Diabetes confers a two times excess risk of cardiovascular disease, yet predicting individual risk remains challenging. The effect of total microvascular disease burden on cardiovascular disease risk ...among individuals with diabetes is unknown.
A population-based cohort of patients with type 2 diabetes from the UK Clinical Practice Research Datalink was studied (n=49 027). We used multivariable Cox models to estimate hazard ratios (HRs) for the primary outcome (the time to first major cardiovascular event, which was a composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischaemic stroke) associated with cumulative burden of retinopathy, nephropathy, and peripheral neuropathy among individuals with no history of cardiovascular disease at baseline.
During a median follow-up of 5·5 years, 2822 (5·8%) individuals experienced a primary outcome. After adjustment for established risk factors, significant associations were observed for the primary outcome individually for retinopathy (HR 1·39, 95% CI 1·09-1·76), peripheral neuropathy (1·40, 1·19-1·66), and nephropathy (1·35, 1·15-1·58). For individuals with one, two, or three microvascular disease states versus none, the multivariable-adjusted HRs for the primary outcome were 1·32 (95% CI 1·16-1·50), 1·62 (1·42-1·85), and 1·99 (1·70-2·34), respectively. For the primary outcome, measures of risk discrimination showed significant improvement when microvascular disease burden was added to models. In the overall cohort, the net reclassification index for USA and UK guideline risk strata were 0·036 (95% CI 0·017-0·055, p<0·0001) and 0·038 (0·013-0·060, p<0·0001), respectively.
The cumulative burden of microvascular disease significantly affects the risk of future cardiovascular disease among individuals with type 2 diabetes. Given the prevalence of diabetes globally, further work to understand the mechanisms behind this association and strategies to mitigate this excess risk are warranted.
Circulation Foundation.
We present evidence that in ~ 1650 BCE (~ 3600 years ago), a cosmic airburst destroyed Tall el-Hammam, a Middle-Bronze-Age city in the southern Jordan Valley northeast of the Dead Sea. The proposed ...airburst was larger than the 1908 explosion over Tunguska, Russia, where a ~ 50-m-wide bolide detonated with ~ 1000× more energy than the Hiroshima atomic bomb. A city-wide ~ 1.5-m-thick carbon-and-ash-rich destruction layer contains peak concentrations of shocked quartz (~ 5-10 GPa); melted pottery and mudbricks; diamond-like carbon; soot; Fe- and Si-rich spherules; CaCO
spherules from melted plaster; and melted platinum, iridium, nickel, gold, silver, zircon, chromite, and quartz. Heating experiments indicate temperatures exceeded 2000 °C. Amid city-side devastation, the airburst demolished 12+ m of the 4-to-5-story palace complex and the massive 4-m-thick mudbrick rampart, while causing extreme disarticulation and skeletal fragmentation in nearby humans. An airburst-related influx of salt (~ 4 wt.%) produced hypersalinity, inhibited agriculture, and caused a ~ 300-600-year-long abandonment of ~ 120 regional settlements within a > 25-km radius. Tall el-Hammam may be the second oldest city/town destroyed by a cosmic airburst/impact, after Abu Hureyra, Syria, and possibly the earliest site with an oral tradition that was written down (Genesis). Tunguska-scale airbursts can devastate entire cities/regions and thus, pose a severe modern-day hazard.
Magnesium and its alloys are ideal candidates for bioabsorbable implants. However, they can dissolve too rapidly in the human body for most applications. In this research, high purified magnesium ...(HP-Mg) was coated with stearic acid (SA) to slow the corrosion rate of magnesium in simulated body fluid at 37 ± 1 °C. HP-Mg was anodized (AC and DC voltages) to form an oxide/hydroxide layer, and then it was immersed in a SA solution. The SA coated layer surface, anodized layer, and the thickness of the oxide/hydroxide layer were investigated with Scanning Electron Microscopy (SEM). Electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization (PDP) were used to estimate the corrosion rate of HP-Mg specimens. The results confirm that the hydrophobic coating can decrease the corrosion rate of HP-Mg by more than 1000x. The protectiveness of coated layer for anodized specimens with AC voltage continue for 2 and 3 weeks. For the HP-Mg coated anodized with DC voltage, the coated layer could improve the corrosion resistance for only a few days.
Evidence from clinical and laboratory investigations into the causes of diverticular disease suggests that disturbances in cholinergic activity are important, the effector mechanisms of which have ...yet to be established. We aimed to investigate the role of smooth muscle and neural cholinergic activity in the pathogenesis of this disease.
Two investigators independently did a blinded immunohistochemical image analysis of localising antibodies to choline acetyltransferase, co-localised with protein gene product (PGP)—a marker of general neural tissue—and smooth muscle muscarinic M3 receptors, on three histological sections of sigmoid colons from ten patients with diverticular disease and ten controls, after resections for rectal tumours. We also did isotonic organ bath experiments to assess muscle strip sensitivities to exogenous acetylcholine.
In circular muscle, activity of choline acetyltransferase was lower in patients with diverticular disease than in controls: median percentage surface area of choline acetyltransferase over PGP was 17·5% (range 10·0–37·0) in patients with diverticular disease and 47·0% (29·0–54·0) in controls (p < 0·0001). M3 receptors were upregulated in patients with diverticular disease compared with controls: the median surface area was 13·2% (6·0–23·3) in patients with diverticular disease and 2·5% (1·6–3·7) in controls (p < 0·0001). The sensitivity to exogenous acetylcholine was increased in patients with diverticular disease (mean -log EC
50 5·6 SD 0·3) compared with controls (4·9 0·5; difference 0·7 95% CI 0·3–1·1, p=0·006). In longitudinal muscle, choline acetyltransferase activity was lower in patients with diverticular disease (median 19·5%, range 12·0–30·0) than in controls (47·0%, 35·0–60·0; p < 0·0001), with upregulation of M3 receptors in diverticular disease (diverticular disease 7·8% 1·9–20·4, controls 1·7% 0·8–3·0; p < 0·0001). However, sensitivity to exogenous acetylcholine did not differ between the two groups (diverticular disease mean 5·6% SD 0·3, controls 5·2% 0·4; difference 0·4% 95% CI −0·02–0·7, p=0·06).
