Predictors of 25(OH)D half-life and plasma 25(OH)D concentration in The Gambia and the UK

Summary: Predictors of 25(OH)D3 half-life were factors associated with vitamin D metabolism, but were different between people in The Gambia and the UK. Country was the strongest predictor of plasma 25(OH)D concentration, probably as a marker of UVB exposure. 25(OH)D3 half-life may be applied as a tool to investigate vitamin D expenditure.  Introduction: The aim of this study was to investigate predictors of 25(OH)D3 half-life and plasma 25(OH)D concentration.  Methods: Plasma half-life of an oral tracer dose of deuterated-25(OH)D3 was measured in healthy men aged 24–39 years, resident in The Gambia, West Africa (n = 18) and in the UK during the winter (n = 18), countries that differ in calcium intake and vitamin D status. Plasma and urinary markers of vitamin D, calcium, phosphate and bone metabolism, nutrient intakes and anthropometry were measured.  Results: Normally distributed data are presented as mean (SD) and non-normal data as geometric mean (95 % CI). Gambian compared to UK men had higher plasma concentrations of 25(OH)D (69 (13) vs. 29 (11) nmol/L; P < 0.0001); 1,25(OH)2D (181 (165, 197) vs. 120 (109, 132) pmol/L; P < 0.01); and parathyroid hormone (PTH) (50 (42, 60) vs. 33 (27, 39); P < 0.0001). There was no difference in 25(OH)D3 half-life (14.7 (3.5) days vs. 15.6 (2.5) days) between countries (P = 0.2). In multivariate analyses, 25(OH)D, 1,25(OH)2D, vitamin D binding protein and albumin-adjusted calcium (Caalb) explained 79 % of variance in 25(OH)D3 half-life in Gambians, but no significant predictors were found in UK participants. For the countries combined, Caalb, PTH and plasma phosphate explained 39 % of half-life variability. 1,25(OH)2D, weight, PTH and country explained 81 % of variability in 25(OH)D concentration; however, country alone explained 74 %.  Conclusion: Factors known to affect 25(OH)D metabolism predict 25(OH)D3 half-life, but these differed between countries. Country predicted 25(OH)D, probably as a proxy measure for UVB exposure and vitamin D supply. This study supports the use of 25(OH)D half-life to investigate vitamin D metabolism

The spectral variability of FSRQs

The optical variability of 29 flat spectrum radio quasars in SDSS Stripe 82 region are investigated by using DR7 released multi-epoch data. All FSRQs show variations with overall amplitude ranging from 0.24 mag to 3.46 mag in different sources. About half of FSRQs show a bluer-when-brighter trend, which is commonly observed for blazars. However, only one source shows a redder-when-brighter trend, which implies it is rare in FSRQs. In this source, the thermal emission may likely be responsible for the spectral behavior.Comment: 4 pages, 1 figure, to be published in Journal of Astrophysics and Astronomy, as a proceeding paper of the conference "Multiwavelength Variability of Blazars", Guangzhou, China, September 22-24, 201

Surgical decisions in older women with early breast cancer: patient and disease factors.

BACKGROUND: Studies reporting lower rates of surgery for older women with early invasive breast cancer have focused on women with oestrogen receptor (ER)-positive tumours. This study examined the factors that influence receipt of breast surgery in older women with ER-positive and ER-negative early invasive breast cancer . METHODS: Women aged 50 years or above with unilateral stage 1-3A early invasive breast cancer diagnosed in 2014-2017 were identified from linked English and Welsh cancer registration and routine hospital data sets. Logistic regression analysis was used to evaluate the influence of tumour and patient factors on receipt of surgery. RESULTS: Among 83 188 women, 86.8 per cent had ER-positive and 13.2 per cent had ER-negative early invasive breast cancer. These proportions were unaffected by age at diagnosis. Compared with women with ER-negative breast cancer, a higher proportion of women with ER-positive breast cancer presented with low risk tumour characteristics: G1 (20.0 versus 1.5 per cent), T1 (60.8 versus 44.2 per cent) and N0 (73.9 versus 68.8 per cent). The proportions of women with any recorded co-morbidity (13.7 versus 14.3 per cent) or degree of frailty (25 versus 25.8 per cent) were similar among women with ER-positive and ER-negative disease respectively. In women with ER-positive early invasive breast cancer aged 70-74, 75-79 and 80 years or above, the rate of no surgery was 5.6, 11.0 and 41.9 per cent respectively. Among women with ER-negative early invasive breast cancer, the corresponding rates were 3.8, 3.7 and 12.3 per cent. The relatively lower rate of surgery for ER-positive breast cancer persisted in women with good fitness. CONCLUSION: The reasons for the observer differences should be further explored to ensure consistency in treatment decisions

Change in the Use of Fractionation in Radiotherapy Used for Early Breast Cancer at the Start of the COVID-19 Pandemic: A Population-Based Cohort Study of Older Women in England and Wales.

