TAVR bei Patienten mit chronischer Niereninsuffizienz, Adipositas und einer Einschränkung der alltäglichen Fähigkeiten

Fragestellung und Ziele: In three separate analyses, we aimed to assess the outcomes of TAVR in patients with BMI ≥ 25, in patients with reduced functional capacity, and in patients with chronic renal failure who underwent TAVR without the use of contrast medium. Methodik: For these analyses, we retrospectively evaluated data from TAVR patients at the Central Hospital Bad Berka, Germany. All decisions regarding the method of TAVR, the choice of prosthesis, and the access route were made by the institutional heart-team, which is comprised of cardiologists, cardiac surgeons, and anesthesiologists. Ergebnisse: In the first study, we included 25 patients with glomerular filtration rate (GFR) <30 mL/min/1.73 m2 who underwent TF-TAVR procedure with the Edwards Sapien balloon-expandable bio prostheses but without the use of contrast between September 2017 and September 2018. The results obtained were compared with data acquired from 73 matched patients (the control group), who underwent TF-TAVR with Edwards Sapien balloon-expandable bio prostheses with the standard technique using CM. We showed that TF-TAVR without the use of CM can be considered a safe and reproducible alternative technique. In the second study, we investigated the influence of BMI on the 1-year outcomes after TF-TAVR in 1609 high- and intermediate-risk TAVR patients who underwent the procedure between March 2014 and March 2018. BMI ≥ 25 kg/m2 was independently associated with lower 1 year mortality after TF-TAVR. The rate of vascular complications was higher in patients with BMI ≥ 25 kg/m2, which indicates the need for optimization of puncture technique and careful selection of closure devices in this group of patients. In the third study, we investigated the influence of functional impairment, as assessed by the BI, on outcomes 3-months after TF-TAVR. The procedures were performed, under general anesthesia, between January 2017 and January 2018 in 336 patients

AN OVERVIEW OF THE AZOLES OF INTEREST

In the last years, the risk of human fungal infections has been extensively increased with the increasing immune suppressed patients. Fortunately, the therapy of fungal infections has been undergone an explosive period of development. It was found that the use of currently available azoles in combination with other antifungals is likely to provide enhanced efficacy. But, several factors lead to therapeutic failure or relapse after the antifungal therapy. These factors are concerned with the different characteristics of the antifungal (s) used. Thus, specialists should be carefully investigated the different characteristics of antifungals to avoid these factors and further to use the antifungals optimally. The present review discussed the different characteristics of the azoles of interest, to recognize the differences in pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and potential drug interactions of these antifungal agents. However, the present review explore that the azoles of interest are sufficiently diverse in pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and potential drug interactions allowing specialists to differentiate among these agents based upon their characteristics when tailoring therapy to meet the needs of a particular patient. Moreover, further advances in antifungal chemotherapy will be necessary to improve management of invasive mycoses in the future

Aortic valve calcium volume as measured by native versus contrast-enhanced computer tomography and the implications for the diagnosis of severe aortic stenosis in TAVR patients with low-gradient aortic stenosis

BACKGROUND: Most of TAVR centers evaluate the calcium score in contrast-enhanced (ce) CT. We compared in this study between different methodologies to measure calcium score. We studied also the difference between patients with low-gradient (LG) and high-gradient (HG) severe aortic stenosis (AS) as regard the burden of aortic valve calcium (AVC). RESULTS: We measured the calcium volume and score using Agatston methodology in non-contrast (nc) CT and with modified and fixed 850 Hounsfield unit (HU) thresholds in ce CT. The calcium score and volume in ceCT using even with modified thresholds is significantly lower than the assessed score and volume in ncCT. The median (IQR) of calcium score in nc CT and in cc CT were 1288 AU (750–1815) versus 947 HU (384–2202). The median (IQR) of calcium volume in nc CT and in cc CT with modified thresholds were 701 mm(3) (239–1632) versus 197 mm(3) (139–532). Agatston score and calcium volume were lower in patients with LG AS than HG AS; 2069 AU (899–2477) versus 928AU (572–1284) and 1537 mm(3) (644–1860) versus 286 mm(3) (160–700), respectively. Only 20% of patients with LGAS had Agatston score higher than the previously supposed AVC score threshold for the diagnosis of severe AS (> 2000AU in men and > 1200 in women). CONCLUSIONS: The diagnosis of severe LGAS should not depend on a single parameter as calcium score. In these patients, calcium score should be measured in nc CT and not in ce CT

