Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other ...in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.
Itraconazole is an FDA‐approved antifungal agent, which has been reported to possess promising anticancer activities in recent years. This study investigates the antiproliferative effects of ...itraconazole on pancreatic cancer cells and the molecular mechanism of its apoptosis‐inducing effects. In this study, our results showed that itraconazole inhibited the growth of pancreatic cancer cells in vitro, and it also significantly inhibited the tumor growth of CFPAC‐1 xenografts in vivo. Itraconazole induced apoptosis through ROS generation and mitochondrial membrane depolarization. A Bak‐1 activation dependent apoptosis was identified in CFPAC‐1 cells. These data suggested that itraconazole exhibited antiproliferative effects in pancreatic cancer cells by inducing apoptosis through Bak‐1 activation.
Itraconazole inhibited the growth of pancreatic cancer cells in vitro, and it also significantly inhibited the tumor growth of CFPAC‐1 xenografts in vivo. Itraconazole induced apoptosis through ROS generation and mitochondrial membrane depolarization.
Parameters of physiological models of glucose-insulin regulation in type 1 diabetes have previously been estimated using data collected over short periods of time and lack the quantification of ...day-to-day variability. We developed a new hierarchical model to relate subcutaneous insulin delivery and carbohydrate intake to continuous glucose monitoring over 12 weeks while describing day-to-day variability. Sensor glucose data sampled every 10-min, insulin aspart delivery and meal intake were analyzed from eight adults with type 1 diabetes (male/female 5/3, age 39.9 ± 9.5 years, BMI 25.4 ± 4.4kg/m 2 , HbA1c 8.4 ± 0.6% ) who underwent a 12-week home study of closed-loop insulin delivery. A compartment model comprised of five linear differential equations; model parameters were estimated using the Markov chain Monte Carlo approach within a hierarchical Bayesian model framework. Physiologically, plausible a posteriori distributions of model parameters including insulin sensitivity, time-to-peak insulin action, time-to-peak gut absorption, and carbohydrate bioavailability, and good model fit were observed. Day-to-day variability of model parameters was estimated in the range of 38-79% for insulin sensitivity and 27-48% for time-to-peak of insulin action. In conclusion, a linear Bayesian hierarchical approach is feasible to describe a 12-week glucose-insulin relationship using conventional clinical data. The model may facilitate in silico testing to aid the development of closed-loop insulin delivery systems.
Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important ...intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.
Muscarinic acetylcholine receptors (mAChRs) belong to the superfamily of G-protein-coupled receptors (GPCRs). The family of mAChRs is composed of five subtypes, M1, M2, M3, M4 and M5, which have ...distinct expression patterns and functions. In the eye and its adnexa, mAChRs are widely expressed and exert multiple functions, such as modulation of tear secretion, regulation of pupil size, modulation of intraocular pressure, participation in cell-to-cell signaling and modula-tion of vascular diameter in the retina. Due to this variety of functions, it is reasonable to assume that abnormalities in mAChR signaling may contribute to the development of various ocular diseases. On the other hand, mAChRs may offer an attractive therapeutic target to treat ocular diseases. Thus far, non-subtype-selective mAChR ligands have been used in ophthalmology to treat dry eye disease, myopia and glaucoma. However, these drugs were shown to cause various side-effects. Thus, the use of subtype-selective ligands would be useful to circumvent this problem. In this review, we give an overview on the localization and on the functional role of mAChR subtypes in the eye and its adnexa with a special focus on the retina. Moreover, we describe the pathophysiological role of mAChRs in retinal diseases and discuss potential therapeutic approaches.
Epidemiological studies showed that dietary fat intake is associated with Alzheimer's disease (AD) and dementia risk, however, the association remain inconsistent. This metaanalysis aimed to ...systematically examine the association of dietary fat intake with AD and dementia risk.
We have systematically searched PubMed, Embase and the Cochrane Library up to May 1st 2017. Prospective cohort studies were included if they reported on the association of dietary fat intake with AD and dementia risk. Multivariate-adjusted relative risks (RRs) for the highest versus lowest category were pooled by using a random-effects model.
A total of 8630 participants and 633 cases from four independent prospective cohort studies were included in the present meta-analysis. A higher dietary saturated fat intake was significantly associated with an increased risk of 39% and 105% for AD (RR: 1.39; 95% CI: 1.00, 1.94) and dementia (RR: 2.05; 95% CI: 1.06, 3.98), respectively. Dose-response analysis indicated a 4 g/day increment of saturated fat intake was related to 15% higher risk of AD (RR: 1.15; 95% CI: 1.01, 1.31). However, there was no significant association found between dietary intake of total, monounsaturated, polyunsaturated fat and AD or dementia risk.
