How social media meet patients’ questions: YouTube™ review for children oral thrush.

YouTube™ is increasingly being used by patients to obtain health-related information. No studies have evaluated the content of YouTube™ videos on children oral thrush. The aim of this work is to examine the quality of information offered by this platform about oral thrush in children. Searching term “oral thrush in children” (OTC) displayed a total of 2.790 results. Of the top 60 videos analyzed, 27 were excluded. The main source of upload was from generalist information YouTube® channels (GC) followed by healthcare professionals (HP), individual users (IU), and healthcare information channels (HC); usefulness of videos is successfully correlated with the number of visualization, number of likes and viewing rate and was interdependent with the number of visualizations, number of likes and VR. However, videos on the oral thrush do not have satisfactory quality information. HP themselves, along with HC, do not seem to provide more appropriate information on COT, than GC or IU.

How social media meet patients’ questions: YouTube™ review for mouth sores in children.

Recurrent aphthous stomatitis (RAS) is one of the most common causes of mouth sores in children so the management of this condition is a matter of great importance. YouTube™ is increasingly being used by patients to obtain health-related information. The aim of this work is to examine the quality of information offered by YouTube™ about mouth sores in children (MSC). Searching the term ‘mouth sores in children’, (MSC) displayed 12.300 results. Of the top 60 videos analyzed, 31 were excluded following exclusion criteria. The major source of upload was from healthcare information channels (HC-41,38%), followed by individual users (HP-25.59%), healthcare professionals (IU-17.24%) and generalist information channels (HC-13.78%); 20.69% of them deal with predisposing factors, and related pathologies, the majority of these propose home remedies (60.72%) rather than topical analgesic drugs (21.43%), antimicrobials (7.14%) and topical steroids (3.57). Most of the videos analyzed were slightly useful (68.97%). Information about mouth sores in children on YouTube™ was poor regardless of the upload source. Analyzing health content on social platforms is a starting point for providing greater quality of health-related information.

Systemic and topical photodynamic therapy (PDT) on oral mucosa lesions: an overview.

Photodynamic Therapy (PDT) is a minimally invasive treatment that has shown promising results in treating preneoplasticlesions. PDT reckons on the administration of a drug (photosensitizer), which can be used in a topical or systemic form. Photodynamic therapy has been successfully used in the management of a variety of pathologies from different anatomical sites, including the head, neck, brain and lungs, hepatobiliary tree and other gastrointestinal and urological pathologies, skin, gynaecological conditions and in vascular anomalies. Starting from these same considerations, PDT has also been adopted for oral malignant and premalignant lesions’ treatment, and should be kept under investigation as a promising therapeutic management of leukoplakia and preneoplastic lesions of the oral cavity.

Endoplasmic reticulum stress and the development of endothelial dysfunction.

The vascular endothelium plays a critical role in cardiovascular homeostasis, and thus identifying the underlying causes of endothelial dysfunction has important clinical implications. In this regard, the endoplasmic reticulum (ER) has recently emerged as an important regulator of metabolic processes. Dysfunction within the ER, broadly termed ER stress, evokes the unfolded protein response (UPR), an adaptive pathway that aims to restore ER homeostasis. Although the UPR is the first line of defense against ER stress, chronic activation of the UPR leads to cell dysfunction and death and has recently been implicated in the pathogenesis of endothelial dysfunction. Numerous risk factors for endothelial dysfunction can induce ER stress, which may in turn disrupt endothelial function via direct effects on endothelium-derived vasoactive substances or by activating other pathogenic cellular networks such as inflammation and oxidative stress. This review summarizes the available data linking ER stress to endothelial dysfunction.

Pomological Traits, Sensory Profile and Nutraceutical Properties of Nine Cultivars of Loquat (Eriobotrya japonica Lindl.) Fruits Grown in Mediterranean Area.

