Association between severity of symptoms and minimum mental health treatment duration in humanitarian contexts: a retrospective observational study.

Background: Understanding and optimising mental health and psychosocial support (MHPSS) interventions in humanitarian crises is crucial, particularly for the most prevalent mental health conditions in conflict settings: anxiety, depression, and post-traumatic stress disorder. However, research on what is the most appropriate length of psychological intervention is lacking in this setting. We aimed to establish which factors are most closely related to improvement and to determine the required number of consultations needed to achieve this improvement. Methods: We retrospectively analysed records from 9028 patients allocated to treatment for anxiety, depression, and post-traumatic symptoms from the MHPSS programme in Borno State, Nigeria, from January 2018 to December 2019. Patient characteristics, severity (Clinical Global Impression of Severity Scale, CGI-S scale), and clinical improvement were assessed by an attending counsellor (CGI-I scale) and by the patient (Mental Health Global State, MHGS scale). Improvement was defined as scores 1, 2, and 3 in the Clinical Global Impression of Improvement (CGI-I) scale, and as a decrease of at least 4 points in the MHGS scale. We investigated the associations between the category of symptoms, the severity of illness, and improvement of symptoms using multivariable logistic regression. We used Kaplan-Meier (KM) curves to assess the number of consultations (i.e., time of treatment) needed to achieve improvement of symptoms, by symptom category and symptom severity. Findings: The patients included were referred to treatment for anxiety (n = 3462), depression (n = 3970), or post-traumatic symptoms (n = 1596). Median age was 31 years (range 16-103), and 84.3% were female. Patients categorised as severe were less likely to present improvement according to the CGI-I scale (OR 0.11, 95% CI 0.05-0.25), while none of the other categories of symptoms showed significant results. Overall, three or more consultations were associated with improvement in both scales (OR 3.55, 95% CI 1.47-8.57 for CGI-I; and OR 3.04, 95% CI 2.36-3.90 for MHGS). KM curves for the category of symptoms showed that around 90% of patients with anxiety, depression, or post-traumatic symptoms, as well as those with mild or moderate severity, presented improvement after three consultations, compared with six consultations for those with severe symptoms. Interpretation: Classification by severity among patients with anxiety, depression, or post-traumatic symptoms could predict the probability of improvement, whereas classification by symptoms could not. Our study highlights the importance of classifying patient severity in MHPSS programmes to plan and implement the appropriate duration of care. A major limitation was the number of patients lost to follow up after the first consultation and excluded from the logistic regression and KM analysis. Funding: The study was funded and staffed entirely by Médicos Sin Fronteras (Médecins Sans Frontières), Spain.

Bioactive Components and Biological Activities of Crocus sativus L. Byproducts: A Comprehensive Review.

The production of saffron spice results in numerous byproducts, as only 15 g of spice can be produced from 1 kg of flowers, indicating that over 90% of the saffron flower material is eventually discarded as waste. In view of this, the paper reviews current knowledge on the natural active components in saffron byproducts and their biological activities, aiming to lay a theoretical and scientific foundation for the further utilization. Saffron byproducts contain a variety of phytochemical components, such as flavonoids, anthocyanins, carotenoids, phenolic acids, monoterpenoids, alkaloids, glycosides, and saponins. The activities of saffron byproducts and their mechanisms are also discussed in detail here.

Seasonal malaria chemoprevention in a context of high presumed sulfadoxine-pyrimethamine resistance: malaria morbidity and molecular drug resistance profiles in South Sudan.

