The impact of COVID-19 on systemic anticancer treatment delivery in Scotland.

Understanding the impact of the COVID-19 pandemic on systemic anticancer therapy delivery (SACT) is crucial to appreciate the short- and long-term consequences for cancer patients and plan future care. Here, we report real-time national SACT delivery data from NHS Scotland. We demonstrate an initial rapid reduction in patient attendance of 28.7% with subsequent rapid recovery following service redesign. The smallest decrease was seen in breast cancer (19.7%), which also had the most rapid recovery and the largest decrease seen in colorectal cancer (43.4%). Regional variation in the magnitude of impact on SACT delivery was observed, but nadirs occurred at the same time and the rate of recovery was similar across all regions. This recovery reflected a coordinated national approach and associated patient and clinician support structures, which facilitated the creation of COVID-19-protected areas for SACT delivery in Scottish cancer centres enabling rapid sharing of successful and innovative strategies. The data show that these actions have limited the disadvantage to cancer patients.

Interactions between protein and vegetable oils in the maternal diet determine the programming of the insulin axis in the rat.

The available evidence suggests that metabolic control mechanisms are programmed early in life. Previous studies of pregnant rats fed low-protein diets have suggested that the vegetable oils used in the experimental diets influence the outcome. The present study investigated the offspring of female rats fed semi-synthetic diets containing either 180 or 90g casein/kg with 70 g/kg (w/w) of either corn oil or soya oil during gestation. During lactation, the dams received stock diet, and the offspring were subsequently weaned onto the stock diet. The offspring of dams fed the low-protein diets were smaller at birth. At 25 weeks of age, the offspring were subjected to an oral glucose tolerance test. In the offspring of dams fed the diet containing soya oil, the area under the insulin curve was affected by the protein content of the maternal diet. There was no effect of protein on the area under the insulin curve in the offspring of dams fed the diet prepared with corn oil. There were no differences in plasma glucose concentrations. The levels of mRNA for acetyl-CoA carboxylase- in the livers of female offspring were affected by the protein and oil content of the maternal diet. The level of carnitine palmitoyl transferase mRNA was affected by the protein content of the maternal diet. The present study suggests that PUFA in the maternal diet can interact with protein metabolism to influence the development of the offspring. This may involve the higher content of alpha-linolenic acid in soya oil compared with corn oil.

Maternal protein restriction and fetal growth: lack of evidence of a role for homocysteine in fetal programming.

The disease-programming effects of a maternal low-protein (MLP) diet in rat pregnancy have been suggested to be attributable of hyperhomocysteinaemia. The aim of the present study was to determine whether MLP feeding impacted upon maternal and day 20 fetal homocysteine concentrations, with ensuing effects upon oxidant/antioxidant status. Sixty-four pregnant rats were fed either MLP diet or control diet before termination of pregnancy at days 4, 10, 18 or 20 gestation (full-term gestation 22 d). Maternal plasma homocysteine concentrations were similar in control and MLP-fed dams at all points in gestation. Fetal plasma homocysteine was similarly unaffected by MLP feeding at day 20 gestation. Activities of superoxide dismutase and glutathione peroxidase were similar in livers of mothers and fetuses in the two groups. Whilst catalase activity was not influenced by diet in maternal liver, MLP exposure increased catalase activity in fetal liver at day 20. Oxidative injury (protein carbonyl concentration) was lower in the livers of MLP-fed animals at day 18 gestation (P<0.05), but significantly greater at day 20. Hepatic expression of methionine synthase was similar in control and MLP-fed dams at all stages of gestation. Expression of DNA methyltransferase 1 in fetal liver was altered by maternal diet in a sex- and gestational age-specific manner. In conclusion, MLP feeding does not impact upon maternal or fetal homocysteine concentrations prior to day 20 gestation in the rat. There was no evidence of increased oxidative injury in fetal tissue that might explain the long-term programming effects of the diet.

The expression of growth-arrest genes in the liver and kidney of the protein-restricted rat fetus.

During fetal life, there are periods of rapid cell proliferation, which are uniquely sensitive to nutritional perturbation. Feeding the pregnant rat a protein-restricted diet alters the growth trajectory of major fetal organs such as the kidney. By day 21 of gestation, the ratio of kidney weight to total body weight is reduced in the fetuses of dams fed a protein-deficient diet. In contrast, the ratio of fetal liver weight to total body weight is unchanged. To investigate the mechanisms underlying this disproportionate change in organ growth in the low-protein group, cell proliferation and differentiation have been assessed in the liver and kidney. The steady-state levels of mRNA for the growth-arrest and DNA-damage gene gadd153/CHOP-10, CCAAT enhancer-binding proteins alpha and beta were unaffected by maternal diet in both fetal liver and kidney. The mRNA for alpha-fetoprotein, albumin and hepatic glucokinase were unchanged in the liver, suggesting that maternal protein deficiency does not alter the state of differentiation. The steady-state levels of the mRNA coding for the cyclin-dependent protein kinase inhibitors (p15(INK4a), p19(INK4d), p21(CIP1), p27(KIP1) and p57(KIP2)) were unchanged in the fetal livers but were significantly increased in the kidneys of fetuses from dams fed the low-protein diet. These results show that the asymmetrical growth of the kidney is associated with increases in mRNA for the Cip/Kip cyclin-dependent kinase inhibitors and that these may reflect specific lesions in organ development.

Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat.

Nutrient restriction in pregnancy has been shown to programme adult obesity. Modulation of feeding behaviour may provide a mechanism through which obesity may be programmed. Pregnant Wistar rats were fed either a control diet or a low-protein (LP) diet throughout gestation. Their offspring were allocated to a self-selected-diet protocol to assess appetite and food preferences at 12 and at 30 weeks of age. Self-selection of high-fat, high-protein or high-carbohydrate foods by 12-week-old rats indicated that the prenatal environment influenced feeding behaviour. Both male and female offspring of LP-fed mothers consumed significantly more of the high-fat (P<0.001) and significantly less (P<0.02) of the high-carbohydrate food than the control animals. Female, but not male, offspring of LP-fed rats failed to adjust food intake to maintain a constant energy intake and had higher fat (P<0.005) and energy intakes (P<0.05) than control female rats. At 30 weeks of age there were no differences in the pattern of food selection between the two groups of animals. Male offspring of LP-fed rats had significantly more gonadal fat than control animals (P<0.05), but analysis of total body fat content indicated that there was no significant difference in overall adiposity. The present study suggests that in young adults at least, early life exposure to undernutrition determines a preference for fatty foods. Maternal nutrition may thus promote changes in systems that are involved in control of appetite or the perception of palatability.