Restructuring of Pancreatic Islets and Insulin Secretion in a Postnatal Critical Window

Function and structure of adult pancreatic islets are determined by early postnatal development, which in rats corresponds to the first month of life. We analyzed changes in blood glucose and hormones during this stage and their association with morphological and functional changes of alpha and beta cell populations during this period. At day 20 (d20), insulin and glucose plasma levels were two- and six-fold higher, respectively, as compared to d6. Interestingly, this period is characterized by physiological hyperglycemia and hyperinsulinemia, where peripheral insulin resistance and a high plasmatic concentration of glucagon are also observed. These functional changes were paralleled by reorganization of islet structure, cell mass and aggregate size of alpha and beta cells. Cultured beta cells from d20 secreted the same amount of insulin in 15.6 mM than in 5.6 mM glucose (basal conditions), and were characterized by a high basal insulin secretion. However, beta cells from d28 were already glucose sensitive. Understanding and establishing morphophysiological relationships in the developing endocrine pancreas may explain how events in early life are important in determining adult islet physiology and metabolism

Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017) includes a comprehensive assessment of incidence, prevalence, and years lived with disability (YLDs) for 354 causes in 195 countries and territories from 1990 to 2017. Previous GBD studies have shown how the decline of mortality rates from 1990 to 2016 has led to an increase in life expectancy, an ageing global population, and an expansion of the non-fatal burden of disease and injury. These studies have also shown how a substantial portion of the world's population experiences non-fatal health loss with considerable heterogeneity among different causes, locations, ages, and sexes. Ongoing objectives of the GBD study include increasing the level of estimation detail, improving analytical strategies, and increasing the amount of high-quality data. Methods: We estimated incidence and prevalence for 354 diseases and injuries and 3484 sequelae. We used an updated and extensive body of literature studies, survey data, surveillance data, inpatient admission records, outpatient visit records, and health insurance claims, and additionally used results from cause of death models to inform estimates using a total of 68 781 data sources. Newly available clinical data from India, Iran, Japan, Jordan, Nepal, China, Brazil, Norway, and Italy were incorporated, as well as updated claims data from the USA and new claims data from Taiwan (province of China) and Singapore. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between rates of incidence, prevalence, remission, and cause of death for each condition. YLDs were estimated as the product of a prevalence estimate and a disability weight for health states of each mutually exclusive sequela, adjusted for comorbidity. We updated the Socio-demographic Index (SDI), a summary development indicator of income per capita, years of schooling, and total fertility rate. Additionally, we calculated differences between male and female YLDs to identify divergent trends across sexes. GBD 2017 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting. Findings: Globally, for females, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and haemoglobinopathies and haemolytic anaemias in both 1990 and 2017. For males, the causes with the greatest age-standardised prevalence were oral disorders, headache disorders, and tuberculosis including latent tuberculosis infection in both 1990 and 2017. In terms of YLDs, low back pain, headache disorders, and dietary iron deficiency were the leading Level 3 causes of YLD counts in 1990, whereas low back pain, headache disorders, and depressive disorders were the leading causes in 2017 for both sexes combined. All-cause age-standardised YLD rates decreased by 3·9% (95% uncertainty interval [UI] 3·1–4·6) from 1990 to 2017; however, the all-age YLD rate increased by 7·2% (6·0–8·4) while the total sum of global YLDs increased from 562 million (421–723) to 853 million (642–1100). The increases for males and females were similar, with increases in all-age YLD rates of 7·9% (6·6–9·2) for males and 6·5% (5·4–7·7) for females. We found significant differences between males and females in terms of age-standardised prevalence estimates for multiple causes. The causes with the greatest relative differences between sexes in 2017 included substance use disorders (3018 cases [95% UI 2782–3252] per 100 000 in males vs s1400 [1279–1524] per 100 000 in females), transport injuries (3322 [3082–3583] vs 2336 [2154–2535]), and self-harm and interpersonal violence (3265 [2943–3630] vs 5643 [5057–6302]). Interpretation: Global all-cause age-standardised YLD rates have improved only slightly over a period spanning nearly three decades. However, the magnitude of the non-fatal disease burden has expanded globally, with increasing numbers of people who have a wide spectrum of conditions. A subset of conditions has remained globally pervasive since 1990, whereas other conditions have displayed more dynamic trends, with different ages, sexes, and geographies across the globe experiencing varying burdens and trends of health loss. This study emphasises how global improvements in premature mortality for select conditions have led to older populations with complex and potentially expensive diseases, yet also highlights global achievements in certain domains of disease and injury

Perinatal development of the pancreatic islet microvasculature in rats

The aim of the present study was to investigate possible changes in the islet microvasculature during the period of pronounced β-cell growth seen perinatally in rats. We studied islet endothelial and β-cell proliferation, as well as islet vascular density, in rats during this period. There was a progressive increase in islet vascular density from day −1 to day 7 postpartum, with values similar to those in adult rats seen at the latter time point. 3H-thymidine-labelled islet endothelial cells were extremely rare in adult rats, whereas such cells were much more frequent perinatally. The β-cell labelling index was higher in all perinatal animals than in adult rats, with peak values seen on day 2. The proliferating endocrine cells were located very close to blood vessels at day 2 after birth. In conclusion, the pronounced growth of islet endocrine cells seen during the first week after birth coincides and co-localizes with an even more pronounced increase in islet endothelial cell proliferation, which results in a marked increase in intra-islet vascular density. This perinatal increase in islet blood vessel density may facilitate glucose sensing and islet hormonal delivery to the systemic circulation