BACKGROUND: Seasonal malaria chemoprevention (SMC) using sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), is a community-based malaria preventive strategy commonly used in the Sahel region of sub-Saharan Africa. However, to date it has not been implemented in East Africa due to high SP resistance levels. This paper is a report on the implementation of SMC outside of the Sahel in an environment with a high level of presumed SP-resistance: five cycles of SMC using SPAQ were administered to children 3-59 months during a period of high malaria transmission (July-December 2019) in 21 villages in South Sudan. METHODS: A population-based SMC coverage survey was combined with a longitudinal time series analysis of health facility and community health data measured after each SMC cycle. SMC campaign effectiveness was assessed by Poisson model. SPAQ molecular resistance markers were additionally analysed from dried blood spots from malaria confirmed patients. RESULTS: Incidence of uncomplicated malaria was reduced from 6.6 per 100 to an average of 3.2 per 100 after SMC administration (mean reduction: 53%) and incidence of severe malaria showed a reduction from 21 per 10,000 before SMC campaign to a mean of 3.3 per 10,000 after each cycle (mean reduction: 84%) in the target group when compared to before the SMC campaign. The most prevalent molecular haplotype associated with SP resistance was the IRNGE haplotype (quintuple mutant, with 51I/59R/108N mutation in pfdhfr + 437G/540E in pfdhps). In contrast, there was a low frequency of AQ resistance markers and haplotypes resistant to both drugs combined (< 2%). CONCLUSIONS: The SMC campaign was effective and could be used as an additional preventive tool in seasonal malaria settings outside of the Sahel, especially in areas where access to health care is unstable. Malaria case load reduction was observed despite the high level of resistance to SP.

Screening for K13-Propeller Mutations Associated with Artemisinin Resistance in Plasmodium falciparum in Yambio County (Western Equatoria State, South Sudan).

Artemisinin-combined treatments are the recommended first-line treatment of Plasmodium falciparum malaria, but they are being threatened by emerging artemisinin resistance. Mutations in pfk13 are the principal molecular marker for artemisinin resistance. This study characterizes the presence of mutations in pfk13 in P. falciparum in Western Equatoria State, South Sudan. We analyzed 468 samples from patients with symptomatic malaria and found 15 mutations (8 nonsynonymous and 7 synonymous). Each mutation appeared only once, and none were validated or candidate markers of artemisinin resistance. However, some mutations were in the same or following position of validated and candidate resistance markers, suggesting instability of the gene that could lead to resistance. The R561L nonsynonymous mutation was found in the same position as the R561H validated mutation. Moreover, the A578S mutation, which is widespread in Africa, was also reported in this study. We found a high diversity of other pfk13 mutations in low frequency. Therefore, routine molecular surveillance of resistance markers is highly recommended to promptly detect the emergence of resistance-related mutations and to limit their spread.

A hybrid physics-based and data-driven framework for cellular biological systems: Application to the morphogenesis of organoids.

How cells orchestrate their cellular functions remains a crucial question to unravel how they organize in different patterns. We present a framework based on artificial intelligence to advance the understanding of how cell functions are coordinated spatially and temporally in biological systems. It consists of a hybrid physics-based model that integrates both mechanical interactions and cell functions with a data-driven model that regulates the cellular decision-making process through a deep learning algorithm trained on image data metrics. To illustrate our approach, we used data from 3D cultures of murine pancreatic ductal adenocarcinoma cells (PDAC) grown in Matrigel as tumor organoids. Our approach allowed us to find the underlying principles through which cells activate different cell processes to self-organize in different patterns according to the specific microenvironmental conditions. The framework proposed here expands the tools for simulating biological systems at the cellular level, providing a novel perspective to unravel morphogenetic patterns.

Antifungal Effect of Autochthonous Aromatic Plant Extracts on Two Mycotoxigenic Strains of Aspergillus flavus.

This study identified the compounds obtained from four native Dehesa plants, which were holm oak, elm, blackberry and white rockrose, and evaluated their ability to inhibit the growth and production of aflatoxins B1 and B2 of two strains of mycotoxigenic Aspergillus flavus. For this purpose, phenolic compounds present in the leaves and flowers of the plants were extracted and identified, and subsequently, the effect on the growth of A. flavus, aflatoxin production and the expression of a gene related to its synthesis were studied. Cistus albidus was the plant with the highest concentration of phenolic compounds, followed by Quercus ilex. Phenolic acids and flavonoids were mainly identified, and there was great variability among plant extracts in terms of the type and quantity of compounds. Concentrated and diluted extracts were used for each individual plant. The influence on mold growth was not very significant for any of the extracts. However, those obtained from plants of the genus Quercus ilex, followed by Ulmus sp., were very useful for inhibiting the production of aflatoxin B1 and B2 produced by the two strains of A. flavus. Expression studies of the gene involved in the aflatoxin synthesis pathway did not prove to be effective. The results indicated that using these new natural antifungal compounds from the Dehesa for aflatoxin production inhibition would be desirable, promoting respect for the environment by avoiding the use of chemical fungicides. However, further studies are needed to determine whether the specific phenolic compounds responsible for the antifungal activity of Quercus ilex and Ulmus sp. produce the antifungal activity in pure form, as well as to verify the action mechanism of these compounds.

