Vitamin D status and non-alcoholic fatty liver disease in patients with type 1 diabetes.

PURPOSE: In patients with type 1 diabetes (T1D), the prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 10 to 53% and contrasting evidence suggests that vitamin D deficiency may favor liver fat accumulation. Here, we investigated the association between vitamin D status and NAFLD in adults with T1D. METHODS: 220 consecutive adult T1D patients on multiple daily injections or continuous subcutaneous insulin infusion and not taking calcium or vitamin D supplements were included. Patient characteristics, 25(OH)D serum levels, and metabolic parameters were analyzed. Vitamin D status was defined as sufficiency ( ≥ 75 nmol/L; 30 ng/ml), insufficiency (50-75 nmol/L; 20-30 ng/ml), or deficiency ( < 50 nmol/L; 20 ng/ml). NAFLD was diagnosed at ultrasound examination and graded 0-3. RESULTS: NAFLD was present in 57 patients (29.5%): 51 grade 1, 5 grade 2, and 1 grade 3. Median 25(OH)D levels were 53 nmol/L (IQR 38-70) in patients with NAFLD and 50 nmol/L (34-69) in patients without (p = 0.46). At multivariable analysis, NAFLD was not associated with 25(OH)D levels (p = 0.42) or vitamin D deficiency (p = 0.55), while BMI (OR 1.16, 95% CI 1.07-1.27) and serum triglycerides (OR 1.02, 95% CI 1.01-1.03) were independently associated with NAFLD. CONCLUSIONS: Vitamin D status appears to have no link with low-grade NAFLD in patients with type 1 diabetes.

Influence of health locus of control and fear of hypoglycaemia on glycaemic control and treatment satisfaction in people with Type 1 diabetes on insulin pump therapy.

AIM: To assess the influence of health locus of control and fear of hypoglycaemia on metabolic control and treatment satisfaction in people with Type 1 diabetes mellitus on continuous subcutaneous insulin infusion. METHODS: People with Type 1 diabetes on continuous subcutaneous insulin infusion for at least 1 year, sub-classified as an 'acceptable glucose control' group [HbA1c ≤ 58 mmol/mol (7.5%)] and a 'suboptimum glucose control' group [HbA1c > 58 mmol/mol (7.5%)], were consecutively enrolled in a multicentre cross-sectional study. Questionnaires were administered to assess health locus of control [Multidimensional Health Locus of Control (MHLC) scale, with internal and external subscales], fear of hypoglycaemia [Hypoglycaemia Fear Survey II (HFS-II)] and treatment satisfaction [Diabetes Treatment Satisfaction Questionnaire (DTSQ)]. RESULTS: We enrolled 214 participants (mean ± sd age 43.4 ± 12.1 years). The suboptimum glucose control group (n = 127) had lower mean ± sd internal MHLC and DTSQ scores than the acceptable glucose control group (19.6 ± 5.2 vs 21.0 ± 5.0, P = 0.04 and 28.8 ± 4.8 vs 30.9 ± 4.5, P < 0.001). HFS-II scores did not differ between the two groups. Internal MHLC score was negatively associated with HbA1c (r = -0.15, P < 0.05) and positively associated with the number of mild and severe hypoglycaemic episodes (r = 0.16, P < 0.05 and r = 0.18, P < 0.001, respectively) and with DTSQ score (r = 0.17, P < 0.05). HFS-II score was negatively associated with DTSQ score (r = -0.18, P < 0.05) and positively with number of severe hypoglycaemic episodes (r = 0.16, P < 0.5). CONCLUSIONS: In adults with Type 1 diabetes receiving continuous subcutaneous insulin infusion, high internal locus represents the most important locus of control pattern for achieving good metabolic control.

Switching from twice-daily glargine or detemir to once-daily degludec improves glucose control in type 1 diabetes. An observational study.

