Living well with diabetes: 24-month outcomes from a randomized trial of telephone-delivered weight loss and physical activity intervention to improve glycemic control

OBJECTIVE: To evaluate the effectiveness of a telephone-delivered behavioral weight loss and physical activity intervention targeting Australian primary care patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Pragmatic randomized controlled trial of telephone counseling (n = 151) versus usual care (n = 151). Reported here are 18-month (end-of-intervention) and 24-month (maintenance) primary outcomes of weight, moderate-to-vigorous-intensity physical activity (MVPA; via accelerometer), and HbA1c level. Secondary outcomes include dietary energy intake and diet quality, waist circumference, lipid levels, and blood pressure. Data were analyzed via adjusted linear mixed models with multiple imputation of missing data. RESULTS: Relative to usual-care participants, telephone counseling participants achieved modest, but significant, improvements in weight loss (relative rate [RR] -1.42% of baseline body weight [95% CI -2.54 to -0.30% of baseline body weight]), MVPA (RR 1.42 [95% CI 1.06-1.90]), diet quality (2.72 [95% CI 0.55-4.89]), and waist circumference (-1.84 cm [95% CI -3.16 to -0.51 cm]), but not in HbA1c level (RR 0.99 [95% CI 0.96-1.02]), or other cardio-metabolic markers. None of the outcomes showed a significant change/deterioration over the maintenance period. However, only the intervention effect for MVPA remained statistically significant at 24 months. CONCLUSIONS: The modest improvements in weight loss and behavior change, but the lack of changes in cardio-metabolic markers, may limit the utility, scalability, and sustainability of such an approach.

Responses in carcass lean pH at 24 hours post-mortem in lines of Large White pigs selected for growth rate on a fixed ration over a set time

A restricted maximum likelihood analysis applied to an animal model showed no significant differences (P > 0.05) in pH value of the longissimus dorsi measured at 24 h post-mortem (pH24) between high and low lines of Large White pigs selected over 4 years for post-weaning growth rate on restricted feeding. Genetic and phenotypic correlations between pH24 and production and carcass traits were estimated using all performance testing records combined with the pH24 measurements (5.05-7.02) on slaughtered animals. The estimate of heritability for pH24 was moderate (0.29 ± 0.18). Genetic correlations between pH24 and production or carcass composition traits, except for ultrasonic backfat (UBF), were not significantly different from zero. UBF had a moderate, positive genetic correlation with pH24 (0.24 ± 0.33). These estimates of genetic correlations affirmed that selection for increased growth rate on restricted feeding is likely to result in limited changes in pH24 and pork quality since the selection does not put a high emphasis on reduced fatness.

Further evidence for linkage of Gilles de la Tourette syndrome (GTS) susceptibility loci on chromosomes 2p11, 8q22 and 11q23-24 in South African Afrikaners

Utilizing DNA samples from 91 Afrikaner nuclear families with one or more affected children, five genomic regions on chromosomes 2p, 8q, 11q, 20q, and 21q that gave evidence for association with GTS in previous case-control association studies were investigated for linkage and association with GTS. Highly polymorphic markers with mean heterozygosity of 0.77 were typed and resulting genotypes evaluated using single marker transmission disequilibrium (TDT), single marker haplotype relative risk (HRR), and multi-marker "extended" TDT and HRR methods. Single marker TDT analysis showed evidence for linkage or association, with p-values near 0.05, for markers D2S139, GATA28F12, and D11S1377 on chromosomes 2p11, 8q22 and 11q23-24, respectively. Extended, two-locus TDT and HRR analysis provided further evidence for linkage or association on chromosome 2 with p-values of 0.007 and 0.025, and chromosome 8 with p-values of 0.059 and 0.013, respectively. These results provide important additional evidence for the location of GTS susceptibility loci.

Vykopirovka iz obshchego plana Biiuk-Onlarskoi dachi razverstaniia na uchastki KOMZET-a pod nazv. Biiuk-Onlarskii fond i Nom 9/10/24

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Plan zemelʻnogo uchastka poselka N 24

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Chemotherapy pretreatment sensitizes solid tumor-derived cell lines to Vα24+ NKT cell-mediated cytotoxicity

There is an increasing awareness of the therapeutic potential for combining immune-based therapies with chemotherapy in the treatment of malignant diseases, but few published studies evaluate possible cytotoxic synergies between chemotherapy and cytotoxic immune cells. Human Vα24 +/Vβ11+ NKT cells are being evaluated for use in cell-based immunotherapy of malignancy because of their immune regulatory functions and potent cytotoxic potential. In this study, we evaluated the cytotoxicity of combinations of chemotherapy and NKT cells to determine whether there is a potential to combine these treatment modalities for human cancer therapy. The cytotoxicity of NKT cells was tested against solid-tumor derived cell lines NCI-H358, DLD-1, HT-29, DU-145, TSU-Pr1 and MDA-MB231, with or without prior treatment of these target cells, with a range of chemotherapy agents. Low concentrations of chemotherapeutic agents led to sensitization of cell lines to NKT-mediated cytotoxicity, with the greatest effect being observed for prostate cancer cells. Synergistic cytotoxicity occurred in an NKT cell in a dose-dependent manner. Chemotherapy agents induced upregulation of cell surface TRAIL-R2 (DR5) and Fas (CD95) expression, increasing the capacity for NKT cells to recognize and kill via TRAIL- and FasL-mediated pathways. We conclude that administration of cytotoxic immune cells after chemotherapy may increase antitumor activities in comparison with the use of either treatment alone.

