Use of natural-based commercial products as an alternative for providing bioprotection against verticillium wilt of olive.

BACKGROUND: As a result of the ineffectiveness of existing control methods against Verticillium dahliae, the causal agent of verticillium wilt of olive (Olea europaea; VWO), it is necessary to search for sustainable and environmentally friendly alternatives, such as bioprotection by products based on plant extracts and other naturally synthesized compounds. Therefore, present study aimed to evaluate the effects of seven natural-based commercial products on the inhibition of mycelial growth, the germination of V. dahliae conidia and microsclerotia, and disease progression in olive plants (cv. Picual). Aluminium lignosulfonate and a copper phosphonate salt (copper phosphite) were included for comparative purposes. RESULTS: The seaweed and willow extracts and copper phosphite inhibited V. dahliae mycelial growth by more than 50% at the high doses tested. Most of the products inhibited conidial germination by up to 90% compared to the control at the high doses tested. However, none of the products showed efficacy above 50% in inhibiting microsclerotia germination. The willow extract was the most effective at reducing disease severity and progression in olive plants, with no significant differences compared to the non-inoculated negative control. CONCLUSION: The results of the present study suggest that the use of natural-based products (i.e. seaweed and willow extracts) is a potential sustainable alternative in an integrated VWO control strategy. © 2024 Society of Chemical Industry.

Future trends of additive manufacturing in medical applications: An overview.

Additive Manufacturing (AM) has recently demonstrated significant medical progress. Due to advancements in materials and methodologies, various processes have been developed to cater to the medical sector's requirements, including bioprinting and 4D, 5D, and 6D printing. However, only a few studies have captured these emerging trends and their medical applications. Therefore, this overview presents an analysis of the advancements and achievements obtained in AM for the medical industry, focusing on the principal trends identified in the annual report of AM3DP.

Facile Synthesis of Ni-Doped ZnO Nanoparticles Using Cashew Gum: Investigation of the Structural, Optical, and Photocatalytic Properties.

This work adopted a green synthesis route using cashew tree gum as a mediating agent to obtain Ni-doped ZnO nanoparticles through the sol-gel method. Structural analysis confirmed the formation of the hexagonal wurtzite phase and distortions in the crystal lattice due to the inclusion of Ni cations, which increased the average crystallite size from 61.9 nm to 81.6 nm. These distortions resulted in the growth of point defects in the structure, which influenced the samples' optical properties, causing slight reductions in the band gaps and significant increases in the Urbach energy. The fitting of the photoluminescence spectra confirmed an increase in the concentration of zinc vacancy defects (VZn) and monovacancies (Vo) as Zn cations were replaced by Ni cations in the ZnO structure. The percentage of VZn defects for the pure compound was 11%, increasing to 40% and 47% for the samples doped with 1% and 3% of Ni cations, respectively. In contrast, the highest percentage of VO defects is recorded for the material with the lowest Ni ions concentration, comprising about 60%. The influence of dopant concentration was also reflected in the photocatalytic performance. Among the samples tested, the Zn0.99Ni0.01O compound presented the best result in MB degradation, reaching an efficiency of 98.4%. Thus, the recovered material underwent reuse tests, revealing an efficiency of 98.2% in dye degradation, confirming the stability of the photocatalyst. Furthermore, the use of different inhibitors indicated that •OH radicals are the main ones involved in removing the pollutant. This work is valuable because it presents an ecological synthesis using cashew gum, a natural polysaccharide that has been little explored in the literature.

Gut dysbiosis induced by florfenicol increases susceptibility to Aeromonas hydrophila infection in Zebrafish Danio rerio after the recommended withdrawal period.

