Proteomic analysis of the mucus of the photosynthetic sea slug Elysia crispata.

Elysia crispata is a tropical sea slug that can retain intracellular functional chloroplasts from its algae prey, a mechanism termed kleptoplasty. This sea slug, like other gastropods, secretes mucus, a viscous secretion with multiple functions, including lubrication, protection, and locomotion. This study presents the first comprehensive analysis of the mucus proteome of the sea slug E. crispata using gel electrophoresis and HPLC-MS/MS. We identified 306 proteins in the mucus secretions of this animal, despite the limited entries for E. crispata in the Uniprot database. The functional annotation of the mucus proteome using Gene Ontology identified proteins involved in different functions such as hydrolase activity (molecular function), carbohydrate-derived metabolic processes (biological processes) and cytoskeletal organization (cell component). Moreover, a high proportion of proteins with enzymatic activity in the mucus of E. crispata suggests potential biotechnological applications including antimicrobial and antitumor activities. Putative antimicrobial properties are reinforced by the high abundance of hydrolases. This study also identified proteins common in mucus samples from various species, supporting a common mechanism of mucus in protecting cells and tissues while facilitating animal movement. SIGNIFICANCE: Marine species are increasingly drawing the interest of researchers for their role in discovering new bioactive compounds. The study "Proteomic Analysis of the Mucus of the Photosynthetic Sea Slug Elysia crispata" is a pioneering effort that uncovers the complex protein content in this fascinating sea slug's mucus. This detailed proteomic study has revealed proteins with potential use in biotechnology, particularly for antimicrobial and antitumor purposes. This research is a first step in exploring the possibilities within the mucus of Elysia crispata, suggesting the potential for new drug discoveries. These findings could be crucial in developing treatments for severe diseases, especially those caused by multidrug-resistant bacteria, and may lead to significant advances in medical research.

Pro-Environmental Behavior and Climate Change Anxiety, Perception, Hope, and Despair According to Political Orientation.

The main objective of this paper is to assess pro-environmental behavior, climate change anxiety, perception, hope, and despair in different political orientations. Our specific aims included to assess the validity of all the instruments used; to assess whether the factor structure of the scales were valid across political orientations; to evaluate their reliability; to assess differences concerning age, gender, and political orientation; to learn the variables that explain pro-environmental behavior; and to evaluate the moderating role of climate change perception, despair, and hope in the relationship between climate change anxiety and pro-environmental behavior. Confirmatory factor analyses (CFAs), multi-group CFAs (to calculate measurement invariance), multiple linear regressions, and moderations were performed. Results showed that pro-environmental behavior and climate change hope achieved the four assessed levels of invariance across different political orientations; climate change anxiety achieved the first three levels of invariance; and climate change perception and climate change despair achieved configural invariance. Climate change anxiety, personal experience with climate change, and climate change perception (total, reality, and consequences) presented higher values for the left political orientation than for the right or the center. Climate change anxiety variables contributed most to explaining pro-environmental behaviors. Hope, despair, and climate change perception (consequences) moderated the relationship between climate change anxiety and pro-environmental behavior. These results open up new avenues for investigation, specifically to understand why high levels of anxiety lead to more pro-environmental behaviors.

Polar Lipids of Marine Microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis Mitigate the LPS-Induced Pro-Inflammatory Response in Macrophages.

Microalgae are recognized as a relevant source of bioactive compounds. Among these bioactive products, lipids, mainly glycolipids, have been shown to present immunomodulatory properties with the potential to mitigate chronic inflammation. This study aimed to evaluate the anti-inflammatory effect of polar lipids isolated from Nannochloropsis oceanica and Chlorococcum amblystomatis. Three fractions enriched in (1) digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG), (2) monogalactosyldiacylglycerol (MGDG), and (3) diacylglyceryl-trimethylhomoserine (DGTS) and phospholipids (PL) were obtained from the total lipid extracts (TE) of N. oceanica and C. amblystomatis, and their anti-inflammatory effect was assessed by analyzing their capacity to counteract nitric oxide (NO) production and transcription of pro-inflammatory genes Nos2, Ptgs2, Tnfa, and Il1b in lipopolysaccharide (LPS)-activated macrophages. For both microalgae, TE and Fractions 1 and 3 strongly inhibited NO production, although to different extents. A strong reduction in the LPS-induced transcription of Nos2, Ptgs2, Tnfa, and Il1b was observed for N. oceanica and C. amblystomatis lipids. The most active fractions were the DGTS-and-PL-enriched fraction from N. oceanica and the DGDG-and-SQDG-enriched fraction from C. amblystomatis. Our results reveal that microalgae lipids have strong anti-inflammatory capacity and may be explored as functional ingredients or nutraceuticals, offering a natural solution to tackle chronic inflammation-associated diseases.

