Exposure to aerosol extract from heated tobacco products causes a drastic decrease of glutathione and protein carbonylation in human lung epithelial cells.

Heated tobacco products (HTPs) are an emerging class of tobacco goods that claim to have lower health risks than those of smoking combustible tobacco products. In this study, we exposed human lung epithelial cell lines to extracts prepared from HTP aerosols and combustible cigarette smoke to compare cytotoxicity. We focused on the effects of aldehydes present in the aerosols of HTPs at levels close to those in combustible cigarette smoke. Significant toxicity was confirmed for the HTP extract, albeit to a lesser extent than that with the combustible cigarette extract. When redox balance was evaluated by the oxidative loss of low-molecular-weight thiols in the cells, we found that total glutathione (GSH) contents and low-molecular-weight thiol levels were significantly decreased after exposure to the aerosol extract of HTPs. These results indicated that GSH is rapidly consumed during the detoxification of xenobiotics, such as aldehydes from tobacco extracts. Accordingly, exposure to the aerosol extract of HTPs resulted in the enhanced carbonylation of many proteins. In a simple comparison, the results for HTPs were significantly different from those obtained with combustible cigarette smoke, suggesting reduced toxicity of HTPs. However, we found significant and harmful effects after exposing lung epithelial cells to the aerosol extract of HTPs. Thus, a further comprehensive study is needed to clarify the lung damage induced via the long-term inhalation of aerosols from HTPs.

Changes of synovial fluid biomarker levels after opening wedge high tibial osteotomy in patients with knee osteoarthritis.

OBJECTIVE: The purpose of this study was to evaluate the effects of high tibial osteotomy (HTO) on the biological status of knee osteoarthritis (OA) using joint markers in synovial fluid (SF). METHODS: Fifty patients with medial compartmental OA of the knee who underwent opening wedge HTO were enrolled. Paired SF samples from the affected knee and arthroscopic evaluation of articular cartilage were collected at the time of HTO surgery and the time of plate removal (postoperative 17 ± 4 months). The concentrations of the following SF biomarkers were measured: interleukin (IL)-1ß, IL-6, IL-8, IL-10, tumour necrosis factor-α, matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, MMP-13, vascular endothelial growth factor (VEGF), and cartilage oligomeric matrix protein (COMP). The Knee Society Score (KSS) and hip-knee-ankle (HKA) angle were assessed before and 2 years after HTO. RESULTS: The KSS knee and function scores were significantly improved after HTO (mean changes of 36.4 and 23.7, respectively). The mean HKA angle was altered from mechanical varus (-8.6°) to valgus (5.2°). Concentrations of IL-6, IL-8, MMP-2, MMP-3, MMP-13, VEGF, and COMP in SF were significantly decreased after HTO (mean changes of -49.1%, -30.2%, -31.1%, -26.3%, -30.8%, -42.5%, and -13.7% from preoperative baseline, respectively). The cartilage status was improved in 19 cases (38%) after HTO. However, changes of all biomarkers were not significantly different between subjects with and without an improved cartilage status. CONCLUSIONS: SF levels of biochemical markers for cartilage degradation and synovial inflammation were altered after HTO, suggesting an improvement in the OA disease state.

Delayed lupus nephritis in the course of systemic lupus erythematosus is associated with a poorer treatment response: a multicentre, retrospective cohort study in Japan.

OBJECTIVE: The objective of this study was to investigate possible differences in treatment responses between two categories for the onset of lupus nephritis. METHODS: We performed a multicentre, retrospective cohort study of class III-V lupus nephritis patients diagnosed between 1997 and 2014. The renal responses to initial induction therapy were compared between patients who developed lupus nephritis within one year from diagnosis of systemic lupus erythematosus (early (E-) LN) and the remainder (delayed (D-) LN) using the Kaplan-Meier method. We determined the predictors of renal response as well as renal flares and long-term renal outcomes using multivariate Cox regression analyses. RESULTS: A total of 107 E-LN and 70 D-LN patients were followed up for a median of 10.2 years. Log-rank tests showed a lower cumulative incidence of complete response in D-LN compared with E-LN patients. Multivariate analysis identified D-LN (hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.33-0.70), nephrotic syndrome at baseline, and a chronicity index greater than 2 as negative predictors of complete response. D-LN patients were more likely to experience renal flares. D-LN (HR 2.54, 95% CI 1.10-5.83) and decreased renal function were significant predictors of chronic kidney disease at baseline. CONCLUSION: D-LN was a predictor of poorer treatment outcomes, in addition to renal histology and severity of nephritis at lupus nephritis onset.

