Combining contextuality and causality: a game semantics approach.

We develop an approach to combining contextuality with causality, which is general enough to cover causal background structure, adaptive measurement-based quantum computation and causal networks. The key idea is to view contextuality as arising from a game played between Experimenter and Nature, allowing for causal dependencies in the actions of both the Experimenter (choice of measurements) and Nature (choice of outcomes). This article is part of the theme issue 'Quantum contextuality, causality and freedom of choice'.

Amperometric bio-sensing of lactate and oxygen concurrently with local field potentials during status epilepticus.

Epilepsy is a prevalent neurological disorder with a complex pathogenesis and unpredictable nature, presenting limited treatment options in >30 % of affected individuals. Neurometabolic abnormalities have been observed in epilepsy patients, suggesting a disruption in the coupling between neural activity and energy metabolism in the brain. In this study, we employed amperometric biosensors based on a modified carbon fiber microelectrode platform to directly and continuously measure lactate and oxygen dynamics in the brain extracellular space. These biosensors demonstrated high sensitivity, selectivity, and rapid response time, enabling in vivo measurements with high temporal and spatial resolution. In vivo recordings in the cortex of anaesthetized rats revealed rapid and multiphasic fluctuations in extracellular lactate and oxygen levels following neuronal stimulation with high potassium. Furthermore, real-time measurement of lactate and oxygen concentration dynamics concurrently with network electrical activity during status epilepticus induced by 4-aminopyridine (4-AP) demonstrated phasic changes in lactate levels that correlated with bursts of electrical activity, while tonic levels of lactate remained stable during seizures. This study highlights the complex interplay between lactate dynamics, electrical activity, and oxygen utilization in epileptic seizures.

A Two-Year Retrospective Analysis of the Clinical Outcomes of Immediate Submuscular Breast Reconstructions With Native® Acellular Dermal Matrix.

BACKGROUND: Implant-based submuscular breast reconstruction (SBR) can be performed with the aid of acellular dermal matrices (ADM) for implant coverage on their inferolateral pole, aiming at providing a biological interface for hiding the implant and therefore reducing the risk of complications. The purpose of this study is to assess the long-term post-operative outcomes obtained using the SBR-specific Native® ADM (DECO med s.r.l., Marcon, Venice, Italy). METHODS: All cases of Native®-assisted immediate SBR performed at our institution between October 2016 and March 2020 were retrospectively analysed. Demographic and surgical data were collected, and post-operative outcomes, including minor and major complications, were evaluated. Particular attention was paid to complications emerging before and after patient discharge. Dependence analyses were performed to uncover statistically significant relationships between risk factors and reconstructive outcomes. RESULTS: Data on 100 patients were collected, for a total of 128 breasts. The mean age of the cohort was 49.5 years, the mean BMI was 23.4 kg/m2, and the mean follow-up was 24 months. Out of this, 14.1% of patients received pre-operative radiotherapy, while 16.4% underwent post-mastectomy radiotherapy. Breasts appeared to develop short-term minor complications more likely during hospitalisation (11.7% vs. 7.8%), while short-term major complications occurred more often after discharge (7.8% vs. 15.6%). The most frequent long-term complications were capsular contracture and contour defects (both 9.4%). Risk factors that showed a statistically significant relationship with complications were pre- and post-mastectomy radiotherapy and post-operative chemotherapy. CONCLUSIONS: The retrospective analysis showed results in line with clinical outcomes reported in the literature for the same reconstructive technique. The use of Native® ADM in SBR is safe and effective in the long term.

Analytical methods for amatoxins: A comprehensive review.

Amatoxins are toxic bicyclic octapeptides found in certain wild mushroom species, particularly Amanita phalloides. These mushrooms contain predominantly α- and ß-amanitin, which can lead to severe health risks for humans and animals if ingested. Rapid and accurate identification of these toxins in mushroom and biological samples is crucial for diagnosing and treating mushroom poisoning. Analytical methods for the determination of amatoxins are critical to ensure food safety and prompt medical treatment. This review provides a comprehensive overview of the research literature on the determination of amatoxins in clinical specimens, biological and mushroom samples. We discuss the physicochemical properties of toxins, highlighting their influence on the choice of the analytical method and the importance of sample preparation, particularly solid-phase extraction with cartridges. Chromatographic methods are emphasised with a focus on liquid chromatography coupled to mass spectrometry as one of the most relevant analytical method for the determination of amatoxins in complex matrices. Furthermore, current trends and future perspectives in amatoxin detection are also suggested.

Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus.

Under physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron-glia interactions. To this purpose, we used high-resolution respirometry to measure oxygen consumption (O2 flux) at the whole tissue level and amperometric lactate microbiosensors to evaluate the concentration dynamics of extracellular lactate. We found that lactate is produced from glucose and transported to the extracellular space by neural cells in hippocampal tissue. Under resting conditions, endogenous lactate was used by neurons to support oxidative metabolism, which was boosted by exogenously added lactate even in the presence of excess glucose. Depolarization of hippocampal tissue with high K+ significantly increased the rate of oxidative phosphorylation, which was accompanied by a transient decrease in extracellular lactate concentration. Both effects were reverted by inhibition of the neuronal lactate transporter, monocarboxylate transporters 2 (MCT2), supporting the concept of an inward flux of lactate to neurons to fuel oxidative metabolism. We conclude that astrocytes are the main source of extracellular lactate which is used by neurons to fuel oxidative metabolism, both under resting and stimulated conditions.

Amanitins in Wild Mushrooms: The Development of HPLC-UV-EC and HPLC-DAD-MS Methods for Food Safety Purposes.

Mushroom poisoning remains a serious food safety and health concern in some parts of the world due to its morbidity and mortality. Identification of mushroom toxins at an early stage of suspected intoxication is crucial for a rapid therapeutic decision. In this study, a new extraction method was developed to determine α- and ß-amanitin in mushroom samples collected from central Portugal. High-performance liquid chromatography with in-line ultraviolet and electrochemical detection was implemented to improve the specificity of the method. The method was fully validated for linearity (0.5-20.0 µg·mL-1), sensitivity, recovery, and precision based on a matrix-matched calibration method. The limit of detection was 55 µg mL-1 (UV) and 62 µg mL-1 (EC) for α-amanitin and 64 µg mL-1 (UV) and 24 µg mL-1 (EC) for ß-amanitin. Intra- and inter-day precision differences were less than 13%, and the recovery ratios ranged from 89% to 117%. The developed method was successfully applied to fourteen Amanita species (A. sp.) and compared with five edible mushroom samples after extraction with Oasis® PRIME HLB cartridges without the conditioning and equilibration step. The results revealed that the A. phalloides mushrooms present the highest content of α- and ß-amanitin, which is in line with the HPLC-DAD-MS. In sum, the developed analytical method could benefit food safety assessment and contribute to food-health security, as it is rapid, simple, sensitive, accurate, and selectively detects α- and ß-amanitin in any mushroom samples.

A Platinized Carbon Fiber Microelectrode-Based Oxidase Biosensor for Amperometric Monitoring of Lactate in Brain Slices.

BACKGROUND: Direct and real-time monitoring of lactate in the extracellular space can help elucidate the metabolic and modulatory role of lactate in the brain. Compared to in vivo studies, brain slices allow the investigation of the neural contribution separately from the effects of cerebrovascular response and permit easy control of recording conditions. METHODS: We have used a platinized carbon fiber microelectrode platform to design an oxidase-based microbiosensor for monitoring lactate in brain slices with high spatial and temporal resolution operating at 32 °C. Lactate oxidase (Aerococcus viridans) was immobilized by crosslinking with glutaraldehyde and a layer of polyurethane was added to extend the linear range. Selectivity was improved by electropolymerization of m-phenylenediamine and concurrent use of a null sensor. RESULTS: The lactate microbiosensor exhibited high sensitivity, selectivity, and optimal analytical performance at a pH and temperature compatible with recording in hippocampal slices. Evaluation of operational stability under conditions of repeated use supports the suitability of this design for up to three repeated assays. CONCLUSIONS: The microbiosensor displayed good analytical performance to monitor rapid changes in lactate concentration in the hippocampal tissue in response to potassium-evoked depolarization.

