Effect of Animal and Industrial Trans Fatty Acids on HDL and LDL Cholesterol Levels in Humans – A Quantitative Review

Background

Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid and trans fatty acids from ruminant animals are less clear. We reviewed the literature, estimated the effects trans fatty acids from ruminant sources and of conjugated trans linoleic acid (CLA) on blood lipoproteins, and compared these with industrial trans fatty acids.

Methodology/Principal Findings

We searched Medline and scanned reference lists for intervention trials that reported effects of industrial trans fatty acids, ruminant trans fatty acids or conjugated linoleic acid on LDL and HDL cholesterol in humans. The 39 studies that met our criteria provided results of 29 treatments with industrial trans fatty acids, 6 with ruminant trans fatty acids and 17 with CLA. Control treatments differed between studies; to enable comparison between studies we recalculated for each study what the effect of trans fatty acids on lipoprotein would be if they isocalorically replaced cis mono unsaturated fatty acids. In linear regression analysis the plasma LDL to HDL cholesterol ratio increased by 0.055 (95%CI 0.044–0.066) for each % of dietary energy from industrial trans fatty acids replacing cis monounsaturated fatty acids The increase in the LDL to HDL ratio for each % of energy was 0.038 (95%CI 0.012–0.065) for ruminant trans fatty acids, and 0.043 (95% CI 0.012–0.074) for conjugated linoleic acid (p = 0.99 for difference between CLA and industrial trans fatty acids; p = 0.37 for ruminant versus industrial trans fatty acids).

Conclusions/Significance

Published data suggest that all fatty acids with a double bond in the trans configuration raise the ratio of plasma LDL to HDL cholesterol.     

An Integrative Model of Patient-Centeredness – A Systematic Review and Concept Analysis

Background

Existing models of patient-centeredness reveal a lack of conceptual clarity. This results in a heterogeneous use of the term, unclear measurement dimensions, inconsistent results regarding the effectiveness of patient-centered interventions, and finally in difficulties in implementing patient-centered care. The aim of this systematic review was to identify the different dimensions of patient-centeredness described in the literature and to propose an integrative model of patient-centeredness based on these results.

Methods

Protocol driven search in five databases, combined with a comprehensive secondary search strategy. All articles that include a definition of patient-centeredness were eligible for inclusion in the review and subject to subsequent content analysis. Two researchers independently first screened titles and abstracts, then assessed full texts for eligibility. In each article the given definition of patient-centeredness was coded independently by two researchers. We discussed codes within the research team and condensed them into an integrative model of patient-centeredness.

Results

4707 records were identified through primary and secondary search, of which 706 were retained after screening of titles and abstracts. 417 articles (59%) contained a definition of patient-centeredness and were coded. 15 dimensions of patient-centeredness were identified: essential characteristics of clinician, clinician-patient relationship, clinician-patient communication, patient as unique person, biopsychosocial perspective, patient information, patient involvement in care, involvement of family and friends, patient empowerment, physical support, emotional support, integration of medical and non-medical care, teamwork and teambuilding, access to care, coordination and continuity of care. In the resulting integrative model the dimensions were mapped onto different levels of care.

Conclusions

The proposed integrative model of patient-centeredness allows different stakeholders to speak the same language. It provides a foundation for creating better measures and interventions. It can also be used to inform the development of clinical guidance documents and health policy directives, and through this support the shift towards patient-centered health care.     

High-Pass Filter Characteristics of the Baroreflex – A Comparison of Frequency Domain and Pharmacological Methods

Pharmacological methods to assess baroreflex sensitivity evoke supra-physiological blood pressure changes whereas computational methods use spontaneous fluctuations of blood pressure. The relationships among the different baroreflex assessment methods are still not fully understood. Although strong advocates for each technique exist, the differences between these methods need further clarification. Understanding the differences between pharmacological and spontaneous baroreflex methods could provide important insight into the baroreflex physiology. We compared the modified Oxford baroreflex gain and the transfer function modulus between spontaneous RR interval and blood pressure fluctuations in 18 healthy subjects (age: 39±10 yrs., BMI: 26±4.9). The transfer function was calculated over the low-frequency range of the RR interval and systolic blood pressure oscillations during random-frequency paced breathing. The average modified Oxford baroreflex gain was lower than the average transfer function modulus (15.7±9.2 ms/mmHg vs. 19.4±10.5 ms/mmHg, P<0.05). The difference between the two baroreflex measures within the individual subjects comprised a systematic difference (relative mean difference: 20.7%) and a random variance (typical error: 3.9 ms/mmHg). The transfer function modulus gradually increased with the frequency within the low-frequency range (LF), on average from 10.4±7.3 ms/mmHg to 21.2±9.8 ms/mmHg across subjects. Narrowing the zone of interest within the LF band produced a decrease in both the systematic difference (relative mean difference: 0.5%) and the random variance (typical error: 2.1 ms/mmHg) between the modified Oxford gain and the transfer function modulus. Our data suggest that the frequency dependent increase in low-frequency transfer function modulus between RR interval and blood pressure fluctuations contributes to both the systematic difference (bias) and the random variance (error) between the pharmacological and transfer function baroreflex measures. This finding suggests that both methodological and physiological factors underlie the observed disagreement between the pharmacological and the transfer function method. Thus both baroreflex measures contribute complementary information and can be considered valid methods for baroreflex sensitivity assessment.     

