Antidiabetic and Anti-Inflammatory Effect of Cinnamomum cassia Oil in Alloxan-Induced Diabetic Rats.

Diabetes mellitus presents a great diversity of treatments that cause adverse effects; therefore, plants are a source of compounds that may have fewer adverse effects; Cinnamomum cassia (C. cassia) has compounds with potential antidiabetic activity. The objective was to evaluate the antidiabetic effect of C. cassia oil (CCO) and its impact on oxidative stress in Wistar rats. Five groups were evaluated: (1) sham (SH), (2) 300 mg/kg CCO (CCO), (3) diabetic (D) induced with alloxan, (4) D + 300 mg/kg of CCO (D + CCO), and (5) D + 500 mg/kg of metformin (D + MET); all were treated for 5 days. CCO did not show alteration in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) vs. SH. D + CCO vs. D significantly reduced glucose (333 ± 109 vs. 458 ± 81 mg/dL), ALT (66 ± 15 vs. 160 ± 54 U/L), AST (119 ± 26 vs. 243 ± 104 U/L), and blood urea nitrogen (18.8 ± 2.3 vs. 29.2 ± 6.9 mg/dL). No significant changes were observed in D + CCO vs. D in malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD), whereas a significant reduction in MDA and GSH was achieved in D + MET, with an increase in SOD. There was a reduction in Rela and Gpx in D + CCO and D + MET vs. D. CCO has antidiabetic and anti-inflammatory effects and reduces ALT, AST, and BUN levels.

Targeted and untargeted serum NMR metabolomics to reveal initial kidney disease in diabetes mellitus.

Serum 1H NMR metabolomics has been used as a diagnostic tool for screening type 2 diabetes (T2D) with chronic kidney disease (CKD) as comorbidity. This work aimed to evaluate 1H NMR data to detect the initial kidney damage and CKD in T2D subjects, through multivariate statistical analysis. Clinical data and biochemical parameters were obtained for classifying five experimental groups using KDIGO guidelines: Control (healthy subjects), T2D, T2D-CKD-mild, T2D-CKD-moderate, and T2D-CKD-severe. Serum 1H NMR spectra were recorded to follow two strategies: one based on metabolite-to-creatinine (Met/Cr) ratios as targeted metabolomics, and the second one based on untargeted metabolomics from the 1H NMR profile. A prospective biomarkers panel of the early stage of T2D-CKD based in metabolite-to-creatinine ratio (ornithine/Cr, serine/Cr, mannose/Cr, acetate/Cr, acetoacetate/Cr, formate/Cr, and glutamate/Cr) was proposed. Later, a statistical model based on non-targeted metabolomics was used to predict initial CKD, and its metabolic pathway analysis allowed identifying the most affected pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine degradation; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and histidine metabolism. Nonetheless, further studies with a larger cohort are advised to precise ranges in metabolite-to-creatinine ratios and evaluate the prediction pertinency to detect initial CKD in T2D patients in both statistical models proposed.

Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity.

An important epigenetic component of tyrosine kinase signaling is the phosphorylation of histones, and epigenetic readers, writers, and erasers. Phosphorylation of protein arginine methyltransferases (PRMTs), have been shown to enhance and impair their enzymatic activity. In this study, we show that the hyperactivation of Janus kinase 2 (JAK2) by the V617F mutation phosphorylates tyrosine residues (Y149 and Y334) in coactivator-associated arginine methyltransferase 1 (CARM1), an important target in hematologic malignancies, increasing its methyltransferase activity and altering its target specificity. While non-phosphorylatable CARM1 methylates some established substrates (e.g. BAF155 and PABP1), only phospho-CARM1 methylates the RUNX1 transcription factor, on R223 and R319. Furthermore, cells expressing non-phosphorylatable CARM1 have impaired cell-cycle progression and increased apoptosis, compared to cells expressing phosphorylatable, wild-type CARM1, with reduced expression of genes associated with G2/M cell cycle progression and anti-apoptosis. The presence of the JAK2-V617F mutant kinase renders acute myeloid leukemia (AML) cells less sensitive to CARM1 inhibition, and we show that the dual targeting of JAK2 and CARM1 is more effective than monotherapy in AML cells expressing phospho-CARM1. Thus, the phosphorylation of CARM1 by hyperactivated JAK2 regulates its methyltransferase activity, helps select its substrates, and is required for the maximal proliferation of malignant myeloid cells.

