Phytochemical and bioactive potentials of African Annonaceae species.

This review aims to gather available information on the medicinal, nutritional, and bioactive profiles of Annonaceae species in the African continent, sponsoring their use worldwide and mainly in African communities, where access to food and medicines for basic health care is scarce. >60 medicinal taxa were compiled, belonging to 22 genera, namely Annickia, Annona, Anonidium, Artabotrys, Cleistochlamys, Cleistopholis, Dennettia, Duguetia, Greenwayodendron, Hexalobus, Isolona, Lettowianthus, Monanthotaxis, Monodora, Neostenanthera, Polyceratocarpus, Sphaerocoryne, Uvaria, Uvariastrum, Uvariodendron, Uvariopsis and Xylopia; the most diverse and economically important genera were the genera Annona, Uvaria and Xylopia with 7 species each. Annonaceae species hold a valuable nutritional profile, rich in proteins, fibers, and minerals, being also good sources of a wide range of bioactive compounds of high biological relevance. These compounds are especially important in developing countries, where most of these species are available for direct use as food and/or medicines by the most deprived populations.

Superficial venous arterialization with the great saphenous vein in situ: a single-center experience.

Background: Arterialization of the dorsal venous arch of the foot is a technique indicated in cases of critical lower limb ischemia that do not have a distal bed that is adequate to enable conventional treatment such as revascularization, angioplasty, or clinical treatment. Objectives: The purpose of this study is to present the result of arterialization of the venous arch of the foot in 16 patients who underwent treatment with this technique. Methods: This is a cross-sectional retrospective descriptive analytical study based on a review of the medical records of 16 patients who underwent arterialization of the dorsal venous arch of the foot for limb salvage from January 2016 to January 2021. Results: Four (25%) of the 16 patients who underwent arterialization of the venous arch of the foot underwent a major amputation during the same hospital stay and one patient (6.25%) had a major amputation within 6 months. The other 11 patients (68.75%) had their limbs preserved, with 10 undergoing minor amputations (toes and forefoot) and one patient having no additional procedures. Conclusions: We conclude that the technique of arterialization of the dorsal venous arch of the foot should be considered in selected cases. It is a valid alternative for limb salvage when conventional treatment is impossible.

Effect of cashew nut flour on hematological parameters of children living with HIV.

Aim: To assess the effect of cashew nut flour on the hematological parameters of children living with HIV-AIDS. Method: A 32-week randomized, blind clinical trial conducted at a specialized outpatient clinic. Children aged 2-12 years were allocated to intervention groups (IGs) (n = 11) receiving 12 g/day of cashew nut flour and control groups (CGs) (n = 9) receiving 12 g/day of carboxymethyl cellulose. Parameters of erythrocytes, leukocytes, platelets, and lipid profiles were evaluated. Results: In the IG, the elevation and reduction of leukocyte and lipid profile biomarkers, respectively, were not statistically significant (p > 0.05). A clinically and statistically significant increase in mean corpuscular hemoglobin concentration was observed in the CG (p = 0.018), with a large effect size (Cohen's d = 0.9). There were no statistically significant changes in platelet counts among participants (p = 0.18). The effect size for white blood cell count, low-density lipoprotein cholesterol, very low-density lipoprotein, and triglycerides was moderate in the IG compared to the CG. Conclusion: Cashew nut flour supplementation may increase levels of leukocytes and lipid profile parameters in children living with HIV. Brazilian Clinical Trials Registry (REBEC): U1111.1276.6591.

The socioeconomic epidemiology of inherited retinal diseases in Portugal.

BACKGROUND: Inherited retinal diseases (IRDs) are a group of rare degenerative disorders of the retina that can lead to blindness from birth to late middle age. Knowing the target population and its resources is essential to better plan support measures. The aim of this study was to evaluate the socioeconomic characteristics of regions in Portugal where IRD patients reside to inform the planning of vision aid and rehabilitation intervention measures. RESULTS: This study included 1082 patients from 973 families, aged 3 to 92 years, with a mean age of 44.8 ± 18.1 years. Patients living with an IRD were identified in 190 of the 308 municipalities. According to this study, the estimated IRD prevalence in Portugal was 10.4 per 100,000 inhabitants, and by municipalities, it ranged from 0 to 131.2 per 100,000 inhabitants. Overall, regions with a higher prevalence of IRD have a lower population density (r=-0.371, p < 0.001), a higher illiteracy rate (r = 0.404, p < 0.001) and an overall older population (r = 0.475, p < 0.001). Additionally, there is a lower proportion of doctor per capita (r = 0.350, p < 0.001), higher social security pensions beneficiaries (r = 0.439, p < 0.001), worse water quality for human consumption (r=-0.194, p = 0.008), fewer audiences at the cinema (r=-0.315, p < 0.001) and lower proportion of foreign guests in tourist accommodations (r=-0.287, p < 0.001). CONCLUSION: The number of identified patients with IRD varied between regions. Using data from national statistics (PORDATA), we observed differences in socioeconomic characteristics between regions. Multiple targeted aid strategies can be developed to ensure that all IRD patients are granted full clinical and socioeconomic support.

