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Can garlic reduce levels of serum lipids? A controlled clinical study.

PURPOSE: To assess the effects of standardized garlic powder tablets on serum lipids and lipoproteins, glucose, and blood pressure. SUBJECTS AND METHODS: Forty-two healthy adults (19 men, 23 women), mean age of 52 +/- 12 years, with a serum total cholesterol (TC) level of greater than or equal to 220 mg/dL received, in a randomized, double-blind fashion, either 300 mg three times a day of standardized garlic powder in tablet form or placebo. Diets and physical activity were unchanged. This study was conducted in an outpatient, clinical research unit. RESULTS: The baseline serum TC level of 262 +/- 34 mg/dL was reduced to 247 +/- 40 mg/dL (p < 0.01) after 12 weeks of standard garlic treatment. Corresponding values for placebo were 276 +/- 34 mg/dL before and 274 +/- 29 mg/dL after placebo treatment. Low-density lipoprotein cholesterol (LDL-C) was reduced by 11% by garlic treatment and 3% by placebo (p < 0.05). There were no significant changes in high-density lipoprotein cholesterol, triglycerides, serum glucose, blood pressure, and other monitored parameters. CONCLUSIONS: Treatment with standardized garlic 900 mg/d produced a significantly greater reduction in serum TC and LDL-C than placebo. The garlic formulation was well tolerated without any odor problems.

Adult↗

Pneumoperitoneum due to peritoneovaginal fistula following hysterectomy.

A patient with pneumoperitoneum that developed due to peritoneovaginal fistula following hysterectomy is presented. In addition, we have reviewed the literature and formulated guidelines for the management of this problem. Most patients present following sexual intercourse and in many cases the fistula can be diagnosed radiographically. Laparotomy may be avoided if the cause of the fistula is suspected. Surgical closure of the fistula may be unnecessary since spontaneous closure occurs frequently.

Adult↗

Kave: a tool for knowledge acquisition to support artificial ventilation.

A decision support system for artificial ventilation is being developed. One of the fundamental goals for this system is the application of the system when a domain expert is not present. Such a system requires a rich knowledge base. The knowledge acquisition process is often considered to be the bottleneck in acquiring such a complete knowledge base. Since no single available method, for example interviewing domain experts, is sufficient for removing this bottleneck, we have chosen a combination of different methods. The different backgrounds of knowledge engineers and domain experts could cause communication restrictions and difficulties between them, e.g. they might not understand each others knowledge domain and this will affect formulation of the knowledge. To solve this problem we needed a tool which supports both the knowledge engineer and the domain expert already from the initial phase of developing the knowledge base. We have developed a knowledge acquisition system called KAVE to elicit knowledge from domain experts and storing it in the knowledge base. KAVE is based on a domain specific conceptual model which is a result of cooperation between knowledge engineers and domain experts during identification, design and structuring of knowledge for this domain. KAVE includes a patient simulator to help validate knowledge in the knowledge base and a knowledge editor to facilitate refinement and maintenance of the knowledge base.

Artificial Intelligence↗

An analysis of numerical models of air pollutant exposure and vegetation response.

A number of empirical (statistical, regression oriented) and mechanistic (process oriented) models are presently available to examine the relationship between air pollution stress and plant response. These models have their strengths and weaknesses. In all these models, a major concern is the numerical definition of the pollutant exposure kinetics (dose). At present there are no numerical definitions of dose which make satisfactory biological sense. A key issue is the existence of a biological time clock where plants respond differently to the pollutant stress at different stages of their growth. On the other hand, policy makers and regulatory personnel prefer a simple approach which would facilitate implementation and administration of ambient air quality standards. Long-term air pollutant averaging techniques create artifacts due to the non-normal distribution of ambient concentrations. A more appropriate approach may be the use of 'median' and 'percentiles' computed from short duration pollutant concentrations. Such an approach would be free of the influence of the non-normal distribution, but would require the development of appropriate exposure-response models. Any transfer of results from unit level models to regional level leads to 'scaling error'. There is no general agreement among researchers on how to deal with the scale problem. While this situation persists, any policy formulated on regional impact assessment must acknowledge the uncertainty.

Journal Article↗

Joint registration and segmentation of neuroanatomic structures from brain MRI.

