Markedly decreasing incidence of cause-specific blindness in Saxony (Eastern Germany).

PURPOSE: To analyze the recent time trend in Saxony. METHODS: Data were based on administrative files in Saxony (Eastern Germany) to assess recipients of blindness allowance newly registered between January 1, 2009, and December 31, 2017. We estimated age-sex standardized incidence of all-cause and cause-specific blindness and used Poisson regression to examine age- and sex-adjusted time trends. RESULTS: We identified 5114 new cases of blindness (63.3% female, 59.9% ≥ 80 years). We observed a markedly decrease in incidence of blindness: all-causes 2009: 15.7 per 100,000 person years [95% confidence interval: 14.6-17.0]; 2017: 8.9 [8.1-9.8]; age-related macular degeneration 2009: 6.9 [6.1-7.7], 2017: 3.8 [3.3-4.3]; glaucoma 2009: 2.6 [2.2-3.1], 2017: 1.8 [1.4-2.2]; diabetic retinopathy 2009: 1.5 [1.2-1.9], 2017: 0.7 [0.5-1.0]; myopia 2009: 0.7 [0.5-1.1], 2017: 0.4 [0.2-0.5]; optic atrophy 2009: 0.9 [0.6-1.2], 2017: 0.5 [0.3-0.7]; and cataract 2009: 0.5 [0.3-0.8], 2017: 0.1 [0.1-0.3]. The annual reduction was between 5 (glaucoma, relative risk 0.95 [0.92-0.98]) and 16% (cataract, relative risk 0.84 [0.78-0.91]). CONCLUSION: The age- and sex-standardized incidence of blindness decreased among all common causes of blindness in Saxony in the last decade.

Consequences of long-term oral corticosteroid therapy and its side-effects in severe asthma in adults: a focused review of the impact data in the literature.

This review provides an overview of the role of long-term treatment of severe asthma with oral corticosteroids (OCS) and its associated side-effects in adults. It is based on a systematic literature search conducted in MEDLINE, Embase and the Cochrane Library to identify relevant studies. After a short overview of severe asthma and its treatment we present studies showing a dose-response relationship in asthmatic patients treated with OCS and then consider by organ systems the undesired effects demonstrated in clinical and epidemiological studies in patients with OCS-dependent asthma. It was found that the risk of developing various OCS-related complications, including infections, diabetes and osteoporosis as well as psychiatric disorders, was higher for patients with long-term exposure to OCS compared with control groups. In addition, studies showed a significant increase in healthcare resource utilisation due to OCS treatment. Therefore, it is incumbent on every clinician to carefully weigh the potential benefit of preventing loss of asthma control against this risk before opting to prescribe long-term OCS therapy. Effective corticosteroid-sparing strategies must be used and should aim at short-term use with the lowest effective dose and start tapering as soon as possible until OCS therapy is terminated.

A randomised, controlled trial of self-monitoring of blood glucose in patients with type 2 diabetes receiving conventional insulin treatment.