Cocrystals Enhance Biopharmaceutical and Antimicrobial Properties of Norfloxacin.

A solvate cocrystal of the antimicrobial norfloxacin (NFX) was formed by using isonicotinamide (INA) as a coformer with the solvent evaporation technique. The cocrystal formation was confirmed by performing solid-state characterization techniques. We evaluated the dissolution under supersaturated conditions and also the solubility at the vertex of triphasic domain of cocrystal and NFX in both water and Fasted-State Simulated Intestinal Fluid (FaSSIF). The antimicrobial activity was evaluated using the microdilution technique. The cocrystal showed 1.8 times higher dissolution than NFX in water at 60 min and 1.3 times higher in FaSSIF at 180 min in the kinetic study. The cocrystal also had an increase in solubility of 8.38 times in water and 6.41 times in FaSSIF. The biopharmaceutical properties of NFX with cocrystallization improved antimicrobial action, as shown in the results of minimum inhibitory concentration (MIC) and inhibitory concentrations of 50% (IC50%) and 90% (IC90%). This paper presents, for the first time, a more in-depth analysis of the cocrystal of NFX-INA concerning its dissolution, solubility, and antimicrobial activity. In all these criteria, the cocrystal obtained better results compared to the pure drug.

Differences and Similarities in Lipid Composition, Nutritional Value, and Bioactive Potential of Four Edible Chlorella vulgaris Strains.

The microalga Chlorella vulgaris is a popular food ingredient widely used in the industry, with an increasing market size and value. Currently, several edible strains of C. vulgaris with different organoleptic characteristics are commercialized to meet consumer needs. This study aimed to compare the fatty acid (FA) and lipid profile of four commercialized strains of C. vulgaris (C-Auto, C-Hetero, C-Honey, and C-White) using gas- and liquid-chromatography coupled to mass-spectrometry approaches, and to evaluate their antioxidant and anti-inflammatory properties. Results showed that C-Auto had a higher lipid content compared to the other strains and higher levels of omega-3 polyunsaturated FAs (PUFAs). However, the C-Hetero, C-Honey, and C-White strains had higher levels of omega-6 PUFAs. The lipidome signature was also different between strains, as C-Auto had a higher content of polar lipids esterified to omega-3 PUFAs, while C-White had a higher content of phospholipids with omega-6 PUFAs. C-Hetero and C-Honey showed a higher content of triacylglycerols. All extracts showed antioxidant and anti-inflammatory activity, highlighting C-Auto with greater potential. Overall, the four strains of C. vulgaris can be selectively chosen as a source of added-value lipids to be used as ingredients in food and nutraceutical applications for different market needs and nutritional requirements.

Synthesis of Submicrometric Chitosan Particles Loaded with Calcium Phosphate for Biomedical Applications.

Chitosan particles loaded with dibasic calcium phosphate anhydrous (DCPA) is a promising strategy for combining antimicrobial and osteoconduction properties in regenerative medicine. However, mostly micrometer-sized particles have been reported in the literature, limiting their use and reducing their effect in the biomedical field. We have recently overcome this limitation by developing submicrometer-sized particles with electrospray technique. The objective of this study was to understand how the process parameters control the size and properties of submicrometer chitosan particles loaded with DCPA. Solutions of 10 mg/mL chitosan and 2.5 mg/mL DCPA in a 90% acetic acid were electrosprayed under three distinct flow rate conditions: 0.2, 0.5, and 1.0 mL/h. The particles were crosslinked in a glutaraldehyde atmosphere and characterized in terms of their morphology, inorganic content, zeta potential, and minimum inhibitory concentration (MIC) against S. mutans. All conditions showed particles with two similar morphologies: one small-sized with a spherical shape and another larger-sized with a bi-concave shape. All generated a broad particle size distribution, with a similar mean size of ~ 235 nm. The addition of DCPA decreased the zeta potential for all the samples, but it was above 30 mV, indicating a low aggregation potential. The lower flow rate showed the worst efficacy for DCPA incorporation. Antimicrobial activity was greater in chitosan/DCPA particles with flow rate of 0.5 mL/h. It can be concluded that the flow rate of 0.5 mL/h presents the best compromise solution in terms of morphology, zeta potential, MIC, and inorganic content.

