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Introduction: Depression is a serious and widespread mental health disorder. A significant proportion of patients with depression fail to remit after two antidepressant treatment trials, a condition named treatment-resistant depression (TRD). Clinical practice guidelines (CPGs) are instruments aimed to improve diagnosis and treatment. This study objective is to systematically appraise the quality and elaborate a comparison of high-quality CPGs with high-quality recommendations aimed at TRD., Methods and Analysis: We searched several specialized databases and organizations that develop CPGs. Independent researchers assessed the quality of the CPGs and their recommendations using AGREE II and AGREE-REX instruments, respectively. We selected only high-quality CPGs that included definition and recommendations for TRD. We investigated their divergencies and convergencies as well as weak and strong points., Results: Among seven high-quality CPGs with high-quality recommendations only two (Germany's Nationale Versorgungs Leitlinie-NVL and US Department of Veterans Affairs and Department of Defense-VA/DoD) included specific TRD definition and were selected. We found no convergent therapeutic strategy among these two CPGs. Electroconvulsive therapy is recommended by the NVL but not by the VA/DoD, while repetitive transcranial magnetic stimulation is recommended by the VA/DoD but not by the NVL. While the NVL recommends the use of lithium, and a non-routine use of thyroid or other hormones, psychostimulants, and dopaminergic agents the VA/DoD does not even include these drugs among augmentation strategies. Instead, the VA/DoD recommends ketamine or esketamine as augmentation strategies, while the NVL does not mention these drugs. Other differences between these CPGs include antidepressant combination, psychotherapy as a therapeutic augmentation, and evaluation of the need for hospitalization all of which are only recommended by the NVL., Conclusions: High-quality CPGs for the treatment of depression diverge regarding the definition and use of the term TRD. There is also no convergent approach to TRD from currently high-quality CPGs., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Ivan Florez is the current leader of the AGREE collaboration., (Copyright: © 2023 Gabriel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Depression is a serious and widespread mental health disorder. Although effective treatment does exist, a significant proportion of patients with depression fail to respond to antidepressant treatment trials, a condition named treatment-resistant depression. Efficient approach should be given this condition in order to revert the burden caused by depression. Clinical practice guidelines (CPGs) are evidence-based health promotion instruments to improve diagnosis and treatment. CPGs recommendations for treatment-resistant depression must be trustworthy. The objective of the proposed study is to systematically identify, appraise the quality of CPGs for the treatment of depression and elaborate a synthesis of recommendations for treatment-resistant depression of CPGs considered to be of high quality and with high quality recommendations., Methods and Analysis: We will search the databases of organizations, such as PubMed, Embase, Cochrane Library, PsycInfo, and the Virtual Health Library, and organizations that develop CPGs. Three independent researchers will assess the quality of the CPGs and their recommendations using the AGREE II and AGREE-REX instruments, respectively. Given the identification of divergences and convergences as well as weak and strong points among high quality CPGs, our work may help developers, clinicians and eventually patients., Ethics and Dissemination: No ethical approval is required for a systematic review, as no patient data will be used. The research results will be disseminated in conferences and submitted to a peer reviewed journal., Competing Interests: Ivan Florez is the current leader in the AGREE collaboration. All other authors declare that they have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Mitochondrial genomes are highly conserved in many fungal groups, and they can help characterize the phylogenetic relationships and evolutionary biology of plant pathogenic fungi. Rust fungi are among the most devastating diseases for economically important crops around the world. Here, we report the complete sequence and annotation of the mitochondrial genome of Austropuccinia psidii (syn. Puccinia psidii), the causal agent of myrtle rust. We performed a phylogenomic analysis including the complete mitochondrial sequences from other rust fungi. The genome composed of 93.299 bp has 73 predicted genes, 33 of which encoded nonconserved proteins (ncORFs), representing almost 45% of all predicted genes. A. psidii mtDNA is one of the largest rust mtDNA sequenced to date, most likely due to the abundance of ncORFs. Among them, 33% were within intronic regions of diverse intron groups. Mobile genetic elements invading intron sequences may have played significant roles in size but not shaping of the rust mitochondrial genome structure. The mtDNAs from rust fungi are highly syntenic. Phylogenetic inferences with 14 concatenated mitochondrial proteins encoded by the core genes placed A. psidii according to phylogenetic analysis based on 18S rDNA. Interestingly, cox1, the gene with the greatest number of introns, provided phylogenies not congruent with the core set. For the first time, we identified the proteins encoded by three A. psidii ncORFs using proteomics analyses. Also, the orf208 encoded a transmembrane protein repressed during in vitro morphogenesis. To the best of our knowledge, we presented the first report of a complete mtDNA sequence of a member of the family Sphaerophragmiacea., Competing Interests: The authors have declared that no competing interests exist.

