Search Results (13)

Lymph nodes (LNs) are believed to be the first organs targeted by colorectal cancer cells detached from a primary solid tumor because of their role in draining interstitial fluids. Better detection and assessment of these organs have the potential to help clinicians in stratification and designing optimal design of oncological treatments for each patient. Whilst highly valuable for the detection of primary tumors, CT and MRI remain limited for the characterization of LNs. B-mode ultrasound (US) and contrast-enhanced ultrasound (CEUS) can improve the detection of LNs and could provide critical complementary information to MRI and CT scans; however, the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines advise that further evidence is required before US or CEUS can be recommended for clinical use. Moreover, knowledge of the lymphatic system and LNs is relatively limited, especially in preclinical models. In this pilot study, we have created a mouse model of metastatic cancer and utilized 3D high-frequency ultrasound to assess the volume, shape, and absence of hilum, along with CEUS to assess the flow dynamics of tumor-free and tumor-bearing LNs in vivo. The aforementioned parameters were used to create a scoring system to predict the likelihood of a disease-involved LN before establishing post-mortem diagnosis with histopathology. Preliminary results suggest that a sum score of parameters may provide a more accurate diagnosis than the LN size, the single parameter currently used to predict the involvement of an LN in disease. Full article

Straw’s low energy content means it is a roughage option for horses with low energy requirements. Previously, in a field study, straw was associated with an increased risk for gastric ulcers. This study evaluated the effect on gastric ulcers, metabolic profile and behaviour of replacing, in a forage-only ration, 50% of the daily allowance with wheat straw. Six equines were studied in a 2 × 21-day cross-over design. The control diet (CON: 100% grass forage) and the straw diet (S: 50% grass forage and 50% straw [DM basis]) were iso-energetic. Gastroscopy was performed prior to the study and on day 21 and blood samples were collected and behavioural observations were performed. Diet did not affect squamous or glandular gastric ulcer scores (p > 0.05). Feed intake time was longer (p < 0.05) plus energy intake and plasma insulin concentrations were lower on diet S compared to CON (p < 0.0001). Plasma serotonin concentrations tended to be higher on diet S compared to CON (p = 0.05). The results suggest that good hygienic quality wheat straw can be included for up to 50% of the diet without causing gastric ulcers and that it can extend feeding time and promote a metabolic profile more suitable for overweight horses. Full article

Background: PAM50 breast cancer intrinsic subtyping adds prognostic information in early breast cancer; however, the role in metastatic disease is unclear. We aimed to identify PAM50 subtypes in primary tumors (PTs) and metastases to outline subtype changes and their prognostic role. Methods: RNA was isolated from PTs, lymph node metastases (LNMs), and distant metastases (DMs) in metastatic breast cancer patients (n = 140) included in a prospective study (NCT01322893). Gene expression analyses were performed using the Breast Cancer 360 (BC360) assay from Nano-String. The subtype shifts were evaluated using McNemar and symmetry tests, and clinical outcomes were evaluated with log-rank tests and Cox regression. Results: The PAM50 subtype changed in 25/59 of paired samples between PTs and LNMs (P_symmetry = 0.002), in 31/61 between PTs and DMs (P_symmetry < 0.001), and in 16/38 between LNMs and DMs (P_symmetry = 0.004). Shifts toward subtypes with worse outcomes were the most common. Patients with shifts from the luminal PT to non-luminal DM subtypes had worse progression-free survival compared to patients with a stable subtype (hazard ratio (HR): 2.3; 95% confidence interval (CI): 1.14–4.68, p = 0.02). Conclusion: Strong evidence of PAM50 subtype shifts toward unfavorable subtypes were seen between PTs and metastatic samples. For patients with a shift in subtype from luminal PT to non-luminal DM, a worse prognosis was noted. Full article

