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Breast cancer remains a leading cause of cancer-related mortality in women. In recent years, regulation of genes involved in heparan sulphate (HS) biosynthesis have received increased interest as regulators of breast cancer cell adhesion and invasion. The exostosin (EXT) proteins are glycosyltransferases involved in elongation of HS, a regulator of intracellular signaling, cell–cell interactions, and tissue morphogenesis. The EXT family contains five members: EXT1, EXT2, and three EXT-like (EXTL) members: EXTL1, EXTL2, and EXTL3. While the expression levels of these enzymes change in tumor cells, little is known how this changes the structure and function of HS. In the present study, we investigated gene expression profiles of the EXT family members, their glycosyltransferase activities and HS structure in the estrogen receptor (ER), and progesterone receptor (PR) positive MCF7 cells, and the ER, PR, and human epidermal growth factor receptor-2 (HER2) negative MDA-MB-231 and HCC38 epithelial breast carcinoma cell lines. The gene expression profiles for MDA-MB-231 and HCC38 cells were very similar. In both cell lines EXTL2 was found to be up-regulated whereas EXT2 was down-regulated. Interestingly, despite having similar expression of HS elongation enzymes the two cell lines synthesized HS chains of significantly different lengths. Furthermore, both MDA-MB-231 and HCC38 exhibited markedly decreased levels of HS 6-O-sulphated disaccharides. Although the gene expression profiles of the elongation enzymes did not correlate with the length of HS chains, our results indicated specific differences in EXT enzyme levels and HS fine structure characteristic of the carcinogenic properties of the breast carcinoma cells. [ABSTRACT FROM AUTHOR]

Changes in mucin-type O-linked glycosylation are seen in over 90% of breast cancers where increased sialylation is often observed and a change from branched glycans to linear glycans is often seen. There are many mechanisms involved including increased/altered expression of glycosyltransferases and relocalisation to the endoplasmic reticulum of the enzymes responsible for the addition of the first sugar, N-acetyl-D-galactosamine. It is now becoming clear that these changes can contribute to tumour growth and progression by modulating the micro-environment through glycan-sensing lectins expressed on immune cells, by modulating interactions with tumour surface receptors and by binding to selectins. The understanding of how changes in mucin-type O-linked glycosylation influence tumour growth and progression reveals new potential targets for therapeutic intervention in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Fucosyltransferases (FUTs) are critical for glycoproteins and glycolipid chains and serve an important role in the adhesive interaction between selectins and their ligands, which contribute to tumor cell spread and metastasis. While multiple cancer cell lines heavily express FUT3, the present study investigated the expression level of FUT3 in different human pancreatic cancer cell lines. Forced expression and knockdown of FUT3 in different pancreatic cancer cell line demonstrated that FUT3 is important in cell proliferation. Using wound healing and transwell assays, it was observed that the migratory ability was decreased in FUT3 downregulated Capan-1 cell line, compared with the normal Capan-1 cell line. Furthermore, it was demonstrated that the knockdown of FUT3 impaired the adhesion of Capan-1 with E-selectin and inhibited transforming growth factor (TGF)-β-induced epithelial-mesenchymal transition. These data suggest that the knockdown of FUT3 inhibits the tumorigenesis in vivo and FUT3 may be a promising target aiming at reducing the metastatic virulence of pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

Triple negative breast cancer (TNBC) is a major global public health problem. The lack of targeted therapy and the elevated mortality evidence the need for better knowledge of the tumor biology. Hypoxia and aberrant glycosylation are associated with advanced stages of malignancy, tumor progression and treatment resistance. Importantly, serum deprivation regulates the invasive phenotype and favors TNBC cell survival. However, in TNBC, the role of hypoxia and serum deprivation in the regulation of glycosylation remains largely unknown. The effects of hypoxia and serum deprivation on the expression of glycosyltransferases and glycan profile were evaluated in the MDA-MB-231 cell line. We showed that the overexpression of HIF-1α was accompanied by acquisition of epithelial-mesenchimal transition features. Significant upregulation of fucosyl- and sialyltransferases involved in the synthesis of tumorassociated carbohydrate antigens was observed together with changes in fucosylation and sialylation detected by Aleuria aurantia lectin and Sambucus nigra agglutinin lectin blots. Bioinformatic analysis further indicated a mechanism by which HIF-1α can regulate ST3GAL6 expression and the relationship within the intrinsic characteristics of TNBC tumors. In conclusion, our results showed the involvement of hypoxia and serum deprivation in glycosylation profile regulation of TNBC cells triggering breast cancer aggressive features and suggesting glycosylation as a potential diagnostic and therapeutic target. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Chemistry is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Friction stir welding (FSW), a highly efficient solid-state joining technique, has been termed as “green” technology due to its energy efficiency and environment friendliness. It is an enabling technology for joining metallic materials, in particular lightweight high-strength aluminum and magnesium alloys which were classified as unweldable by traditional fusion welding. It is thus considered to be the most significant development in the area of material joining over the past two decades. Friction stir processing (FSP) was later developed based on the basic principles of FSW. FSP has been proven to be an effective and versatile metal-working technique for modifying and fabricating metallic materials. FSW/FSP of aluminum alloys has prompted considerable scientific and technological interest since it has a potential for revolutionizing the manufacturing process in the aerospace, defense, marine, automotive, and railway industries. To promote widespread applications of FSW/FSP technology and ensure the structural integrity, safety and durability of the FSW/FSP components, it is essential to optimize the process parameters, and to evaluate thoroughly the microstructural changes and mechanical properties of the welded/processed samples. This review article is thus aimed at summarizing recent advances in the microstructural evolution and mechanical properties of FSW/FSP aluminum alloys. Particular attention is paid to recrystallization mechanism, grain boundary characteristics, phase transformation, texture evolution, characteristic microstructures, and the effect of these factors on the hardness, tensile and fatigue properties as well as superplastic behavior of FSW/FSP aluminum alloys. [ABSTRACT FROM AUTHOR]

