Hyaluronic acid in vulvar and vaginal administration: evidence from a literature systematic review.

Vulvovaginal pathology impairs the quality of life of both women in menopause and those who are not. Different therapies have been proposed, mainly related to estrogen therapy in postmenopausal women. However, some contraindications limit its use, and different moisturizers or lubricants have been tested. Hyaluronic acid is a promising and widely used vaginal medical treatment with a moisturizing action and appears to provide a solution. For this reason, we performed a systematic review of the literature. We searched for original articles without date restriction until 30 April 2020. We included all clinical trials which administered local hyaluronic acid in the vulva or vagina. Only English studies and those performed in humans were eligible. Seventeen original studies were included in the review (from randomized controlled trials to longitudinal studies). Hyaluronic acid was generally found to be effective in improving vulvovaginal symptoms (dyspareunia, itching, burning, dryness) and signs (bleeding, atrophy, vaginal pH). In conclusion, hyaluronic acid has the properties to be an efficient moisturizer for women suffering from vulvovaginal atrophy who have contraindications for estrogen therapy and for vulvovaginal signs and symptoms affecting sexual well-being. However, a well-designed randomized controlled trial is needed in order to clarify its efficacy and safety profile.

Prevalence and pattern of energy drink intake among Australian adolescents.

BACKGROUND: Energy drinks (ED) are popular among young people despite evidence of associated health risks. Research into the prevalence and pattern of ED intake among young people is sparse. The present study investigates the prevalence and pattern of ED intake among a large sample of adolescents, including how many consume them, how often, for what reasons and in what contexts. METHODS: In 2018, all students in grades 7-12 attending 25 randomly selected Western Australian schools were invited to complete an online self-report survey about EDs. RESULTS: Of the 3688 respondents, 51.2% reported consuming an ED. Of these 'ever consumers', 23.4% drank them monthly, 19.2% weekly and 2% every day. The average age of first intake was 10.7 years. One-fifth (19.7%) of 'ever consumers' reported consuming more than two EDs in 1 day. Reasons for ED use included taste, to boost energy levels, sport performance and studying. CONCLUSIONS: The findings add to limited international evidence about adolescent ED use and provide valuable information to help ensure interventions to reduce intake address the underlying reasons and contexts of ED consumption.

Chromatin three-dimensional interactions mediate genetic effects on gene expression.

Studying the genetic basis of gene expression and chromatin organization is key to characterizing the effect of genetic variability on the function and structure of the human genome. Here we unravel how genetic variation perturbs gene regulation using a dataset combining activity of regulatory elements, gene expression, and genetic variants across 317 individuals and two cell types. We show that variability in regulatory activity is structured at the intra- and interchromosomal levels within 12,583 cis-regulatory domains and 30 trans-regulatory hubs that highly reflect the local (that is, topologically associating domains) and global (that is, open and closed chromatin compartments) nuclear chromatin organization. These structures delimit cell type-specific regulatory networks that control gene expression and coexpression and mediate the genetic effects of cis- and trans-acting regulatory variants on genes.

Is corifollitropin alfa effective in controlled ovarian stimulation among all poor ovarian responders? A retrospective comparative study.

Several studies have compared the effectiveness of corifollitropin alfa versus daily gonadotropins in poor ovarian responders (PORs) undergoing controlled ovarian stimulation (COS), showing conflicting results in terms of IVF outcomes. Given the heterogeneity of patients included in the classification of POR according to 'Bologna criteria', the aim of this study was to evaluate the impact of corifollitropin alfa in two different categories of POR distinguished according to patients' antral follicle count (AFC). We retrospectively evaluated 104 infertile POR, split into two groups according to AFC (Group A ≤ 5; Group B > 5) and subgroups according to the ovarian stimulation regimen (corifollitropin alfa plus daily gonadotropins (Subgroup 1) versus daily gonadotropins alone (Subgroup 2)). Outcome measures were total oocytes, MII oocytes, total embryos, follicular output rate (FORT), implantation rate (IR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR). Subgroup A1 experienced a lower number of total oocytes, MII oocytes, total embryos, and FORT (p < .05) in comparison to Subgroup A2, while no difference was found when comparing Subgroups B1 and B2. No difference was found between subgroups even in terms of IR, CPR, MR, and LBR. In conclusion, corifollitropin alfa may be as effective as daily gonadotropins in POR with AFC > 5 undergoing COS, while it might be inferior to daily gonadotropins in POR with AFC ≤ 5.