RATIONALE AND OBJECTIVES: Segmentation of anatomic structures from magnetic resonance brain scans can be a daunting task because of large inhomogeneities in image intensities across an image and possible lack of precisely defined shape boundaries for certain anatomical structures. One approach that has been quite popular in the recent past for these situations is the atlas-based segmentation. The atlas, once constructed, can be used as a template and can be registered nonrigidly to the image being segmented thereby achieving the desired segmentation. The goal of our study is to segment these structures with a registration assisted image segmentation technique. MATERIALS AND METHODS: We present a novel variational formulation of the registration assisted image segmentation problem which leads to solving a coupled set of nonlinear Partial Differential Equations (PDEs) that are solved using efficient numeric schemes. Our work is a departure from earlier methods in that we can simultaneously register and segment in three dimensions and easily cope with situations where the source (atlas) and target images have very distinct intensity distributions. RESULTS: We present several examples (20) on synthetic and (3) real data sets along with quantitative accuracy estimates of the registration in the synthetic data case. CONCLUSION: The proposed atlas-based segmentation technique is capable of simultaneously achieve the nonrigid registration and the segmentation; unlike previous methods of solution for this problem, our algorithm can accommodate for image pairs having very distinct intensity distributions.

Algorithms↗

Determination of residual styrene monomer in polystyrene granules by gas chromatography-mass spectrometry.

Polystyrene is widely used in formulations intended for children use. The main problem with this plastic is the residual styrene, which can migrate from the product, and therefore, be in contact with children. The acute toxicity of styrene is well known, raising the need of an efficient and fast method of analysis for this compound. Several extraction methods have been evaluated and compared for the determination of residual styrene monomer in polystyrene granules used in toys: supercritical fluid extraction (SFE), microwave-assisted extraction (MAE), Soxhlet extraction, headspace emission and dissolution-precipitation. The analyte was subsequently detected by gas chromatography (GC) with MS detection. The results indicated that the most efficient method was dissolution-precipitation giving even higher extraction efficiency than SFE. For validating the method, PS samples spiked with known quantities of styrene at three concentration levels were prepared to calculate the extraction recovery. The founded validation data proved the suitability of the proposed method.

Gas Chromatography-Mass Spectrometry↗

A method to combine numerical optimization and EMG data for the estimation of joint moments under dynamic conditions.

To solve the problem of muscle redundancy at the level of opposing muscle groups, an alternative method to inverse dynamics must be employed. Considering the advantages of existing alternatives, the present study was aimed to compute knee joint moments under dynamic conditions using electromyographic (EMG) signals combined with non-linear constrained optimization in a single routine. The associated mathematical problems accounted for muscle behavior in an attempt to obtain accurate predictions of the resultant moment as well as physiologically realistic estimates of agonist and antagonist moments. The experiment protocol comprised (1) isometric trials to determine the most effective EMG processing for the prediction of the resultant moment and (2) stepping-in-place trials for the calculation of joint moments from processed EMG under dynamic conditions. Quantitative comparisons of the model predictions with the output of a biological-based model, showed that the proposed method (1) produced the most accurate estimates of the resultant moment and (2) avoided possible inconsistencies by enforcing appropriate constraints. As a possible solution for solving the redundancy problem under dynamic conditions, the proposed optimization formulation also led to realistic predictions of agonist and antagonist moments.

Adult↗

Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles.

Biotechnology allows tailor-made production of biopharmaceuticals and biotechnological drugs; however, many of them require special formulation technologies to overcome drug-associated problems. Such potential challenges to solve are: poor solubility, limited chemical stability in vitro and in vivo after administration (i.e. short half-life), poor bioavailability and potentially strong side effects requiring drug enrichment at the site of action (targeting). This review describes the use of nanoparticulate carriers, developed in our research group, as one solution to overcome such delivery problems, i.e. drug nanocrystals, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and lipid-drug conjugate (LDC) nanoparticles, examples of drugs are given. As a recently developed targeting principle, the concept of differential protein adsorption is described (PathFinder Technology) using as example delivery to the brain.

Biotechnology↗

Amino acid contribution to protein solubility: Asp, Glu, and Ser contribute more favorably than the other hydrophilic amino acids in RNase Sa.

Poor protein solubility is a common problem in high-resolution structural studies, formulation of protein pharmaceuticals, and biochemical characterization of proteins. One popular strategy to improve protein solubility is to use site-directed mutagenesis to make hydrophobic to hydrophilic mutations on the protein surface. However, a systematic investigation of the relative contributions of all 20 amino acids to protein solubility has not been done. Here, 20 variants at the completely solvent-exposed position 76 of ribonuclease (RNase) Sa are made to compare the contributions of each amino acid. Stability measurements were also made for these variants, which occur at the i+1 position of a type II beta-turn. Solubility measurements in ammonium sulfate solutions were made at high positive net charge, low net charge, and high negative net charge. Surprisingly, there was a wide range of contributions to protein solubility even among the hydrophilic amino acids. The results suggest that aspartic acid, glutamic acid, and serine contribute significantly more favorably than the other hydrophilic amino acids especially at high net charge. Therefore, to increase protein solubility, asparagine, glutamine, or threonine should be replaced with aspartic acid, glutamic acid or serine.