In this paper the diversity of fruit quality within nine loquat cultivars, including five international affirmed cultivars (Algerie, Golden Nugget, Peluche, Bueno, El Buenet) and four local cultivars (Sanfilippara, Nespolone di Trabia, BRT20 and Claudia), were investigated in order to discriminate the variation in pomological characteristics, sensory profile, and antioxidant properties. Finally, to evaluate potential bioactivity, antiproliferative activity of hydrophilic extracts from loquat fruits was assessed, at dietary relevant concentrations, against three human epithelial cell lines. Even though the international cultivars confirmed an appropriate level of commercial qualities in association to high levels in antioxidant compounds, the local cultivars revealed the best performances in a wide range of chemical-physical and sensory characteristics. Concerning bioactivity, our results indicate that hydrophilic extracts from all tested cultivars showed concentration-dependent antiproliferative activity with a significant variability of effects between different cell lines and between different cultivars. HeLa cells, the most sensitive and hydrophilic extracts from Peluche, showed the highest inhibitory effect followed by Nespolone di Trabia and Claudia. The results of this trial provide useful information on the pomological traits and the not yet known specific nutritional and functional properties of loquat fruits. Our data, besides helping to promote specific local cultivars, could serve to establish a database that will permit to improve the utilization of specific genetic resources in breeding programs.

Sicilian pistachio (Pistacia vera L.) nut inhibits expression and release of inflammatory mediators and reverts the increase of paracellular permeability in IL-1ß-exposed human intestinal epithelial cells.

BACKGROUND: Dietary approaches to control inflammatory bowel diseases (IBD) may include proanthocyanidin-rich foods. Our previous research showed that a hydrophilic extract from Sicilian pistachio nut (HPE) contains substantial amounts of proanthocyanidins and possesses anti-inflammatory activities. PURPOSE: We studied the effects of HPE and of its polymeric proanthocyanidin fraction (PPF) in a cell model that simulated some conditions of IBD, consisting of interleukin (IL)-1ß-stimulated Caco-2 cells. METHODS: HPE was prepared by Pistacia vera L. nuts, and PPF was isolated from HPE by adsorbance chromatography. Proanthocyanidins were quantified as anthocyanidins after acidic hydrolysis. Differentiated Caco-2 cells were pre-incubated with HPE or PPF and then were exposed to IL-1ß. Cell viability and parameters associated with nuclear factor-κB (NF-κB) activation were assayed. Adsorption of polymeric proanthocyanidins to the cell membrane was investigated by transepithelial electrical resistance (TEER) measurements. RESULTS: HPE decreased prostaglandin (PG)E2 production, IL-6 and IL-8 release, and cyclooxygenase (COX)-2 expression. HPE also inhibited the increase in paracellular permeability and reduced NF-κB activation. Polymeric proanthocyanidins, tested at a concentration comparable with their content in HPE, produced effects comparable to HPE. Finally, cell exposure to PPF increases TEER of the epithelial monolayers. CONCLUSION: Our results provide evidence that pistachio nut components inhibit inflammatory response of intestinal epithelial cells in vitro and indicate polymeric proanthocyanidins as the major bioactive nut components. The protection implies inhibition of NF-κB activation and occurs in parallel with the adsorption of polymeric proanthocyanidins to cell membrane. Our findings suggest that intake of small amounts of pistachio nut can exert beneficial effects to gastrointestinal pathophysiology.

Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents the increase of epithelial permeability in IL-1ß-exposed Caco-2 cells.

Dietary redox-active/antioxidant phytochemicals may help control or mitigate the inflammatory response in chronic inflammatory bowel disease (IBD). In the present study, the anti-inflammatory activity of indicaxanthin (Ind), a pigment from the edible fruit of cactus pear (Opuntia ficus-indica, L.), was shown in an IBD model consisting of a human intestinal epithelial cell line (Caco-2 cells) stimulated by IL-1ß, a cytokine known to play a major role in the initiation and amplification of inflammatory activity in IBD. The exposure of Caco-2 cells to IL-1ß brought about the activation of NADPH oxidase (NOX-1) and the generation of reactive oxygen species (ROS) to activate intracellular signalling leading to the activation of NF-κB, with the over-expression of inflammatory enzymes and release of pro-inflammatory mediators. The co-incubation of the cells with Ind, at a nutritionally relevant concentration (5-25 µM), and IL-1ß prevented the release of the pro-inflammatory cytokines IL-6 and IL-8, PGE2 and NO, the formation of ROS and the loss of thiols in a dose-dependent manner. The co-incubation of the cells with Ind and IL-1ß also prevented the IL-1ß-induced increase of epithelial permeability. It was also shown that the activation of NOX-1 and NF-κB was prevented by Ind and the expression of COX-2 and inducible NO synthase was reduced. The uptake of Ind in Caco-2 cell monolayers appeared to be unaffected by the inflamed state of the cells. In conclusion, our findings suggest that the dietary pigment Ind may have the potential to modulate inflammatory processes at the intestinal level.