Associations between major dietary patterns and testicular function in a population-based cohort of young men: results from the Western Australian Pregnancy Cohort (Raine) Study.

BACKGROUND: Controversial speculation suggestions that dietary intake may affect semen quality and testicular function, however, there are limited comprehensive studies observing dietary patterns. OBJECTIVE: To study associations between major dietary patterns and markers of testicular function in adulthood. MATERIAL AND METHODS: Observational cross-sectional study of two hundred and ninety men with an average age of 20 years, from the Western Australian Pregnancy Cohort (Raine) Study. Usual dietary intake assessed using a semi-quantitative food frequency questionnaire at 20 years of age. Two dietary patterns previously identified using exploratory factor analysis ("Healthy" or "Western") and participants received z-scores for each dietary pattern. Primary endpoints were testicular volume, total sperm per ejaculate, morning serum testosterone concentration. Secondary endpoints were semen sample parameters, inhibin B and sex steroids (DHT: 3α-diol, 3ß-diol; LH; FSH; DHEA; estradiol; estrone). RESULT(S): Participants were on average 20.0 ± 0.4 years old, had a median of 2 days sexual abstinence and a body mass index of 24.1 ± 3.9 kg/m2 , 13% were smokers, 52% were 'moderate' alcohol drinkers, 23% frequently used recreational drugs and 68% reported 'high' physical activity levels. Sperm concentration and DHT 3α-diol were negatively associated with a greater z-score for the "Western" dietary pattern (p = 0.007 and; p = 0.044, respectively), and serum estradiol concentration was positively associated with a "Western" dietary pattern (p = 0.007) after adjustment for BMI, varicocele, cryptorchidism and sexual abstinence. DISCUSSION: Despite associations between greater intake of the "Western" dietary pattern and a decreased male reproductive health markers, our lack of consistent associations of either a "Healthy" or a "Western" dietary pattern, limit clinical or biological significance in isolation. CONCLUSIONS: A potential negative association of a "Western" dietary pattern with male reproductive health was detected and should be studied further in population-based studies.

The influence of thyroid autoimmunity on embryo quality in women undergoing assisted reproductive technology.

The influence of thyroid autoimmunity in assisted reproductive technology (ART) outcome in euthyroid women is still controversial. In this study, we retrospectively evaluated embryo quality in 123 euthyroid women undergoing ART with or without thyroid autoantibodies (TAA). Embryo quality was assessed in 119 embryos of 29 infertile patients with TAA and in 394 embryos of 94 infertile patients without TAA. Our results showed not statistically significant differences in age, body mass index, anti-Müllerian hormone, follicle stimulating hormone, free triiodothyronine, and free thyroxine levels between cases and controls. Thyroid stimulating hormone was within the normal range, but significantly higher in TAA patients compared with the controls (2.4 ± 0.8 vs. 2 ± 0.9 mIU/L, respectively, p < .01). The number of oocytes picked up and fertilized was comparable between the two groups. Embryo quality was significantly impaired in women with at least one autoantibody (p < .001). Implantation rate, pregnancy rate, and ongoing pregnancy rate were comparable in the two groups. These results suggest a negative impact of thyroid autoimmunity in embryo quality in women undergoing ART even when thyroid function is normal.

Determinants of a dietary pattern linked with greater metabolic risk and its tracking during adolescence.

BACKGROUND: Although growing evidence suggests that dietary patterns associated with noncommunicable diseases in adulthood may develop early in life, when these are established, as well as their determinants, remains unclear. METHODS: We examined determinants and tracking of a dietary pattern (DP) associated with metabolic risk and its key food groups among 860 adolescents in the Western Australian Pregnancy (Raine) Cohort study. Food intake was reported using a food frequency questionnaire (FFQ) at 14 and 17 years. Z-scores for an 'energy-dense, high-fat, low-fibre' DP were estimated by applying reduced rank regression at both ages. Tracking was based on the predictive value (PV) of remaining in the DPZ-score or food intake quartile at 14 and 17 years. Early-life exposures included: maternal age; maternal pre-pregnancy body mass index; parent smoking status during pregnancy; and parent socio-economic position (SEP) at 14 and 17 years. Associations between the DPZ-scores, early-life factors and SEP were analysed using regression analysis. RESULTS: Dietary tracking was strongest among boys with high DPZ-scores, high intakes of processed meat, low-fibre bread, crisps and savoury snacks (PV > 1) and the lowest intakes of vegetables, fruit and legumes. Lower maternal education (ß = 0.09, P = 0.002 at 14 years; ß = 0.14, P < 0.001 at 17 years) and lower maternal age at birth (ß = 0.09, P = 0.003 at 14 years; ß = 0.11, P = 0.004 at 17 years) were positively associated with higher DPZ-scores. CONCLUSIONS: An energy-dense, high-fat, low-fibre dietary pattern tracks more strongly among adolescent boys who have high scores for this pattern at 14 years of age. These findings highlight target foods and population subgroups for early interventions aiming to improve dietary behaviours.

