Does Diabetes Increase the Frequency of Root-Filled teeth: Systematic Review and Meta-Analysis of Observational Studies.

Background: The indicated treatment in cases of apical periodontitis (AP), a disease very prevalent in diabetic patients, is root canal treatment (RCT). This study aims to conduct a systematic review with meta-analysis to answer the following PICO question: In adult patients, does the absence or presence of diabetes affect the prevalence of root filled teeth (RFT)"? Material and Methods: PRISMA Guidelines have been followed to carry out this systematic review. A literature search was undertaken in PubMed-MEDLINE, Embase and Scielo. All studies reporting the prevalence of RFT in diabetic patients and control subjects using radiographic examination were included. Study characteristics and risk ratios with 95% CIs were extracted. Random-effects meta-analyses were performed. Results: Five studies fulfilled the inclusion criteria. Prevalence of RFT were estimated with 701 people and 15,882 teeth. Among diabetic patients, 6.1% of teeth had undergone RCT, while in controls this percentage was 3% (OR = 1.7; 95% CI = 1.0 - 2.9; p = 0.065). Among diabetic patients, 65% had at least one RFT, while in controls this percentage dropped to 55% (OR = 1.4; 95% CI = 0.5 - 3.7; p> 0.05). The certainty of evidence was low. Conclusions: The prevalence of RFT in diabetic patients is almost double that in the control population, however this result is only marginally significant. Dentists must take into account the high prevalence of RFT in diabetic patients, investigating the presence of diabetes in those patients in whom a high frequency of RCT is observed. Key words:Diabetes, endodontics, epidemiology, root canal treatment, root filled teeth, prevalence, survey, population-based study.

Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE.

Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In both, MS and its preclinical model, the experimental autoimmune encephalomyelitis (EAE) gastrointestinal symptoms including "leaky gut" have been reported. Oleacein (OLE), a phenolic compound from extra virgin olive oil or olive leaves, harbors a wide range of therapeutic properties. Previously, we showed OLE effectiveness preventing motor defects and inflammatory damage of CNS tissues on EAE mice. The current studies examine its potential protective effects on intestinal barrier dysfunction using MOG35-55-induced EAE in C57BL/6 mice. OLE decreased EAE-induced inflammation and oxidative stress in the intestine, preventing tissue injury and permeability alterations. OLE protected from EAE-induced superoxide anion and accumulation of protein and lipid oxidation products in colon, also enhancing its antioxidant capacity. These effects were accompanied by reduced colonic IL-1ß and TNFα levels in OLE-treated EAE mice, whereas the immunoregulatory cytokines IL-25 and IL-33 remained unchanged. Moreover, OLE protected the mucin-containing goblet cells in colon and the serum levels of iFABP and sCD14, markers that reflect loss of intestinal epithelial barrier integrity and low-grade systemic inflammation, were significantly reduced. These effects on intestinal permeability did not draw significant differences on the abundance and diversity of gut microbiota. However, OLE induced an EAE-independent raise in the abundance of Akkermansiaceae family. Consistently, using Caco-2 cells as an in vitro model, we confirmed that OLE protected against intestinal barrier dysfunction induced by harmful mediators present in both EAE and MS. This study proves that the protective effect of OLE in EAE also involves normalizing the gut alterations associated to the disease.

Prevalence of undiagnosed diabetes and prediabetes related to periodontitis and its risk factors in elderly individuals.