MicroRNA-204 Regulates Angiogenesis and Vasculogenic Mimicry in CD44+/CD24- Breast Cancer Stem-like Cells.

Tumors have high requirements in terms of nutrients and oxygen. Angiogenesis is the classical mechanism for vessel formation. Tumoral vascularization has the function of nourishing the cancer cells to support tumor growth. Vasculogenic mimicry, a novel intratumoral microcirculation system, alludes to the ability of cancer cells to organize in three-dimensional (3D) channel-like architectures. It also supplies the tumors with nutrients and oxygen. Both mechanisms operate in a coordinated way; however, their functions in breast cancer stem-like cells and their regulation by microRNAs remain elusive. In the present study, we investigated the functional role of microRNA-204 (miR-204) on angiogenesis and vasculogenic mimicry in breast cancer stem-like cells. Using flow cytometry assays, we found that 86.1% of MDA-MB-231 and 92% of Hs-578t breast cancer cells showed the CD44+/CD24- immunophenotype representative of cancer stem-like cells (CSCs). The MDA-MB-231 subpopulation of CSCs exhibited the ability to form mammospheres, as expected. Interestingly, we found that the restoration of miR-204 expression in CSCs significantly inhibited the number and size of the mammospheres. Moreover, we found that MDA-MB-231 and Hs-578t CSCs efficiently undergo angiogenesis and hypoxia-induced vasculogenic mimicry in vitro. The transfection of precursor miR-204 in both CSCs was able to impair the angiogenesis in the HUVEC cell model, which was observed as a diminution in the number of polygons and sprouting cells. Remarkably, miR-204 mimics also resulted in the inhibition of vasculogenic mimicry formation in MDA-MB-231 and Hs-578t CSCs, with a significant reduction in the number of channel-like structures and branch points. Mechanistically, the effects of miR-204 were associated with a diminution of pro-angiogenic VEGFA and ß-catenin protein levels. In conclusion, our findings indicated that miR-204 abrogates the angiogenesis and vasculogenic mimicry development in breast cancer stem-like cells, suggesting that it could be a potential tool for breast cancer intervention based on microRNA replacement therapies.

The Promotion of Mental Health and Prevention of First-Episode Psychosis: A Pilot and Feasibility Non-Randomised Clinical Trial.

BACKGROUND: Mental-health-related stigma prevents active help seeking and therefore early therapeutic approaches and the recovery of functionality. National and international agencies recommend the implementation of prevention and mental health promotion programs that support the elimination of stigma in the classroom, since most mental health problems usually start in the adolescent stage. In view of the evidence that teachers present stigmatizing attitudes towards mental health, it has been considered as convenient to carry out an anti-stigma program with the main objective of evaluating the impact of an intervention based on the education and promotion of mental health, aimed at teachers and counsellors of a secondary school. The specific objectives were to get to know which were the most stigmatising attitudes that prevailed in the sample before and after the intervention; to evaluate the knowledge of the teaching staff and counsellors on psychosis before the intervention; to analyse correlations between clinically relevant variables; and assess whether this programme was beneficial and feasible for alphabetising counsellors/teachers of educational centres on stigma and FEP. METHODS: This was a non-randomised clinical trial in which a nursing intervention was performed. TOOLS: a psychosis test (pre), Stigma Attribution Questionnaire (AQ-27) (pre-post), and satisfaction survey (post) were used. The inferential analysis included the Wilcoxon and the Pearson Correlation Test. RESULTS: In the sample (n = 22), the predominant stigmatising attitude was "Help". The p-values obtained in the Wilcoxon Test were statistically significant, except for "Responsibility" and "Pity". The following constructs of interest were faced: "Fear"-"Age" and "Professional experience"; and "Help"-"Psychosis test". CONCLUSIONS: Despite the scores obtained in "Responsibility" and "Pity", the intervention was useful for reducing stigma in the sample. Implications for the profession: There are adolescents who have suffered stigma from their teachers, and consequently have minimized their symptoms and not asked for help. For this reason, we implemented a nursing intervention based on the education and promotion of mental health, with the aim of expanding knowledge and reducing stigma. In fact, this intervention, which we carried out on high school teachers, managed to reduce the majority of stigmatizing attitudes measured on the stigma attribution scale.

