Society of Critical Care Medicine and American Society of Health-System Pharmacists Guideline for the Prevention of Stress-Related Gastrointestinal Bleeding in Critically Ill Adults.

RATIONALE: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB). OBJECTIVES: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU. DESIGN: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting. METHODS: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance. RESULTS: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing. CONCLUSIONS: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status.

Toxicity of Trixis vauthieri DC essential oil on Lutzomyia longipalpis (Diptera, Psychodidae, Phlebotominae), a proven vector of visceral leishmaniasis in Brazil.

BACKGROUND OBJECTIVES: In Brazil, one of the visceral leishmaniasis control measures in urban environments is the elimination of Lutzomyia longipalpis, which occurs through the application of pyrethroid insecticides with residual action in homes and outbuildings. Due to the loss of sensitivity of this vector to these insecticides, the search for more efficient insecticide compounds against L. longipalpis has been intensified. The objective of this work was to evaluate the toxicity of Trixis vauthieri essential oil on adult sandflies of the species L. longipalpis, and identify the phytochemical composition of these essential oils. METHODS: Essential oils from leaves collected from T. vauthieri at different times were obtained at concentrations of 5, 10 and 20 mg/mL. Twenty sandflies were exposed to the essential oils and the mortality was evaluated after 1, 2, 4, 16, 24, 48 and 72 h. The chemical constituents of the essential oil were also identified. RESULTS: The essential oils of T. vauthieri at a concentration of 20 mg/mL were the most toxic to sandflies, reaching a mortality rate of 98.33% and 95%, respectively, after 72 h of exposure. The analysis of chemical constituents revealed the presence of triterpenes and/or steroids, tannins, flavonoids, alkaloids, saponins and coumarins. INTERPRETATION CONCLUSION: The results obtained suggest that T. vauthieri essential oil is fairly promising as an insecticidal potential against L. longipalpis. A more detailed analysis of the oil's phytochemical composition is necessary to identify active and pure compounds that can be used in vector control of visceral leishmaniasis.

USP15-USP7 Axis and UBE2T Differential Expression May Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm.

The aim of this study was to evaluate the expression of USP7, USP15, UBE2O, and UBE2T genes in Myelodysplastic neoplasm (MDS) to identify possible targets of ubiquitination and deubiquitination in MDS pathobiology. To achieve this, eight datasets from the Gene Expression Omnibus (GEO) database were integrated, and the expression relationship of these genes was analyzed in 1092 MDS patients and healthy controls. Our results showed that UBE2O, UBE2T, and USP7 were upregulated in MDS patients compared with healthy individuals, but only in mononucleated cells collected from bone marrow samples (p < 0.001). In contrast, only the USP15 gene showed a downregulated expression compared with healthy individuals (p = 0.03). Additionally, the upregulation of UBE2T expression was identified in MDS patients with chromosomal abnormalities compared with patients with normal karyotypes (p = 0.0321), and the downregulation of UBE2T expression was associated with MDS hypoplastic patients (p = 0.033). Finally, the USP7 and USP15 genes were strongly correlated with MDS (r = 0.82; r2 = 0.67; p < 0.0001). These findings suggest that the differential expression of the USP15-USP7 axis and UBE2T may play an important role in controlling genomic instability and the chromosomal abnormalities that are a striking characteristic of MDS.

Encapsulation of Bromelain in Combined Sodium Alginate and Amino Acid Carriers: Experimental Design of Simplex-Centroid Mixtures for Digestibility Evaluation.

Bromelain has potential as an analgesic, an anti-inflammatory, and in cancer treatments. Despite its therapeutic effects, this protein undergoes denaturation when administered orally. Microencapsulation processes have shown potential in protein protection and as controlled release systems. Thus, this paper aimed to develop encapsulating systems using sodium alginate as a carrier material and positively charged amino acids as stabilizing agents for the controlled release of bromelain in in vitro tests. The systems were produced from the experimental design of centroid simplex mixtures. Characterizations were performed by FTIR showing that bromelain was encapsulated in all systems. XRD analyses showed that the systems are semi-crystalline solids and through SEM analysis the morphology of the formed systems followed a pattern of rough microparticles. The application of statistical analysis showed that the systems presented behavior that can be evaluated by quadratic and special cubic models, with a p-value < 0.05. The interaction between amino acids and bromelain/alginate was evaluated, and free bromelain showed a reduction of 74.0% in protein content and 23.6% in enzymatic activity at the end of gastric digestion. Furthermore, a reduction of 91.6% of protein content and 65.9% of enzymatic activity was observed at the end of intestinal digestion. The Lis system showed better interaction due to the increased stability of bromelain in terms of the amount of proteins (above 63% until the end of the intestinal phase) and the enzymatic activity of 89.3%. Thus, this study proposes the development of pH-controlled release systems aiming at increasing the stability and bioavailability of bromelain in intestinal systems.