OBJECTIVE: Florfenicol (FFC) is a broad-spectrum antibiotic approved by the U.S. Food and Drug Administration to treat both systemic and external bacterial infections in food fish. The objective of this study was to evaluate the effect of FFC-medicated feed on the gut microbiota of Zebrafish Danio danio to determine (1) if the therapeutic dose of FFC-medicated feed induces dysbiosis and (2) if fish with altered gut microbiota were more susceptible to subsequent infection by the common opportunistic fish pathogen Aeromonas hydrophila. METHODS: Zebrafish that were treated with regular and FFC-medicated feeds were artificially challenged with A. hydrophila at the end of the recommended 15-day antibiotic withdrawal period. The gut microbiota of the Zebrafish at different stages was analyzed using 16S ribosomal RNA gene sequencing. RESULT: Our results found that FFC-medicated feed induced disruption of the gut microbiota. Dysbiosis was observed in all treated groups, with a significant increase in bacterial diversity, and was characterized by a remarkable bloom of Proteobacteria and a drastic decline of Mycoplasma and Cetobacterium in treated animals but without noticeable clinical signs or mortalities. In addition, the increase of Proteobacteria was not significantly reduced after the recommended 15-day withdrawal period, and the Zebrafish treated with FFC-medicated feed exhibited a significantly higher mortality rate when they were subsequently challenged with A. hydrophila compared to the control (regular feed) groups. Interestingly, the most dramatic changes in the gut microbiome composition occurred at the transition time between the late stage of the medicated treatment and the beginning of the withdrawal period instead of the time during the Aeromonas infection. CONCLUSION: The administration of FFC-medicated feed at the recommended dose induced gut dysbiosis in Zebrafish, and fish did not recover to the baseline after the recommended withdrawal period. Our findings suggest that the use of antibiotics in fish elicits a response similar to those previously described in mammals and possibly makes the host more susceptible to subsequent infections of opportunistic pathogens. This study using a controlled model system suggests that antibiotics in aquaculture may have long-term effects on the general well-being of the fish.

Improved accuracy in pentraxin-3 quantification assisted by aqueous biphasic systems as serum pretreatment strategies.

Although pentraxin-3 holds promise as a diagnosis/prognosis biomarker of microbial infections and lung cancer, its analysis in human serum can be constrained by matrix effects caused by high abundance proteins - human serum albumin and immunoglobulin G. Aqueous biphasic systems composed of polymers and citrate buffer are here proposed as a serum pretreatment step to improve the accuracy of pentraxin-3 analysis. Binodal curves were determined to identify the compositions required to form two phases and to correlate the polymers' properties and performance in serum pretreatment and biomarker extraction. Aqueous biphasic systems were evaluated regarding their ability to deplete human serum albumin and immunoglobulin G at the interphase. Polymers of relatively high to intermediate hydrophobicity were unveiled as efficient components to deplete high abundance serum proteins. Considering the possibility to extract pentraxin-3 from human serum into the polymer-rich phase, the system composed of polyethylene glycol with a molecular weight of 1000 g·mol-1 simultaneously achieved >93 % of human serum albumin and immunoglobulin G depletion and complete biomarker extraction. The accuracy of analysis of pretreated human serum by enzyme-linked immunosorbent assays outperformed that of a non-pretreated sample, with a relative error of 0.8 % compared to 14.6 %, contributing to boost pentraxin-3 usefulness as a biomarker.

Biointerfacial behavior of stallion spermatozoa adhered to hydrogel surfaces: Impact of the hydrogel chemical composition and the culture medium.

Novel soft materials based on hydrogel are proposed to enhance the selection of high-quality stallion sperm based on their adhesion capacity. The hydrogel surfaces are derived from polyacrylamide (PAAm), which is copolymerized with neutral and ionic co-monomers to modify the interfacial properties. The hydrogels undergo characterization through FTIR spectroscopy, assessment of swelling capacity, and wettability under various experimental conditions. Sperm adhesion capacity on the hydrogels is examined through several parameters including the percentage of bound sperm (%Sp) to hydrogels, tail oscillation intensity and flagellar movement. The biointerfacial properties of sperm-hydrogel systems vary based on the chemical composition of hydrogel as well as the components present in the culture medium. High %Sp and excellent metabolic activity of the spermatozoa are observed on hydrogel surfaces that possess moderate hydrophilicity. Specifically, a cationic hydrogel in BGM3 culture medium and a neutral surface in BGM3 medium supplemented with BSA exhibit favorable outcomes. Scanning Electron Microscopy (SEM) reveals the normal morphology of the head and tail in spermatozoa adhered to the hydrogel. Therefore, these hydrogel surfaces are potential materials for selecting stallion sperm with high quality, and their application could be extended to the study of other mammalian reproductive cells.

