The loss of antioxidant activities impairs intestinal epithelium homeostasis by altering lipid metabolism.

Reactive oxygens species (ROS) are common byproducts of metabolic reactions and could be at the origin of many diseases of the elderly. Here we investigated the role of ROS in the renewal of the intestinal epithelium in mice lacking catalase (CAT) and/or nicotinamide nucleotide transhydrogenase (NNT) activities. Cat-/- mice have delayed intestinal epithelium renewal and were prone to develop necrotizing enterocolitis upon starvation. Interestingly, crypts lacking CAT showed fewer intestinal stem cells (ISC) and lower stem cell activity than wild-type. In contrast, crypts lacking NNT showed a similar number of ISCs as wild-type but increased stem cell activity, which was also impaired by the loss of CAT. No alteration in the number of Paneth cells (PCs) was observed in crypts of either Cat-/- or Nnt-/- mice, but they showed an evident decline in the amount of lysozyme. Cat deficiency caused fat accumulation in crypts, and a fall in the remarkable high amount of adipose triglyceride lipase (ATGL) in PCs. Notably, the low levels of ATGL in the intestine of Cat -/- mice increased after a treatment with the antioxidant N-acetyl-L-cysteine. Supporting a role of ATGL in the regulation of ISC activity, its inhibition halt intestinal organoid development. These data suggest that the reduction in the renewal capacity of intestine originates from fatty acid metabolic alterations caused by peroxisomal ROS.

K2CO3-Modified Smectites as Basic Catalysts for Glycerol Transcarbonation to Glycerol Carbonate.

A novel and cost-effective heterogeneous catalyst for glycerol carbonate production through transesterification was developed by impregnating smectite clay with K2CO3. Comprehensive structural and chemical analyses, including X-ray diffraction Analysis (XRD), Scanning Electron Microscopy (SEM)-Electron Dispersion Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FTIR), and Brunauer-Emmett-Teller (BET) surface area analysis measurements, were employed to characterize the catalysts. Among the various catalysts prepared, the one impregnated with 40 wt% K2CO3 on smectite and calcined at 550 °C exhibited the highest catalytic activity, primarily due to its superior basicity. To enhance the efficiency of the transesterification process, several reaction parameters were optimized, including the molar ratio between propylene carbonate and glycerol reactor loading of the catalyst and reaction temperature. The highest glycerol carbonate conversion rate, approximately 77.13% ± 1.2%, was achieved using the best catalyst under the following optimal conditions: 2 wt% reactor loading, 110 °C reaction temperature, 2:1 propylene carbonate to glycerol molar ratio, and 6h reaction duration. Furthermore, both the raw clay and the best calcined K2CO3-impregnated catalysts demonstrated remarkable stability, maintaining their high activity for up to four consecutive reaction cycles. Finally, a kinetic analysis was performed using kinetic data from several runs employing raw clay and the most active K2CO3-modified clay at different temperatures, observing that a simple reversible second-order potential kinetic model of the quasi-homogeneous type fits perfectly to such data in diverse temperature ranges.

Synthesis of Glycerol Carbonate from Ethylene Carbonate Using Zinc Stearate as a Catalyst: Operating Conditions and Kinetic Modeling.

With the advent of biodiesel as a substitute/additive for diesel, the production of glycerol has experienced an increase, as it is an unavoidable byproduct of the biodiesel process; therefore, novel products and processes based on this triol are being very actively researched. Glycerol carbonate emerges as an advanced humectant from glycerol and a monomer for diverse polycarbonates. Its production in high yields and amounts can be achieved through the solventless transcarbonation of glycerol with other organic carbonates driven by alkaline catalysts, standing out amongst the cyclic carbonates due to its reactivity. Here, we have studied the main operational variables that affect the transcarbonation reaction of glycerol and ethylene carbonate catalyzed by zinc stearate: catalyst concentration, reagent molar ratio, and temperature. Subsequently, an appropriate kinetic model was fitted to all data obtained at 80 °C and several catalyst concentrations as well as reagent molar ratios. Finally, the selected kinetic model was extended and validated by fitting it to data obtained at several temperatures, finding that the activation energy of this reaction with this catalyst is around 69.2 kJ·mol-1. The kinetic model suggests that the reaction is bimolecular and elemental and that the process is interfacial in essence, with the catalyst dispersed in a narrow space between polar (glycerol) and nonpolar (ethylene carbonate) phases.