The antibodies with different effector functions evoked by Human Immunodeficiency Virus type 1 (HIV-1) transmitted from mother to child, and their role in the pathogenesis of infected children remain unresolved. So, too, the kinetics and breadth of these responses remain to be clearly defined, compared to those developing in adults. Here, we studied the kinetics of the autologous and heterologous neutralizing antibody (Nab) responses, in addition to antibody-dependent cellular cytotoxicity (ADCC), in HIV-1 infected children with different disease progression rates followed from close after birth and five years on. Autologous and heterologous neutralization were determined by Peripheral blood mononuclear cells (PBMC)- and TZMbl-based assays, and ADCC was assessed with the GranToxiLux assay. The reactivity to an immunodominant HIV-1 gp41 epitope, and childhood vaccine antigens, was assessed by ELISA. Newborns displayed antibodies directed towards the HIV-1 gp41 epitope. However, antibodies neutralizing the transmitted virus were undetectable. Nabs directed against the transmitted virus developed usually within 12 months of age in children with slow progression, but rarely in rapid progressors. Thereafter, autologous Nabs persisted throughout the follow-up of the slow progressors and induced a continuous emergence of escape variants. Heterologous cross-Nabs were detected within two years, but their subsequent increase in potency and breadth was mainly a trait of slow progressors. Analogously, titers of antibodies mediating ADCC to gp120 BaL pulsed target cells increased in slow progressors during follow-up. The kinetics of antibody responses to the immunodominant viral antigen and the vaccine antigens were sustained and independent of disease progression. Persistent autologous Nabs triggering viral escape and an increase in the breadth and potency of cross-Nabs are exclusive to HIV-1 infected slowly progressing children. Full article

Orthopteran insects have high reproductive rates leading to boom-bust population dynamics with high local densities that are ideal for short, episodic disease epidemics. Viruses are particularly well suited for such host population dynamics, due to their supreme ability to adapt to changing transmission criteria. However, very little is known about the viruses of Orthopteran insects. Since Orthopterans are increasingly reared commercially, for animal feed and human consumption, there is a risk that viruses naturally associated with these insects can adapt to commercial rearing conditions, and cause disease. We therefore explored the virome of the house cricket Acheta domesticus, which is both part of the natural Swedish landscape and reared commercially for the pet feed market. Only 1% of the faecal RNA and DNA from wild-caught A. domesticus consisted of viruses. These included both known and novel viruses associated with crickets/insects, their bacterial-fungal microbiome, or their plant food. Relatively abundant among these viral Operational Taxonomic Units (OTUs) was a novel Iflavirus, tentatively named Acheta domesticus Iflavirus (AdIV). Quantitative analyses showed that AdIV was also abundant in frass and insect samples from commercially reared crickets. Interestingly, the wild and commercial AdIV strains had short, extremely divergent variation hotspots throughout the genome, which may indicate specific adaptation to their hosts’ distinct rearing environments. Full article

Background: The estrogen receptor (ER) can change expression between primary tumor (PT) and distant metastasis (DM) in breast cancer. A tissue biopsy reflects a momentary state at one location, whereas circulating tumor cells (CTCs) reflect real-time tumor progression. We evaluated ER-status during tumor progression from PT to DM and CTCs, and related the ER-status of CTCs to prognosis. Methods: In a study of metastatic breast cancer, blood was collected at different timepoints. After CellSearch^® enrichment, CTCs were captured on DropMount slides and evaluated for ER expression at baseline (BL) and after 1 and 3 months of therapy. Comparison of the ER-status of PT, DM, and CTCs at different timepoints was performed using the McNemar test. The primary endpoint was progression-free survival (PFS). Results: Evidence of a shift from ER positivity to negativity between PT and DM was demonstrated (p = 0.019). We found strong evidence of similar shifts from PT to CTCs at different timepoints (p < 0.0001). ER-positive CTCs at 1 and 3 months were related to better prognosis. Conclusions: A shift in ER-status from PT to DM/CTCs was demonstrated. ER-positive CTCs during systemic therapy might reflect the retention of a favorable phenotype that still responds to therapy. Full article