Lipidomic Characterization and Antioxidant Activity of Macro- and Microalgae Blend.

Macro- and microalgae are currently recognized sources of lipids with great nutritional quality and attractive bioactivities for human health promotion and disease prevention. Due to the lipidomic diversity observed among algae species, giving rise to different nutritional and functional characteristics, the mixture of macro- and microalgae has the potential to present important synergistic effects resulting from the complementarity among algae. The aim of this work was to characterize for the first time the lipidome of a blend of macro- and microalgae and evaluate the antioxidant capacity of its lipid fraction. Fatty acids were profiled by GC-MS, the polar lipidome was identified by high resolution LC-MS, and ABTS+• and DPPH• assays were used to assess the antioxidant potential. The most abundant fatty acids were oleic (18:1 n-9), α-linolenic (18:3 n-3), and linoleic (18:2 n-6) acids. The lipid extract presented a beneficial n-6/n-3 ratio (0.98) and low values of atherogenic (0.41) and thrombogenic indices (0.27). The polar lipidome revealed 462 lipid species distributed by glycolipids, phospholipids, and betaine lipids, including some species bearing PUFA and a few with reported bioactivities. The lipid extract also showed antioxidant activity. Overall, the results are promising for the valorization of this blend for food, nutraceutical, and biotechnological applications.

Bioprospecting antibiotic properties in photodynamic therapy of lipids from Codium tomemtosum and Chlorella vulgaris.

The growing resistance from pathogens against antibiotics has increased the research for new compounds and strategies with antibacterial potential. Lipids from algae are emerging as natural and potent bioactive molecules with interesting results regarding the inactivation of bacteria, viruses, and fungi. The combination of algae lipids with innovative strategies, such as antibacterial photodynamic therapy (aPDT) can enhance their antimicrobial potential. In this work, we aimed to evaluate the antibacterial potential in aPDT of total lipid extracts and polar lipid fractions from the green macroalga, Codium tomentosum, and the green microalga, Chlorella vulgaris on a Gram-positive bacteria Staphylococcus aureus. Total lipid extracts and polar lipid fractions were characterized by LC-MS. The results revealed that the total extracts of algae promote S. aureus inhibition after light irradiation, with a decrease of ca. 6 log10 (CFU/mL) after 15 min of treatment with both extracts of algae. The polar lipid fractions, composed by phospholipids, glycolipids and betaine lipids, from C. tomentosum and C. vulgaris also revealed antibacterial potential in combination with aPDT, but a decrease of ca. 6 log10 (CFU/mL) was reached at 60 min of treatment, later than with the total extracts. These results unveil algae lipids as antibacterial compounds in combination with aPDT displaying an alternative from natural origin to tackle pathogen resistance.

Aposymbiotic Specimen of the Photosynthetic Sea Slug Elysia crispata.

Elysia crispata is a sacoglossan sea slug that retains intracellular, functional chloroplasts stolen from their macroalgal food sources. Elysia crispata juveniles start feeding on the algae following metamorphosis, engulfing chloroplasts and turning green. In laboratory-reared animals, we report one juvenile "albino" specimen unable to retain chloroplasts. Within 6 weeks post-metamorphosis, the aposymbiotic sea slug was significantly smaller than its chloroplast-bearing siblings. This evidence highlights that chloroplast acquisition is required for the normal development of E. crispata.

Sea Slug Mucus Production Is Supported by Photosynthesis of Stolen Chloroplasts.

A handful of sea slugs of the order Sacoglossa are able to steal chloroplasts-kleptoplasts-from their algal food sources and maintain them functionally for periods ranging from several weeks to a few months. In this study, we investigated the role of kleptoplast photosynthesis on mucus production by the tropical sea slug Elysia crispata. Animals reared for 5 weeks in quasi dark (5 µmol photons m-2 s-1) showed similar growth to those under regular light (60-90 µmol photons m-2 s-1), showing that kleptoplast photosynthesis was not relevant for growth when sea slugs were fed ad libitum. However, when subjected to short-term desiccation stress, animals reared under regular light produced significantly more mucus. Furthermore, the carbohydrate content of secreted mucus was significantly lower in slugs limited in the photosynthetic activity of their kleptoplasts by quasi-dark conditions. This study indicates that photosynthesis supports the synthesis of protective mucus in kleptoplast-bearing sea slugs.

Applications of lipidomics in marine organisms: progress, challenges and future perspectives.