Use of Tribulus terrestris and Lepidium meyenii extract in rats: reproductive, biochemical and body parameters.

The oral administration of Tribulus terrestris and Lepidium meyenii extracts on reproductive, biochemical and body parameters was evaluated in rats. Thirty-six male Wistar rats weighting 210 ± 18 g were divided into six experimental groups (n = 6). Each group received, daily for 28 days, different solutions: T. terrestris (100 mg/kg), L. meyenii (1 g/kg) and T. terrestris at doses of 75, 50 and 25 mg/kg combined with L. meyenii at doses of 0.25, 0.5 and 0.75 g/kg, respectively, and distilled water (control). T. terrestris increased (p < 0.05) the serum testosterone, regardless of dose. Combined use of the extracts increased (p < 0.05) the diameter of the epididymal duct and epididymis lumen. The combinations of T. terrestris (75 and 50 mg/kg) with L. meyenii increased (p < 0.05) the sperm concentration. There were no differences (p > 0.05) in the other semen characteristics; relative weight of organs; and serum levels of urea, creatinine, alanine and aspartate transaminase, gamma glutamyl transferase, cholesterol, triglycerides, glucose, follicle-stimulating hormone and luteinizing hormone. No histopathological changes were observed (p > 0.05). It is concluded that the association of T. terrestris and L. meyenii has positive effects on serum testosterone, sperm concentration and epididymal morphology, with no evidence of effects in the testis, liver, spleen and kidneys.

A biological condition gradient for Caribbean coral reefs: Part II. Numeric rules using sessile benthic organisms.

The Biological Condition Gradient (BCG) is a conceptual model used to describe incremental changes in biological condition along a gradient of increasing anthropogenic stress. As coral reefs collapse globally, scientists and managers are focused on how to sustain the crucial structure and functions, and the benefits that healthy coral reef ecosystems provide for many economies and societies. We developed a numeric (quantitative) BGC model for the coral reefs of Puerto Rico and the US Virgin Islands to transparently facilitate ecologically meaningful management decisions regarding these fragile resources. Here, reef conditions range from natural, undisturbed conditions to severely altered or degraded conditions. Numeric decision rules were developed by an expert panel for scleractinian corals and other benthic assemblages using multiple attributes to apply in shallow-water tropical fore reefs with depths <30 m. The numeric model employed decision rules based on metrics (e.g., % live coral cover, coral species richness, pollution-sensitive coral species, unproductive and sediment substrates, % cover by Orbicella spp.) used to assess coral reef condition. Model confirmation showed the numeric BCG model predicted the panel's median site ratings for 84% of the sites used to calibrate the model and 89% of independent validation sites. The numeric BCG model is suitable for adaptive management applications and supports bioassessment and criteria development. It is a robust assessment tool that could be used to establish ecosystem condition that would aid resource managers in evaluating and communicating current or changing conditions, protect water and habitat quality in areas of high biological integrity, or develop restoration goals with stakeholders and other public beneficiaries.

A biological condition gradient for coral reefs in the US Caribbean Territories: Part I. Coral narrative rules.