Angiomiofibroblastoma vulvoperineal, presentación de un caso / Vulvoperineal angiomyofibroblatoma, a case report

An angiomyofibroblastoma is a benign tumor that may present itself in the genital tract of a reproductive age woman. Despite it being a benign neoplasia, unable to be invasive, it can reach large sizes, producing discomfort, pain, and anatomical deformation. A late diagnosis may result in increased surgical difficulty for resection. The following is the clinical case of a woman with a vulvo-perineal tumor of 6 years of evolution, with a final diagnosis of angiomyofibroblastoma, in which complete resection of the lesion was achieved with good cosmetic results. The highlight of this tumor is its slow, silent, but progressive growth, leading to diagnoses that are often confused and late, with a consequent delay in treatment. Among the common differential diagnoses are the Bartholin gland cyst and the aggressive angiomyxoma.

El angiomiofibroblastoma es un tumor benigno que puede presentarse en el tracto genital de la mujer en edad reproductiva. A pesar de ser una neoplasia benigna, sin capacidad invasora, puede alcanzar grandes tamaños, produciendo molestia, dolor y alteración importante de la anatomía. Si el diagnóstico es tardío, aumenta la dificultad quirúrgica en su resección. A continuación, se presenta el caso clínico de una mujer con un tumor vulvoperineal de 6 años de evolución, con diagnóstico final de angiomiofibroblastoma, en el que se logró la resección completa de la lesión con un buen resultado estético. La importancia de este tumor está dada por su crecimiento lento, silencioso, pero progresivo, llevando a que su diagnóstico sea en muchas ocasiones confuso y tardío, con el consecuente retraso en el tratamiento. Dentro de los diagnósticos diferenciales comunes se encuentran el quiste de la glándula de Bartholino y el angiomixoma agresivo.

Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort.

BACKGROUND: Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. OBJECTIVES: The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. METHODS: We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. RESULTS: The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (ß = -5.60 kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (ß = -10.26 mm Hg per FT3/FT4 unit, p = 0.002), and lower left ventricular ejection fraction (LVEF) (ß = 3.60% per FT3/FT4 unit, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95% CI: 1.04-5.88, per 1-unit decrease in FT3/FT4, p = 0.041). CONCLUSIONS: In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP, and lower LVEF. Lower FT3/FT4 predicted a higher risk of diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

The impact of heart failure therapy in patients with mildly reduced ejection fraction: a network meta-analysis.

BACKGROUND: Recent heart failure (HF) guidelines have re-classified HF patients with left ventricular ejection fraction (LVEF) between 41% and 49% as HF with mildly reduced ejection fraction (HFmrEF). HFmrEF treatment is often considered a grey zone as no randomized controlled trials (RCTs) were conducted exclusively on these patients. AIMS: A network meta-analysis (NMA) was performed to compare treatment effect of mineralocorticoid receptor antagonists (MRA), angiotensin receptor neprilysin inhibitor (ARNi), angiotensin receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and beta-blockers (BB) in HFmrEF cardiovascular (CV) outcomes. METHODS AND RESULTS: RCTs sub-analyses evaluating the efficacy of pharmacological treatment in HFmrEF patients were searched. Hazard ratios (HRs) and their variance were extracted from each RCT for (i) composite of CV death or HF hospitalizations, (ii) CV death, and (iii) HF hospitalizations. A random-effects NMA was performed to compare and assess the treatment efficiency. Six RCTs with subgroup analysis according to participants' ejection fraction, a patient-level pooled meta-analysis of two RCTs, and an individual patient-level analysis of eleven BB RCTs were included, totalling 7966 patients. To our primary endpoint, SGLT2i vs. placebo was the only comparison with significant results, with a 19% risk reduction in the composite of CV death or HF hospitalizations [HR 0.81, 95% confidence interval (CI) 0.67-0.98]. In HF hospitalizations, the impact of the pharmacological therapies was more notorious, and ARNi reduced in 40% the risk of HF hospitalizations (HR 0.60, 95% CI 0.39-0.92), SGLT2i in 26% (HR 0.74, 95% CI 0.59-0.93) and renin-angiotensin system inhibition (RASi) with ARB and ACEi in 28% (HR 0.72, 95% CI 0.53-0.98). Although BBs were globally less beneficial, they were the only class that supported a reduced risk of CV death (HR vs. placebo: 0.48, 95% CI 0.24-0.95). We did not observe a statistically significant difference in any comparison between active treatments. There was a sound reduction with ARNi on the primary endpoint (HR vs. BB: 0.81, 95% CI 0.47-1.41; HR vs. MRA 0.94, 95% CI 0.53-1.66) and on HF hospitalizations (HR vs. RASi 0.83, 95% CI 0.62-1.11; HR vs. SGLT2i 0.80, 95% CI 0.50-1.30). CONCLUSIONS: In addition to SGLT2i, pharmacological treatment recommended for HF with reduced LVEF, namely, ARNi, MRA, and BB, can also be effective in HFmrEF. This NMA did not show significant superiority over any pharmacological class.