OBJECTIVE: The prevalence of undiagnosed diabetes was estimated to increase with age and can reach 3.5%. The purpose of the study was to evaluate the prevalence of undiagnosed diabetes and prediabetes in the elderly patients who attended a dental clinic and to find common risk factors. METHODS: Male patients, older than 50 years, attended their first dental visit to the School of Dentistry for a period of two years, and it was proposed to evaluate undiagnosed type 2 diabetes mellitus. Periodontal, biochemical, microbiological examinations, nutritional profile, and physical activity were performed. RESULTS: A total of 106 patients were examined, 6 (5.6%) had diabetes, and 37 (34.9%) had prediabetes without prior diagnosis. The severity of periodontitis was greater in patients with diabetes. Most of the patients were overweight and had increased systolic blood pressure. Patients with prediabetes and periodontitis had a low adherence to the Mediterranean diet. Tannerella forsythia was present in more patients with periodontitis, and the prevalence of Aggregatibacter actinomycetemcomitans is practically absent in groups with periodontitis, except for the group with diabetes. CONCLUSIONS: In the population studied, the prevalence of patients without a diagnosis of diabetes and prediabetes was very high and underestimated. The increased severity of periodontitis in patients with diabetes and in conjunction with the high level of cortisol seen in patients with periodontitis, especially those with diabetes, emphasize the dysregulation of the immunoinflammatory system. CLINICAL SIGNIFICANCE: It is essential to add all this data to our dental practice to cover patient health with a broader landscape.

Antibiotics prescription habits of Spanish endodontists: Impact of the ESE awareness campaign and position statement.

BACKGROUND: The inadequate use of antibiotics by dentists can contribute to antibiotic resistance. The European Society of Endodontology (ESE) has published a scientific evidence-based position on antibiotic use in endodontic infec-tions. The aim of this study was to analyze the antibiotics prescription habits of Spanish endodontists in the management of endodontic infections, comparing them with those they had 10 years ago, to assess the impact of the ESE awareness campaign and position statement on antibiotics in endodontics. MATERIAL AND METHODS: One hundred Spanish endodontists were requested to answer to a one-page survey, similar to that used previously ten years ago in another study, on indications for systemic antibiotics in the management of endodontic infections. Data were analyzed using descriptive statistics and chi-square test. Seventy-seven endodontists (77%) completed satisfactorily the survey and were included in the study. RESULTS: The average duration of antibiotic therapy was 5.64 ± 1.75 days. In patients with no medical allergies, 97.1% selected amoxicillin as the first-choice antibiotic. The first drug of choice for patients with an allergy to penicillin, was clindamycin 300 mg (74.03%). For cases of pulp necrosis with asymptomatic apical periodontitis, fistulous tract and mild/symptomatic symptoms, 100% of endodontists would prescribe antibiotics. For the scenario of a pulp necrosis with symptomatic periodontitis apical and no swelling, 20% endodontists would prescribe antibiotics. CONCLUSIONS: Antibiotics prescription habits of Spanish endodontists has improved after the ESE awareness campaign and position statement on antibiotics in endodontics. Even so, there are a percentage of professionals that still prescribe antibiotics erro-neously. Key words:Antibiotic, antibiotics resistance, dentistry, endodontists, endodontics, prescription habits, primary care.

LARP6C orchestrates posttranscriptional reprogramming of gene expression during hydration to promote pollen tube guidance.

Increasing evidence suggests that posttranscriptional regulation is a key player in the transition between mature pollen and the progamic phase (from pollination to fertilization). Nonetheless, the actors in this messenger RNA (mRNA)-based gene expression reprogramming are poorly understood. We demonstrate that the evolutionarily conserved RNA-binding protein LARP6C is necessary for the transition from dry pollen to pollen tubes and the guided growth of pollen tubes towards the ovule in Arabidopsis thaliana. In dry pollen, LARP6C binds to transcripts encoding proteins that function in lipid synthesis and homeostasis, vesicular trafficking, and polarized cell growth. LARP6C also forms cytoplasmic granules that contain the poly(A) binding protein and possibly represent storage sites for translationally silent mRNAs. In pollen tubes, the loss of LARP6C negatively affects the quantities and distribution of storage lipids, as well as vesicular trafficking. In Nicotiana benthamiana leaf cells and in planta, analysis of reporter mRNAs designed from the LARP6C target MGD2 provided evidence that LARP6C can shift from a repressor to an activator of translation when the pollen grain enters the progamic phase. We propose that LARP6C orchestrates the timely posttranscriptional regulation of a subset of mRNAs in pollen during the transition from the quiescent to active state and along the progamic phase to promote male fertilization in plants.