Reliability of roadside oral fluid testing devices for ∆9 -tetrahydrocannabinol (∆9 -THC) detection.

Driving under the influence of cannabis (DUIC) is increasing worldwide, and cannabis is the most prevalent drug after alcohol in impaired driving cases, emphasizing the need for a reliable traffic enforcement strategy. ∆9 -tetrahydrocannabinol (THC) detection in oral fluid has great potential for identifying recent cannabis use; however, additional data are needed on the sensitivities, specificities, and efficiencies of different oral fluid devices for detecting cannabinoids at the roadside by police during routine traffic safety enforcement efforts. At the roadside, 8945 oral fluid THC screening tests were performed with four devices: AquilaScan®, Dräger DrugTest®, WipeAlyser Reader®, and Druglizer®. A total of 530 samples screened positive for THC (5.9%) and were analyzed by liquid chromatography-tandem mass spectrometry at multiple cutoff concentrations (2 ng/mL, 10 ng/mL, and manufacturers' recommended device cutoffs) to investigate device performance. Results varied substantially, with sensitivities of 0%-96.8%, specificities of 89.8%-98.5%, and efficiencies of 84.3%-97.8%. The Dräger DrugTest® outperformed the other devices with a 96.8% sensitivity, 97.1% specificity, and 97.0% efficiency at a 5-ng/mL LC-MS/MS confirmation cutoff. The WipeAlyser Reader® had good performance with a 91.4% sensitivity, 97.2% specificity, and 96.4% efficiency. AquilaScan® and Druglizer® had unacceptable performance for cannabinoid detection, highlighted by sensitivity <13%. The choice of roadside oral fluid testing device must offer good analytical performance for cannabinoids because of its high prevalence of use and impact on road safety.

The Contribution of Inherited Thrombophilia to Venous Thromboembolism in Cancer Patients.

Although the relationship between venous thromboembolism (VTE) and cancer has been a subject of study, knowledge of the contribution of thrombophilia to thrombosis in patients with cancer is still very limited. The aim of this article is to collect present knowledge on the contribution of inherited thrombophilia to VTE in cancer patients. We performed a search in Google Scholar and PubMed and selected 21 from 76 returned articles. Then we made a narrative review of the selected articles. We describe 11 studies on the contribution of inherited thrombophilia to VTE in cancer patients in general and 10 on that contribution in specific types of cancer: 1 in colorectal cancer, 4 in breast cancer, 1 in gynecologic cancer and 4 in hematopoietic malignancies. All studies investigate the relation of factor V Leiden (FVL) to VTE, 13 that of the prothrombin G20210A mutation (PTG20210A) and 7 studies also investigate other inherited thrombophilias, such methylenetetrahydrofolate reductase gene mutations, although only 2 investigate the contribution of deficiencies of the natural anticoagulants. Studies are very heterogeneous, in design and sample size and conclusions differ considerably. There is no consensus on the contribution of inherited thrombophilia to VTE in cancer patients except for acute lymphoblastic leukemia in children. Probably, that contribution is not the same for all types of cancer and more studies are needed to bring more knowledge on this subject.

Transcriptome Analyses in Adult Olive Trees Indicate Acetaldehyde Release and Cyanide-Mediated Respiration Traits as Critical for Tolerance against Xylella fastidiosa and Suggest AOX Gene Family as Marker for Multiple-Resilience.