Background: N-glycolylneuraminic acid (Neu5Gc) is a non-human red-meat-derived sialic acid immunogenic to humans. Neu5Gc can be metabolically incorporated into glycan chains on human endothelial and epithelial surfaces. This represents the first example of a “xeno-autoantigen”, against which circulating human “xeno-autoantibodies” can react. The resulting inflammation (“xenosialitis”) has been demonstrated in human-like Neu5Gc-deficient mice and contributed to carcinoma progression via antibody-mediated inflammation. Anti-Neu5Gc antibodies have potential as biomarkers for diseases associated with red meat consumption such as carcinomas, atherosclerosis, and type 2 diabetes. Methods: ELISA assays measured antibodies against Neu5Gc or Neu5Gc-glycans in plasma or serum samples from the Nurses’ Health Studies, the Health Professionals Follow-up Study, and the European Prospective Investigation into Cancer and Nutrition, including inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over 1–3 years in archived samples. We also assessed associations between antibody levels and coronary artery disease risk (CAD) or red meat intake. A glycan microarray was used to detected antibodies against multiple Neu5Gc-glycan epitopes. A nested case-control study design assessed the association between total anti-Neu5Gc antibodies detected in the glycan array assay and the risk of colorectal cancer (CRC). Results: ELISA assays showed a wide range of anti-Neu5Gc responses and good inter-assay reproducibility, stability with delayed sample processing, and within-person reproducibility over time, but these antibody levels did not correlate with CAD risk or red meat intake. Antibodies against Neu5Gc alone or against individual Neu5Gc-bearing epitopes were also not associated with colorectal cancer (CRC) risk. However, a sialoglycan microarray study demonstrated positive association with CRC risk when the total antibody responses against all Neu5Gc-glycans were combined. Individuals in the top quartile of total anti-Neu5Gc IgG antibody concentrations had nearly three times the risk compared to those in the bottom quartile (Multivariate Odds Ratio comparing top to bottom quartile: 2.98, 95% CI: 0.80, 11.1; P for trend = 0.02). Conclusions: Further work harnessing the utility of these anti-Neu5Gc antibodies as biomarkers in red meat-associated diseases must consider diversity in individual antibody profiles against different Neu5Gc-bearing glycans. Traditional ELISA assays for antibodies directed against Neu5Gc alone, or against specific Neu5Gc-glycans may not be adequate to define risk associations. Our finding of a positive association of total anti-Neu5Gc antibodies with CRC risk also warrants confirmation in larger prospective studies. [ABSTRACT FROM AUTHOR]

The estuarine crocodile (Crocodylus porosus) is one of the largest and most widespread crocodilians in the world. Although considered an apex species, the role of the estuarine crocodile in aquatic foodwebs is poorly understood; we know what crocodiles ingest, but not what nourishes them. In this study, we used a combination of stable isotope measurements (δ13C, δ15N, and δ34S) and direct feeding observations to identify the source of nutrition of estuarine crocodiles in Kakadu National Park, Northern Australia. Our results show that most crocodiles sampled (size 850 – 4200mm, with 76% of them being > 2.5 m) consume a large variety of prey, however a large proportion of their nutrition is derived from terrestrial prey. Introduced species such as water buffaloes (Bubalus bubalis) and pigs (Sus scrofa) could contribute between 53 and 84% to the nutrition of the sampled crocodiles. The isotopic composition of large crocodiles (total length > 3 m) suggested possible increase in marine prey consumption with size (R2 = 0.30; p = 0.005). Additionally, we found crocodiles sampled in the dry season had on average higher terrestrial contributions compared to crocodiles sampled during the wet season (84.1 ± 2.4% versus 55.4 ± 7.0%). Overall, we found that terrestrial prey are important source of nutrition for many crocodiles in this region where introduced herbivorous mammals are abundant. [ABSTRACT FROM AUTHOR]

Beyond its physical importance in both fundamental and climate research, atmospheric icing is considered as a severe operational condition in many engineering applications like aviation, electrical power transmission and windenergy production. To reproduce such icing conditions in a laboratory environment, icing wind tunnels are frequently used. In this paper, a comprehensive overview on the design, construction and commissioning of the Braunschweig Icing Wind Tunnel is given. The tunnel features a test section of 0.5m x 0.5m with peak velocities of up to 40ms-1. The static air temperature ranges from -25 to +30 °C. Supercooled droplet icing with liquid water contents up to 3 gm-3 can be reproduced. The unique aspect of this facility is the combination of an icing tunnel with a cloud chamber system for making ice particles. These ice particles are more realistic in shape and density than those usually used for mixed phase and ice crystal icing experiments. Ice water contents up to 20 gm-3 can be generated. We further show how current state-of-the-art measurement techniques for particle sizing are performed on ice particles. The data are compared to those of in-flight measurements in mesoscale convective cloud systems in tropical regions. Finally, some applications of the icing wind tunnel are presented. [ABSTRACT FROM AUTHOR]

Metastatic breast cancer is currently incurable. It has recently emerged that different metabolic pathways support metastatic breast cancer. To further uncover metabolic pathways enabling breast cancer metastasis, we investigated metabolic differences in mouse tumors of differing metastatic propensities using mass spectrometry-based metabolomics. We found that sialic acid metabolism is upregulated in highly metastatic breast tumors. Knocking out a key gene in sialic acid metabolism, Cmas, inhibits synthesis of the activated form of sialic acid, cytidine monophosphate-sialic acid and decreases the formation of lung metastases in vivo. Thus, the sialic acid pathway may be a new target against metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Altered surface glycosylation is a key feature of cancers, including gynecologic malignancies. Hypersialylation, the overexpression of sialic acid, is known to promote tumor progression and to dampen antitumor responses by mechanisms that also involve sialic acid binding immunoglobulin-like lectins (Siglecs), inhibitory immune receptors. Here, we discuss the expression patterns of Siglecs and sialyltransferases (STs) in gynecologic cancers, including breast, ovarian, and uterine malignancies, based on evidence from The Cancer Genome Atlas. The balance between sialosides generated by specific STs within the tumor microenvironment and Siglecs on leukocytes may play a decisive role for antitumor immunity. An interdisciplinary effort is required to decipher the characteristics and biological impact of the altered tumor sialome in gynecologic cancers and to exploit this knowledge to the clinical benefit of patients. [ABSTRACT FROM AUTHOR]