AIMS/HYPOTHESIS: We evaluated whether self-monitoring of blood glucose (SMBG) leads to better glycaemic control (HbA(1c)) in patients with type 2 diabetes on conventional insulin regimens. METHODS: Patients with type 2 diabetes on a conventional insulin regimen (basal or premixed insulin with or without additional oral glucose-lowering agents) were recruited at study centres led by members of the German Diabetes Association. In a randomised, prospective, open 2 × 2 factorial design, the once-weekly performance of four-point glucose profiles (SMBG +; n = 151 patients) was compared with no SMBG (SMBG -; n = 149), and the measuring and transmitting of HbA1c results to the study centres (HbA(1c) +; n = 158, of these 82 SMBG - and 76 SMBG +) was compared with HbA1c measurement without disclosure of results (HbA(1c) -; n = 142, of these 67 SMBG - and 75 SMBG +). Randomised allocation was carried out by a central office, using sequentially numbered, sealed envelopes. The primary endpoint was the reduction of HbA(1c) compared with baseline after 12 months. Secondary analyses were of therapy intensification in response to higher blood or urinary glucose or HbA(1c). Participants and caregivers were not blinded as to the allocation of interventions, whereas the laboratory determining HbA(1c) remained blinded. RESULTS: Patient characteristics were balanced across groups. A total of 56 patients dropped out. In completers, HbA(1c) was reduced in the SMBG + group from 7.3% to 7.0%, i.e. by 0.3% (0.1%, 0.5%) vs SMBG - from 7.3% to 7.0% and 0.3% (0.2%, 0.5%), respectively, the difference being 0.0% (-0.2%, 0.2%) (p = 0.93). The disclosure of HbA(1c) results had no significant influence, with a difference of 0.1% (-0.1%, 0.4%) (p = 0.28). Values above are mean (95% CI). The ORs for therapy intensification significantly rose as the following increased: proportions of urine samples testing positive for glucose, HbA1c concentrations, and fasting or postprandial glucose concentrations. No important adverse events were associated with the interventions. CONCLUSIONS/INTERPRETATION: SMBG profiles once weekly or the disclosure of HbA(1c) results did not improve glycaemic control in patients with type 2 diabetes on conventional insulin treatment, although indicators of hyperglycaemia increased the likelihood of therapy intensification. Greater intensification may be necessary to impact on glycaemic control. TRIAL REGISTRATION: www.clinicaltrials.gov (registration code NCT00688363) FUNDING: Deutsche Diabetes-Gesellschaft, Deutsche Diabetes-Stiftung, Bayer Vital GmbH.

The sll1951 gene encodes the surface layer protein of Synechocystis sp. strain PCC 6803.

Sll1951 is the surface layer (S-layer) protein of the cyanobacterium Synechocystis sp. strain PCC 6803. This large, hemolysin-like protein was found in the supernatant of a strain that was deficient in S-layer attachment. An sll1951 deletion mutation was introduced into Synechocystis and was easily segregated to homozygosity under laboratory conditions. By thin-section and negative-stain transmission electron microscopy, a ~30-nm-wide S-layer lattice covering the cell surface was readily visible in wild-type cells but was absent in the Δsll1951 strain. Instead, the Δsll1951 strain displayed a smooth lipopolysaccharide surface as its most peripheral layer. In the presence of chaotropic agents, the wild type released a large (>150-kDa) protein into the medium that was identified as Sll1951 by mass spectrometry of trypsin fragments; this protein was missing in the Δsll1951 strain. In addition, Sll1951 was prominent in crude extracts of the wild type, indicating that it is an abundant protein. The carotenoid composition of the cell wall fraction of the Δsll1951 strain was similar to that of the wild type, suggesting that the S-layer does not contribute to carotenoid binding. Although the photoautotrophic growth rate of the Δsll1951 strain was similar to that of the wild-type strain, the viability of the Δsll1951 strain was reduced upon exposure to lysozyme treatment and hypo-osmotic stress, indicating a contribution of the S-layer to the integrity of the Synechocystis cell wall. This work identifies the S-layer protein in Synechocystis and shows that, at least under laboratory conditions, this very abundant, large protein has a supportive but not a critical role in the function of the cyanobacterium.

Evidence for a considerable decrease in total and cause-specific incidences of blindness in Germany.

The objectives of this study are to estimate the recent population-based incidences of all-cause and cause-specific blindness in Germany and compare them with results from a similar study conducted in 1994-1998. All blindness allowance recipients newly registered between January 2008 and December 2009 in a region in southern Germany (population, approximately 3.5 million) were assessed and their ophthalmological reports reviewed. The main causes of blindness were identified and their incidences estimated. There were 572 newly registered cases of blindness allowance. The all-cause incidence of blindness (per 100,000 person-years) in the general population was 8.4 (95 % confidence interval, 7.8-9.2), and the highest incidences were for macular degeneration (3.4; 3.0-3.9), diabetic retinopathy (0.8; 0.6-1.1) and glaucoma (0.7; 0.5-0.9). During the last two decades, blindness incidences decreased for all the main causes (standardised to the West German population 1991: 12.3; 11.9-12.7 in 1994-1998 vs. 7.3; 6.7-8.0 in 2008-2009). The highest absolute decrease was for macular degeneration and the highest relative decrease was for cataract. The most frequent main causes of blindness in Germany remained macular degeneration, diabetic retinopathy and glaucoma. Our findings suggest a remarkable decrease in the incidences of blindness, probably because of new diagnostic options and effective treatments.

