Single closed-loop acoustic stimulation targeting memory consolidation suppressed hippocampal ripple and thalamo-cortical spindle activity in mice

Brain rhythms of sleep reflect neuronal activity underlying sleep-associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed-loop acoustic stimulation in humans targeted to the SO Up-state successfully enhanced the slow oscillation rhythm and phase-dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation-induced hippocampo-thalamo-cortical activity and retention performance on a hippocampus-dependent object-place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3-h retention interval at the beginning of the light phase closed-loop stimulation failed to improve retention significantly over sham. However, retention during SO Up-state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second-long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo-cortical spindle activity. Importantly, dynamics of SO-coupled hippocampal ripple activity distinguished SOUp-state stimulation. Non-rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed-loop acoustic stimulation in mice to investigate the inter-regional mechanisms underlying memory consolidation.     

Associations between Intra-Pancreatic Fat Deposition,Pancreas Size,and Pancreatic Enzymes in Health and after an Attack of Acute Pancreatitis

IntroductionEctopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes.MethodsThis cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders.ResultsA total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (β = −0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (β = −3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (β = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (β = −10.533, p = 0.024 in the most adjusted model).ConclusionIncreased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.     

Corrosion Behavior of Candidate Functional Materials for Molten Salts Reactors in LiF–NaF–KF Containing Actinide Fluoride Imitators

Molten fluorides of alkali metals are considered a technological medium for molten salt reactors (MSRs). However, these media are known to be extremely corrosive. The successful implementation of high-temperature technological devices using molten alkali metal fluorides requires the selection of such structural materials that have high corrosion resistance in melts with compositional characteristic of MSRs. In this research, the corrosion behavior of 12Cr18Ni10Ti steel, the alloy Ni60Cr20Mo15, and the alloy Monel 404 (Ni50Cu50) was investigated in the LiF–NaF–KF eutectic melt, containing additions of CeF₃ and NdF₃ from 0 to 5 wt.% as imitator fluorides of actinides in an inert argon atmosphere at 550 °C for 100 h. Gravimetry, energy-dispersive X-ray (EDX) microanalysis of surfaces and cross-section of samples, and ICP-MS were used to establish the corrosion behavior of the investigated alloys. Corrosion resistance of the studied materials was found to decrease in a row from Monel 404 > Hastelloy C2000 > 12Cr18Ni10Ti. The addition of cerium fluoride into the melt resulted in the additional etching of the alloy surface. The addition of neodymium fluoride resulted in the formation of the point/inter-crystalline corrosion damages in the sample bulk. The samples of steel 12Cr18Ni10Ti were subjected to local cracking corrosion. The austenitic nickel-based alloys suffered specific local corrosion with formation of subsurface voids. Excellent corrosion resistance of the Monel alloy under the test conditions was found.     

Non-uniform expression of α subunit isoforms of the Na/K pump in rat dorsal root ganglia neurons

Tissue sections and antibodies selectively recognizing isoforms of the α subunit of the Na⁺/K⁺ pump were used to determine the expression of α₁, α₂ and α₃ pump isoforms in the plasma membrane of adult rat dorsal root ganglia (DRG) neurons. There was no detectable membrane signal from DRG neurons that were probed with antibodies to the α₂ isoform of the Na⁺/K⁺ pump. The α₁ isoform of the Na⁺/K⁺ pump was found in most (77±4%) studied DRG neurons, regardless of cell size. Only 16±7% of the neurons expressed a detectable level of the α₃ Na⁺/K⁺ pump and all were apparently from a subpopulation of large DRG neurons. Comparison of cell size distributions and a study of neurons identified in serial sections suggested that of the α₃ positive DRG neurons about 75% coexpressed the α₁ isoform of the Na⁺/K⁺ pump. These data show that the expression of the protein of the α subunit isoforms of the Na⁺/K⁺ pump is not uniform throughout the population of DRG neurons and that α₁ is the predominant isoform in the plasma membrane of these neurons.     

