Priorities and Preferences of Patients With Head and Neck Cancer for Discussing and Receiving Information About Sexuality and Perception of Self-Report Measures.

BACKGROUND: Head and neck cancer and its treatment can cause impairment in survivors' sexuality. Previous studies show a need for education and psychological support. AIM: To examine patients' priorities and preferences for discussing and receiving information about sexuality and to examine patient perceptions of existing self-report measures used in research. METHODS: This descriptive, cross-sectional, Web-based study recruited adults with a current or previous diagnosis of head and neck cancer. Participants answered questions about their priority and preference for receiving information about sexuality and reviewed 4 self-report measures commonly used in the research of this population. RESULTS: More than 80% (n = 61) of participants reported that it was important to receive information about sexual issues. Participants chose "at the time of diagnosis" as the most frequent answer for preferred time to receive this information. Half of the participants (n = 35) indicated that they prefer discussing sexual issues with a health-care provider. The most frequent answer for the method of receiving information was through discussions. Participants endorsed 4 themes not addressed by self-report surveys: (i) elicitation of important information, (ii) symptom burden issues, (iii) psychological issues, and (iv) physical barriers. CLINICAL IMPLICATIONS: Providers, regardless of specialty, must attempt or facilitate discussions around these issues at various times within the treatment and recovery phases. STRENGTHS & LIMITATIONS: Although limited by sample representation and cross-sectional design, this study addresses an important patient-centered issue that is a critical aspect of quality of life. CONCLUSIONS: Patients prefer to discuss sexual issues in person with their health-care providers at the time of diagnosis. Participants reacted positively to the self-report measures, but they felt that important issues faced by patients with head and neck cancer were not fully addressed. Rhoten BA, Davis AJ, Baraff BN, et al. Priorities and Preferences of Patients With Head and Neck Cancer for Discussing and Receiving Information About Sexuality and Perception of Self-Report Measures. J Sex Med 2020;17:1529-1537.

A Randomized Clinical Trial Comparing the Impact of a Web-Based Multimedia Intervention Versus an Educational Pamphlet on Patient Outcomes in Breast Cancer Survivors with Chronic Secondary Lymphedema.

Objective: The purpose of this study was to evaluate the effects of a Web-based Multimedia Intervention (WBMI) for breast cancer-related lymphedema (BCRL) patients on symptom burden, function, psychological well-being, costs, and arm volume. Methods: Women with BCRL were randomized to intervention (n = 80) or control (n = 80) groups. The WBMI offered 12 modules, each of which took about 30 minutes to complete. The Pamphlet took about 2 hours to read. Data on symptom burden, psychological well-being, function, and costs were collected preintervention; and 1, 3, 6, and 12 months postintervention. A subgroup of 45 regional patients had arm extracellular fluid measured by bioimpedance at baseline and at 3, 6, and 12 months postintervention. Intervention perceived value was also captured. Results: A statistically significant difference (p = 0.011) was observed for rates of intervention completion, WBMI (58%), and Pamphlet (77%). With the exception of the number of biobehavioral symptoms (mood), no statistically significant differences between groups in symptom reduction were apparent between baseline and 1 or 12 months (effect sizes = 0.05-0.28, p > 0.05) based on the Lymphedema Symptom Intensity and Distress Scale-Arm (LSIDS-A). No statistically significant differences between the groups were observed for changes in other variables. The WBMI was perceived as providing better self-care information than the Pamphlet (p = 0.001). Conclusions: WBMI participants experienced improved biobehavioral symptoms and higher perceived quality of information. The lack of significant differences on other variables may be due to the high percentage of participants who did not complete the WBMI.

Effects of a dietary supplement on gastric ulcer number and severity in exercising horses.