Don't Shut the Stable Door after the Phage Has Bolted-The Importance of Bacteriophage Inactivation in Food Environments.

In recent years, a new potential measure against foodborne pathogenic bacteria was rediscovered-bacteriophages. However, despite all their advantages, in connection to their widespread application in the food industry, negative consequences such as an uncontrolled phage spread as well as a development of phage resistant bacteria can occur. These problems are mostly a result of long-term persistence of phages in the food production environment. As this topic has been neglected so far, this article reviews the current knowledge regarding the effectiveness of disinfectant strategies for phage inactivation and removal. For this purpose, the main commercial phage products, as well as their application fields are first discussed in terms of applicable inactivation strategies and legal regulations. Secondly, an overview of the effectiveness of disinfectants for bacteriophage inactivation in general and commercial phages in particular is given. Finally, this review outlines a possible strategy for users of commercial phage products in order to improve the effectiveness of phage inactivation and removal after application.

Markedly Decreasing Incidence of Blindness in People With and Without Diabetes in Southern Germany.

OBJECTIVE: Studies comparing the incidence of blindness in persons with and without diabetes are scarce worldwide. In Germany, a decline in the incidence of blindness was found during the 1990s. The aim of this study was to analyze the recent time trend. RESEARCH DESIGN AND METHODS: Data were based on administrative files in southern Germany to assess recipients of blindness allowance newly registered between 1 January 2008 and 31 December 2012. We estimated age- and sex-standardized incidence of blindness in people with and people without diabetes and the corresponding relative risk. Poisson regression was used to examine age- and sex-adjusted time trends. RESULTS: We identified 1,897 new cases of blindness (23.7% of which were associated with diabetes). We observed a strong decrease in incidence in both the population with diabetes (2008, 17.3 per 100,000 person-years [95% CI 13.6-21.1], and 2012, 8.9 per 100,000 person-years [6.3-11.6]: 16% decrease [10-22] per year) and that without diabetes (2008, 9.3 per 100,000 person-years [8.3-10.3], and 2012, 6.6 [5.8-7.4]: 9% decrease [5-13] per year). The relative risk comparing those incidences was 1.70 (95% CI 1.32-2.16) and remained constant in the observation period. Regarding time trend, we found similar results for both sexes. CONCLUSIONS: We found a significant reduction in incidence of blindness in the populations with and without diabetes, which was more prominent among individuals with diabetes compared with the 1990s. Our findings may be explained by effective secondary prevention therapies and improved ophthalmologic care beyond diabetic retinopathy, particularly regarding macular degeneration, which means earlier detection and earlier and better treatment.

Incidence of blindness in southern Germany due to glaucoma and degenerative conditions.