Oleanolic acid ameliorates intestinal alterations associated with EAE.

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment. METHODS: Mice with MOG35-55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects. RESULTS: We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS. CONCLUSION: These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.

Oleacein Attenuates the Pathogenesis of Experimental Autoimmune Encephalomyelitis through Both Antioxidant and Anti-Inflammatory Effects.

Oxidative stress and proinflammatory cytokines are factors affecting multiple sclerosis (MS) disease progression. Oleacein (OLE), an olive secoiridoid, possesses powerful antioxidant and anti-inflammatory activities, which suggests its potential application to treat neuroinflammatory disorders. Herein, we investigated the impact of OLE on the main clinic-pathological features of experimental autoimmune encephalomyelitis (EAE), an animal model for MS, including paralysis, demyelination, central nervous system (CNS) inflammation/oxidative stress and blood-brain barrier (BBB) breakdown. METHODS: Mice were immunized with the myelin oligodendrocyte glycoprotein peptide, MOG35-55, to induce EAE, and OLE was administrated from immunization day. Serum, optic nerve, spinal cord and cerebellum were collected to evaluate immunomodulatory activities at a systemic level, as well as within the CNS. Additionally, BV2 microglia and the retinal ganglion cell line RGC-5 were used to confirm the direct effect of OLE on CNS-resident cells. RESULTS: We show that OLE treatment effectively reduced clinical score and histological signs typical of EAE. Histological evaluation confirmed a decrease in leukocyte infiltration, demyelination, BBB disruption and superoxide anion accumulation in CNS tissues of OLE-treated EAE mice compared to untreated ones. OLE significantly decreased expression of proinflammatory cytokines (IL-13, TNFα, GM-CSF, MCP-1 and IL-1ß), while it increased the anti-inflammatory cytokine IL-10. Serum levels of anti-MOG35-55 antibodies were also lower in OLE-treated EAE mice. Further, OLE significantly diminished the presence of oxidative system parameters, while upregulated the ROS disruptor, Sestrin-3. Mechanistically, OLE prevented NLRP3 expression, phosphorylation of p65-NF-κB and reduced the synthesis of proinflammatory mediators induced by relevant inflammatory stimuli in BV2 cells. OLE did not affect viability or the phagocytic capabilities of BV2 microglia. In addition, apoptosis of RGC-5 induced by oxidative stressors was also prevented by OLE. CONCLUSION: Altogether, our results show that the antioxidant and anti-inflammatory OLE has neuroprotective effects in the CNS of EAE mice, pointing out this natural product as a candidate to consider for research on MS treatments.

El cuerpo duele, y el dolor social... ¿duele también? / The body hurts, and what about social pain? Does it hurts too?

En este trabajo se habla del concepto de dolor social relacionándolo con el dolor físico, y se hace una revisión profunda sobre su fisiología, vías comunes y diferenciales de procesamiento con el dolor físico, e interacciones entre ambos. El dolor social se define como una experiencia emocional desagradable desencadenada al percibirse el individuo como excluido o rechazado por parte de personas o grupos con los que desea relacionarse, lo que produce los mismos sentimientos de sufrimiento que el dolor físico. Se procesa en las mismas áreas cerebrales que el dolor físico en su dimensión afectiva. Puede revivirse mentalmente, aunque la situación conflictiva interpersonal haya terminado hace tiempo. Ambos tipos de dolor son fuentes de estrés. La confluencia en el sujeto de ambos complica y suma más presión a la que ejercen ambos estresores por separado. Esto debe ser tenido en cuenta a la hora de abordar a pacientes con dolor crónico

This paper studies the concept of «social pain» and its relationship with physical pain. An in-depth review of its physiology has been carried out, including similarities and differences in processing with relation to physical pain, as well as the interactions between both processes. Social pain is defined as an unpleasant emotional experience which is triggered when the individual feels excluded or rejected by people or social groups with whom they wish have a relationship. This perceived situation produces the same feelings of suffering as that of physical pain. This kind of pain is processed in the same brain areas as physical pain in its affective dimension. It may be revived mentally, even though the interpersonal conflictive situation may have ended long ago. Both types of pain are sources of stress. The confluence of both situations in the same individual adds complications and more pressure to that which is already exerted separately by both stressing factors. This circumstance must be taken into account when dealing with patients with chronic pain

[The body hurts, and what about social pain? Does it hurts too?] / El cuerpo duele, y el dolor social ¿duele también?

