From sensor fusion to knowledge distillation in collaborative LIBS and hyperspectral imaging for mineral identification.

Multimodal spectral imaging offers a unique approach to the enhancement of the analytical capabilities of standalone spectroscopy techniques by combining information gathered from distinct sources. In this manuscript, we explore such opportunities by focusing on two well-known spectral imaging techniques, namely laser-induced breakdown spectroscopy, and hyperspectral imaging, and explore the opportunities of collaborative sensing for a case study involving mineral identification. In specific, the work builds upon two distinct approaches: a traditional sensor fusion, where we strive to increase the information gathered by including information from the two modalities; and a knowledge distillation approach, where the Laser Induced Breakdown spectroscopy is used as an autonomous supervisor for hyperspectral imaging. Our results show the potential of both approaches in enhancing the performance over a single modality sensing system, highlighting, in particular, the advantages of the knowledge distillation framework in maximizing the potential benefits of using multiple techniques to build more interpretable models and paving for industrial applications.

Identification of Relevant Spectral Ranges in Laser-Induced Breakdown Spectroscopy Imaging Using the Fourier Space.

Laser-induced breakdown spectroscopy (LIBS) imaging has now a well-established position in the subject of spectral imaging, leveraging multi-element detection capabilities and fast acquisition rates to support applications both at academic and technological levels. In current applications, the standard processing pipeline to explore LIBS imaging data sets revolves around identifying an element that is suspected to exist within the sample and generating maps based on its characteristic emission lines. Such an approach requires some previous expert knowledge both on the technique and on the sample side, which hinders a wider and more transparent accessibility of the LIBS imaging technique by non-specialists. To address this issue, techniques based on visual analysis or peak finding algorithms are applied on the average or maximum spectrum, and may be employed for automatically identifying relevant spectral regions. Yet, maps containing relevant information may often be discarded due to low signal-to-noise ratios or interference with other elements. In this context, this work presents an agnostic processing pipeline based on a spatial information ratio metric that is computed in the Fourier space for each wavelength and that allows for the identification of relevant spectral ranges in LIBS. The results suggest a more robust and streamlined approach to feature extraction in LIBS imaging compared with traditional inspection of the spectra, which can introduce novel opportunities not only for spectral data analysis but also in the field of data compression.

Characterization of Functional Coatings on Cork Stoppers with Laser-Induced Breakdown Spectroscopy Imaging.

Evaluating the efficiency of surface treatments is a problem of paramount importance for the cork stopper industry. Generically, these treatments create coatings that aim to enhance the impermeability and lubrification of cork stoppers. Yet, current methods of surface analysis are typically time-consuming, destructive, have poor representativity or rely on indirect approaches. In this work, the use of a laser-induced breakdown spectroscopy (LIBS) imaging solution is explored for evaluating the presence of coating along the cylindrical surface and in depth. To test it, several cork stoppers with different shaped areas of untreated surface were analyzed by LIBS, making a rectangular grid of spots with multiple shots per spot, to try to identify the correspondent shape. Results show that this technique can detect the untreated area along with other features, such as leakage and holes, allowing for a high success rate of identification and for its performance at different depths, paving the way for future industry-grade quality control solutions with more complex surface analysis.

Folate-Targeted Liposomal Formulations Improve Effects of Methotrexate in Murine Collagen-Induced Arthritis.

Methotrexate (MTX) is first-line therapy for the treatment of rheumatoid arthritis (RA), however, its use may be limited by side effects notably post-injection malaise. When patients are intolerant or become unresponsive, second-line or antibody therapy may be indicated. A folate-targeted liposomal formulation of MTX (FL-MTX) is tropic to arthritic paws and prevents the onset of collagen-induced arthritis (CIA) in the mouse. We optimized the drug-to-lipid molar ratio to 0.15 and demonstrated the therapeutic efficacy of this form at 2 mg/kg MTX intraperitoneal (i.p.) twice a week. These improved liposomes were present in inflamed joints in proportion to the degree of swelling of the paw and bone remodeling activity. FL-MTX had lower hepatic and renal elimination of MTX than the free substance. FL-MTX provided equivalent results when given i.p. or subcutaneous (s.c.) and FL-MTX 2 mg/kg (drug/lipid 0.15), twice weekly, was similar to or more effective than 35 mg/kg MTX (same route and schedule) in reducing the incidence and swelling in the murine CIA model. These results suggest that FL-MTX is a more potent nanotherapeutic formulation than free MTX treatment. Its potential benefits for patients may include reduced frequency of treatment and lower overall doses for a given response.