Effects of once-monthly minodronate versus risedronate in osteoporosis patients with rheumatoid arthritis: a 12-month randomized head-to-head comparison.

A head-to-head comparison of once-monthly oral bisphosphonates minodronate (MIN) and risedronate (RIS) in patients with rheumatoid arthritis (RA) demonstrated that MIN has the same effect as RIS on increase in bone mineral density (BMD) and a stronger effect on inhibition of bone resorption than RIS, suggesting that MIN is a promising treatment option for osteoporosis patients with RA. INTRODUCTION: To evaluate the effect of once-monthly oral MIN in patients with RA, a prospective, randomized, open-label, head-to-head comparison with once-monthly oral RIS was conducted. METHODS: A total of 83 patients with RA were randomly assigned to either once-monthly oral MIN 50 mg (n = 42) or once-monthly oral RIS 75 mg (n = 41). Serial BMD and bone turnover markers were measured and compared between the treatment groups. RESULTS: BMD (lumbar spine, total hip, femoral neck) increased significantly after 12 months of treatment with MIN (3.8, 2.0, and 2.2%, respectively, P < 0.05) and RIS (3.6, 1.9, and 1.9%, respectively, P < 0.05). There were no significant differences between the treatment groups. Percent changes of bone turnover markers from baseline to 12 months in the MIN group were significantly greater than those in the RIS group (TRACP-5b: - 36.3 vs - 19.3%, P < 0.05; NTX: - 27.1 vs - 17.3%, P < 0.05; BAP: -30.2 vs -19.4%, P < 0.05). CONCLUSIONS: The present study of RA patients demonstrated that MIN has the same effect as RIS on increase in BMD and a stronger effect on inhibition of bone resorption than RIS. The results suggest that MIN is a promising treatment option for osteoporosis patients with RA.

Sorafenib plus hepatic arterial infusion chemotherapy with cisplatin versus sorafenib for advanced hepatocellular carcinoma: randomized phase II trial.

BACKGROUND: Sorafenib (Sor) is acknowledged as a standard therapy for advanced hepatocellular carcinoma (HCC). This trial was conducted to evaluate the effect of addition of hepatic arterial infusion chemotherapy with cisplatin (SorCDDP) to Sor for the treatment of advanced HCC. PATIENTS AND METHODS: We conducted a multicenter open-labeled randomized phase II trial in chemo-naïve patients with advanced HCC with Child-Pugh scores of 5-7. Eligible patients were randomly assigned 2:1 to receive SorCDDP (sorafenib: 400 mg bid; cisplatin: 65 mg/m2, day 1, every 4-6 weeks) or Sor (400 mg bid). The primary end point was overall survival. RESULTS: A total of 108 patients were randomized (Sor, n = 42; SorCDDP, n = 66). The median survival in the Sor and SorCDDP arms were 8.7 and 10.6 months, respectively [stratified hazard ratio (95% confidence interval), 0.60 (0.38-0.96), P = 0.031]. The median time to progression and the response rate were, respectively, 2.8 months and 7.3% in the Sor arm and 3.1 months and 21.7% in the SorCDDP arm. The adverse events were more frequent in the SorCDDP arm than in the Sor arm, but well-tolerated. CONCLUSION: SorCDDP yielded favorable overall survival when compared with Sor in patients with advanced HCC. CLINICAL TRIAL REGISTRATION: UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703.

Viral load and ganciclovir (GCV) concentration in cerebrospinal fluid of patients successfully treated with GCV or valGCV for human herpesvirus 6 encephalitis/myelitis following umbilical cord blood transplantation.

We describe successful treatment of 3 cases of human herpesvirus 6 (HHV-6) encephalitis/myelitis following cord blood transplantation (CBT). Ganciclovir (GCV) (10 mg/kg/day) reduced HHV-6 load to undetectable levels in cerebrospinal fluid (CSF). Early dose reduction in the presence of HHV-6 detectable in CSF resulted in an increased HHV-6 load. GCV was capably shifted to valganciclovir (VGCV) with an almost equivalent concentration. GCV/VGCV may be effective for HHV-6 encephalitis/myelitis after CBT, although HHV-6 load in CSF should be monitored.