As coral reef condition and sustainability continue to decline worldwide, losses of critical habitat and their ecosystem services have generated an urgency to understand and communicate reef response to management actions, environmental contamination, and natural disasters. Increasingly, coral reef protection and restoration programs emphasize the need for robust assessment tools for protecting high-quality waters and establishing conservation goals. Of equal importance is the need to communicate assessment results to stakeholders, beneficiaries, and the public so that environmental consequences of decisions are understood. The Biological Condition (BCG) model provides a structure to evaluate the condition of a coral reef in increments of change along a gradient of human disturbance. Communication of incremental change, regardless of direction, is important for decision makers and the public to better understand what is gained or lost depending on what actions are taken. We developed a narrative (qualitative) Biological Condition Gradient (BCG) from the consensus of a diverse expert panel to provide a framework for coral reefs in US Caribbean Territories. The model uses narrative descriptions of biological attributes for benthic organisms to evaluate reefs relative to undisturbed or minimally disturbed conditions. Using expert elicitation, narrative decision rules were proposed and deliberated to discriminate among six levels of change along a gradient of increasing anthropogenic stress. Narrative rules for each of the BCG levels are presented to facilitate the evaluation of benthic communities in coral reefs and provide specific narrative features to detect changes in coral reef condition and biological integrity. The BCG model can be used in the absence of numeric, or quantitative metrics, to evaluate actions that may encroach on coral reef ecosystems, manage endangered species habitat, and develop and implement management plans for marine protected areas, watersheds, and coastal zones. The narrative BCG model is a defensible model and communication tool that translates scientific results so the nontechnical person can understand and support both regulatory and non-regulatory water quality and natural resource programs.

Electrocardiographic Diagnosis of Acute Coronary Occlusion Myocardial Infarction in Ventricular Paced Rhythm Using the Modified Sgarbossa Criteria.

STUDY OBJECTIVE: Ventricular paced rhythm is thought to obscure the electrocardiographic diagnosis of acute coronary occlusion myocardial infarction. Our primary aim was to compare the sensitivity of the modified Sgarbossa criteria (MSC) to that of the original Sgarbossa criteria for the diagnosis of occlusion myocardial infarction in patients with ventricular paced rhythm. METHODS: In this retrospective case-control investigation, we studied adult patients with ventricular paced rhythm and symptoms of acute coronary syndrome who presented in an emergency manner to 16 international cardiac referral centers between January 2008 and January 2018. The occlusion myocardial infarction group was defined angiographically as thrombolysis in myocardial infarction grade 0 to 1 flow or angiographic evidence of coronary thrombosis and peak cardiac troponin I ≥10.0 ng/mL or troponin T ≥1.0 ng/mL. There were 2 control groups: the "non-occlusion myocardial infarction-angio" group consisted of patients who underwent coronary angiography for presumed type I myocardial infarction but did not meet the definition of occlusion myocardial infarction; the "no occlusion myocardial infarction" control group consisted of randomly selected emergency department patients without occlusion myocardial infarction. RESULTS: There were 59 occlusion myocardial infarction, 90 non-occlusion myocardial infarction-angio, and 102 no occlusion myocardial infarction subjects (mean age, 72.0 years; 168 [66.9%] men). For the diagnosis of occlusion myocardial infarction, the MSC were more sensitive than the original Sgarbossa criteria (sensitivity 81% [95% confidence interval [CI] 69 to 90] versus 56% [95% CI 42 to 69]). Adding concordant ST-depression in V4 to V6 to the MSC yielded 86% (95% CI 75 to 94) sensitivity. For the no occlusion myocardial infarction control group of ED patients, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 96% (95% CI 90 to 99) versus 97% (95% CI 92 to 99); negative likelihood ratio (LR) 0.19 (95% CI 0.11 to 0.33) versus 0.45 (95% CI 0.34 to 0.65); and positive LR 21 (95% CI 7.9 to 55) versus 19 (95% CI 6.1 to 59). For the non-occlusion myocardial infarction-angio control group, additional test characteristics of MSC and original Sgarbossa criteria, respectively, were as follows: specificity 84% (95% CI 76 to 91) versus 90% (95% CI 82 to 95); negative LR 0.22 (95% CI 0.13 to 0.38) versus 0.49 (95% CI 0.35 to 0.66); and positive LR 5.2 (95% CI 3.2 to 8.6) versus 5.6 (95% CI 2.9 to 11). CONCLUSION: For the diagnosis of occlusion myocardial infarction in the presence of ventricular paced rhythm, the MSC were more sensitive than the original Sgarbossa criteria; specificity was high for both rules. The MSC may contribute to clinical decisionmaking for patients with ventricular paced rhythm.