FRETboard: Semisupervised classification of FRET traces.

Förster resonance energy transfer (FRET) is a useful phenomenon in biomolecular investigations, as it can be leveraged for nanoscale measurements. The optical signals produced by such experiments can be analyzed by fitting a statistical model. Several software tools exist to fit such models in an unsupervised manner but lack the flexibility to adapt to different experimental setups and require local installations. Here, we propose to fit models to optical signals more intuitively by adopting a semisupervised approach, in which the user interactively guides the model to fit a given data set, and introduce FRETboard, a web tool that allows users to provide such guidance. We show that our approach is able to closely reproduce ground truth FRET statistics in a wide range of simulated single-molecule scenarios and correctly estimate parameters for up to 11 states. On in vitro data, we retrieve parameters identical to those obtained by laborious manual classification in a fraction of the required time. Moreover, we designed FRETboard to be easily extendable to other models, allowing it to adapt to future developments in FRET measurement and analysis.

Through the fingers: Use of plastinated anatomical specimens for visually impaired students.

The plastination technique produces non-toxic human tissues, ensuring their safe handling in educational settings. This investigation aimed to understand if visually impaired students profit from the use of plastinated anatomical specimens in learning the anatomy of the nervous system. For this purpose, their learning performance was compared to sighted and blindfolded students recruited from three primary schools in Fortaleza city, in the state of Ceará. Initially, a questionnaire was applied before carrying out the pedagogical practice, followed by an anatomy lecture with practical components with the use of plastinated anatomical specimens and synthetic anatomical models of the nervous system. After these steps, the students answered the questionnaire previously applied. Our results showed that the tactile perception of the visually impaired participants was significantly more developed compared to sighted (p < 0.001) and the blindfolded (p < 0.0001) students. The average of correct answers in the reapplied questionnaire was higher in the groups that used plastinated specimens (p < 0.05). In conclusion, the use of plastinated specimens has proven to be an effective tool in promoting a better understanding of anatomical structures, mainly for students with or without visual impairments, making it a valuable asset in anatomy teaching.

Pollen grain morphology of Fabaceae in the Special Protection Area (SPA) Pau-de-Fruta, Diamantina, Minas Gerais, Brazil.

The presented paper considered the pollen morphology of thirteen species belonging to seven genera of the Fabaceae family occurring in the Pau-de-Fruta Special Protection Area (SPA), Diamantina, state of Minas Gerais, Brazil. The pollen grains of six species of Chamaecrista [C. cathartica (Mart.) H.S. Irwin & Barneby, C. debilis Vogel, C. flexuosa (L.) Greene, C. hedysaroides (Vogel) H.S. Irwin & Barneby, C. glandulosa (L.) Greene, and C. papillata H.S. Irwin & Barneby] have a similar morphology, characterized by three long colporated apertures with a central constriction. The species share specific morphological features regarding pollen size, endoaperture type (circular, lalongate or lolongate) and SEM ornamentation patterns of the exine (rugulate with perforations or perforate). Andira fraxinifolia Benth., Dalbergia miscolobium Benth, Galactia martii DC, Periandra mediterranea (Vell.) Taub., Senna rugosa (G.Don) H.S. Irwin & Barneby and Zornia diphylla (L.) Pers showed different pollen types in small to large size; oblate spheroidal to prolate form; colpus or colporus apertures; circular, lalongate or lolongate endoapertures and distinctive SEM ornamentation patterns of the exine (perforate, microreticulate, reticulate or rugulate with perforations). Only Stryphnodendron adstringens (Mart.) Coville presents polyads. The pollen morphology variation of these species allowed the Fabaceae family to be characterized as eurypalynous in the SPA Pau-de-Fruta.