Combined Use of Ionic Liquid-Based Aqueous Biphasic Systems and Microfluidic Devices for the Detection of Prostate-Specific Antigen.

Prostate cancer (PCa) is one of the cancer types that most affects males worldwide and is among the highest contributors to cancer mortality rates. Therefore, there is an urgent need to find strategies to improve the diagnosis of PCa. Microtechnologies have been gaining ground in biomedical devices, with microfluidics and lab-on-chip systems potentially revolutionizing medical diagnostics. In this paper, it is shown that prostate-specific antigen (PSA) can be detected through an immunoassay performed in a microbead-based microfluidic device after being extracted and purified from a serum sample through an aqueous biphasic system (ABS). Given their well-established status as ABS components for successful bioseparations, ionic liquids (ILs) and polymers were used in combination with buffered salts. Using both IL-based and polymer-based ABS, it was demonstrated that it is possible to detect PSA in non-physiological environments. It was concluded that the ABS that performed better in extracting the PSA from serum were those composed of tetrabutylammonium chloride ([N4444]Cl) and tetrabutylphosphonium bromide ([P4444]Br), both combined with phosphate buffer, and constituted by polyethylene glycol with a molecular weight of 1000 g/mol (PEG1000) with citrate buffer. In comparison with the assay with PSA prepared in phosphate-buffered saline (PBS) or human serum in which no ABS-mediated extraction was applied, assays attained lower limits of detection after IL-based ABS-mediated extraction. These results reinforce the potential of this method in future point-of-care (PoC) measurements.

Nutritional Status Is Associated With Clinical Progression in Alzheimer's Disease: The NUDAD Project.

OBJECTIVE: In cognitively normal adults, nutritional parameters are related to cognitive decline and incidence of dementia. Studies on the role of nutrition in predementia stages subjective cognitive decline and mild cognitive impairment, and mild stages of Alzheimer's disease (AD) dementia in a clinical setting are lacking. In the absence of a curative treatment, this evidence is important for targeting nutritional factors to potentially prevent or delay further cognitive decline. Our aim is to investigate associations of nutritional parameters with clinical progression in patients ranging from those who are cognitively normal to those who have AD dementia. DESIGN: Longitudinal. SETTING AND PARTICIPANTS: Memory clinic, 551 patients (219 with subjective cognitive decline, 135 with mild cognitive impairment, and 197 with AD dementia), mean age 64 ± 8 years. MEASUREMENTS: We assessed body mass index, fat-free mass, Mini-Nutritional Assessment, and dietary intake with the Dutch Healthy Diet food frequency questionnaire and the 238-item healthy life in an urban setting (HELIUS) food frequency questionnaire at baseline. Cox proportional hazard models were used to evaluate associations of nutritional parameters with clinical progression. Additional analyses were restricted to patients who were amyloid positive. RESULTS: We observed clinical progression in 170 patients (31%) over 2.2 ± 0.9 years. Poorer Mini-Nutritional Assessment score [hazard ratio (95% confidence interval) 1.39 (1.18-1.64)], lower body mass index [1.15 (0.96-1.38)], lower fat-free mass [1.40 (0.93-2.10)], and a less healthy dietary pattern [1.22 (1.01-1.48)] were associated with a higher risk of clinical progression. Similar effect sizes were found in patients who were amyloid positive. CONCLUSIONS AND IMPLICATIONS: Poorer nutritional status and a less healthy dietary pattern are associated with a higher risk of clinical progression. This study provides support for investigating whether improving nutritional status can alter the clinical trajectory of AD.

Multidrug-Resistant Biofilms (MDR): Main Mechanisms of Tolerance and Resistance in the Food Supply Chain.