Our results suggest that cholinergic denervation hypersensitivity can affect smooth muscle. Upregulation of smooth muscle M3 receptors might account for specific clinical, physiological, and pharmacological abnormalities associated with diverticular disease.
The addition of silicon carbide (SiC) nanoparticles into electroless nickel (Ni)-based coatings improves both corrosion resistance and mechanical properties of the resulting Ni-P/SiC nanocomposite ...coatings, making them potential candidate as protective coatings in aggressive environments. Ni-P/SiC nanocomposite coatings were produced from precursor bath with small SiC loading levels (0.25 or 1.0 g/L) and characterized for morphology, corrosion resistance, and hardness. Microstructural examination using FE-SEM and AFM revealed that incorporation of uniformly dispersed SiC nanoparticles leads to smaller nodule size with fine-grain structure and low surface roughness. Electrochemical impedance spectroscopy studies in 4 wt.% NaCl solution showed that the nanocomposite coatings exhibit excellent corrosion resistance, as indicated by high charge-transfer resistance and low double-layer capacitance values of ~137 kΩ cm
2
and 19 µF cm
−2
, respectively. The coatings maintained their structural integrity even after 5 days of saline bath immersion, as there was no cracking in the deposit microstructure besides formation of shallow pits and submicron-sized pores. A two-fold increase in the average hardness value was noticed from 4.5 (pure Ni-P) to 8.5 GPa (Ni-P/SiC coating) which can be ascribed to modified deposit morphology and uniformly dispersed SiC nanoparticles that act as obstacles to plastic deformation.
The library channel is often underappreciated as a key part of a publisher’s business strategy. In an age where publishers are constantly seeking new revenue and marketing opportunities, presence in ...the library—digitally—can yield significant growth. This paper examines the library channel, its business model based on library lending, the performance of eBooks and audiobooks across all subjects, and consumer reading behavior. Digital Book Clubs, a relatively new phenomenon, are also defined and illustrated with examples demonstrating the library’s valuable role in increasing discoverability and ultimately sales.
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Vasoactive intestinal peptide (VIP) has been demonstrated in intestinal mucosal neurones and elicits chloride secretion from enterocytes. These findings have led to the proposal that VIP is a ...secretomotor neurotransmitter. Confirmation of such a role may now be possible with the development of PG 97–269, a high‐affinity, selective antagonist of VIP type 1 (VPAC1) receptor, which is expressed by gut epithelial cells. We have evaluated the VIP antagonism and antisecretory potential of this novel compound using in vitro and in vivo models of intestinal secretion.
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Monolayers of the human colonic cell line (T84) and muscle‐stripped preparations of rat jejunum and human ileum were set up in Ussing chambers for recording of transepithelial resistance and short‐circuit current. Ussing chambers were modified to allow electrical stimulation of mucosal neurones. Effects of PG 97–269 on enterotoxin‐induced secretion were investigated in perfused rat jejunum in vivo.
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PG 97–269 competitively antagonised VIP in T84 monolayers. In rat jejunum and human ileum, responses to VIP were inhibited as were responses of rat jejunum to electrical stimulation of mucosal neurons.
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In perfused rat jejunum, PG 97–269 abolished the effects of VIP on fluid and electrolyte transport and attenuated cholera toxin and Escherichia coli heat labile toxin‐induced net fluid and electrolyte secretion.
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PG 97–269 is a competitive antagonist of enterocyte VIP receptors and effectively inhibits responses of rat and human intestinal mucosa to VIP. Antagonism of secretory responses to electrical stimulation of mucosal neurons and lumenal application of enterotoxins imply a secretory role for VIP in these processes.
British Journal of Pharmacology (2005) 144, 994–1001. doi:10.1038/sj.bjp.0706128
Ethnicity recording within primary care computerised medical record (CMR) systems is suboptimal, exacerbated by tangled taxonomies within current coding systems.Objective To develop a method for ...extending ethnicity identification using routinely collected data.
We used an ontological method to maximise the reliability and prevalence of ethnicity information in the Royal College of General Practitioner's Research and Surveillance database. Clinical codes were either directly mapped to ethnicity group or utilised as proxy markers (such as language spoken) from which ethnicity could be inferred. We compared the performance of our method with the recording rates that would be identified by code lists utilised by the UK pay for the performance system, with the help of the Quality and Outcomes Framework (QOF).
Data from 2,059,453 patients across 110 practices were included. The overall categorisable ethnicity using QOF codes was 36.26% (95% confidence interval (CI): 36.20%-36.33%). This rose to 48.57% (CI:48.50%-48.64%) using the described ethnicity mapping process. Mapping increased across all ethnic groups. The largest increase was seen in the white ethnicity category (30.61%; CI: 30.55%-30.67% to 40.24%; CI: 40.17%-40.30%). The highest relative increase was in the ethnic group categorised as the other (0.04%; CI: 0.03%-0.04% to 0.92%; CI: 0.91%-0.93%).
This mapping method substantially increases the prevalence of known ethnicity in CMR data and may aid future epidemiological research based on routine data.
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