Nanostructured Titanium Dioxide Surfaces for Electrochemical Biosensing.

TiO2 electrochemical biosensors represent an option for biomolecules recognition associated with diseases, food or environmental contaminants, drug interactions and related topics. The relevance of TiO2 biosensors is due to the high selectivity and sensitivity that can be achieved. The development of electrochemical biosensors based on nanostructured TiO2 surfaces requires knowing the signal extracted from them and its relationship with the properties of the transducer, such as the crystalline phase, the roughness and the morphology of the TiO2 nanostructures. Using relevant literature published in the last decade, an overview of TiO2 based biosensors is here provided. First, the principal fabrication methods of nanostructured TiO2 surfaces are presented and their properties are briefly described. Secondly, the different detection techniques and representative examples of their applications are provided. Finally, the functionalization strategies with biomolecules are discussed. This work could contribute as a reference for the design of electrochemical biosensors based on nanostructured TiO2 surfaces, considering the detection technique and the experimental electrochemical conditions needed for a specific analyte.

Decreasing Heart Failure Readmissions Among Older Patients With Cognitive Impairment by Engaging Caregivers.

BACKGROUND: Cognitive impairment is common in older patients with heart failure (HF), leading to higher 30-day readmission rates than those without cognitive impairment. OBJECTIVES: The aim of this study was to determine whether increased readmissions in older adults with cognitive impairment are related to HF severity and whether readmissions can be modified by caregiver inclusion in nursing discharge education. METHODS: This study used prospective quality improvement program of cognitive testing and inclusion of caregivers in discharge education with chart review. Two hundred thirty-two patients older than 70 years admitted with HF were screened for cognitive impairment using the Mini-Cog; if score was less than 4, nurses were asked to include caregivers in education on 2 cardiovascular units with an enhanced discharge program. Individuals with ventricular assist device, transplant, or hospice were excluded. Measurements include Mini-Cog score, 30-day readmissions, readmission risk score, ejection fraction, brain natriuretic peptide, and medical comorbidities. RESULTS: Readmission Risk Scores for HF did not correlate with Mini-Cog scores, but admission brain natriuretic peptide levels were less abnormal in those with better Mini-Cog scores. Only for patients with cognitive impairment, involving caregivers in discharge teaching given by registered and advanced practice nurses was associated with decreased 30-day readmissions from 35% to 16% (P = .01). Readmission rates without/with cognitive impairment were 14.1% and 23.8%, respectively (P = .09). Abnormal Mini-Cog screen was associated with a significantly increased risk of 30-day readmission (odds ratio, 2.23; 95% confidence interval, 1.06-4.68; P = .03), whereas nurse documentation of education with family was associated with a significantly decreased risk of 30-day readmission (odds ratio, 0.46; 95% confidence interval, 0.24-0.90; P = .02). CONCLUSIONS: Involving caregivers in discharge education significantly reduced 30-day readmission rates for patients with HF and cognitive impairment. The Readmission Risk Score was similar between patients older than 70 years with and without cognitive impairment. We have hypothesis-generating evidence that identification of cognitive impairment and targeted caregiver engagement by nurses may be critical in the reduction of readmission rates for older patients with HF.

Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory.

Erasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (an LPA1/3 receptor antagonist) or a vehicle solution, and they were tested 23 days later for CPP retention and extinction. The results of immunohistochemical experiments showed that the LPA-treated mice exhibited reduced long-term CPP retention and an approximately twofold increase in the number of adult-born hippocampal cells that differentiated into mature neurons. Importantly, mediation analyses confirmed a causal role of AHN in reducing CPP maintenance. In contrast, the ki16425-treated mice displayed aberrant responses, with initially decreased CPP retention that progressively increased across the extinction sessions, leading to no effect on AHN. The pharmacological treatments did not affect locomotion or general exploratory or anxiety-like responses. In a second experiment, normal and LPA1 -receptor-deficient mice were acutely infused with LPA, which revealed that LPA1 -mediated signaling was required for LPA-induced proliferative actions. These results suggest that the LPA/LPA1 pathway acts as a potent in vivo modulator of AHN and highlight the potential usefulness of pro-AHN strategies to treat aberrant cognition in those addicted to cocaine.