Biofilms are mono- or multispecies microbial communities enclosed in an extracellular matrix (EPS). They have high potential for dissemination and are difficult to remove. In addition, biofilms formed by multidrug-resistant strains (MDRs) are even more aggravated if we consider antimicrobial resistance (AMR) as an important public health issue. Quorum sensing (QS) and horizontal gene transfer (HGT) are mechanisms that significantly contribute to the recalcitrance (resistance and tolerance) of biofilms, making them more robust and resistant to conventional sanitation methods. These mechanisms coordinate different strategies involved in AMR, such as activation of a quiescent state of the cells, moderate increase in the expression of the efflux pump, decrease in the membrane potential, antimicrobial inactivation, and modification of the antimicrobial target and the architecture of the EPS matrix itself. There are few studies investigating the impact of the use of inhibitors on the mechanisms of recalcitrance and its impact on the microbiome. Therefore, more studies to elucidate the effect and applications of these methods in the food production chain and the possible combination with antimicrobials to establish new strategies to control MDR biofilms are needed.

Clinical associations and prognostic implications of 6-minute walk test in rheumatoid arthritis.

The clinical associations and prognostic implications of the 6-minute walk test (6MWT) distance in patients with rheumatoid arthritis (RA) is yet to be explored. To identify the clinical features and prognostic implications associated with the 6MWT in patients with RA. Cohort study including 387 RA patients who underwent 6MWT. Regression models (linear and logistic) were built to identify independent predictors of shorter 6MWT distance. Cox proportional models were used to study the association of 6MWT distance with cardiovascular outcomes. Patients were subdivided according to 6MWT tertiles: 126 patients walked > 405 m, 129 walked 345-405 m, and 132 walked < 345 m. Older age (> 55 years), elevated waist circumference, NT-pro BNP > 125 pg/mL, anemia, C-reactive protein ≥ 3 mg/dL, and troponin T ≥ 14 pg/mL were independent predictors of walking shorter distances. Patients walking less than 345 m had higher risk of a subsequent cardiovascular hospitalization or cardiovascular death compared with patients walking 345 m or more (adjusted HR: 2.98, 95%CI: 1.37-6.51, p = 0.006). Older age, abdominal obesity, anemia, cardiac dysfunction, and inflammation were associated with walking shorter distances in patients with RA. Walking less than 345 m in the 6MWT was associated with a poor cardiovascular prognosis. The 6MWT is simple, reproducible, and inexpensive, easily performed in routine practice, and provides important information regarding the patients´ status and outcomes, enabling the monitorization of the therapeutic optimization of the various domains of the RA.

Multi-omic Analysis of the Gut Microbiome in Rats with Lithium-Pilocarpine-Induced Temporal Lobe Epilepsy.

Evidence supports that the gut microbiota and bacteria-dependent metabolites influence the maintenance of epileptic brain activity. However, the alterations in the gut microbiota between epileptic versus healthy individuals are poorly understood. We used a multi-omic approach to evaluate the changes in the composition of gut metagenome as well in the fecal metabolomic profile in rats before and after being submitted to status epilepticus (SE)-induced temporal lobe epilepsy (TLE). The 16S ribosomal RNA (rRNA) sequencing of fecal samples coupled to bioinformatic analysis revealed taxonomic, compositional, and functional shifts in epileptic rats. The species richness (Chao1 index) was significantly lower in the post-TLE group, and the ß-diversity analysis revealed clustering separated from the pre-TLE group. The taxonomic abundance analysis showed a significant increase of phylum Desulfobacterota and a decrease of Patescibacteria in the post-TLE group. The DESEq2 and LEfSe analysis resulted in 18 genera significantly enriched between post-TLE and pre-TLE groups at the genus level. We observed that epileptic rats present a peculiar metabolic phenotype, including a lower concentration of D-glucose and L-lactic acid and a higher concentration of L-glutamic acid and glycine. The microbiota-host metabolic correlation analysis showed that the genera differentially abundant in post-TLE rats are associated with the altered metabolites, especially the proinflammatory Desulfovibrio and Marvinbryantia, which were enriched in epileptic animals and positively correlated with these excitatory neurotransmitters and carbohydrate metabolites. Therefore, our data revealed a correlation between dysbacteriosis in epileptic animals and fecal metabolites that are known to be relevant for maintaining epileptic brain activity by enhancing chronic inflammation, an excitatory-inhibitory imbalance, and/or a metabolic disturbance. These data are promising and suggest that targeting the gut microbiota could provide a novel avenue for preventing and treating acquired epilepsy. However, the causal relationship between these microbial/metabolite components and the SRS occurrence still needs further exploration.

