Reported Concerns and Acceptance of Information or Referrals Among Breast Cancer Survivors Seen for Care Planning Visits: Results from the University of Wisconsin Carbone Cancer Center Survivorship Program.

Breast cancer survivors' experience physical and psychosocial concerns following active curative-intent treatment. Survivors' complex needs are often reviewed at survivorship care planning visits (SCP visits). However, little is known about the post-treatment concerns and resource needs addressed within the context of SCP visits. Using discretely collected electronic health record data, we examined characteristics, concerns, and acceptance of education materials and/or referrals among stages 0-3 breast cancer survivors seen for SCP visits. Most survivors reported concerns related to activity (n = 739; 72.7%) and nutrition (n = 677; 66.6%). Survivors of color were more likely to report concerns related to pain/swelling (odds ratio (OR), 4.4; 95% CI, 1.7-11.4) and employment/insurance (2.8; 1.4-5.7) compared to Whites. More than half accepted materials or referrals for concerns related to nutrition, activity/pain, substance use, sexual health, mood, and sleep (padj-value < 0.05). However, not all reported concerns led to acceptance of materials or referrals. Survivors seen for SCP visits report a wide range of concerns at the end of active curative-intent treatment but may not necessarily accept materials or referrals for their concerns within the context of these visits. Our findings highlight the importance of exercise, physical rehabilitation, and nutrition interventions for survivors following active curative-intent treatment. Further study is needed to elucidate the reasons for acceptance vs. non-acceptance of resources addressing reported concerns.

Development of nutrition counselling resources for family medicine using the knowledge to action framework.

BACKGROUND: Obesity within the USA is a public health crisis. Nutrition counselling in primary care is an effective yet underutilized intervention because of both health care professional (HCP) barriers and patient barriers. OBJECTIVE: The purpose of this study was to: (i) identify HCP and patient perceptions, needs and barriers surrounding nutrition counselling, (ii) develop nutrition resources for HCPs and patients and (iii) assess utility of the approach. METHODS: Paper surveys were completed by 48 HCPs (response rate: 63.2%) and 185 patients in five family medicine clinics. Based on results, nutrition resources were developed and integrated into the electronic medical record. To assess utility, paper surveys were completed by 25 HCPs (response rate: 32.9%) after 4 weeks. Results were presented as descriptive statistics. RESULTS: Both HCPs and patients indicated that nutrition counselling is necessary to improve dietary behaviours, but barriers prevented HCPs from providing counselling and patients from improving dietary behaviours. HCPs indicated that improved patient handouts (74.5%), community nutrition classes (72.3%) and community cooking classes (63.8%) could enhance nutrition counselling. Patients identified that coupons and discounts (45.5%), sample meal plans and recipes (44.3%) and websites for recipes, grocery guides, and cooking videos (35.9%) would help them to consume a healthy diet. Patient education handouts, patient resource guides and HCP education were created. Following receipt, most HCPs (85%) indicated that the resources enhanced their nutrition counselling. CONCLUSIONS: HCP and patient barriers to nutrition counselling are multiple and varied. Design and implementation of an approach tailored to stakeholders' needs have potential to improve nutrition counselling in primary care.

Discovery of Novel Integrase Inhibitors Acting outside the Active Site Through High-Throughput Screening.

Currently, an increasing number of drugs are becoming available to clinics for the treatment of HIV infection. Even if this targeted therapy is highly effective at suppressing viral replication, caregivers are facing growing therapeutic failures in patients, due to resistance with or without treatment adherence concerns. Accordingly, it is important to continue to discover small molecules that have a novel mechanism of inhibition. In this work, HIV integrase inhibitors were selected by high-throughput screening. Chemical structure comparisons enabled the identification of stilbene disulfonic acids as a potential new chemotype. Biochemical characterization of the lead compound stilbenavir (NSC34931) and a few derivatives was performed. Stilbene disulfonic acid derivatives exhibit low to sub-micromolar antiviral activity, and they inhibit integrase through DNA-binding inhibition. They probably bind to the C-terminal domain of integrase, in the cavity normally occupied by the noncleaved strand of the viral DNA substrate. Because of this original mode of action compared to active site strand transfer inhibitors, they do not exhibit cross-resistance to the three main resistance pathways to integrase inhibitors (G140S-Q148H, N155H, and Y143R). Further structure-activity optimization should enable the development of more active and less toxic derivatives with potential clinical relevance.

