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Aggregation of tau into paired helical filament (PHF) is a hallmark of Alzheimer's disease (AD), and Cys-mediated disulfide bond formation plays a vital role in tau fibrillation. While intermolecular disulfide bond between Cys residues in microtubule-binding repeat (MTBR) region facilitates tau aggregation, intramolecular disulfide bond attenuates the same, though the molecular basis for such phenomenon remains obscure. Thus intramolecular disulfide-bonded tau monomer might be an excellent model to understand the unique features of aggregation-resistant tau conformer. We synthesized the Cys cross-linked tau40 monomer by oxidation and characterized the altered conformational dynamics in the molecule by Hydrogen-deuterium exchange, limited proteolysis and fluorescence quenching. Deuterium exchange study showed that rigidity was imparted in the core PHF region of oxidized tau40 in MTBR segment, consisting of the fundamental PHF6 motif. Conformational rigidity was prominent in C-terminal tail region also. Limited proteolysis supported reduced accessibility of MTBR region in the molecule. PHF formation of oxidized tau40 might be attenuated either by induction of intramolecular H-bonding between the regions of high β-structure propensity in second and third MTBR (R 2 , R 3), thus preventing intermolecular interaction between them, or by imparted rigidity in R 2 –R 3 , preventing the formation of extended β-structure preceding fibrillation. Data indicated plausible effect of conformational adaptation on the nucleation process of oxidized tau40 assembly. Our findings unravel the essential molecular features of aggregation-resistant tau conformer. Therapeutics stabilizing such conformers in vivo might be of high benefit in arresting tau assembly during AD and other tauopathies. Unlabelled Image • Conformational features of aggregation-resistant tau monomer were explored. • Tau hexapeptide region and C-terminus were significantly protected in the molecule. • Conformational change in the molecule interfered with nucleation step of assembly. • Stabilizing such aggregation-resistant conformer might prevent tau assembly in vivo. [ABSTRACT FROM AUTHOR]

Objective: To review current data on vaginal, vulvar, and fallopian tube cancers, including incidence, diagnosis, staging, risk reduction measures, and management. Data Sources: A review of retrieved articles dated 2006-2018 from PubMed. Conclusion: Early diagnosis and treatment of rare gynecologic cancers is dependent on a thorough history and examination. Of particular interest is the role of fallopian tube as the location of primary origin of ovarian and peritoneal cancers as well as the potential for vaccination prevention of vaginal and vulvar cancers. Implications for Nursing Practice: Nurses in diverse roles should have an understanding of these rare tumor types to support assessment and early identification with their patients. [ABSTRACT FROM AUTHOR]

Ytterbium-175 (T1/2=4.2d, Eβ(max)=480keV) has radionuclidic properties suitable to be used in palliative therapy of bone metastases. 175Yb can be produced in moderate specific activity and good radionuclidic purity by thermal neutron bombardment of natural Yb target. The analysis of the neutron irradiated sample exhibited the presence of 96.2% 175Yb along with 2.1% 169Yb and 1.7% 177Lu at 6h post-EOB. Four polyaminomethylene phosphonic acid ligands, ethylenediamine tetramethylene phosphonic acid, propylenediamine tetramethylene phosphonic acid, triethylenetetramine hexamethylene phosphonic acid and diethylenetriamine pentamethylene phosphonic acid were synthesized and radiolabeled with 175Yb. Complexation parameters were optimized to achieve maximum yields (92–99%). All complexes were found to retain their stability at room temperature even after 10d of preparation. Biodistribution studies of the complexes carried out in Wistar rats showed significant bone uptake (3–4.4%/g in tibia at 3h post-injection) with rapid clearance from blood and minimum uptake in soft tissues for all the complexes (bone/blood ratio ∼40–150 and bone/muscles ratio ∼40–400 at 3h post-injection). These studies suggest that 175Yb complexes with the phosphonate ligands have potential for use in palliative treatment of painful bone metastases. [Copyright &y& Elsevier]

Background: We implemented a systematic multidisciplinary process to engage new outpatients with cancer in selecting and preparing a medical decision-maker.Measures: Templated advance care planning notes and medical power of attorney documents were used in the electronic health record by the third office visit.Intervention: Patients were coached to meet with social work from a "culture of yes," viewed a video about the importance of selecting a prepared medical a decision-maker in English or in Spanish, and referenced cards containing simple explanations of advance directives when responding to advance directive questions.Outcomes: A total of 351 patients were evaluated. By visit 3, there was no increase in documented social work advance care planning notes in intervention or scanned medical power of attorney documents in the electronic health record.Conclusions/lessons Learned: This systematic multidisciplinary approach did not engage new outpatients with cancer in preparing a medical decision-maker. More active physician involvement and varied ways of engagement are needed. [ABSTRACT FROM AUTHOR]