Umbilical intra-abdominal vein varix: a case report and review of the literature.

Fetal umbilical intra-abdominal vein varix (FIUV) is a rare congenital malformation characterized by focal dilatation of the umbilical vein. The authors report a case of pregnant woman at 32 weeks of gestation with a fetus affected by dilatation of an intra-abdominal portion of the umbilical vein. They performed continuous ultrasound and cardiotocographic monitoring, from admission to the delivery. They describe the case and perform a review of the literature.

Holt Oram syndrome: a case report and review of the literature.

Holt Oram syndrome is a rare autosomal dominant syndrome on average, of varying severity, which may result in heterogeneous pictures, predominantly with involvement of the bony segments of the upper limbs and the cardiovascular system. The syndrome is caused by mutations in two genes of the T-box (TBX5, 601 620 and TBX 3) located on the 12q24.1p. The authors report a case and review the literature.

Spironolactone and intermenstrual bleeding in polycystic ovary syndrome with normal BMI.

PURPOSE: Spironolactone (SP) is an effective treatment for polycystic ovary syndrome (PCOS), but it is often associated with menstrual abnormalities whose mechanism is still under investigation. In this study, we investigated the serum sex steroids and endometrial thickness in 30 PCOS patients, before and after one-month 100 mg SP treatment. METHODS: Serum FSH, LH, estradiol, progesterone and endometrial thickness were evaluated at the 14th and 16th day of the menstrual cycle, before and during short-term SP treatment. According to the presence (15 cases) or absence (15 cases) of menstrual bleeding at the 14th day during SP, the patients were divided into two groups, which were then compared using a two-tailed Student's t test. RESULTS: Serum estradiol and endometrial thickness were lower than pretreatment at both determinations in all patients, but patients with bleeding had significantly lower estradiol values than non-bleeding ones, both before and after therapy. Endometrial thickness was significantly lower in the bleeding group compared with non-bleeding group only at the 16th day of the cycle. These differences were significant, even though the values of estradiol and endometrial thickness remained in the normal range. CONCLUSIONS: SP therapy can reduce the values of estradiol and the endometrial thickness in patients with PCOS compared with pretreatment, but PCOS patients with bleeding had pretreatment estradiol values lower than the patients who did not complain of this side effect. Intermenstrual abnormalities may represent the low estrogen impregnation of endometrium due to SP, whose mechanism is complex, involving several factors, such as the effects of some metabolites of SP on estradiol and progesterone production, on their receptors, and the individual metabolism of SP in vivo.

A randomized trial of intensive versus minimal surveillance of patients with resected Dukes B2-C colorectal carcinoma.

BACKGROUND: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty. PATIENTS AND METHODS: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL. RESULTS: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens. CONCLUSION: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit. CLINICALTRIALSGOV: NCT02409472.

Identification of a dietary pattern associated with greater cardiometabolic risk in adolescence.

BACKGROUND AND AIMS: Energy dense, high fat, low fibre diets may contribute to obesity in young people, however their relationships with other cardiometabolic risk factors are unclear. We examined associations between an 'energy-dense, high-fat and low-fibre' dietary pattern (DP) and cardiometabolic risk factors, and the tracking of this DP in adolescence. METHODS AND RESULTS: Data was sourced from participants in the Western Australian Pregnancy (Raine) Cohort Study. At 14 and 17 y, dietary intake, anthropometric and biochemical data were measured and z-scores for an 'energy dense, high fat and low fibre' DP were estimated using reduced rank regression (RRR). Associations between DP z-scores and cardiometabolic risk factors were examined using regression models. Tracking of DP z-scores was assessed using Pearson's correlation coefficient. A 1 SD unit increase in DP z-score between 14 and 17 y was associated with a 20% greater odds of high metabolic risk (95% CI: 1.01, 1.41) and a 0.04 mmol/L higher fasting glucose in boys (95% CI: 0.01, 0.08); a 28% greater odds of a high-waist circumference (95% CI: 1.00, 1.63) in girls. An increase of 3% and 4% was observed for insulin and HOMA (95% CI: 1%, 7%), respectively, in boys and girls, for every 1 SD increase in DP z-score and independently of BMI. The DP showed moderate tracking between 14 and 17 y of age (r = 0.51 for boys, r = 0.45 for girls). CONCLUSION: An 'energy dense, high fat, low fibre' DP is positively associated with cardiometabolic risk factors and tends to persist throughout adolescence.