Analytical approximation for photonic array modes in 1D photonic crystal superlattices.

We present a comprehensive analytical approximation for array modes (both the modal fields and their associated propagation constants) for 1D photonic crystal superlattices (i.e., large periodic arrays of repeated sequences of different coupled waveguides/lasers). In this class, a regular periodicity of a photonic lattice is supplemented with the additional periodicity of a larger scale. Our approximation is a vectorial approach, accounting for the TE and TM polarizations. It can be applied to both the low- and high-contrast photonic devices. We used the model of standing waves for analytical evaluation of envelopes of array modes in a photonic superlattice. Combination of the model of standing waves with the coupled-mode formalism for infinite photonic superlattices allows evaluation of propagation constants of the array modes. Both the evaluations require only a fraction of a second for computation. Still, the results, acquired with the analytical approximation, are very close to those of well-established approaches. Furthermore, for the first time, analytical expressions for the modal fields and propagation constants become available.

Analytical approximation for photonic array modes in two-dimensional photonic crystal lattices.

We presented here a comprehensive analytical approximation, describing array modes (both the modal fields and their associated propagation constants) in 2D photonic lattices (i.e., arrays of identical coupled waveguides/lasers). Our approximation is a vectorial approach, accounting for the TE and TM polarizations. It is applicable to both the low-contrast and high-contrast photonic devices. The model of standing waves of a membrane was used for analytical evaluation of envelopes of the array modes and the total modal fields. Combination of this model with the coupled-mode formalism for 2D infinite photonic lattices allowed for evaluation of propagation constants of the array modes. Both the computations required only a few seconds. Still, the results, acquired with the analytical approximation, are in close agreement with those acquired with well-established approaches. Moreover, for the first time, analytical expressions for the modal fields and propagation constants become available.

Analytical approximation for photonic array modes in one-dimensional photonic crystal devices.

A new analytical approximation for photonic array modes is presented. We consider the specific class of one-dimensional (1D) photonic crystals (encompassing large arrays of coupled identical planar waveguides, large arrays of identical phase-locked lasers, etc.), in which light propagates along the optical axis of the device. Approximate analytical expressions for the array modes (both spatial distribution and propagation constants) become available. This approach allows a fast, simple, and accurate analytical evaluation of the electromagnetic field in 1D photonic crystal devices.

Recommending ultra-processed oral nutrition supplements for unintentional weight loss: Are there risks?

Oral nutrition supplements (ONS) are widely recommended for the management of unintentional weight loss in patient populations, long-term care residents, and community-dwelling older adults. Most marketed ONS are ultra-processed, with precision nutrition and aseptic composition, as well as convenience and availability, driving their selection. However, therapeutic effectiveness is mixed and the potential health risks of consuming ultra-processed ONS long-term in lieu of less-processed foods have received little attention. A diverse and balanced microbiota supporting immunity and wellness is maintained by a diet rich in plant-sourced foods. The implications of ultra-processed ONS displacing plant-sourced foods, and specifically the potential for undesirable impacts on the gut microbiota, require consideration. Most ONS are either devoid of fiber or are supplemented with isolated or purified fibers that may contribute to adverse gastrointestinal symptoms and appetite suppression. In contrast, the diversity of microbial-available, nondigestible carbohydrates, together with the array of phytochemicals found in plant-sourced foods, support microbial diversity and its resiliency. This review outlines the clinical dilemma of recommending commercial ultra-processed ONS vs nutritionally adequate (eg, high-energy/high-protein) foods and beverages that contribute to diet quality, maintenance of a diverse and stable gut microbiota composition, and support nutrition status and health. Ultra-processed ONS may fall short of expected health benefits, and overreliance may potentially contribute to the risk for patient and older adult populations because of the displacement of a variety of healthful foods.

