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Background: Superparamagnetic iron nanoparticles perform comparably to radioisotope ± blue dye for sentinel lymph node detection in breast cancer, even when injected up to 8 weeks before surgery. Using superparamagnetic iron nanoparticles for sentinel lymph node detection after primary systemic therapy, and the maximum time frame of superparamagnetic iron nanoparticle administration have not been investigated. Methods: This cohort study included cN0/1-to-ycN0 patients undergoing sentinel lymph node detection or targeted axillary dissection. All patients received superparamagnetic iron nanoparticles either before primary systemic therapy or before surgery, and radioisotope on the day of surgery. Results: For 113 patients analysed, superparamagnetic iron nanoparticles were injected a median of 3 (range 0–248) days before surgery, with a 97.4% detection rate compared with 91.2% for radioisotope (P = 0.057). Concordance for radioisotope was 97.1% and this was not affected by timing of superparamagnetic iron nanoparticle injection (Kendall's tau 0.027; P = 0.746). The median sentinel lymph node yield was 3 (interquartile range (i.q.r.) 2–3) for superparamagnetic iron nanoparticles and 2 (i.q.r. 2–3) for radioisotope (P < 0.001). In targeted axillary dissection, detection was 100% for superparamagnetic iron nanoparticles and 81.8% for radioisotope (P = 0.124). The index node was magnetic in 93.9% and radioactive in 66.7% (P = 0.007), an outcome that was not affected by any factors. For patients with metastases, superparamagnetic iron nanoparticle detection was 100% and radioisotope-based detection was 84.2% (P = 0.083), with superparamagnetic iron nanoparticles detecting more metastatic sentinel lymph nodes (median of 1 (i.q.r. 1–2) for superparamagnetic iron nanoparticles compared with a median of 1 (i.q.r. 0–1) for radioisotope; P = 0.005). Conclusion: Injection before primary systemic therapy is feasible and does not affect concordance with radioisotope. Superparamagnetic iron nanoparticles perform comparably to radioisotope, but detect more sentinel lymph nodes and have a higher rate of detection of metastatic sentinel lymph nodes. In this study, patients with breast cancer who received oncological treatment before surgery underwent axillary surgery by means of a superparamagnetic iron nanoparticle tracer, which was injected at any time point, ranging from the day before surgery to before the start of oncological treatment. All patients received a radioisotope tracer, the standard, as a comparator. The superparamagnetic iron nanoparticle detection rate and accuracy for sentinel lymph node detection were not affected by the time of injection (before or after preoperative oncological therapy) and superparamagnetic iron nanoparticles detected more lymph nodes, especially for patients with nodal metastases. Graphical abstract [ABSTRACT FROM AUTHOR]

Introduction: Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer. Methods: The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples. Results: The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis. Conclusions: These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Superparamagnetic iron oxide nanoparticles (SPIO) have been used as a tracer for sentinel lymph node (SLN) localization in breast cancer, demonstrating comparable performance to the combination of radioisotope (RI) and blue dye (BD). Methods: A systematic literature search and meta-analysis with subgroup and meta-regression analysis were undertaken to update the available evidence, assess technique evolution, and define knowledge gaps. Recommendations were made using the GRADE approach. Results: In 20 comparative studies, the detection rate was 97.5 per cent for SPIO and 96.5 per cent for RI±BD (risk ratio 1.006, 95 per cent c.i. 0.992 to 1.019; P=0.376, high-certainty evidence). Neoadjuvant therapy, injection site, injection volume or nodal metastasis burden did not affect the detection rate, but injection over 24 h before surgery increased the detection rate on meta-regression. Concordance was 99.0 per cent and reverse concordance 97.1 per cent (rate difference 0.003, 95 per cent c.i. -0.009 to 0.015; P = 0.656, high-certainty evidence). Use of SPIO led to retrieval of slightly more SLNs (pooled mean 1.96 versus 1.89) with a higher nodal detection rate (94.1 versus 83.5 per cent; RR 1.098, 1.058 to 1.140; P < 0.001; low-certainty evidence). In meta-regression, injection over 24 h before surgery increased the SPIO nodal yield over that of RI±BD. The skin-staining rate was 30.8 per cent (very low-certainty evidence), and possibly prevented with use of smaller doses and peritumoral injection. Conclusion: The performance of SPIO is comparable to that of RI±BD. Preoperative injection increases the detection rate and nodal yield, without affecting concordance. Whether skin staining and MRI artefacts are reduced by lower dose and peritumoral injection needs to be investigated. [ABSTRACT FROM AUTHOR]

This study investigated if behavioral factors, treatment with behavioral support, readiness to change, fall self-efficacy, and activity habits could predict long-term adherence to an exercise program. Included in this study were 114 community-dwelling older adults who had participated in one of two home-based exercise interventions. Behavioral factors associated with adherence to the exercise program over 52 weeks were analyzed. The behavioral factors, specifically activity habits at baseline, significantly predicted adherence to the exercise program, with an odds ratio = 3.39, 95% confidence interval [1.38, 8.32], for exercise and an odds ratio = 6.11, 95% confidence interval [2.34, 15.94], for walks. Being allocated to a specific treatment including motivational interviewing was also significantly predictive: odds ratio = 2.47, 95% confidence interval [1.11, 5.49] for exercise adherence. In conclusion, activity habits and exercise in combination with motivational interviewing had a significant association with adherence to the exercise program at a 1-year follow-up. [ABSTRACT FROM AUTHOR]