Training memory without aversion: Appetitive hole-board spatial learning increases adult hippocampal neurogenesis.

Learning experiences are potent modulators of adult hippocampal neurogenesis (AHN). However, the vast majority of findings on the learning-induced regulation of AHN derive from aversively-motivated tasks, mainly the water maze paradigm, in which stress is a confounding factor that affects the AHN outcome. Currently, little is known regarding the effect of appetitively-motivated training on AHN. Hence we studied how spatial learning to find food rewards in a hole-board maze modulates AHN (cell proliferation and immature neurons) and AHN-related hippocampal neuroplasticity markers (BDNF, IGF-II and CREB phosphorylation) in mice. The 'Trained' mice were tested for both spatial reference and working memory and compared to 'Pseudotrained' mice (exposed to different baited holes in each session, thus avoiding the reference memory component of the task) and 'Control' mice (exposed to the maze without rewards). In contrast to Pseudotrained and Control mice, the number of proliferating hippocampal cells were reduced in Trained mice, but they notably increased their population of immature neurons assessed by immunohistochemistry. This evidence shows that hole-board spatial reference learning diminishes cell proliferation in favor of enhancing young neurons' survival. Interestingly, the enhanced AHN in the Trained mice (specifically in the suprapyramidal blade) positively correlated with their reference memory performance, but not with their working memory. Furthermore, the Trained animals increased the hippocampal protein expression of all the neuroplasticity markers analyzed by western blot. Results show that the appetitively-motivated hole-board task is a useful paradigm to potentiate and/or investigate AHN and hippocampal plasticity minimizing aversive variables such as fear or stress.

Conceptual density functional theory for electron transfer and transport in mesoscopic systems.

Molecular and supramolecular systems are essentially mesoscopic in character. The electron self-exchange, in the case of energy fluctuations, or electron transfer/transport, in the case of the presence of an externally driven electrochemical potential, between mesoscopic sites is energetically driven in such a manner where the electrochemical capacitance (C[small mu, Greek, macron]) is fundamental. Thus, the electron transfer/transport through channels connecting two distinct energetic (ΔE[small mu, Greek, macron]) and spatially separated mesoscopic sites is capacitively modulated. Remarkably, the relationship between the quantum conductance (G) and the standard electrochemical rate constant (kr), which is indispensable to understanding the physical and chemical characteristics governing electron exchange in molecular scale systems, was revealed to be related to C[small mu, Greek, macron], that is, C[small mu, Greek, macron] = G/kr. Accordingly, C[small mu, Greek, macron] is the proportional missing term that controls the electron transfer/transport in mesoscopic systems in a wide-range, and equally it can be understood from first principles density functional quantum mechanical approaches. Indeed the differences in energy between states is calculated (or experimentally accessed) throughout the electrochemical capacitance as ΔE[small mu, Greek, macron] = ß/C[small mu, Greek, macron], and thus constitutes the driving force for G and/or kr, where ß is only a proportional constant that includes the square of the unit electron charge times the square of the number of electron particles interchanged.

[Relevance of Simpson's grading system for resections in WHO grade I meningiomas]. / Relevancia de la escala de Simpson en la resección de meningiomas de grado I de la OMS.