Comparison of Outcomes in Immediate Implant-Based Breast Reconstruction: Acellular Dermal Matrix versus Inferior Dermal Flap.

Background Implant-based breast reconstruction has evolved tremendously in the last decades, mainly due to the development of new products and techniques that make the procedure safer and more reliable. The purpose of this study was to compare the outcomes in immediate one-stage breast reconstruction between acellular dermal matrix (ADM) and inferior dermal flap (IDF). Methods We conducted a retrospective comparative study of patients submitted to immediate breast reconstructions with an anatomical implant and ADM or IDF in a single center between 2016 and 2018. Outcomes evaluated included major complications, early complications, reinterventions, readmissions, and reconstruction failure. Simple descriptive statistics and univariate analysis were performed. Results A total of 118 breast reconstructions (85 patients) were included in the analysis. Patients in the IDF group had a higher body mass index (median = 27.0) than patients in the ADM group (median = 24). There were no statistically significant differences among both groups regarding immediate major complication, early complications, readmissions, and reinterventions. Conclusion There are no significant differences in complications between the ADM and IDF approach to immediate implant breast reconstruction. In patients with higher body mass index and large, ptotic breasts, we recommend an immediate implant reconstruction with IDF.

Design and Evaluation of a Lactate Microbiosensor: Toward Multianalyte Monitoring of Neurometabolic Markers In Vivo in the Brain.

Direct in vivo measurements of neurometabolic markers in the brain with high spatio-temporal resolution, sensitivity, and selectivity is highly important to understand neurometabolism. Electrochemical biosensors based on microelectrodes are very attractive analytical tools for continuous monitoring of neurometabolic markers, such as lactate and glucose in the brain extracellular space at resting and following neuronal activation. Here, we assess the merits of a platinized carbon fiber microelectrode (CFM/Pt) as a sensing platform for developing enzyme oxidase-based microbiosensors to measure extracellular lactate in the brain. Lactate oxidase was immobilized on the CFM/Pt surface by crosslinking with glutaraldehyde. The CFM/Pt-based lactate microbiosensor exhibited high sensitivity and selectivity, good operational stability, and low dependence on oxygen, temperature, and pH. An array consisting of a glucose and lactate microbiosensors, including a null sensor, was used for concurrent measurement of both neurometabolic substrates in vivo in the anesthetized rat brain. Rapid changes of lactate and glucose were observed in the cortex and hippocampus in response to local glucose and lactate application and upon insulin-induced fluctuations of systemic glucose. Overall, these results indicate that microbiosensors are a valuable tool to investigate neurometabolism and to better understand the role of major neurometabolic markers, such as lactate and glucose.

Highly sensitive and selective nanostructured microbiosensors for glucose and lactate simultaneous measurements in blood serum and in vivo in brain tissue.

Highly sensitive and selective nanostructured lactate and glucose microbiosensors for their in vivo simultaneous determination in rat brain were developed based on carbon fiber microelectrodes (CFM) modified with nanoporous gold (NPG) using the Dynamic Hydrogen Bubble Template (DHBT) method. Electrodeposition of platinum nanoparticles (PtNP) onto the NPG film enhances the sensitivity and the electrocatalytic properties towards H2O2 detection. The nanostructured microelectrode platform was modified by glucose oxidase (GOx) and lactate oxidase (LOx) enzyme immobilization. High selective measurements were achieved by covering with a perm-selective layer of electropolymerized m-phenylenediamine, deposition of a Nafion® film and by using a null sensor. The morphological characteristics and electroanalytical performance of the microbiosensors were assessed, by scanning electron microscopy and electrochemical techniques, respectively. The PtNP/NPG/CFM shows a high sensitivity to H2O2 (5.96 A M-1 cm-2) at 0.36 V vs. Ag/AgCl, with a linear range from 0.2 to 200 µM, and an LOD of 10 nM. The microbiosensors were applied to the simultaneous determination of lactate and glucose in blood serum samples. Moreover, the basal extracellular concentrations of lactate and glucose were measured in vivo in four different rat brain structures. These results support the potential of the microbiosensor to be used as a valuable tool to investigate brain neurochemicals in vivo.

