Type 1 diabetes in North East England and North Cumbria: patterns and time trends in 0-14-year-olds from 2012 to 2020.

Introduction: It is important to understand patterns in the epidemiology of type 1 diabetes because they may provide insight into its etiology. We examined the incidence of type 1 diabetes in children aged 0-14 years, and patient demographics and clinical parameters at presentation, over the period 2012-2020 using the North East and North Cumbria Young Persons diabetes register. Methods: Patients up to the age of 14 years with type 1 diabetes, and their families- managed in a total of 18 young persons diabetes clinics-were approached in person at the time of clinic appointments or in the days following diagnosis and they consented to their data being included in the register. Data were submitted regionally to a central unit. Descriptive statistics including crude and age-specific incidence rates were calculated. Temporal trends were analyzed using Joinpoint regression. Comparisons in incidence rates were made between age, sex and areas of higher and lower affluence as measured by the Index of Multiple Deprivation (IMD). Results: A total of 943 cases were recorded between January 2012 and December 2020. Median age at diagnosis was 8.8 years (Q1: 5.3, Q3: 11.7). There were more males than females (54% male). The median HbA1c at diagnosis was 100 mmoL/L (IQR: 39) and over one third (35%) were in ketoacidosis (pH < 7.3). Crude incidence decreased from 25.5 (95% confidence interval [CI] 20.9, 29.9) in 2012 to 16.6 (95% CI: 13.0, 20.2) per 100,000 in 2020 (5.1% per annum, 95% CI 1.1, 8.8%). During the period of the study there was no evidence of any trends in median age, HbA1c, BMI or birthweight (p = 0.18, 0.80, 0.69, 0.32) at diagnosis. Higher rates were observed in males aged 10-14 years, but similar rates were found for both sexes aged 0-9 years and there was no difference between areas of higher or lower deprivation (p = 0.22). Conclusion: The incidence of diabetes in the young may be falling in the North East of England and North Cumbria. The reasons are unclear as there were no associations identified between levels of deprivation or anthropometric measurements. Potential mechanisms include alterations in socioeconomic background or growth pattern. Further research is needed to understand the reasons behind this finding.

A prospective cohort study of the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland.

INTRODUCTION: In order to minimise the risk of breast cancer patients for COVID-19 infection related morbidity and mortality prioritisation of care has utmost importance since the onset of the pandemic. However, COVID-19 related risk in patients undergoing breast cancer surgery has not been studied yet. We evaluated the safety of breast cancer surgery during COVID-19 pandemic in the West of Scotland region. METHODS: A prospective cohort study of patients having breast cancer surgery was carried out in a geographical region during the first eight weeks of the hospital lockdown and outcomes were compared to the regional cancer registry data of pre-COVID-19 patients of the same units (n = 1415). RESULTS: 188 operations were carried out in 179 patients. Tumour size was significantly larger in patients undergoing surgery during hospital lockdown than before (cT3-4: 16.8% vs. 7.4%; p < 0.001; pT2 - pT4: 45.5% vs. 35.6%; p = 0.002). ER negative and HER-2 positive rate was significantly higher during lockdown (ER negative: 41.3% vs. 17%, p < 0.001; HER-2 positive: 23.4% vs. 14.8%; p = 0.004). While breast conservation rate was lower during lockdown (58.6% vs. 65%; p < 0.001), level II oncoplastic conservation was significantly higher in order to reduce mastectomy rate (22.8% vs. 5.6%; p < 0.001). No immediate reconstruction was offered during lockdown. 51.2% had co-morbidity, and 7.8% developed postoperative complications in lockdown. There was no peri-operative COVID-19 infection related morbidity or mortality. CONCLUSION: breast cancer can be safely provided during COVID-19 pandemic in selected patients.

Genotype by Yield*Trait (GYT) Biplot: a Novel Approach for Genotype Selection based on Multiple Traits.

Genotype selection based on multiple traits is a key issue in plant breeding; it has been dependent on setting a subjective weight for each trait in index selection and a subjective truncation point for each trait in independent culling, and the weights and truncation points can be highly subjective. In this paper we proposed and demonstrated a novel approach for genotype selection based on multiple traits, the genotype by yield*trait (GYT) biplot, where "trait" can be any breeding objective other than yield; it may be an agronomic trait, a grain quality, processing quality, or nutritional quality trait, or a disease resistance. The GYT biplot ranks genotypes based on their levels in combining yield with other target traits and at the same time shows their trait profiles, i.e., their strengths and weaknesses. Compared to existing methods, this approach is graphical, objective, effective, and straightforward. Underlying the GYT biplot approach is the paradigm shift that genotypes should be evaluated by their levels in combining yield with other traits as opposed to by their levels in individual traits. An oat dataset from multi-year multi-locations trials was used to demonstrate the GYT biplot approach.