Steps toward nebulization in-use studies to understand the stability of new biological entities.

The need for novel biological drugs against respiratory diseases has been highlighted during the Coronavirus (COVID-19) pandemic. The use of inhalation presents challenges to drug product stability, which is especially true for delivery using nebulizers (jet versus mesh technologies). The late-stage process of drug development in the pharmaceutical industry requires the investigation of in-use stability. In-use studies generate data that are guided by the requirements of regulatory authorities for inclusion in the clinical trial application dossier. In this review, I introduce the initial aspects of in-use stability studies during the development of an aerosol formulation to deliver biologics with a nebulizer. Lessons learned from this experience can guide future development and planning for formulation, analytics, material compatibility, nebulization process, and clinical trial preparations.

Cold plasma as a pre-treatment for processing improvement in food: A review.

Thermal processes can be very damaging to the nutritional and sensory quality of foods. Non-thermal technologies have been applied to reduce the impact of heat on food, reducing processing time and increasing its efficiency. Among many non-thermal technologies, cold plasma is an emerging technology with several potential applications in food processing. This technique can be used to preserve and sanitize food products, and act as a pre-treatment for drying, extraction, cooking, curing, and hydrogenation of foods. Furthermore, the reacting plasma species formed during the plasma application can change positively the sensory and nutritional aspects of foods. The aim of this review is to analyze the main findings on the application of cold plasma as a pre-treatment technology to improve food processing. In its current maturity stage, the cold plasma technology is suitable for reducing drying time, increasing extraction efficiency, as well as curing meats. This technology can convert unsaturated into saturated fats, without forming trans isomers, which can be an alternative to healthier foods. Although many advantages come from cold plasma applications, this technology still has several challenges, such as the scaling up, especially in increasing productivity and treating foods with large formats. Optimization and control of the effects of plasma on nutritional and sensory quality are still under investigation. Further improvement of the technology will come with a higher knowledge of the effects of plasma on the different chemical groups present in foods, and with the development of bigger or more powerful plasma systems.

Taenia solium: Socioeconomic changes and prevalence evolution in four endemic communities in northwestern Mexico.

In Mexico, for the past 30 years, a continuous decrease in the incidence of clinical taeniosis/cysticercosis has been documented. This work aimed to determine the influence of improvement in socioeconomic conditions on the prevalence of Taenia solium in four endemic communities in northwestern Mexico. This study was carried out in two phases. First, documentary information (1989-2018) was collected about the prevalence of Theridion solium in the federal entity of Sinaloa State. Second, a pilot study was performed in four communities of Sinaloa, which had an endemic history of Taenia transmission. In each community, a risk factor questionnaire was applied, and serum and stool samples were collected for convenience in a non-probabilistic way. Anti-cysticercus antibodies and adult worm coproantigen were determined. The documentary analysis showed the incidence of taeniosis and cysticercosis to have decreased by 98 and 53%, respectively, while the human development index increased by 5% (1992-2017). Our data suggest that the risk of parasitic transmission is low, although female sex was a risk factor for reporting tremors or seizures (prevalence rate 2.1336, CI: 1.1821-3.8508) and background of tapeworm infection (prevalence rate 1.2893, CI: 0.9795-1.6972). No tapeworms or eggs were found while examining stool samples, but protozoa cysts were observed in four samples. Unexpectedly, only one of the 79 stool samples was positive for coproantigens. This positive result was confirmed in a second sample. However, the evaluation of a third sample was negative. No antibodies were found in human (n = 377) or pig (n = 69) samples. These data suggest parasite transmission has been interrupted and could be possibly associated with improving socioeconomic conditions. Further studies are needed to determine the real prevalence of zoonoses in Mexico.

Discrepancy in transcriptomic profiling between CD34 + stem cells and primary bone marrow cells in myelodysplastic neoplasm.