Gestão em foco / Management in focus

Este e-book tem como objetivo trazer um compêndio de relatos de experiência relacionados à gestão de saúde do Estado de Goiás. Cada capítulo traz a descrição dos projetos desenvolvidos no âmbito da Secretaria de Estado da Saúde de Goiás, que são vinculados aos objetivos estratégicos do órgão. Estes projetos têm como objetivo fortalecer as ações estratégicas para otimizar o planejamento do Sistema Único de Saúde

This e-book aims to bring a compendium of experience reports related to health management in the State of Goiás. Each chapter brings a description of the projects developed within the scope of the State Department of Health of Goiás, which are linked to the strategic objectives of the agency. These projects aim to strengthen strategic actions to optimize the planning of the Unified Health System

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part I - Theoretical Rationale.

Heart failure (HF) is a multifactorial chronic syndrome with progressive increasing incidence causing a huge financial burden worldwide. Remote monitoring should, in theory, improve HF management, but given increasing morbidity and mortality, a question remains: are we monitoring it properly? Device-based home monitoring enables objective and continuous measurement of vital variables and non-invasive devices should be first choice for elderly patients. There is no shortage of literature on the subject, however, most studies were designed to monitor a single variable or class of variables that were not properly assembled and, to the best of our knowledge, there are no large randomized studies about their impact on HF patient management. To overcome this problem, we carefully selected the most critical possible HF decompensating factors to design MONITORIA, a non-invasive device for comprehensive HF home monitoring. MONITORIA stands for MOnitoring Non-Invasively To Overcome mortality Rates of heart Insufficiency on Ambulatory, and in this paper, which is part I of a series of three articles, we discuss the theoretical basis for its design. MONITORIA and its inherent follow-up strategy will optimize HF patient care as it is a promising device, which will essentially adapt innovation not to the disease but rather to the patients.

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part II - Design.

INTRODUCTION: Heart failure (HF) represents a huge financial and economic burden worldwide. Some authors advocate that remote monitoring should be implemented to improve HF management, but given its increasing incidence, as well as its morbidity and mortality, a question still remains: are we monitoring it properly? There is no shortage of literature on home monitoring devices, however, most of them are designed to monitor an unsuitable array of variables and, to the best of our knowledge, there are no large randomized studies about their impact on morbidity/mortality of HF patients. OBJECTIVE: Description of a novel monitoring device. METHODS: As a solution, we designed MONITORIA (MOnitoring NonInvasively To Overcome mortality Rates of heart Insufficiency on Ambulatory). RESULTS: This is a multimodal device that will provide real time monitoring of vital, electrophysiological, hemodynamic and chemical signs, transthoracic impedance, and physical activity levels. The device is meant to perform continuous analysis and transmission of all data. Significant alterations in a patient's variable will alert the attending physician and, in case of potentially life-threatening situations, the national emergency medical system. The MONITORIA device will, also, have a function that sends shocks or functions as a pacemaker to treat certain arrhythmias/blockades. This function can be activated the very first time the patient utilizes it, based on their risk of sudden cardiac death. DISCUSSION/CONCLUSIONS: MONITORIA is a promising device mostly because it is included in a follow-up program that takes into account a multi-perspective feature of HF development and is based on the real world patient, adapting innovations not to the disease but rather to the patients.

Comparing the delivery to the hair bulb of two fluorescent molecules of distinct hydrophilicities by different nanoparticles and a serum formulation.

