Acetylsalicylic acid and dihydroartemisinin combined therapy on experimental malaria-associated acute lung injury: analysis of lung function and the inflammatory process.

BACKGROUND: Severe malaria can cause respiratory symptoms, which may lead to malaria-acute lung injury (MA-ALI) due to inflammation and damage to the blood-gas barrier. Patients with severe malaria also often present thrombocytopenia, and the use of acetylsalicylic acid (ASA), a commonly used non-steroidal anti-inflammatory drug with immunomodulatory and antiplatelet effects, may pose a risk in regions where malaria is endemic. Thus, this study aimed to investigate the systemic impact of ASA and dihydroartemisinin (DHA) on ALI induced in mice by Plasmodium berghei NK65 (PbNK65). METHODS: C57BL/6 mice were randomly divided into control (C) and PbNK65 infected groups and were inoculated with uninfected or 104 infected erythrocytes, respectively. Then, the animals were treated with DHA (3 mg/kg) or vehicle (DMSO) at the 8-day post-infection (dpi) for 7 days and with ASA (100 mg/kg, single dose), and analyses were performed at 9 or 15 dpi. Lung mechanics were performed, and lungs were collected for oedema evaluation and histological analyses. RESULTS: PbNK65 infection led to lung oedema, as well as increased lung static elastance (Est, L), resistive (ΔP1, L) and viscoelastic (ΔP2, L) pressures, percentage of mononuclear cells, inflammatory infiltrate, hemorrhage, alveolar oedema, and alveolar thickening septum at 9 dpi. Mice that received DHA or DHA + ASA had an increase in Est, L, and CD36 expression on inflammatory monocytes and higher protein content on bronchoalveolar fluid (BALF). However, only the DHA-treated group presented a percentage of inflammatory monocytes similar to the control group and a decrease in ΔP1, L and ΔP2, L compared to Pb + DMSO. Also, combined treatment with DHA + ASA led to an impairment in diffuse alveolar damage score and lung function at 9 dpi. CONCLUSIONS: Therapy with ASA maintained lung morpho-functional impairment triggered by PbNK65 infection, leading to a large influx of inflammatory monocytes to the lung tissue. Based on its deleterious effects in experimental MA-ALI, ASA administration or its treatment maintenance might be carefully reconsidered and further investigated in human malaria cases.

Exploiting tropical fruit processing coproducts as circular resources to promote the growth and maintain the culturability and functionality of probiotic lactobacilli.

This study evaluated the use of acerola (Malpighia glabra L., CACE), cashew (Anacardium occidentale L., CCAS), and guava (Psidium guayaba L., CGUA) fruit processing coproducts as substrates to promote the growth, metabolite production, and maintenance of the viability/metabolic activity of the probiotics Lactobacillus acidophilus LA-05 and Lacticaseibacillus paracasei L-10 during cultivation, freeze-drying, storage, and exposure to simulated gastrointestinal digestion. Probiotic lactobacilli presented high viable counts (≥8.8 log colony-forming units (CFU)/mL) and a short lag phase during 24 h of cultivation in CACE, CCAS, and CGUA. Cultivation of probiotic lactobacilli in fruit coproducts promoted sugar consumption, medium acidification, and production of organic acids over time, besides increasing the of several phenolic compounds and antioxidant activity. Probiotic lactobacilli cultivated in fruit coproducts had increased survival percentages after freeze-drying and during 120 days of refrigerated storage. Moreover, probiotic lactobacilli cultivated and freeze-dried in fruit coproducts had larger subpopulations of live and metabolically active cells when exposed to simulated gastrointestinal digestion. The results showed that fruit coproducts not only improved the growth and helped to maintain the viability and metabolic activity of probiotic strains but also enriched the final fermented products with bioactive compounds, being an innovative circular strategy for producing high-quality probiotic cultures.

Interventions based on alternative and sustainable strategies for postharvest control of anthracnose and maintain quality in tropical fruits.