Differentially expressed genes (DEGs) biomarkers can be used to help diagnose and monitor the disease, as well as to determine which treatments are most effective. So, given the complexity of Myelodysplastic neoplasm (MDS), it is difficult to determine the impact and disparities of DEGs between CD34+ HSC (hematopoietic stem cells) or primary bone marrow cells (PBMC) in MDS pathogenesis, and therefore it remains largely unknown. Here, we performed an in-silico transcriptome analysis on CD34+ HSC and PBMC from 1092 MDS patients analyzing the divergences between differential gene expression patterns in these two cell types as potential pathogenic biomarkers for MDS. Initially, we observed a difference of 7117 expressed transcripts between PBMC (n = 40,165) and CD34 +HSC (n = 33,048). Also, we identified that CD34+ HSC and PBMC samples showed 240 and 2948 DEGs, respectively. In summary, we identified DEGs disparities in CD34+ HSC and PBMC cell types. However, there was a certain similarity of the activated pathways in both cellular samples based on Gene Ontology and KEGG pathways enrichment analyses. Our results provide novel insights into novel DEGs biomarkers to MDS pathogenesis with clinical significance. AVAILABILITY OF DATA AND MATERIALS: All microarray databases were obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). To evaluate the biological function of differentially expressed genes, the DAVID (Database for Annotation, Visualization and Integrated Discovery tool was used) (https://david.ncifcrf.gov/).

Effect of incorporating prebiotics in coating materials for the microencapsulation of Saccharomyces boulardii.

The objective of this study was to microencapsulate Saccharomyces boulardii using the emulsion technique. To microencapsulate the yeast, alginate sodium blended with inulin and mucilage from Opuntiaficus-indica was used as a coating material. The textural properties of the gels formed by the encapsulating materials and the in vitro viability of the yeast strain in the simulated conditions were studied. Textural profile analyses of the gels revealed differences (p < 0.05) in hardness because alginate produced stronger gels, whereas the incorporation of other hydrocolloids with alginate decreased gel strength and resulted in a more uniform, cohesive gel matrix. When alginate was blended with mucilage and inulin, encapsulated yeast presented higher counts and more viable cells, as compared to free yeast following 30 days of storage at 4 °C. Encapsulated and free yeast had 76.1% and 63.3%, respectively, of cell viability after 35 days of storage.

Ficus spp. fruits: Bioactive compounds and chemical, biological and pharmacological properties.

The aim of this review was to compile the main reports over the last 5 years concerning the Ficus spp. fruits (Moraceae family) based on chemistry, properties, and applications as products. About 30 Ficus spp. fruits were reported focusing on their chemical composition rich in phenolic acids such as gallic, caffeic and chlorogenic acids, as well as quercetin and cyanidin derivatives. The fruits from Moraceae family presented mainly antioxidant and antimicrobial properties in addition to other functional properties to consumers health. Therefore, these fruits can be successfully considered by the food industry for the development of new products with high added value and also be considered a source of bioactive compounds.

Buriti (Mauritia flexuosa L. f.): An Amazonian fruit with potential health benefits.

The Amazon region has a significant biodiversity composed of several fruits with health benefits and distinguished potential for technological application and development of novel products. Buriti (Mauritia flexuosa) is one of the main Amazonian fruits with expressive nutraceutical properties. For this reason, this review aims to elucidate the current state of knowledge on buriti, providing information on its bioactive compounds, nutraceutical, and health potential for both technological and economic development especially in food and pharmaceutical areas. Different parts of buriti are important sources of carotenoids, fatty acids, phenolic compounds, and fibers. Antioxidant, antimicrobial, prebiotic, anti-diabetes, and anti-cancer properties have also been reported. In addition, the buriti oil presents a synergistic effect with antibiotics and it has been also an alternative to artificial dyes. However, there is a lack of information about the in vivo evaluation of the buriti's bioactive compounds providing a clearer elucidation on its biological potential, toxicity information and mechanisms of action. Proper sensory methods and the relationship between sensory quality and consumer perception are also needed to extend the possibility of developing new products. Finally, the use of non-thermal techniques is encouraged to improve the bioavailability of nutraceutical compounds and potentiate their action on human health.

Role of Sirtuins in the Pathobiology of Onco-Hematological Diseases: A PROSPERO-Registered Study and In Silico Analysis.