All I missed in the therapeutic relationship: The lived experience narrative of a mental health nurse receiving mental healthcare.

WHAT IS KNOWN ON THE SUBJECT?: The therapeutic relationship is crucial for mental health practice, especially to practice that is recovery-orientated. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: This lived experience suggests that mental health professionals can be a long way from knowing the service users' feelings and their precise needs. The narrative reveals how mental health professionals maintain stereotypes and prejudices against people with mental health conditions and how these are reflected in their practice through lack of respect and users' dignity. WHAT ARE THE IMPLICATIONS FOR MENTAL HEALTH NURSING?: This lived experience narrative highlights the need to humanize care. ABSTRACT: INTRODUCTION: The therapeutic relationship is not always functional in clinical practice due to various factors, such as lack of time, lack of job motivation, exhaustion and rejection towards the person cared for. AIM: The aim of this study is to illustrate to professionals the needs of the persons they care for and how they see the world. METHOD: The aim was achieved through the development of a lived experience narrative. RESULTS: This lived experience narrative describes the experience of a mental health nurse since her first psychotic symptoms and her perceptions of the therapeutic relationship with mental health staff in her trajectory from the first psychiatric appointment until her last contact with the community mental health services. DISCUSSION: This narrative suggests that mental health professionals are sometimes far from discovering what service users are feeling and their precise needs. This highlights the need to humanize mental healthcare.

Non-tunneled catheter tip depth position in urgent hemodialysis: a randomized controlled trial.

BACKGROUND: The average accepted depth for non-tunneled catheters (NTC) insertion does not guarantee its correct position, so controversy exists. The aim of this study was to assess the effect of two NTC placement depths on the number of NTC complication episodes. METHODS: We designed a triple blind, parallel group, randomized controlled trial in a single Hemodialysis Center in Mexico (Registry: ACTRN12619000774123). We included patients in urgent need of hemodialysis via internal right jugular vein NTC. The length of the NTC tip placement depth was randomized to second intercostal space (2ICS) or fourth intercostal space (4ICS), using physical landmarks. The primary outcome was to compare the composite number of NTC dysfunction, repositioning, and relocation episodes for 48 hours post-procedure. RESULTS: One hundred and sixty-five patients were included, 86 and 79 patients to NTC placement in the 2ICS and 4ICS, respectively. All patients underwent intention-to-treat analysis. The incidence of the composite outcome was lower in the 2ICS group compared to the 4ICS group, 4 (4.6%) and 50 (63%) combined episodes, respectively (P<0.001). Compared to the 4ICS group, the 2ICS group presented a relative risk of 0.06 (CI: 0.02-0.21, P<0.001) and number needed to treat (NNT) of 2.1. No adverse events occurred, derived from the NTC placement. CONCLUSIONS: NTC tip placement in the 2ICS compared to 4ICS decreases the incidence of the combined number of dysfunctions, repositioning and relocation episodes, with a NNT of 2 for its prevention.

Using nuclear magnetic resonance urine metabolomics to develop a prediction model of early stages of renal disease in subjects with type 2 diabetes.