The petrogenesis of sodic island arc magmas at Savo volcano, Solomon Islands

Savo, Solomon Islands, is a historically active volcano dominated by sodic, alkaline lavas, and pyroclastic rocks with up to 7.5 wt% Na2O, and high Sr, arc-like trace element chemistry. The suite is dominated by mugearites (plagioclase–clinopyroxene–magnetite ± amphibole ± olivine) and trachytes (plagioclase–amphibole–magnetite ± biotite). The presence of hydrous minerals (amphibole, biotite) indicates relatively wet magmas. In such melts, plagioclase is relatively unstable relative to iron oxides and ferromagnesian silicates; it is the latter minerals (particularly hornblende) that dominate cumulate nodules at Savo and drive the chemical differentiation of the suite, with a limited role for plagioclase. This is potentially occurring in a crustal “hot zone”, with major chemical differentiation occurring at depth. Batches of magma ascend periodically, where they are subject to decompression, water saturation and further cooling, resulting in closed-system crystallisation of plagioclase, and ultimately the production of sodic, crystal and feldspar-rich, high-Sr rocks. The sodic and hydrous nature of the parental magmas is interpreted to be the result of partial melting of metasomatised mantle, but radiogenic isotope data (Pb, Sr, Nd) cannot uniquely identify the source of the metasomatic agent. Electronic supplementary material The online version of this article (doi:10.1007/s00410-009-0410-9) contains supplementary material, which is available to authorized users

Experimental loss of menisci, cartilage and subchondral bone gradually increases anteroposterior knee laxity

Purpose: Anteroposterior knee stability is a relevant factor for the decision-making process of various surgical procedures. In degenerative joints when the implantation of unicompartimental prostheses or corrective osteotomies of the limb are planned, the integrity of the anteroposterior stability with an intact ACL has been regarded as a necessary prerequisite. We hypothesise that joint degeneration, however, may influence the anteroposterior knee laxity. Therefore, we set out to test this hypothesis simulating a progressively ‘degenerated’ joint in an experimental cadaveric setting. Methods: Twelve intact transfemorally resected Thiel-fixated cadaver knee joints were divided into 2 groups for manipulation in the medial or lateral compartment. In each knee, we performed (1) unilateral total meniscectomy; (2) simulation of advanced osteoarthritis, by unilateral total cartilage debridement; (3) simulation of a unilateral tibial impression fracture, by resection of 5 mm of the tibial plateau; (4) transection of the ACL. The KT-1000 arthrometer was used to measure the extent of anteroposterior translation at 30° of knee flexion. Results: The mean value for tibial anteroposterior translation before intervention was 3.2 mm (SD: ±0.8). The mean translation after each intervention was 4.6 mm (SD: ±0.9; +44%; n.s.) after meniscectomy, 5.9 mm (SD: ±1.5; +84%; P < 0.05) after cartilage debridement, 8 mm (SD: ±1.5; +150%; P < 0.01) after bone debridement, and finally 9.7 mm (SD: ±2.2; +203%; P < 0.05) after resection of the ACL. There were no significant differences between the medial and lateral compartment. Conclusion: In absence of massive osteophytes or capsular shrinkage, rapid loss of meniscus, cartilage and particularly loss of subchondral bone may result in a massive increase in anteroposterior translation, mimicking a tear of the ACL. In such a situation, a false positive impression of a ligamentous injury may arise, and decision making is falsely directed away from totally or partially knee joint-preserving procedures. Therefore, in degenerate joints, clinical evaluation of anteroposterior stability should rather rely on the presence of a firm stop than an overall increased joint translation

Effects of Soil Temperature and Nitrogen Status on Kinetics of 15NO3 Uptake by Roots of Field-grown Agropyron Desertorum

Plant NO8‐ acquisition is largely determined by root uptake capacity. Although root uptake capacity has been shown to be sensitive to both root temperature and previous nitrogen (N) supply in hydroponic systems, the uptake capacity response to similar environmental factors under field conditions has not been investigated. Using 15NO3−, root uptake capacities were determined in excised roots of Agropyron desertorum (Fisch. ex Link) Schult grown in the field at two soil temperatures and two N fertilization treatments. Variation in soil and root temperatures was achieved by application of clear plastic film or insulating mulch to the soil immediately around the target plants. Uptake rates were measured at six different assay solution concentrations (from 1 to 1000 μM external 15NO3− concentration range). Two months after the imposition of soil N and temperature treatments, a biphasic transport system (a high‐affinity) saturable phase and a low‐affinity transport phase) was apparent in low N‐treated plants. Nitrate uptake capacity in the low‐concentration range (1–500μM) was significantly reduced in N‐fertilized plants compared with unfertilized control plants and the effect was more pronounced at high (27 °C) than low (17 °C) soil and assay temperatures. Furthermore, high soil N status inhibited the expression of a low‐affinity NO3− transport system which was clearly apparent at external NO3− concentration ranges between 500 and 1000 mM in plants grown at low soil N. Prior soil N and temperature history may ultimately determine root ability to exploit NO3− flushes which can result from changes in soil environmental conditions