Assessing the stability-indicating properties of alternative potency assays for inactivated influenza vaccine.

Determination of the potency of a vaccine is critical to ensuring that an appropriate dose is delivered, lot-to-lot consistency is maintained, and that the formulation is stable over the life of the vaccine. The potency of inactivated influenza vaccines is determined routinely by the Single Radial Immunodiffusion (SRID) assay. A number of alternative potency assays have been proposed and have been under evaluation in recent years. The aim of this study was to compare a surface plasmon resonance-based assay and two different enzyme linked immunoassays against the current potency assay, SRID, and against mouse immunogenicity when haemagglutinin antigen of the A(H1N1)pdm09 component of an inactivated influenza vaccine is stressed by elevated temperature, low pH and freezing. This analysis demonstrated that the alternative assays had good correspondence with SRID for samples from most stress conditions and that the immunogenicity in mice corresponded with potency in SRID for all stress samples. Subject to further analysis, the assays have been shown to have the potential to possibly replace, and at least complement, SRID.

Comparison of diet quality of US adults based on primary motivation for following a vegetarian diet: A cross-sectional online study.

Adults adopt a vegetarian diet for various motivations, but it is unknown their overall diet quality based on a primary motivation. The purpose of the study was to compare overall diet quality, nutrient intake and related food groups based on primary motivation for following a vegetarian diet. It was hypothesized that vegetarians who chose the diet for health-related motivations would have a higher diet quality based on the Healthy Eating Index (HEI)-2015 scores compared to those following the diet for other motivations. A cross-sectional study was conducted online in the United States. Participants (n = 511) completed an 18-item questionnaire and a 24-hour recall using the Automated Self-Administered 24-hour Dietary Recall (ASA24-2018) and were divided into one of three groups (Health, Animal, Other [family, religious beliefs, or environment]) based on their primary motivation for following a vegetarian diet. Total HEI-2015 scores were determined and Kruskal-Wallis ANOVA on Ranks with a Dunn's Method for all pairwise comparisons (p < 0.05) were conducted. Results showed that total HEI-2015 scores differed among groups (p = 0.022) with the Health group having a higher score than the Other group (70.2 [57.0, 79.1] versus 63.6 [52.2, 77.1], median 25th, 75th) but not the animal rights group (66.5 [55.1, 77.0]). Higher component scores for total protein foods, seafood and plant proteins and fatty acids contributed to the significant difference. Adults who were motivated by health to follow a vegetarian diet had a higher diet quality than those who cited Other as their primary motivation. As motivations may impact diet quality of vegetarians, it is necessary to account for them.

Patterns and predictors of cancer-specific patient health portal usage among patients with cancer: results from the UWCCC Survivorship Program.

BACKGROUND: Portals can assist patients in managing their healthcare. Understanding how patients with cancer use portals can facilitate improvements in patient engagement in cancer care. This study sought to determine if patients with cancer used portals differently for cancer versus noncancer purposes. The effects of geographic residence (rural vs. urban residence) and cancer stage on portal usage were also investigated. METHODS: We conducted a retrospective analysis of portal usage by patients seen at an NCI-designated cancer center between 2015 and 2019. Demographics, cancer characteristics, and portal usage (number of successful logins, messages sent, and results viewed) were extracted. Messages sent and results viewed in the portal were deemed oncologist-specific and cancer specific if sent to or ordered in medical oncology departments, respectively. RESULTS: The analysis included a total of 5950 patients with cancer. Patients were less likely to send and view oncologist-specific messages compared to non-oncologist-specific messages. They were also less likely to view cancer results compared to noncancer results. Compared to urban counterparts, patients residing in rural areas had lower odds of having any logins and logged in less frequently during the year of diagnosis. Compared to patients with non-metastatic disease, individuals with metastatic disease were more likely to become frequent portal users. CONCLUSIONS: Patients may use portals differently for cancer versus noncancer purposes; urban residence and metastatic cancer were associated with more frequent usage. Further investigation can inform interventions to increase accessibility for groups at a disadvantage related to the use of this technology and to help patients better leverage portals to manage their cancer.