High rate fabrication of copper and copper–gold electrodes by laser-induced selective electroless plating for enzyme-free glucose sensing

In the current study, the method of Selective Surface Activation Induced by Laser (SSAIL) was used for the fabrication of metallic and bimetallic structures based on copper and gold on the surface of glass and glass-ceramics. It was shown that the fabricated electrodes are suitable for non-enzymatic detection of biologically essential analytes such as glucose. The implemented approach allows performing high-rate metallization of various dielectrics. Voltammetric methods were applied to evaluate the electrocatalytic activity of the obtained structures, which were used as working electrodes. The most promising results were revealed by copper–gold electrode structures manufactured on glass-ceramics. For these structures, sensitivity towards glucose sensing was 3060 μA mM⁻¹ cm⁻². The linear range of glucose detection varied between 0.3 and 1000 μM. Besides, the manufactured electrodes exhibited high selectivity and long-term stability.

In the current study, the method of Selective Surface Activation Induced by Laser (SSAIL) was used for the fabrication of metallic and bimetallic structures based on copper and gold on the surface of glass and glass-ceramics.     

Enhancing the Antiviral Potency of Nucleobases for Potential Broad-Spectrum Antiviral Therapies

Broad-spectrum antiviral therapies hold promise as a first-line defense against emerging viruses by blunting illness severity and spread until vaccines and virus-specific antivirals are developed. The nucleobase favipiravir, often discussed as a broad-spectrum inhibitor, was not effective in recent clinical trials involving patients infected with Ebola virus or SARS-CoV-2. A drawback of favipiravir use is its rapid clearance before conversion to its active nucleoside-5′-triphosphate form. In this work, we report a synergistic reduction of flavivirus (dengue, Zika), orthomyxovirus (influenza A), and coronavirus (HCoV-OC43 and SARS-CoV-2) replication when the nucleobases favipiravir or T-1105 were combined with the antimetabolite 6-methylmercaptopurine riboside (6MMPr). The 6MMPr/T-1105 combination increased the C-U and G-A mutation frequency compared to treatment with T-1105 or 6MMPr alone. A further analysis revealed that the 6MMPr/T-1105 co-treatment reduced cellular purine nucleotide triphosphate synthesis and increased conversion of the antiviral nucleobase to its nucleoside-5′-monophosphate, -diphosphate, and -triphosphate forms. The 6MMPr co-treatment specifically increased production of the active antiviral form of the nucleobases (but not corresponding nucleosides) while also reducing levels of competing cellular NTPs to produce the synergistic effect. This in-depth work establishes a foundation for development of small molecules as possible co-treatments with nucleobases like favipiravir in response to emerging RNA virus infections.     

Predictors of Critical Acute Pancreatitis: A Prospective Cohort Study

Critical acute pancreatitis (CAP) has recently emerged as the most ominous severity category of acute pancreatitis (AP). As such there have been no studies specifically designed to evaluate predictors of CAP. In this study, we aimed to evaluate the accuracy of 4 parameters (Acute Physiology and Chronic Health Evaluation [APACHE] II score, C-reactive protein [CRP], D-dimer, and intra-abdominal pressure [IAP]) for predicting CAP early after hospital admission. During the study period, data on patients with AP were prospectively collected and D-dimer, CRP, and IAP levels were measured using standard methods at admission whereas the APACHE II score was calculated within 24 hours of hospital admission. The receiver-operating characteristic (ROC) curve analysis was applied and the likelihood ratios were calculated to evaluate the predictive accuracy. A total of 173 consecutive patients were included in the analysis and 47 (27%) of them developed CAP. The overall hospital mortality was 11% (19 of 173). APACHE II score ≥11 and IAP ≥13 mm Hg showed significantly better overall predictive accuracy than D-dimer and CRP (area under the ROC curve—0.94 and 0.92 vs 0.815 and 0.667, correspondingly). The positive likelihood ratio of APACHE II score is excellent (9.9) but of IAP is moderate (4.2). The latter can be improved by adding CRP (5.8). In conclusion, of the parameters studied, APACHE II score and IAP are the best available predictors of CAP within 24 hours of hospital admission. Given that APACHE II score is rather cumbersome, the combination of IAP and CRP appears to be the most practical way to predict critical course of AP early after hospital admission.     