Colletotrichum spp. is a phytopathogen causing anthracnose in a variety of tropical fruits. Strategies used to control postharvest diseases in tropical fruits typically rely on the use of synthetic fungicides, which have stimulated the emergence of resistant pathogens. Safer alternative strategies to control anthracnose in tropical fruits have been described in the literature. This review presents and discusses the main innovative interventions concerning the application of sustainable alternative strategies in the postharvest control of pathogenic Colletotrichum species in tropical fruits, with a particular emphasis on the studies published in the last 5 years. The available studies have shown the use of various methods, including physical barriers, natural antimicrobials, and biological control with antagonistic microorganisms, to reduce anthracnose lesion severity and incidence in tropical fruits. The available literature showed high inhibitory activity in vitro, reduced anthracnose incidence and lesion diameter, and total disease inhibition in tropical fruits. Most studies focused on the inhibition of Colletotrichum gloeosporioides on avocado, papaya, and mango, as well as of Colletotrichum musae on banana; however, the inhibition of other Colletotrichum species was also demonstrated. The application of emerging sustainable alternative methods, including natural antimicrobial substances, also stimulated the induction of defense systems in tropical fruits, including enzymatic activity, such as polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase. The retrieved data helped to understand the current state of the research field and reveal new perspectives on developing efficient and sustainable intervention strategies to control pathogenic Colletotrichum species and anthracnose development in tropical fruits.

Exploring the antimicrobial effects of a phenolic-rich extract from jabuticaba depulping waste against enterotoxigenic Escherichia coli.

This study evaluated the effects of a phenolic-rich extract from jabuticaba [Myrciaria jaboticaba (Vell.) Berg] depulping waste (PEJ) on the survival, antibiotic susceptibility, virulence, and cellular functions of various enterotoxigenic Escherichia coli (ETEC) strains. The minimum inhibitory concentration of PEJ against the five tested ETEC strains was 125 mg mL-1. PEJ at 125 and 250 mg mL-1 caused reductions in viable cell counts of ≥ 3 and ≥ 5 log CFU mL-1 in ETEC over 24 h, respectively. PEJ at subinhibitory concentrations (31.25 and 62.5 mg mL-1) reduced the viable cell counts of ETEC when exposed to in vitro gastrointestinal conditions, besides decreasing the biofilm formation, cell surface hydrophobicity, mucin adhesion, and swimming and swarming motility. PEJ (31.25 and 62.5 mg mL-1) increased the susceptibility of the tested ETEC strains to various clinically relevant antibiotics. The exposure to PEJ (62.5 and 125 mg mL-1) impaired the membrane permeability and enzymatic and efflux pump activities in ETEC cells. PEJ effectively reduces survival, increases antibiotic susceptibility, and attenuates virulence in ETEC. These effects could be linked to a PEJ multi-target action disturbing various cellular functions in ETEC cells. PEJ could be a candidate for developing innovative solutions to prevent and treat ETEC infections.

A systematic quantitative analysis of the published literature on the efficacy of essential oils as sanitizers in fresh leafy vegetables.

This study carried out a systematic quantitative analysis of published literature on the efficacy of essential oils (EOs) as sanitizers in fresh leafy vegetables (FLVs). Efficacy of EO was measured by determining if their application could cause a reduction of microbial population in FLV, as well as by identifying experimental factors that might affect the achieved reduction levels. Data on efficacy of EO to reduce the microbial population and experimental conditions were collected from selected studies and compiled for a distribution and relational analysis. Reduction of an artificial inoculum and/or natural microbiota of FLV caused by 14 different EO were measured in 404 (73.8%) and 143 (26.2%) experiments, respectively. Results of quantitative analysis showed that EO are consistently effective to reduce microbial population in FLV either when the target microorganisms are forming an artificial inoculum or the natural microbiota, being overall similarly effective to or more effective than substances used ordinarily as sanitizers. EO were more effective to reduce the population of microorganisms forming an artificial inoculum than the natural microbiota. EO concentration and inoculum size had no significant effect on achieved reductions. Duration of sanitization treatment with EO had significant effect on achieved reductions and highest reductions were found when the sanitization time was >3 min. Although with the inherent variability in experimental designs found in available literature, the results of this quantitative analysis provide strong evidence that EO are promising candidates for use in strategies to sanitize FLV.