Tumour growth: An approach to calibrate parameters of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment.

To unravel processes that lead to the growth of solid tumours, it is necessary to link knowledge of cancer biology with the physical properties of the tumour and its interaction with the surrounding microenvironment. Our understanding of the underlying mechanisms is however still imprecise. We therefore developed computational physics-based models, which incorporate the interaction of the tumour with its surroundings based on the theory of porous media. However, the experimental validation of such models represents a challenge to its clinical use as a prognostic tool. This study combines a physics-based model with in vitro experiments based on microfluidic devices used to mimic a three-dimensional tumour microenvironment. By conducting a global sensitivity analysis, we identify the most influential input parameters and infer their posterior distribution based on Bayesian calibration. The resulting probability density is in agreement with the scattering of the experimental data and thus validates the proposed workflow. This study demonstrates the huge challenges associated with determining precise parameters with usually only limited data for such complex processes and models, but also demonstrates in general how to indirectly characterise the mechanical properties of neuroblastoma spheroids that cannot feasibly be measured experimentally.

Antimicrobial Properties of Essential Oils Obtained from Autochthonous Aromatic Plants.

The aim of this work was to determine the antimicrobial activity of the essential oils of six plants widely distributed in the Dehesa of Extremadura, such as Calendula officinalis, Cistus ladanifer, Cistus salviifolius, Cistus multiflorus, Lavandula stoechas, and Rosmarinus officinalis. The content of total phenolic compounds (TPC) and the antimicrobial activity of the essential oils against pathogenic and spoilage bacteria and yeasts as well as aflatoxin-producing molds were determined. A great variability was observed in the composition of the essential oils obtained from the six aromatic plants. The Cistus ladanifer essential oil had the highest content of total phenols (287.32 ppm), followed by the Cistus salviifolius essential oil; and the Rosmarinus officinalis essential oil showed the lowest amount of these compounds. The essential oils showed inhibitory effects on the tested bacteria and also yeasts, showing a maximum inhibition diameter of 11.50 mm for Salmonella choleraesuis and Kregervanrija fluxuum in the case of Cistus ladanifer and a maximum diameter of 9 mm for Bacillus cereus and 9.50 mm for Priceomyces carsonii in the case of Cistus salviifolius. The results stated that antibacterial and antiyeast activity is influenced by the concentration and the plant material used for essential oil preparation. In molds, aflatoxin production was inhibited by all the essential oils, especially the essential oils of Cistus ladanifer and Cistus salviifolius. Therefore, it can be concluded that the essential oils of native plants have significant antimicrobial properties against pathogenic and spoilage microorganisms, so they could be studied for their use in the industry as they are cheap, available, and non-toxic plants that favor the sustainability of the environment of the Dehesa of Extremeña.

Plasmodium falciparum pfhrp2 and pfhrp3 Gene Deletions in Malaria-Hyperendemic Region, South Sudan.

Pfhrp2 and pfhrp3 gene deletions threaten the use of Plasmodium falciparum malaria rapid diagnostic tests globally. In South Sudan, deletion frequencies were 15.6% for pfhrp2, 20.0% for pfhrp3, and 7.5% for double deletions. Deletions were approximately twice as prevalent in monoclonal infections than in polyclonal infections.

Effects of Polyphenols and Glucosinolates in Broccoli Extract on Human Gut Microorganisms Based on Simulation In Vitro.