Immunotherapies are set to become part of the therapeutic repertoire for breast cancer in the near future. Active vaccination is a promising strategy, especially in tumors that have a specific tumor-associated antigen. Although cellular immunotherapies have not yet shown efficacy, new technologies are on the way to improve this approach. Given the recent Food and Drug Administration approval of chimeric antigen receptor (CAR) T cells for leukemia, it is only a question of time before solid tumors will follow. However, not all breast cancer patients will respond to cellular or other immunotherapy. Hence, we must define subpopulations of breast cancer patients who benefit from this new approach. [ABSTRACT FROM AUTHOR]

Abstract: The present study evaluates the protective effect of α‐lipoic acid (LA) against arsenic‐induced testicular and epididymal oxidative damage in rats. Arsenic caused significant reduction in the reproductive organ weights, serum testosterone levels, testicular daily sperm count, epididymal sperm count, sperm motility, sperm viability, and sperm membrane integrity. Significant reduction in the activity levels of superoxide dismutase, catalase, and glutathione levels with a concomitant increase in the lipid peroxidation and protein carbonyl content in the testis and the cauda epididymis of arsenic‐exposed rats. Arsenic intoxication also enhanced the testicular caspase‐3 mRNA levels, disorganization of testicular and cauda epididymal architecture as well as increased arsenic content in the testis and the cauda epididymis of rats. Arsenic exposure also deteriorated fertility ability in male rats over controls. Conversely, α‐LA negated the testicular and cauda epididymal oxidative stress and restored the male reproductive health in arsenic‐exposed rats. [ABSTRACT FROM AUTHOR]

Association between altered glycosylation patterns and poor prognosis in cancer points glycans as potential specific tumor markers. Most proteins are glycosylated and functionally arranged on cell surface and extracellular matrix, mediating interactions and cellular signaling. Thereby, aberrant glycans may be considered a pathological phenotype at least as important as changes in protein expression for cancer and other complex diseases. As most serum glycoproteins have hepatic origin, liver disease phenotypes, such as hepatocellular carcinoma (HCC), may present altered glycan profile and display important modifications. One of the prominent obstacles in HCC is the diagnostic in advanced stages when patients have several liver dysfunctions, limiting treatment options and life expectancy. The characterization of glycomic profiles in pathological conditions by means of mass spectrometry (MS) may lead to the discovery of early diagnostic markers using non-invasive approaches. MS is a powerful analytical technique capable of elucidating many glycobiological issues and overcome limitations of the serological markers currently applied in clinical practice. Therefore, MS-based glycomics of tumor biomarkers is a promising tool to increase early detection and monitoring of disease. [ABSTRACT FROM AUTHOR]

Several studies have shown that the origin of carbon fuelling food webs in streams depends on riparian cover type. In forested stream sites allochthonous resources fuel food webs, whereas autochthonous resources support biomass in grassland (open-canopy) stream sites. However, some studies suggest that autochthonous carbon (of highest quality) is preferentially assimilated regardless of riparian cover and that the food-chain length (FCL) may be larger in grassland than in forested sites. We used stable isotopes of carbon and nitrogen in adjacent grassland and forested reaches to compare the contribution of autochthonous vs. allochthonous resources to the biomass of the whole macroinvertebrate assemblage and to the most abundant taxa. Moreover, we compared the FCL between forested and grassland sites by estimating the trophic position of brown trout, Salmo trutta. Autochthonous support to macroinvertebrate biomass was higher in grassland than in forested sites, often changing from a dominantly autochthonous to an allochthonous-generated biomass from grassland to forested. This held true for the whole macroinvertebrate assemblage and for specific species. FCL remained similar between reach types. Our study suggests that autochthonous resources are assimilated to a higher extent when their availability increases with canopy openness but allochthonous carbon sustain macroinvertebrate biomass in forested reaches. [ABSTRACT FROM AUTHOR]

Caridean shrimp have considerable effects on ecosystem processes and, thus, understanding their use of key habitats is important for determining their potential ecological effect. The present study examined the meso-habitat use of Macrobrachium spinipes, a large-bodied and important amphidromous species, in the Daly River, northern Australia. We examined shrimp abundance at four common meso-habitat types; sand bank, rock bars, undercut and structurally complex banks and mid-channel areas at five sites on three occasions during the dry season (May to October). We found that habitat use changed considerably first, with ontogeny, and, second, with the colonisation of habitats with algae and macrophytes as the dry season progressed. As juveniles, their habitat use was strongly associated with well structured bank environments early in the dry season. By the mid-dry season, juveniles were more abundant within sand habitats recently colonised with macrophytes and filamentous algae. Females showed little change in habitat use, whereas large-bodied dominant males generally favoured rock bars and heavily structured bank environments. The present study has provided significant insights into the changes in use of key riverine habitats throughout the dry season by an ecologically important species. This information will be of considerable value to the determination of environmental flow requirements and food-web investigations. [ABSTRACT FROM AUTHOR]

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis. [ABSTRACT FROM AUTHOR]

Background: Caowu (Radix Aconiti kusnezoffii, CW), the root of Aconitum kusnezoffii Reichb., has widely used clinically in rheumatic arthritis, painful joints, and tumors for thousands of years. However, the toxicity of heart and central nervous system induced by CW still limited the application. Materials and Methods: Metabolomics was performed to identify the sensitive and reliable biomarkers and to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity, and the detoxification by combinatorial intervention of CW with Gancao (Radix Glycyrrhizae) (CG), Baishao (Radix Paeoniae Alba) (CB), and Renshen (Radix Ginseng) (CR) was also analyzed by pattern recognition methods. Results: As a result, the metabolites were characterized and responsible for pentose and glucuronate interconversions, tryptophan metabolism, amino sugar and nucleotide sugar metabolism, taurine and hypotaurine metabolism, fructose and mannose metabolism, and starch and sucrose metabolism, six networks of which were the same to the metabolic pathways of Chuanwu (Radix Aconiti, CHW) group. The ascorbate and aldarate metabolism was also characterized by CW group. The urinary metabolomics also revealed CW-induced serious toxicity to heart and liver. Thirteen significant metabolites were identified and had validated as phenotypic toxicity biomarkers of CW, five biomarkers of which were commonly owned in Aconitum. The changes of toxicity metabolites obtained from combinatorial intervention of CG, CB, and CR also were analyzed to investigate the regulation degree of toxicity biomarkers adjusted by different combinatorial interventions at 6th month. Conclusion: Metabolomics analyses coupled with pattern recognition methods in the evaluation of drug toxicity and finding detoxification methods were highlighted in this work. [ABSTRACT FROM AUTHOR]