Comparison of pelvic masses score (PMS) and Risk of Malignancy Index (RMI 3) in the evaluation of pelvic masses.

PURPOSE: Ovarian cancer is the fourth cause of death from cancer in women worldwide and the majority of its diagnoses is made in an advanced stage of the disease. Several sonographic scoring systems have been created for a better preoperative discrimination between benign and malignant pelvic masses. The aim of this study was to evaluate the performances of the Risk of the Malignancy Index 3 (RMI 3) and the Pelvic Masses Score (PMS). MATERIALS AND METHODS: This retrospective study was performed in 55 women admitted to the department of Obstetrics and Gynecology of University of Udine for surgical exploration of pelvic masses between 2009 and 2012. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both the scores. RESULTS: PMS showed a sensitivity of 100%, a specificity of 93.8%, a PPV of 70%, and a NPV of 100%, while RMI 3 yielded a sensitivity of 85%, a specificity of 91%, a PPV of 60%, and a NPV of 97.8%. CONCLUSION: The authors found that, in discriminating between benign and malignant pelvic disease, the PMS method was more reliable than RMI3. PMS is a simple scoring system which can be used in clinical practice.

TVT-ABBREVO: efficacy and two years follow-up for the treatment of stress urinary incontinence.

PURPOSE: To assess the effectiveness of inside-out TVT-ABBREVO in the surgical treatment of female stress urinary incontinence (SUI) with mean two-year follow-up. MATERIALS AND METHODS: Fifty-six women underwent surgery for moderate-severe SUI. The technology used was the TVT-ABBREVO inside-out. Each woman at 12 and 24 months underwent postoperative evaluation by means of urodynamics, Q-tip test, CST, transperineal ultrasonography, and administration of "King's Health Questionnaire" (KHQ). RESULTS: The mean age of the women was 57.03 +/- 11.1 years (range 42-75). Postoperative urodynamics (12 months follow-up) resulted to be normal in 43/56 patients (76.79%), in 10/56 (17.86%) cases resulted in a considerable improvement of the symptomatology, and only 1/56 (1.78%) case had de novo overactive bladder (OAB), in 2/56 (3.57%) symptomatology unchanged. After administration of the KHQ 43/56 cases (76.79%) had resolution of the symptomatology, 10/56 cases (17.86%) improvement of the symptomatology, and no change in 3/56 cases (5.36%). CONCLUSION: In the authors' experience, the TVT-ABBREVO resulted technically simple. The TVT-ABBREVO procedure provides high objective and subjective long-term efficacy, a clinically meaningful improvement in patient quality of life, and an excellent safety profile.

Management of breast lobular carcinoma in situ: radio-pathological correlation, clinical implications, and follow-up.

PURPOSE OF INVESTIGATION: To show management of patients with breast lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This study is the retrospective review of 65 patients, between 1996 and 2012, with isolated LCIS of the breast, evaluated through clinical examination, ultrasound, and mammography at the first examination and follow-up. RESULTS: In 53 patients (81.54%), clinical examination was negative. In 14/65 (21.54%) cases, ultrasound was positive and led to biopsy. The clusters of tiny calcifications were the predominant mammographic pattern (45 cases, 69.23%). Forty-six patients (70.77%) underwent surgical biopsy after guided stereotactic placement of metallic marker (hook-wire), 12 (18.46%) by stereotactic vacuum biopsy (SVB), 5 (7.69%) by core needle biopsy (CNB) under ultrasound guidance, two (3.08%) patients CNB with clinically palpable nodules. Fourteen (21.54%) women underwent a quadrantectomy or total mastectomy after the first diagnosis; in this latter group follow-up was negative. Among the 51 patients (78.46%) who did not undergo quadrantectomy or total mastectomy, five relapses occurred, respectively, three LCIS and two infiltrating ductal carcinomas (IDC). Follow-up ranged from 12 to 144 months. CONCLUSION: LCIS is a risk factor for invasive carcinoma and should be managed with careful follow-up, but if there is a discrepancy between pathology and imaging, surgical excision is mandatory.