Comprehensive analysis of body composition and insulin traits associated with intra-pancreatic fat deposition in healthy individuals and people with new-onset prediabetes/diabetes after acute pancreatitis

Current knowledge of biomarkers of intra-pancreatic fat deposition (IFD) is limited. We aimed to analyse comprehensively body composition and insulin traits as biomarkers of IFD in healthy normoglycaemic individuals as well as in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP). A total of 29 healthy individuals and 34 individuals with NODAP took part in this cross-sectional study. The studied biomarkers belonged to the following domains: body composition (anthropometric and MRI-derived variables); indices of insulin secretion; indices of insulin sensitivity; incretins and related peptides; and pancreatitis-related factors. All MRI-derived variables (including IFD) were measured using ImageJ software. Univariate and step-wise regression analyses were conducted to determine variables that best explained variance in IFD. Visceral fat volume and oxyntomodulin were the best biomarkers of IFD in normoglycaemic healthy individuals, contributing to 64% variance. The Raynaud index was the best biomarker of IFD in individuals with NODAP, contributing to 20% variance. Longitudinal studies are warranted to investigate the cause and effect relationship between oxyntomodulin and IFD in healthy individuals, as well as insulin sensitivity and IFD in individuals with NODAP.     

Attitudes Toward Addiction,Methadone Treatment,and Recovery Among HIV-Infected Ukrainian Prisoners Who Inject Drugs: Incarceration Effects and Exploration of Mediators

In this study, we use data from a survey conducted in Ukraine among 196 HIV-infected people who inject drugs, to explore attitudes toward drug addiction and methadone maintenance therapy (MMT), and intentions to change drug use during incarceration and after release from prison. Two groups were recruited: Group 1 (n = 99) was currently incarcerated and Group 2 (n = 97) had been recently released from prison. This paper’s key finding is that MMT treatment and addiction recovery were predominantly viewed as mutually exclusive processes. Group comparisons showed that participants in Group 1 (pre-release) exhibited higher optimism about changing their drug use, were less likely to endorse methadone, and reported higher intention to recover from their addiction. Group 2 participants (post-release), however, reported higher rates of HIV stigma. Structural equation modeling revealed that in both groups, optimism about recovery and awareness of addiction mediated the effect of drug addiction severity on intentions to recover from their addiction.     

Aptamers Selected to Postoperative Lung Adenocarcinoma Detect Circulating Tumor Cells in Human Blood

Circulating tumor cells (CTCs) are rare cells and valuable clinical markers of prognosis of metastasis formation and prediction of patient survival. Most CTC analyses are based on the antibody-based detection of a few epithelial markers; therefore miss an important portion of mesenchymal cancer cells circulating in blood. In this work, we selected and identified DNA aptamers as specific affinity probes that bind to lung adenocarcinoma cells derived from postoperative tissues. The unique feature of our selection strategy is that aptamers are produced for lung cancer cell biomarkers in their native state and conformation without previous knowledge of the biomarkers. The aptamers did not bind to normal lung cells and lymphocytes, and had very low affinity to A549 lung adenocarcinoma culture. We applied these aptamers to detect CTCs, apoptotic bodies, and microemboli in clinical samples of peripheral blood of lung cancer and metastatic lung cancer patients. We identified aptamer-associated protein biomarkers for lung cancer such as vimentin, annexin A2, annexin A5, histone 2B, neutrophil defensin, and clusterin. Tumor-specific aptamers can be produced for individual patients and synthesized many times during anticancer therapy, thereby opening up the possibility of personalized diagnostics.