BACKGROUND AND AIMS: Degludec is an ultralong-acting insulin analogue with a flat and reproducible pharmacodynamic profile. As some patients with type 1 diabetes (T1D) fail to achieve 24-h coverage with glargine or detemir despite twice-daily injections, we studied the effect of switching T1D patients from twice-daily glargine or detemir to degludec. METHODS AND RESULTS: In this prospective observational study, T1D patients on twice-daily glargine or detemir were enrolled. At baseline and 12 weeks after switching to degludec, we recorded HbA1c, insulin dose, 30-day blood glucose self monitoring (SMBG) or 14-day continuous glucose monitoring (CGM), treatment satisfaction (DTSQ), fear of hypoglycemia (FHS). We included 29 patients (mean age 34 ± 11 years; diabetes duration 18 ± 10 years). After switching to degludec, HbA1c decreased from 7.9 ± 0.6% (63 ± 6 mmol/mol) to 7.7 ± 0.6% (61 ± 6 mmol/mol; p = 0.028). SMBG showed significant reductions in the percent and number of blood glucose values <70 mg/dl and in the low blood glucose index (LBGI) during nighttime. CGM showed a significant reduction of time spent in hypoglycemia, an increase in daytime spent in target 70-180 mg/dl, and a reduction in glucose variability. Total insulin dose declined by 17% (p < 0.001), with 24% reduction in basal and 10% reduction in prandial insulin. DTSQ and FHS significantly improved. CONCLUSION: Switching from twice-daily glargine or detemir to once daily degludec improved HbA1c, glucose profile, hypoglycemia risk and treatment satisfaction, while insulin doses decreased. ClinicalTrials.govNCT02360254.

Trends in overweight and obesity prevalence in Tuscan schoolchildren (2002-2012).

OBJECTIVE: The aim of the present study was to examine the prevalence and time trends in childhood overweight including obesity and obesity among Tuscan children from 2002 to 2012. DESIGN: Cross-sectional study at five time points (Tuscan Nutritional Surveillance Surveys conducted in the years of 2002, 2006, 2008, 2010 and 2012). Trained personnel directly measured the height and weight of the subjects. BMI was assessed by means of the International Obesity Task Force (IOTF) and WHO cut-offs. SETTING: Representative sample of children in the Tuscany region (Italy). SUBJECTS: Children (n 7183) aged between 7·5 and 9·5 years (3711 boys and 3472 girls). RESULTS: With respect to the estimation of the absolute prevalence level of childhood overweight, a discrepancy was observed between the two criteria. In all surveys, more boys than girls were overweight (including obesity). Trend analysis showed a significant decrease in the prevalence of overweight including obesity and obesity in Tuscan children from 2002 to 2012 (32·0 % v. 25·8 %, P<0·001 on using IOTF criteria and 37·7 % v. 34·3 %, P<0·001 on using WHO criteria for overweight including obesity; and 10·0 % v. 6·7 %, P<0·001 on using IOTF criteria and 12·5 % v. 11·3 %, P=0·035 on using WHO criteria for obesity). CONCLUSIONS: The present study is the first report from an Italian region showing a significant decrease in childhood obesity and overweight in the last 10 years. This reduction is probably a result of regional and local actions that have taken place in many sectors of society. However, efforts should be made to lower the prevalence of childhood obesity and overweight further.

Protective Effect of Plantago major Extract against t-BOOH-Induced Mitochondrial Oxidative Damage and Cytotoxicity.

Plantago major L. produces several chemical substances with anti-inflammatory and analgesic activities and its use in the treatment of oral and throat inflammation in popular medicine is well described. In this study, the antioxidant potential of the Plantago major hydroethanolic extract was screened and its protective action was evaluated against t-BOOH-induced oxidative stress. The extract was obtained by fractionated percolation using 50% ethanolic solution and, after drying, suspended in dimethyl sulfoxide. The chromatographic profile of crude extract was obtained with the identification of some phytochemical markers and the total phenols and flavonoids were quantified. The scavenger activity against DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals was determined and the antioxidant activity in biological systems was evaluated in isolated rat liver mitochondria and HepG2 cells. The extract exhibited a significant free radical scavenger activity at 0.1 mg/mL, and decreased the ROS (reactive oxygen species) generation in succinate-energized mitochondria. Such an effect was associated with the preservation of the intrinsic antioxidant defenses (reduced glutathione and NAD(P)H) against the oxidation by t-BOOH, and also to the protection of membranes from lipid oxidation. The cytoprotective effect of PmHE against t-BOOH induced cell death was also shown. These findings contribute to the understanding of the health benefits attributed to P. major.

