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Sanfilippo syndrome is a fatal childhood neurodegenerative disorder involving neuroinflammation among multiple pathologies. We hypothesized that anakinra, a recombinant interleukin-1 receptor antagonist, could improve neurobehavioral and functional symptoms owing to its capacity to treat neuroinflammation. This phase 1/2 trial aimed to test the safety, tolerability and effects of anakinra on neurobehavioral, functional and quality-of-life outcomes in patients and their caregivers. The primary outcome was the percent of participants requiring a dose increase at week 8 or week 16. Secondary efficacy outcomes included a multi-domain responder index (MDRI). Twenty-three participants (6–26 years of age) were enrolled. Twenty continued treatment to week 8, and 15 (75%) required an increased dose at week 8 or week 16. There was an improvement in at least one domain in the MDRI in 18 of 21 (86%) at week 8 and in 15 of 16 (94%) at week 36. Seven participants withdrew (intolerability of daily injections and lost to follow-up) before week 36. Adverse events occurred in 22 of 23 (96%) participants, most commonly mild injection site reactions. No serious adverse events were related to anakinra. In conclusion, anakinra was safe and associated with improved neurobehavioral and functional outcomes, supporting continued investigation of anakinra in Sanfilippo syndrome and other mucopolysaccharidoses. ClinicalTrials.gov identifier: NCT04018755.

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene–smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

To study the differences in immune cell profiles in uterine fibroids (Fibs) and matched myometrium (Myo).

There is mounting evidence emphasizing the importance of intracellular antioxidant levels for maintenance of the immune function. The flavonoid quercetin, a natural antioxidant, has been shown to modulate enzymes involved in the regulation of the inflammatory response. However, up to now, there have been no studies describing quercetin levels in cells of the immune system. A gradient reversed-phase HPLC technique to identify and quantify intracellular levels of quercetin and its application in mice splenocytes are described. Mobile phases were a 0.01 M sodium phosphate monobasic solution adjusted to pH 2.8 with 85% orthophosphoric acid (buffer, Solvent A) and methanol (Solvent B) with a flow rate of 1 ml/min. An eight-channel coulometric electrode array detector was used. In vitro supplementation with increasing concentration of quercetin (25, 50, and 100 μM) raises intracellular quercetin levels in a dose-dependent manner. The method has the required features of specificity and sensitivity for monitoring quercetin uptake in cells of the immune system. Copyright 2000 Academic Press.

The quantity of β-carotene (BC) accumulated in colonic polyps and colonic cancererous tissue in humans in situ was determined relative to the quantity accumulated in normal colon and rectal tissue. Serum concentration of BC, retinol, and α-tocopherol and tissue BC concentration were determined by high-performance liquid chromatography in samples obtained before and after oral supplementation with BC (30 mg/day). The serum BC and retinol concentrations significantly increased in response to supplementation in control, polyp, and cancer patients, but there was no change in serum α-tocopherol concentration. The BC concentration in tissue (colon, rectum, and tumor) of cancer patients was significantly less than that in tissue samples from control and polyp patients. Relative to baseline values, BC accumulated to a significant extent in tissues from all patients, including polyp and tumor tissue, during supplementation. The results indicate that BC does accumulate in colonic neoplastic tissue in humans and may potentially be utilized to augment cytotoxicity of chemotherapeutics or to prevent malignant transformation of cells.

