Predicting Sensitivity to Adverse Lifestyle Risk Factors for Cardiometabolic Morbidity and Mortality

People appear to vary in their susceptibility to lifestyle risk factors for cardiometabolic disease; determining a priori who is most sensitive may help optimize the timing, design, and delivery of preventative interventions. We aimed to ascertain a person’s degree of resilience or sensitivity to adverse lifestyle exposures and determine whether these classifications help predict cardiometabolic disease later in life; we pooled data from two population-based Swedish prospective cohort studies (n = 53,507), and we contrasted an individual’s cardiometabolic biomarker profile with the profile predicted for them given their lifestyle exposure characteristics using a quantile random forest approach. People who were classed as ‘sensitive’ to hypertension- and dyslipidemia-related lifestyle exposures were at higher risk of developing cardiovascular disease (CVD, hazards ratio 1.6 (95% CI: 1.3, 1.91)), compared with the general population. No differences were observed for type 2 diabetes (T2D) risk. Here, we report a novel approach to identify individuals who are especially sensitive to adverse lifestyle exposures and who are at higher risk of subsequent cardiovascular events. Early preventive interventions may be needed in this subgroup.     

Einfluss des Liquordrucks auf die glaukomatöse Schädigung des Nervus opticus

Eyes with normal pressure glaucoma and eyes with high pressure glaucoma show a similar optic disc appearance with marked differences to eyes with vascular optic neuropathy. Non-vascular, potentially barotraumatic factors in addition to intraocular pressure (IOP) may thus play a role in glaucoma. Recent studies have shown that cerebrospinal fluid pressure (CSFP), arterial blood pressure and IOP are correlated with each other, higher CSFP is associated with younger age, higher blood pressure and higher body mass index, some patients with normal (IOP) pressure glaucoma have abnormally low CSFP and thus an abnormally high trans-lamina cribrosa pressure difference and a small orbital CSF space, the orbital CSF space width is associated with CSFP and the estimated CSFP correlated better with open-angle glaucoma-related parameters than IOP. The orbital CSFP as counter-pressure against IOP may play a role in the pathogenesis of glaucoma.     

Seawater activated TiO2 photocatalyst for degradation of organic compounds

The world's oceans are polluted by a continuous inflow of plastic. Plastic fragments finally into microplastic, which can be taken up, for example by plankton, and subsequently by the entire ocean food web. An approach to reduce plastic pollution constitutes the accelerated microplastic degradation in marine environments. TiO₂ (anatase) is commonly used as an oxidative photocatalyst and well known to catalyze the degradation of organic compounds upon UV irradiation.In this study, a selective activation of TiO₂ (anatase) particles encapsulated by Ca- or Sr-polyphosphate is presented. The TiO₂ polyphosphate core-shell particles are envisaged as additives in plastic products. The highly concentrated cations from seawater, viz. Na⁺ and Mg²⁺, displace the Ca²⁺ or Sr²⁺ cations from the polyphosphate shell. As a result, the polyphosphate coating dissolves and thus the photocatalytically active TiO₂ core is released. The stability of the TiO₂ polyphosphate particles in potable water and the seawater activated disintegration of methylene blue, methyl methacrylate, terephtalic acid, and poly(vinyl alcohol) was shown. It has been demonstrated, that the sweetwater stable polyphosphate coating degrades in the presence of seawater, which could be monitored by the activation of the TiO₂ (anatase) photocatalyst.     

Max Br?del (1870-1941) and Howard A. Kelly (1858-1943)--urogynecology and the birth of modern medical illustration.

In 1894 the German artist Max Br?del came to America and started work with the famous gynecologist Howard A. Kelly. By developing a profound medical knowledge especially in the field of gynecology, and creating new artistic techniques for medical illustration, Br?del revolutionized the appearance of medical literature and founded the profession of medical artist and illustrator. In 1911, Br?del became head of the first 'Department of Art as Applied to Medicine' in the world. The ingenious cooperation of the artist Br?del and the gynecologist Kelly and their influence on modem medical illustration is reflected in this historical article.     