The sirtuins (SIRT) gene family (SIRT1 to SIRT7) contains the targets implicated in cellular and organismal aging. The role of SIRTs expression in the pathogenesis and overall survival of patients diagnosed with solid tumors has been widely discussed. However, studies that seek to explain the role of these pathways in the hematopoietic aging process and the consequences of their instability in the pathogenesis of different onco-hematological diseases are still scarce. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42022310079) and in silico analysis (based on GEPIA database) to discuss the role of SIRTs in the advancement of pathogenesis and/or prognosis for different hematological cancer types. In summary, given recent available scientific evidence and in silico gene expression analysis that supports the role of SIRTs in pathobiology of hematological malignances, such as leukemias, lymphomas and myeloma, it is clear the need for further high-quality research and clinical trials that expands the SIRT inhibition knowledge and its effect on controlling clonal progression caused by genomic instability characteristics of these diseases. Finally, SIRTs represent potential molecular targets in the control of the effects caused by aging on the failures of the hematopoietic system that can lead to the involvement of hematological neoplasms.

Evaluation of FRET X for single-molecule protein fingerprinting.

Single-molecule protein identification is an unrealized concept with potentially ground-breaking applications in biological research. We propose a method called FRET X (Förster Resonance Energy Transfer via DNA eXchange) fingerprinting, in which the FRET efficiency is read out between exchangeable dyes on protein-bound DNA docking strands and accumulated FRET efficiencies constitute the fingerprint for a protein. To evaluate the feasibility of this approach, we simulated fingerprints for hundreds of proteins using a coarse-grained lattice model and experimentally demonstrated FRET X fingerprinting on model peptides. Measured fingerprints are in agreement with our simulations, corroborating the validity of our modeling approach. In a simulated complex mixture of >300 human proteins of which only cysteines, lysines, and arginines were labeled, a support vector machine was able to identify constituents with 95% accuracy. We anticipate that our FRET X fingerprinting approach will form the basis of an analysis tool for targeted proteomics.

Decoding (patho-)physiology of the lung by advanced in vitro models for developing novel anti-infectives therapies.

Advanced lung cell culture models provide physiologically-relevant and complex data for mathematical models to exploit host-pathogen responses during anti-infective drug testing.

Cold plasma technique as a pretreatment for drying fruits: Evaluation of the excitation frequency on drying process and bioactive compounds.

The present work aims to evaluate the effect of different excitation frequency (200, 500 and 800 Hz) of cold plasma technique as a pretreatment for drying tucumã. SEM images showed changes on the pretreated tucumã's surface, favoring the drying rate and diffusivity of water as well as reducing the drying time. Marginal variation of color and reduced drying time were observed in the samples treated using 200 and 800 Hz. The pretreatment improved the concentration of phenolic (45.3 mg GAE g-1) and antioxidant compounds (799.8 µM ET) (p-value < 0.05). Carotenoids were more sensitive to the drying time, presenting significant degradation at 500 Hz. For this reason, the propose pretreatment based on the application of cold plasma technique for drying foods can preserve/improve their nutritional quality.

Amazonian Bacuri (Platonia insignis Mart.) Fruit Waste Valorisation Using Response Surface Methodology.

Bacuri (Platonia insignis Mart) is a species from the Clusiaceae genus. Its fruit pulp is commonly used in South America in several food products, such as beverages, ice cream and candies. Only the pulp of the fruit is used, and the peels and seeds are considered waste from these industries. As a trioxygenated xanthone source, this species is of high interest for bioproduct development. This work evaluated the mesocarp and epicarp of bacuri fruits through different extraction methods and experimental conditions (pH, temperature and solvent) in order to determine the most effective method for converting this agro-industrial waste in a value-added bioproduct. Open-column procedures and HPLC and NMR experiments were performed to evaluate the chemical composition of the extracts, along with total phenols, total flavonoids and antioxidant activities (sequestration of the DPPH and ABTS radicals). A factorial design and response surface methodology were used. The best extraction conditions of substances with antioxidant properties were maceration at 50 °C with 100% ethanol as solvent for mesocarp extracts, and acidic sonication in 100% ethanol for epicarp extracts, with an excellent phenolic profile and antioxidant capacities. The main compounds isolated were the prenylated benzophenones garcinielliptone FC (epicarp) and 30-epi-cambogin (mesocarp). This is the first study analysing the performance of extraction methods within bacuri agro-industrial waste. Results demonstrated that shells and seeds of bacuri can be used as phenolic-rich bioproducts obtained by a simple extraction method, increasing the value chain of this fruit.