FORMULATION AND EVALUATION OF FLURBIPROFEN SUSTAINED RELEASE MATRIX TABLETS USING AN ALTERNATIVE TECHNIQUE AS POTENTIAL ECONOMIC APPROACH

Objective: Development of sustained released tablets of flurbiprofen (FP) using an alternative technique to the traditional method of wet granulation process aiming to lower labor cost of the granulation process and formulating tablets with better characteristics. Methods: Eight matrix tablets formulae of FP were prepared by the alternative technique. The various characteristics of FP prepared tablets were investigated and comparatively evaluated by FP tablets prepared by the traditional method. The release data was analyzed according to various kinetic equations. The ulcerogenic effects of some FP tablets formulae were evaluated. Results: FP tablets prepared by the alternative technique displayed the best physical characteristics. All FP prepared tablets displayed good sustained-release patterns. FP tablets prepared by the traditional method showed a progress decrease in drug dissolution by increasing matrix concentration and hence, more matrix agent or multiple granulations was needed which makes granulation process to be difficult and cost. While, FP tablets prepared by the alternative technique displayed dissolution profiles with minimal differences in-between reflecting the low labor cost of granulation process where good sustained patterns could be obtained by a minor of the matrix agent. Histologically, the ulcerogenic effects of FP on the rats were highly reduced by FP tablets prepared by the alternative technique rather than others. The release kinetics of different prepared FP tablets displayed a coupled release pattern between diffusion and dissolution. Conclusion: This work proved the potential of the alternative technique as an effective economic approach for formulating FP sustained released tablets with better characteristics and low labor cost

أثر المنطقة الديموجرافية ومستوى الدخل على سلوك المستهلك نحو الألبان ومنتجاتها في مصر

The study of consumption is of great importance for the formulation of economic policies and the identification of the projection of consumer behavior and its impact on the quantities consumed by each commodity, thus contributing to the definition of the objectives of economic development plans and hence the policies leading to the achievement of those goals and aimed at satisfying the needs of the population of various goods and services while rationalizing consumption rates. Despite the nutritional importance of dairy products and the availability of a comparative advantage for Egypt in dairy production, the average per capita milk and dairy products are still very low, with a high rate of dependence of domestic consumption on imports to fill the gap between domestic production and consumption, which in turn affects the increase in the deficit in the balance of trade and hence the Egyptian balance of payments. The study aimed at estimation of the dairy products consumption functions as an important component in the Egyptian consumer map to identify the difference between urban and rural communities, besides estimation of impacts in the difference of the level of per capita income on the consumption of milk and dairy products in the two regions, measured as the average of the income elasticity, to determine the current status of food consumption patterns of the per capita consumption behavior in both urban and rural areas. The study relied, mainly, on the field sample data of the household budget survey for the year 2015, conducted by the Central Agency for Public Mobilization and Statistics. The estimated consumption functions for milk and dairy products included the effects of both the average annual income per capita and the demographic region (urban and rural). Derived results showed that the urban community had a statistically positive impact on consuming of packaged milk (either pasteurized or sterile), as well as the consumption of both yogurt and full-fat white cheese, while there was a statistically negative effect of the damage on the consumption of fatless chees and the urban community had no statistically significant impact on the consumption of fresh milk consumption. The average estimated income elasticity coefficient indicated that the consumer considered both fresh milk and full cream white cheese as semi-superior goods (estimated income elasticity was between greater than 0.5, to less than 1), while packaged milk and yogurt are superior goods (their elasticity was greater than 1), and fatless-cheese is a necessary commodity for low income levels and an inferior commodity for higher income groups

Protective effect of zinc against cadmium toxicity on pregnant rats and their fetuses at morphological, physiological and molecular level