This paper studies the concept of «social pain¼ and its relationship with physical pain. An in-depth review of its physiology has been carried out, including similarities and differences in processing with relation to physical pain, as well as the interactions between both processes. Social pain is defined as an unpleasant emotional experience which is triggered when the individual feels excluded or rejected by people or social groups with whom they wish have a relationship. This perceived situation produces the same feelings of suffering as that of physical pain. This kind of pain is processed in the same brain areas as physical pain in its affective dimension. It may be revived mentally, even though the interpersonal conflictive situation may have ended long ago. Both types of pain are sources of stress. The confluence of both situations in the same individual adds complications and more pressure to that which is already exerted separately by both stressing factors. This circumstance must be taken into account when dealing with patients with chronic pain.

Examining Maladaptive Functioning in Physical Education: A Psychometric Analysis of the Psychological Need Thwarting Scale Among Spanish Secondary Students.

This research aimed to adapt the Psychological Need Thwarting Scale for use in the Spanish physical education (PE) context and to examine its psychometric properties with secondary school students. Participants were 459 secondary school PE students (206 boys and 253 girls, Mage = 15.41, SDage = 1.05). A confirmatory factor analysis supported an 11-item three-factor correlated model that remained invariant across gender and age. Internal consistency analysis showed adequate values for autonomy (α = .79, ρ = .80, average variance extracted [AVE] = .50), competence (α = .85, ρ = .86, AVE = .61), and relatedness (α = .86, ρ = .86, AVE = .68) need frustration. Temporal stability analysis displayed appropriate values for autonomy (intraclass correlation coefficient [ICC] = .81), competence (ICC = .89), and relatedness (ICC = .78) need frustration. Structural equation modeling showed that, while psychological need satisfaction positively predicted autonomous motivation (ß = .72, p < .001), psychological need frustration positively predicted controlled motivation (ß = .43, p < .001) and amotivation (ß = .48, p < .001). The adapted Psychological Need Thwarting Scale was shown to be a valid and reliable measure for assessing psychological need frustration in Spanish secondary school students.

LARP4A recognizes polyA RNA via a novel binding mechanism mediated by disordered regions and involving the PAM2w motif, revealing interplay between PABP, LARP4A and mRNA.

LARP4A belongs to the ancient RNA-binding protein superfamily of La-related proteins (LARPs). In humans, it acts mainly by stabilizing mRNAs, enhancing translation and controlling polyA lengths of heterologous mRNAs. These activities are known to implicate its association with mRNA, protein partners and translating ribosomes, albeit molecular details are missing. Here, we characterize the direct interaction between LARP4A, oligoA RNA and the MLLE domain of the PolyA-binding protein (PABP). Our study shows that LARP4A-oligoA association entails novel RNA recognition features involving the N-terminal region of the protein that exists in a semi-disordered state and lacks any recognizable RNA-binding motif. Against expectations, we show that the La module, the conserved RNA-binding unit across LARPs, is not the principal determinant for oligoA interaction, only contributing to binding to a limited degree. Furthermore, the variant PABP-interacting motif 2 (PAM2w) featured in the N-terminal region of LARP4A was found to be important for both RNA and PABP recognition, revealing a new role for this protein-protein binding motif. Our analysis demonstrates the mutual exclusive nature of the PAM2w-mediated interactions, thereby unveiling a tantalizing interplay between LARP4A, polyA and PABP.

Correction: Criteria and treatment decisions in the management of deep caries lesions: Is there endodontic overtreatment?

[This corrects the article on p. 751 in vol. 10, PMID: 30305872.].