Prediction of large-for-gestation neonates with first-trimester maternal serum PAPP-A.

AIM: The aim of this paper was to identify maternal/pregnancy characteristics, first trimester ultrasound parameters and biochemical indices which are significant independent predictors of large-for-gestational age (LGA) neonates. METHODS: An Observational cross-sectional study was conducted at the Fetal Medicine Unit, Department of Obstetrics and Gynecology of the University of Udine (Italy). Seventy-two singleton pregnancies presenting for screening for chromosomal abnormalities by nuchal translucency and maternal serum biochemistry at 11-14 weeks. Linear regression was applied to develop first trimester prediction models for LGA. RESULTS: Maternal height, parity, smoking, assisted conception and pregnancy-associated plasma protein-A were significant independent predictors of LGA. PAPP-A cut-off value expressed in MoM of 1.25 used for the study was chosen to obtain good sensitivity and specificity values. CONCLUSION: Prediction for birthweight deviations (LGA) is feasible using data available at the routine 11-14 weeks' examination.

P16 immunostaining and HPV testing in histological specimens from the uterine cervix.

BACKGROUND: The cellular tumor suppressor protein pl61NK4a (p16) has been identified as a biomarker for transforming human papilloma virus (HPV) infections. P16 is a cyclin-dependent kinase inhibitor that regulates the cell cycle and cell proliferation by inhibiting cell cycle G1 progression. PURPOSE OF THE STUDY: To confirm the role of p16 as biomarker for transforming HPV infections and possible clinical applications in histological samples from the uterine cervix. MATERIALS AND METHODS: The subject of this study included 56 biopsies of the cervical canal collected from January 2012 to September 2012 in the Institute of Pathology of the University of Sassari. The search for HPV immunohistochemistry was performed with the monoclonal antibody DAKO 1:25, while for the detection of p16 was used CINtecTM p16 (INK4a) histology kit. RESULTS: In 56 biopsies performed in women aged between 23 and 69 years, the authors highlighted, by histological analysis, 24 cases of low-grade squamous intraepithelial lesion (LSIL) - cervical intraepithelial neoplasia (CIN1) and 31 cases of high-grade squamous intraepithelial lesion (HSIL) - CIN2/3); 15 CIN2, 14 CIN3, and two cervical squamous cell carcinoma in situ (SCIS). One case was an infiltrating squamous cell carcinoma (ISC). In 24 CIN1, there was a 16.67% positivity for p16 and an equal percentage occurred for HPV. In 15 cases of CIN2 the percentage of positivity for p16 was considerably increased (73.33%), unlike the search for HPV which had a positivity rate of 20%. Finally, in 14 cases of CIN3, and in three carcinomas, the positivity for p16 was equal to 100%, however the search for HPV positivity was between 0% and 7.14%. CONCLUSIONS: These results demonstrated that p16 was a highly sensitive marker of cervical dysplasia. The authors have shown that p16 overexpression increased with the severity of cytological abnormalities and that had a greater ability to identify the viral infection compared to the classical immunohistochemical staining for HPV.

Immunohistochemical evaluation of epithelial antigen Ber-Ep4 and CD10: new markers for endometriosis?

BACKGROUND: Early and certain diagnoses of endometriosis are mandatory to begin the correct treatment and to exclude the risk of endometriosis-associated ovarian carcinoma (EOC) and endometrial stromal sarcoma (ESS). PURPOSE OF THE STUDY: To assess the immunohistochemical expression of Ber-Ep4, an epithelial antigen, and CD10 in endometriosis. MATERIALS AND METHODS: Forty-eight women underwent laparoscopic surgery for endometriosis and endometriotic samples were recovered for histology. In all surgical specimens Ber-Ep4 and CD10 were searched by an immnohistochemical method. The authors evaluated the correlations among the immunohistochemical positivity and the location of endometriosis. RESULTS: Most cases (40/48 83.34%) were represented by ovarian endometriotic cyst. Among the eight remaining cases, three (3/48, 6.25%) were pelvic endometriotic lesions, two (2/48, 4.17%) peritoneum of vesico-uterine pouch, one vaginal lesion (2.08%), one salpinx lesion (2.08%), and one inguinal location (2.08%). Ber-Ep4 and CD10 were expressed in 90% and in 100% of the ovarian lesions, respectively. In pelvic lesions Ber-Ep4 and CD10 showed both 66.67% of positivity and had the same pattern in peritoneal, salpinx, vaginal, and inguinal lesions (50%, 100%, 100%, 100%, respectively). Ber-Ep4 was negative in 6/48 (12.5%) cases whereas CDO10 was negative in 2/48 (4.17%) cases of endometriosis. The sensitivity of Ber-Ep4 and CD10 for endometriosis diagnosis were 87.50% and 95.83%, respectively. Immunohistochemistry for Ber-Ep4 showed positivity in all cases of endometriosis with typical cubic epithelium, whereas CD10 was positive in 1/2 (50%) atypical case. CONCLUSION: Immunohistochemical expression of Ber-Ep4 and CD10 was positive in most cases of endometriosis and was useful in differential diagnosis with mesothelial cysts. Ber-Ep4 was negative in cases of hyperplastic epithelium or cytological atypia; these cases are not well-differentiated and could be optimally treated by surgery and not by hormonal therapy because of the risk of cancer degeneration.

