with prospectively collected data. Patients with gastric varices (GV) were included and were treated by endoscopic ultrasound-guided injection of CYA and a less-expensive coil. Technical success, complete and immediate variceal obliteration, rebleeding, complication and survival rates were evaluated. RESULTS: Thirty patients with GV with a mean age of 62 years (range: 44-76 years) were treated. Median number of coils used was 2 (range: 1-3), and median volume of CYA was 1.8 mL (1.2-2.4 mL). Technical success rate was 100%. EV technical success was observed in 26/30 patients. Complete variceal obliteration was observed in 96.6% of patients, and immediate disappearance of the varix was observed in 24 (80%) patients. The complication rate was 6.7%. CONCLUSIONS: Endoscopic-ultrasound guidance for gastric varix treatment with the addition of EV and the use of a less-expensive coil is a safe and effective technique that results in the immediate disappearance of GV after targeting the feeding vessel.

Candidate Polyurethanes Based on Castor Oil (Ricinus communis), with Polycaprolactone Diol and Chitosan Additions, for Use in Biomedical Applications.

Polyurethanes are widely used in the development of medical devices due to their biocompatibility, degradability, non-toxicity and chemical versatility. Polyurethanes were obtained from polyols derived from castor oil, and isophorone diisocyanate, with the incorporation of polycaprolactone-diol (15% w/w) and chitosan (3% w/w). The objective of this research was to evaluate the effect of the type of polyol and the incorporation of polycaprolactone-diol and chitosan on the mechanical and biological properties of the polyurethanes to identify the optimal ones for applications such as wound dressings or tissue engineering. Polyurethanes were characterized by stress-strain, contact angle by sessile drop method, thermogravimetric analysis, differential scanning calorimetry, water uptake and in vitro degradation by enzymatic processes. In vitro biological properties were evaluated by a 24 h cytotoxicity test using the colorimetric assay MTT and the LIVE/DEAD kit with cell line L-929 (mouse embryonic fibroblasts). In vitro evaluation of the possible inflammatory effect of polyurethane-based materials was evaluated by means of the expression of anti-inflammatory and proinflammatory cytokines expressed in a cellular model such as THP-1 cells by means of the MILLIPLEX® MAP kit. The modification of polyols derived from castor oil increases the mechanical properties of interest for a wide range of applications. The polyurethanes evaluated did not generate a cytotoxic effect on the evaluated cell line. The assessed polyurethanes are suggested as possible candidate biomaterials for wound dressings due to their improved mechanical properties and biocompatibility.

Reliability and accuracy of a novel classification system using peroral cholangioscopy for the diagnosis of bile duct lesions.

BACKGROUND: The aim of this study was to propose a novel, comprehensive, macroscopic classification for bile duct lesions. METHODS: A two-stage protocol was designed. In Stage I, a retrospective study (September 2013 to September 2015) of patients with bile duct lesions detected by peroral cholangioscopy (POCS) was performed. A total of 315 images with at least 6 months of follow-up were recorded, analyzed, and correlated to histology, and were classified as non-neoplastic (one of three types, 1 - 3) or neoplastic (one of four types, 1 - 4) based on morphological and vascular patterns. In Stage II, a prospective, nonrandomized, double-blind study was performed from December 2015 to December 2016 to validate the proposed classification. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and positive and negative likelihood ratios (LR + and LR - , respectively) were calculated (gold standard: 6-month follow-up). Inter- and intraobserver agreement (kappa value, κ) among experts and non-experts were calculated. RESULTS: 171 patients were included (65 retrospective; 106 prospective). In Stage I, 28/65 cases were neoplastic and 37 /65 were non-neoplastic, according to the final diagnosis. In Stage II, 56/106 were neoplastic with a sensitivity, specificity, PPV, NPV, LR + , and LR - for neoplastic diagnosis of 96.3 %, 92.3 %, 92.9 %, 96 %, 12.52, and 0.04, respectively. The proposed classification presented high reproducibility among observers, for both neoplastic and subtypes categories. However, it was better for experts (κ > 80 %) than non-experts (κ 64.7 % - 81.9 %). CONCLUSION: The novel classification system could help physicians to distinguish non-neoplastic from neoplastic bile duct lesions.

Surface Response Methodology-Based Mixture Design to Study the Influence of Polyol Blend Composition on Polyurethanes' Properties.