Dietary patterns and risk of cardiovascular deaths among middle-aged Japanese: JACC Study.

BACKGROUND AND AIMS: Little evidence showed the association between dietary patterns and cardiovascular disease among Japanese. The objective of this study was to examine whether dietary patterns are associated with cardiovascular disease among middle-aged Japanese. METHODS AND RESULTS: At baseline (1988-1990), 26,598 men and 37,439 women aged 40-79 years enrolled in the Japan Collaborative Cohort (JACC) Study. During the follow-up through 2003, 578 men and 499 women died from stroke, and 272 men and 207 women died from coronary heart disease. We identified three major dietary patterns, 'vegetable', 'animal food' and 'dairy product', by factor analysis for both sexes. The multivariable hazard ratio (HR) and 95% confidence intervals of mortality from total cardiovascular disease in the highest versus lowest quintiles of the vegetable pattern were 0.93 (0.78-1.13), p for trend=0.73 for men and 0.82 (0.67-1.00), p for trend=0.04 for women. The respective HRs of mortality from stroke in the highest versus lowest quintiles of the dairy product pattern were 0.65 (0.49-0.86), p for trend=0.01 for men and 0.70 (0.51-0.97), p for trend=0.02 for women, and those of total cardiovascular disease were 0.89 (0.74-1.08), p for trend=0.23 for men and 0.76 (0.61-0.94), p for trend=0.01 for women. The animal food pattern was not associated with mortality from stroke, coronary heart disease or total cardiovascular disease for either sex. CONCLUSION: We found that 'vegetable' and 'dairy product' patterns were associated with lower morality from cardiovascular disease, while the 'animal food' pattern was not associated with mortality from cardiovascular disease among Japanese.

Relationship between body mass index of offspring and maternal smoking during pregnancy.

OBJECTIVE: To examine the relationship between maternal smoking during pregnancy and the body composition of offspring. SUBJECTS: Grade 4 elementary school children (n=1366; boys/girls, 724/642; 9-10 years old) were enrolled in this study. All parents answered a lifestyle questionnaire, and children underwent passive smoking tests. Urinary cotinine measurement and lifestyle screening test parameters (that is, body weight, body length, body mass index (BMI), obesity index (OI), blood tests for liver function and lipid profile and questions regarding maternal smoking and lifestyle) were evaluated in terms of their relationship with maternal smoking. In addition, urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration was measured in 80 randomly selected children to assess its relationship with oxidative stress. RESULTS: Both BMI and OI were significantly higher in children whose mothers smoked during pregnancy than in those whose mothers never smoked (BMI: 17.2±2.7 vs 16.9±2.5 kg m(-2), P=0.016; OI: 2.7±14.3% vs 0.4±14.0%, P=0.003). The degree of elevation was positively correlated with the duration of maternal smoking. The increases in BMI and OI resulted from increased body weight and reduced height. The confounding factors-'breakfast with family', 'watching television at dinner', 'eating and drinking before sleep', 'watching television for >2 h', 'sleep duration <8 h' and 'playing sports'-were statistically significant. BMI and OI were significantly high in children whose mothers smoked during pregnancy in these six confounders. On the other hand, urinary 8-OHdG concentration was negatively correlated with BMI in children who had >1.3 ng ml(-1) urinary cotinine, suggesting that it may be related to basal metabolism due to oxidative stress. CONCLUSION: Maternal smoking is a risk factor for higher BMI and OI in 9- to 10-year-old children whose mothers smoke during pregnancy and may be independent of other confounding factors.

Effects of repeated oral intake of a quercetin-containing supplement on allergic reaction: a randomized, placebo-controlled, double-blind parallel-group study.

OBJECTIVE: The present study aimed to investigate the effects of a 4-week repeated oral intake of a quercetin-containing supplement on allergen-induced reactions and relative subjective symptoms in Japanese adults who complained of discomfort in the eyes and nose. SUBJECTS AND METHODS: A randomized, placebo-controlled, double-blind parallel-group study was conducted on 66 subjects (22-78 years old) with allergic symptoms of pollinosis. The subjects were given the test product (200 mg quercetin) or the control product (vehicle) daily for 4 weeks. The Japanese Rhino-conjunctivitis Quality of Life Questionnaire (JRQLQ) scores and other tests were examined in each subject before and after starting the product intake. A new food-grade bioavailable formulation of quercetin, Quercetin phytosome®, was used. RESULTS: At 1:4 weeks after the start of the supplement intake, several scores of JRQLQ, including allergic symptoms, such as eye itching, sneezing, nasal discharge, and sleep disorder, were significantly improved in the quercetin-containing supplement group compared with the placebo group. Furthermore, the quality of life of these subjects significantly improved based on the original questionnaire and visual analog scale. Minor notable adverse effects were noted throughout the study. CONCLUSIONS: The results indicated that oral intake of quercetin-containing supplements might effectively reduce some allergy symptoms derived from pollinosis.