Horse grazing can be favorable from a biological diversity perspective. This study documented the occurrence of endo- and ectoparasites and sought to reduce parasite egg excretion with the anthelmintic drug pyrantel in 12 Gotlandsruss stallions maintained in a year-round grazing system for 2.5 years. Feces samples were collected monthly and all horses were treated with pyrantel, the anthelmintic drug of choice in biological diversity preservation, at study population mean cyathostomin eggs per gram (EPG) of >200. The relationship between cyathostomin EPG and body condition was studied, as was horse behavioral response to Bovicola equi (chewing louse) infestation. Eggs of cyathostomins (small strongyles), Parascaris spp. (roundworm), Oxyuris equi (pinworm), Anoplocephala perfoliata (tapeworm), and Gasterophilus spp. (botfly) were detected at least once during the trial. Excretion of cyathostomin eggs was highest during summer–autumn and increased year-on-year. No relationship was found between cyathostomin EPG and body condition. Infestation with B. equi did not affect the number of scratching sessions compared with unaffected horses. Therefore, in this year-round grazing system, pyrantel treatment had to be complemented with moxidectin to reduce excretion of cyathostomin eggs, thus compromising biological diversity. Full article

The study describes development of a glycan biosensor for detection of a tumor-associated antibody. The glycan biosensor is built on an electrochemically activated/oxidized graphene screen-printed electrode (GSPE). Oxygen functionalities were subsequently applied for covalent immobilization of human serum albumin (HSA) as a natural nanoscaffold for covalent immobilization of Thomsen-nouvelle (Tn) antigen (GalNAc-O-Ser/Thr) to be fully available for affinity interaction with its analyte—a tumor-associated antibody. The step by step building process of glycan biosensor development was comprehensively characterized using a battery of techniques (scanning electron microscopy, atomic force microscopy, contact angle measurements, secondary ion mass spectrometry, surface plasmon resonance, Raman and energy-dispersive X-ray spectroscopy). Results suggest that electrochemical oxidation of graphene SPE preferentially oxidizes only the surface of graphene flakes within the graphene SPE. Optimization studies revealed the following optimal parameters: activation potential of +1.5 V vs. Ag/AgCl/3 M KCl, activation time of 60 s and concentration of HSA of 0.1 g L⁻¹. Finally, the glycan biosensor was built up able to selectively and sensitively detect its analyte down to low aM concentration. The binding preference of the glycan biosensor was in an agreement with independent surface plasmon resonance analysis. Full article

This study examined the effects of two housing systems (free-range and box stalls) on recovery of energy balance after competition-like exercise in Standardbred horses. Eight adult geldings (mean age 11 years) were used. The study had a change-over design, with the box stall (BOX) and free-range group housing (FreeR) treatments each run for 21 days. The horses were fed forage ad libitum and performed two similar race-like exercise tests (ET), on day 7 and day 14 in each treatment. Forage intake was recorded during the last 6–7 days in each period. Blood samples were collected before, during, and until 44 h after ET. Voluntary forage intake (measured in groups with four horses in each group) was higher in FreeR horses than BOX horses (FreeR: 48, BOX: 39, standard error of the mean (SEM) 1.7 kg (p = 0.003)). Plasma non-esterified fatty acids (NEFA) was lower at 20–44 h of recovery than before in FreeR horses (p = 0.022), but not in BOX horses. Housing did not affect exercise heart rate, plasma lactate, plasma urea, or total plasma protein concentration. Thus the free-range housing system hastened recovery in Standardbred trotters, contradicting anecdotal claims that it delays recovery. The free-range housing also had positive effects on appetite and recovery of energy balance. Full article