Neurovascular Interactions in Malaria.

Malaria is caused by Plasmodium infection and remains a serious public health problem worldwide, despite control efforts. Malaria can progress to severe forms, affecting multiple organs, including the brain causing cerebral malaria (CM). CM is the most severe neurological complication of malaria, and cognitive and behavior deficits are commonly reported in surviving patients. The number of deaths from malaria has been reducing in recent years, and as a consequence, neurological sequelae have been more evident. Neurological damage in malaria might be related to the neuroinflammation, characterized by glia cell activation, neuronal apoptosis and changes in the blood-brain barrier (BBB) integrity. The neurovascular unit (NVU) is responsible for maintaining the homeostasis of the BBB. Endothelial and pericytes cells in the cerebral microvasculature and neural cells, as astrocytes, neurons, and microglia, compose the NVU. The NVU can be disturbed by parasite metabolic products, such as heme and hemozoin, or cytokines that can promote activation of endothelial and glial cells and lead to increased BBB permeability and subsequently neurodegeneration. In this review, we will approach the main changes that happen in the cells of the NVU due to neuroinflammation caused by malaria infection, and elucidate how the systemic pathophysiology is involved in the onset and progression of CM.

Infectious disease-associated encephalopathies.

Infectious diseases may affect brain function and cause encephalopathy even when the pathogen does not directly infect the central nervous system, known as infectious disease-associated encephalopathy. The systemic inflammatory process may result in neuroinflammation, with glial cell activation and increased levels of cytokines, reduced neurotrophic factors, blood-brain barrier dysfunction, neurotransmitter metabolism imbalances, and neurotoxicity, and behavioral and cognitive impairments often occur in the late course. Even though infectious disease-associated encephalopathies may cause devastating neurologic and cognitive deficits, the concept of infectious disease-associated encephalopathies is still under-investigated; knowledge of the underlying mechanisms, which may be distinct from those of encephalopathies of non-infectious cause, is still limited. In this review, we focus on the pathophysiology of encephalopathies associated with peripheral (sepsis, malaria, influenza, and COVID-19), emerging therapeutic strategies, and the role of neuroinflammation.

Mesenchymal Stromal Cells Protect the Blood-Brain Barrier, Reduce Astrogliosis, and Prevent Cognitive and Behavioral Alterations in Surviving Septic Mice.

OBJECTIVES: Survivors of sepsis are frequently left with significant cognitive and behavioral impairments. These complications derive from nonresolving inflammation that persists following hospital discharge. To date, no study has investigated the effects of mesenchymal stromal cell therapy on the blood-brain barrier, astrocyte activation, neuroinflammation, and cognitive and behavioral alterations in experimental sepsis. DESIGN: Prospective, randomized, controlled experimental study. SETTING: Government-affiliated research laboratory. SUBJECTS: Male Swiss Webster mice (n = 309). INTERVENTIONS: Sepsis was induced by cecal ligation and puncture; sham-operated animals were used as control. All animals received volume resuscitation (1 mL saline/mouse subcutaneously) and antibiotics (meropenem 10 mg/kg intraperitoneally at 6, 24, and 48 hours). Six hours after surgery, mice were treated with mesenchymal stromal cells IV (1 × 10 cells in 0.05 mL of saline/mouse) or saline (0.05 mL IV). MEASUREMENTS AND MAIN RESULTS: At day 1, clinical score and plasma levels of inflammatory mediators were increased in cecal ligation and puncture mice. Mesenchymal stromal cells did not alter clinical score or survival rate, but reduced levels of systemic interleukin-1ß, interleukin-6, and monocyte chemoattractant protein-1. At day 15, survivor mice completed a battery of cognitive and behavioral tasks. Cecal ligation and puncture mice exhibited spatial and aversive memory deficits and anxiety-like behavior. These effects may be related to increased blood-brain barrier permeability, with altered tight-junction messenger RNA expression, increased brain levels of inflammatory mediators, and astrogliosis (induced at day 3). Mesenchymal stromal cells mitigated these cognitive and behavioral alterations, as well as reduced blood-brain barrier dysfunction, astrocyte activation, and interleukin-1ß, interleukin-6, tumor necrosis factor-α, and interleukin-10 levels in vivo. In cultured primary astrocytes stimulated with lipopolysaccharide, conditioned media from mesenchymal stromal cells reduced astrogliosis, interleukin-1ß, and monocyte chemoattractant protein-1, suggesting a paracrine mechanism of action. CONCLUSIONS: In mice who survived experimental sepsis, mesenchymal stromal cell therapy protected blood-brain barrier integrity, reduced astrogliosis and neuroinflammation, as well as improved cognition and behavior.