PURPOSE: To estimate population-based incidence rates of registered blindness separately, to determine its main causes. METHODS: The files of all newly registered blindness-allowance recipients in Württemberg-Hohenzollern, Germany (population: approximately 5 million), between 1994 and 1998 were reviewed. From ophthalmological reports on file the fulfillment of the German criteria for blindness (visual acuity of 1/50 or less or equivalent reduction of visual function) was ascertained, and the causes of blindness were obtained. Incidence rates of blindness due to macular degeneration, glaucoma, cataract, optic atrophy, and diabetic retinopathy were estimated. RESULTS: There were 3531 newly registered blindness-allowance recipients (67.1% female; mean age, 72.8 +/- 21.0 years). Standardized incidence rates in the general population (per 100,000 person-years; 95% confidence interval): All causes 12.27 (11.87-12.68), macular degeneration 5.29 (5.02-5.55), cataract 3.32 (3.11-3.52), optic atrophy 2.86 (2.66-3.05), glaucoma 2.43 (2.25-2.61), diabetic retinopathy 2.13 (1.96-2.30), other or unknown causes 5.17 (4.91-5.43). In many cases, blindness was attributable to more than one cause. Assuming that incidence rates are the same in other parts of the country, 9,939 (9,608-10,270) new cases of blindness were estimated to occur in Germany per year. CONCLUSIONS: The most common single cause of blindness was macular degeneration. Incidence rates of blindness due to such treatable conditions as glaucoma were also high. This finding suggests that the taking of measures for secondary prevention (e.g., early detection and optimal treatment of patients with glaucoma and diabetic retinopathy) should be intensified.

The endothelin system in Morris hepatoma-7777: an endothelin receptor antagonist inhibits growth in vitro and in vivo.

1. Plasma concentrations of endothelin are increased in patients with hepatocellular cancer as well as in patients with liver metastasis. However, the impact of these findings remains uncertain. 2. We thus analyzed the endothelin system in a rat hepatoma model (Morris hepatoma 7777) in vitro and in vivo. 3. Our study revealed that tissue concentrations of endothelin-1 (ET-1) and big-ET-1, the precursor of ET-1, were significantly elevated in Morris hepatoma 7777 as compared to normal liver. The ETA receptor density was significantly elevated, whereas the density of the ETB receptor was decreased in Morris hepatoma 7777. 4. We could also demonstrate that hepatoma cells secrete ET-1. 5. Exogenously added ET-1 enhances hepatoma cell growth in a dose-dependent manner. Endothelin receptor antagonists (ETA and combined ETA/ETB receptor antagonists) inhibit tumor cell growth in vitro. Since the combined ETA/ETB receptor antagonist was more effective in vitro, we used this compound also for in vivo studies and could demonstrate that a combined ETA/ETB receptor antagonist is able to reduce hepatoma growth in vivo. 6. In conclusion, the endothelin system is activated in Morris hepatoma 7777 and contributes to hepatoma growth. Since endothelin receptor antagonists are well-tolerated upcoming clinically used drugs without major side effects, our data might provide a new pharmacological approach to reduce hepatoma growth in vivo.

Reduced incidence of lower-limb amputations in the diabetic population of a German city, 1990-2005: results of the Leverkusen Amputation Reduction Study (LARS).

OBJECTIVE: We evaluated whether the incidence of amputations in one German city (Leverkusen, population approximately 160,000) had decreased between 1990 and 2005. RESEARCH DESIGN AND METHODS: From all three hospitals in the city, we obtained complete lists of nontraumatic lower-limb amputations in 1990-1991 and 1994-2005. Only the first observed amputation in residents of Leverkusen was counted. A total of 692 patients met the inclusion criteria. Data about the population structure, separately for each year of the observation period, were received from the city administration and the Federal Office of Statistics. To test for time trend, we fitted Poisson regression models. RESULTS: Of all subjects, 72% had known diabetes and 58% were male. Mean age was 71.7 years. Incidence rates in the diabetic population (standardized to the estimated German diabetic population per 100,000 person-years) varied considerably between years (maximum 549 in 1990, minimum 281 in 2004). In the diabetic population, the estimated relative risk (RR) per year was 0.976 (95% CI 0.958-0.996, P = 0.0164). The same trend was observed when only amputations above the ankle (n = 352) (RR 0.970 [95% CI 0.943-0.997], P = 0.0318) were considered. Over 15 years, an estimated reduction of amputations above the toe level by 37.1% (95% CI 12.3-54.8) results. There was no significant change of incident amputations in the nondiabetic population (RR 1.022 [0.989-1.056], P = 0.1981). CONCLUSIONS: This finding is likely to be due to improved management of the diabetic foot syndrome after a network of specialized physicians and defined clinical pathways for wound treatment and metabolic control were introduced.