Beneficial effects of substrate reduction therapy in a mouse model of GM1 gangliosidosis.

GM1 gangliosidosis is an inherited neurodegenerative disorder caused by lysosomal beta-galactosidase deficiency, resulting in the storage of GM1 and GA1, primarily in the central nervous system. This disease typically afflicts infants and young children and there is currently no effective therapy. Substrate reduction therapy (SRT) could be of potential benefit. The imino sugars N-butyldeoxynojirimycin (NB-DNJ, miglustat, Zavesca) and N-butyldeoxygalactonojirimycin (NB-DGJ) used for SRT inhibit glucosylceramide synthase (GlcCerS) that catalyses the first committed step in glycosphingolipid biosynthesis. We have compared the efficacy and tolerability of NB-DNJ and NB-DGJ in the beta-galactosidase knockout mouse. NB-DGJ was better tolerated than NB-DNJ, due to intrinsic gastrointestinal tract dysfunction that was exacerbated by NB-DNJ. However, functional improvement was greatest with NB-DNJ treatment which may potentially be caused by novel anti-inflammatory properties of NB-DNJ.

Niemann-Pick disease type C1 is a sphingosine storage disease that causes deregulation of lysosomal calcium.

Niemann-Pick type C1 (NPC1) disease is a neurodegenerative lysosomal storage disorder caused by mutations in the acidic compartment (which we define as the late endosome and the lysosome) protein, NPC1. The function of NPC1 is unknown, but when it is dysfunctional, sphingosine, glycosphingolipids, sphingomyelin and cholesterol accumulate. We have found that NPC1-mutant cells have a large reduction in the acidic compartment calcium store compared to wild-type cells. Chelating luminal endocytic calcium in normal cells with high-affinity Rhod-dextran induced an NPC disease cellular phenotype. In a drug-induced NPC disease cellular model, sphingosine storage in the acidic compartment led to calcium depletion in these organelles, which then resulted in cholesterol, sphingomyelin and glycosphingolipid storage in these compartments. Sphingosine storage is therefore an initiating factor in NPC1 disease pathogenesis that causes altered calcium homeostasis, leading to the secondary storage of sphingolipids and cholesterol. This unique calcium phenotype represents a new target for therapeutic intervention, as elevation of cytosolic calcium with curcumin normalized NPC1 disease cellular phenotypes and prolonged survival of the NPC1 mouse.

An inducible mouse model of late onset Tay-Sachs disease.

Mouse models of the G(M2) gangliosidoses, Tay-Sachs and Sandhoff disease, are null for the hexosaminidase alpha and beta subunits respectively. The Sandhoff (Hexb-/-) mouse has severe neurological disease and mimics the human infantile onset variant. However, the Tay-Sachs (Hexa-/-) mouse model lacks an overt phenotype as mice can partially bypass the blocked catabolic pathway and escape disease. We have investigated whether a subset of Tay-Sachs mice develop late onset disease. We have found that approximately 65% of the mice develop one or more clinical signs of the disease within their natural life span (n = 52, P < 0.0001). However, 100% of female mice with repeat breeding histories developed late onset disease at an earlier age (n = 21, P < 0.0001) and displayed all clinical features. Repeat breeding of a large cohort of female Tay-Sachs mice confirmed that pregnancy induces late onset Tay-Sachs disease. Onset of symptoms correlated with reduced up-regulation of hexosaminidase B, a component of the bypass pathway.