AIMS: Adjuvant radiotherapy is recommended for most patients with early breast cancer (EBC) receiving breast-conserving surgery and those at moderate/high risk of recurrence treated by mastectomy. During the first wave of COVID-19 in England and Wales, there was rapid dissemination of randomised controlled trial-based evidence showing non-inferiority for five-fraction ultra-hypofractionated radiotherapy (HFRT) regimens compared with standard moderate-HFRT, with guidance recommending the use of five-fraction HFRT for eligible patients. We evaluated the uptake of this recommendation in clinical practice as part of the National Audit of Breast Cancer in Older Patients (NABCOP). MATERIALS AND METHODS: Women aged ≥50 years who underwent surgery for EBC from January 2019 to July 2020 were identified from the Rapid Cancer Registration Dataset for England and from Wales Cancer Network data. Radiotherapy details were from linked national Radiotherapy Datasets. Multivariate mixed-effects logistic regression models were used to assess characteristics influential in the use of ultra-HFRT. RESULTS: Among 35 561 women having surgery for EBC, 71% received postoperative radiotherapy. Receipt of 26 Gy in five fractions (26Gy5F) increased from <1% in February 2020 to 70% in April 2020. Regional variation in the use of 26Gy5F during April to July 2020 was similar by age, ranging from 49 to 87% among women aged ≥70 years. Use of 26Gy5F was characterised by no known nodal involvement, no comorbidities and initial breast-conserving surgery. Of those patients receiving radiotherapy to the breast/chest wall, 85% had 26Gy5F; 23% had 26Gy5F if radiotherapy included regional nodes. Among 5139 women receiving postoperative radiotherapy from April to July 2020, nodal involvement, overall stage, type of surgery, time from diagnosis to start of radiotherapy were independently associated with fractionation choice. CONCLUSIONS: There was a striking increase in the use of 26Gy5F dose fractionation regimens for EBC, among women aged ≥50 years, within a month of guidance published at the start of the COVID-19 pandemic in England and Wales

Sister Mary Joseph's Nodule at a University Teaching Hospital in Northwestern Tanzania: A Retrospective Review of 34 cases.

Sister Mary Joseph's nodule is a metastatic tumor deposit in the umbilicus and often represents advanced intra-abdominal malignancy with dismal prognosis. There is a paucity of published data on this subject in our setting. This study was conducted to describe the clinicopathological presentation and treatment outcome of this condition in our environment and highlight challenges associated with the care of these patients, and to proffer solutions for improved outcome. This was a retrospective study of histologically confirmed cases of Sister Mary Joseph's nodule seen at Bugando Medical Centre between March 2003 and February 2013. Data collected were analyzed using descriptive statistics. A total of 34 patients were enrolled in the study. Males outnumbered females by a ratio of 1.4:1. The vast majority of patients (70.6%) presented with large umbilical nodule > 2 cm in size. The stomach (41.1%) was the most common location of the primary tumor. Adenocarcinoma (88.2%) was the most frequent histopathological type. Most of the primary tumors (52.9%) were poorly differentiated. As the disease was advanced and metastatic in all patients, only palliative therapy was offered. Out of 34 patients, 11 patients died in the hospital giving a mortality rate of 32.4%. Patients were followed up for 24 months. At the end of the follow-up period, 14(60.9%) patients were lost to follow-up and the remaining 9 (39.1%) patients died. Patients survived for a median period of 28 weeks (range, 2 to 64 weeks). The nodule recurred in 6 (26.1%) patients after complete excision. Sister Mary Joseph's nodule of the umbilicus is not rare in our environment and often represents manifestation of a variety of advanced intra-abdominal malignancies. The majority of the patients present at a late stage and many with distant metastases. The patient's survival is very short leading to a poor outcome. Early detection of primary cancer at an early stage may improve the prognosis

Mapping Helminth Co-Infection and Co-Intensity: Geostatistical Prediction in Ghana

Urinary schistosomiasis and hookworm infections cause considerable morbidity in school age children in West Africa. Severe morbidity is predominantly observed in individuals infected with both parasite types and, in particular, with heavy infections. We investigated for the first time the distribution of S. haematobium and hookworm co-infections and distribution of co-intensity of these parasites in Ghana. Bayesian geostatistical models were developed to generate a national co-infection map and national intensity maps for each parasite, using data on S. haematobium and hookworm prevalence and egg concentration (expressed as eggs per 10 mL of urine for S. haematobium and expressed as eggs per gram of faeces for hookworm), collected during a pre-intervention baseline survey in Ghana, 2008. In contrast with previous findings from the East Africa region, we found that both S. haematobium and hookworm infections are highly focal, resulting in small, localized clusters of co-infection and areas of high co-intensity. Overlaying on a single map the co-infection and the intensity of multiple parasite infections allows identification of areas where parasite environmental contamination and morbidity are at its highest, while providing an evidence base for the assessment of the progress of successive rounds of mass drug administration (MDA) in integrated parasitic disease control programs

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

Growth and Differentiation of the Larval Mosquito Midgut

Factors affecting larval growth and nutrition have consequences on adult fecundity. Since the mosquito larval midgut is the primary organ of digestion and nutrient absorption, factors that affect the growth and development of the midgut may have potential consequences on the reproductive potential of the adult. To gain a better understanding of mosquito midgut development the growth and metamorphic remodeling of the Aedes aegypti L. and Culex pipiens L. (Diptera: Culicidae) midguts were investigated. Cytological evidence was obtained suggesting that, in both the anterior and posterior Ae. aegypti larval midgut, diploid regenerative cells give rise to new endoreplicating cells that significantly contribute to the growth and metabolism of the midgut. This hypothesis was supported by BrdU incorporation studies showing that diploid cells, as well as large and small endoreplicating cells, synthesize DNA during the 2nd, 3rd and 4th instars. Cytological studies of the Cx. pipiens larval midgut suggest that anterior midgut growth in this species is primarily by cell enlargement. To study metamorphic remodeling of the midgut, DNA synthesis in Ae. aegypti 4th instar midguts was followed by using 5-bromo-2-deoxyuridine (BrdU) incorporation. During the 24 hr period after the last larval-larval molt both endoreplicating and diploid cells incorporate BrdU. After the critical weight is achieved, endoreplicating cell BrdU incorporation gradually ceases while diploid cells continue to replicate. The period of maximum diploid cell incorporation correlated with the period of maximum ecdysone titer