Defective trained immunity in patients with STAT-1-dependent chronic mucocutaneaous candidiasis.

Patients with signal transducer and activator of transcription-1 (STAT1)-dependent chronic mucocutaneous candidiasis (CMC) and patients with STAT3-dependent hyper-immunoglobulin (Ig)E syndrome (HIES) display defects in T helper type 17 (Th17) cytokine production capacity. Despite this similar immune defect in Th17 function, they show important differences in the type of infections to which they are susceptible. Recently, our group reported differential regulation of STAT-1 and STAT-3 transcription factors during epigenetic reprogramming of trained immunity, an important host defence mechanism based on innate immune memory. We therefore hypothesized that STAT1 and STAT3 defects have different effects on trained immunity, and this may partly explain the differences between CMC and HIES regarding the susceptibility to infections. Indeed, while trained immunity was normally induced in cells isolated from patients with HIES, the induction of innate training was defective in CMC patients. This defect was specific for training with Candida albicans, the main pathogen encountered in CMC, and it involved a type II interferon-dependent mechanism. These findings describe the role of STAT-1 for the induction of trained immunity, and may contribute to the understanding of the differences in susceptibility to infection between CMC and HIES patients. This study could also provide directions for personalized immunotherapy in patients suffering from these immunodeficiencies.

Cumulative glycaemia as measured by lens fluorometry: association with retinopathy in type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to assess the association between lifelong cumulative glycaemia estimated by lens fluorometry and the presence of retinopathy in individuals with type 2 diabetes. METHODS: We carried out a cross-sectional population-based study of 970 participants aged between 30 and 60 years, of which 170 were diagnosed with diabetes on screening (WHO 1999 criteria) and 35 had known type 2 diabetes. Procedures included clinical and laboratory examinations, non-invasive assessment of the intrinsic fluorescence of the lens of the eye, and seven-field fundus photography. RESULTS: Retinopathy was found in 46 (22%) of 205 participants with type 2 diabetes. In a logistic regression analysis controlling for age, sex and diabetes status (screen-detected or known), a two-fold increase in lens fluorescence increased the odds for retinopathy by 3.46 (95% CI 1.25-9.55, p = 0.017). The association was marginally significant (OR 3.00 [95% CI 1.00-9.01], p = 0.050) when also adjusted for smoking, systolic blood pressure, body mass index and HbA(1c). CONCLUSIONS/INTERPRETATION: Diabetic retinopathy was related to cumulative lifelong glycaemia as estimated by lens fluorometry in participants with type 2 diabetes. This supports the hypothesis that retinopathy is a marker of lifelong elevated glycaemia as well as of the unknown, pre-diagnostic duration of type 2 diabetes. The powerful association between lens fluorescence and retinopathy underscores the importance of strict long-term glycaemic control in the prevention of retinopathy in people with diabetes.

Straight versus tortuous retinal arteries in relation to blood pressure and genetics.

BACKGROUND/AIMS: To assess the relative influence of genetic and environmental factors on retinal arterial tortuosity and the association between tortuosity and various health indices in healthy young to middle-aged persons. METHODS: This cross-sectional study included 57 monozygotic and 52 dizygotic same-sex healthy twin pairs, aged 20 to 46 years, who were characterised by determination of retinal vessel diameters, arterial blood pressure, blood glucose, body mass index, smoking habits and retinal arterial tortuosity, using a three-level grading scale (straight, wavy, tortuous). Heritability of retinal arterial tortuosity was estimated using structural equation modelling. RESULTS: Of 218 subjects, 79 (36.2%) had straight retinal arteries, 110 (50.5%) had wavy arteries, and 29 (13.3%) had tortuous arteries. Heritability of tortuosity was 82% (CI(95 )64, 92%), with unshared environmental factors accounting for the remaining 18% (CI(95 )8, 36%). Increasing values of mean arterial blood pressure and body mass index were both associated with decreasing levels of retinal arterial tortuosity. CONCLUSION: There was a large variation in tortuosity of retinal arteries in these healthy subjects and the predominant determinant was genetic influence, accounting for 82% of the observed variation in tortuosity.