Polyurethanes are materials with a strong structure-property relationship. The goal of this research was to study the effect of a polyol blend composition of polyurethanes on its properties using a mixture design and setting mathematic models for each property. Water absorption, hydrolytic degradation, contact angle, tensile strength hardness and modulus were studied. Additionally, thermal stability was studied by thermogravimetric analysis. Area under the curve was used to evaluate the effect of polyol blend composition on thermal stability and kinetics of water absorption and hydrolytic degradation. Least squares were used to calculate the regression coefficients. Models for the properties were significant, and lack of fit was not (p < 0.05). Fit statistics suggest both good fitting and prediction. Water absorption, hydrolytic degradation and contact angle were mediated by the hydrophilic nature of the polyols. Tensile strength, modulus and hardness could be regulated by the PE content and the characteristics of polyols. Regression of DTG curves from thermal analysis showed improvement of thermal stability with the increase of PCL and PE. An ANOVA test of the model terms demonstrated that three component influences on bulk properties like water absorption, hydrolytic degradation, hardness, tensile strength and modulus. The PEG*PCL interaction influences on the contact angle, which is a surface property. Mixture design application allowed for an understanding of the structure-property relationship through mathematic models.

Non-enzymatic browning due to storage is reduced by using clarified lemon juice as acidifier in industrial-scale production of canned peach halves.

Non-enzymatic browning (NEB) in canned peach halves in syrup during storage was investigated. Absorbance at 420 nm (A420), colorimetric parameters (CIELab, TCD and La/b), fructose, glucose and sucrose, total sugar, organic acids, ascorbic acid (AA), dehydroascorbic acid, and 2,3-diketogulonic acid were used to estimate the extent of NEB during 1 year of storage at 30 °C and the relationships between each of these parameters and A420 were established. The investigation was carried out to explore the possibility of replacing the E330 commonly used as acidifier by turbid or clarified lemon juice (TLJ or CLJ) to obtain a product having good nutrition with better retention of quality. The a, La/b, glucose and fructose were positively correlated with A420 and all proved to be good indicators of browning development. Overall results showed that replacement of acidifier E330 with CLJ for controlling pH in canned peach halves in syrup had some advantages.

Proximodistal structure of theta coordination in the dorsal hippocampus of epileptic rats.

Coherent neuronal activity in the hippocampal-entorhinal circuit is a critical mechanism for episodic memory function, which is typically impaired in temporal lobe epilepsy. To better understand how this mechanism is implemented and degraded in this condition, we used normal and epileptic rats to examine theta activity accompanying active exploration. Assisted by multisite recordings of local field potentials (LFPs) and layer-specific profiling of input pathways, we provide detailed quantification of the proximodistal coherence of theta activity in the dorsal hippocampus of these animals. Normal rats showed stronger coordination between the temporoammonic and perforant entorhinal inputs (measured from lamina-specific current source density signals) at proximal locations, i.e., closer to CA3; while epileptic rats exhibited stronger interactions at distal locations, i.e., closer to subiculum. This opposing trend in epileptic rats was associated with the reorganization of the temporoammonic and perforant pathways that accompany hippocampal sclerosis, the pathological hallmark of this disease. In addition to this connectivity constraint, we discovered that the appropriate timing between entorhinal inputs arriving over several theta cycles at the proximal and distal ends of the dorsal hippocampus was impaired in epileptic rats. Computational reconstruction of LFP signals predicted that restoring timing variability has a major impact on repairing theta coherence. This manipulation, when tested pharmacologically via systemic administration of group III mGluR antagonists, successfully re-established theta coordination of LFPs in epileptic rats. Thus, proximodistal organization of entorhinal inputs is instrumental in temporal lobe physiology and a candidate mechanism to study cognitive comorbidities of temporal lobe epilepsy.

Extracellular calcium controls the expression of two different forms of ripple-like hippocampal oscillations.

Hippocampal high-frequency oscillations (HFOs) are prominent in physiological and pathological conditions. During physiological ripples (100-200 Hz), few pyramidal cells fire together coordinated by rhythmic inhibitory potentials. In the epileptic hippocampus, fast ripples (>200 Hz) reflect population spikes (PSs) from clusters of bursting cells, but HFOs in the ripple and the fast ripple range are vastly intermixed. What is the meaning of this frequency range? What determines the expression of different HFOs? Here, we used different concentrations of Ca(2+) in a physiological range (1-3 mM) to record local field potentials and single cells in hippocampal slices from normal rats. Surprisingly, we found that this sole manipulation results in the emergence of two forms of HFOs reminiscent of ripples and fast ripples recorded in vivo from normal and epileptic rats, respectively. We scrutinized the cellular correlates and mechanisms underlying the emergence of these two forms of HFOs by combining multisite, single-cell and paired-cell recordings in slices prepared from a rat reporter line that facilitates identification of GABAergic cells. We found a major effect of extracellular Ca(2+) in modulating intrinsic excitability and disynaptic inhibition, two critical factors shaping network dynamics. Moreover, locally modulating the extracellular Ca(2+) concentration in an in vivo environment had a similar effect on disynaptic inhibition, pyramidal cell excitability, and ripple dynamics. Therefore, the HFO frequency band reflects a range of firing dynamics of hippocampal networks.