OBJECT: The aim of this study is to assess if the recurrence rates and recurrence/progression-free survivals (RFS) are different after Simpson's grades I, II, III and IV resections in World Health Organization (WHO) grade I meningiomas. MATERIAL AND METHODS: A retrospective review was conducted on the data of patients who underwent surgical treatment of WHO grade I meningiomas located in convexity, falx/parasagittal, and skull base (anterior/media/posterior) between June 1991 and December 2011. In Simpson's grade IV resections, surgical treatment was supplemented with radiotherapy/radiosurgery on the tumour remains. A comparison was made on the recurrence rates and RFSs between Simpson's grades I, II, III, and IV resections, both overall and in tumour subsets according to their location. RESULTS: A total of 208 meningiomas were included in this study. There were no significant differences in recurrence rates and RFSs between Simpson's grades I, II, III, and IV. No significant differences were noted between the different degrees of Simpson in any of the location groups. In convexity meningiomas, the recurrence rates were 7% and 33% in Simpson's grades I and III resections, respectively (P=.131). CONCLUSIONS: It has been shown that the rates of tumour control in meningiomas are not related to Simpson grades. In falx/parasagittal and skull base meningiomas, more aggressive attempts of tumour resection must be balanced against the risks of damaging critical neurovascular structures. In convexity meningiomas, a Simpson's grade I resection should be attempted first.

Tumor infiltrating immune cells in gliomas and meningiomas.

Tumor-infiltrating immune cells are part of a complex microenvironment that promotes and/or regulates tumor development and growth. Depending on the type of cells and their functional interactions, immune cells may play a key role in suppressing the tumor or in providing support for tumor growth, with relevant effects on patient behavior. In recent years, important advances have been achieved in the characterization of immune cell infiltrates in central nervous system (CNS) tumors, but their role in tumorigenesis and patient behavior still remain poorly understood. Overall, these studies have shown significant but variable levels of infiltration of CNS tumors by macrophage/microglial cells (TAM) and to a less extent also lymphocytes (particularly T-cells and NK cells, and less frequently also B-cells). Of note, TAM infiltrate gliomas at moderate numbers where they frequently show an immune suppressive phenotype and functional behavior; in contrast, infiltration by TAM may be very pronounced in meningiomas, particularly in cases that carry isolated monosomy 22, where the immune infiltrates also contain greater numbers of cytotoxic T and NK-cells associated with an enhanced anti-tumoral immune response. In line with this, the presence of regulatory T cells, is usually limited to a small fraction of all meningiomas, while frequently found in gliomas. Despite these differences between gliomas and meningiomas, both tumors show heterogeneous levels of infiltration by immune cells with variable functionality. In this review we summarize current knowledge about tumor-infiltrating immune cells in the two most common types of CNS tumors-gliomas and meningiomas-, as well as the role that such immune cells may play in the tumor microenvironment in controlling and/or promoting tumor development, growth and control.

Density functional theory and an experimentally-designed energy functional of electron density.

We herein demonstrate that capacitance spectroscopy (CS) experimentally allows access to the energy associated with the quantum mechanical ground state of many-electron systems. Priorly, electrochemical capacitance, C[small mu, Greek, macron][ρ], was previously understood from conceptual and computational density functional theory (DFT) calculations. Thus, we herein propose a quantum mechanical experiment-based variational method for electron charging processes based on an experimentally-designed functional of the ground state electron density. In this methodology, the electron state density, ρ, and an energy functional of the electron density, E[small mu, Greek, macron][ρ], can be obtained from CS data. CS allows the derivative of the electrochemical potential with respect to the electron density, (δ[small mu, Greek, macron][ρ]/δρ), to be obtained as a unique functional of the energetically minimised system, i.e., ß/C[small mu, Greek, macron][ρ], where ß is a constant (associated with the size of the system) and C[small mu, Greek, macron][ρ] is an experimentally observable quantity. Thus the ground state energy (at a given fixed external potential) can be obtained simply as E[small mu, Greek, macron][ρ], from the experimental measurement of C[small mu, Greek, macron][ρ]. An experimental data-set was interpreted to demonstrate the potential of this quantum mechanical experiment-based variational principle.

Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model.

Lacaziosis-like disease among bottlenose dolphins Tursiops truncatus photographed in Golfo Dulce, Costa Rica.