Marine ecosystems comprise a high diversity of life forms, such as algae, invertebrates, and vertebrates. These organisms have adapted their physiology according to the conditions of the environments in which they inhabit. In the last few years, the study of lipids of marine origin has received increasing attention due to the diversity of their composition. The progress of analytical techniques such as LC-MS and MS/MS has allowed researchers to improve accurate processing of samples and lipid characterization. Lipidomics is a useful research field to understand marine ecosystems and the physiology of their organisms. The screening of biological systems in marine environments has demonstrated a significant diversity of lipids in their living resources. In this review, we provide the state-of-the-art marine of lipidomics studies. We describe in detail the lipidomics approach for the analysis of marine lipidomes, including sample collection and preparation, interpretation of MS/MS fragmentation fingerprinting, data analysis and processing. Special attention is also given to illustrate the latest applications and advances of applied LC-MS lipidomic analyses in diversified studies of different marine organisms, as well as the challenges and future perspectives of marine lipidomics.

Algal Lipids as Modulators of Skin Disease: A Critical Review.

The prevalence of inflammatory skin diseases continues to increase with a high incidence in children and adults. These diseases are triggered by environmental factors, such as UV radiation, certain chemical compounds, infectious agents, and in some cases, people with a genetic predisposition. The pathophysiology of inflammatory skin diseases such as psoriasis or atopic dermatitis, but also of skin cancers, is the result of the activation of inflammation-related metabolic pathways and the overproduction of pro-inflammatory cytokines observed in in vitro and in vivo studies. Inflammatory skin diseases are also associated with oxidative stress, overproduction of ROS, and impaired antioxidant defense, which affects the metabolism of immune cells and skin cells (keratinocytes and fibroblasts) in systemic and skin disorders. Lipids from algae have been scarcely applied to modulate skin diseases, but they are well known antioxidant and anti-inflammatory agents. They have shown scavenging activities and can modulate redox homeostasis enzymes. They can also downmodulate key inflammatory signaling pathways and transcription factors such as NF-κB, decreasing the expression of pro-inflammatory mediators. Thus, the exploitation of algae lipids as therapeutical agents for the treatment of inflammatory skin diseases is highly attractive, being critically reviewed in the present work.

Multi-Omic Profiling of Macrophages Treated with Phospholipids Containing Omega-3 and Omega-6 Fatty Acids Reveals Complex Immunomodulatory Adaptations at Protein, Lipid and Metabolic Levels.

In recent years, several studies have demonstrated that polyunsaturated fatty acids have strong immunomodulatory properties, altering several functions of macrophages. In the present work, we sought to provide a multi-omic approach combining the analysis of the lipidome, the proteome, and the metabolome of RAW 264.7 macrophages supplemented with phospholipids containing omega-3 (PC 18:0/22:6; ω3-PC) or omega-6 (PC 18:0/20:4; ω6-PC) fatty acids, alone and in the presence of lipopolysaccharide (LPS). Supplementation of macrophages with ω3 and ω6 phospholipids plus LPS produced a significant reprogramming of the proteome of macrophages and amplified the immune response; it also promoted the expression of anti-inflammatory proteins (e.g., pleckstrin). Supplementation with the ω3-PC and ω6-PC induced significant changes in the lipidome, with a marked increase in lipid species linked to the inflammatory response, attributed to several pro-inflammatory signalling pathways (e.g., LPCs) but also to the pro-resolving effect of inflammation (e.g., PIs). Finally, the metabolomic analysis demonstrated that supplementation with ω3-PC and ω6-PC induced the expression of several metabolites with a pronounced inflammatory and anti-inflammatory effect (e.g., succinate). Overall, our data show that supplementation of macrophages with ω3-PC and ω6-PC effectively modulates the lipidome, proteome, and metabolome of these immune cells, affecting several metabolic pathways involved in the immune response that are triggered by inflammation.

Seaweed Blends as a Valuable Source of Polyunsaturated and Healthy Fats for Nutritional and Food Applications.