Trends in thinness prevalence among adolescents in ten European countries and the USA (1998-2006): a cross-sectional survey.

OBJECTIVE: To describe the prevalence of 'graded thinness' in children aged 11, 13 and 15 years in eleven developed countries and to identify trends in the prevalence of 'thinness' (BMI < 17 kg/m2 at age 18 years) by age and gender. DESIGN: Cross-sectional study using data collected through self-reported questionnaires. SETTING: Data were taken from the 1997/1998, 2001/2002 and 2005/2006 surveys of the Health Behaviours in School-aged Children (HBSC) Study. SUBJECTS: Children and adolescents from ten European countries and the USA (n 158 000). RESULTS: Prevalence of grades 1, 2 and 3 of thinness was higher among 11-year-old students compared with the 13- and 15-year-olds in all countries. A higher prevalence of thinness was observed in girls than in boys. Since 1998 the prevalence of thinness decreased steadily in Czech boys and girls, while it increased for French girls. In the total European sample of females, thinness decreased from 1998 to 2006 (χ 2 for trend, P < 0·01). Age-adjusted logistic regression analysis showed that Czech boys and girls, and Flemish and American girls were less likely to be thin in 2006 than in 1998; while a noteworthy increment, even if borderline significant, was observed for French girls with a 41% increase in the likelihood to be thin. CONCLUSIONS: Our findings suggest that thinness is an important overlooked phenomenon with wide variation in prevalence and trends across developed countries. It deserves further longitudinal studies in a multinational context that could increase the understanding of the factors associated with thinness and contribute to developing preventive and nutritional programmes targeted at controlling obesity and chronic diseases, while monitoring thinness.

Morphology, body proportions, and postcranial hypertrophy of a female Neandertal from the Sima de las Palomas, southeastern Spain.

Considerations of Neandertal geographical variation have been hampered by the dearth of remains from Mediterranean Europe and the absence there of sufficiently complete associated postcrania. The 2006 and 2007 excavation of an articulated partial skeleton of a small adult female Neandertal at the Sima de las Palomas, Murcia, southeastern Spain (Sima de las Palomas 96) provides substantial and secure information on body proportions among southern European Neandertals, as well as further documenting the nature of Neandertal biology in southern Iberia. The remains exhibit a suite of cranial, mandibular, dental, and postcranial features, of both Neandertals and archaic Homo generally, that distinguish them from contemporary and subsequent early modern humans. Its lower limbs exhibit the robustness of later Pleistocene Homo generally, and its upper limbs conform to the pattern of elevated robustness of the Neandertals. Its body proportions, including relative clavicular length, distal limb segment lengths, and body mass to stature indicators, conform to the "cold-adapted" pattern of more northern Neandertals. Palomas 96 therefore documents the presence of a suite of "Neandertal" characteristics in southern Iberia and, along with its small body size, the more "Arctic" body proportions of other European Neandertals despite the warmer climate of southern Iberia during marine isotope stage 3.

Optimized glycaemic control achieved with add-on basal insulin therapy improves indexes of endothelial damage and regeneration in type 2 diabetic patients with macroangiopathy: a randomized crossover trial comparing detemir versus glargine.

AIMS: In diabetes, endothelial damage promotes macroangiopathy and endothelial regeneration is impaired, owing to reduced endothelial progenitor cells (EPCs). Given that insulin influences endothelial biology, we compared the effects of add-on basal insulin analogues on endothelial damage and regeneration in type 2 diabetes (T2D). METHODS: This was a 6-month randomized crossover trial comparing add-on insulin detemir versus glargine in poorly controlled T2D with macroangiopathy. At baseline, crossover (3 months) and study end (6 months), we measured HbA1c, EPCs, circulating endothelial cells (CECs), VCAM-1, ICAM-1 and E-selectin. Body weight and hypoglycaemic episodes were also recorded. RESULTS: Forty-two patients completed the study, randomly assigned to the glargine-detemir (n = 21) or the detemir-glargine (n = 21) schedule. At crossover, EPC levels did not change compared with baseline, but significantly increased at study end. CECs decreased over time and were significantly reduced at study end. ICAM-1, VCAM-1 and E-selectin were significantly reduced at crossover and further decreased at study end. No differences were seen in these effects between detemir and glargine. HbA1c showed a carryover effect and its reduction was similar with detemir and glargine in the first arm. Incidence of hypoglycaemia and weight gain was lower with detemir than with glargine in both arms. CONCLUSION: Optimized glycaemic control by add-on basal insulin improved indexes of endothelial damage and regeneration. Compared to glargine, detemir achieved similar endothelial protection with lower weight gain and less hypoglycaemia. These results might have implications for therapy of aging T2D patients with cardiovascular disease.