This study evaluated the effect of a dietary supplement on the treatment of equine gastric ulcer syndrome (EGUS). Gastroscopy was performed on university riding horses of mixed breeds at two locations and only horses exhibiting gastric ulcers were selected to participate in this study (location A, n = 13; location B, n = 15). Gastric ulcer severity was assessed using two different methods depending on location before treatment (Pre). After gastroscopy, horses were fed the supplement in addition to their regular diet for 44 d (14-d adaptation period followed by 30-d feeding period). All horses were subjected to gastroscopy again at the end of the feeding period (Post) to evaluate changes in gastric lesions. Statistical analysis was performed using SAS. Individual horses were the experimental unit with dependent variables including severity and number of gastric ulcers. At location A, dependent variable included severity of gastric lesions with fixed effects of time (Pre and Post) and location (stall or pasture). For location B, dependent variables included severity and number of gastric lesions with fixed effects of time. Severity of gastric ulcers decreased at both locations in horses following the feeding period. Gastric lesion scores decreased from 2.2990 to 1.3760 (P = 0.0015) at location A and gastric lesion severity from 3.8000 to 2.5667 (P = 0.0322) at location B. No differences were found in gastric lesion scores at location A between horses housed in stalls or pastures (1.8750 and 1.8000; P = 0.7783). The number of gastric ulcers observed at location B were similar Pre and Post treatment (3.4667 and 3.5333; P = 0.8363). There were no changes in body condition score (P ≥ 0.2607), BW (P ≥ 0.4551), or behavior at either location. Results suggest that oral supplementation may decrease severity of gastric ulcers in horses participating in university riding programs.

Characterization and comparative analysis of Arabidopsis phosphatidylinositol phosphate 5-kinase 10 reveals differences in Arabidopsis and human phosphatidylinositol phosphate kinases.

Arabidopsis phosphatidylinositol phosphate (PtdInsP) kinase 10 (AtPIPK10; At4g01190) is shown to be a functional enzyme of the subfamily A, type I AtPtdInsP kinases. It is biochemically distinct from AtPIPK1 (At1g21980), the only other previously characterized AtPtdInsP kinase which is of the B subfamily. AtPIPK10 has the same K(m), but a 10-fold lower V(max) than AtPIPK1 and it is insensitive to phosphatidic acid. AtPIPK10 transcript is most abundant in inflorescence stalks and flowers, whereas AtPIPK1 transcript is present in all tissues. Comparative analysis of recombinant AtPIPK10 and AtPIPK1 with recombinant HsPIPKIalpha reveals that the Arabidopsis enzymes have roughly 200- and 20-fold lower V(max)/K(m), respectively. These data reveal one explanation for the longstanding mystery of the relatively low phosphatidylinositol-(4,5)-bisphosphate:phosphatidylinositol-4-phosphate ratio in terrestrial plants.

The N-terminal membrane occupation and recognition nexus domain of Arabidopsis phosphatidylinositol phosphate kinase 1 regulates enzyme activity.

The type I B family of phosphatidylinositol phosphate kinases (PIPKs) contain a characteristic region of Membrane Occupation and Recognition Nexus (MORN) motifs at the N terminus. These MORN motifs are not found in PIPKs from other eukaryotes. To understand the impact of the additional N-terminal domain on protein function and subcellular distribution, we expressed truncated and full-length versions of AtPIPK1, one member of this family of PIPKs, in Escherichia coli and in tobacco cells grown in suspension culture. Deletion of the N-terminal MORN domain (amino acids 1-251) of AtPIPK1 increased the specific activity of the remaining C-terminal peptide (DeltaMORN) >4-fold and eliminated activation by phosphatidic acid (PtdOH). PtdOH activation could also be eliminated by mutating Pro(396) to Ala (P396A) in the predicted linker region between the MORN and the kinase homology domains. AtPIPK1 is product-activated and the MORN domain binds PtdIns(4,5)P(2). Adding back the MORN peptide to DeltaMORN or to the PtdOH-activated full-length protein increased activity approximately 2-fold. Furthermore, expressing the MORN domain in vivo increased the plasma membrane PtdInsP kinase activity. When cells were exposed to hyperosmotic stress, the MORN peptide redistributed from the plasma membrane to a lower phase or endomembrane fraction. In addition, endogenous PtdInsP kinase activity increased in the endomembrane fraction of hyperosmotically stressed cells. We conclude that the MORN peptide can regulate both the function and distribution of the enzyme in a manner that is sensitive to the lipid environment.