Cadmium is a potent teratogen in laboratory animals, causing exencephaly when administered at early stages of development. Due to its heterogenicity with respect to molecular targets, the mechanisms behind cadmium toxicity are not well understood. In the present study, 40 pregnant rats (Sprague-Dawley) were divided into four groups (10 each); first group served as the control (G1), the second group (G2) received 61.3 mg/kg cadmium chloride daily from 7th to 16th day of gestation (organogenesis period) by oral tube. Group 3 (G3) was administrated a solution of 25 mg/kg zinc chloride orally from the 1st day to 20th day of pregnancy. Group 4 were administrated a solution of cadmium chloride (61.3 mg/kg) and zinc chloride (25 mg /kg) daily from the 7th to16th day of gestation. Maternal body weights were measured on gestational day 0, 6, 9, 12, 15 and 20. At the 20th day of gestation, blood samples were collected from the eye, using orbital sinus technique. Serum aspartate transaminase (AST) and alanine transaminase (ALT) were determined calorimetrically and serum, urea and creatinine were determined. All of the pregnant rats were sacrificed by ether anaesthesia at the 20th day of gestation and foetuses were removed from the uterus. The implantation sites, corpora lutea, living, dead and reabsorbed foetuses were counted and recorded. Liver of pregnant rats and their fetuses were used to isolate a total RNA for quantification of Msx1, Cx43, Bcl2 and Bax genes. The results show the toxic effect of Cd on the pregnant rats and their fetuses, at morphological, physiological and molecular level but, zinc has a very effective protection against cadmium-induced developmental toxicity.Keywords: Cadmium, zinc, rat, organogenesis, gene expressionAfrican Journal of Biotechnology Vol. 12(16), pp. 2110-211

Brain Emotional Learning Based Intelligent Decoupler for Nonlinear Multi-Input Multi-Output Distillation Columns

The distillation process is vital in many fields of chemical industries, such as the two-coupled distillation columns that are usually highly nonlinear Multi-Input Multi-Output (MIMO) coupled processes. The control of MIMO process is usually implemented via a decentralized approach using a set of Single-Input Single-Output (SISO) loop controllers. Decoupling the MIMO process into group of single loops requires proper input-output pairing and development of decoupling compensator unit. This paper proposes a novel intelligent decoupling approach for MIMO processes based on new MIMO brain emotional learning architecture. A MIMO architecture of Brain Emotional Learning Based Intelligent Controller (BELBIC) is developed and applied as a decoupler for 4 input/4 output highly nonlinear coupled distillation columns process. Moreover, the performance of the proposed Brain Emotional Learning Based Intelligent Decoupler (BELBID) is enhanced using Particle Swarm Optimization (PSO) technique. The performance is compared with the PSO optimized steady state decoupling compensation matrix. Mathematical models of the distillation columns and the decouplers are built and tested in simulation environment by applying the same inputs. The results prove remarkable success of the BELBID in minimizing the loops interactions without degrading the output that every input has been paired with

Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies

This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P &lt; 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein. Most mutations were private, but three recurrent mutations (p.Met2242Cysfs*5, p.Arg417*, and p.Gln336Arg) indicated possible founder effects. Presentation was mainly neonatal, with marked hypotonia and feeding difficulties. In addition to the five principal features (callosal agenesis, cataracts, hypopigmentation, cardiomyopathy, and immune dysfunction), we identified three equally consistent features (profound developmental delay, progressive microcephaly, and failure to thrive). The manifestation of all eight of these features has a specificity of 97%, and a sensitivity of 89% for the presence of an EPG5 mutation and will allow informed decisions about genetic testing. Clinical progression was relentless and many children died in infancy. Survival analysis demonstrated a median survival time of 24 months (95% confidence interval 0–49 months), with only a 10th of patients surviving to 5 years of age. Survival outcomes were significantly better in patients with compound heterozygous mutations (P = 0.046), as well as in patients with the recurrent p.Gln336Arg mutation. Acquired microcephaly and regression of skills in long-term survivors suggests a neurodegenerative component superimposed on the principal neurodevelopmental defect. Two-thirds of patients had a severe seizure disorder, placing EPG5 within the rapidly expanding group of genes associated with early-onset epileptic encephalopathies. Consistent neuroradiological features comprised structural abnormalities, in particular callosal agenesis and pontine hypoplasia, delayed myelination and, less frequently, thalamic signal intensity changes evolving over time. Typical muscle biopsy features included fibre size variability, central/internal nuclei, abnormal glycogen storage, presence of autophagic vacuoles and secondary mitochondrial abnormalities. Nerve biopsy performed in one case revealed subtotal absence of myelinated axons. Post-mortem examinations in three patients confirmed neurodevelopmental and neurodegenerative features and multisystem involvement. Finally, downregulation of epg5 (CG14299) in Drosophila resulted in autophagic abnormalities and progressive neurodegeneration. We conclude that EPG5-related Vici syndrome defines a novel group of neurodevelopmental disorders that should be considered in patients with suggestive features in whom mitochondrial, glycogen, or lysosomal storage disorders have been excluded. Neurological progression over time indicates an intriguing link between neurodevelopment and neurodegeneration, also supported by neurodegenerative features in epg5-deficient Drosophila, and recent implication of other autophagy regulators in late-onset neurodegenerative disease