Resonance assignment of human LARP4A La module.

Human LARP4A belongs to a superfamily of RNA binding proteins called La-related proteins (LARPs). Whilst being a positive regulator of protein synthesis and a promoter of mRNA stability, LARP4A also controls cell morphology and motility in human breast and prostate cancer cells. All LARPs share a characteristic RNA binding unit named the La-module, which despite a high level of primary structure conservation exhibits a great versatility in RNA target selection. Human LARP4A La-module is the most divergent compared with other LARPs and its RNA recognition properties have only recently started to be revealed. Given the key role of LARP4A protein in cancer cell biology, we have initiated a complete NMR characterisation of its La-module and here we report the assignment of 1H, 15N and 13C resonances resulting from our studies.

Criteria and treatment decisions in the management of deep caries lesions: Is there endodontic overtreatment?

BACKGROUND: The aim of this study was to investigate the diagnostic criteria and treatment decisions in the management of deep caries lesions (DCLs). The null hypothesis tested was that DCLs are managed according to the current scientific evidence. MATERIAL AND METHODS: A total of 288 dentists were contacted directly or by mail, and 125 (43%) were included in the study. Dentists were requested to answer a questionnaire about the routine approach to the diagnosis and treatment of DCLs. Logistic regression analyses were carried out to calculate odds ratios (OR). RESULTS: Pulp sensitivity tests were used by 65% of dentists when assessing pulpal health in cases of DCLs, particularly those who had followed courses in cariology (OR = 3.8; p = 0.005). Dentine hardness was the most frequent criterion used during DCLs excavation (98%). Two thirds of the respondents (65%) removed carious tissue until they felt hard dentine, and feeling hard dentine correlated with caries removal even at the risk of pulpal exposure (OR = 15.8; p = 0.0000). Acute transient pain or sensitivity to cold or heat (reversible pulpitis) were considered by 58% of respondents as a reason to provide endodontic therapy. CONCLUSIONS: The null hypothesis tested is rejected. The evidence-based more conservative approach on the management of DCLs is not being translated to clinical dentistry. Root canal treatment is being indicated in cases of DCLs in which the diagnosis is reversible pulpitis. Likewise, it can be concluded that non-conservative management of DCLs, with endodontic overtreatment, could be occurring. Key words:Deep caries lesions, dental pulp capping, dental pulp health, dentists, endodontic therapy, pulpal diagnosis, reversible pulpitis, treatment decisions.

A putative RNA binding protein from Plasmodium vivax apicoplast.

Malaria is caused by Apicomplexa protozoans from the Plasmodium genus entering the bloodstream of humans and animals through the bite of the female mosquitoes. The annotation of the Plasmodium vivax genome revealed a putative RNA binding protein (apiRBP) that was predicted to be trafficked into the apicoplast, a plastid organelle unique to Apicomplexa protozoans. Although a 3D structural model of the apiRBP corresponds to a noncanonical RNA recognition motif with an additional C-terminal α-helix (α3), preliminary protein production trials were nevertheless unsuccessful. Theoretical solvation analysis of the apiRBP model highlighted an exposed hydrophobic region clustering α3. Hence, we used a C-terminal GFP-fused chimera to stabilize the highly insoluble apiRBP and determined its ability to bind U-rich stretches of RNA. The affinity of apiRBP toward such RNAs is highly dependent on ionic strength, suggesting that the apiRBP-RNA complex is driven by electrostatic interactions. Altogether, apiRBP represents an attractive tool for apicoplast transcriptional studies and for antimalarial drug design.