Detection of DNA from Toxoplasma gondii oocysts in water for reuse.

The absence of a standardized method for detecting oocysts in water samples makes it difficult to characterize them, including in water for reuse. This study aimed to detect Toxoplasma gondii oocysts using two extraction methods. Using method 1693/2014 USEPA, 30 L of water for reuse from two wastewater treatment plants (WWTPs) in the city of São Paulo, Brazil, was concentrated, totaling 20 samples. The supernatant generated from the immunomagnetic separation (IMS) step was collected for detection of T. gondii oocysts. For DNA extraction, two techniques were used: the commercial kit DNeasy PowerSoil Kit® optimized with the enzyme Zymolyase® and with freeze-thaw steps. DNA quantification was performed with the target sequence of gene B1. From 16 samples submitted to enzymatic extraction, four were positive. In freeze-thaw extraction, no DNA was detected. DNA extraction was the essential step for oocyst detection given the resistant nature of their wall.

Multiple versus single arterial grafting in the elderly: a meta-analysis of randomized controlled trials and propensity score studies.

INTRODUCTION: The benefit of adding a second arterial conduit is still controversial, mainly in specific subgroups. We conducted a meta-analysis of randomized controlled trials (RCTs) and propensity score (PS) studies comparing survival and early results in elderly patients who underwent coronary artery bypass grafting (CABG) with multiple (MAG) versus single arterial grafting (SAG). EVIDENCE ACQUISITION: MEDLINE, Web of Science and Cochrane Library were used to find relevant literature (1960-April 2020). Survival at a ≥1-year follow-up and early outcomes were evaluated. Outcomes were collected from matched samples or PS adjusted analysis: hazard ratio (HR) along with their variance, frequencies or odds ratios. Random effect models were used to compute combined statistical measures and 95% confidence intervals (CI) through generic inverse variance method (time-to-event) or Mantel-Haenszel method (binary events). EVIDENCE SYNTHESIS: Eleven PS cohorts and 1 RCT comprising >18,800 patients older than 70 (>6200 MAG and >12,500 SAG) were included in this meta-analysis. MAG was associated with lower long-term mortality (pooled HR: 0.81, 95% CI: 0.72-0.91, P<0.01, I2=64%) in the absence of higher risk of early mortality (pooled OR: 0.74, 95% CI: 0.44 to 1.25, P=0.27, I2=0%). In a meta-regression, MAG survival advantage was more pronounced in studies with a higher MAG usage rate (ß=-0.0052, P=0.021). CONCLUSIONS: Current evidence suggests that advanced age should not limit MAG's use considering its benefits in long-term survival. Of note, an individualized patient selection for this approach is warranted.

A systematic review and meta-analysis of randomized controlled studies comparing off-pump versus on-pump coronary artery bypass grafting in the elderly.

INTRODUCTION: Comparison of short and mid-term outcomes between off-pump CABG (OPCAB) and on-pump CABG (ONCAB) in patients older than 65 throughout a meta-analysis of randomized clinical trials (RCTs). EVIDENCE ACQUISITION: A literature search was conducted using 3 databases. RCTs reporting mortality outcomes of OPCAB versus ONCAB among the elderly were included. Data on myocardial infarction, stroke, re-revascularization, renal failure and composite endpoints after CABG were also collected. Random effects models were used to compute statistical combined measures and 95% confidence intervals (CI). EVIDENCE SYNTHESIS: Five RCTs encompassing 6221 patients were included (3105 OPCAB and 3116 ONCAB). There were no significant differences on mid-term mortality (pooled HR: 1.02, 95%CI: 0.89-1.17, P=0.80) and composite endpoint incidence (pooled HR: 0.98, 95%CI: 0.88-1.09, P=0.72) between OPCAB and ONCAB. At 30-day, there were no differences in mortality, myocardial infarction, stroke and renal complications. The need for early re-revascularization was significantly higher in OPCAB (pooled OR: 3.22, 95%CI: 1.28-8.09, P=0.01), with a higher percentage of incomplete revascularization being reported for OPCAB in trials included in this pooled result (34% in OPCAB vs. 29% in ONCAB, P<0.01). CONCLUSIONS: Data from RCTs in elderly patients showed that OPCAB and ONCAB provide similar mid-term results. OPCAB was associated with a higher risk of early re-revascularization. As CABG on the elderly is still insufficiently explored, further RCTs, specifically designed targeting this population, are needed to establish a better CABG strategy for these patients.