Regression equations for estimating body density and fatness from anthropometric measurements are usually specific to the populations from which they are derived, owing to methodological and biological factors. Some equations are, however, regarded as having general validity for subjects of different ages, levels of fatness and fitness. In this study, five such general equations were tested by comparing estimated body density (Dest) with measured body density (Dmeas) in 138 European men employed in an Italian shipyard. Body density was measured by underwater weighing with the simultaneous determination of lung residual volume. Measurements were also made of height, weight, eight skinfolds, four circumferences and seven diameters by standard techniques.&(D)dot;est from the five general equations were significantly different from &(D)dot;meas (P<0·001). New prediction equations for estimating D were drawn up by simple and multiple regression of various combinations of skinfolds expressed as individual skinfolds, sums, log sums and the quadratic form. Equations were drawn up on a validation sample (N = 92) and tested on a cross-validation sample (N = 46). The form of skinfolds and the combination selected made little difference to the SEEs and R2 but the inclusion of age resulted in lower SEEs. Stepwise multiple regression produced an equation incorporating thorax and triceps skinfolds and age with an SEE of 6 kg/m3 and R2 of 79%. The derived equations were successfully cross-validated, &(D)dot;meas and &(D)dot;est were not significantly different, ryy, and SEE were similar to those of the validation sample. When the cross-validation sample was divided into two according to age, density or &(V)dot;O2 max, the derived equations were applicable to the upper and lower groups for age or physical fitness but not to the groups differing in fatness. These equations should be validated further on other samples by studies performed with due regard to the methodological factors, both technical and statistical, that may result in specificity. However, the poor performance of the general equations tested and the specificity for fatness of the derived equations suggest that biological factors may preclude the development of general prediction equations for body density.

An increase in the polyunsaturated to saturated fatty acid ratio (PS) in the diet has been reported to reduce blood pressure in man. We have investigated whether an increase in the percentage of saturated fatty acids in the typical Mediterranean diet would affect blood pressure in a sample of healthy rural population of southern Italy. Fifty-seven non-hospitalized normotensive volunteers (29 male, 28 female, aged 30-50 years) were studied. After a 2-week baseline period on their customary diet (PS0.44), they underwent a 6-week isocaloric dietary intervention with a 70 increase in energy from saturated fatty acids and a corresponding decrease in carbohydrate and mono-unsaturated fat (PS0.23). Thereafter they returned to their usual diet and were followed-up for 6 more weeks (switch-back period).

The variations, throughout the year, of the 90Sr and 137Cs concentrations in the diet and in the urine of a group of thirty healthy children, have been investigated. This set of experimental measurements has allowed us to establish a correlation between the Cs contamination in diets and in the corresponding urines. The ratio between the contamination, in C.U. and S.U., of the diets and of the urines, has been found to be < 1.

The foods which contribute most to the intake of selected vitamins and minerals were evaluated for the elderly in Italy and compared to food sources of nutrients in the US. A sample of 945 Italians, aged ≥60, from 14 centres throughout Italy, each completed weighed 7-day food records during the period 1983–1987. These data were used to quantify the contribution of individual foods to the total intake of and variability in intake of vitamin A, thiamin, riboflavin, vitamin C, calcium, and iron. In addition, those foods contributing most to micronutrient intake for the Italians were compared to those foods contributing most for the elderly in the US as recorded by the NHANES II Survey (1976–1980). Overall, there was a preponderance of vegetable rather than animal sources, and of less processed food sources in Italy. In Italy, wine was an important source of several nutrients, including iron and riboflavin. These data are useful for characterizing diet in a well-nourished population with marked differences in diet from the US. They may also form the basis for a quantitative food frequency questionnaire for epidemiological studies in Italy.

The major sources of macronutrients in the Italian diet were assessed. Elderly Italians, aged ≥60 recorded their weighed intake for a 7-day period. A total of 945 subjects from 14 centres throughout Italy participated during the period 1983–1987. Thgese data were used to quantify the contribution of individual foods to the total intake of and variability in intake of kilocalories, protein, carbohydrate, total fat, saturated fat, oleic acid, polyunsaturated fatty acids, linoleic acid, and cholesterol. The foods ranked one to five for Italy were compared to the top five foods contributing to these nutrients in the diet of the elderly in the US based on the NHANES II Survey (1976–1980). These data provide information for the design of an Italian data-based quantitative food frequency questionnaire. They are also of interest in their description of an industrialized, well-nourished population with a dietary pattern markedly different from the US-lower in saturated fat, higher in complex carbohydrate and higher in alcohol.