Horse grazing may benefit biodiversity, but the impact of year-round grazing on nutrient dynamics has not been evaluated previously. This study compared pasture quality in a forest-grassland landscape grazed year-round by horses with that in exclosed mown areas. Twelve Gotlandsruss stallions were kept without supplementary feeding in three enclosures (~0.35 horse/ha) outside Uppsala, Sweden, from May 2014 to September 2016. Each enclosure contained three mown exclosures, where grass sward samples were collected monthly and analyzed for chemical composition and vegetation density. Fecal grab samples were collected and analyzed for crude protein (CP) and organic matter (OM) content. There were no differences in exclosure pasture energy or CP content between enclosures (p > 0.05). In grazed areas, there were differences in grass energy and CP content (p > 0.05) between enclosures. During the three summers studied, energy and CP content increased in the enclosures, but decreased in the exclosures. By the end, biomass content/ha was greater in the enclosures than in the exclosures. Fecal OM and CP content showed moderate to strong correlations with pasture nutrient content (r = 0.3–0.8, p < 0.05). Thus, in contrast to monthly mowing, horse grazing diversified pasture chemical composition and increased its nutritive value. Full article

This study aimed to investigate the periodontal health of patients with established rheumatoid arthritis (RA) in relation to oral microbiota, systemic and oral inflammatory mediators, and RA disease activity. Forty patients underwent full-mouth dental/periodontal and rheumatological examination, including collection of blood, saliva, gingival crevicular fluid (GCF) and subgingival plaque. Composition of plaque and saliva microbiota were analysed using 16S rRNA sequencing and levels of inflammatory mediators by multiplex-immunoassay. The majority of the patients (75%) had moderate or severe periodontitis and the rest had no/mild periodontitis. Anti-citrullinated protein antibody (ACPA) positivity was significantly more frequent in the moderate/severe periodontitis (86%) compared to the no/mild group (50%). No significance between groups was observed for RA disease duration or activity, or type of medication. Levels of sCD30/TNFRSF8, IFN-α2, IL-19, IL-26, MMP-1, gp130/sIL-6Rß, and sTNF-R1 were significantly higher in serum or GCF, and April/TNFSF13 was significantly higher in serum and saliva samples in moderate/severe periodontitis. The microbial composition in plaque also differed significantly between the two groups. In conclusion, the majority of RA patients had moderate/severe periodontitis and that this severe form of the disease was significantly associated with ACPA positivity, an altered subgingival microbial profile, and increased levels of systemic and oral inflammatory mediators. Full article

Dairy products are important constituents of most diets, and their association with adverse health outcomes remains a focus. We characterized dairy food intake and examined associations with the incidence of type 2 diabetes (T2D), myocardial infarction (MI) or stroke among 108,065 Swedish men and women. Hazard ratios (HRs) and 95% CIs were estimated using the multivariable Cox proportional hazards models in a population characterized by high milk tolerance. During a mean follow-up of 14.2 years, 11,641 first-time events occurred. Non-fermented milk intake decreased, whereas butter intake increased over the period. For high intake of non-fermented milk, the HR (95% CI) for developing T2D and MI was 1.17 (1.03, 1.34) and 1.23 (1.10, 1.37), respectively, in men. A greater intake of butter, fermented milk, and cheese tended to be associated with a reduced risk of T2D and/or MI. Non-consumers and those who chose low-fat variants of the targeted dairy products had increased risk for T2D, MI, or stroke compared to those in the non-case group. Generally, effect-sizes were small. This prospective study found that non-fermented milk was associated with an increased risk for developing T2D and MI and that subjects abstaining from dairy products or choosing low-fat variants were at greater risk. However, the overall cardiometabolic risk of non-fermented milk intake was judged as low, since the effect sizes were small. Full article

Since the majority of top-level researchers are men, how does this vertical gender-segregation affect students’ perceptions of a research career? In the current study, an experimental manipulation either reminded students of academia’s current dominance of men or of its improving gender-balance. The results showed that women primed with the dominance of men anticipated much higher social identity threats (e.g., fear of discrimination) in a future research career as compared to a control group. In contrast, women primed with the improving gender-balance anticipated much lower threat. Further, the dominance of men prime increased men’s interest in the PhD program, as compared to controls. Women’s interest was unaffected by the prime, but their lower interest as compared to men’s across conditions was mediated by their lower research self-efficacy (i.e., competence beliefs). The results imply that communicating gender-equality progress may allow women to consider a career in research without the barrier of social identity threat. Full article