CTLA‐4 (CD152) enhances the Tc17 differentiation program

Although CD8⁺ T cells that produce IL‐17 (Tc17 cells) have been linked to host defense, Tc17 cells show reduced cytotoxic activity, which is the characteristic function of CD8⁺ T cells. Here, we show that CTLA‐4 enhances the frequency of IL‐17 in CD8⁺ T cells, indicating that CTLA‐4 (CD152) specifically promotes Tc17 differentiation. Simultaneous stimulation of CTLA‐4^+/+ and CTLA‐4^?/? T cells in cocultures and agonistic CTLA‐4 stimulation unambiguously revealed a cell‐intrinsic mechanism for IL‐17 control by CTLA‐4. The quality of CTLA‐4‐induced Tc17 cells was tested in vivo, utilizing infection with the facultative intracellular bacterium Listeria monocytogenes (LM). Unlike CTLA‐4^+/+ Tc17 cells, CTLA‐4^?/? were nearly as efficient as Tc1 CTLA‐4^+/+ cells in LM clearance. Additionally, adoptively transferred CTLA‐4^?/? Tc17 cells expressed granzyme B after rechallenge, and produced Tc1 cytokines such as IFN‐γ and TNF‐α, which strongly correlate with bacterial clearance. CTLA‐4^+/+ Tc17 cells demonstrated a high‐quality Tc17 differentiation program ex vivo, which was also evident in isolated IL‐17‐secreting Tc17 cells, with CTLA‐4‐mediated enhanced upregulation of Tc17‐related molecules such as IL‐17A, RORγt, and IRF‐4. Our results show that CTLA‐4 promotes Tc17 differentiation that results in robust Tc17 responses. Its inactivation might therefore represent a central therapeutic target to enhance clearance of infection.     

Ecological-level associations between highly processed food intakes and plasma phospholipid elaidic acid concentrations: results from a cross-sectional study within the European prospective investigation into cancer and nutrition (EPIC)

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.     

Inositol 1,4,5-trisphosphate formation, cytoplasmic calcium dynamics, and α-amylase secretion of pancreatic acini isolated from aged and chronically alcohol-fed rats

Methods. Three-month-old female Wistar rats were fed with 20% alcohol in their drinking fluid over 6–17 mo using an interrupted feeding regimen. At different times, pancreatic acini were isolated by mild collagenase digestion. The concentrations of inositol-1,4,5-trisphosphate (1,4,5-IP3) were determined by a specific radioreceptor assay, before and at different times after stimulation with varying concentrations of CCK-8. CCK-induced dynamics of cytoplasmic calcium ([Ca²⁺]_c) was investigated in acinar cells by confocal laser raster microscopy. Acinar α-amylase (Aml) secretion was measured as enzyme activity in the medium compared to the total activity in the suspension. Results. In 12–13-mo-old rats, the CCK-stimulated 1,4,5-IP₃ formation in acini was found to be decreased compared to young rats (age 4 mo). In rats of the same age fed with ethanol from the age of 3 mo on, 1,4,5-IP₃ concentrations in acini were higher and reached values comparable to those in young rats. Corre-spondingly, the CCK-induced [Ca²⁺]_c dynamics in acini isolated from 9-mo-old rats was impaired compared to that of young rats but normal in aged, chronically alcohol-fed rats. Aml secretion under CCK stimulation, however, which was decreased in aged rats, was additionally impaired after alcohol feeding.     

Cost of Hypoglycemia in Patients with Type 2 Diabetes in Sweden

OBJECTIVES: Hypoglycemia is a common side effect of antidiabetic therapy. In addition to reducing well-being, hypoglycemic events may lead to substantial costs of medical care and lost productivity. The cost of hypoglycemia is, however, not well identified, particularly in patients with Type 2 diabetes. The purpose of this study was to assess the cost of hypoglycemia in Type 2 diabetes in Sweden. METHODS: A cost-of-illness approach, based on an incidence methodology, was used to estimate the cost of hypoglycemia in patients with Type 2 diabetes. A hypoglycemic event was defined as an episode with symptoms of low blood glucose levels during which the patient required assistance from another person. The events were divided into mild, moderate, and severe, and the incidence and costs of the different events were estimated based on data in the literature. RESULTS: Assuming that there are 300,000 patients with Type 2 diabetes in Sweden, it was estimated that 26,942 hypoglycemic events would occur annually in these patients, corresponding to a rate of 0.09 events per patient-year. The total cost of hypoglycemia was, in base case, estimated at about Euro 4,250,000 (Euro 14 per patient with Type 2 diabetes) per year. Moderate hypoglycemia contributed the largest proportion of these costs. CONCLUSIONS: The results indicate that hypoglycemic events lead to substantial costs, but data are scarce and more studies are needed to better understand the cost and consequences of hypoglycemia.