Relationship between 8/9-yr-old school children BMI, parents' BMI and educational level: a cross sectional survey.

BACKGROUND: Parents are responsible not only for the genetic structure of their children, but also for passing onto them their behaviours and attitudes toward life. The aim of this study was to analyse the connection between school-age children's obesity and that of their parents as well as between child obesity and parents' educational level, as a proxy indicator of the socio-economic status (SES) of families in Tuscany. METHODS: The children sample was selected from "OKkio alla Salute 2010" (a cross sectional survey carried out by the Italian Institute of Health) and consisted of 1,751 (922 males and 855 females) 8-9 year-old school children. Weight and height were measured by ad hoc trained personnel, and Body Mass Index (BMI) categories were calculated using Cole et al.'s cut-off. Parents' weight, height and educational level were collected by a self-administered questionnaire. The educational levels were classified as high, medium and low. RESULTS: The prevalence of obese children increased along the parents' BMI category: from 1.4% for underweight mothers to 30.3% for obese mothers and from 4% for under-normal-weight fathers to 23.9% for obese fathers (p < 0.001). An inverse relationship was observed between the parents' educational level and child obesity, the lowest educational level corresponding to the highest prevalence of obese children: 9.3% for mothers with a low educational level compared to 5.8% for mothers with a high educational level (p = 0.15); similarly, the corresponding prevalence for fathers was 9.5% compared to 4.5% (p = 0.03). CONCLUSION: Parents' obesity and the cultural resources of the family, particularly the father's, seem to influence the prevalence of overweight and obesity in Tuscan children.

Neandertal postcranial remains from the Sima de las Palomas del Cabezo Gordo, Murcia, southeastern Spain.

The Sima de las Palomas, southeastern Spain, has yielded a series of Neandertal postcranial remains, including immature and mature isolated elements and the fragmentary partial skeleton of a young adult (Palomas 92). The remains largely conform to the general late archaic/Neandertal morphological pattern in terms of humeral diaphyseal shape, pectoralis major tuberosity size and pillar thickness, ulnar coronoid process height, manual middle phalangeal epiphyseal breadth, manual distal phalangeal tuberosity shape and breadth, femoral diaphyseal shape, and probably body proportions. Palomas 92 contrasts with the Neandertals in having variably gracile hand remains, a more sellar trapezial metacarpal 1 facet, more anteroposteriorly expanded mid-proximal femoral diaphysis, and less robust pedal proximal phalanges. The Palomas Neandertals contrast with more northern European Neandertals particularly in various reflections of overall body size.

Late neandertals in southeastern Iberia: Sima de las Palomas del Cabezo Gordo, Murcia, Spain.

Middle Paleolithic fossil human remains from the Sima de las Palomas in southeastern Iberia (dated to

How do surgeons feel about the 'Getting it Right First Time' national audit? Results from a qualitative assessment.

The implementation of the national 'Getting It Right First Time' was assessed by interviewing six surgeons involved at various levels in surgical site infection (SSI) audit. The positive impacts were to create new professional collaboration, improve stakeholder engagement, and increase the profile of SSIs. One particular knowledge gap highlighted was that some participants had been unaware until that point of the criteria for diagnosing an SSI. The quality of data collected was felt to be poor due to methodological flaws. The audit was described as highly time-consuming and unsustainable if leaning on junior surgeons, without protected time and designated responsibility.