Thermal stress has been shown to increase the chances of unsafe behavior during industrial and driving performances due to reductions in mental and attentional resources. Nonetheless, establishing appropriate safety standards regarding environmental temperature has been a major problem, as modulations are also be affected by the task type, complexity, workload, duration, and previous experience with the task. To bypass this attentional and thermoregulatory problem, we focused on the body rather than environmental temperature. Specifically, we measured tympanic, forehead, finger and environmental temperatures accompanied by a battery of attentional tasks. We considered a 10 min baseline period wherein subjects were instructed to sit and relax, followed by three attentional tasks: a continuous performance task (CPT), a flanker task (FT) and a counting task (CT). Using multiple linear regression models, we evaluated which variable(s) were the best predictors of performance. The results showed a decrement in finger temperature due to instruction and task engagement that was absent when the subject was instructed to relax. No changes were observed in tympanic or forehead temperatures, while the environmental temperature remained almost constant for each subject. Specifically, the magnitude of the change in finger temperature was the best predictor of performance in all three attentional tasks. The results presented here suggest that finger temperature can be used as a predictor of alertness, as it predicted performance in attentional tasks better than environmental temperature. These findings strongly support that peripheral temperature can be used as a tool to prevent unsafe behaviors and accidents. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine urban and rural adolescents' behavioral regulation in exercise according to their body weight status. The sample size consisted of 513 adolescents (51.5% males, 48.5% females) aged 15-18 (M = 16.49, SD = 1.11) years old and living in urban and rural areas in Turkey. The Turkish version of Behavioral Regulation in Exercise Questionnaires-2 was used as a measurement tool for the study. The study demonstrated a significant difference in the sub-domain of amotivation toward exercise between urban and rural groups (p < .05). However, the mean scores of external, intrinsic and introjected sub-domains and the relative autonomy index were not significantly different (p > .05). Our results indicated that urban adolescents were less motivated to do exercise than rural adolescents. Obese adolescents living in rural areas had higher amotivation to exercise than normal weight ones. [ABSTRACT FROM AUTHOR]

Investigations on the marine feeding of Atlantic salmon ( Salmo salar L.) in the Northwest Atlantic are limited compared with the Northeast Atlantic. Climate-induced changes to food webs in Atlantic salmon feeding areas have been noted, alongside increased mortality despite a cessation of most marine fisheries. As forage efficiency may be hampering survival, it was important to address this knowledge gap. Atlantic salmon were sampled at three sites on the West Greenland coast (Sisimiut, Nuuk and Qaqortoq) between 2009 and 2011. Gut content and stable isotope analyses were combined to assess spatial and temporal differences in feeding. Capelin ( Mallotus villosus) dominated the diet at Nuuk and Qaqortoq, whereas boreoatlantic armhook squid ( Gonatus fabricii) was the dominant prey at Sisimiut. Hyperiid amphipods ( Themisto spp.) and sand lance ( Ammodytes spp.) were also important. Significant differences were found among sites for both gut contents and stable isotope analyses, with fewer differences evident temporally. Dietary differences were also evident across larger scales, with little overlap demonstrated with Northeast Atlantic diets and the emergence of boreoatlantic armhook squid as an important prey item over time. Atlantic salmon diets are frequently anchored on one or two prey items, on which they appear to specialize, but they will diversify to consume other available pelagic prey. Thus, Atlantic salmon are an opportunistic, generalist predator within the pelagic food web. The variability evident in diet suggests that the limited data available are insufficient to appropriately understand potential vulnerabilities that the species may have to ecosystem changes, and suggest further research is needed. [ABSTRACT FROM AUTHOR]

When interacting with people with aphasia, communication partners use a range of subtle strategies to scaffold, or facilitate, expression and comprehension. The present article analyses the unintended effects of these ostensibly helpful acts. Twenty people with aphasia and their main communication partners (n = 40) living in the UK were video recorded engaging in a joint task. Three analyses reveal that: (1) scaffolding is widespread and mostly effective, (2) the conversations are dominated by communication partners, and (3) people with aphasia both request and resist help. We propose that scaffolding is inherently paradoxical because it has contradictory effects. While helping facilitates performing an action, and is thus enabling, it simultaneously implies an inability to perform the action independently, and thus it can simultaneously mark the recipient as disabled. Data are in British English. [ABSTRACT FROM AUTHOR]

Purpose: To establish whether objective measurements of symmetry of volume and shape using three-dimensional surface imaging (3D-SI) can be used as surrogate markers of aesthetic outcome in patients who have undergone breast conserving therapy (BCT). Methods: Women who had undergone unilateral BCT in the preceding 1-6 years were invited to participate. Participants completed a satisfaction questionnaire (BREAST-Q) and underwent 3D-SI. Volume and surface symmetry were measured on the images. Assessment of aesthetic outcome was undertaken by a panel of clinicians. The Kruskal-Wallis test was used to assess the relationship between volume and shape symmetry measurements with the panel score. Spearman's rho correlations were used to assess the relationship between the measurements and patient satisfaction. Results: 200 women participated. Median volume symmetry was 87% (IQR 78-93) and shape symmetry was 5.9 mm (IQR 4.2-8.0). The participants were grouped according to panel assessment of aesthetic outcome (poor, fair, good, excellent) and the median volume and shape symmetry was calculated for each group. Volume symmetry significantly differed between the groups. Post hoc pairwise comparisons demonstrated that these differences existed between panel scores of fair versus good and good versus excellent. Median shape symmetry also differed according to patient panel groups with four significant pairwise comparisons between poor versus good, poor versus excellent, fair versus good and fair versus excellent. There was a significant but weak correlation of both volume symmetry and surface asymmetry with BREAST-Q scores (correlation coefficients 0.187 and −0.229, respectively). Conclusion: Breast volume and shape symmetry are both associated with panel assessment scores and patient satisfaction. The objective volume and shape symmetry measures were strongly associated with panel assessment scores, such that a 3D-SI tool could replace panel assessment as a faster and more objective method of evaluating aesthetic outcomes. [ABSTRACT FROM AUTHOR]