Impact of Body Mass Index, Age and Tobacco Use on the Outcomes of Immediate Breast Reconstruction with Implants and Acellular Dermal Matrix.

Background This study aimed to analyze the effect of body mass index (BMI), age, and tobacco use on alloplastic breast reconstruction. Methods We conducted a retrospective study of patients who submitted to immediate breast reconstructions with an anatomical implant and acellular dermal matrix in a single center between 2016 and 2018. Outcomes evaluated included immediate complications, early complications, reinterventions, readmissions, and reconstruction failure. Patients were divided into two groups concerning each potential risk factor (BMI < or ≥25; age < or ≥ 50 years; and smokers vs nonsmokers). Simple descriptive statistics and univariate analysis were performed. Results A total of 101 breast reconstructions (73 patients) were included in the analysis. The mean BMI was 24, and the mean age was 44.5 years old. Smokers accounted for 14 breast reconstructions (13.9%). The rate of early infections, mastectomy flap necrosis, and implant removal was significantly higher in overweight patients. The total volume of breast drainage was higher in the age ≥ 50 years group. Smoking did not alter the outcomes. Conclusions A BMI ≥ 25 is a risk factor for early infections and reconstructive failure. Age ≥ 50 years is associated with a higher volume of breast drainage but does not seem to impact the success of the reconstruction. Smoking does not appear to affect the outcomes significantly in this type of reconstruction. Surgeons should consider delaying the reconstruction or using autologous tissue when patients are overweight.

Microelectrode Sensor for Real-Time Measurements of Nitrite in the Living Brain, in the Presence of Ascorbate.

The impaired blood flow to the brain causes a decrease in the supply of oxygen that can result in cerebral ischemia; if the blood flow is not restored quickly, neuronal injury or death will occur. Under hypoxic conditions, the production of nitric oxide (●NO), via the classical L-arginine-●NO synthase pathway, is reduced, which can compromise ●NO-dependent vasodilation. However, the alternative nitrite (NO2-) reduction to ●NO, under neuronal hypoxia and ischemia conditions, has been viewed as an in vivo storage pool of ●NO, complementing its enzymatic synthesis. Brain research is thus demanding suitable tools to probe nitrite's temporal and spatial dynamics in vivo. In this work, we propose a new method for the real-time measurement of nitrite concentration in the brain extracellular space, using fast-scan cyclic voltammetry (FSCV) and carbon microfiber electrodes as sensing probes. In this way, nitrite was detected anodically and in vitro, in the 5-500 µM range, in the presence of increasing physiological concentrations of ascorbate (100-500 µM). These sensors were then tested for real-time and in vivo recordings in the anesthetized rat hippocampus; using fast electrochemical techniques, local and reproducible transients of nitrite oxidation signals were observed, upon pressure ejection of an exogenous nitrite solution into the brain tissue. Nitrite microsensors are thus a valuable tool for investigating the role of this inorganic anion in brain redox signaling.

The Peculiar Facets of Nitric Oxide as a Cellular Messenger: From Disease-Associated Signaling to the Regulation of Brain Bioenergetics and Neurovascular Coupling.