The diagnostic accuracy of high-resolution endoscopy, autofluorescence imaging and narrow-band imaging for differentially diagnosing colon adenoma.

BACKGROUND AND STUDY AIMS: Conventional colonoscopy can result in unnecessary biopsy or endoscopic resection due to its inability to distinguish adenomas from hyperplastic polyps. This study therefore evaluated the efficacy of high-resolution endoscopy (HRE), autofluorescence imaging (AFI), and narrow-band imaging (NBI) in discriminating colon adenoma from hyperplastic polyps. PATIENTS AND METHODS: This was a prospective multicenter study in patients undergoing AFI and NBI examinations. HRE, AFI, and NBI images were classified into two groups based on morphological characteristics, the predominant color intensities, and the visibility of meshed capillary vessels, respectively. Each of the endoscopic photographs were independently evaluated by a single endoscopist. The images were then assessed by three specialists and three residents, the latter having performed < 500 colonoscopies and < 30 NBI and AFI examinations. Diagnostic test statistics were calculated to compare the accuracy in differentiating colon adenoma from hyperplastic polyps for each method. RESULTS: A total of 183 patients were enrolled in the study and 339 adenomas and 85 hyperplastic polyps were identified. AFI and NBI could distinguish adenoma from hyperplastic polyps with an accuracy of 84.9 % and 88.4 %, respectively, whereas HRE exhibited an accuracy of 75.9 %. In the 358 lesions in which the AFI diagnosis was consistent with that of NBI, the accuracy, sensitivity, and specificity were high, at 91.9 %, 92.7 %, and 92.9 %, respectively. During the study comparing specialists and residents, AFI and NBI dramatically improved the diagnostic accuracy of residents from 69.1 % to 86.1 % and 84.7 %, respectively. CONCLUSIONS: Both AFI and NBI are considered to be feasible tools that can discriminate colon adenoma from hyperplastic polyps, and their use may be particularly beneficial for less-experienced endoscopists.

Culture of bovine embryos in polyester mesh sections: the effect of pore size and oxygen tension on in vitro development.

The purpose of this study was to assess the feasibility of polyester mesh culture for the in vitro production of bovine embryos, as polyester mesh is an alternative way for tracking individual embryos throughout culture using time-lapse cinematography (TLC). Bovine embryos were isolated during in vitro culture using sections of three different polyethylene terephthalate (PET) mesh products. In vitro matured and fertilized bovine oocytes were cultured in the 217 × 217, 230 × 230 or 238 × 238-µm openings of PET mesh sections or in simple micro-drops (control) for 7 days under either 20% or 5% O(2) tensions. No difference in embryo developmental rates was found between the culture groups in terms of cleavage, blastocyst formation and blastocyst expansion irrespective of O(2) tension. In contrast, under 20% O(2) tension, blastocysts that developed in PET mesh with 217 × 217-µm opening had significantly higher numbers of total and trophectoderm (TE) cells than control embryos; however, the numbers and proportions of inner cell mass (ICM) cells did not differ. Under 5% O(2) tension, no difference was found among the culture groups in the numbers of total, ICM and TE cells in embryos. All three PET mesh products investigated in this study were proven to be effective to prevent embryo movement. The results demonstrate that bovine embryos can be cultured in PET mesh sections without negative side-effects and suggest that embryo distance determined by the mesh affects embryo quality at atmospheric oxygen tension. Polyethylene terephthalate mesh with 217 × 217-µm openings was found to be the most suitable for further application in TLC.

Phase I/II clinical study of percutaneous vertebroplasty (PVP) as palliation for painful malignant vertebral compression fractures (PMVCF): JIVROSG-0202.