Insect pests are one of the factors that most impact plant yield. The magnitude of the losses and the spatiotemporal pest distribution in crops is a result of their interactions with the environment. Therefore, the understanding of the causes of production losses and the pest spatial patterns is important for the development of suitable sampling plans and pest management programs. Thus, this study aimed to quantify grain losses caused by insects and to determine the spatial distribution pattern of arthropod pest species in Bt and non-Bt corn. The prevailing insect pests in the corn ears were the earworm and fall armyworm caterpillars (Helicoverpa spp. and Spodoptera frugiperda), the cornsilk fly (Euxesta spp.), the maize weevil (Sitophilus zeamais), and the square-necked grain beetle (Cathartus quadricollis). The non-Bt corn was more attacked by the caterpillars and the weevil, while Bt corn was more affected by the cornsilk fly Euxesta spp. Spatial dependence was significant for the damage caused by the caterpillars, the grain beetle and the maize weevil in both the Bt and non-Bt corn genotypes. The range of the damage caused by the insects was between 9.0-9.7 m for the caterpillars, 6.9-12.20 m for the cornsilk fly, 10.7-80.4 m for the square-necked grain beetle, and 51.9-170.7 m for the maize weevil. The pattern of the spatial distribution of pest damage in both corn genotypes (i.e., Bt and non-Bt corn) was similar with a prevalence of moderate to strong spatial dependence and aggregate damage distribution. The plants near to the sampling points exhibited injury and infestation levels similar to those of the sampled plants., Competing Interests: The authors have declared that no competing interests exist.

A growing body of evidence suggests a protective role of polyphenols and exercise training on the disorders of type 2 diabetes mellitus (T2DM). We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on diabetic complications induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks and a single dose of STZ (35 mg/kg i.p.). Control (C) and Diabetic (D) animals were subdivided into four groups each: Sedentary, Training, ASE Sedentary, and ASE Training. ASE (200 mg/kg/day) was administered by gavage and the exercise training was performed on a treadmill (30min/day; 5 days/week) for 4 weeks after the diabetes induction. In type 2 diabetic rats, the treatment with ASE reduced blood glucose, insulin resistance, leptin and IL-6 levels, lipid profile, and vascular dysfunction. ASE increased the expression of insulin signaling proteins in skeletal muscle and adipose tissue and plasma GLP-1 levels. ASE associated with exercise training potentiated the reduction of glycemia by decreasing TNF-α levels, increasing pAKT and adiponectin expressions in adipose tissue, and IR and pAMPK expressions in skeletal muscle of type 2 diabetic rats. In conclusion, ASE treatment has an antidiabetic effect in type 2 diabetic rats by activating the insulin-signaling pathway in muscle and adipose tissue, increasing GLP-1 levels, and an anti-inflammatory action. Exercise training potentiates the glucose-lowering effect of ASE by activating adiponectin-AMPK pathway and increasing IR expression., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: Roberto Soares de Moura is the inventor of the following patent application: Process to obtain decoctions of skins and stone of the fruit of Euterpe oleracea (Açai); process to obtain a hydro-alcoholic extract from the decoctions; process to obtain a lyophilized and/or spray dried from the hydro-alcoholic extracts; process to obtain pharmaceutical preparations containing the lyophilized and/or spay dried, and therapeutic indications of the preparations as vasodilators and on the prevention and treatment of vasospastic ischemical syndromes and arterial hypertension (PI/0604281-3). The other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1) on adiposity and hepatic steatosis in mice that were fed a high-fat (HF) diet and its underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control), 10% fat + ASE (ASE), 60% fat (HF), and 60% fat + ASE (HF + ASE) for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG), hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase) and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis.