Shooting for the STARS: Implementing an Evidence-Based Program to Meet the End of Treatment Needs of Childhood Cancer Survivors and Their Families.

Background: The end of treatment (EOT) is a significant time point along the childhood cancer treatment-survivorship continuum, and is recognized as a time when childhood cancer survivors (CCS) and their families experience significant vulnerability and stress. There is a call by families and healthcare professionals alike for standardized, comprehensive EOT services to successfully navigate through this transition period and better cope with posttreatment medical, physical, and social-emotional issues. Method: A multidisciplinary team of pediatric oncology health care professionals developed and implemented a two-session psychoeducational program to address these EOT needs. To evaluate the Shooting for the STARS (Survivors Tackling All Roadblocks Successfully) EOT Transition Program, a pretest-posttest repeated measures design was utilized. A convenience sample of 47 parents/caregivers and 29 CCS completed surveys before, during, and after the EOT services were received. Analysis of relationships and changes over time was conducted using Spearman-ranked correlations and Friedman tests, a nonparametric repeated measures analysis of variance. Results: All respondents reported program satisfaction, with 94.7% feeling somewhat or very prepared for ending treatment. Participants' distress levels tended to decrease over time. Parent/caregiver-reported levels of CCS' anxiety, fatigue, pain interference, and physical mobility significantly improved over the time period during which families participated in the Shooting for the STARS Program. Discussion: This nurse-led, evidence-based program was determined to be feasible and acceptable. It may contribute to improved health-related quality of life and decrease distress over time.

We Are Done! Now What? Exploring End of Treatment Needs of Childhood Cancer Survivors and Their Parents.

Background: Increased childhood cancer survival rates have spurred a new body of research pertaining to the cancer-survivorship continuum. Literature suggests a lack of research and guidelines for care at the end of treatment (EOT). To improve the transition to survivorship and determine any posttreatment challenges, this study explored the experiences of childhood cancer survivors (CCSs), parents/caregivers, and pediatric oncology health care professionals (HCPs) at EOT. Method: This study employed a mixed methods design. EOT Questionnaires were completed by CCSs and parents/caregivers within 6 months of completing treatment, and by pediatric oncology HCPs. Results: A total of 75 CCSs and parents/caregivers and 21 HCPs completed the study. The majority of parents/caregivers (78%) and older CCSs (94%) recalled having an EOT "meeting." Most were satisfied with the meeting, but described unexpected worries/problems following EOT. Family members stating they were "very satisfied" with the EOT meeting increased significantly relative to the number of EOT topics addressed. In contrast, the omission of certain psychosocial discussion topics negatively correlated with satisfaction. Oncologists provided the majority of EOT services, with infrequent provision by other HCPs. Less than 20% of HCPs characterized families as "very satisfied" with EOT services and suggested improvements to meet families' needs. Discussion: This study found unmet psychosocial and anticipatory guidance needs, indicating a lack of preparedness. The results suggest that end of cancer treatment requires a more standardized, comprehensive, and multidisciplinary approach. Enhanced education and support services are needed to promote the successful navigation of all families through this period of transition.

Artists on the edge of the world: An integrated approach to the study of Magdalenian engraved stone plaquettes from Jersey (Channel Islands).

The Upper Palaeolithic is characterised by the appearance of iconographic expressions most often depicting animals, including anthropomorphic forms, and geometric signs. The Late Upper Palaeolithic Magdalenian saw a flourishing of such depictions, encompassing cave art, engraving of stone, bone and antler blanks and decoration of tools and weapons. Though Magdalenian settlement exists as far northwest as Britain, there is a limited range of art known from this region, possibly associated with only fleeting occupation of Britain during this period. Stone plaquettes, flat fragments of stone engraved on at least one surface, have been found in large quantities at numerous sites spanning the temporal and geographical spread of the Magdalenian, but they have been absent so far from the archaeological record of the British Isles. Between 2015 and 2018, ten fragments of stone plaquettes extensively engraved with abstract designs were uncovered at the Magdalenian site of Les Varines, Jersey, Channel Islands. In this paper, we report detailed analyses of these finds, which provide new evidence for technologies of abstract mark-making, and their significance within the lives of people on the edge of the Magdalenian world. These engraved stone fragments represent important, rare evidence of artistic expression in what is the far northern and western range of the Magdalenian and add new insight to the wider significance of dynamic practices of artistic expression during the Upper Palaeolithic.

The end of cancer treatment experience for children, adolescents, and their parents: A systematic review of the literature.

PROBLEM IDENTIFICATION: To date, there is limited study of the end of treatment (EOT) transition experiences and needs of children/adolescents with cancer and their parents. LITERATURE SEARCH: A systematic search identified primary research focusing on EOT, describing child, adolescent, and parental perceptions, experiences, and needs during this transition period. Of 170 articles identified, 22 met inclusion criteria. DATA EVALUATION/SYNTHESIS: Studies were appraised for level and quality of evidence. Narrative synthesis was performed to extract themes and integrate the literature. Family members' perceived needs, factors influencing the EOT experience, and consequences of this transition emerged as themes. CONCLUSIONS: Uncertainty and heightened anxiety at EOT highlight the need for increased education and support for family members. Family functioning and distress influence the EOT experience, with variable effects on each family member. There is a call for individualized interventions to promote coping and positive outcomes.