Type 2 diabetes mellitus (DM2) is a multimorbidity, long-term condition, and one of the worldwide leading causes of chronic kidney disease (CKD) -a silent disease, usually detected when non-reversible renal damage have already occurred. New strategies and more effective laboratory methods are needed for more opportune diagnosis of DM2-CKD. This study comprises clinical parameters and nuclear magnetic resonance (NMR)-based urine metabolomics data from 60 individuals (20-65 years old, 67.7% females), sorted in 5 experimental groups (healthy subjects; diabetic patients without any clinical sign of CKD; and patients with mild, moderate, and severe DM2-CKD), according to KDIGO. DM2-CKD produces a continuous variation of the urine metabolome, characterized by an increase/decrement of a group of metabolites that can be used to monitor CKD progression (trigonelline, hippurate, phenylalanine, glycolate, dimethylamine, alanine, 2-hydroxybutyrate, lactate, and citrate). NMR profiles were used to obtain a statistical model, based on partial least squares analysis (PLS-DA) to discriminate among groups. The PLS-DA model yielded good validation parameters (sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic curve (ROC) plot: 0.692, 0.778 and 0.912, respectively) and, thus, it can differentiate between subjects with DM2-CKD in early stages, from subjects with a mild or severe condition. This metabolic signature exhibits a molecular variation associated to DM2-CKD, and data suggests it can be used to predict risk of DM2-CKD in patients without clinical signs of renal disease, offering a new alternative to current diagnosis methods.

Involving Persons With Lived Experience to Improve Vocational Students' Stigmatizing Attitudes Toward Mental Disorders: A Quasi-Experimental Study.

BACKGROUND: Mental health problems are estimated to affect one in six individuals in the European Union. Fifty percent of mental disorders start in adolescence, around the age of 14. The stigma associated with having a mental health problem is one of the main barriers to seeking help for psychiatric and psychological disorders among adolescents and young adults. Interventions to reduce social stigma could contribute to increased help-seeking behavior in this population. AIMS: To assess the effectiveness of a direct contact intervention in the classroom by persons with lived experience to reduce vocational students' stigmatizing attitudes. METHOD: One person with lived experience and one first-degree relative implemented a classroom intervention lasting 90 min. Its effectiveness was measured using a quasi-experimental study with a pretest-posttest design and within-subject control. RESULTS: A total of 128 students from three different Vocational and Technical Schools from Spain participated in the study. After the intervention, statistically significant differences were observed in the scores of 11 of the 13 dimensions measured with the Spanish Mental Illness Stigma Attribution Questionnaire (AQ-27-E) and the Community Attitudes toward Mental Illness (CAMI) questionnaires. No differences associated with gender or familiarity with the mental disorder were observed. CONCLUSION: Vocational students' negative attitudes and emotions can be improved through a direct contact intervention in the classroom involving people who have experienced a mental disorder themselves. The age range for optimal results with this type of intervention appears to be 18 to 20 years.

The utility of the Barthel index as an outcome predictor in older patients with acute infection attending the emergency department.

BACKGROUND: Functional decline and frailty are common in older adults and influence the risk of adverse outcomes. We aimed to assess the value of a Barthel index at the Emergency Department (ED-BI) score in predicting 30-day mortality and ED reconsultation among older patients with acute infection. METHODS: We performed a prospective multicentre cohort study of older patients (≥75 years) diagnosed with acute infection in 69 Spanish EDs. Demographic, comorbidities, functional status, clinical and analytical data were collected. Unadjusted and adjusted logistic regression models were used to assess the association between ED-BI score, mortality and ED reconsultation. RESULTS: In total 1596 patients with a mean age of 84.7 years were included in the study and 51.7% female. The most frequent focus of infection was respiratory in 918 patients (57.5%). Patients with an ED-BI< 60 points were significantly older, predominantly female, more likely institutionalized and more urinary infections. When comparing patients with an ED-BI score ≥ 60 points with those< 60 points no differences were found in ED reconsultation but in the latter group mortality at 30-days was higher (p < 0.001). CONCLUSION: An ED-BI score< 60 points appears to be a strong predictor of mortality at the 30-day follow up in older patients with acute infection. DATA AVAILABILITY: The data used to support the findings of this study are included within the article.