BACKGROUND: The safety and efficacy of percutaneous vertebroplasty (PVP), a new treatment modality for painful malignant vertebral compression fractures (PMVCF) using interventional radiology techniques, were evaluated prospectively. MATERIALS AND METHODS: After confirming the absence of safety issues in phase 1, a total of 33 cases were registered up to and including phase 2. Safety and efficacy were evaluated by National Cancer Institute-Common Toxicity Criteria version 2 and Visual Analogue Scale (VAS) at 1 week after PVP. Based on VAS score decreases, efficacy was classified into significantly effective (SE; > or = 5 or reached 0-2), moderately effective (ME; 2-4), or ineffective (NE; <2 or increase). RESULTS: Procedures were completed in all 33 patients (42 vertebrae). Thirty days after PVP, two patients died of primary disease progression, but no major adverse reactions (>grade 2) were observed. Response rate was 70% (95% confidence interval 54% to 83%) [61% (n = 20) with SE, 9% (n = 3) with ME, and 30% (n = 10) with NE] and increased to 83% at week 4. Median time to response was 1 day (mean 2.4). Median pain-mitigated survival period was 73 days. CONCLUSION: For PMVCF, PVP is a safe and effective treatment modality with immediate onset of action.

Fruit and vegetable intake and risk of amyotrophic lateral sclerosis in Japan.

BACKGROUND: There has been little interest in the role of nutrition in the prevention of amyotrophic lateral sclerosis (ALS). We investigated the relationship between dietary intake of vegetables, fruit, and antioxidants and the risk of ALS in Japan. METHODS: Between 2000 and 2004, we recruited 153 ALS patients aged 18-81 years with disease duration of 3 years within the study period in accordance with El Escorial World Federation of Neurology criteria. Three hundred and six gender- and age-matched controls were randomly selected from the general population. Information on dietary factors was collected using a validated self-administered diet history questionnaire. RESULTS: A higher consumption of all fruits and vegetables and fruit alone in the highest quartiles was associated with a statistically significantly reduced risk of ALS. Although not statistically significant, a beneficial association between intake of all vegetables, green and yellow vegetables and other vegetables and ALS was found. No statistically significant dose-response relationship was observed between intake of beta-carotene, vitamin C and vitamin E and the risk of ALS. CONCLUSION: Our findings suggest that higher intake of food rich in antioxidants such as fruit and vegetables confer protection against the development of ALS.

Effect of radiation monitoring method and formula differences on estimated physician dose during percutaneous coronary intervention.

BACKGROUND: Currently, one or two dosimeters are used to monitor radiation exposure in most cardiac laboratories. In addition, several different formulas are used to convert exposure data into an effective dose (ED). PURPOSE: To clarify the effect of monitoring methods and formula selection on the estimated ED for physicians during percutaneous coronary interventions (PCIs). MATERIAL AND METHODS: The ED of physicians during cardiac catheterization was determined using an optically stimulated luminescence dosimeter (Luxel badge). Two Luxel badges were worn: one beneath a personal lead apron (0.35-mm lead equivalent) at the chest and one outside of the apron at the neck. RESULTS: The difference in the average ED of seven physicians was approximately fivefold (range 1.13-5.43 mSv/year) using the six different formulas in the clinical evaluation. The estimated physician ED differed markedly according to both the monitoring method and formula selected. CONCLUSION: ED estimation is dependent on both the monitoring method and the formula used. Therefore, it is important that comparisons among laboratories are based on the same monitoring method and same formula for calculating the ED.

A PHANTOM STUDY TO DETERMINE THE OPTIMAL PLACEMENT OF EYE DOSEMETERS ON INTERVENTIONAL CARDIOLOGY STAFF.

The International Commission on Radiological Protection has substantially reduced the recommended maximum annual eye lens dose for workers. Use of a dedicated eye dosemeter is one method for accurate dose monitoring. The main aim of this study was to yield recommendations for optimal placement of eye dosemeters to estimate the eye dose to interventional cardiology physicians and nurses. A phantom measurement was conducted to simulate typical interventional cardiology procedures. Considering eight X-ray tube angulations, the left side of the head position provide good estimates for physician, and the forehead position provide good estimates for nurse.

A comparison of the effect of large and small metal-on-metal bearings in total hip arthroplasty on metal ion levels and the incidence of pseudotumour: a five-year follow-up of a previous report.