Industrial Applications of Solid-Phase Peptide Synthesis – A Status Report

Despite the fact that the structure of peptides has been known for more than a century, it was not until du Vigneaud published the synthesis of oxytocin 50 years later that the field was truly launched and the use of peptides as pharmaceuticals began. Since then, technical progress in the field has been astonishing, and the synthesis of peptides of virtually any size and complexity is now possible, with scale-up to the level of metric tonnes a reality. Perhaps the most important development was Merrifield’s publication of the solid-phase peptide synthesis (SPPS) method, which completely revolutionized the field, both from the perspective of accelerating research and discovery, and also because of its now widespread use for the manufacture of peptides for use as active pharmaceutical ingredients (APIs). The application of the SPPS method to the manufacture of peptide APIs will be reviewed, including both a historical overview and a summary of the current status. Some of the remaining challenges will also be discussed.     

Cost-Effectiveness of HBV and HCV Screening Strategies – A Systematic Review of Existing Modelling Techniques

Introduction

Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches.

Methods

A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions.

Results

The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology.

Conclusion

When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers.     

Emerging multilevel environmental governance – A case of public participation in Poland

In recent decades, nature conservation policies have increasingly considered the participation of various actors. However, the effectiveness of such efforts is often questionable, and better methods of engaging stakeholders are still being sought. In this paper, we present an analysis of a consultation program conducted in the final stage of site selection for Natura 2000 in Małopolska, a region located in southern Poland. Based on a desk study and qualitative research, we analysed the modes and degrees of participation, the normative foundations of the consultation program, and the goals and expectations that characterise participants. The results are discussed using Unnestall's and Arnstein's typologies of participation, which show the limited success of the participatory process in representing all relevant stakeholders and enabling their actual influence on final decisions. The importance of implementing the EU directives for emerging multilevel governance in the nature conservation sector in Central and Eastern Europe, including Poland, is highlighted. In the context of Poland, the consultation program analysed appeared to be a novel and innovative step forward towards the development of a meaningful participatory approach in this region of Europe.     

Evaluation of “Classic” and Emerging Contaminants Resulting from the Application of Biosolids to Agricultural Lands: A Review

The presence of detectable amounts of contaminants in treated sewage sludge (concentrations μg/kg – mg/kg) has led to concerns that land applications of biosolids may result in an accumulation of contaminants in the soil and their subsequent translocation through the food chain. Despite advances in wastewater management (e.g., anaerobic, thermophilic, and mesophilic digestion), many compounds and their metabolites remain intact following treatment. This review looks at the main risk factors relating to the occurrence of “classic” (persistent organic pollutants [POPs]) and emerging pollutants (pharmaceuticals and personal care products) in biosolids. Relevant EU legislation and risk assessment strategies for the control of emerging contaminants are also considered. Organic pollutants regulated under the Stockholm Convention on POPs along with PPCPs were identified as contaminants of concern based on the risk factors: persistence, bioaccumulation, and toxicity (PBT). PPCPs were recognized as being of particular concern as their high transformation/removal rates are compensated by their continuous introduction into the environment. This study highlights the growing concern in relation to emerging contaminants in biosolids and highlights risk assessment strategies that can be used to characterize potential human/environmental risks.     

Zinc–Ligand Interactions Modulate Assembly and Stability of the Insulin Hexamer – A Review

Zinc and calcium ions play important roles in the biosynthesis and storage of insulin. Insulin biosynthesis occurs within the β-cells of the pancreas via preproinsulin and proinsulin precursors. In the golgi apparatus, proinsulin is sequestered within Zn²⁺- and Ca²⁺-rich storage/secretory vesicles and assembled into a Zn²⁺ and Ca²⁺ containing hexameric species, (Zn²⁺)₂(Ca²⁺)(Proin)₆. In the vesicle, (Zn²⁺)₂(Ca²⁺)(Proin)₆ is converted to the insulin hexamer, (Zn²⁺)₂(Ca²⁺)(In)₆, by excision of the C-peptide through the action of proteolytic enzymes. The conversion of (Zn²⁺)₂(Ca²⁺)(Proin)₆to (Zn²⁺)₂(Ca²⁺)(In)₆ significantly lowers the solubility of the hexamer, causing crystallization within the vesicle. The (Zn²⁺)₂(Ca²⁺)(In)₆ hexamer is an allosteric protein that undergoes ligand-mediated interconversion among three global conformation states designated T₆, T₃R₃ and R₆. Two classes of allosteric sites have been identified; hydrophobic pockets (3 in T₃R₃ and 6 in R₆) that bind phenolic ligands, and anion sites (1 in T₃R₃ and 2 in R₆) that bind monovalent anions. The allosteric states differ widely with respect to the physical and chemical stability of the insulin subunits. Fusion of the vesicle with the plasma membrane results in the expulsion of the insulin crystals into the intercellular fluid. Dissolution of the crystals, dissociation of the hexamers to monomer and transport of monomers to the liver and other tissues then occurs via the blood stream. Insulin action then follows binding to the insulin receptors. The role of Zn²⁺ in the assembly, structure, allosteric properties, and dynamic behavior of the insulin hexamer will be discussed in relation to biological function.     