In cancer cells, the glycoprotein Mucin 1 (MUC1) undergoes abnormal, truncated glycosylation. The truncated glycosylation exposes cryptic peptide epitopes that can be recognized by antibodies. Since these immunogenic regions are cancer specific, they represent ideal targets for therapeutic antibodies. We investigated the role of tumor-specific glycosylation on antigen recognition by the therapeutic antibody AR20.5. We explored the affinity of AR20.5 to a synthetic cancer-specific MUC1 glycopeptide and peptide. The antibody bound to the glycopeptide with an order of magnitude stronger affinity than the naked peptide. Given these results, we postulated that AR20.5 must specifically bind the carbohydrate as well as the peptide. Using X-ray crystallography, we examined this hypothesis by determining the structure of AR20.5 in complex with both peptide and glycopeptide. Surprisingly, the structure revealed that the carbohydrate did not form any specific polar contacts with the antibody. The high affinity of AR20.5 for the glycopeptide and the lack of specific binding contacts support a hypothesis that glycosylation of MUC1 stabilizes an extended bioactive conformation of the peptide recognized by the antibody. Since high affinity binding of AR20.5 to the MUC1 glycopeptide may not driven by specific antibody-antigen contacts, but rather evidence suggests that glycosylation alters the conformational equilibrium of the antigen, which allows the antibody to select the correct conformation. This study suggests a novel mechanism of antibody-antigen interaction and also suggests that glycosylation of MUC1 is important for the generation of high affinity therapeutic antibodies. [ABSTRACT FROM AUTHOR]

Here, we introduce a novel scFv antibody, G2-D11, specific for two adjacent Tn-antigens (GalNAc-Ser/Thr) binding equally to three dimeric forms of the epitope, Ser-Thr, Thr-Thr and Thr-Ser. Compared to other anti-Tn reagents, the binding of G2-D11 is minimally influenced by the peptide structure, which indicates a high degree of carbohydrate epitope dominance and a low influence from the protein backbone. With a high affinity (KDapp = 1.3 × 10-8 M) and no cross-reactivity to either sialyl-Tn epitope or blood group A antigens, scFv G2-D11 is an excellent candidate for a well-defined anti-Tn-antigen reagent. Detailed immunohistochemical evaluation of tissue sections from a cohort of 80 patients with gastric carcinoma showed in all cases positive tumor cells. The observed staining was localized to the cytoplasm and in some cases to the membrane, whereas the surrounding tissue was completely negative demonstrating the usefulness of the novel Tn-antigen binding antibody. [ABSTRACT FROM AUTHOR]

The continuous evolution in preventive medicine has anointed vaccination a versatile, human-health improving tool, which has led to a steady decline in deaths in the developing world. Maternal immunization represents an incisive step forward for the field of vaccination as it provides protection against various life-threatening diseases in pregnant women and their children. A number of studies to improve prevention rates and expand protection against the largest possible number of infections are still in progress. The complex unicity of the mother-infant interaction, both during and after pregnancy and which involves immune system cells and molecules, is an able partner in the success of maternal immunization, as intended thus far. Interestingly, new studies have shed light on the versatility of maternal immunization in protecting infants from non-infectious related diseases, such as allergy, asthma and congenital metabolic disorders. However, barely any attempt at applying maternal immunization to the prevention of childhood cancer has been made. The most promising study reported in this new field is a recent proof of concept on the efficacy of maternal immunization in protecting cancer-prone offspring against mammary tumor progression. New investigations into the possibility of exploiting maternal immunization to prevent the onset and/or progression of neuroblastoma, one of the most common childhood malignancies, are therefore justified. Maternal immunization is presented in a new guise in this review. Attention will be focused on its versatility and potential applications in preventing tumor progression in neuroblastoma-prone offspring. [ABSTRACT FROM AUTHOR]

Copyright of Kosmos is the property of Polish Copernicus Society of Naturalists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A feasible label-free electrochemiluminescence (ECL) aptasensor that uses an Au-nanoparticle-functionalized g-C3N4 nanohybrid (Au-g-C3N4 NH) as the luminophore was constructed for highly sensitive acetylcholinesterase (AChE) detection. The sensor was fabricated by successively modifying a glassy carbon electrode with Au-g-C3N4 NH and thiol-modified AChE-specific aptamers. In the presence of AChE, the ECL signal decreased significantly, because AChE could hydrolyze the substrate acetylthiocholine to generate acetic acid, which could react with the co-reactant triethylamine (Et3N), leading to evident consumption of the co-reactant. The ECL response of the aptasensor was linearly proportional to the concentration of AChE ranging from 0.1 pg/mL to 10 ng/mL, with a detection limit of 42.3 fg/mL ( S/ N=3). This novel ECL sensing strategy demonstrated a highly sensitive and selective method for AChE detection and was expected to possess potential applications in clinical diagnosis and biomedical technology. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to identify the clinical significance of serum autoantibodies against dickkopf-1 (DKK1) and evaluate their feasibility in the immunodiagnosis and prognosis of non-small cell lung cancer (NSCLC). Experimental design: Epitope mapping by peptide microarray-based serum screening of NSCLC patients (n=72) and healthy controls (n=16) was performed. Indirect ELISA with peptides was used to measure the serum levels of autoantibodies in 206 NSCLC patients and 99 healthy controls. A 3-year follow-up was monitored to evaluate the correlation between serological levels of autoantibodies and overall survival (OS) and progression-free survival (PFS). Results: Four highly reactive epitopes were identified, which included peptides 67-84 (Pep A), 37-54 (Pep B), 145-156 (Pep C) and 247-261 (Pep D). The autoantibodies levels were considerably higher in sera of NSCLC patients compared with controls (P<0.001), and a highly significant correlation with distant metastases was observed (Pep A: P=0.09, Pep B: P<0.01, Pep C: P<0.01 and Pep D: P<0.01). High levels of antibody subtype to Pep B were remarkably associated with better OS (P=0.004) and PFS (P=0.006). Subsequent Cox regression analysis disclosed that antibody to Pep B was an independent prognostic factor for NSCLC (OS: P=0.008, HR =0.435, 95% CI 0.236-0.802; PFS: P=0.032, HR =0.533, 95% CI 0.322-0.950). Conclusion: Identified linear epitopes of antigens by peptide microarray are easily available, and subtype classification of DKK1 autoantibodies as novel biomarkers for the diagnosis and prognosis of NSCLC. Our results also highlight the antibody subtype to Pep B as the most valuable biomarker for favorable prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