The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats / El impacto de la obesidad sobre el lipidoma cardiaco y sus consecuencias en el daño cardiaco en ratas obesas

Aims: To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. Methods: Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. Results: HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O2), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. Conclusions: These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels (AU)

Objetivos: Explorar el impacto de la obesidad sobre el perfil lipídico cardiaco en ratas con obesidad inducida por dieta. Se evaluó, además, si estos cambios se asocian con fibrosis cardiaca. Métodos: Ratas macho Wistar fueron alimentadas con una dieta con alto contenido en grasa (HFD; 35% grasa) o con una dieta estándar (3,5% grasa) durante 6 semanas. El análisis del lipidoma cardiaco se realizó mediante cromatografía líquida en tándem con espectrofotometría de masas. Resultados: Las ratas HFD presentaron fibrosis cardiaca, estrés oxidativo y un aumento en el índice HOMA, adiposidad y los niveles circulantes de leptina así como una reducción en los niveles cardiacos del transportador de glucosa (GLUT 4) en comparación con las ratas controles. El análisis del lipidoma cardiaco mostró un aumento de los niveles de triglicéridos especialmente los que contenían ácido palmítico, esteárico o araquidónico, un incremento en los de diacilglicerol (DAG) aunque no cambios en los de diacilfosfatidilcolina y una reducción en los de diacilfosofatidiletanolamina, diacilfosfatidilinositol o de esfingomielinas (SM) en las ratas HFD en comparación con las control. Después del ajuste por otras variables (estrés oxidativo, hipertrofia cardiaca, índice HOMA), los niveles de DAG fueron predictores independientes de fibrosis cardiaca mientras que los de SM fueron de los de niveles de GLUT4. Conclusiones: La obesidad ejerce un impacto importante sobre el lipidoma cardiaco. Estos cambios parecen participar en el daño cardiaco en el contexto de la obesidad ya que los niveles de DAG podrían facilitar el desarrollo de fibrosis miocárdica y los de SM los de GLUT 4 (AU)

Inhibition of galectin-3 ameliorates the consequences of cardiac lipotoxicity in a rat model of diet-induced obesity.

Obesity is accompanied by metabolic alterations characterized by insulin resistance and cardiac lipotoxicity. Galectin-3 (Gal-3) induces cardiac inflammation and fibrosis in the context of obesity; however, its role in the metabolic consequences of obesity is not totally established. We have investigated the potential role of Gal-3 in the cardiac metabolic disturbances associated with obesity. In addition, we have explored whether this participation is, at least partially, acting on mitochondrial damage. Gal-3 inhibition in rats that were fed a high-fat diet (HFD) for 6 weeks with modified citrus pectin (MCP; 100 mg/kg/day) attenuated the increase in cardiac levels of total triglyceride (TG). MCP treatment also prevented the increase in cardiac protein levels of carnitine palmitoyl transferase IA, mitofusin 1, and mitochondrial complexes I and II, reactive oxygen species accumulation and decrease in those of complex V but did not affect the reduction in 18F-fluorodeoxyglucose uptake observed in HFD rats. The exposure of cardiac myoblasts (H9c2) to palmitic acid increased the rate of respiration, mainly due to an increase in the proton leak, glycolysis, oxidative stress, ß-oxidation and reduced mitochondrial membrane potential. Inhibition of Gal-3 activity was unable to affect these changes. Our findings indicate that Gal-3 inhibition attenuates some of the consequences of cardiac lipotoxicity induced by a HFD since it reduced TG and lysophosphatidyl choline (LPC) levels. These reductions were accompanied by amelioration of the mitochondrial damage observed in HFD rats, although no improvement was observed regarding insulin resistance. These findings increase the interest for Gal-3 as a potential new target for therapeutic intervention to prevent obesity-associated cardiac lipotoxicity and subsequent mitochondrial dysfunction.

Dentist´s knowledge, attitudes and determining factors of the conservative approach in teeth with reversible pulpitis and deep caries lesions.