No dose-dependent increase in fracture risk after long-term exposure to high doses of retinol or beta-carotene.

UNLABELLED: Uncertainty remains over whether or not high intakes of retinol or vitamin A consumed through food or supplements may increase fracture risk. This intervention study found no increase in fracture risk among 2,322 adults who took a controlled, high-dose retinol supplement (25,000 IU retinyl palmitate/day) for as long as 16 years. There was some evidence that beta-carotene supplementation decreased fracture risk in men. INTRODUCTION: There is conflicting epidemiological evidence regarding high intakes of dietary or supplemental retinol and an increased risk for bone fracture. We examined fracture risk in a study administering high doses of retinol and beta-carotene (BC) between 1990 and 2007. METHODS: The Vitamin A Program was designed to test the efficacy of retinol and BC supplements in preventing malignancies in persons previously exposed to blue asbestos. Participants were initially randomised to 7.5 mg retinol equivalents (RE)/day as retinyl palmitate, 30 mg/day BC or 0.75 mg/day BC from 1990 to 1996; after which, all participants received 7.5 mg RE/day. Fractures were identified by questionnaire and hospital admission data up until 2006. Risk of any fracture or osteoporotic fracture according to cumulative dose of retinol and BC supplementation was examined using conditional logistic regression models adjusting for age, sex, smoking, body mass index, medication use and previous fracture. RESULTS: Supplementation periods ranged from 1 to 16 years. Of the 2,322 (664 females and 1,658 males) participants, 187 experienced 237 fractures. No associations were observed between cumulative dose of retinol and risk for any fracture (OR per 10 g RE=0.83; 95% CI, 0.63-1.08) or osteoporotic fracture (OR per 10 g RE=0.95; 95% CI 0.64-1.40). Among men, cumulative dose of BC was associated with a slightly reduced risk of any fracture (OR per 10 g=0.89; 95% CI 0.81-0.98) and osteoporotic fracture (OR per 10 g=0.84; 95% CI 0.72-0.97). CONCLUSIONS: This study observed no increases in fracture risk after long-term supplementation with high doses of retinol and/or beta-carotene.

Identification of a dietary pattern prospectively associated with increased adiposity during childhood and adolescence.

BACKGROUND: Specific dietary risk factors for excess adiposity in young people are poorly understood. However, studies in adults suggest dietary energy density, fat and fibre are critical dietary factors. OBJECTIVE: To examine longitudinal relationships between a dietary pattern (DP) characterised by dietary energy density, % total energy from fat and fibre density and fat mass (FM) in children from 7 to 15 years of age. DESIGN: Subjects were 6772 children from the UK Avon Longitudinal Study of Parents and Children. Dietary intake was assessed using a 3-day food diary at 7, 10 and 13 years of age. An energy-dense, high-fat, low-fibre DP was identified using reduced rank regression and subjects scored for the DP at each age. FM was measured at 11, 13 and 15 years and FM index (FMI) calculated as FM/height((x)). Longitudinal models were adjusted for dietary misreporting, physical activity and maternal factors. RESULTS: DP z-scores at all ages were positively associated with later FMI. A 1 s.d. unit increase in DP z-score was longitudinally associated with an average increase in FMI z-score of 0.04 s.d. units (95% confidence interval (CI), 0.01-0.07). For each 1 s.d. unit increase in DP z-score, the odds of being in the highest quintile for FMI (as a marker of excess adiposity) increased by 13% (95% CI, 1-27%). CONCLUSIONS: Dietary habits during childhood are associated with increased adiposity in adolescence, with specific implications for dietary energy density, fat and fibre intake. Improving diet quality may reduce the risk of obesity in young people.