Mozzarella Cheese – A Review of the Structural Development During Processing

From its journey from milk through to its end use, Mozzarella cheese undergoes significant transformations in its makeup of components and their structural arrangement. The typical Mozzarella processing steps each alter the structural configuration of the system. The colloidal dispersion of proteins, fat, lactose and minerals that is milk experiences physical, thermal, chemical, biological and ionic induced changes to its composition and structure throughout the manufacturing process and storage. This review critically evaluates the literature related to the structural changes occurring as a result of each step in Mozzarella cheese production process. Emphasis is placed on the role of each step and the induced transformations at the micro and macro scale in the system. Additionally, the review also looks at the changes that occur as a result of storage. This evolution in structure culminates in the creation of an end product with a bi-continuous gel structure that has a desired functionality in its end use.     

Methods Used in Economic Evaluations of Chronic Kidney Disease Testing — A Systematic Review

BackgroundThe prevalence of chronic kidney disease (CKD) is high in general populations around the world. Targeted testing and screening for CKD are often conducted to help identify individuals that may benefit from treatment to ameliorate or prevent their disease progression.AimsThis systematic review examines the methods used in economic evaluations of testing and screening in CKD, with a particular focus on whether test accuracy has been considered, and how analysis has incorporated issues that may be important to the patient, such as the impact of testing on quality of life and the costs they incur.MethodsArticles that described model-based economic evaluations of patient testing interventions focused on CKD were identified through the searching of electronic databases and the hand searching of the bibliographies of the included studies.ResultsThe initial electronic searches identified 2,671 papers of which 21 were included in the final review. Eighteen studies focused on proteinuria, three evaluated glomerular filtration rate testing and one included both tests. The full impact of inaccurate test results was frequently not considered in economic evaluations in this setting as a societal perspective was rarely adopted. The impact of false positive tests on patients in terms of the costs incurred in re-attending for repeat testing, and the anxiety associated with a positive test was almost always overlooked. In one study where the impact of a false positive test on patient quality of life was examined in sensitivity analysis, it had a significant impact on the conclusions drawn from the model.ConclusionFuture economic evaluations of kidney function testing should examine testing and monitoring pathways from the perspective of patients, to ensure that issues that are important to patients, such as the possibility of inaccurate test results, are properly considered in the analysis.     

Effect of Diabetes Mellitus Type 2 on Salivary Glucose – A Systematic Review and Meta-Analysis of Observational Studies

Background

Early screening of type 2 diabetes mellitus (DM) is essential for improved prognosis and effective delay of clinical complications. However, testing for high glycemia often requires invasive and painful blood testing, limiting its large-scale applicability. We have combined new, unpublished data with published data comparing salivary glucose levels in type 2 DM patients and controls and/or looked at the correlation between salivary glucose and glycemia/HbA1c to systematically review the effectiveness of salivary glucose to estimate glycemia and HbA1c. We further discuss salivary glucose as a biomarker for large-scale screening of diabetes or developing type 2 DM.

Methods and Findings

We conducted a meta-analysis of peer-reviewed published articles that reported data regarding mean salivary glucose levels and/or correlation between salivary glucose levels and glycemia or HbA1c for type 2 DM and non-diabetic individuals and combined them with our own unpublished results. Our global meta-analysis of standardized mean differences on salivary glucose levels shows an overall large positive effect of type 2 DM over salivary glucose (Hedge''s g = 1.37). The global correlation coefficient (r) between salivary glucose and glycemia was large (r = 0.49), with subgroups ranging from medium (r = 0.30 in non-diabetics) to very large (r = 0.67 in diabetics). Meta-analysis of the global correlation between salivary glucose and HbA1c showed an overall association of medium strength (r = 0.37).