Broccoli extract mainly contains polyphenols and glucosinolates (GSLs). GSLs can be hydrolyzed by gut microorganisms into isothiocyanates (ITCs) and other active substances. These substances have anticancer, anti-inflammatory, antimicrobial, and atherosclerosis-reducing functions. In this study, a high concentration (2000 µmol/L GSLs and 24 µmol/L polyphenols) and a low concentration (83 µmol/L GSLs and 1 µmol/L polyphenols) of broccoli extract were prepared. Gut microorganisms from fresh human feces were cultured to simulate the gut environment in vitro. The GSL content decreased and the types and content of ITCs increased with broccoli extract hydrolysis through cyclic condensation and gas chromatography-mass spectrometry (GC-MS) analyses. Broccoli extract significantly increased probiotics and inhibited harmful bacteria through 16S rDNA sequencing. Based on phylum level analysis, Firmicutes and Lachnospiraceae increased significantly (P < 0.05). At the genus level, both high- and low-concentration groups significantly inhibited Escherichia and increased Bilophila and Alistipes (P < 0.05). The high-concentration group significantly increased Bifidobacterium (P < 0.05). The broccoli extract improved the richness of gut microorganisms and regulated their structure. The GSL hydrolysis was significantly correlated with Bilophila, Lachnospiraceae, Alistipes, Bifidobacterium, Escherichia, and Streptococcus (P < 0.05). These study findings provide a theoretical foundation for further exploring a probiotic mechanism of broccoli extract in the intestine.

A 3D multi-agent-based model for lumen morphogenesis: the role of the biophysical properties of the extracellular matrix.

The correct function of many organs depends on proper lumen morphogenesis, which requires the orchestration of both biological and mechanical aspects. However, how these factors coordinate is not yet fully understood. Here, we focus on the development of a mechanistic model for computationally simulating lumen morphogenesis. In particular, we consider the hydrostatic pressure generated by the cells' fluid secretion as the driving force and the density of the extracellular matrix as regulators of the process. For this purpose, we develop a 3D agent-based-model for lumen morphogenesis that includes cells' fluid secretion and the density of the extracellular matrix. Moreover, this computer-based model considers the variation in the biological behavior of cells in response to the mechanical forces that they sense. Then, we study the formation of the lumen under different-mechanical scenarios and conclude that an increase in the matrix density reduces the lumen volume and hinders lumen morphogenesis. Finally, we show that the model successfully predicts normal lumen morphogenesis when the matrix density is physiological and aberrant multilumen formation when the matrix density is excessive. Supplementary Information: The online version contains supplementary material available at 10.1007/s00366-022-01654-1.

A mechanistic protrusive-based model for 3D cell migration.

Cell migration is essential for a variety of biological processes, such as embryogenesis, wound healing, and the immune response. After more than a century of research-mainly on flat surfaces-, there are still many unknowns about cell motility. In particular, regarding how cells migrate within 3D matrices, which more accurately replicate in vivo conditions. We present a novel in silico model of 3D mesenchymal cell migration regulated by the chemical and mechanical profile of the surrounding environment. This in silico model considers cell's adhesive and nuclear phenotypes, the effects of the steric hindrance of the matrix, and cells ability to degradate the ECM. These factors are crucial when investigating the increasing difficulty that migrating cells find to squeeze their nuclei through dense matrices, which may act as physical barriers. Our results agree with previous in vitro observations where fibroblasts cultured in collagen-based hydrogels did not durotax toward regions with higher collagen concentrations. Instead, they exhibited an adurotactic behavior, following a more random trajectory. Overall, cell's migratory response in 3D domains depends on its phenotype, and the properties of the surrounding environment, that is, 3D cell motion is strongly dependent on the context.

Characterization of autochthonal Hafnia spp. strains isolated from Spanish soft raw ewe's milk PDO cheeses to be used as adjunct culture.