Metal ions play an important role in many metabolic processes in all living organisms. At low concentrations, heavy metals such as Fe2+, Cu2+ and Zn2+ are essential cofactors for many enzymes. However, at high concentrations they are toxic. Mesorhizobium species belong to the class α-proteobacteria and have high tolerance to soil acidity, salinity, temperature extremes, and metallicolous conditions. To identify factors responsible for this tolerance we have studied the effects of metal ions on Mesorhizobium delmotii thymidylate kinase (MdTMPK), an essential enzyme in the synthesis of dTTP, thus being vital for cell growth. We show that Mg2+ and Mn2+ are the divalent metal ions required for catalysis and that Mn2+ gives the highest catalytic efficiency. MdTMPK activity in the presence of Mg2+ was strongly inhibited by the co-presence of Zn2+, Ni2+ and Co2+. However, the addition of Cs+ caused >2-fold enhanced MdTMPK activity. For TMPK from Bacilus anthracis and humans, the effects of Mg2+ and Mn2+ were similar, whereas the effects of other divalent metal ions were different, and no stimulatory effect of Cs+ was observed. Together, our results demonstrate that MdTMPK and BaTMPK function well in the presence of high concentrations of heavy metal ions, introducing a potential contribution of these enzymes to the heavy metal tolerance of Mesorhizobium delmotii and Bacillus anthracis [ABSTRACT FROM AUTHOR]

Simple Summary: Both superparamagnetic iron oxide nanoparticles (SPIO) and blue dye (BD) have been reported to cause skin staining after breast-conserving surgery. SPIO is a novel tracer that has been shown to identify sentinel lymph nodes (SLNs) in patients with breast cancer. Our study was the first to compare the incidence and size of skin staining between the two tracers. We reported on these outcomes in a preplanned secondary analysis of a prospective clinical trial in which women received both SPIO and BD. This study investigated whether there was a difference in the incidence and size of skin staining between SPIO and BD after SLN-dissection. In all, 270 women were operated on with breast-conserving surgery and received SPIO, and 204 of these women also received BD. After 24 months of follow up, there was no statistically significant difference between the two tracers with regard to the size and incidence of skin staining. Superparamagnetic iron oxide nanoparticles (SPIO) are a tracer for sentinel lymph node (SLN) detection. In a preplanned secondary analysis of a prospective clinical trial (SentiDose) we reported on skin staining after SPIO and blue dye (BD) injections. For SPIO, either a 1.5 mL retroareolar injection on the day of surgery or a 1.0 mL peritumoral/retroareolar injection 1–7 days before surgery was given. A 1.0 mL sub-/intradermal periareolar injection of BD was also administered to all these women. Staining was then assessed at 6, 12 and 24 months after surgery. A total of 270 women received SPIO and were operated on with breast-conserving surgery. Of these, 204 women also received BD. A total of 58 (21.5%) women had an SPIO stain 6 months postoperatively with a median size of 6.8 cm2 (p = 0.56), while 51 (25.0%) had a BD stain with a median size of 8.5 cm2 (p = 0.93). The incidence and size of SPIO and BD staining decreased over time reciprocally. At 24 months, the incidence and median size of SPIO was 23 (8.6%) and 4 cm2, respectively. For BD, the incidence was 14 (6.3%, p = 0.13), and the median size was 3.5 cm2 (p = 0.18). There was, therefore, no statistically significant difference in the incidence or size of skin staining between SPIO and BD over time. [ABSTRACT FROM AUTHOR]

Conformational changes in purified human deoxycytidine kinase (dCK) in solution before and after substrate binding by employing fluorescence energy transfer experiments is examined to resolve the discrepancy between the kinetic results and the structural model. Kinetic studies showed that the addition of probe N(1-pyrene)-maleimide (PM) did not have any influence on the enzymatic activity of Cys-185-Ala, although there were changes in substrate specificity.

Cytosolic thymidine kinase 1, TK1, is a well known cell-cycle-regulated enzyme of importance in nucleotide metabolism as well as an activator of antiviral and anticancer drugs such as 3'-azido3'-deoxythymidine (AZT). We have now determined the structures of the TK1 family, the human and Ureaplasma urealyticum enzymes, in complex with the feedback inhibitor dTTP. The TKls have a tetrameric structure in which each subunit contains an [alpha]/[beta]domain that is similar to ATPase domains of members of the RecA structural family and a domain containing a structural zinc. The zinc ion connects [beta]-structures at the root of a [beta]-ribbon that forms a stem that widens to a lasso-type loop. The thymidine of dTTP is hydrogen-bonded to main-chain atoms predominantly coming from the lasso loop. This binding is in contrast to other deoxyribonucleoside kinases where specific interactions occur with side chains. The TK1 structure differs fundamentally from the structures of the other deoxyribonucleoside kinases, indicating a different evolutionary origin. crystal structures | deoxynucleotide metabolism | prodrug activation