Conclusions

Our systematic review reports an overall meaningful salivary glucose concentration increase in type 2 DM and a significant overall relationship between salivary glucose concentration and associated glycemia/HbA1c values, with the strength of the correlation increasing for higher glycemia/HbA1c values. These results support the potential of salivary glucose levels as a biomarker for type 2 DM, providing a less painful/invasive method for screening type 2 DM, as well as for monitoring blood glucose levels in large cohorts of DM patients.     

Medical Therapies for Uterine Fibroids – A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials

Background

Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence.

Purpose

To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence.

Study Selection

Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013.

Data Extraction

Two authors independently extracted data from identified studies.

Data Synthesis

A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence—Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated.

Results and Limitations

A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes.

Conclusions

There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed.     

Glioma Cell and Astrocyte Co-cultures As a Model to Study Tumor–Tissue Interactions: A Review of Methods

Astrocytes are a dominant cell type that envelopes the glioma bed. Typically, that is followed by formation of contacts between astrocytes and glioma cells and accompanied by change in astrocyte phenotype, a phenomenon known as a ‘reactive astrogliosis.’ Generally considered glioma-promoting, astrocytes have many controversial peculiarities in communication with tumor cells, which need thorough examination in vitro. This review is devoted to in vitro co-culture studies of glioma cells and astrocytes. Firstly, we list several fundamental works which allow understanding the modalities of co-culturing. Cell-to-cell interactions between astrocytes and glioma cells, the roles of astrocytes in tumor metabolism, and glioma-related angiogenesis are reviewed. In the review, we also discuss communications between glioma stem cells and astrocytes. Co-cultures of glioma cells and astrocytes are used for studying anti-glioma treatment approaches. We also enumerate surgical, chemotherapeutic, and radiotherapeutic methods assessed in co-culture experiments. In conclusion, we underline collisions in the field and point out the role of the co-cultures for neurobiological studies.     

Modeling of Novel Diagnostic Strategies for Active Tuberculosis – A Systematic Review: Current Practices and Recommendations

Introduction

The field of diagnostics for active tuberculosis (TB) is rapidly developing. TB diagnostic modeling can help to inform policy makers and support complicated decisions on diagnostic strategy, with important budgetary implications. Demand for TB diagnostic modeling is likely to increase, and an evaluation of current practice is important. We aimed to systematically review all studies employing mathematical modeling to evaluate cost-effectiveness or epidemiological impact of novel diagnostic strategies for active TB.

Methods

Pubmed, personal libraries and reference lists were searched to identify eligible papers. We extracted data on a wide variety of model structure, parameter choices, sensitivity analyses and study conclusions, which were discussed during a meeting of content experts.

Results & Discussion

From 5619 records a total of 36 papers were included in the analysis. Sixteen papers included population impact/transmission modeling, 5 were health systems models, and 24 included estimates of cost-effectiveness. Transmission and health systems models included specific structure to explore the importance of the diagnostic pathway (n = 4), key determinants of diagnostic delay (n = 5), operational context (n = 5), and the pre-diagnostic infectious period (n = 1). The majority of models implemented sensitivity analysis, although only 18 studies described multi-way sensitivity analysis of more than 2 parameters simultaneously. Among the models used to make cost-effectiveness estimates, most frequent diagnostic assays studied included Xpert MTB/RIF (n = 7), and alternative nucleic acid amplification tests (NAATs) (n = 4). Most (n = 16) of the cost-effectiveness models compared new assays to an existing baseline and generated an incremental cost-effectiveness ratio (ICER).

Conclusion

Although models have addressed a small number of important issues, many decisions regarding implementation of TB diagnostics are being made without the full benefits of insight from mathematical models. Further models are needed that address a wider array of diagnostic and epidemiological settings, that explore the inherent uncertainty of models and that include additional epidemiological data on transmission implications of false-negative diagnosis and the pre-diagnostic period.     

Science and Knowledge of Free-Roaming Donkeys—A Critical Review

The emergence of free-roaming donkey (Equus asinus) populations globally has brought novel challenges for conservationists, land managers, and those concerned about animal welfare. We provide a review of the scientific literature pertaining to the place and role of free-roaming donkeys from 1950 until 2020. Using quantitative and qualitative techniques, namely categorical and thematic analysis and critical discourse analysis, to review >100 articles, we critically examine the logics and rationales that are used to either support or denounce donkey presence in particular landscapes and discuss their place and role in different ecological contexts. Free-roaming donkeys are largely understudied and clouded by dichotomous points of view, different conservation agendas, and the presence of other species in donkey habitat. There is an important need for more in-depth, site-specific studies on free-roaming donkeys that draw on tools and techniques from across the social and natural sciences. Such efforts would offer a richer, more holistic, and comprehensive picture of free-roaming donkeys that consider both human and animal perspectives and the wider environment. This has important implications for generating long-term sustainable management solutions for free-roaming donkeys. © 2021 The Authors. The Journal of Wildlife Management published by Wiley Periodicals LLC on behalf of The Wildlife Society.