The follicular route is an important drug penetration pathway in any topical application, either concerning dermatological and cosmetic skin treatments or any transdermal administration regimen. Efficient transport into follicles will depend on drug inherent properties but also on the chosen vehicle. The main study goal was to compare several systems for the delivery to the hair bulb of two fluorescent molecules of different water affinities: the hydrophobic Nile Red and the quite similar but hydrophilic Nile Blue. Three common nanoparticle types were compared in terms of encapsulation efficiency and stability: liposomes, ethosomes and polymeric nanoparticles. A liquid serum-like formulation was also developed, adjusting the final ethanol amount to the type of dye to be solubilized. Then, this formulation and the nanoparticle systems that successfully passed characterization and stability stages were further studied on their ability to reach the bulb. The serum formulation was able to deliver, both drug models, to deeper follicular regions than nanoparticles. Attending to the envisioned zone target of the follicle, the simplest approach proved to be the best choice from all the systems tested in this work. Nonetheless, nanocarriers and the inherent complexity of their manufacturing processes may be justified under very specific requirements.

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part II - Design.

INTRODUCTION: Heart failure (HF) represents a huge financial and economic burden worldwide. Some authors advocate that remote monitoring should be implemented to improve HF management, but given its increasing incidence, as well as its morbidity and mortality, a question still remains: are we monitoring it properly? There is no shortage of literature on home monitoring devices, however, most of them are designed to monitor an unsuitable array of variables and, to the best of our knowledge, there are no large randomized studies about their impact on morbidity/mortality of HF patients. OBJECTIVE: Description of a novel monitoring device. METHODS: As a solution, we designed MONITORIA (MOnitoring NonInvasively To Overcome mortality Rates of heart Insufficiency on Ambulatory). RESULTS: This is a multimodal device that will provide real time monitoring of vital, electrophysiological, hemodynamic and chemical signs, transthoracic impedance, and physical activity levels. The device is meant to perform continuous analysis and transmission of all data. Significant alterations in a patient's variable will alert the attending physician and, in case of potentially life-threatening situations, the national emergency medical system. The MONITORIA device will, also, have a function that sends shocks or functions as a pacemaker to treat certain arrhythmias/blockades. This function can be activated the very first time the patient utilizes it, based on their risk of sudden cardiac death. DISCUSSION/CONCLUSIONS: MONITORIA is a promising device mostly because it is included in a follow-up program that takes into account a multi-perspective feature of HF development and is based on the real world patient, adapting innovations not to the disease but rather to the patients.

Antioxidant films and coatings based on starch and phenolics from Spondias purpurea L.

The objective of this study was to prepare, for the first time, active films and coatings from fruit starch (SPFS) and phenolic stem bark extract (SBPE) from Spondias purpurea L. Starch film formulations were prepared with different SBPE contents (5-20 wt% on starch), then cast and dried into films. SBPE showed higher antioxidant activity and antimicrobial activity against both Gram-negative and Gram-positive bacteria. Chemical, morphological, thermal, optical, mechanical, and barrier properties were studied for SPFS-SBPE films. In general, the phenolic extract caused significant changes in starch films (especially when in excess), such as gradual reduction of elastic modulus and tensile strength, increased elongation, opacity, and thermal properties (e.g. glass transition and melting enthalpy). On the other hand, SBPE provided the films with active properties (antioxidant and UV-absorbing). Coatings were applied to minimally processed mangoes (MPM), which were stored for 10 days at 12 °C. SBPE-containing coatings provided better protective action, reducing the total color difference (∆E⁎) and delaying the browning index (BI) during storage as well as reducing fungus attack. The active SPFS-SBPE films showed great potential as environmentally friendly active films and coatings.

Design of liposomes as drug delivery system for therapeutic applications.