Silk fibroin increases the elasticity of alginate-gelatin hydrogels and regulates cardiac cell contractile function in cardiac bioinks.

Silk fibroin (SF) is a natural protein extracted fromBombyx morisilkworm thread. From its common use in the textile industry, it emerged as a biomaterial with promising biochemical and mechanical properties for applications in the field of tissue engineering and regenerative medicine. In this study, we evaluate for the first time the effects of SF on cardiac bioink formulations containing cardiac spheroids (CSs). First, we evaluate if the SF addition plays a role in the structural and elastic properties of hydrogels containing alginate (Alg) and gelatin (Gel). Then, we test the printability and durability of bioprinted SF-containing hydrogels. Finally, we evaluate whether the addition of SF controls cell viability and function of CSs in Alg-Gel hydrogels. Our findings show that the addition of 1% (w/v) SF to Alg-Gel hydrogels makes them more elastic without affecting cell viability. However, fractional shortening (FS%) of CSs in SF-Alg-Gel hydrogels increases without affecting their contraction frequency, suggesting an improvement in contractile function in the 3D cultures. Altogether, our findings support a promising pathway to bioengineer bioinks containing SF for cardiac applications, with the ability to control mechanical and cellular features in cardiac bioinks.

Role of 18F-FDG PET in the management of gestational trophoblastic neoplasia.

PURPOSE: Gestational trophoblastic neoplasia (GTN) is a rare and aggressive tumour that is usually sensitive to chemotherapy. The usefulness of conventional imaging modalities in evaluating treatment response is limited, mainly due to the difficulty in differentiating between residual tumour tissue and necrosis. The aim of the present study was to evaluate the role of FDG PET or PET/CT in primary staging and in monitoring treatment efficacy. The effect of FDG PET and combined PET/CT on the management of patients with GTN was also evaluated comparing the differences between standard treatments based on conventional imaging and alternative treatments based on PET. METHODS: This retrospective study included 41 patients with GTN referred to San Raffaele Hospital between 2002 and 2010. All patients were studied by either PET or PET/CT in addition to conventional imaging. Of the 41 patients, 38 were evaluated for primary staging of GTN and 3 patients for chemotherapy resistance after first-line chemotherapy performed in other Institutions. To validate the PET data, PET and PET/CT findings were compared with those from conventional imaging, including transvaginal ultrasonography (TV-US) in those with uterine disease, CT and chest plain radiography in those with lung disease and whole-body CT in those with systemic metastases. Conventional imaging was considered positive for the presence of uterine disease and/or metastases when abnormal findings relating to GTN were reported. PET and PET/CT were considered concordant with conventional imaging when metabolic active disease was detected at the sites corresponding to the pathological findings on conventional imaging. In addition, in 12 of the 41 patients showing extrauterine disease, FDG PET/CT was repeated to monitor treatment efficacy, in 8 after normalization of beta human chorionic gonadotropin (ßHCG) and in 4 with ßHCG resistance. In some patients, PET or PET/CT findings led to an alternative nonconventional treatment, and this was considered a change in patient management for the study analysis. RESULTS: When compared to TV-US, chest radiography and CT for staging, PET showed a concordance in 91 %, 84 % and 81 % of patients, respectively. In 8 of the 41 patients with extrauterine disease during staging, PET/CT showed a complete response to therapy after ßHCG normalization. PET and PET/CT identified the sites of persistent disease in all seven high-risk patients with ßHCG resistance, of whom four underwent second-line chemotherapy, two surgical removal of resistant disease instead of additional chemotherapy, and one surgical removal of resistant disease and second-line chemotherapy with subsequent negative ßHCG. CONCLUSION: In staging, PET cannot replace conventional imaging and does not show any information in addition to that shown by conventional imaging. The additional value of PET/CT in GTN with respect to conventional imaging is found in patients with high-risk disease. PET can identify the sites of primary and/or metastatic disease in patients with persistent high levels of ßHCG after first-line chemotherapy and may be of additional value in patient management for guiding alternative treatment.

Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix.

PURPOSE: This study investigated the absorption mechanism of the phytochemicals indicaxanthin and betanin and the influence of their food matrix (cactus pear and red beet) on the intestinal transport. METHODS: Trans-epithelial transport of dietary-consistent amounts of indicaxanthin and betanin in Caco-2 cell monolayers seeded on Transwell(R) inserts was measured in apical to basolateral (AP-BL) and basolateral to apical (BL-AP) direction, under an inwardly directed pH gradient (pH 6.0/7.4, AP/BL) mimicking luminal and serosal sides of human intestinal epithelium. The effect of inhibitors of membrane transporters on the absorption was also evaluated. Contribution of the paracellular route was investigated after EDTA treatment of the cell monolayer. In vitro digestion of betalainic food was performed to provide a post-intestinal fraction containing bioaccessible pigments. RESULTS: Apparent permeability coefficients (P(app)) in the absorptive direction were (4.4 ± 0.4) × 10⁻6 and (3.2 ± 0.3) × 10⁻6 cm s⁻¹ for indicaxanthin and betanin, respectively. Transport of indicaxanthin was non-polarized, linear as a function of time and concentration, and unaffected by inhibitors of membrane transporters. Betanin exhibited significantly different bidirectional P(app) values and non-linear efflux kinetics. The concentration-dependent betanin efflux was described by a kinetic model including one non-saturable (K(d) = 0.042 µL cm⁻² min⁻¹) and one saturable component identified as the apical multidrug resistance-associated protein 2 (MRP2; K(m) = 275 µM; J(max) = 42 pmol min⁻¹ cm⁻²). Permeation of both betalains increased remarkably after EDTA treatment of the cell monolayer. Neither indicaxanthin nor betanin underwent metabolic transformation. Food matrix did not affect trans-epithelial transfer of indicaxanthin, but reduced the absorption rate of betanin, red beet more than cactus pear. CONCLUSIONS: Dietary indicaxanthin and betanin can substantially be absorbed through paracellular junctions of intestinal epithelial cells. Additional trans-membrane permeation can be considered for betanin, whose absorption is limited by a MRP2-mediated efflux and negatively affected by its food matrix. Present findings are consistent with the quite higher bioavailability of indicaxanthin over betanin established in humans.

Silver coins analyses by X-ray fluorescence methods.

The investigation on the differences occurring in the manufacture of silver coins allows to get information on their elemental composition and represents a powerful support to the methodology to identify the producing technologies, workshops being also instrumental to distinguish between original and counterfeit ones. Aim of the present work is to study recent and old silver coins through non-destructive X-Ray Fluorescence (XRF) analysis. The XRF was applied to extend the analysis to the deepest layers of the coins; for surface layers an X-ray tube or an electron beam were employed to induce the atom fluorescence to obtain information on the surface elemental composition. Moreover, a detailed study has been performed to evaluate the influence of the surface curvature on the measurement, by deducing a proper corrective factor to keep into account in the data analysis. The elemental atomic composition was measured for each coin, mainly by means of the X-ray tube excitation for the bulk and the electron Scanning Electron Microscope (SEM) microbeam probe for the surface patina analysis. Ionization was induced by an X-ray tube using an Ag anode for the bulk and by an electron microprobe for the surface composition. X-ray detection was performed by using a semiconductor Si device cooled by a Peltier system. The Ag L-lines X-ray yield is affected by coin surface morphology and geometry. The comparison between coin spectra and standard samples, shows that the Ag quantitative analysis is influenced by error of the atomic concentration lower that 10%.

Drosophila as a tool for studying the conserved genetics of pain.