Model predictive control as a tool for improving the process operation of MSW combustion plants.

In this paper a feasibility study is presented on the application of the advanced control strategy called model predictive control (MPC) as a tool for obtaining improved process operation performance for municipal solid waste (MSW) combustion plants. The paper starts with a discussion of the operational objectives and control of such plants, from which a motivation follows for applying MPC to them. This is followed by a discussion on the basic idea behind this advanced control strategy. After that, an MPC-based combustion control system is proposed aimed at tackling a typical MSW combustion control problem and, using this proposed control system, an assessment is made of the improvement in performance that an MPC-based MSW combustion control system can provide in comparison to conventional MSW combustion control systems. This assessment is based on simulations using an experimentally obtained process and disturbance model of a real-life large-scale MSW combustion plant.

Lens fluorescence and metabolic control in type 1 diabetic patients: a 14 year follow up study.

BACKGROUND/AIMS: In this prospective study the authors followed the post-translational modification of the proteins of the lens of the eye by fluorometry over a period of 14 years in patients with type 1 diabetes mellitus. METHODS: Twenty patients were examined at 6 years (baseline) and 20 years (follow up) after onset of diabetes mellitus. Glycaemic levels were assessed from HbA1c measured at regular intervals from the onset of diabetes mellitus. RESULTS: Lens fluorescence at follow up was significantly related to mean HbA1c during the study period and to lens fluorescence at baseline (p<0.0001). Sixty per cent of the variation in rate of increase in lens fluorescence during the study period was statistically attributable to glycaemia levels. CONCLUSION: The results confirm that the rate of fluorophore accumulation in the lens of adult diabetic patients is increased in proportion to glycaemic control. This parameter alone is, however, not sufficient to explain the entire variation in lens fluorophore accumulation. Consequently, lens fluorescence must be influenced by other factors before initiation and during the study period, and possibly even before onset of diabetes mellitus. The underlying mechanism could be a variation in susceptibility to lens protein denaturation by glycation.

Lens ageing as an indicator of tissue damage associated with smoking and non-enzymatic glycation--a twin study.

AIMS/HYPOTHESIS: With ageing the long-lived proteins of the human lens undergo denaturation by non-enzymatic glycation. The denaturated proteins are fluorescent, a property that can be assessed in vivo by fluorometry. Our aim was to examine the relative contribution of hereditary and environmental effects on the accumulation of fluorescent compounds in the lens. METHODS: We examined 59 monozygotic and 55 dizygotic healthy twin pairs recruited from a population-based register of twins. Lens autofluorescence was measured on the undilated eye. All subjects underwent an OGTT and information on smoking habits was obtained. The genetic and environmental effects were estimated by structural equation modelling. RESULTS: Lens autofluorescence was related to age (R(2)=53%), current glucose homeostasis (R(2)=10%) and smoking habits (R(2)=10%). After adjusting for these factors, interindividual variation in lens autofluorescence was statistically attributable to hereditary factors by approximately 28% as well as shared environment by 58% and non-shared environment by 14%. The hereditary factor seems not to be linked to a genetic predisposition to diabetes. CONCLUSION/INTERPRETATION: The correlation in lens fluorescence was greater in monozygotic twins than dizygotic twins indicating a genetically predetermined susceptibility for the accumulation of fluorophores in the lens, the relative importance of which was found to increase with age. Since fluorophore formation in the lens is attributable to non-enzymatic glycation our results support that genetic characteristics to some degree determine the susceptibility to glycation related diabetes complications and ageing processes.

Monofocal outer retinitis associated with hand, foot, and mouth disease caused by coxsackievirus.

PURPOSE: To report symptoms and signs from an otherwise healthy man with photopsia and monofocal outer retinitis occurring 3 days after the onset of hand, foot, and mouth disease. METHOD: Case report. RESULTS: Ophthalmic examination revealed a single circumscribed area of pigment epithelial mottling in the left eye and a corresponding nonarcuate absolute scotoma. Fluorescein angiography demonstrated attenuation of the retinal pigment epithelium. Serologic tests at 1 month after the onset disclosed serum antibody to enterovirus. CONCLUSION: The close association between the cutaneous eruption and the onset of visual symptoms suggests that the retinal lesion was caused by coxsackievirus infection.