The α' subunit of ß-conglycinin and various glycinin subunits of soy are not required to modulate hepatic lipid metabolism in rats.

PURPOSE: This study examined the effect of soy proteins with depletion of different subunits of the two major storage proteins, ß-conglycinin and glycinin, on hepatic lipids and proteins involved in lipid metabolism in rats, since the bioactive component of soy responsible for lipid-lowering is unclear. METHODS: Weanling Sprague Dawley rats were fed diets containing either 20% casein protein in the absence (casein) or presence (casein + ISF) of isoflavones or 20% alcohol-washed soy protein isolate (SPI) or 20% soy protein concentrates derived from a conventional (Haro) or 2 soybean lines lacking the α' subunit of ß-conglycinin and the A1-3 (1TF) or A1-5 (1a) subunits of glycinin. After 8 weeks, the rats were necropsied and liver proteins and lipids were extracted and analysed. RESULTS: The results showed that soy protein diets reduced lipid droplet accumulation and content in the liver compared to casein diets. The soy protein diets also decreased the level of hepatic mature SREBP-1 and FAS in males, with significant decreases in diets 1TF and 1a compared to the casein diets. The effect of the soy protein diets on female hepatic mature SREBP-1, FAS, and HMGCR was confounded since casein + ISF decreased these levels compared to casein alone perhaps muting the decrease by soy protein. A reduction in both phosphorylated and total STAT3 in female livers by ISF may account for the gender difference in mechanism in the regulation and protein expression of the lipid modulators. CONCLUSIONS: Overall, soy protein deficient in the α' subunit of ß-conglycinin and A1-5 subunits of glycinin maintain similar hypolipidemic function compared to the conventional soy protein. The exact bioactive component(s) warrant identification.

The α' subunit of ß-conglycinin and the A1-5 subunits of glycinin are not essential for many hypolipidemic actions of dietary soy proteins in rats.

PURPOSE: This study examined the effects of dietary soy protein (SP) lacking different storage protein subunits and isoflavones (ISF) on the abdominal fat, blood lipids, thyroid hormones, and enzymatic activities in rats. METHODS: Weanling Sprague-Dawley rats (8 males and 8 females/group) were fed diets containing either 20 % casein without or with supplemental isoflavones or alcohol-washed SP isolate or SP concentrates (SPC) prepared from 6 different soy bean lines for 8 weeks. RESULTS: Feeding of diets containing SPC regardless of their subunit compositions significantly lowered relative liver weights, blood total, free, and LDL cholesterol in both genders (P < 0.05) and also reduced serum free fatty acids (FFA) and abdominal fat in females (P < 0.05) compared to the casein or casein + ISF diets. Dietary SPC significantly elevated the plasma free triiodothyronine (T3) in both genders and total T3 in females compared to the casein diet (P < 0.05). The SPC lacking ß-conglycinin α' and either the glycinin A1-3 or A1-5 subunits increased total T3 in males and reduced plasma enzymatic activities of creatine kinase and lactate dehydrogenase compared to casein or casein + ISF diet (P < 0.05). CONCLUSIONS: Soy isoflavones were mainly responsible for the hypocholesterolemic effects and increased plasma free T3, whereas reduction in FFA, abdominal fat, liver weight and increased plasma total T3 were the effects of the soy proteins. Neither the α' subunit of ß-conglycinin nor the A1-5 subunits of glycinin are essential for the hypolipidemic properties of soy proteins.

Evaluation of outcome measures for use in clinical practice for adults with musculoskeletal conditions of the knee: a systematic review.