Glycemic Control in Diabetic Pregnancies: Effects on Fetal and Maternal Outcome

Background: Both maternal and fetal complications are increased in diabetic pregnancies. Although hypertensive complications are increased in pregnant women with pregestational diabetes, reports on hypertensive complications in women with gestational diabetes mellitus (GDM) have been contradictory. Congenital malformations and macrosomia are the main fetal complications in Type 1 diabetic pregnancies, whereas fetal macrosomia and birth trauma but not congenital malformations are increased in GDM pregnancies. Aims: To study the frequency of hypertensive disorders in gestational diabetes mellitus. To evaluate the risk of macrosomia and brachial plexus injury (Erb’s palsy) and the ability of the 2-hour glucose tolerance test (OGTT) combined with the 24-hour glucose profile to distinguish between low and high risks of fetal macrosomia among women with GDM. To evaluate the relationship between glycemic control and the risk of fetal malformations in pregnancies complicated by Type 1 diabetes mellitus. To assess the effect of glycemic control on the occurrence of preeclampsia and pregnancy-induced hypertension in Type 1 diabetic pregnancies. Subjects: A total of 986 women with GDM and 203 women with borderline glucose intolerance (one abnormal value in the OGTT) with a singleton pregancy, 488 pregnant women with Type 1 diabetes (691 pregnancies and 709 offspring), and 1154 pregnant non-diabetic women (1181 pregnancies and 1187 offspring) were investigated. Results: In a prospective study on 81 GDM patients the combined frequency of preeclampsia and PIH was higher than in 327 non-diabetic controls (19.8% vs 6.1%, p<0.001). On the other hand, in 203 women with only one abnormal value in the OGTT, the rate of hypertensive complications did not differ from that of the controls. Both GDM women and those with only one abnormal value in the OGTT had higher pre-pregnancy weights and BMIs than the controls. In a retrospective study involving 385 insulin-treated and 520 diet-treated GDM patients, and 805 non-diabetic control pregnant women, fetal macrosomia occurred more often in the insulin-treated GDM pregnancies (18.2%, p<0.001) than in the diet-treated GDM pregnancies (4.4%), or the control pregnancies (2.2%). The rate of Erb’s palsy in vaginally delivered infants was 2.7% in the insulin-treated group of women and 2.4% in the diet-treated women compared with 0.3% in the controls (p<0.001). The cesarean section rate was more than twice as high (42.3% vs 18.6%) in the insulin-treated GDM patients as in the controls. A major fetal malformation was observed in 30 (4.2%) of the 709 newborn infants in Type 1 diabetic pregnancies and in 10 (1.4%) of the 735 controls (RR 3.1, 95% CI 1.6–6.2). Even women whose levels of HbA1c (normal values less than 5.6%) were only slightly increased in early pregnancy (between 5.6 and 6.8%) had a relative risk of fetal malformation of 3.0 (95% CI 1.2–7.5). Only diabetic patients with a normal HbA1c level (<5.6%) in early pregnancy had the same low risk of fetal malformations as the controls. Preeclampsia was diagnosed in 12.8% and PIH in 11.4% of the 616 Type 1 diabetic women without diabetic nephropathy. The corresponding frequencies among the 854 control women were 2.7% (OR 5.2; 95% CI 3.3–8.4) for preeclampsia and 5.6% (OR 2.2, 95% CI 1.5–3.1) for PIH. Multiple logistic regression analysis indicated that glycemic control, nulliparity, diabetic retinopathy and duration of diabetes were statistically significant independent predictors of preeclampsia. The adjusted odds ratios for preeclampsia were 1.6 (95% CI 1.3–2.0) for each 1%-unit increment in the HbA1c value during the first trimester and 0.6 (95% CI 0.5–0.8) for each 1%-unit decrement during the first half of pregnancy. In contrast, changes in glycemic control during the second half of pregnancy did not alter the risk of preeclampsia. Conclusions: In type 1 diabetic pregnancies it is extremely important to achieve optimal glycemic control before pregnancy and maintain it throughout pregnancy in order to decrease the complication rates both in the mother and in her offspring. The rate of fetal macrosomia and birth trauma in GDM pregnancies, especially in the group of insulin-treated women, is still relatively high. New strategies for screening, diagnosing, and treatment of GDM must be developed in order to decrease fetal and neonatal complications.

Synthesis, aggregation behavior and cholesterol solubilization studies of 16-epi-pythocholic acid (3 alpha,12 alpha,16 beta-trihydroxy-5 beta-cholan-24-oic acid)

Synthesis, aggregation behavior and in vitro cholesterol solubilization studies of 16-epi-pythocholic acid (3 alpha,12 alpha,16 beta-trihydroxy-5 beta-cholan-24-oic acid, EPCA) are reported. The synthesis of this unnatural epimer of pythocholic acid (3 alpha,12 alpha,16 alpha-trihydroxy-5 beta-cholan-24-oic acid, PCA) involves a series of simple and selective chemical transformations with an overall yield of 21% starting from readily available cholic acid (CA). The critical micellar concentration (CMC) of 16-epi-pythocholate in aqueous media was determined using pyrene as a fluorescent probe. In vitro cholesterol solubilization ability was evaluated using anhydrous cholesterol and results were compared with those of other natural di-and trihydroxy bile acids. These studies showed that 16-epi-pythocholic acid (16 beta-hydroxy-deoxycholic acid) behaves similar to cholic acid (CA) and avicholic acid (3 alpha,7 alpha,16 alpha-trihydroxy-5 beta-cholan-24-oic acid, ACA) in its aggregation behavior and cholesterol dissolution properties. (C) 2010 Elsevier Inc. All rights reserved.

Silva Fennica Vol. 24, 1990.

Julkaistu Silva Fennica Vol. 24(4) -numeron liitteenä.