Xylella fastidiosa (Xf) is a global bacterial threat for a diversity of plants, including olive trees. However, current understanding of host responses upon Xf-infection is limited to allow early disease prediction, diagnosis, and sustainable strategies for breeding on plant tolerance. Recently, we identified a major complex trait for early de novo programming, named CoV-MAC-TED, by comparing early transcriptome data during plant cell survival with SARS-CoV-2-infected human cells. This trait linked ROS/RNS balancing during first hours of stress perception with increased aerobic fermentation connected to alpha-tubulin-based cell restructuration and control of cell cycle progression. Furthermore, our group had advanced concepts and strategies for breeding on plant holobionts. Here, we studied tolerance against Xf-infection by applying a CoV-MAC-TED-related gene set to (1) progress proof-of-principles, (2) highlight the importance of individual host responses for knowledge gain, (3) benefit sustainable production of Xf-threatened olive, (4) stimulate new thinking on principle roles of secondary metabolite synthesis and microbiota for system equilibration and, (5) advance functional marker development for resilience prediction including tolerance to Xf-infections. We performed hypothesis-driven complex analyses in an open access transcriptome of primary target xylem tissues of naturally Xf-infected olive trees of the Xf-tolerant cv. Leccino and the Xf-susceptible cv. Ogliarola. The results indicated that cyanide-mediated equilibration of oxygen-dependent respiration and carbon-stress alleviation by the help of increased glycolysis-driven aerobic fermentation paths and phenolic metabolism associate to tolerance against Xf. Furthermore, enhanced alternative oxidase (AOX) transcript levels through transcription Gleichschaltung linked to quinic acid synthesis appeared as promising trait for functional marker development. Moreover, the results support the idea that fungal endophytes strengthen Xf-susceptible genotypes, which lack efficient AOX functionality. Overall, this proof-of-principles approach supports the idea that efficient regulation of the multi-functional AOX gene family can assist selection on multiple-resilience, which integrates Xf-tolerance, and stimulates future validation across diverse systems.

Molecular Profiling of Axial Spondyloarthritis Patients Reveals an Association between Innate and Adaptive Cell Populations and Therapeutic Response to Tumor Necrosis Factor Inhibitors.

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients (n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3, the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Osseodensification vs. Conventional Osteotomy: A Case Series with Cone Beam Computed Tomography.

Introduction: Osseodensification is a non-extraction technique using specially designed drills to increase bone density while extending an osteotomy, allowing bone to be preserved and condensed by compacting autograft during osteotomy preparation, increasing bone density around implants, and improving mechanical stability. Aim: The objective of this study is to compare conventional osteotomy and osseodensification protocols in implant placement and analyze whether there are differences in bone density. Materials and Methods: Study variables were defined, namely, osseodensification technique, conventional osteotomy technique, bone density, sex, area of location, implant dimensions, implant dimensions, and implant stability. Eligibility and exclusion criteria were defined. A step-by-step surgical protocol was developed. The surgeon and radiologist underwent intra-examiner calibration. A total of 15 patients were selected according to the eligibility criteria, and a total of 41 implants were inserted, 20 implants by conventional osteotomy and 21 by osseodensification. A cone beam computed tomography was performed one year after prosthetic rehabilitation to estimate bone density. Data were collected and recorded, and in the analysis of the association of variables, non-parametric tests were applied. Results: Significant statistical results were found in bone density values, with higher values being obtained with the osseodensification technique, that is, median density values of 1020, and median density values of 732 for the bone drilling technique. The results of the correlation between bone density in both techniques and sex, primary implant stability, implant dimensions and location area were statistically non-significant. Conclusions: Within the limitations of this study, there are differences in bone density between conventional osteotomy and osseodensification protocols. Bone density is increased with osseodensification over a study period of one year.

Solidagenone from Solidago chilensis Meyen Protects against Acute Peritonitis and Lipopolysaccharide-Induced Shock by Regulating NF-κB Signaling Pathway.

Anti-inflammatory agents are widely used for the treatment of inflammatory diseases. Nevertheless, the associated side effects of the available drugs make it necessary to search for new anti-inflammatory drugs. Here, we investigated the anti-inflammatory activity of solidagenone. Initially, we observed that a single dose of 30, 60, or 90 mg/kg of solidagenone did not result in mortality or elicit any discernible signs of toxicity in mice. At the same doses, solidagenone promoted a significant reduction in the migration of neutrophils in an acute peritonitis model and decreased mortality in a lipopolysaccharide-induced endotoxic shock model. Interestingly, treatment with solidagenone conferred a protective effect against leukopenia and thrombocytopenia, hematological disorders commonly observed in sepsis conditions. In addition, treatment with all the doses of solidagenone promoted a significant reduction in nitric oxide, TNF-α, and IL-1ß levels relative to the LPS-stimulated vehicle-treated cultures. Furthermore, gene expression and in silico analyses also supported the modulation of the NF-κB pathway by solidagenone. Finally, in silico pharmacokinetics predictions indicated a favorable drugability profile for solidagenone. Taken together, the findings of the present investigation show that solidagenone exhibits significant anti-inflammatory properties in acute experimental models, potentially through the modulation of the NF-κB signaling pathway.

Green Analytical Toxicology procedure for determination of ketamine, its metabolites and analogues in oral fluid samples using dispersive liquid-liquid microextraction (DLLME).