Survival of all animals depends on an accurate representation of the world, and an organism must be capable of prioritizing and responding to potentially hazardous conditions. This ability is dependent on nociception, the sensory process allowing animals to detect and avoid potentially harmful stimuli. Nociception is the sensory process that results in the subjective experience of 'pain' in humans. Because of its vital and broad role in animal biology, pain/nociception is a complex, whole-body physiological process that is under stringent evolutionary pressure. Here, we discuss the utility of Drosophila melanogaster as an emerging model organism for studying the conserved genetics of nociception, particularly with respect to recently developed high-throughput Drosophila 'pain' paradigms.

Transvaginal ultrasound predicts delayed response to chemotherapy and drug resistance in stage I low-risk trophoblastic neoplasia.

OBJECTIVES: Methotrexate (MTX) resistance is defined on the basis of the human chorionic gonadotropin (hCG) curve. The aim of this study was to identify low-risk non-metastatic patients with gestational trophoblastic neoplasia (GTN) who can achieve resolution by continuing MTX treatment despite a transient hCG plateau. METHODS: Before starting chemotherapy, 24 patients with FIGO Stage I GTN underwent transvaginal ultrasonography with power Doppler in order to identify myometrial lesions (areas of increased echogenicity and increased power Doppler signal). Ultrasound response to chemotherapy was defined when myometrial lesions decreased in echogenicity, Doppler signal or size. When ultrasound response occurred, despite chemoresistance defined by hCG values, MTX treatment was continued. RESULTS: MTX was continued in three out of seven chemoresistant patients because ultrasound suggested response to MTX. All three of these patients achieved a complete response, thus nearly halving the MTX-resistance rate. CONCLUSION: Among patients who are candidates for second-line treatment on the basis of hCG, ultrasound may identify those in whom further MTX administration can induce a delayed complete response.

Polymeric proanthocyanidins from Sicilian pistachio (Pistacia vera L.) nut extract inhibit lipopolysaccharide-induced inflammatory response in RAW 264.7 cells.

BACKGROUND: Positive effects of pistachio nut consumption on plasma inflammatory biomarkers have been described; however, little is known about molecular events associated with these effects. PURPOSE: We studied the anti-inflammatory activity of a hydrophilic extract from Sicilian Pistacia L. (HPE) in a macrophage model and investigated bioactive components relevant to the observed effects. METHODS: HPE oligomer/polymer proanthocyanidin fractions were isolated by adsorbance chromatography, and components quantified as anthocyanidins after acidic hydrolysis. Isoflavones were measured by gradient elution HPLC analysis. RAW 264.7 murine macrophages were pre-incubated with either HPE (1- to 20-mg fresh nut equivalents) or its isolated components for 1 h, then washed before stimulating with lipopolysaccharide (LPS) for 24 h. Cell viability and parameters associated with Nuclear Factor-κB (NF-κB) activation were assayed according to established methods including ELISA, Western blot, or cytofluorimetric analysis. RESULTS: HPE suppressed nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production and inducible NO-synthase levels dose dependently, whereas inhibited prostaglandin E2 (PGE2) release and decreased cyclo-oxygenase-2 content, the lower the HPE amount the higher the effect. Cytotoxic effects were not observed. HPE also caused a dose-dependent decrease in intracellular reactive oxygen species and interfered with the NF-κB activation. Polymeric proanthocyanidins, but not isoflavones, at a concentration comparable with their content in HPE, inhibited NO, PGE2, and TNF-α formation, as well as activation of IκB-α. Oligomeric proanthocyanidins showed only minor effects. CONCLUSIONS: Our results provide molecular evidence of anti-inflammatory activity of pistachio nut and indicate polymeric proanthocyanidins as the bioactive components. The mechanism may involve the redox-sensitive transcription factor NF-κB. Potential effects associated with pistachio nut consumption are discussed in terms of the proanthocyanidin bioavailability.

C-reactive protein does not impair insulin suppression of glucose release in primary hepatocytes.

Recent studies have suggested that CRP may interfere with insulin signaling in skeletal muscle and endothelial cells. The aim of this study was to determine whether highly purified CRP increased the rate of glucose appearance in primary hepatocytes in the absence or presence of insulin. Primary rat hepatocytes were provided glucose-free media containing 10 mM lactate, 1 mM pyruvate, 0, 1 or 10 nM insulin, and 0 or 10 µg/ml of purified CRP for 6h. Purified CRP did not increase glucose release in the absence of insulin and did not reduce the ability of insulin to suppress glucose release.