The present work was performed to study the enterobacteria involved in the ripening of the artisanal raw ewe's milk PDO cheeses 'Torta del Casar' and 'Queso de la Serena' produced in Extremadura (Spain). These isolates were strain-typed, safety tested and characterized for some important technological properties. A total of 485 enterobacterial isolates were clustered by RAPD-PCR and subsequently identified by partial sequencing of the 16S rRNA gene. Among the 17 different species identified, Hafnia paralvei was the predominant species; H. alvei and Lelliottia amnigena were present to a lesser extent. Therefore, 55 Hafnia spp. strains, selected according to their genetic profile and dairy origin, were tested for the safe application. Overall, they were able to produce the biogenic amines putrescine and cadaverine under favourable conditions, presented α-haemolytic activity and did not produce cytolytic toxin active against HeLa cells or contain virulence genes. In addition, antibiotic susceptibility profiles showed that 17 Hafnia spp. strains were less resistant to the 33 antibiotics tested; subsequently, they were further technologically characterized. Although they showed differences, in general, they were well adapted to the stress conditions of cheese ripening. Among them, two strains, H. alvei 544 and 1142, are highlighted mainly due to their proteolytic activity at refrigeration temperatures and their low or null gas production. Although further studies are necessary before industrial application, these two strains are proposed for potential use as adjunct cultures to favour the homogeneity of these PDO cheeses, preserving their unique sensory characteristics.

Unravelling cell migration: defining movement from the cell surface.

Cell motility is essential for life and development. Unfortunately, cell migration is also linked to several pathological processes, such as cancer metastasis. Cells' ability to migrate relies on many actors. Cells change their migratory strategy based on their phenotype and the properties of the surrounding microenvironment. Cell migration is, therefore, an extremely complex phenomenon. Researchers have investigated cell motility for more than a century. Recent discoveries have uncovered some of the mysteries associated with the mechanisms involved in cell migration, such as intracellular signaling and cell mechanics. These findings involve different players, including transmembrane receptors, adhesive complexes, cytoskeletal components , the nucleus, and the extracellular matrix. This review aims to give a global overview of our current understanding of cell migration.

Characterization of autochthonal yeasts isolated from Spanish soft raw ewe milk protected designation of origin cheeses for technological application.

The yeasts involved in the ripening process of artisanal soft raw ewe milk Protected Designation of Origin (PDO) Torta del Casar and Queso de la Serena cheeses produced in Extremadura, Spain, were isolated throughout their ripening process, strain typed, and characterized for some important technological properties. A total of 508 yeast isolates were obtained and identified by inter-single sequence repeat anchored PCR amplification analysis and subsequent sequencing of the internal transcribed spacer ITS1/ITS2 5.8S rRNA. A total of 19 yeast species representing 8 genera were identified. Debaryomyces hansenii, Pichia kudriavzevii, Kluyveromyces lactis, and Yarrowia lipolytica were the predominant species. We selected 157 isolates, by genotyping and origin, for technological characterization. The evaluation of yeast isolates' growth under stress conditions of cheese ripening showed that 87 presented better performance. Among them, 71 isolates were not able to catabolize tyrosine to produce a brown pigment. Principal component analysis of the biochemical features of these isolates showed that 9 strains stood out, 3 K. lactis strains (2287, 2725, and 1507), 2 Pichia jadinii (1731 and 433), 2 Yarrowia alimentaria (1204 and 2150), Y. lipolytica 2495 and P. kudriavzevii 373. These strains displayed strong extracellular proteolytic activity on skim milk agar as well as an adequate enzymatic profile (strong aminopeptidase and weak protease activity), suggesting their great potential for cheese proteolysis. Extracellular lipolytic activity was mainly restricted to Yarrowia spp. isolates and weakly present in P. kudriavzevii 373 and K. lactis 2725, although enzymatic characterization by API-ZYM (bioMérieux SA) evidenced that all may contribute, at least in part, to the lipolysis process. Moreover, these strains were able to assimilate lactose, galactose, and glucose at NaCl concentrations higher than that usually found in cheese. However, lactate and citrate assimilation were limited to Y. lipolytica 2495, P. kudriavzevii 373, and P. jadinii 433, and may contribute to the alkalinizing process relevant to biochemical processes that take place in the last stages of ripening. By contrast, K. lactis strains showed acidifying capacity and ß-galactosidase activity and may take part in the initial stages of ripening, together with lactic acid bacteria. Thus, considering the technological characteristics studied, the 9 selected strains presented biochemical features well suited to their potential use as adjunct cultures, alone or in combination with autochthonous starter bacteria in the cheesemaking process, to overcome the heterogeneity of these PDO cheeses, preserving their unique sensory characteristics.