New psychoactive substances (NPS) are often synthesized via small changes in the molecular structure, producing drugs whose effect and potency are not yet fully known. Ketamine is one of the oldest NPS, with therapeutic use in human and veterinary medicine authorized in several countries, being metabolized mainly into norketamine and 6-hydroxy-norketamine. Furthermore, two structural analogues of ketamine have recently been identified, deschloroketamine and 2-fluorodeschloroketamine, marketed as drugs of abuse. To comply with Green Analytical Toxicology (GAT) fundamentals, miniaturized techniques such as dispersive liquid-liquid microextraction (DLLME) were employed to determine toxicants in biological fluids. An analytical method for determining ketamine, its metabolites and its analogues in oral fluid was fully developed and validated by using DLLME and liquid chromatography-tandem mass spectrometry (LC-MS-MS). The extraction parameters were optimized by multivariate analysis, obtaining the best conditions with 200 µL of sample, 100 µL of methanol as dispersive solvent and 50 µL of chloroform as extractor solvent. Linearity was obtained from 10 to 1,000 ng/mL, with limit of detection (LOD) and lower limit of quantification (LLOQ) at 10 ng/mL. Imprecision (% relative standard deviation) and bias (%) were less than 8.2% and 9.5%, respectively. The matrix effect did not exceed 10.6%, and the recovery values varied from 24% to 42%. No matrix interference and good selectivity in the evaluation of 10 different sources of oral fluid and 42 drugs at 500 ng/mL, respectively, were observed. The method was applied in the analysis of 29 authentic oral fluid samples and had its green characteristic evaluated by three different tools: the Green Analytical Procedure Index (GAPI), the Analytical Eco-Scale and the Analytical GREEnness (AGREE) metrics.

Solvent-free parallel artificial liquid membrane extraction for drugs of abuse in plasma samples using LC-MS/MS.

BACKGROUND: Parallel artificial liquid membrane extraction (PALME) is a 96-well plate setup variant of liquid-phase microextraction. Basic or acidic analytes are extracted in neutral form from the sample, through a supported liquid membrane (SLM), and into aqueous acceptor. PALME is already considered a green extraction technique, but in the current conceptual work, we sought to make it even greener by replacing the use of organic solvents with essential oils (EO). PALME was combined with LC-MS/MS for analysis of plasma samples and multiple drugs of abuse with toxicological relevance (amphetamines, phenethylamines, synthetic cathinones, designer benzodiazepines, ayahuasca alkaloids, lysergic acid diethylamide, and ketamine). RESULTS: Fourteen EO were compared to organic solvents frequently used in PALME. The EO termed smart & sassy yielded the best analyte recovery for all drugs studied and was thus selected as SLM. Then, factorial screening and Box-Behnken were employed to optimize the technique. The extraction time, concentration of base, sample volume, and percentage of trioctylamine significantly impacted analyte recovery. The optimum values were defined as 120 min, 10 mmol/L of NaOH, 150 µL, and 0%, respectively. Once optimized, validation parameters were 1-100 ng mL-1 as linear range, accuracy ±16.4%, precision >83%, 1 ng mL-1 as limit of quantitation, 0.1-0.75 ng mL-1 as limit of detection, matrix effect <20%, and recovery 20-106%. Additionally, EO purchased from different production batches were tested and achieved acceptable reproducibility. Data were in compliance with requirements set by internationally accepted validation guidelines and the applicability of the technique was proven using authentic samples. SIGNIFICANCE: In this study, the use of an EO provided a solvent-free sample preparation technique suited to extract different classes of drugs of abuse from plasma samples, dismissing the use of hazardous organic solvents. The method also provided excellent sample clean-up, thus being a simple and efficient tool for toxicological applications that is in agreement with the principles of sustainable chemistry.

The Physician Surprise Question in the Emergency Department: prospective cohort study.

OBJECTIVES: This study aims to test the ability of the surprise question (SQ), when asked to emergency physicians (EPs), to predict in-hospital mortality among adults admitted to an emergency room (ER). METHODS: This prospective cohort study at an academic medical centre included consecutive patients 18 years or older who received care in the ER and were subsequently admitted to the hospital from 20 April 2018 to 20 October 2018. EPs were required to answer the SQ for all patients who were being admitted to hospital. The primary outcome was in-hospital mortality. RESULTS: The cohort included 725 adults (mean (SD) age, 60 (17) years, 51% men) from 58 128 emergency department (ED) visits. The mortality rates were 20.6% for 30-day all-cause in-hospital mortality and 23.6% for in-hospital mortality. The diagnostic test characteristics of the SQ have a sensitivity of 53.7% and specificity of 87.1%, and a relative risk of 4.02 (95% CI 3.15 to 5.13), p<0.01). The positive and negative predictive values were 57% and 86%, respectively; the positive likelihood ratio was 4.1 and negative likelihood ratio was 0.53; and the accuracy was 79.2%. CONCLUSIONS: We found that asking the SQ to EPs may be a useful tool to identify patients in the ED with a high risk of in-hospital mortality.