The literature indicates that glucose deprivation, dehydration, decreased sleep quality and quantity, and mood changes, independently and adversely can influence cognitive functions and therefore learning. The Ramadan fast is an annual religious act undertaken by Muslims where individuals refrain from consuming food and fluid during daylight hours, daily over 30 days. Alteration in eating times and sleep–wake cycles lead to a disruption in the body's daily circadian rhythm resulting in sleep perturbations and mood swings. Consequently, Ramadan fasting is linked to daytime lower glucose concentration, dehydration, decreased sleep quality and quantity, mood swings and elevated subjective feelings of fatigue and malaise. This review highlights how Ramadan fasting potentially poses learning difficulties as a result of the independent and/or combined effects of these factors. [ABSTRACT FROM PUBLISHER]

Many freshwater systems receive substantial inputs of terrestrial organic matter. Terrestrially derived dissolved organic carbon (t-DOC) inputs can modify light availability, the spatial distribution of primary production, heat, and oxygen in aquatic systems, as well as inorganic nutrient bioavailability. It is also well-established that some terrestrial inputs (such as invertebrates and fruits) provide high-quality food resources for consumers in some systems., In small to moderate-sized streams, leaf litter inputs average approximately three times greater than the autochthonous production. Conversely, in oligo/mesotrophic lakes algal production is typically five times greater than the available flux of allochthonous basal resources., Terrestrial particulate organic carbon (t-POC) inputs to lakes and rivers are comprised of 80%-90% biochemically recalcitrant lignocellulose, which is highly resistant to enzymatic breakdown by animal consumers. Further, t-POC and heterotrophic bacteria lack essential biochemical compounds that are critical for rapid growth and reproduction in aquatic invertebrates and fishes. Several studies have directly shown that these resources have very low food quality for herbivorous zooplankton and benthic invertebrates., Much of the nitrogen assimilated by stream consumers is probably of algal origin, even in systems where there appears to be a significant terrestrial carbon contribution. Amino acid stable isotope analyses for large river food webs indicate that most upper trophic level essential amino acids are derived from algae. Similarly, profiles of essential fatty acids in consumers show a strong dependence on the algal food resources., Primary production to respiration ratios are not a meaningful index to assess consumer allochthony because respiration represents an oxidised carbon flux that cannot be utilised by animal consumers. Rather, the relative importance of allochthonous subsidies for upper trophic level production should be addressed by considering the rates at which terrestrial and autochthonous resources are consumed and the growth efficiency supported by this food., Ultimately, the biochemical composition of a particular basal resource, and not just its quantity or origin, determines how readily this material is incorporated into upper trophic level consumers. Because of its highly favourable biochemical composition and greater availability, we conclude that microalgal production supports most animal production in freshwater ecosystems. [ABSTRACT FROM AUTHOR]

Flow regimes are fundamental to sustaining ecological characteristics of rivers worldwide, including their associated floodplains. Recent advances in understanding tropical river-floodplain ecosystems suggest that a small set of basic ecological concepts underpins their biophysical characteristics, especially the high levels of productivity, biodiversity and natural resilience. The concepts relate to (1) river-specific flow patterns, (2) processes 'fuelled' by a complex of locally generated carbon and nutrients seasonally mixed with carbon and nutrients from floodplains and catchments, (3) seasonal movements of biota facilitated by flood regimes, (4) food webs and overall productivity sustained by hydrological connectivity, (5) fires in the wet/dry tropical floodplains and riparian zones being major consumers of carbon and a key factor in the subsequent redistribution of nutrients, and (6) river-floodplains having inherent resilience to natural variability but only limited resilience to artificial modifications. Understanding these concepts is particularly timely in anticipating the effects of impending development that may affect tropical river-floodplains at the global scale. Australia, a region encompassing some of the last relatively undisturbed tropical riverine landscapes in the world, provides a valuable case study for understanding the productivity, diversity and resilience of tropical river-floodplain systems. However, significant knowledge gaps remain. Despite substantial recent advances in understanding, present knowledge of these highly complex tropical rivers is insufficient to predict many ecological responses to either human-generated or climate-related changes. The major research challenges identified herein (for example, those related to food web structure, nutrient transfers, productivity, connectivity and resilience), if accomplished in the next decade, will offer substantial insights toward assessing and managing ecological changes associated with human alterations to rivers and their catchments. [ABSTRACT FROM AUTHOR]

Studies in freshwater ecosystems are seeking to improve understanding of carbon flow in food webs and stable isotopes have been influential in this work. However, variation in isotopic values of basal production sources could either be an asset or a hindrance depending on study objectives. We assessed the potential for basin geology and local limnological conditions to predict stable carbon and nitrogen isotope values of six carbon sources at multiple locations in four Neotropical floodplain ecosystems (Paraná, Pantanal, Araguaia, and Amazon). Limnological conditions exhibited greater variation within than among systems. δ15N differed among basins for most carbon sources, but δ13C did not (though high within-basin variability for periphyton, phytoplankton and particulate organic carbon was observed). Although δ13C and δ15N values exhibited significant correlations with some limnological factors within and among basins, those relationships differed among carbon sources. Regression trees for both carbon and nitrogen isotopes for all sources depicted complex and in some cases nested relationships, and only very limited similarity was observed among trees for different carbon sources. Although limnological conditions predicted variation in isotope values of carbon sources, we suggest the resulting models were too complex to enable mathematical corrections of source isotope values among sites based on these parameters. The importance of local conditions in determining variation in source isotope values suggest that isotopes may be useful for examining habitat use, dispersal and patch dynamics within heterogeneous floodplain ecosystems, but spatial variability in isotope values needs to be explicitly considered when testing ecosystem models of carbon flow in these systems. [ABSTRACT FROM AUTHOR]