In this review, we address the regulatory and toxic role of ·NO along several pathways, from the gut to the brain. Initially, we address the role on ·NO in the regulation of mitochondrial respiration with emphasis on the possible contribution to Parkinson's disease via mechanisms that involve its interaction with a major dopamine metabolite, DOPAC. In parallel with initial discoveries of the inhibition of mitochondrial respiration by ·NO, it became clear the potential for toxic ·NO-mediated mechanisms involving the production of more reactive species and the post-translational modification of mitochondrial proteins. Accordingly, we have proposed a novel mechanism potentially leading to dopaminergic cell death, providing evidence that NO synergistically interact with DOPAC in promoting cell death via mechanisms that involve GSH depletion. The modulatory role of NO will be then briefly discussed as a master regulator on brain energy metabolism. The energy metabolism in the brain is central to the understanding of brain function and disease. The core role of ·NO in the regulation of brain metabolism and vascular responses is further substantiated by discussing its role as a mediator of neurovascular coupling, the increase in local microvessels blood flow in response to spatially restricted increase of neuronal activity. The many facets of NO as intracellular and intercellular messenger, conveying information associated with its spatial and temporal concentration dynamics, involve not only the discussion of its reactions and potential targets on a defined biological environment but also the regulation of its synthesis by the family of nitric oxide synthases. More recently, a novel pathway, out of control of NOS, has been the subject of a great deal of controversy, the nitrate:nitrite:NO pathway, adding new perspectives to ·NO biology. Thus, finally, this novel pathway will be addressed in connection with nitrate consumption in the diet and the beneficial effects of protein nitration by reactive nitrogen species.

Cognitive performance in older adults across Europe based on the SHARE database.

With ageing mental health issues, as age-related cognitive decline, increase. This study aims to evaluate the prevalence of cognitive impairment among older European adults and to evaluate its association with clinical and sociodemographic variables, using SHARE. Numeracy, temporal orientation, verbal fluency, and memory were the measures used to evaluate cognitive performance. From 44 963 individuals included, mean age was 70.0±9.0 years old and 56.3% were female. Overall prevalence of impairment was of 13.0% (temporal orientation), 24.8% (numeracy), 27.6% (verbal fluency) and 50.5% (memory). Men showed higher impairment prevalence in temporal orientation and memory and lower in numeracy and verbal fluency. Age, fewer years of education, difficulties performing iADLs, physical inactivity, and poor self-perceived health were independently associated with impairment in all cognitive abilities. These results showed the burden of cognitive impairment across Europe. Factors identified as associated should be taken in consideration to develop effective interventions to prevent cognitive decline.

Electrochemical Evaluation of a Multi-Site Clinical Depth Recording Electrode for Monitoring Cerebral Tissue Oxygen.

The intracranial measurement of local cerebral tissue oxygen levels-PbtO2-has become a useful tool for the critical care unit to investigate severe trauma and ischemia injury in patients. Our preliminary work in animal models supports the hypothesis that multi-site depth electrode recording of PbtO2 may give surgeons and critical care providers needed information about brain viability and the capacity for better recovery. Here, we present a surface morphology characterization and an electrochemical evaluation of the analytical properties toward oxygen detection of an FDA-approved, commercially available, clinical grade depth recording electrode comprising 12 Pt recording contacts. We found that the surface of the recording sites is composed of a thin film of smooth Pt and that the electrochemical behavior evaluated by cyclic voltammetry in acidic and neutral electrolyte is typical of polycrystalline Pt surface. The smoothness of the Pt surface was further corroborated by determination of the electrochemical active surface, confirming a roughness factor of 0.9. At an optimal working potential of -0.6 V vs. Ag/AgCl, the sensor displayed suitable values of sensitivity and limit of detection for in vivo PbtO2 measurements. Based on the reported catalytical properties of Pt toward the electroreduction reaction of O2, we propose that these probes could be repurposed for multisite monitoring of PbtO2 in vivo in the human brain.

Basal cell carcinoma: multimodal treatment and the role of neoadjuvant vismodegib

Basal cell carcinoma (BCC) is the most common skin cancer. It generally has an indolent course with low rates of metastasis and mortality. However, BCC is locally invasive and can cause significant morbidity due to destructive local spread. We report our experience with a patient who was referred to our skin cancer unit due to a previously neglected lesion on the parietal region of the scalp, which had developed for 7 years. The patient was prescribed vismodegib on the basis that surgery could cause excessive functional and aesthetic damage. The patient had an objective partial response after 20 months of treatment. He was then submitted to radical skin excision, leaving a large defect that was reconstructed using a free latissimus dorsi muscle flap. The patient recovered well, and at the 1-year follow-up there were no signs of local recurrence. Our case demonstrates the value of vismodegib treatment prior to surgery in a locally advanced, high-risk scalp BCC and highlights the importance of an individualized and specialized approach with these patients, within a multidisciplinary team.

