The relationship between changes in retinal vessel morphology and the onset and progression of diseases such as diabetes, hypertension and retinopathy of prematurity (ROP) has been the subject of several large scale clinical studies. However, the difficulty of quantifying changes in retinal vessels in a sufficiently fast, accurate and repeatable manner has restricted the application of the insights gleaned from these studies to clinical practice. This paper presents a novel algorithm for the efficient detection and measurement of retinal vessels, which is general enough that it can be applied to both low and high resolution fundus photographs and fluorescein angiograms upon the adjustment of only a few intuitive parameters. Firstly, we describe the simple vessel segmentation strategy, formulated in the language of wavelets, that is used for fast vessel detection. When validated using a publicly available database of retinal images, this segmentation achieves a true positive rate of 70.27%, false positive rate of 2.83%, and accuracy score of 0.9371. Vessel edges are then more precisely localised using image profiles computed perpendicularly across a spline fit of each detected vessel centreline, so that both local and global changes in vessel diameter can be readily quantified. Using a second image database, we show that the diameters output by our algorithm display good agreement with the manual measurements made by three independent observers. We conclude that the improved speed and generality offered by our algorithm are achieved without sacrificing accuracy. The algorithm is implemented in MATLAB along with a graphical user interface, and we have made the source code freely available.

Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased retinal arteriolar tone during diabetes remain unclear. Normally, local Ca ²⁺ release events (Ca ²⁺ -sparks), trigger the activation of large-conductance Ca ²⁺ -activated K ⁺ (BK)-channels which hyperpolarize and relax vascular smooth muscle cells, thereby causing vasodilatation. In the present study, we examined BK channel function in retinal vascular smooth muscle cells from streptozotocin-induced diabetic rats. The BK channel inhibitor, Penitrem A, constricted nondiabetic retinal arterioles (pressurized to 70mmHg) by 28%. The BK current evoked by caffeine was dramatically reduced in retinal arterioles from diabetic animals even though caffeine-evoked [Ca ²⁺ ] _i release was unaffected. Spontaneous BK currents were smaller in diabetic cells, but the amplitude of Ca ²⁺ -sparks was larger. The amplitudes of BK currents elicited by depolarizing voltage steps were similar in control and diabetic arterioles and mRNA expression of the pore-forming BKα subunit was unchanged. The Ca ²⁺ -sensitivity of single BK channels from diabetic retinal vascular smooth muscle cells was markedly reduced. The BKβ1 subunit confers Ca ²⁺ -sensitivity to BK channel complexes and both transcript and protein levels for BKβ1 were appreciably lower in diabetic retinal arterioles. The mean open times and the sensitivity of BK channels to tamoxifen were decreased in diabetic cells, consistent with a downregulation of BKβ1 subunits. The potency of blockade by Pen A was lower for BK channels from diabetic animals. Thus, changes in the molecular composition of BK channels could account for retinal hypoperfusion in early diabetes, an idea having wider implications for the pathogenesis of diabetic hypertension.

A study has been made of the action of adenosine on surface slices of guinea‐pig olfactory cortex in vitro. With extracellular recordings from the pial surface and stimulation of the presynaptic input, the lateral olfactory tract (LOT) generated a monosynaptic negative wave representing dendritic excitatory potentials. This negative wave was depressed by bath application of 1 μm adenosine with increasing effect up to 1 mm. Adenosine 5′‐triphosphate (ATP), adenosine 5′‐monophosphate (AMP) and cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) had similar depressant actions. Adenine and guanosine were very weak depressants. Theophylline concentrations in the range 10 μm to 3 mm progressively antagonized the action of adenosine. Dibutyryl cyclic AMP (100 μm) and agents which increase intracellular cyclic AMP were not depressants, suggesting that the action of adenosine was not cyclic AMP‐mediated. Intracellular recordings confirmed the depressant effect of adenosine on excitatory potentials generated by LOT stimulation and also showed that postsynaptic action potentials and the membrane of the soma were unaffected by adenosine. Since presynaptic action potentials were also unaffected by adenosine, these experiments suggest that adenosine reduces excitatory transmission at LOT synapses and fortifies the idea that adenosine has a ‘neurohumoral’ action.

Smoking and asbestos exposure are important risks for lung cancer. Several epidemiological studies have linked asbestos exposure and smoking to lung cancer. To reconcile and unify these results, we conducted a systematic review and meta-analysis to provide a quantitative estimate of the increased risk of lung cancer associated with asbestos exposure and cigarette smoking and to classify their interaction. Five electronic databases were searched from inception to May, 2015 for observational studies on lung cancer. All case-control (N = 10) and cohort (N = 7) studies were included in the analysis. We calculated pooled odds ratios (ORs), relative risks (RRs) and 95% confidence intervals (CIs) using a random-effects model for the association of asbestos exposure and smoking with lung cancer. Lung cancer patients who were not exposed to asbestos and non-smoking (A-S-) were compared with; (i) asbestos-exposed and non-smoking (A+S-), (ii) non-exposure to asbestos and smoking (A-S+), and (iii) asbestos-exposed and smoking (A+S+). Our meta-analysis showed a significant difference in risk of developing lung cancer among asbestos exposed and/or smoking workers compared to controls (A-S-), odds ratios for the disease (95% CI) were (i) 1.70 (A+S-, 1.31–2.21), (ii) 5.65; (A-S+, 3.38–9.42), (iii) 8.70 (A+S+, 5.8–13.10). The additive interaction index of synergy was 1.44 (95% CI = 1.26–1.77) and the multiplicative index = 0.91 (95% CI = 0.63–1.30). Corresponding values for cohort studies were 1.11 (95% CI = 1.00–1.28) and 0.51 (95% CI = 0.31–0.85). Our results point to an additive synergism for lung cancer with co-exposure of asbestos and cigarette smoking. Assessments of industrial health risks should take smoking and other airborne health risks when setting occupational asbestos exposure limits.

Background: Medication non-adherence in ambulatory care has received substantial attention in the literature, but less so as it affects acute care. Accordingly, we aimed to estimate the frequency with which non-adherence to medication contributes to hospital admissions. Methods: We searched the Cochrane Library, EMBASE, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts and PubMed (until December 2017) to identify prospective observational studies that examined prevalence rates of hospital admissions associated with medication non-adherence. A quality assessment was performed using an expanded Crombie checklist. Data extraction covered patterns, circumstances, and patient and other key characteristics of non-adherence. Pooled estimates were obtained using a random-effect model. Results: Of 24 included studies, 8 were undertaken in North America, 7 from Europe, 6 from Asia and 3 from Australia. Most studies (79%) were rated as low risk of bias. All but three studies used combination measures to detect non-adherence, but approaches to assess preventability varied considerably. Across the studies, there was high heterogeneity among prevalence estimates (χ²=548, df 23, p<0.001, I²=95.8%). The median prevalence rate of hospital admissions associated with non-adherence was 4.29% (IQR 3.22%–7.49%), with prevalence rates ranging from 0.72% to 10.79%. By definition, almost all of these admissions were considered preventable. The underlying causes contributing to these admissions included medication cost and side effects, and non-adherence most often involved cardiovascular medicines. Conclusions: Hospital admissions associated with non-adherence to medication are a common problem. This systematic review highlights important targets for intervention. Greater attention could be focused on adherence to medication during the hospital stay as part of an enhanced medication reconciliation process. Standardisation in study methods and definitions is needed to allow future comparisons among settings; future studies should also encompass emerging economies.