Food web studies integrate ecological information and provide understanding of ecosystem function. Aquatic ecosystems of the Kimberley region (north-western Australia) have high conservation significance as hotspots for maintaining local and regional biodiversity. This study investigated the influence of waterhole type and persistence on the strength of consumer reliance on local energy resources for aquatic food webs. Changes in water isotopic composition indicated groundwater inputs were enough to overcome evaporative losses in some waterholes. Other waterholes had varying levels of isotope enrichment suggesting insufficient groundwater input to 'compensate' for evaporative loss. Cand N isotope analysis indicated considerable overlap among energy sources in waterholes between macrophytes and periphyton but gradient analysis indicated that periphyton is a major carbon source for aquatic consumers. Groundwaterfed waterholes appeared to have higher quality food sources (indicated by lower C : N ratios), but there was minimal evidence that direct groundwater contributions were related to food web processes. Nonetheless, in a region where groundwater is influential in maintaining aquatic habitats, future development of groundwater reserves will likely affect the ecological and cultural value of freshwater wetlands by either reducing their permanence or size or indirectly through possible alteration to the role of periphyton in supporting the food web. [ABSTRACT FROM AUTHOR]

Submerged plants are often abundant in lowland streams in agricultural landscapes, but little is known of their role in stream ecosystems compared to riparian vegetation. We investigated the importance of submerged macrophytes as a basal resource of food webs in stream reaches with good and poor riparian vegetation condition, using mixing model analysis with stable carbon and nitrogen isotopes. Epilithic periphyton and terrestrial detritus were important basal resources in good condition reaches, although where macrophytes were present they contributed to food webs. Higher assimilation of either the macrophyte Cycnogeton huegelii or conspicuous epiphytes on C. huegelii leaves was associated with poor riparian condition. Where Potamogeton ochreatus and Ottelia ovalifolia occurred in poor condition reaches, these macrophytes contributed moderately to the food web, but were probably of greater importance as substrates for epiphytic algae. Mixing models indicated invertebrates commonly had generalist feeding strategies, feeding on the most available resource at each reach. Thus, where riparian vegetation is limited, submerged macrophytes may support opportunistic consumers both directly and as a substrate for epiphytes, thereby partially compensating for the loss of allochthonous resources in lowland agricultural streams. [ABSTRACT FROM AUTHOR]

High blood glucose has long been established as a risk factor for tumor metastasis, yet the molecular mechanisms underlying this association have not been elucidated. Here we describe that hyperglycemia promotes tumor metastasis via increased platelet activity. Administration of glucose, but not fructose, reprogrammed the metabolism of megakaryocytes to indirectly prime platelets into a prometastatic phenotype with increased adherence to tumor cells. In megakaryocytes, a glucose metabolism-related gene array identified the mitochondrial molecular chaperone glucose-regulated protein 75 (GRP75) as a trigger for platelet activation and aggregation by stimulating the Ca 2+ -PKCα pathway. Genetic depletion of Glut1 in megakaryocytes blocked MYC-induced GRP75 expression. Pharmacologic blockade of platelet GRP75 compromised tumor-induced platelet activation and reduced metastasis. Moreover, in a pilot clinical study, drinking a 5% glucose solution elevated platelet GRP75 expression and activated platelets in healthy volunteers. Platelets from these volunteers promoted tumor metastasis in a platelet-adoptive transfer mouse model. Together, under hyperglycemic conditions, MYC-induced upregulation of GRP75 in megakaryocytes increases platelet activation via the Ca 2+ -PKCα pathway to promote cancer metastasis, providing a potential new therapeutic target for preventing metastasis. SIGNIFICANCE: This study provides mechanistic insights into a glucose-megakaryocyte-platelet axis that promotes metastasis and proposes an antimetastatic therapeutic approach by targeting the mitochondrial protein GRP75., (©2021 American Association for Cancer Research.)

Prostate cancer (PCa) is one of the most prominent causes of cancer-related mortality in the male population. A highly impactful prognostic factor for patients diagnosed with PCa is the presence or absence of bone metastases. The formation of secondary tumours at the bone is the most commonly observed site for the establishment of PCa metastases and is associated with reduced survival of patients in addition to a cohort of life-debilitating symptoms, including mobility issues and chronic pain. Despite the prevalence of this disease presentation and the high medical relevance of bone metastases, the mechanisms underlying the formation of metastases to the bone and the understanding of what drives the osteotropism exhibited by prostate tumours remain to be fully elucidated. This lack of in-depth understanding manifests in limited effective treatment options for patients with advanced metastatic PCa and culminates in the low rate of survival observed for this sub-set of patients. The present review aims to summarise the most recent promising advances in the understanding of how and why prostate tumours metastasise to the bone, with the ultimate aim of highlighting novel treatment and prognostic targets, which may provide the opportunity to improve the diagnosis and treatment of patients with PCa with bone metastases. [ABSTRACT FROM AUTHOR]

A new concept to prepare nanocomposite thin films is explored. Two chemical-based bottom-up steps are used to design functional films including (i) the block copolymer-assisted self-assembly of a porous matrix; and (ii) the impregnation of nanoparticles from a ferroic phase into the pores by supercritical CO2 deposition. Porous nanopatterned BaTiO3 thin films with ca. 17 nm thickness are prepared using a cost-effective sol–gel solution containing a block copolymer and evaporation-induced self-assembly methodology. Hexagonally arranged pores with a diameter of ca. 95 nm, running perpendicular to the substrate, are filled with Ni nanoparticles using the supercritical fluid deposition technique, obtained from the reduction of hydrated nickel nitrate in a supercritical CO2–ethanol mixture at 250 °C. Small Ni nanoparticles of 21 ± 5 nm size are selectively deposited inside the pores of the porous matrix. Structural and magnetic properties prove the coexistence of both phases. [ABSTRACT FROM AUTHOR]

Food web subsidies from external sources ('allochthony') can support rich biological diversity and high secondary and tertiary production in aquatic systems, even those with low rates of primary production. However, animals vary in their degree of dependence on these subsidies. We examined dietary sources for aquatic animals restricted to refugial habitats (waterholes) during the dry season in Australia's wet-dry tropics, and show that allochthony is strongly size dependent. While small-bodied fishes and invertebrates derived a large proportion of their diet from autochthonous sources within the waterhole (phytoplankton, periphyton, or macrophytes), larger animals, including predatory fishes and crocodiles, demonstrated allochthony from seasonally inundated floodplains, coastal zones or the surrounding savanna. Autochthony declined roughly 10% for each order of magnitude increase in body size. The largest animals in the food web, estuarine crocodiles ( Crocodylus porosus), derived ~80% of their diet from allochthonous sources. Allochthony enables crocodiles and large predatory fish to achieve high biomass, countering empirically derived expectations for negative density vs. body size relationships. These results highlight the strong degree of connectivity that exists between rivers and their floodplains in systems largely unaffected by river regulation or dams and levees, and how large iconic predators could be disproportionately affected by these human activities. [ABSTRACT FROM AUTHOR]

