Improved Mitochondrial Function with Diet-Induced Increase in Either Docosahexaenoic Acid or Arachidonic Acid in Membrane Phospholipids

Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP). We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA; 22:6n3) and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6) in mitochondrial membranes is associated with a greater Ca2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6). Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs

Enhanced Leishmania braziliensis Infection Following Pre-Exposure to Sandfly Saliva

Parasites of the genus Leishmania cause a variety of diseases known as leishmaniasis, that are transmitted by bites of female sand flies that, during blood-feeding, inject humans with parasites and saliva. It was shown that, in mice, immunity to sand-fly saliva is able to protect against the development of leishmaniasis. We have investigated, in the present study, whether this finding extends the sand fly species Lutzomyia intermedia, which is responsible for transmission of Leishmania braziliensis, a parasite species able to cause destructive skin lesions that can be fatal if left untreated. We observed that mice injected with sand fly saliva develop a specific immune response against salivary proteins. Most importantly, however, this immune response was unable to protect mice against a challenge infection with L. braziliensis, indicating that exposure to this sand fly saliva is harmful to the host. Indeed, subjects with cutaneous leishmaniasis have a higher immune response against L. intermedia saliva. These findings indicate that the anti-saliva immune response to sand fly saliva plays an important role in the outcome of leishmaniasis caused by L. braziliensis, in both mice and humans, and emphasize possible hurdles in the development of vaccines based on sand fly saliva

Impact of supragingival therapy on subgingival microbial profile in smokers versus non-smokers with severe chronic periodontitis

The aim of this study was to assess subgingival microbiological changes in smokers versus non-smokers presenting severe chronic periodontitis after supragingival periodontal therapy (ST).Non-smokers (n=10) and smokers (n=10) presenting at least nine teeth with probing pocket depth (PPD) (≥5 mm), bleeding on probing (BoP), and no history of periodontal treatment in the last 6 months were selected. Clinical parameters assessed were plaque index (PI), BoP, PPD, relative gingival margin position (rGMP) and relative clinical attachment level (rCAL). Subgingival biofilm was collected before and 21 days after ST. DNA was extracted and the 16S rRNA gene was amplified with the universal primer pair, 27F and 1492R. Amplified genes were cloned, sequenced, and identified by comparison with known 16S rRNA sequences. Statistical analysis was performed by Student's t and Chi-Square tests (α=5%).Clinically, ST promoted a significant reduction in PI and PPD, and gain of rCAL for both groups, with no significant intergroup difference. Microbiologically, at baseline, data analysis demonstrated that smokers harbored a higher proportion of Porphyromonas endodontalis, Bacteroidetes sp., Fusobacterium sp. and Tannerella forsythia and a lower number of cultivated phylotypes (p<0.05). Furthermore, non-smokers featured significant reductions in key phylotypes associated with periodontitis, whereas smokers presented more modest changes.Within the limits of the present study, ST promoted comparable clinical improvements in smokers and non-smokers with severe chronic periodontitis. However, in smokers, ST only slightly affected the subgingival biofilm biodiversity, as compared with non-smokers

The association between bullying and early stages of suicidal ideation in late adolescents in Greece

<p>Abstract</p> <p>Background</p> <p>Bullying in schools has been associated with suicidal ideation but the confounding effect of psychiatric morbidity has not always been taken into account. Our main aim was to test the association between bullying behavior and early stages of suicidal ideation in a sample of Greek adolescents and to examine whether this is independent of the presence of psychiatric morbidity, including sub-threshold symptoms.</p> <p>Methods</p> <p>5614 pupils 16-18 years old and attending 25 senior high schools were screened in the first phase and a stratified random sample of 2431 were selected for a detailed interview at the second phase. Psychiatric morbidity and suicidal ideation were assessed with the revised Clinical Interview Schedule (CIS-R) while bullying was assessed with the revised Olweus bully/victim questionnaire.</p> <p>Results</p> <p>Victims of bullying behavior were more likely to express suicidal ideation. This association was particularly strong for those who were bullied on a weekly basis and it was independent of the presence of psychiatric morbidity (Odds Ratio: 7.78; 95% Confidence Interval: 3.05 - 19.90). In contrast, being a perpetrator ("bullying others") was not associated with this type of ideation after adjustment. These findings were similar in both boys and girls, although the population impact of victimization in the prevalence of suicidal ideation was potentially higher for boys.</p> <p>Conclusions</p> <p>The strong cross-sectional association between frequent victimization and suicidal ideation in late adolescence offers an opportunity for identifying pupils in the school setting that are in a higher risk for exhibiting suicidal ideation.</p

Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation

Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR–significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression–SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD–relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms

Bullying behaviour in schools, socioeconomic position and psychiatric morbidity: a cross-sectional study in late adolescents in Greece

<p>Abstract</p> <p>Background</p> <p>Bullying is quite prevalent in the school setting and has been associated with the socioeconomic position and psychiatric morbidity of the pupils. The aim of the study was to investigate the association between bullying and socioeconomic status in a sample of Greek adolescents and to examine whether this is confounded by the presence of psychiatric morbidity, including sub-threshold forms of illness.</p> <p>Methods</p> <p>5,614 adolescents aged 16-18 years old and attending 25 senior high schools were screened and a stratified random sample of 2,427 were selected for a detailed interview. Psychiatric morbidity was assessed with a fully structured psychiatric interview, the revised Clinical Interview Schedule (CIS-R), while bullying was assessed with the revised Olweus bully/victim questionnaire. The following socio-economic variables were assessed: parental educational level and employment status, financial difficulties of the family and adolescents' school performance. The associations were investigated using multinomial logit models.</p> <p>Results</p> <p>26.4% of the pupils were involved in bullying-related behaviours at least once monthly either as victims, perpetrators or both, while more frequent involvement (at least once weekly) was reported by 4.1%. Psychiatric morbidity was associated with all types of bullying-related behaviours. No socioeconomic associations were reported for victimization. A lower school performance and unemployment of the father were significantly more likely among perpetrators, while economic inactivity of the mother was more likely in pupils who were both victims and perpetrators. These results were largely confirmed when we focused on high frequency behaviours only. In addition, being overweight increased the risk of frequent victimization.</p> <p>Conclusions</p> <p>The prevalence of bullying among Greek pupils is substantial. Perpetration was associated with some dimensions of adolescents' socioeconomic status, while victimization showed no socioeconomic associations. Our findings may add to the understanding of possible risk factors for bullying behaviours in adolescence.</p