Liposomes are spherical vesicles consisting of one or more concentric phospholipid bilayers enclosing an aqueous core. Being both nontoxic and biodegradable, liposomes represent a powerful delivery system for several drugs. They have improved the therapeutic efficacy of drugs through stabilizing compounds, overcoming obstacles to cellular and tissue uptake and increasing drug biodistribution to target sites in vivo, while minimizing systemic toxicity. This review offers an overview of liposomes, thought the exploration of their key fundamentals. Initially, the main design aspects to obtain a successful liposomal formulation were addressed, following the techniques for liposome production and drug loading. Before application, liposomes required an extensive characterization to assurance in vitro and in vivo performance. Thus, several properties to characterize liposomes were explored, such as size, polydispersity index, zeta potential, shape, lamellarity, phase behavior, encapsulation efficiency, and in vitro drug release. Topics related with liposomal functionalization and effective targeting strategies were also addressed, as well as stability and some limitations of liposomes. Finally, this review intends to explore the current market liposomes used as a drug delivery system in different therapeutic applications.

MONITORIA: The start of a new era of ambulatory heart failure monitoring? Part I - Theoretical Rationale.

Heart failure (HF) is a multifactorial chronic syndrome with progressive increasing incidence causing a huge financial burden worldwide. Remote monitoring should, in theory, improve HF management, but given increasing morbidity and mortality, a question remains: are we monitoring it properly? Device-based home monitoring enables objective and continuous measurement of vital variables and non-invasive devices should be first choice for elderly patients. There is no shortage of literature on the subject, however, most studies were designed to monitor a single variable or class of variables that were not properly assembled and, to the best of our knowledge, there are no large randomized studies about their impact on HF patient management. To overcome this problem, we carefully selected the most critical possible HF decompensating factors to design MONITORIA, a non-invasive device for comprehensive HF home monitoring. MONITORIA stands for MOnitoring Non-Invasively To Overcome mortality Rates of heart Insufficiency on Ambulatory, and in this paper, which is part I of a series of three articles, we discuss the theoretical basis for its design. MONITORIA and its inherent follow-up strategy will optimize HF patient care as it is a promising device, which will essentially adapt innovation not to the disease but rather to the patients.

Increased Encapsulation Efficiency of Methotrexate in Liposomes for Rheumatoid Arthritis Therapy.

Methotrexate (MTX) is a common drug used to treat rheumatoid arthritis. Due to the excessive side effects, encapsulation of MTX in liposomes is considered an effective delivery system, reducing drug toxicity, while maintaining its efficacy. The ethanol injection method is an interesting technique for liposome production, due to its simplicity, fast implementation, and reproducibility. However, this method occasionally requires the extrusion process, to obtain suitable size distribution, and achieve a low level of MTX encapsulation. Here, we develop a novel pre-concentration method, based on the principles of the ethanol injection, using an initial aqueous volume of 20% and 1:1 ratio of organic:aqueous phase (v/v). The liposomes obtained present small values of size and polydispersity index, without the extrusion process, and a higher MTX encapsulation (efficiency higher than 30%), suitable characteristics for in vivo application. The great potential of MTX to interact at the surface of the lipid bilayer was shown by nuclear magnetic resonance (NMR) studies, revealing mutual interactions between the drug and the main phospholipid via hydrogen bonding. In vivo experiments reveal that liposomes encapsulating MTX significantly increase the biological benefit in arthritic mice. This approach shows a significant advance in MTX therapeutic applications.

A study of lead uptake and distribution in horns from lead-dosed goats using synchrotron radiation-induced micro X-ray fluorescence elemental imaging.