This meta-analysis provides significant evidence of positive association between higher saturated fat intake and AD and dementia risk.
Purpose
To investigate the anxiety and depression levels of frontline clinical nurses working in 14 hospitals in Gansu Province, China, during this period.
Design
A cross‐sectional survey was ...conducted online between February 7 and 10, 2020, with a convenience sample of 22,034 nurses working in 14 prefecture and city hospitals in Gansu Province, located in northwest China.
Methods
A self‐reported questionnaire with four parts (demographic characteristics, general questions related to novel coronavirus‐infected pneumonia, self‐rating anxiety scale, and self‐rating depression scale) was administered. Descriptive statistics including frequencies, means, and SDs were computed. The associations between anxiety and depression with sociodemographic characteristics, work‐related concerns, and impacts were analyzed, followed by multiple stepwise linear regression to identify factors that best predicted the nurses’ anxiety and depression levels.
Findings
A total of 21,199 questionnaires were checked to be valid, with an effective recovery rate of 96.21%. The mean ± SD age of the respondents was 31.89 ± 7.084 years, and the mean ± SD length of service was 9.40 ± 7.638 years. The majority of the respondents were female (98.6%) and married (73.1%). Some demographic characteristics, related concerns, and impacts of COVID‐19 were found to be significantly associated with both anxiety (p < .001) and depression (p < .001). Nurses who needed to take care of children or elderly relatives, took leave from work because they were worried about COVID‐19, avoided contact with family and friends, and wanted to obtain more COVID‐19‐related knowledge had higher levels of both anxiety and depression.
Conclusions
Results show that nurses faced with the COVID‐19 outbreak are at risk for experiencing anxiety and depression. Demographic background, psychosocial factors, and work‐related factors predicted the psychological responses. The family responsibilities and burdens of women may explain the higher levels of anxiety and depression among nurses with these obligations as compared to those without. On the other hand, nurses who chose not to take leave from work or who did not avoid going to work during this period were less anxious and depressed.
Clinical Relevance
Professional commitment might be a protective factor for adverse psychological responses. It is pertinent to provide emotional support for nurses and recognize their professional commitment in providing service to people in need.
Aims/hypothesis
We analysed data obtained from the electronic patient records of inpatients with diabetes admitted to a large university hospital to understand the prevalence and distribution of ...inpatient hypoglycaemia.
Methods
The study was conducted using electronic patient record data from Oxford University Hospitals NHS Foundation Trust. The dataset contains hospital admission data for patients coded for diabetes. We used the recently agreed definition for a level 1 hypoglycaemia episode as any blood glucose measurement <4 mmol/l and a level 2 hypoglycaemia episode as any blood glucose measurement <3 mmol/l. Any two or more consecutive low blood glucose measurements within a 2 h time window were considered as one single hypoglycaemic episode.
Results
We analysed data obtained from 17,658 inpatients with diabetes (1696 with type 1 diabetes, 14,006 with type 2 diabetes, and 1956 with other forms of diabetes; 9277 men; mean ± SD age, 66 ± 18 years) who underwent 32,758 hospital admissions between July 2014 and August 2018. The incidence of level 1 hypoglycaemia was 21.5% and the incidence of level 2 hypoglycaemia was 9.6%. Recurrent level 1 and level 2 hypoglycaemia occurred, respectively, in 51% and 39% of hospital admissions in people with type 2 diabetes with at least one hypoglycaemic episode, and in 55% and 45% in those with type 1 diabetes. The incidence of level 2 hypoglycaemia in people with type 2 diabetes, when corrected for the number of people who remained in hospital, remained constant for the first 100 h at approximately 0.15 events per h per admission. With regards to the hypoglycaemia distribution during the day, after correcting for the number of blood glucose tests per h, there were two clear spikes in the rate of hypoglycaemia approximately 3 h after lunch and after dinner. The highest rate of hypoglycaemia per glucose test was seen between 01:00 hours and 05:00 hours. Medication had a significant impact on the incidence of level 2 hypoglycaemia, ranging from 1.5% in people with type 2 diabetes on metformin alone to 33% in people treated with a combination of rapid-acting insulin analogue, long-acting insulin analogue and i.v.-administered insulin.
Conclusions/interpretation
Retrospective analysis of data from electronic patient records enables clinicians to gain a greater understanding of the incidence and distribution of inpatient hypoglycaemia. This information should be used to drive evidence-based improvements in the glycaemic control of inpatients through targeted medication adjustment for specific populations at high risk of hypoglycaemia.
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