Diabetic versus non-diabetic colour vision after cataract surgery.

AIMS: To examine whether the colour vision abnormalities found in phakic patients with diabetes mellitus is preserved after removal of the lens by cataract surgery. METHODS: 21 diabetic (16 IDDM and five NIDDM) and 19 non-diabetic patients of comparable age, postoperative visual acuity, and sex distribution, all aphakic or pseudophakic following cataract surgery, had their monocular colour vision examined using the Farnsworth-Munsell 100 hue test. The fundus status of the diabetic patients ranged from no retinopathy to photocoagulation treated proliferative diabetic retinopathy. Patients with macular oedema were specifically excluded from the study. RESULTS: The error scores of both the diabetic (mean 146 (SD 94)) and the non-diabetic patients (83 (79)) did not deviate significantly from the age related normal range. The error score in the diabetic group was significantly higher than in the non-diabetic group (p=0.02) but the amplitude of the difference was small in comparison with previous studies of phakic subjects. The error scores in the diabetic group were not correlated with the degree of retinopathy (p>0.2). CONCLUSION: After cataract surgery only a minor difference exists between the colour vision scores of diabetic and non-diabetic patients. This indicates that accelerated yellowing of the lens in diabetes is the predominant cause of the colour vision anomaly found in phakic diabetic patients.

Sick sinus syndrome cured by ... vitamin D?

I have presented the case of a 77-year-old woman with SSS who was treated unsuccessfully with antiarrhythmic drugs for 5 years. During the fifth year, she developed chronic atrial fibrillation. Two years later she started to take vitamin D for unrelated reasons, and first regained regular sinus rhythm and later stopped having episodes of atrial fibrillation. The patient has been now asymptomatic for over 2 years.

Arthrography of the shoulder after operative repair of the torn rotator cuff.

Double-contrast shoulder arthrograms were performed in 20 patients at an average of 30 months after operative repair of a torn rotator cuff. In 18 out of 20 shoulders the contrast medium leaked into the subacromial bursa indicating a defect in the rotator cuff. Despite this, 17 patients had complete relief of pain and 15 had a full range of shoulder elevation. The results suggest that a completely watertight closure is not essential for a good functional result, and that arthrography may not be helpful in the investigation of failure of repair.

Operative treatment of chronic ruptures of the rotator cuff of the shoulder.

The results of 63 operative repairs of chronic tears of the rotator cuff in 61 patients are reviewed retrospectively; the mean follow-up was 32.7 months. Fifty-four patients presented with symptoms of persistent pain and seven patients with gross loss of movement. All the patients had failed to respond to conservative treatment. Results were assessed in terms of relief of pain, restoration of movement, the patients' ability to return to work and whether they were satisfied with the results. Overall, a good result in terms of relief of pain was achieved in 40 shoulders. In 31 shoulders (30 with pain and one without pain) the operation included particular measures to decompress the subacromial space; 26 of the patients achieved relief of pain which was significantly better than in those patients whose operation did not include a decompression. The complications and failures are discussed. It is suggested that operative repair of the chronically torn rotator cuff of the shoulder is a worthwhile operation and that the operation should include an adequate decompression of the subacromial space.

Hip adduction/abduction deformity and apparent leg-length inequality.

The amount of apparent leg-length inequality attributable to given angles of hip adduction/abduction has been expressed quantitatively. The inequality is related to the sine of the angle of adduction/abduction and the distance between the centers of the femoral heads. In a study of 50 adults, the mean figure for this distance in men and women was 18.6 cm. As a rough guide, each 10 degrees of deformity up to 40 degrees produce approximately 3 cm of inequality.

Disruption of the acromioclavicular joint: surgical anatomy and biological reconstruction.

The pathological anatomy of acromioclavicular joint disruption is discussed in the light of operative findings. A method of repairing the dislocated joint is described using the coraco-acromial ligament and temporary internal fixation. It has been found to be useful in those patients who present late with pain and symptoms of instability.