Amino Acids↗

Robustness: predicting the effects of life history perturbations on stage-structured population dynamics.

Matrix-based models lie at the core of many applications across the physical, engineering and life sciences. In ecology, matrix models arise naturally via population projection matrices (PPM). The eigendata of PPMs provide detailed quantitative and qualitative information on the dynamic behaviour of model populations, especially their asymptotic rates of growth or decline. A fundamental task in modern ecology is to assess the effect that perturbations to life-cycle transition rates of individuals have on such eigendata. The prevailing assessment tools in ecological applications of PPMs are direct matrix simulations of eigendata and linearised extrapolations to the typically non-linear relationship between perturbation magnitude and the resulting matrix eigenvalues. In recent years, mathematical systems theory has developed an analytical framework, called 'Robustness Analysis and Robust Control', encompassing also algorithms and numerical tools. This framework provides a systematic and precise approach to studying perturbations and uncertainty in systems represented by matrices. Here we lay down the foundations and concepts for a 'robustness' inspired approach to predictive analyses in population ecology. We treat a number of application-specific perturbation problems and show how they can be formulated and analysed using these robustness methodologies.

Animals↗

Methods for nano-particle based vaccine formulation and evaluation of their immunogenicity.

Nano- and microparticles have long been used for the delivery of drugs and are currently being evaluated as vaccine delivery systems. Particulates can elicit potent immune responses, either by direct immuno-stimulation of antigen presenting cells (APC) or/and by delivering antigen to specific cellular compartments and promoting antigen uptake by appropriate stimulatory cell types. Herein, we describe a detailed method for the preparation of a novel nanoparticle-based antigen delivery system which induces strong cellular and humoral immune responses in mice and sheep. This simple system is based on the use of 40 nanometer (nm) inert solid carrier beads to which antigen is covalently coupled before injection. Covalent conjugation of antigen to the nanobeads, assessment of conjugation efficiency, characterisation and measurement of in vivo immunogenicity by cytokine ELISPOT (to measure antigen-specific T-cell responses) and ELISA (to measure antibody titers), are described. Emphasis is placed on providing trouble-shooting advice to enable the reproducible production of soluble nano-size formulations that do not suffer from common problems such as aggregation, as well as understanding the causes and thus avoiding a range of prevalent technical problems that occur when using immune response detection assays, such as the cytokine ELISPOT assay and ELISA.

Animals↗

Are female sex hormones teratogenic?

An analysis of available epidemiologic data leads the present reviewers to conclude that the use of exogenous hormones during human pregnancy has not been proved to cause developmental abnormality in nongenital organs and tissues. This conclusion is further supported by the animal laboratory data. The preponderance of evidence at this writing indicates a lack of causal association between hormonal use during pregnancy and nongenital malformation of the offspring. The quality of the epidemiologic data does not, at this time, permit a definitive conclusion that sex hormones during pregnancy may not, under as yet to be defined conditions, have some adverse effect on human prenatal development. If there are increased risks of nongenital malformations associated with the administration of certain sex steroids, the risks are very small, may not be causal, and are substantially below the spontaneous risk of malformations. In spite of the present degree of uncertainty, the clinical, epidemiologic, and laboratory data do permit the formulation of a rational approach to handling problems related to sex steroid usage and exposure in pregnant women.

Abnormalities, Drug-Induced↗

Fluoride release of glass ionomer-based luting cements in vitro.

STATEMENT OF PROBLEM: There is considerable variation in generic formulation and in reported fluoride release from resin-modified glass ionomer luting cements. PURPOSE: This study compared fluoride release from 2 generically similar resin-modified glass ionomer luting cements (Vitremer and Advance) with release from 2 conventional glass ionomer luting cements (Ketac-Cem and Fuji I). MATERIAL AND METHODS: Ten specimen disks of each of the 4 luting cements were fabricated and immersed in deionized water in individual polystyrene jars. The jars were stored in a humidor at 37 degrees C between test periods. At the same time each day, for 28 days, fluoride release from each specimen disk was measured in parts per million by testing the storage water. RESULTS: The 4 luting cements tested showed an initial high concentration of fluoride release during the first week, followed by a gradual decrease over the study period. Vitremer luting cement demonstrated the greatest mean cumulative fluoride release in parts per million over the study period (198), followed by Fuji I (140), Ketac-Cem (110), and Advance (99) luting cements. CONCLUSIONS: Resin-modified glass ionomer luting cements showed fluoride release comparable to the conventional glass ionomer luting cements. Vitremer luting cement released more fluoride over the 28-day period than the other cements.