Class III plant peroxidases: From classification to physiological functions.

Peroxidases (EC 1.11.1.7) are involved in a wide range of physiological processes, hence their broad distribution across biological systems. These proteins can be classified as haem or non-haem enzymes. According to the RedOxiBase database, haem peroxidases are approximately 84 % of all known peroxidase enzymes. Class III plant peroxidases are haem-enzymes that share similar three-dimensional structures and a common catalytic mechanism for hydrogen peroxide degradation. They exist as large multigene families and are involved in metabolizing Reactive Oxygen Species (ROS), hormone synthesis and decomposition, fruit growth, defense, and cell wall synthesis and maintenance. As a result, plant peroxidases gained attention in research and became one of the most extensively studied groups of enzymes. This review provides an update on the database, classification, phylogeny, mechanism of action, structure, and physiological functions of class III plant peroxidases.

Plantar pressure thresholds as a strategy to prevent diabetic foot ulcers: A systematic review.

Background: The development of ulcers in the plantar region of the diabetic foot originates mainly from sites subjected to high pressure. The monitoring of these events using maximum allowable pressure thresholds is a fundamental procedure in the prevention of ulceration and its recurrence. Objective: The aim of this review was to identify data in the literature that reveal an objective threshold of plantar pressure in the diabetic foot, where pressure is classified as promoting ulceration. The aim is not to determine the best and only pressure threshold for ulceration, but rather to clarify the threshold values most used in clinical practice and research, also considering the devices used and possible applications for offloading plantar pressure. Design: A systematic review. Methods: The search was performed in three electronic databases, by the PRISMA methodology, for studies that used a pressure threshold to minimize the risk of ulceration in the diabetic foot. The selected studies were subjected to eligibility criteria. Results: Twenty-six studies were included in this review. Seven thresholds were identified, five of which are intended for the inside of the shoe: a threshold of average peak pressure of 200 kPa; 25 % and 40-80 % reduction from initial baseline pressure; 32-35 mm Hg for a capillary perfusion pressure; and a matrix of thresholds based on patient risk, shoe size and foot region. Two other thresholds are intended for the barefoot, 450 and 750 kPa. The threshold of 200 kPa of pressure inside the shoe is the most agreed upon among the studies. Regarding the prevention of ulceration and its recurrence, the efficacy of the proposed threshold matrix and the threshold of reducing baseline pressure by 40-80 % has not yet been evaluated, and the evidence for the remaining thresholds still needs further studies. Conclusions: Some heterogeneity was found in the studies, especially regarding the measurement systems used, the number of regions of interest and the number of steps to be considered for the threshold. Even so, this review reveals the way forward to obtain a threshold indicative of an effective steppingstone in the prevention of diabetic foot ulcer.

Forest waste composting-operational management, environmental impacts, and application.

In Portugal, the number of fires and the size of burnt areas are rising dramatically every year, increasing with improper management of agroforestry wastes (AFRs). This work aims to study the composting of these wastes with minimal operational costs and understand the environmental impact and the compost application on burnt soil. Thus, a study of life cycle assessment (LCA) was carried out based on windrow composting processes, considering the avoided environmental impacts associated with the end-product quality and its application as an organic amendment. Three composting piles were made with AFRs from the Residual Biomass Collection Centre (RBCC) in Bodiosa (Portugal). Sewage sludges (SS) from an urban wastewater treatment plant were used as conditioning agent. One pile with AFRs (MC) and another with AFRs and SS (MCS) were managed according to good composting practices. Another pile with the AFRs was developed without management (NMC), thus with a minimal operational cost. Periodically, it was measured several physical and chemical parameters according to standard methodologies. Eleven environmental impacts of compost production, MC and MCS, were analyzed by a LCA tool, and their effect on the growth of Pinus pinea was evaluated, using peat as reference. Composting evolution was expected for both piles. Final composts, MC and MCS, were similar, complying with organic amendment quality parameters. Compost NMC, with no operational management, showed the highest germination index. Piles MC and MCS showed similar environmental impacts, contributing to a negative impact on global warming, acidification, and eutrophication. Greater growth was obtained with application of MCS, followed by MC, and finally, peat. Composting is a sustainable way to valorize AFRs wastes, producing compost that could restore burnt soils and promote plant growth and circular economy.