BACKGROUND: The aim of this study was to investigate dentists` knowledge, attitudes and factors regarding the conservative approach in the management of deep caries lesions (DCLs) in teeth with reversible pulpitis. MATERIAL AND METHODS: 187 dentists were contacted directly or by mail, and 125 (67%) were finally included in the study. Dentists were requested to answer an open/discursive questionnaire about the routine approach to the diagnosis and treatment of DCLs, including knowledge-related attitudinal items. RESULTS: Total caries excavation was the preferred treatment option for more than 80% of dentists in case of DCL with reversible pulpitis. Only a small percentage (8%) chose partial caries removal, leaving some carious dentin close to the pulp to avoid pulp exposure. More than a half (51%) of respondents considered that cariogenic microorganisms must be removed or caries would progress. Dentists teaching at the University strongly disagreed with this statement (OR = 4.6; 95% C.I. = 1.3 - 15.8; p = 0.017). Good clinical result was the most chosen reason (83%) to choose a specific treatment. Patient's oral health (84%) and patient's age (70%) were the two patient-related factors most taken into account for the choice of treatment. CONCLUSIONS: Total caries excavation is still the most frequently chosen treatment in teeth with DCL and reversible pulpitis. The joint assessment of the answers given by respondents allows to conclude that the new knowledge and concepts about caries lesions and the more conservative approach to DCLs have not still been incorporated by dentists into their usual clinical practice. Key words:Caries, deep caries lesions, dental pulp capping, dental pulp health, dentists, endodontic therapy, reversible pulpitis, treatment decisions.

The impact of obesity in the cardiac lipidome and its consequences in the cardiac damage observed in obese rats.

AIMS: To explore the impact of obesity on the cardiac lipid profile in rats with diet-induced obesity, as well as to evaluate whether or not the specific changes in lipid species are associated with cardiac fibrosis. METHODS: Male Wistar rats were fed either a high-fat diet (HFD, 35% fat) or standard diet (3.5% fat) for 6 weeks. Cardiac lipids were analyzed using by liquid chromatography-tandem mass spectrometry. RESULTS: HFD rats showed cardiac fibrosis and enhanced levels of cardiac superoxide anion (O2), HOMA index, adiposity, and plasma leptin, as well as a reduction in those of cardiac glucose transporter (GLUT 4), compared with control animals. Cardiac lipid profile analysis showed a significant increase in triglycerides, especially those enriched with palmitic, stearic, and arachidonic acid. An increase in levels of diacylglycerol (DAG) was also observed. No changes in cardiac levels of diacyl phosphatidylcholine, or even a reduction in total levels of diacyl phosphatidylethanolamine, diacyl phosphatidylinositol, and sphingomyelins (SM) was observed in HFD, as compared with control animals. After adjustment for other variables (oxidative stress, HOMA, cardiac hypertrophy), total levels of DAG were independent predictors of cardiac fibrosis while the levels of total SM were independent predictors of the cardiac levels of GLUT 4. CONCLUSIONS: These data suggest that obesity has a significant impact on cardiac lipid composition, although it does not modulate the different species in a similar manner. Nonetheless, these changes are likely to participate in the cardiac damage in the context of obesity, since total DAG levels can facilitate the development of cardiac fibrosis, and SM levels predict GLUT4 levels.

The role of oxidative stress in the crosstalk between leptin and mineralocorticoid receptor in the cardiac fibrosis associated with obesity.

We have investigated whether mineralocorticoid receptor activation can participate in the profibrotic effects of leptin in cardiac myofibroblasts, as well as the potential mechanisms involved. The presence of eplerenone reduced the leptin-induced increase in protein levels of collagen I, transforming growth factor ß, connective tissue growth factor and galectin-3 and the levels of both total and mitochondrial of superoxide anion (O2.-) in cardiac myofibroblasts. Likewise, the MEK/ERK inhibitor, PD98059, and the PI3/Akt inhibitor, LY294002, showed a similar pattern. Mitochondrial reactive oxygen species (ROS) scavenger (MitoTempo) attenuated the increase in body weight observed in rats fed a high fat diet (HFD). No differences were found in cardiac function or blood pressure among any group. However, the cardiac fibrosis and enhanced O2.-levels observed in HFD rats were attenuated by MitoTempo, which also prevented the increased circulating leptin and aldosterone levels in HFD fed animals. This study supports a role of mineralocorticoid receptor in the cardiac fibrosis induced by leptin in the context of obesity and highlights the role of the mitochondrial ROS in this process.