Aims: The purpose of this study was to compare two different types of metal-on-metal (MoM) bearing for total hip arthroplasty (THA): one with a large femoral head (38 mm to 52 mm) and the other with a conventional femoral head (28 mm or 32 mm). We compared clinical outcome, blood metal ion levels, and the incidence of pseudotumour in the two groups. Patients and Methods: Between December 2009 and December 2011, 62 patients underwent MoM THA with a large femoral head (Magnum group) and 57 patients an MoM THA with a conventional femoral head (conventional group). Clinical outcome was assessed using the Harris Hip score, University of California, Los Angeles (UCLA) activity score and EuroQol-5D (EQ-5D). Blood metal ion levels were measured and MRI scans were analyzed at a minimum of five years postoperatively. Results: No acetabular component was implanted with more than 50° of inclination in either group. The Harris Hip Score, UCLA activity score, and EQ-5D improved postoperatively in both groups; no significant clinical differences were noted between the groups. The blood cobalt ion levels in the conventional group continued to rise postoperatively to five years while reaching a plateau at two years postoperatively in the Magnum group. At five years, the mean cobalt ion level of 1.16 µg/l (sd 1.32) in the Magnum group was significantly lower than the 3.77 µg/l (sd 9.80) seen in the conventional group (p = 0.0015). The incidence of moderate to severe pseudotumour was 4.7% in the Magnum group and 20.6% in the conventional group. There were no dislocations in the Magnum group and two in the conventional group. One patient in the Magnum group underwent revision for pseudotumour at 4.7 years postoperatively. Conclusion: At five years, a well-positioned large head MoM THA has a significantly lower level of metal ion release and a lower incidence of moderate to severe pseudotumour than a MoM bearing of conventional size. Cite this article: Bone Joint J 2018;100-B:1018-24.

The effect of a natural, standardized bilberry extract (Mirtoselect®) in dry eye: a randomized, double blinded, placebo-controlled trial.

OBJECTIVE: Dry eye, a chronic disease of lachrymal fluid and corneo-conjunctival epithelium, could significantly impact visual function, affects quality of life and work productivity. Beside several conventional treatments, nutritional supplements based on bilberry extract have been identified as effective contributors to eye health. Here, we aim at investigating the bioavailability of a standardized bilberry extract, its ability to alleviate dry eye symptoms and its antioxidant potential. MATERIALS AND METHODS: Either bilberry dried standardized extract derived from Vaccinium myrtillus L. fresh frozen fruits (Mirtoselect®) or a highly purified anthocyanin-rich extract, devoid of the non anthocyanin component and supported on maltodextrins, were each orally administrated to 5 male rats. Blood samples were collected at 5, 10, 15, 20, 30, 45, 60, 90, 120 minutes after treatment, processed and analyzed by UV spectrophotometric method. In a parallel analysis, 22 otherwise healthy subjects suffering from dry eye symptoms were enrolled randomly assigned to receive the more bioavailable bilberry extract or placebo. Ophthalmological and clinical examinations including Schirmer's test, pupil constriction, diacron-reactive oxygen metabolites (d-ROMs) test and biological antioxidant potential (BAP) test were performed at inclusion and after the 4-week study period. RESULTS: The area under the curve of plasmatic levels of anthocyanosides in rats resulted 202.34±24.23 µg·min/ml for Mirtoselect® and 130.93±4.93 µg·min/ml for the highly purified anthocyanin-rich bilberry extract, notwithstanding the fact that the highly purified anthocyanin-rich extract group received an anthocyanins dosage much higher than the Mirtoselect® group (354 mg/Kg in anthocyanosides vs. 136 mg/Kg in anthocyanosides). 21 subjects, 11 subjects in the bilberry extract (Mirtoselect®) group and 10 subjects in the placebo group completed the clinical study. Schirmer's test values indicating the volume of tear secretion were significantly improved in the bilberry extract group (p=0.019), whereas no significant changes were observed in the placebo group. A subset analysis revealed that Mirtoselect® could be more effective in subjects with higher tendency of dry eye. In terms of antioxidant potential, the bilberry extract produced significant improvement of BAP (p=0.003) and an increase of modified BAP/d-ROMs ratio, an indicator of overall balance between antioxidant potential and oxidative stress. CONCLUSIONS: Our results suggested that natural, standardized bilberry extract (Mirtoselect®) is a natural more bioavailable delivery form anthocyanins, suggesting a strong matrix effect exerted by the non-anthocyanin component. Furthermore, it can improve tear secretion and plasmatic antioxidant potential in subjects suffering from DED symptoms.