Challenges in telemedicine for adult patients with drug-resistant epilepsy undergoing ketogenic diet treatment during the COVID-19 pandemic in the public healthcare system in Brazil.

Hygienic and sanitary measures and social distancing policies implemented during the new coronavirus disease - COVID-19 - pandemic have altered the care and follow-up provided by healthcare professionals for patients with chronic diseases, including patients with epilepsy (PWEs). Telemedicine has become a solution for the healthcare of PWEs in many developed countries. In this short communication, we trace a particular perspective for the application of telemedicine for PWEs undergoing ketogenic diet (KD) treatment, considering the social and economic difficulties faced by healthcare teams in resource-poor countries, such as Brazil. During the pandemic, financial strain was the main impediment to following KD. The pandemic increased socioeconomic insecurity and access to KD-related products, as well as increasing anxiety in 71% of PWE, impacting their KD treatment follow-up. The challenges of telemedicine in Brazil include not only social and economic issues but also access to food, healthcare services, and education for the population, in addition to digital inclusion.

Phagocytosis of Leptospira by leukocytes from mice with different susceptibility to leptospirosis and possible role of chemokines.

BACKGROUND: Leptospirosis is a widespread zoonosis caused by pathogenic prokaryotic microbes of the genus Leptospira. Although there are several reports in the literature, host-pathogen interaction is still poorly understood. The role of chemokine expression is important on the chemotaxis, activation and regulation of immune cells. Recent studies have shown that their expression profiles play an important role on the severity of leptospirosis outcome. We evaluated the phagocytosis of Leptospira by spleens cells from C3H/HeJ, C3H/HePas and BALB/c mouse strains, respectively susceptible, intermediate and resistant to leptospirosis, and by RAW 264.7 macrophages. Besides, we evaluated the effects of CCL2 treatment on the phagocytosis. The cells were incubated with or without CCL2 chemokine, and infected with virulent L. interrogans sv Copenhageni. Cells and culture supernatants were collected for subsequent analysis. RESULTS: The number of leptospires was higher in BALB/c cells, CCL2 pre-treated or only infected groups, when compared to C3H/HeJ and C3H/HePas cells. Indeed, CCL2 activation did not interfere in the phagocytosis of Leptospira. Expression of chemokines CXCL5 and CCL8 levels were significantly inhibited in infected BALB/c cells when compared to the non-infected control. CONCLUSIONS: Higher ability to phagocytosis and early modulation of some chemokines correlated with the resistance to leptospirosis disease. Exposure to CCL2 did not interfere on phagocytosis of Leptospira in our experimental conditions, but acted in the modulation of chemokines expression during Leptospira infection.

Potential prebiotic properties of cashew apple (Anacardium occidentale L.) agro-industrial byproduct on Lactobacillus species.