Effects of inhalation aromatherapy as a complementary therapy in pediatric patients in the clinical practice: A systematic review.

BACKGROUND: Inhalation aromatherapy is a complementary therapy in different clinical settings, but there is little evidence about its effectiveness in childcare. OBJECTIVE: To assess the effectiveness of inhalational aromatherapy in the care of hospitalized pediatric patients. METHODS: Systematic review of clinical trials and quasi-experimental studies, based on PRISMA recommendations, searching Medline, Web of Science, Scopus, SciELO, LILACS, CINAHL, Science Direct, EBSCO, and updated databases. The Down and Black 2020, RoB 2020 CLARITY, and ROBINS-I 2020 scales were used through the Distiller SR software to verify the studies' internal validity and risk of bias. RESULTS: From 446 articles identified, 9 fulfilled the inclusion criteria. Seven were randomized controlled trials (RCTs), one pilot RCT, and one non-randomized quasi-experimental trial. Different outcomes were analyzed, with pain being the most frequently measured variable. None of the 6 studies that evaluated pain showed significant effects with inhalation aromatherapy. Additionally, non-significant effects were found regarding nausea, vomiting, and behavioral/emotional variables. CONCLUSIONS: The findings are still inconclusive, and more evidence is required from future studies with high methodological quality, blinding, and adequate sample sizes.

Wnt/ß-Catenin-Dependent Transcription in Autism Spectrum Disorders.

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by synaptic dysfunction and defects in dendritic spine morphology. In the past decade, an extensive list of genes associated with ASD has been identified by genome-wide sequencing initiatives. Several of these genes functionally converge in the regulation of the Wnt/ß-catenin signaling pathway, a conserved cascade essential for stem cell pluripotency and cell fate decisions during development. Here, we review current information regarding the transcriptional program of Wnt/ß-catenin signaling in ASD. First, we discuss that Wnt/ß-catenin gain and loss of function studies recapitulate brain developmental abnormalities associated with ASD. Second, transcriptomic approaches using patient-derived induced pluripotent stem cells (iPSC) cells, featuring mutations in high confidence ASD genes, reveal a significant dysregulation in the expression of Wnt signaling components. Finally, we focus on the activity of chromatin-remodeling proteins and transcription factors considered high confidence ASD genes, including CHD8, ARID1B, ADNP, and TBR1, that regulate Wnt/ß-catenin-dependent transcriptional activity in multiple cell types, including pyramidal neurons, interneurons and oligodendrocytes, cells which are becoming increasingly relevant in the study of ASD. We conclude that the level of Wnt/ß-catenin signaling activation could explain the high phenotypical heterogeneity of ASD and be instrumental in the development of new diagnostics tools and therapies.

Advances Brought by Hydrophilic Ionic Liquids in Fields Involving Pharmaceuticals.

The negligible volatility and high tunable nature of ionic liquids (ILs) have been the main drivers of their investigation in a wide diversity of fields, among which is their application in areas involving pharmaceuticals. Although most literature dealing with ILs is still majorly devoted to hydrophobic ILs, evidence on the potential of hydrophilic ILs have been increasingly provided in the past decade, viz., ILs with improved therapeutic efficiency and bioavailability, ILs with the ability to increase drugs' aqueous solubility, ILs with enhanced extraction performance for pharmaceuticals when employed in biphasic systems and other techniques, and ILs displaying low eco/cyto/toxicity and beneficial biological activities. Given their relevance, it is here overviewed the applications of hydrophilic ILs in fields involving pharmaceuticals, particularly focusing on achievements and advances witnessed during the last decade. The application of hydrophilic ILs within fields involving pharmaceuticals is here critically discussed according to four categories: (i) to improve pharmaceuticals solubility, envisioning improved bioavailability; (ii) as IL-based drug delivery systems; (iii) as pretreatment techniques to improve analytical methods performance dealing with pharmaceuticals, and (iv) in the recovery and purification of pharmaceuticals using IL-based systems. Key factors in the selection of appropriate ILs are identified. Insights and perspectives to bring renewed and effective solutions involving ILs able to compete with current commercial technologies are finally provided.