A Coordinated Microstructural and Isotopic Study of a Wark-Lovering Rim on a Vigarano CAI.

We carried out a coordinated mineralogical and isotopic study of a Wark-Lovering (WL) rim on a Ca,Al-rich inclusion (CAI) from the reduced CV3 chondrite Vigarano. The outermost edge of the CAI mantle is mineralogically and texturally distinct compared to the underlying mantle that is composed of coarse, zoned melilite (Åk~10-60) grains. The mantle edge contains fine-grained gehlenite with hibonite and rare grossite that likely formed by rapid crystallization from a melt enriched in Ca and Al. These gehlenite and hibonite layers are surrounded by successive layers of spinel, zoned melilite (Åk~0-10), zoned diopside that grades outwards from Al,Ti-rich to Al,Ti-poor, and forsteritic olivine intergrown with diopside. These layered textures are indicative of sequential condensation of spinel, melilite, diopside, and forsterite onto hibonite. Anorthite occurs as a discontinuous layer that corrodes adjacent melilite and Al-diopside, and appears to have replaced them, probably even later than the forsterite layer formation. Based on these observations, we conclude that the WL rim formation was initiated by flash melting and extensive evaporation of the original inclusion edge, followed by subsequent gas-solid reactions under highly dynamic conditions. All the WL rim minerals are 16O-rich (Δ17O = ~-23‰), indicating their formation in an 16O-rich nebular reservoir. Our Al-Mg measurements of hibonite, spinel, and diopside from the WL rim, as well as spinel and Al,Ti-diopside in the core, define a single, well-correlated isochron with an inferred initial 26Al/27Al ratio of (4.94 ± 0.12) × 10-5. This indicates that the WL rim formed shortly after the host CAI. In contrast, the lack of 26Mg excesses in the WL rim anorthite suggest its later formation or later isotopic disturbance in the solar nebula, after 26Al had decayed.

Development and Content Validation of End of Treatment Questionnaires for Children With Cancer.

Purpose: To describe the development and content validation of measures to assess the psychoeducational needs of children, adolescents/young adults (AYAs), and their parents at the end of successful treatment for cancer. Method: Professional experts, which included pediatric oncology nurses and advanced practice registered nurses, conducted a systematic review of the literature to determine specific end of treatment (EOT) needs of children and AYAs with cancer and their parents and evaluate available tools to measure these needs. From this review, two EOT questionnaires were initially developed. Oncology Family Advisory Board (FAB) members served as experiential experts in refining and validating these questionnaires. FAB members participated in a content validation process, rating questionnaires online, and subsequently participating in a focus group to establish content validity (n = 6). Results: Three EOT questionnaires were ultimately developed. The Child/AYA questionnaire was divided into two separate measures for developmental and literacy considerations. The Parent/Caregiver and the AYA questionnaires each contain 38 items with a content validity index score of 100%. The Child questionnaire contains 37 items with a content validity index score of 100%. Conclusion: Content validity was established for three EOT questionnaires, each of which has the potential to elicit information regarding needs and potential gaps in services perceived by childhood cancer survivors and their parents. Further psychometric testing is needed to determine stability (test-retest reliability) and construct validity of the questionnaires.

The Polycystin-1, Lipoxygenase, and α-Toxin Domain Regulates Polycystin-1 Trafficking.

Mutations in polycystin-1 (PC1) give rise to autosomal dominant polycystic kidney disease, an important and common cause of kidney failure. Despite its medical importance, the function of PC1 remains poorly understood. Here, we investigated the role of the intracellular polycystin-1, lipoxygenase, and α-toxin (PLAT) signature domain of PC1 using nuclear magnetic resonance, biochemical, cellular, and in vivo functional approaches. We found that the PLAT domain targets PC1 to the plasma membrane in polarized epithelial cells by a mechanism involving the selective binding of the PLAT domain to phosphatidylserine and L-α-phosphatidylinositol-4-phosphate (PI4P) enriched in the plasma membrane. This process is regulated by protein kinase A phosphorylation of the PLAT domain, which reduces PI4P binding and recruits ß-arrestins and the clathrin adaptor AP2 to trigger PC1 internalization. Our results reveal a physiological role for the PC1-PLAT domain in renal epithelial cells and suggest that phosphorylation-dependent internalization of PC1 is closely linked to its function in renal development and homeostasis.

Receptor protein tyrosine phosphatases are novel components of a polycystin complex.