BACKGROUND: The prebiotic effects of a cashew apple (Anacardium occidentale L.) agro-industrial byproduct powder (CAP) on different potentially probiotic Lactobacillus strains, namely Lactobacillus acidophilus LA-05, Lactobacillus casei L-26 and Lactobacillus paracasei L-10, were assessed using in vitro experimental models. Accordingly, the growth of the Lactobacillus strains when cultivated in a broth containing CAP (20 or 30 g L-1 ), glucose (20 g L-1 ) or fructooligosaccharides (FOS) (20 g L-1 ) was monitored over 48 h; the prebiotic activity scores of CAP were determined; and the changes in pH values, production of organic acids and consumption of sugars in growth media were verified. RESULTS: During the 48-h cultivation, similar viable cell counts were observed for the Lactobacillus strains grown in the different media tested. The CAP presented positive prebiotic activity scores toward all the tested Lactobacillus strains, indicating a desirable selective fermentable activity relative to enteric organisms. The cultivation of the Lactobacillus strains in broth containing glucose, FOS or CAP resulted in high viable cell counts, a decreased pH, the production of organic acids and the consumption of sugars over time, revealing intense bacterial metabolic activity. CONCLUSION: The CAP exerts potential prebiotic effects on different potentially probiotic Lactobacillus strains and should be an added-value ingredient for the food industry. © 2017 Society of Chemical Industry.

Exploring the Effects of Freeze-Dried Sourdoughs with Lactiplantibacillus pentosus 129 and Limosilactobacillus fermentum 139 on the Quality of Long-Fermentation Bread.

Sourdough production is a complex fermentation process. Natural sourdough fermentation without standardization causes great variability in microbial communities and derived products. Starter cultures have emerged as alternatives to natural fermentation processes, which could improve bakery quality and produce bioactive compounds. This study aimed to evaluate the impacts of freeze-drying on the production and viability of sourdoughs with Lactiplantibacillus pentosus 129 (Lp) and Limosilactobacillus fermentum 139 (Lf), as well as their effects on the quality of long-fermentation bread. These strains were selected based on their better performance considering acidification and exopolysaccharide production capacity. Sourdough with Lp and Lf were propagated until the 10th day, when physicochemical and microbiological parameters were determined. The produced sourdoughs were freeze-dried, and bread samples were produced. The freeze-drying process resulted in high survival rates and few impacts on the metabolic activity of Lp and Lf until 60 days of storage. Incorporating Lp and Lf improved the microbiological and physicochemical properties of sourdough and long-fermentation breads. Tested freeze-dried sourdoughs led to reduced bread aging (higher specific volume and decreased starch retrogradation) and increased digestibility. The results show the potential of the freeze-dried sourdoughs produced with Lp and Lf as innovative strategies for standardizing production protocols for the bakery industry, especially for producing long-term fermentation bread.

Evidence for the Beneficial Effects of Brazilian Native Fruits and Their By-Products on Human Intestinal Microbiota and Repercussions on Non-Communicable Chronic Diseases-A Review.

Non-communicable chronic diseases (NCDs) are the most widespread cause of mortality worldwide. Intestinal microbiota balance can be altered by changes in the abundance and/or diversity of intestinal microbiota, indicating a role of intestinal microbiota in NCD development. This review discusses the findings of in vitro studies, pre-clinical studies and clinical trials on the effects of Brazilian native fruits, their by-products, as well as their bioactive compounds on human intestinal microbiota and NCD. The major bioactive compounds in Brazilian native fruits and their by-products, and the impacts of their administration on outcomes linked to intestinal microbiota modulation are discussed. Mechanisms of intestinal microbiota affecting NCD could be linked to the modulation of absorption and energy balance, immune and endocrine systems, and inflammatory response. Brazilian native fruits, such as acerola, açaí, baru, buriti, guava, jabuticaba, juçara, and passion fruit, have several bioactive compounds, soluble and insoluble fibers, and a variety of phenolic compounds, which are capable of changing these key mechanisms. Brazilian native fruits and their by-products can help to promote positive intestinal and systemic health benefits by driving alterations in the composition of the human intestinal microbiota, and increasing the production of distinct short-chain fatty acids and phenolic metabolites, thereby enhancing intestinal integrity and homeostasis. Evidence from available literature shows that the modulatory impacts of Brazilian native fruits and their by-products on the composition and metabolic activity of the intestinal microbiota could improve several clinical repercussions associated with NCD, reinforcing the influence of intestinal microbiota in extra-intestinal outcomes.