Dermatology Life Quality Index score in vitiligo patients: a pilot study among young Italian males.

AIM: A negative impact on vitiligo patients in terms of quality of life (QoL) has been suggested. The aim of this report was to study the QoL in a sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire. METHODS: A sample of forty seven vitiligo subjects, identified among 34,740 potential conscripts resident in southern Italy underwent the Italian version of the DLQI questionnaire. RESULTS: The median total DLQI score was 1 (IQR: 2; mean: 1.82). In univariate analysis, DLQI total score was significantly influenced by the clinical course of vitiligo, disease extension over the body, and location on face and/or hands. Multivariate analysis using logistic stepwise regression showed that only the localization on the hands and on the face influenced significantly the mean DLQI. CONCLUSION: Our study conducted on a random sample of individuals affected by vitiligo selected from the general young male population in Italy, does not document a large impact of vitiligo on QoL. However, variations exist and the location of lesions on the face and/or hands may impact on QoL. Population-based studies are not affected by selection biases connected with seeking medical care and should be more widely performed.

Vitiligo and autoimmunity: an epidemiological study in a representative sample of young Italian males.

BACKGROUND: It is stated that patients with vitiligo have an increased risk of developing autoimmune diseases. OBJECTIVE: The aim of this study was to estimate the prevalence of autoantibodies or overt autoimmune diseases in a group of vitiligo patients examined among a sample deemed to be representative of the general population of young men living in southern Italy. METHODS: A total of 60 vitiligo patients were identified among 34,740 potential conscripts visited to evaluate their fitness to compulsory service in Italian Navy, obtaining a prevalence of 0.17% (95% CI: 0.13-0.22), which was deemed the prevalence of vitiligo in the Italian general population of the same age and sex. Forty of these vitiligo patients underwent blood test including also the search of the main autoantibodies. RESULTS: Circulating autoantibodies were detected in 42.5% of subjects. Anti-thyroglobulin antibodies were documented in 27.5%, anti-thyroperoxidase in 22.5%, anti-smooth muscle in 17.3%, anti-nuclear, anti-mitochondrial and anti-gastric parietal cells in 2.5% respectively. Only in two cases (5%) an overt thyroid disease was diagnosed. No significant association between the extension of the skin involved / clinical course of the disease and circulating autoantibodies was detected. Circulating autoantibodies (particularly anti-thyroid antibodies) were statistically associated with a lower duration of the disease. CONCLUSIONS: In agreement with other studies, autoantibodies in the lack of clinical manifestations have been frequently observed in our vitiligo patients, especially during the early phase of the disease. The clinical significance of this finding seems to be limited, with the possible exception of thyroid disease, and it needs further exploration, through large cohort studies.

Carotid intima media-thickness is increased in obese children metabolically healthy, metabolically unhealthy, and with metabolic syndrome, compared to the non-obese controls.

The prevalence of obesity continues to increase. Obesity is associated with cardiovascular risk factors: elevated blood pressure, dyslipidemia and glycemic alterations, causing metabolic syndrome. A subgroup of obese, Metabolically Healthy Obese (MHO), appears to be less prone to the development of metabolic disturbances. Carotid intima-media thickness (cIMT) is a non-invasive marker of subclinical atherosclerosis and it is associated with increased risk of CVD events. To investigate the cardiovascular risk, demonstrated through the increase of cIMT in obese subjects without Metabolic Syndrome (MetS), we have studied cIMT in MHO, metabolically unhealthy obese (MUO) and obese with MetS diagnosed with the IDEFICS criteria and compared to a control group. 224 obese children aged 6 to 21 years (13,50 ± 4.01 years) and 103 normal weight subjects aged 7 to 19 years (13.2 ± 4.1 years) were studied. The body mass index (BMI) of the obese children was ≥ the 95th percentile. Based on the IDEFICS criteria, we divided the obese subjects in three groups: MHO if no criteria were out of range, MUO if, at least, one of the criteria was out of range and MetS group if all the IDEFICS criteria were present. In all the subjects cIMT was measured with color Doppler by a vascular surgeon. Differences in the means of the variables were tested by ANOVA. Based on the IDEFICS criteria, 32 subjects were affected by MetS (14..3%), 66 were considered MUO (29.4%) and 126 MHO (56.3%). Comparison of mean cIMT highlighted a significant difference (p < 0.05) between the groups of obese children (MHO, MUO and MetS) and controls for both carotid arteries. We did not find significative difference in the value of cIMT in MHO, MUO and MetS subjects, and all groups showed cIMT value higher compared to cIMT of the controls.