Case-control study to determine whether river water can spread tetracycline resistance to unexposed impala (Aepyceros melampus) in Kruger National Park (South Africa).

A case-control study was performed in the Kruger National Park (KNP), South Africa, to find out whether impala (Aepyceros melampus) were more likely to harbor tetracycline-resistant Escherichia coli (TREC) in their feces when they drank from rivers that contained these bacteria than when they drank from rivers that were uncontaminated with TREC. The following five perennial rivers were selected: the Crocodile, the Letaba, the Olifants, the Sabie, and the Sand. Samples of river water (n = 33) and feces (n = 209), collected at 11 different sites, were cultured for E. coli. The resulting colonies were screened for tetracycline resistance by use of the Lederberg replica plating method (breakpoint, 4 mg/liter). A resistant and/or a susceptible isolate was then selected from each sample and subjected to the CLSI MIC broth microdilution test for tetracyclines. Among the 21 water specimens contaminated by E. coli, 19.05% (n = 4) were found to be resistant by the MIC method (breakpoint, >/=8 mg/liter). This led to the Crocodile, Olifants, and Letaba rivers being classified as TREC positive. Among the 209 impala feces sampled, 191 were positive for the presence of E. coli (91.38%). Within these (n = 191), 9.95% (n = 19) of the isolates were shown to be TREC by the MIC method. It was found that 1.11% (n = 1) of the E. coli isolates cultured from the feces of the control group (n = 90) were TREC, in comparison with 17.82% (n = 18) of those in feces from the exposed group (n = 101). The calculation of the odds ratio showed that impala drinking from TREC-contaminated rivers were 19.3 (2.63 to 141.69) times more likely to be infected with TREC than were unexposed impala. This is a significant finding, indicating that surface water could be a possible source of antimicrobial resistance in naïve animal populations and that impala could act as sentinels for antimicrobial resistance.

Trends in adolescent overweight prevalence in Italy according to socioeconomic position.

BACKGROUND: The aim of this research is to update the trend in overweight (including obesity) prevalence among Italian adolescents, evaluating possible differences by age and gender, and analyzing their relationships with socioeconomic status, between 2002 and 2014. METHODS: The present study is based on data from the Italian HBSC study at four time points (2002, 2006, 2010 and 2014), which involved 15 035 adolescents, aged 11-13-15 (7540 boys and 7495 girls). RESULTS: Gender and age were associated with the occurrence of overweight. In all surveys, boys had a higher prevalence of excess weight compared to girls (p < 0.001), but only among girls there was a significant increasing trend (from 11.2% in 2002 to 13.3% in 2014). From 2002 to 2014, the risk of being overweight was inversely associated with the economic level of the family, for both genders and all age groups. CONCLUSIONS: Data collected between 2002 and 2014 in Italy showed a low overall increase in prevalence of obesity and overweight and an inverse association between SES and obesity in all age groups and in both genders. These findings suggest that concerted, multi-sectorial, efforts are needed in Italy, in combination with a sound political will, focused on reducing social inequality associate.

Myofilament-polyribosome association in muscle cells of rat left atrium after short-term hypertension.

Hypertension was induced in uninephrectomized Wistar rats by administration of deoxycorticosterone acetate (DOCA) and by addition of NaCl to their drinking water. The ultrastructure of atrial and ventricular cells of left hearts was compared after short-term (2 and 6 weeks) increased blood pressure. No morphological features could distinguish cells of treated animals from cells of normotensive rats after 2 weeks of treatment. The sarcoplasm of the atrial cells of 6-week-treated hypertensive rats presented an abnormally high number of helical arrangement of ribosomes often associated with abundant unorganized thick filaments, irregular nuclear profiles showing foldings and convolutions, and enlarged mitochondria. The only fine structural changes observed in the ventricular cells of the same animals was a moderate mitochondrial enlargement. The described alterations of atrial cells probably correspond to enhanced synthesis of contractile elements associated with increased nuclear-cytoplasmic exchanges; their absence in ventricular cells suggests that short-term and moderate pressure overload induces adaptative changes in left atrial cells at a stage when ventricular cells have morphological characteristics close to normal cells.