Effects of nutritional interventions on the severity of depressive and anxiety symptoms of women in the menopausal transition and menopause: a systematic review, meta-analysis, and meta-regression.

IMPORTANCE: Depression and anxiety may significantly affect women during the menopausal transition. In addition to traditional treatment strategies such as hormone therapy, antidepressants, and psychotherapy, nutritional interventions have been increasingly studied, but there is no consensus about their role in this patient population. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effect of nutritional interventions on the severity of depressive (DS) and anxiety (AS) symptoms in women during the menopausal transition or menopausal years. EVIDENCE REVIEW: Electronic search using databases PubMed, Cochrane, and Embase to identify articles indexed until January 31, 2021, focusing on randomized placebo-controlled trials documenting the effect of diet, food supplements, and nutraceuticals on DS and AS. FINDINGS: Thirty-two studies were included (DS, n = 15; AS, n = 1; DS and AS combined, n = 16). We found two studies that demonstrated data combined with other interventions: one with lifestyle interventions (vitamin D plus lifestyle-based weight-loss program) and another with exercise (omega 3 plus exercise). The pooled effect size favored the intervention group over placebo for both DS and AS (DS: standardized mean difference, -0.35 [95% confidence interval, -0.68 to -0.03; P = 0.0351]; AS: standardized mean difference, -0.74 [95% CI, -1.37 to -0.11; P = 0.0229]). There was significant heterogeneity in the pooled results, which can be attributed to differences in assessment tools for depression and anxiety as well as the variety of nutritional interventions studied. The subgroup analysis showed a statistically significant effect of menopausal status (perimenopausal or menopausal) but not the type or duration of nutritional intervention. Older age was the only significant predictor of the effect size of nutritional interventions in the meta-regression. CONCLUSIONS AND RELEVANCE: Nutritional interventions are promising tools for the management of mood/anxiety symptoms in women during the menopausal transition and in postmenopausal years. Because of significant heterogeneity and risk of bias among studies, the actual effect of different approaches is still unclear.

Microglial Priming in Infections and Its Risk to Neurodegenerative Diseases.

Infectious diseases of different etiologies have been associated with acute and long-term neurological consequences. The primary cause of these consequences appears to be an inflammatory process characterized primarily by a pro-inflammatory microglial state. Microglial cells, the local effectors' cells of innate immunity, once faced by a stimulus, alter their morphology, and become a primary source of inflammatory cytokines that increase the inflammatory process of the brain. This inflammatory scenario exerts a critical role in the pathogenesis of neurodegenerative diseases. In recent years, several studies have shown the involvement of the microglial inflammatory response caused by infections in the development of neurodegenerative diseases. This has been associated with a transitory microglial state subsequent to an inflammatory response, known as microglial priming, in which these cells are more responsive to stimuli. Thus, systemic inflammation and infections induce a transitory state in microglia that may lead to changes in their state and function, making priming them for subsequent immune challenges. However, considering that microglia are long-lived cells and are repeatedly exposed to infections during a lifetime, microglial priming may not be beneficial. In this review, we discuss the relationship between infections and neurodegenerative diseases and how this may rely on microglial priming.

New perspectives for mesenchymal stromal cells as an adjuvant therapy for infectious disease-associated encephalopathies.

Knowledge of the mechanisms that trigger infection-related encephalopathies is still very limited and cell therapies are one of the most promising alternatives for neurodegenerative diseases, and its application in infectious diseases can be of great relevance. Mesenchymal stromal cells are cells with great immunomodulatory potential; therefore, their use in clinical and preclinical studies in a variety of diseases, including central nervous system diseases, increased in the last decade. Mesenchymal stromal cells can exert their beneficial effects through several mechanisms, such as direct cell contact, through surface receptors, and also through paracrine or endocrine mechanisms. The paracrine mechanism is widely accepted by the scientific community and involves the release of soluble factors, which include cytokines, chemokines and trophic factors, and extracellular vesicles. This mini review discusses mesenchymal stromal cells mechanisms of action in neurological disorders, the neuroinflammatory process that takes place in the brain as a result of peripheral inflammation and changes in the brain's cellular scenario as a common factor in central nervous system diseases, and mesenchymal stromal cells therapy in encephalopathies. Mesenchymal stromal cells have been shown to act in neuroinflammation processes, leading to improved survival and mitigating behavioral damage. More recently, these cells have been tested in preclinical models of infectious diseases-associated encephalopathies (e.g., cerebral malaria and sepsis associated encephalopathy) and have shown satisfactory results.

