Psychological, emotional and social impairments are associated with adherence and healthcare spending in type 2 diabetic patients: an observational study

OBJECTIVE: The aim of the present study was to assess the association among anxiety, depression, stress, social support and emotional abilities with adherence and healthcare spending in type 2 diabetic patients. PATIENTS AND METHODS: Sixty-four patients were enrolled and completed: Interpersonal Processes of Care (IPC), 20-item Toronto Alexithymia Scale (TAS-20), Rapid Stress Assessment Scale (RSAS), Morisky Medication Adherence Scale (MMAS-4), International Physical Activity Questionnaire (IPAQ)-Short Form and a socio-anamnestic questionnaire regarding also the healthcare spending. RESULTS: Mathematical linear regressions models were performed showing the predictive effects of: anxiety and social support scores (RSAS) on adherence levels (respectively p =. 019; p =. 016); adherence levels on anxiolytic use (p =.04); aggressiveness scores (RSAS) on the number of general check-ups (p =.031); TAS-20 and physician-patient communication (IPC) on the number of hospitalization days (respectively p=.001; p=.008); physician patient decision making (IPC) scores on physical activity (IPAQ) levels (p=.025); physical activity (IPAQ) on the number of medical examinations (p=.039). CONCLUSIONS: An association among psychosocial impairment, adherence and health- care spending was found. Future studies should investigate the effect of a brief psychological intervention in increasing adherence levels and reducing the healthcare spending in this clinical population

Transcriptomics and Functional Genomics of ROS-Induced Cell Death Regulation by RADICAL-INDUCED CELL DEATH1

Peer reviewe

Expression of selected marker genes in lesion mimic mutants.

<p>Samples from three lesion mimic genotypes (<i>acd2</i>, <i>acd5</i> and <i>lsd1</i>) 3 d after the transfer to LD were classified as samples from plants with no lesions (labelled 0); leaves with no lesions from plants with lesions (labelled −); leaves with lesions (labelled +). Averages of qPCR results (arbitrary units) from three biological replicates are shown; error bars depict standard deviation. Asterisks depict statistical significance (P<0.05) between to Col-0 (within 0 samples) or to 0 samples within the respective genotype (− and + samples).</p

Cluster analysis of genes differentially regulated in <i>rcd1</i> compared to Col-0.

<p>Bootstrapped Bayesian hierarchical clustering of 423 genes with at least two-fold changed expression (log₂ ratio ±1, q<0.05) in clean air or O₃-treated <i>rcd1</i> is shown. Data sets used were <i>rcd1</i> mutant grown in control conditions, O₃-treated Col-0, O₃-treated <i>rcd1</i> and several other available experiments related to stress signaling and cell death (see “<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004112#s3" target="_blank">Materials and Methods</a>” for the complete set of experiments). Six main clusters (I to VI) with subclusters (marked with a or b) were identified. GO and promoter element enrichment results are provided in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004112#pgen.1004112.s004" target="_blank">Table S1</a>. Magenta and green indicate increased and decreased expression as log₂ ratio compared with untreated or wild type plants, respectively.</p

Cluster analysis of gene expression in clean air and O₃-treated plants.

<p>Three-week-old plants were treated with 6 h of O₃ (350 nL L⁻¹) and samples harvested at 2 and 8 h after the start of the O₃ exposure. Expression of selected marker genes in each genotype was studied with qPCR and bootstrapped Bayesian hierarchical clustering was applied to log₂-transformed expression values in arbitrary units (A). Gene expression in mutant genotypes was compared to the respective Col-0 sample at each time point (2 h, 8 h) and log₂-transformed fold changes were calculated for O₃ treatment (B) and control plants (C). Asterisks mark statistical significance according to the linear model (P<0.10:“.”; P<0.05:“*”; P<0.01:“**”; P<0.001:“***”.).</p

Enhanced SIMR in <i>rcd1</i> double mutants.

<p>Enhanced SIMR, defined as increased growth defects and/or dwarfism, is observed in the listed <i>rcd1</i> double mutants. The biological process(es) altered in the mutant crossed with <i>rcd1</i> is briefly summarized. Of the double mutants used for cell death experiments (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004112#pgen-1004112-g005" target="_blank">Figure 5</a> and <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004112#pgen-1004112-g006" target="_blank">6</a>) only <i>rcd1 vtc2</i> displayed enhanced SIMR. In addition <i>rcd1 agb1-2</i>, <i>rcd1 gpa1-4</i> and <i>rcd1 agb1-2 gpa1-4</i> displayed leaf characteristics of both parents: round leaves like the G-protein mutants and wavy, bushy leaves like <i>rcd1</i>.</p

Constitutive SIMR in the <i>rcd1</i> mutant is enhanced by ascorbate deficiency.