Familial apparently balanced translocations (ABTs) segregating with discordant phenotypes are extremely challenging for interpretation and counseling due to the scarcity of publications and lack of routine techniques for quick investigation. Recently, next generation sequencing has emerged as an efficacious methodology for precise detection of translocation breakpoints. However, studies so far have mainly focused on de novo translocations. The present study focuses specifically on familial cases in order to shed some light to this diagnostic dilemma. Whole-genome mate-pair sequencing (WG-MPS) was applied to map the breakpoints in nine two-way ABT carriers from four families. Translocation breakpoints and patient-specific structural variants were validated by Sanger sequencing and quantitative Real Time PCR, respectively. Identical sequencing patterns and breakpoints were identified in affected and non-affected members carrying the same translocations. PTCD1, ATP5J2-PTCD1, CADPS2, and STPG1 were disrupted by the translocations in three families, rendering them initially as possible disease candidate genes. However, subsequent mutation screening and structural variant analysis did not reveal any pathogenic mutations or unique variants in the affected individuals that could explain the phenotypic differences between carriers of the same translocations. In conclusion, we suggest that NGS-based methods, such as WG-MPS, can be successfully used for detailed mapping of translocation breakpoints, which can also be used in routine clinical investigation of ABT cases. Unlike de novo translocations, no associations were determined here between familial two-way ABTs and the phenotype of the affected members, in which the presence of cryptic imbalances and complex chromosomal rearrangements has been excluded. Future whole-exome or whole-genome sequencing will potentially reveal unidentified mutations in the patients underlying the discordant phenotypes within each family. In addition, larger studies are needed to determine the exact percentage for phenotypic risk in families with ABTs. [ABSTRACT FROM AUTHOR]

We have developed a combinatory antibody–antigen microarray for direct screening of multiple single-chain fragment variable (scFv) clones with no need for pre-purification or enrichment before screening. The straightforward workflow allows for early selection of binders to predefined peptide and glycopeptide targets. A capture antibody is contact printed on microarray slides, side by side with the antigens of interest. A large number of scFv clones, in supernatants, are printed on top of the capture antibody and the antigen in a “spot-on-spot” print. The printed scFv clones, which bind to the capture antibody, are detected using biotinylated antigen, while the binding of scFv clones to the printed antigen is detected through a mouse anti-tag antibody. Two different analyses are thus performed on the same slide, generating two kinds of information: one on the ability of an individual scFv clone to bind to the soluble form of the antigen, which may favour selection for higher affinity rather than avidity, while the other allows the identification of large numbers of clones, simultaneously, due to the binding of scFv clones to densely presented antigens, thus providing an overall increased hit rate. The functionality of the new screening approach was illustrated through the generation of antibodies against peptides from the chaperone complex Ku70/Ku80 and the GalNAcα-serine/threonine epitope on the IgA1 alpha chain hinge region. In total, 659 scFv clones were screened with a hit rate of approximately 20%. This approach allowed the identification of functional antibodies in both cases, illustrating the usefulness and capacity of this combinatory microarray screening technique for efficient analysis and validation of antibodies at an early stage of antibody generation. [ABSTRACT FROM AUTHOR]

Glycosylation is one of the major posttranslational modifications of proteins. N-glycosylation (Asn-linked) and O-glycosylation (Ser/Thr-linked) are the two main forms. Abnormal O-glycosylation is frequently observed on the surface of tumor cells, and is associated with an adverse outcome and poor prognosis in patients with cancer. O-glycans (Tn, sTn, and T antigen) can be synthesized in the Golgi apparatus with the aid of several glycosyltransferases (such as T-synthase and ST6GalNAc-I) in a suitable environment. The unique molecular chaperone of T-synthase is Cosmc, which helps T-synthase to fold correctly in the endoplasmic reticulum. Dysregulation of these glycosyltransferases, molecular chaperones, or the environment is involved in the dysregulation of O-glycans. Tn, sTn, and T antigen neo- or over-expression occurs in many types of cancer including gastric, colon, breast, lung, esophageal, prostate, and endometrial cancer. This review discusses the major synthetic pathway of O-glycans and the mechanism by which Tn, sTn, and T antigens promote tumor metastasis. [ABSTRACT FROM AUTHOR]

Background: Given that we know that interventions shown to be effective in improving the health of a population may actually widen the health inequalities gap while others reduce it, it is imperative that all systematic reviewers consider how the findings of their reviews may impact (reduce or increase) on the health inequality gap. This study reviewed existing guidance on incorporating considerations of health inequalities in systematic reviews in order to examine the extent to which they can help reviewers to incorporate such issues. Methods: A mapping review was undertaken to identify guidance documents that purported to inform reviewers on whether and how to incorporate considerations of health inequalities. Searches were undertaken in Medline, CINAHL and The Cochrane Library Methodology Register. Review guidance manuals prepared by international organisations engaged in undertaking systematic reviews, and their associated websites were scanned. Studies were included if they provided an overview or discussed the development and testing of guidance for dealing with the incorporation of considerations of health inequalities in evidence synthesis. Results are summarised in narrative and tabular forms. Results: Twenty guidance documents published between 2009 and 2016 were included. Guidance has been produced to inform considerations of health inequalities at different stages of the systematic review process. The Campbell and Cochrane Equity Group have been instrumental in developing and promoting such guidance. Definitions of health inequalities and guidance differed across the included studies. All but one guidance document were transparent in their method of production. Formal methods of evaluation were reported for six guidance documents. Most of the guidance was operationalised in the form of examples taken from published systematic reviews. The number of guidance items to operationalise ranges from 3 up to 26 with a considerable overlap noted. Conclusions: Adhering to the guidance will require more work for the reviewers. It requires a deeper understanding of how reviewers can operationalise the guidance taking into consideration the barriers and facilitators involved. This has implications not only for understanding the usefulness and burden of the guidance but also for the uptake of guidance and its ultimate goal of improving health inequalities considerations in systematic reviews. [ABSTRACT FROM AUTHOR]