Arabidopsis phosphatidylinositol phosphate kinase 1 binds F-actin and recruits phosphatidylinositol 4-kinase beta1 to the actin cytoskeleton.

The actin cytoskeleton can be influenced by phospholipids and lipid-modifying enzymes. In animals the phosphatidylinositol phosphate kinases (PIPKs) are associated with the cytoskeleton through a scaffold of proteins; however, in plants such an interaction was not clear. Our approach was to determine which of the plant PIPKs interact with actin and determine whether the PIPK-actin interaction is direct. Our results indicate that AtPIPK1 interacts directly with actin and that the binding is mediated through a predicted linker region in the lipid kinase. AtPIPK1 also recruits AtPI4Kbeta1 to the cytoskeleton. Recruitment of AtPI4Kbeta1 to F-actin was dependent on the C-terminal catalytic domain of phosphatidylinositol-4-phosphate 5-kinase but did not require the presence of the N-terminal 251 amino acids, which includes 7 putative membrane occupation and recognition nexus motifs. In vivo studies confirm the interaction of plant lipid kinases with the cytoskeleton and suggest a role for actin in targeting PIPKs to the membrane.

Increasing plasma membrane phosphatidylinositol(4,5)bisphosphate biosynthesis increases phosphoinositide metabolism in Nicotiana tabacum.

A genetic approach was used to increase phosphatidylinositol(4,5)bisphosphate [PtdIns(4,5)P2] biosynthesis and test the hypothesis that PtdInsP kinase (PIPK) is flux limiting in the plant phosphoinositide (PI) pathway. Expressing human PIPKIalpha in tobacco (Nicotiana tabacum) cells increased plasma membrane PtdIns(4,5)P2 100-fold. In vivo studies revealed that the rate of 32Pi incorporation into whole-cell PtdIns(4,5)P2 increased >12-fold, and the ratio of [3H]PtdInsP2 to [3H]PtdInsP increased 6-fold, but PtdInsP levels did not decrease, indicating that PtdInsP biosynthesis was not limiting. Both [3H]inositol trisphosphate and [3H]inositol hexakisphosphate increased 3-and 1.5-fold, respectively, in the transgenic lines after 18 h of labeling. The inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] binding assay showed that total cellular Ins(1,4,5)P3/g fresh weight was >40-fold higher in transgenic tobacco lines; however, even with this high steady state level of Ins(1,4,5)P3, the pathway was not saturated. Stimulating transgenic cells with hyperosmotic stress led to another 2-fold increase, suggesting that the transgenic cells were in a constant state of PI stimulation. Furthermore, expressing Hs PIPKIalpha increased sugar use and oxygen uptake. Our results demonstrate that PIPK is flux limiting and that this high rate of PI metabolism increased the energy demands in these cells.

Cyclodextrins enhance recombinant phosphatidylinositol phosphate kinase activity.

Inositol lipid kinases have been studied extensively in both plant and animal systems. However, major limitations for in vitro studies of recombinant lipid kinases are the low specific activity and instability of the purified proteins. Our goal was to determine if cyclodextrins would provide an effective substrate delivery system and enhance the specific activity of lipid kinases. For these studies, we have used recombinant Arabidopsis thaliana phosphatidylinositol phosphate kinase 1 (At PIPK1). At PIPK1 was produced as a fusion protein with glutathione-S-transferase and purified on glutathione-Sepharose beads. A comparison of lipid kinase activity using substrate prepared in alpha-, beta-, or gamma-cyclodextrin indicated that beta-cyclodextrin was most effective and enhanced lipid kinase activity 6-fold compared with substrate prepared in Triton X-100-mixed micelles. We have optimized reaction conditions and shown that product can be recovered from the cyclodextrin-treated recombinant protein, which reveals a potential method for automating the assay for pharmacological screening.