Ketogenic diet, epilepsy and cognition: what do we know so far? A systematic review.

CONTEXT: Epilepsy is a chronic neurological disorder that has social, cognitive, and psychological consequences to the patient. OBJECTIVE: The effects of the ketogenic diet (KD) in children and adults with pharmacoresistant epilepsy on cognitive function were evaluated in this systematic review. DATA SOURCES: The MEDLINE, Cochrane Library, Scopus, Web of Science, and LILACS databases were searched up to February 2021. STUDY SELECTION AND DATA EXTRACTION: From the 2973 records initially identified, 24 studies were included in the systematic review. These records were screened via PICO criteria, focusing on studies that evaluated the effects of KD on cognitive function of patients with pharmacoresistant epilepsy. RESULTS: Nineteen studies described improvements in cognitive function attributed to KD; improvements were not observed in 2 studies, but neither was aggravation. Contradictory results were reported in 3 studies, depending on the method used to assess cognition. At first glance, cognitive function appears to be associated with the number of seizures, diet effectiveness, amount of carbohydrate ingested, and antiseizure medication used. However, due to the diversity of methods used to assess cognitive function, especially self-perception of cognitive improvement by the patient, it was not possible to confirm this hypothesis. CONCLUSION: It was not possible to confirm if KD itself promotes improvements in cognitive function in patients with pharmacoresistant epilepsy. Certainly, more studies are needed with better methodological quality, larger and more homogeneous samples in relation to epileptic syndrome and clinical aspects of the disease, more rigid monitoring of adherence to the diet, and use of standardized tests for neuropsychological assessment. Systematic Review Registration: PROSPERO registration no. CRD42019129236.

Survival during long-term storage, membrane integrity, and ultrastructural aspects of Lactobacillus acidophilus 05 and Lacticaseibacillus casei 01 freeze-dried with freshwater microalgae biomasses.

This study aimed to assess Spirulina platensis, Chlorella vulgaris, Scenedesmus quadricauda, and Lagerheimia longiseta microalgae potential as protective agents for probiotic cultures [(Lactobacillus acidophilus (La-05) and Lacticaseibacillus casei (Lc-01)] during freeze-drying, refrigeration storage (4 °C, 120 days), and in vitro simulated gastrointestinal conditions (SGIC). The occurrence of membrane damage and ultrastructural aspects of the cells were also verified. Fructooligosaccharides (FOS) were used as a positive control and saline solution as a negative control. The effects of the cryoprotectants on probiotic survival depended on the tested probiotic culture and microalgae biomass. For La-05, all tested cryoprotectants caused a lower reduction in probiotic counts during the freeze-drying and up to 90 days of storage. S. platensis kept higher probiotic counts during storage, while C. vulgaris protected the probiotic against the SGIC. L. longiseta decreased the probiotic membrane damage, mainly due to the production of exopolysaccharides, which was observed in the scanning electron microscopy (SEM). For Lc-01, all tested cryoprotectants promoted a lower reduction in probiotic counts up to 120 days of storage. FOS and S. quadricauda protected the probiotics during freeze-drying and refrigeration storage, while C. vulgaris protected the probiotic against the SGIC and caused lower membrane damage, mainly due to physical protection observed in SEM. In conclusion, microalgae biomasses exerted similar or better cryoprotectant effects on probiotics than FOS, a recognized cryoprotective agent.

Coatings with chitosan and phenolic-rich extract from acerola (Malpighia emarginata D.C.) or jabuticaba (Plinia jaboticaba (Vell.) Berg) processing by-product to control rot caused by Lasiodiplodia spp. in papaya (Carica papaya L.) fruit.