Hydroxyl scavenging activity accounts for differential antioxidant protection of Plantago major against oxidative toxicity in isolated rat liver mitochondria.

OBJECTIVES: The aim of this work was to study the effects of P. major against the oxidative damage of isolated rat liver mitochondria. METHODS: The extracts were obtained using methanol (MeOH), ethyl acetate (EAc), dichloromethane (DCM), and hexane (Hex) as solvents. KEY FINDINGS: Hex, DCM, and EAc totally, and MeOH partially, inhibited ROS generation and lipid peroxidation of membranes induced by Fe(2+) or t-BOOH. However, only MeOH was able to prevent the t-BOOH-induced glutathione and NAD(P)H oxidation. All extracts chelated Fe(2+) and reduced DPP Hradicals. EPR analysis revealed that P. major exhibited potent scavenger activity for hydroxyl radicals. CONCLUSIONS: The potent antioxidant activity exhibited by P. major was able to prevent oxidative mitochondrial damage, contributing to the understanding of its hepatoprotective action against ROS-mediated toxicity.

Comparison of a short food-frequency questionnaire and derived indices with a seven-day diet record in Belgian and Italian children.

OBJECTIVES: To compare food group intakes and dietary indices estimated from a 14-item food frequency questionnaire (FFQ) with a seven day diet record. METHODS: 112 Belgian and 114 Italian children (11-12 years) completed the FFQ followed by a seven-day diary (FD) and a retest one week later. Dietary indices were calculated from the FFQ and the FD. RESULTS: Spearman's correlations between the FFQ items and the diary varied between -0.13 and 0.67. When comparing the FFQ with the FD an overestimation was found for most items. The Excess Index was significantly correlated with energy intake (respectively 0.35 and 0.25 for Belgian and Italian children); the Variety Index with fiber intake (0.26 for both) and Calcium intake (respectively 0.32 and 0.41); the Fiber Index with fiber intake (respectively 0.30 and 0.37) and the Calcium Index with Calcium intake (respectively 0.47 and 0.50). CONCLUSION: When the FFQ is used for estimating consumption frequencies, overestimation must be considered. The ability to rank individuals varies considerably between food items. The Calcium index can be useful in situations requiring brief dietary instruments. The value of the other indices is lower although still associations in the expected directions were found.

Thrombotic thrombocytopenic purpura associated with primary tuberculosis.

Thrombotic thrombocytopenic purpura (TTP) during infectious diseases is a known, but rare event. In this paper a case of TTP associated with primary infection by Mycobacterium tuberculosis is described. Various therapeutic approaches were used with the patient: fresh frozen plasma infusions and plasma exchange, specific anti-tuberculous therapy, anti-platelet drugs and steroids. A complete remission occurred 3 months after the onset of the acute disease. A hypothesis on the pathogenesis of TTP might be an increased pro-coagulant activity of interleukin 1 (IL-1) on endothelial cells.

Brain abscess caused by Cladophialophora (Xylohypha) bantiana in a renal transplant patient.

Infectious disease is the most significant cause of morbidity and mortality in allotransplantation because of heavy immunosuppression. Brain abscesses caused by melanized fungi have been found occasionally and are an example of this complication. In this paper, we describe a case in a 61-year-old black man, who received a cadaveric kidney transplantation in December 1993, followed by triple therapy with cyclosporine, azathioprine, and prednisone. The patient developed right hemiparesis at the beginning of April 1998. A computed tomography scan showed a mass in the left parieto-temporal region of the brain. The patient underwent surgery and a brown-colored encapsulated brain abscess was resected. Histology of the tissue revealed a large number of pigmented fungal hyphae. Culture in a Sabouraud dextrose medium with cyclohexamide and chloramphenicol at 25 degrees C resulted in the growth of dark-green colonies. The fungus identified was Cladophialophora bantiana, based on characteristic microscopic features and on growth at 40 degrees C. The abscess recurred in spite of treatment with fluconazole. The patient was submitted to a second brain surgical procedure and was treated with amphotericin B in addition to fluconazole. Ten days later the patient's blood cultures became positive for Escherichia coli. After 3 days the patient died due to septic shock.