Fatty acids regulate CREBh via transcriptional mechanisms that are dependent on proteasome activity and insulin.

Excess fatty acids are closely associated with metabolic dysfunction. The deleterious effects of fatty acids relate, in part, to their ability to up-regulate pro-inflammatory cytokines and propagate a state of systemic inflammation. CREBh is a recently identified transcription factor that appears to be required for hepatic synthesis of C-reactive protein. Recent data suggest that fatty acids can up-regulate CREBh, thus establishing a potential molecular link between fatty acids and inflammation. The aim of this study was to examine the nature and mechanisms of fatty acid-mediated regulation of CREBh. H4IIE liver cells were incubated in the absence or presence of varying concentrations (50-500 µM) of albumin-bound, long-chain saturated (palmitate, stearate) or unsaturated (oleate, linoleate) fatty acids (1-16 h). All fatty acids significantly increased CREBh gene expression via transcriptional mechanisms, at concentrations as low as 50 µM. Palmitate- or oleate-mediated up-regulation of CREBh was not inhibited by triacsin C, an inhibitor of long-chain fatty acyl CoA synthetase, or by the PPARα antagonist, MK886. Inhibition of proteasome activity with MG132 or lactacystin, or inclusion of insulin reduced palmitate- and oleate-mediated increases in CREBh mRNA. Finally, we examined fatty acid regulation of CREBh in vivo. Male Wistar rats were exposed to a 4-h pancreatic clamp combined with infusion of saline or a mixed lipid emulsion. CREBh mRNA and protein were significantly increased in rats exposed to the lipid infusion compared to the saline group. Collectively, these results may have important implications for metabolic diseases characterized by excess fatty acids, insulin resistance, and inflammation.

Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults.

Cardiovascular disease (CVD) is the leading cause of death in the US and worldwide. By 2030 it is anticipated that CVD will claim the lives of more than 24 million people. Throughout the last decade, researchers have investigated the role of the gut microbiota in the development of CVD. Evidence exists for a positive correlation between Bifidobacterium and vascular function, glucose tolerance, and reduced systemic inflammation. Another probiotic species, Bacillus subtilis, has also been found to reduce cholesterol levels in human and animal models. In light of these data, we examined various measures of cardiovascular health after consumption of Bifidobacterium animalis subsp. lactis strain BL04, with and without a cocktail of Escherichia coli-targeting bacteriophages (marketed as PreforPro), Bacillus subtilis strain DE111 or a maltodextrin-based placebo in a healthy human population. In a randomised, double-blind, placebo-controlled 4-week intervention conducted in individuals 18 to 65 years of age with a body mass index of 20 to 34.9, we saw no significant changes in measured CVD parameters among individuals consuming B. lactis with or without bacteriophages. However, B. subtilis supplementation resulted in a significant reduction in total cholesterol relative to baseline measures (-8 mg/dl; P=0.04, confidence interval (CI): -13.40, -0.19), as well as non-high-density lipoprotein-cholesterol (-11 mg/dl; P=0.01, CI: -12.43, -2.07). In addition we observed trending improvements in endothelial function (P=0.05, CI: -0.003, 0.370) and in low-density lipoprotein-cholesterol (P=0.06, CI:-12.29, 0.2864). Strikingly, these effects were seen in a largely healthy population. These data suggest that B. subtilis supplementation may be beneficial for improving risk factors associated with CVD. Further studies in populations of older adults or those with dyslipidaemia and endothelial dysfunction is warranted.