OBJECTIVE: The principal goal of this study was to investigate the uptake and distribution of lead (Pb) in the horns of Pb-dosed goats, and to explore possible links to their historical Pb dosing records. Horn is a keratinized material that grows in discrete increments with the potential to preserve the historical record of past environmental exposures. While previous studies have leveraged this potential to examine environmental and biological phenomena in horns, Pb uptake has never been explored. METHODS: Horns were collected post-mortem from three goats that had been previously used to produce blood lead reference materials for the New York State proficiency testing program. The animals were periodically dosed with lead acetate, administered orally in a capsule, over a 5 to 8-year period. Horn cross sections were taken from each animal and analyzed using synchrotron radiation-induced micro X-ray fluorescence spectrometry (SR-µXRF) at the Cornell High Energy Synchrotron Source (CHESS). RESULTS: Elemental distribution maps were obtained by SR-µXRF for Pb, Ca, S, Se, and three other elements (Br, Zn and Cu), with values reported quantitatively as a mass fraction (µg/g for trace elements and mg/g for Ca and S). Accumulations of Pb were clearly visible as a series of narrow "rings" in each of the horn samples analyzed. The elements Ca, S, Br, Zn, and Cu were also detected as discrete rings within each cross-section, with Br strongly correlated with S in the samples examined. A marginal increase in Se may coincide with Pb accumulation in horn cross-sections. Annual mineralization estimates based on the relative distribution of Ca and S were used to establish a tentative timeline for horn growth, with each timeline linked to the pattern of Pb accumulation in the corresponding horn cross-section sample. CONCLUSIONS: Following ingestion, absorbed Pb is eventually deposited into caprine horns, resulting in discrete accumulations or "rings." Elemental mapping by SR-µXRF clearly show Ca-rich layers that vary with annual periodicity, consistent with previous reports of horn mineralization. Localized enrichment of Cu, Zn, Br and S appear to coincide with the keratinized regions related to the annual growth ring pattern in horns. Spatial analysis of horns for Pb accumulation may be useful as a qualitative marker of time-resolved exposures that may reflect specific periods of acute Pb absorption.

PTS micelles for the delivery of hydrophobic methotrexate.

Polyoxyethanyl-α-tocopheryl sebacate (PTS) is an amphiphilic compound with self-emulsifying properties known to form micelles. In this work, we report the production of PTS micelles for the encapsulation and delivery of a hydrophobic derivative of methotrexate, MTX di-ethylated (MTX-OEt). We optimized the micelles production by testing two different techniques: auxiliary solvent and sonication. Small and homogeneous micelles (≈40 nm) were obtained through the auxiliary solvent method performed at 30 °C and using 15 mg/mL of PTS. The produced micelles with the most promising physicochemical properties did not induce cytotoxicity when tested in normal human cells (BJ5ta cells), being considered for the encapsulation of MTX-OEt. This prodrug was achieved by Fisher esterification using ethanol, being isolated in good yield (η = 68%). MTX-OEt was efficiently encapsulated onto the produced micelles which preserved their physicochemical properties. The PTS micelles loaded with MTX-OEt, free MTX-OEt and free unmodified MTX revealed similar biological effect against cancer cells (Caco-2 cells). These results demonstrated that the biological activity of MTX is not altered after modification. The developed PTS micelles revealed a promising intracellular delivery performance with potentiality for cancer therapy.

Quantification of drugs encapsulated in liposomes by 1H NMR.

Liposomes are one of the most important and extensively studied drug delivery system due to their ability to encapsulate different kinds of drugs. Exploiting the advantages of 1H Nuclear Magnetic Resonance (NMR) spectrometry, we established a rapid and easy method for quantification of drugs encapsulated in liposomes. An internal standard, pyridine, was used for quantitative determination of drug concentration. Two different drugs were involved in this work, one hydrophilic, methotrexate disodium salt, and another hydrophobic, tamoxifen. The specificity and selectivity of the suggested method were evaluated by the absence of overlapping of at least one signal of each drug with pyridine in the NMR spectrum. The accuracy and precision of the method were assessed by adding a known amount of each drug to unloaded liposomes. Results obtained by quantitative NMR (qNMR) were validated and confirmed by comparing with two other traditional techniques, Ultraviolet-Visible (UV-vis) spectrophotometry and High-Performance Liquid Chromatography (HPLC). It was found that the results were consistent with the ones obtained from our proposed qNMR method. Considering all the experiments conducted in this study, we deliberate that qNMR can be a suitable tool for the determination of drugs encapsulated in liposomes.

Protective Effect of Saccharides on Freeze-Dried Liposomes Encapsulating Drugs.