Seaweeds are considered healthy and sustainable food. Although their consumption is modest in Western countries, the demand for seaweed in food markets is increasing in Europe. Each seaweed species has unique nutritional and functional features. The preparation of blends, obtained by mixing several seaweeds species, allows the obtaining of maximum benefits and ingredients with single characteristics. In this work, five seaweed blends, commercially available and produced under organic conditions in Europe, were characterized. The proximal composition included contents of ash (20.28-28.68% DW), proteins (17.79-26.61% DW), lipids (0.55-1.50% DW), and total carbohydrates (39.47-47.37% DW). Fatty acid profiles were determined by gas chromatography-mass spectrometry (GC-MS), allowing quantification of healthy fatty acids, namely n-3 and n-6 polyunsaturated fatty acids (PUFA), and calculation of lipid quality indices. Each blend showed a characteristic PUFA content in the lipid pool (35.77-49.43% of total fatty acids) and the content in essential and healthy n-3 PUFA is highlighted. The atherogenicity (0.54-0.72) and thrombogenicity (0.23-0.45) indices evidenced a good nutritional value of lipid fractions. As nutritional and environmentally attractive products, the consumption of the studied seaweed blends can contribute to a healthy lifestyle.

Bioactivities of Lipid Extracts and Complex Lipids from Seaweeds: Current Knowledge and Future Prospects.

While complex lipids of seaweeds are known to display important phytochemical properties, their full potential is yet to be explored. This review summarizes the findings of a systematic survey of scientific publications spanning over the years 2000 to January 2021 retrieved from Web of Science (WoS) and Scopus databases to map the state of the art and identify knowledge gaps on the relationship between the complex lipids of seaweeds and their reported bioactivities. Eligible publications (270 in total) were classified in five categories according to the type of studies using seaweeds as raw biomass (category 1); studies using organic extracts (category 2); studies using organic extracts with identified complex lipids (category 3); studies of extracts enriched in isolated groups or classes of complex lipids (category 4); and studies of isolated complex lipids molecular species (category 5), organized by seaweed phyla and reported bioactivities. Studies that identified the molecular composition of these bioactive compounds in detail (29 in total) were selected and described according to their bioactivities (antitumor, anti-inflammatory, antimicrobial, and others). Overall, to date, the value for seaweeds in terms of health and wellness effects were found to be mostly based on empirical knowledge. Although lipids from seaweeds are little explored, the published work showed the potential of lipid extracts, fractions, and complex lipids from seaweeds as functional ingredients for the food and feed, cosmeceutical, and pharmaceutical industries. This knowledge will boost the use of the chemical diversity of seaweeds for innovative value-added products and new biotechnological applications.

Bis-thiobarbiturates as Promising Xanthine Oxidase Inhibitors: Synthesis and Biological Evaluation.

Xanthine oxidase (XO) is the enzyme responsible for the conversion of endogenous purines into uric acid. Therefore, this enzyme has been associated with pathological conditions caused by hyperuricemia, such as the disease commonly known as gout. Barbiturates and their congeners thiobarbiturates represent a class of heterocyclic drugs capable of influencing neurotransmission. However, in recent years a very large group of potential pharmaceutical and medicinal applications have been related to their structure. This great diversity of biological activities is directly linked to the enormous opportunities found for chemical change off the back of these findings. With this in mind, sixteen bis-thiobarbiturates were synthesized in moderate to excellent reactional yields, and their antioxidant, anti-proliferative, and XO inhibitory activity were evaluated. In general, all bis-thiobarbiturates present a good antioxidant performance and an excellent ability to inhibit XO at a concentration of 30 µM, eight of them are superior to those observed with the reference drug allopurinol (Allo), nevertheless they were not as effective as febuxostat. The most powerful bis-thiobarbiturate within this set showed in vitro IC50 of 1.79 µM, which was about ten-fold better than Allo inhibition, together with suitable low cytotoxicity. In silico molecular properties such as drug-likeness, pharmacokinetics, and toxicity of this promising barbiturate were also analyzed and herein discussed.

Photosynthesis from stolen chloroplasts can support sea slug reproductive fitness.

Some sea slugs are able to steal functional chloroplasts (kleptoplasts) from their algal food sources, but the role and relevance of photosynthesis to the animal host remain controversial. While some researchers claim that kleptoplasts are slowly digestible 'snacks', others advocate that they enhance the overall fitness of sea slugs much more profoundly. Our analysis shows light-dependent incorporation of 13C and 15N in the albumen gland and gonadal follicles of the sea slug Elysia timida, representing translocation of photosynthates to kleptoplast-free reproductive organs. Long-chain polyunsaturated fatty acids with reported roles in reproduction were produced in the sea slug cells using labelled precursors translocated from the kleptoplasts. Finally, we report reduced fecundity of E. timida by limiting kleptoplast photosynthesis. The present study indicates that photosynthesis enhances the reproductive fitness of kleptoplast-bearing sea slugs, confirming the biological relevance of this remarkable association between a metazoan and an algal-derived organelle.