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutation of PKD1 and PKD2 that encode polycystin-1 and polycystin-2. Polycystin-1 is tyrosine phosphorylated and modulates multiple signaling pathways including AP-1, and the identity of the phosphatases regulating polycystin-1 are previously uncharacterized. Here we identify members of the LAR protein tyrosine phosphatase (RPTP) superfamily as members of the polycystin-1complex mediated through extra- and intracellular interactions. The first extracellular PKD1 domain of polycystin-1 interacts with the first Ig domain of RPTPσ, while the polycystin-1 C-terminus of polycystin-1 interacts with the regulatory D2 phosphatase domain of RPTPγ. Additional homo- and heterotypic interactions between RPTPs recruit RPTPδ. The multimeric polycystin protein complex is found localised in cilia. RPTPσ and RPTPδ are also part of a polycystin-1/E-cadherin complex known to be important for early events in adherens junction stabilisation. The interaction between polycystin-1 and RPTPγ is disrupted in ADPKD cells, while RPTPσ and RPTPδ remain closely associated with E-cadherin, largely in an intracellular location. The polycystin-1 C-terminus is an in vitro substrate of RPTPγ, which dephosphorylates the c-Src phosphorylated Y4237 residue and activates AP1-mediated transcription. The data identify RPTPs as novel interacting partners of the polycystins both in cilia and at adhesion complexes and demonstrate RPTPγ phosphatase activity is central to the molecular mechanisms governing polycystin-dependent signaling. This article is part of a Special Issue entitled: Polycystic Kidney Disease.

Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is essential for its effects on cell growth and calcium channel activity.

PKD2 is mutated in 15% of patients with autosomal dominant polycystic kidney disease. The PKD2 protein, polycystin-2 or TRPP2, is a nonselective Ca2+-permeable cation channel that has been shown to function at several locations, including primary cilia, basolateral membrane, and at the endoplasmic reticulum (ER). Nevertheless, the factors that regulate the channel activity of polycystin-2 are not well understood. Polycystin-2 has been shown previously to be regulated by phosphorylation at two serine residues (Ser812 and Ser76) with distinct functional consequences. Here, we report the identification of a previously unrecognized phosphorylation site within the polycystin-2 C terminus (Ser801), and we demonstrate that it is phosphorylated by protein kinase D. Phosphorylation at this site was significantly increased in response to serum and epidermal growth factor stimulation. In nonciliated Madin-Darby canine kidney I cells, inducible expression of polycystin-2 inhibited cell proliferation compared with wild-type cells. Mutagenesis at Ser801 abolished these effects and reduced ATP-stimulated Ca2+ release from ER stores. Finally, we show that a pathogenic mutation (S804N) within the consensus kinase recognition sequence abolished Ser801 phosphorylation. These results suggest that growth factor-stimulated, protein kinase D-mediated phosphorylation of polycystin-2 is essential for its ER channel function and links extracellular stimuli to its effects on cell growth and intracellular calcium regulation.

Invertebrates as animal models for Staphylococcus aureus pathogenesis: a window into host-pathogen interaction.

Recently, the use of invertebrate models of infection has given exciting insights into host-pathogen interaction for a number of bacteria. In particular, this has revealed important factors of the host response with remarkable parallels in higher organisms. Here, we review the advances attained in the elucidation of virulence determinants of a major human pathogen, Staphylococcus aureus, in relation to the invertebrate models thus far applied, the silkworm (Bombyx mori), the fruit fly (Drosophila melanogaster) and the roundworm (Caenorhabditis elegans). Also, the major pathways of host defence are covered in light of the response to S. aureus and the similarities and divergences in innate immunity of vertebrates and invertebrates. Consequently, we comparatively consider pathogen recognition receptors, signal transduction pathways (including Toll, Imd and others), and the humoral and cellular antimicrobial effectors. The technically convenient and ethically acceptable invertebrates appear as a valuable first tool to discriminate molecules participating from both sides of the host-S. aureus interaction as well as a high throughput method for antimicrobial screening.

Drosophila melanogaster as a model host for Staphylococcus aureus infection.

Staphylococcus aureus is an important pathogen of humans, causing a range of superficial and potentially life-threatening diseases. Infection of the fruit fly Drosophila melanogaster with S. aureus results in systemic infection followed by death. Screening of defined S. aureus mutants for components important in pathogenesis identified perR and pheP, with fly death up to threefold slower after infection with the respective mutants compared to the wild-type. Infection of D. melanogaster with reporter gene fusion strains demonstrated the in vivo expression levels of the accessory gene regulator, agr, alpha-toxin, hla, and a manganese transporter, mntA. The use of the green fluorescent protein as a reporter under the control of the agr promoter (P3) showed S. aureus microcolony formation in vivo. The disease model also allowed the effect of antibiotic treatment on the flies to be determined. D. melanogaster is a genetically tractable model host for high-throughput analysis of S. aureus virulence determinants.

Entry of antibiotic ointment into the anterior chamber after uneventful phacoemulsification.

A 77-year-old woman had uneventful phacoemulsification. Postoperative examination revealed that chloramphenicol ointment instilled in the conjunctival fornix had entered the anterior chamber and smeared the intraocular lens (IOL). Immediate surgical removal of the ointment with IOL exchange was performed. The eye settled in 6 weeks with a best corrected visual acuity of 6/9. This case raises concerns about the integrity of clear corneal incisions and the need for postoperative review of uneventful phacoemulsification surgery.