<p>Plants were grown for four weeks and photos taken. Scale bar = 1 cm.</p

Quantification of O₃ -induced cell death in Col-0, <i>rcd1</i> and various double mutants.

<p>Plants were exposed to 6₃ (400 nL L⁻¹) and after 2 h recovery in the clean air, they were harvested for ion leakage measurements. Samples of untreated plants grown in clean air were simultaneously collected. Samples are ranked according to their ion leakage in O₃. Ion leakage percentages of O₃ samples were compared to O₃-treated Col-0 and <i>rcd1-1</i> with linear models. Ion leakages of samples belonging to groups A and C did not differ from Col-0 and <i>rcd1</i>, respectively. Group B and C samples showed elevated O₃-damage compared to Col-0 (P<0.01), whereas samples in groups A and B had decreased O₃-damage in comparison to <i>rcd1</i> (P<0.01). In clean air samples, only <i>vtc2</i> differed from Col-0 (P<0.001). Bars represent means of two to seven biological repeats with standard error.</p

Response to apoplastic ROS in <i>rcd1</i> is not influenced by AOX1 or UPOX.

<p>Genotypes studied were Col-0, <i>AOX1a</i> OE (overexpression), <i>AOX1a</i> OE-CA (overexpression of constitutively active AOX1a), the corresponding vector control (VC) and the mutants <i>aox1a</i>, <i>upox1</i>, <i>rcd1-1</i>, <i>rcd1-4</i>, <i>rcd1-1 upox1</i>, <i>rcd1-1 aox1a</i> and <i>rcd1-4 aox1a</i>. Plants were exposed to 6 h of O₃ (350 nL L⁻¹) and after 2 hour recovery in the clean air they were harvested for ion leakage measurements. Samples of untreated plants grown in clean air were simultaneously collected. Clean air and O₃ samples were compared to wild type Col-0 with linear models (P<0.05:*; P<0.01:** and P<0.001:***). Double mutants (<i>rcd1-1 aox1a</i>, <i>rcd1-4 aox1a</i> and <i>rcd1-1 upox1</i>) were also compared to <i>rcd1-1</i> and <i>rcd1-4</i>. Bars represent means of four to six biological repeats with standard deviation.</p

Gene expression of Col-0 and <i>rcd1</i> mutant in clean air and O₃-treated plants.

<p>A) Experimental design with each sample hybridized against a reference RNA (solid arrows) enables multidirectional comparisons between genotypes and treatments with a linear mixed model (dotted arrows). The experiment described was repeated at each time point (0, 1, 2, 4, 8 and 24 h) and lists of differentially expressed transcripts (log₂ ratio ±1, q<0.05) were made from each comparison. Number of differentially expressed unique genes at all time points is shown. The 0 h comparison of O₃-treated <i>rcd1</i> and O₃-treated Col-0 was analyzed together with <i>rcd1</i> and Col-0 grown in clean air to comprise the list of genes differentially regulated in <i>rcd1</i> in normal growth conditions (<i>rcd1</i>-Col-0). Simultaneously, this 0 h comparison was omitted from the <i>rcd1</i>-Col-0 O₃ data set. B) Venn diagram showing the overlap of gene lists. Transcripts at least two-fold differentially regulated between <i>rcd1</i> and Col-0 in response to apoplastic ROS are divided into several subcategories discussed in the results. C, D) Transcript levels of 4544 genes responsive to O₃-treatment (log₂ ratio ±1, q<0.05) in one or both of the genotypes were compared. Genes were divided into O₃-induced (C) and O₃-repressed (D) according to the O₃-response specifically at each time point (0, 1, 2, 4, 8 and 24 h). For each gene the difference between O₃-treated <i>rcd1</i> and Col-0 was calculated (log₂ ratio) and the number of genes in each range of differential expression (depicted in color) is shown on the y-axis. The percentage of genes with higher (<i>rcd1</i>>Col-0) and lower (<i>rcd1</i>rcd1 compared to Col-0 was calculated. E) Expression of selected marker genes was studied in Col-0 and <i>rcd1</i> plants with qPCR. Bars represent means of three biological repeats, error bars show standard deviation. Statistically significant difference between genotypes is depicted with asterisk (P<0.05:*; P<0.01:** and P<0.001:***).</p