Cardiac phospholipidome is altered during ischemia and reperfusion in an ex vivo rat model.

Acute myocardial infarction (AMI) is the leading cause of death, morbidity, and health costs worldwide. In AMI, a sudden blockage of blood flow causes myocardial ischemia and cell death. Reperfusion after ischemia has paradoxical effects and may exacerbate the myocardial injury, a process known as ischemic reperfusion injury. In this work we evaluated the lipidome of isolated rat hearts, maintained in controlled perfusion (CT), undergoing global ischemia (ISC) or ischemia followed by reperfusion (IR). 153 polar lipid levels were significantly different between conditions. 48 features had q < 0.001 and included 8 phosphatidylcholines and 4 lysophospholipids, which were lower in ISC compared to CT, and even lower in the IR group, suggesting that IR induces more profound changes than ISC. We observed that the levels of 16 alkyl acyl phospholipids were significantly altered during ISC and IR. Overall, these data indicate that myocardial lipid remodelling and possibly damage occurs to a greater extent during reperfusion. The adaptation of cardiac lipidome during ISC and IR described is consistent with the presence of oxidative damage and may reflect the impact of AMI on the lipidome at the cellular level and provide new insights into the role of lipids in the pathophysiology of acute myocardial ischemia/reperfusion injury.

The health workforce demand: a systematic literature review.

Understanding imbalances between the supply and demand of the human resour- ces for health (HRH) is essential for enhancing health outcomes. Addressing the HRH demand is particularly challenging, especially given the deficit of accurate data and surplus of unresolved methodological flaws. This study presents a systematic review of the literature surrounding HRH demand and answers the following key questions: How has HRH demand been addressed? What are the harms and barriers that accompany HRH demand modeling? This systematic review was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement. Relevant keywords were used in a thorough search of the PubMed/MEDLINE, SCOPUS, and Web of Science databases. A total of 2,599 papers were retrieved and evaluated according to their title and abstract. Of these, the full-text of 400 papers was analyzed, 53 of which successfully met the inclusion criteria in our study. While the topic's relevance is widespread, it still lacks a validated approach to model HRH demand adequately. The main characteristics of the applied methods are presented, such as their application complexity by health policymakers. Opportunities and orientations for further research are also highlighted.

The health workforce demand: a systematic literature review / A procura por recursos humanos em saúde: revisão sistemática da literatura

Abstract Understanding imbalances between the supply and demand of the human resour- ces for health (HRH) is essential for enhancing health outcomes. Addressing the HRH demand is particularly challenging, especially given the deficit of accurate data and surplus of unresolved methodological flaws. This study presents a systematic review of the literature surrounding HRH demand and answers the following key questions: How has HRH demand been addressed? What are the harms and barriers that accompany HRH demand modeling? This systematic review was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement. Relevant keywords were used in a thorough search of the PubMed/MEDLINE, SCOPUS, and Web of Science databases. A total of 2,599 papers were retrieved and evaluated according to their title and abstract. Of these, the full-text of 400 papers was analyzed, 53 of which successfully met the inclusion criteria in our study. While the topic's relevance is widespread, it still lacks a validated approach to model HRH demand adequately. The main characteristics of the applied methods are presented, such as their application complexity by health policymakers. Opportunities and orientations for further research are also highlighted.

Resumo A compreensão dos desequilíbrios entre a demanda e a oferta da mão de obra em saúde (MOS) é essencial para a melhoria dos resultados em saúde. A demanda por MOS, em particular, é bastante desafiante dada a falta de dados e aspetos metodológicos que ainda estão por abordar. Este estudo apresenta uma revisão sistemática da literatura procurando responder às seguintes questões: Como tem sido abordada a demanda por MOS? Quais são as barreiras e limitações neste processo? A metodologia adotada baseou-se no PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-analyses). A pesquisa foi realizada nas bases de dados PubMed/MEDLINE, SCOPUS e Web of Science, usando palavras-chave relevantes. No total 2 599 artigos foram recolhidos e analisados de acordo com os respetivos títulos e resumos. O texto integral de 400 artigos foi alvo de análise, tendo sido selecionados 53 artigos com base em critérios pré-definidos. Apesar da relevância do tema, não existe, ainda, um método para modelar a procura por MOS validado pela literatura científica. Esta revisão, além de destacar oportunidades e apontar direções de investigação futura, apresenta as principais características da modelação da procura de MOS, como a sua aplicabilidade na ótica do utilizador (decisor político).