Analysis of Variance↗

The problem of lindane.

The human clinical use of 1% lindane formulations has become somewhat controversial during the past five years. This review is an in-depth report of the efficacy and safety of 1% lindane compared with the agents that have been preferred as alternative. Almost all of the suspected adverse drug reactions (ADR) from 1% lindane have involved substantial misuse. The number of suspected ADRs remains small, especially when compared with the magnitude of human clinical use of 1% lindane preparations in the United States (50 million ounces during the past five years). One percent lindane should continue to remain the preparation of choice for nearly all patients with scabies and lice, but dermatologists should appreciate that these views are not necessarily shared by all health professionals. Consequently, it is most appropriate to explain the possible side effects from misuse of lindane to each patient. This brief period of patient education is time well spent--it will help maintain proper compliance and allay the upset that many of your patients may have if they encounter negative opinions about lindane in the lay and medical press or from other health professionals.

Absorption↗

Production and characterisation of highly concentrated nanosuspensions by high pressure homogenisation.

Nanosuspensions produced by high-pressure homogenisation are a solution for the formulation of poorly soluble drugs with bioavailability problems. The typical solid concentration of the nanosuspensions is 10%. However, to transfer the nanosuspensions to a dry product (e.g. granulation, tablets, pellets), a higher solid content is required to remove less water. Nanosuspensions with 20 and 30% solid content were produced, the effect of surfactant concentration assessed and their quality (size data) compared with the lower standard concentrations of 1-10% solid.

Particle Size↗

Optimal multiple trait selection for multiple linked quantitative trait loci.

A method was developed to optimize selection on multiple traits with multiple quantitative trait loci (QTLs) over multiple generations. The basis of the method was to replace in the objective function the genotypic value of a single trait with an aggregate genotypic value of multiple traits weighted by their corresponding economic weight, and to maximize the weighted sum of the selection response in the planning horizon. The optimization was formulated as a multiple stage optimal control problem and solved by a forward and backward iteration cycle. The practical utility of this method was illustrated in an example of pig breeding population, in which the number born alive (NBA) and days to 100 kg (D100) were used as parameters. The selection response of this method was compared with standard QTL selection and regular best linear unbiased prediction (BLUP) selection. Results showed that optimal selection achieved greater selection response than either standard QTL or regular BLUP selections. The influence of economic weight to optimal selection was significant, and the optimization was better as the economic weight of D100 increased. Optimal selection increased the total selection response by two ways: 1) it sacrificed some QTL responses during early generations and 2) it put more emphasis on D100. Optimal cumulative discounted selection gave more weight to D100 than optimal terminal selection in the longer generations.

Algorithms↗

A comprehensive medical evaluation of patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) is a common and distressful condition. It is imperative that all physicians do their best to help these suffering patients with understanding and respect, since the primary responsibility of a physician is to ameliorate suffering of a patient, irrespective of the type of the disease or the illness. (The authors use the terms "disease" and "illness" synonymously, since any distinction between these two terms are really pointless because the word "disease" means lack of ease or presence of suffering.) It is clear that a physician cannot optimize management of a patient with FMS without a thorough medical and psychologic evaluation. A good evaluation helps to make a proper diagnosis, assess severity, recognize aggravating and relieving factors of symptoms, appraise psychologic factors, evaluate relevant associated or concomitant conditions, document individualized problems in a given patient, and subsequently formulate proper and individualized management. This article focuses on the major elements of a comprehensive medical evaluation, with some reference to psychologic aspects--are covered in detail in the article by Turk et al in this issue.

Diagnosis, Differential↗

Evaluation of health information systems-problems and challenges.

OBJECTIVES: Information technology (IT) is emerging in health care. A rigorous evaluation of this technology is recommended and of high importance for decision makers and users. However, many authors report problems during the evaluation of information technology in health care. In this paper, we discuss some of these problems, and propose possible solutions for these problems. METHODS: Based on own experience and backed up by a literature review, some important problems during IT evaluation in health care together with their reasons, consequences and possible solutions are presented and structured. RESULTS AND CONCLUSIONS: We define three main problem areas-the complexity of the evaluation object, the complexity of an evaluation project, and the motivation for evaluation. Many evaluation problems can be subsumed under those three problem areas. A broadly accepted framework for evaluation of IT in healthcare seems desirable to address those problems. Such a framework should help to formulate relevant questions, to find adequate methods and tools, and to apply them in a sensible way.

Attitude to Computers↗