This study evaluated if coatings with chitosan (Chi) and phenolic-rich extract from acerola (Malpighia emarginata D.C., PEA) or jabuticaba (Plinia jaboticaba (Vell.) Berg, PEJ) processing by-products are effective to control the development of rot caused by Lasiodiplodia pseudotheobromae, L. viticola, L. euphorbicola, L. theobromae and L. hormozganensis in papaya (Carica papaya L.) fruit. Effects of formulated coatings on some physicochemical parameters indicative of postharvest quality of papaya were investigated. Twenty-six different phenolics were found in PEA and PEJ, including flavonoids, stilbenes, tannins and phenolic acids. Chi (1-5 mg/mL), PEA and PEJ (25-100 mg/mL) separately caused mycelial growth inhibition on all isolates. Combinations of Chi (3 and 4 mg/mL) and PEA (50 and 75 mg/mL) or PEJ (75 and 100 mg/mL) had additive interactions. Coatings with Chi (4 mg/mL) and PEA (50 or 75 mg/mL) or PEA (75 or 100 mg/mL) inhibited rot development in papaya fruit infected with Lasiodiplodia isolates during 8 days of room temperature storage. Coatings with 4 mg/mL Chi and 75 mg/mL PEA or 100 mg/mL PEJ were the most effective to control rot development. These coatings did not affect negatively physicochemical parameters indicative of postharvest quality of papaya fruit during storage. Coatings with combined Chi and PEA or PEJ could be novel strategies to control postharvest rot caused by Lasiodiplodia in papaya fruit.

Mesenchymal stromal cells protect against vascular damage and depression-like behavior in mice surviving cerebral malaria.

BACKGROUND: Malaria is one of the most critical global infectious diseases. Severe systemic inflammatory diseases, such as cerebral malaria, lead to the development of cognitive and behavioral alterations, such as learning disabilities and loss of memory capacity, as well as increased anxiety and depression. The consequences are profound and usually contribute to reduce the patient's quality of life. There are no therapies to treat the neurological sequelae of cerebral malaria. Mesenchymal stromal cells (MSCs) may be an alternative, since they have been used as therapy for neurodegenerative diseases and traumatic lesions of the central nervous system. So far, no study has investigated the effects of MSC therapy on the blood-brain barrier, leukocyte rolling and adherence in the brain, and depression like-behavior in experimental cerebral malaria. METHODS: Male C57BL/6 mice were infected with Plasmodium berghei ANKA (PbA, 1 × 106 PbA-parasitized red blood cells, intraperitoneally). At day 6, PbA-infected animals received chloroquine (25 mg/kg orally for seven consecutive days) as the antimalarial treatment and were then randomized to receive MSCs (1 × 105 cells in 0.05 ml of saline/mouse) or saline (0.05 ml) intravenously. Parasitemia, clinical score, and survival rate were analyzed throughout the experiments. Evans blue assay was performed at 6, 7, and 15 days post-infection (dpi). Behavioral tests were performed at 5 and 15 dpi. Intravital microscopy experiments and brain-derived neurotrophic factor (BDNF) protein expression analyses were performed at 7 dpi, whereas inflammatory mediators were measured at 15 dpi. In vitro, endothelial cells were used to evaluate the effects of conditioned media derived from MSCs (CMMSC) on cell viability by lactate dehydrogenase (LDH) release. RESULTS: PbA-infected mice presented increased parasitemia, adherent leukocytes, blood-brain barrier permeability, and reduced BDNF protein levels, as well as depression-like behavior. MSCs mitigated behavioral alterations, restored BDNF and transforming growth factor (TGF)-ß protein levels, and reduced blood-brain barrier dysfunction and leukocyte adhesion in the brain microvasculature. In a cultured endothelial cell line stimulated with heme, CMMSC reduced LDH release, suggesting a paracrine mechanism of action. CONCLUSION: A single dose of MSCs as adjuvant therapy protected against vascular damage and improved depression-like behavior in mice that survived experimental cerebral malaria.