Basal cell carcinoma: multimodal treatment and the role of neoadjuvant vismodegib.

Basal cell carcinoma (BCC) is the most common skin cancer. It generally has an indolent course with low rates of metastasis and mortality. However, BCC is locally invasive and can cause significant morbidity due to destructive local spread. We report our experience with a patient who was referred to our skin cancer unit due to a previously neglected lesion on the parietal region of the scalp, which had developed for 7 years. The patient was prescribed vismodegib on the basis that surgery could cause excessive functional and aesthetic damage. The patient had an objective partial response after 20 months of treatment. He was then submitted to radical skin excision, leaving a large defect that was reconstructed using a free latissimus dorsi muscle flap. The patient recovered well, and at the 1-year follow-up there were no signs of local recurrence. Our case demonstrates the value of vismodegib treatment prior to surgery in a locally advanced, high-risk scalp BCC and highlights the importance of an individualized and specialized approach with these patients, within a multidisciplinary team.

Platinized carbon fiber-based glucose microbiosensor designed for metabolic studies in brain slices.

In order to understand how energy metabolism adapts to changes in neuronal activity it is imperative to perform direct measurements of the flux of glucose (and other metabolites) in brain tissue. Metabolic studies using brain slice preparations are attractive due to the controllability of recording conditions, absence of anesthetic interference and refined animal experimental protocols. In this work, taking advantage of the small size and versatility of carbon fiber microelectrodes (CFMs), we aimed to develop an amperometric glucose microbiosensor suitable for glucose measurement in brain slices. Potentiostatic- or galvanostatic-driven platinum electrodeposition was used to improve the analytical properties of CFMs towards detection of hydrogen peroxide. The platinized CFMs served as platform for the development of glucose microbiosensors through the immobilization of glucose-oxidase (GOx) by cross-linking with glutaraldehyde in the presence of BSA. Selective glucose measurements were attained by modifying the electrode with a permselective layer of meta-phenylenediamine and by integrating a null sensor. The in vitro characterization studies support the good analytical features of the CFM/Pt-based microbiosensors to reliably measure glucose in brain tissue. The ex vivo experiments in rodent hippocampal slices validated their suitability to measure evoked changes in extracellular glucose. This approach, encompassing the use of null sensor to cross-check the selectivity on a moment-to-moment basis, allowed us to provide the temporal and quantitative profile of extracellular glucose changes in hippocampal slices following a spreading depolarization event. Overall, these results support the potential of these microbiosensors to be used as a valuable tool to investigate the complex nature of glucose utilization in brain tissue linked to neuronal activation both in physiological and pathological conditions.

A Micro-Analytical Study of the Scarabs of the Necropolis of Vinha das Caliças (Portugal).

Five scarabs and one scaraboid found in Vinha das Caliças 4 (Beja, Portugal) were analyzed using a micro-analytical methodology in order to determine their mineralogical and chemical composition. Microstructural characterization and chemical analysis revealed that all were composed of a white body of crushed feldspathic sand covered by a lead-rich, alkaline-depleted silicate blue-green glaze showing evident signs of glass deterioration. Variable pressure scanning electron microscopy with X-ray energy dispersive spectrometry, handheld X-ray fluorescence spectroscopy, and micro X-ray diffraction results show that blue-green color of the glaze was produced by using copper ions (Cu2+) in conjunction with the lead antimonate bindheimite, a yellow-colored opacifier. The introduction of small amounts of tin in the structure of bindheimite enabled the production of a ternary Pb-Sb-Sn oxide. Tin, which was most likely added with the copper source (bronze scrapings), is known to facilitate the crystallization of bindheimite. The results are consistent with the five scarabs and one scaraboid being manufactured in Egypt. This study, the first archeometric study of scarabs found in the Iberian peninsula, has greatly contributed to the understanding of the influence of the Eastern and Central Mediterranean world in the Southwestern Iberia during the first millennium B.C.