The production of freeze-dried liposomes encapsulating drugs is considered a key challenge since the drugs are prone to leakage. The aim of this work was to study the effect of different saccharides on preserving the stability and drug retention capacity of a previously developed liposomal formulation, when subjected to a freeze-drying process. The protective role of trehalose, lactose, glucose, mannitol and sucrose, known for their cryo/lyoprotective effect, was tested by addition of different concentrations to liposomes. Sucrose, in a concentration dependent manner (8:1 sugar:lipids mass ratio) proved to be a suitable cryo/lyoprotectant of these liposomes. Effectively, this saccharide prevents the fusion or/and aggregation of the liposomal formulation, protecting the integrity of the freeze-dried empty liposomes. The liposomal formulation containing sucrose was studied in terms of morphology, concentration, and anticancer drugs retention ability. The study involved two drugs encapsulated in the aqueous core, methotrexate (MTX) and doxorubicin (DOX), and one drug located in the lipid bilayer, tamoxifen (TAM). After the freeze-drying process, liposomes with sucrose encapsulating drugs revealed high physical stability, maintaining their narrow and monodisperse character, however high leakage of the drugs encapsulated in the aqueous core was observed. Otherwise, no significant drug leakage was detected on liposomes containing the TAM, which maintained its biological activity after the freeze-drying process. These findings reveal that sucrose is a good candidate for the cryo/lyoprotection of liposomes with drugs located in the lipid bilayer.

Internalization of Methotrexate Conjugates by Folate Receptor-α.

The folate antagonist methotrexate is a cytotoxic drug used in the treatment of several cancer types. The entry of methotrexate into the cell is mediated by two main transport systems: the reduced folate carrier and membrane-associated folate receptors. These transporters differ considerably in their mechanism of (anti)folate uptake, substrate specificity, and tissue specificity. Although the mechanism of action of the reduced folate carrier is fairly well-established, that of the folate receptor has remained unknown. The development of specific folate receptor-targeted antifolates would be accelerated if additional mechanistic data were to become available. In this work, we used two fluorescently labeled conjugates of methotrexate, differently linked at the terminal groups, to clarify the uptake mechanism by folate receptor-α. The results demonstrate the importance of methotrexate amino groups in the interaction with folate receptor-α.

Characterization of Arsenic in dried baby shrimp (Acetes sp.) using synchrotron-based X-Ray Spectrometry and LC coupled to ICP-MS/MS.

The arsenic content of dried baby shrimp (Acetes sp.) was investigated as part of an independent field study of human exposure to toxic metals/metalloids among the ethnic Chinese community located in Upstate New York. The dried baby shrimp were analyzed in a home environment using a portable X-ray Fluorescence (XRF) instrument based on monochromatic excitation. Study participants had obtained their dried baby shrimp either from a local Chinese market or prepared them at home. The shrimp are typically between 10-20 mm in size and are consumed whole, without separating the tail from the head. Elevated levels of As were detected using portable XRF, ranging between 5-30 µg/g. Shrimp samples were taken to the Cornell High Energy Synchrotron Source (CHESS) for Synchrotron Radiation µXRF (SR-µXRF) elemental mapping using a 384-pixel Maia detector system. The Maia detector provided high resolution trace element images for As, Ca, and Br, (among others) and showed localized accumulation of As within the shrimp's cephalothorax (head), and various abdominal segments. As quantification by SR-µXRF was performed using a Lobster hepatopancreas reference material pellet (NRC-CNRC TORT-2), with results in good agreement with both portable XRF and ICP-MS. Additional As characterization using µX-ray Absorption Near Edge Spectroscopy (µXANES) with the Maia XRF detector at CHESS identified arsenobetaine and/or arsenocholine as the possible As species present. Further arsenic speciation analysis by LC-ICP-MS/MS confirmed that the majority of As (>95%) is present as the largely non-toxic arsenobetaine species with trace amounts of arsenocholine, methylated As and inorganic As species detected.