BACKGROUND: This systematic review reported on the clinimetric properties of outcome measures for use in clinical practice for adults with musculoskeletal conditions of the knee. METHODS: A systematic search was performed in Medline, EMBASE, Cinahl and AMED to identify studies examining the clinimetric properties of outcome measures for adults undergoing conservative treatment of ligament injuries, meniscal lesions, patellofemoral pain and osteoarthritis of the knee. Outcomes measures taking less than 20 min to administer and requiring minimal equipment and space were included. Pairs of authors used a checklist to record the characteristics of the outcome measures, their reported clinimetric properties and the demographics of the study populations. The OMERACT filters of 'truth' and 'discrimination' were applied to the data for each outcome measure by an expert panel. RESULTS: Forty-seven studies were included evaluating 37 outcome measures. Ten outcome measures had adequate supporting evidence for 'truth' and 'discrimination': AAOS, AKPS, goniometer measurement, IKDC, KOOS, LEFS, Lysholm, Tegner, WOMAC and WOMET. However none of the outcome measures had been comprehensively tested across all clinimetric properties. CONCLUSION: Despite the widespread use of some outcome measures in clinical practice and primary research, data on the clinimetric properties were available for only 37 and of these only 10 had adequate supporting evidence for use in this population. However, before a core set of outcome measures can be recommended use in clinical practice, for adults with musculoskeletal conditions of the knee, consensus should be obtained on 'feasibility' in terms of burden on the clinician and the participant.

Discordant phenotypes in a mother and daughter with mosaic supernumerary ring chromosome 19 explained by a de novo 7q36.2 deletion and 7p22.1 duplication.

We report on a patient with severe intellectual disability, microcephaly, short stature, and dysmorphic features who, based on standard karyotyping, has two cytogenetic abnormalities: an apparently balanced paracentric inversion of chromosome 7, inv(7)(q31.2q36), and a small supernumerary ring chromosome derived entirely of material from chromosome 19. While the inversion was detected in all cells, mosaicism was observed for the ring chromosome. Interestingly, apparently identical cytogenetic abnormalities were detected in the patient's mother, who presented with normal stature, few dysmorphic features, and normal cognition without microcephaly. While the level of mosaicism could not adequately explain the phenotypic discordance, comparative genome hybridization revealed a de novo terminal deletion of chromosome 7, del(7)(q36.2), and a terminal duplication of chromosome 7, dup(7)(p22.1) in the patient. Additional cytogenetic investigation revealed that the patient inherited a recombinant chromosome derived from a cryptic maternal pericentric inversion: inv(7)(p22q36). The patient's distinctive features are consistent with the wide phenotypic spectrum reported in 7p duplication and 7q terminal deletion syndromes. These chromosomal regions contain several candidate genes of clinical significance, including SHH, EN2, and FAM20C. Our findings strongly suggest that our patient's phenotype is largely attributable to partial 7pter trisomy and partial 7qter monosomy rather than mosaic supernumerary ring chromosome 19.

Prolonged honeymoon phase in an adolescent with diabetes and thyrotoxicosis provides support for the accelerator hypothesis.

A 14-yr-old female presented with diabetes and Graves' disease. Eighteen months later, she was euthyroid on carbimazole, and her haemoglobin A1c (HbA1c) was normal (5.2%) on a small insulin dose (0.3-0.4 units/kg/day). An assessment of her pancreatic beta-cell reserve, determined by comparing HbA1c and insulin dose, suggested that this was greater than other patients with type 1 diabetes in our service 18 months postdiagnosis (n = 185). We suspect that excess thyroid hormone led to an insulin-resistant state and accelerated her presentation with hyperglycaemia. Insulin resistance fell once normal thyroid function was restored and helped to attenuate further beta-cell destruction when beta-cell mass was relatively well preserved.

Identification and quantification of seed carotenoids in selected wheat species.

Selected primitive and modern wheat species were evaluated on the basis of their carotenoid composition and effects of the genotype and environment on lutein using spectrometry and liquid chromatography. Carotenoids in the wheat extracts were identified and confirmed on the basis of their UV/vis and mass spectra compared with those of authentic standards. The protonated molecule (M + 1)+ at m/z 569 was the predominant ion for zeaxanthin compared to the fragment ion at m/z 551 for lutein. A similar carotenoid profile was obtained for the wheat species investigated, but significant differences were observed in the concentration of carotenoids. Einkorn (Triticum monococcum) exhibited the highest level of all-trans-lutein, averaging 7.41 microg/g with small amounts of all-trans-zeaxanthin, cis-lutein isomers, and beta-carotene. Durum, Kamut, and Khorasan (Triticum turgidum) had intermediate levels of lutein (5.41-5.77 microg/g), while common bread or pastry wheat (Triticum aestivum) had the lowest content (2.01-2.11 microg/g). Lutein in einkorn appeared to be influenced significantly by environmental growing conditions.