Lacaziosis (also known as lobomycosis) is a chronic dermal disease caused by the fungal agent Lacazia loboi, which affects both humans and dolphins. Photographic data have been used to identify lacaziosis-like disease (LLD) among dolphins in the waters of North and South America, and here we report LLD in bottlenose dolphins Tursiops truncatus off the coast of Costa Rica, the first reporting in Central American waters. During the periods of 1991 to 1992 and 2010 to 2011, 3 research teams conducted separate dolphin surveys in the Pacific tropical fiord Golfo Dulce, and each documented skin lesions in the resident population of bottlenose dolphins. Photo-ID records were used to identify LLD-affected bottlenose dolphins and to assess their lesions. Findings showed between 13.2 and 16.1% of the identified dolphins exhibited lesions grossly resembling lacaziosis. By combining efforts and cross-referencing photographic data, the teams explored the presence of LLD in Golfo Dulce over a time gap of approximately 20 yr. Our findings expand the geographical range of the disease and offer insight into its longevity within a given population of dolphins.

Exploring the Relationship between Mechanical Properties and Electrical Impedance in Cement-Based Composites Incorporating Gold Nanoparticles.

Structural health monitoring applications have gained significant attention in recent research, particularly in the study of the mechanical-electrical properties of materials such as cement-based composites. While most researchers have focused on the piezoresistive properties of cement-based composites under compressive stress, exploring the electrical impedance of such materials can provide valuable insights into the relationship between their mechanical and electrical characteristics. In this study, we investigated the connection between the mechanical properties and electrical impedance of cement-based composites modified with Au nanoparticles. Cylindrical samples with dimensions of 3 cm in diameter and 6 cm in length were prepared with a ratio of w/c = 0.47. The Au nanoparticles (Au NPs) were synthesized using pulsed laser ablation in liquids, and their size distribution was analyzed through dynamical light scattering. Mechanical properties were evaluated by analyzing the Young modulus derived from strain-stress curves obtained at various force rates. Electrical properties were measured by means of electrical impedance spectroscopy. The experimental results revealed a notable reduction of 91% in the mechanical properties of Au NPs-cement compounds, while their electrical properties demonstrated a significant improvement of 65%. Interestingly, the decrease in mechanical properties resulting from the inclusion of gold nanoparticles in cementitious materials was found to be comparable to that resulting from variations in the water/cement ratios or the hydration reaction.

Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis.

Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (N = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU+ DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.

Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial.

BACKGROUND: Monitoring supine pulmonary artery pressures to guide heart failure (HF) management has reduced HF hospitalizations in select patients. OBJECTIVES: The purpose of this study was to evaluate the effect of managing seated mean pulmonary artery pressure (mPAP) with the Cordella Pulmonary Artery sensor on outcomes in patients with HF. METHODS: Following GUIDE-HF (Hemodynamic-GUIDEd Management of Heart Failure Trial), with U.S. Food and Drug Administration input, PROACTIVE-HF (A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial) was changed from a randomized to a single-arm, open label trial, conducted at 75 centers in the USA and Europe. Eligible patients had chronic HF with NYHA functional class III symptoms, irrespective of the ejection fraction, and recent HF hospitalization and/or elevated natriuretic peptides. The primary effectiveness endpoint at 6 months required the HF hospitalization or all-cause mortality rate to be lower than a performance goal of 0.43 events/patient, established from previous hemodynamic monitoring trials. Primary safety endpoints at 6 months were freedom from device- or system-related complications or pressure sensor failure. RESULTS: Between February 7, 2020, and March 31, 2023, 456 patients were successfully implanted in modified intent-to-treat cohort. The 6-month event rate was 0.15 (95% CI: 0.12-0.20) which was significantly lower than performance goal (0.15 vs 0.43; P < 0.0001). Freedom from device- or system-related complications was 99.2% and freedom from sensor failure was 99.8% through 6 months. CONCLUSIONS: Remote management of seated mPAP is safe and results in a low rate of HF hospitalizations and mortality. These results support the use of seated mPAP monitoring and extend the growing body of evidence that pulmonary artery pressure-guided management improves outcomes in heart failure. (Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients trial [PROACTIVE-HF]; NCT04089059).