Improving the Viability and Metabolism of Intestinal Probiotic Bacteria Using Fibre Obtained from Vegetable By-Products.

This study evaluated the effect of dietary fibre obtained from pomegranate, tomato, grape and broccoli by-products on the gastrointestinal transit survival, growth, and metabolism of six probiotic strains. The results showed that the studied by-products contained variable amounts of polysaccharides that affected the six probiotic microorganisms in different ways. In addition, the protective effect of the fibre obtained on the probiotic strains was more effective in the case of the fibre obtained from tomato peel. In terms of growth, grape stems showed the best results, favouring the growth of lactic acid bacteria. Finally, all fibres were able to increase the content of short-chain fatty acids in the in vitro test, but broccoli stems and pomegranate peel stimulated higher production of short-chain fatty acids. The results of this study demonstrate that plant by-product fibres can improve survival, growth, and metabolism in terms of the fatty acid profiles of probiotic strains, highlighting the desirability of harnessing these by-product fibres to develop new high-value-added ingredients as probiotic carriers.

Strategies to Increase the Biological and Biotechnological Value of Polysaccharides from Agricultural Waste for Application in Healthy Nutrition.

Nowadays, there is a growing interest in the extraction and identification of new high added-value compounds from the agro-food industry that will valorize the great amount of by-products generated. Many of these bioactive compounds have shown beneficial effects for humans in terms of disease prevention, but they are also of great interest in the food industry due to their effect of extending the shelf life of foods by their well-known antioxidant and antimicrobial activity. For this reason, an additional research objective is to establish the best conditions for obtaining these compounds from complex by-product structures without altering their activity or even increasing it. This review highlights recent work on the identification and characterization of bioactive compounds from vegetable by-products, their functional activity, new methodologies for the extraction of bioactive compounds from vegetables, possibly increasing their biological activity, and the future of the global functional food and nutraceuticals market.

Chemical Composition and Functional Properties of Dietary Fibre Concentrates from Winemaking By-Products: Skins, Stems and Lees.

The objective of this study was to evaluate, from a technological and nutritional point of view, the chemical composition and functional properties of the industrial winemaking by-products, namely skins, stems and lees. The chemical and physical characteristics, as well as the functional properties (fat and water retention and swelling capacity, antioxidant capacity, and their prebiotic effect), of the dietary fibre of these by-products were studied. The results showed that the skins, stems, and lees are rich in fibre, with the stem fibre containing the highest amounts of non-extractable polyphenols attached to polysaccharides with high antioxidant activity and prebiotic effect. Lee fibre had the highest water retention capacity and oil retention capacity. The results reveal that winemaking by-products could be used as a source of dietary fibre with functional characteristics for food applications.

Time-dependent in silico modelling of orthognathic surgery to support the design of biodegradable bone plates.

Orthognathic surgery is performed to realign the jaws of a patient through several osteotomies. The state-of-the-art bone plates used to maintain the bone fragments in place are made of titanium. The presence of these non-degradable plates can have unwanted side effects on the long term (e.g. higher infection risk) if they are not removed. Using a biodegradable material such as magnesium may be a possible solution to this problem. However, biodegradation leads to a decrease of mechanical strength, therefore a time-dependent computational approach can help to evaluate the performance of such plates. In the present work, a computational framework has been developed to include biodegradation and bone healing algorithms in a finite element model. It includes bone plates and the mandible, which are submitted to masticatory loads during the early healing period (two months following the surgery). Two different bone plate designs with different stiffnesses have been tested. The stiff design exhibited good mechanical stability, with maximum Von Mises stress being less than 40% of the yield strength throughout the simulation. The flexible design shows high stresses when the bone healing has not started in the fracture gaps, indicating possible failure of the plate. However, this design leads to a higher bone healing quality after two months, as more cartilage is formed due to higher strains exerted in fracture gaps. We therefore conclude that in silico modelling can support tuning of the design parameters to ensure mechanical stability and while promoting bone healing.