Screening for Social Determinants of Health in Transitional Care Patients and Partnering With the Faith Community to Address Food Insecurity.

PURPOSE/OBJECTIVES: The purposes of this project were to collect and document social determinants of health (SDOH) data, and to partner with the faith community to address identified food insecurity. PRIMARY PRACTICE SETTING: The setting for this project was an ambulatory care clinic in Guilford County, North Carolina. The clinic offers care to patients discharged from a regional medical center who have no insurance and/or primary care providers. FINDINGS/CONCLUSIONS: Clinic staff successfully developed and implemented a screening tool for entering SDOH data into the electronic health record (EHR) charts of clinic patients. Results demonstrated that 52% of clinic patients reported food insecurity. The clinic collaborated with the faith community to provide donated food bags to patients in need. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: SDOH data were largely absent from the EHR before the clinic case manager started this project. Results of the screening tool demonstrated higher rates of food insecurity than expected. The case manager worked with the faith community to address immediate needs of food insecurity. The case manager plans to share SDOH information with the wider community to affect positive change and to encourage other clinics and departments to start collecting SDOH data.

A pilot study of the mistletoe and breast cancer (MAB) trial: a protocol for a randomised double-blind controlled trial.

BACKGROUND: A Cochrane review of mistletoe therapy concludes that there is some evidence that mistletoe extracts may offer benefits on measures of quality of life during chemotherapy for breast cancer, but these results need replication. Our aim is to add to this evidence base by initially testing the feasibility of a UK pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer undergoing chemotherapy with or without radiotherapy. METHODS/DESIGN: A mixed phase pilot placebo-controlled, double-blind randomised controlled trial of mistletoe therapy in patients with breast cancer (EudraCT number: 2018-000279-34). There will be three arms (groups) in the trial: Iscador M, Iscador P, with physiological saline as the placebo. The aim is to recruit 45 adult patients with a new diagnosis of early or locally advanced breast cancer, up to 12 weeks following definitive breast surgery whose standard treatment plan includes chemotherapy with or without radiotherapy. They will be taught to administer the mistletoe and breast cancer (MAB) therapies subcutaneously. MAB therapy will continue throughout their standard chemotherapy and radiotherapy and 1 month beyond. The main outcome of the MAB study is the feasibility of conducting such a trial within the NHS in order to inform a future fully powered investigative trial. Feasibility will be measured through recruitment, retention and patient experience using clinical research forms, patient diaries, cancer-related questionnaires and qualitative interviews conducted with both patients and oncology staff. DISCUSSION: This trial is the first of its kind in the UK. Currently, mistletoe therapy is mostly available through private practice in the UK. Completion of this feasibility study will support applications for further funding for a fully powered randomised controlled trial which will measure effectiveness and cost-effectiveness of this herbal therapy.

Regeneration: sooner rather than later.

The explosive growth of information from genetics and genomics has led to an appreciation of the conservation of gene regulatory networks between organisms, and between development and regeneration. With ever increasing knowledge, it will be possible to intervene therapeutically to regulate these networks, which will lead to new therapies to induce regeneration. The question then becomes how to do this, rather then when to try. Our thesis is that the time is now, and that this feat can be achieved by combining the insights provided by developmental biologists with the technologies being developed by biomaterial engineers, to achieve the goal of engineering regeneration. We thus envision regenerative engineering as the next step toward achieving the goal of human regeneration. Among the most important discoveries about regeneration from studies of salamanders that regenerate exceptionally well, is that both pattern-following and pattern-forming cells are required. Much progress is being made toward understanding the former cells, but little is known about the cells that control positional information and pattern formation. Within the near future, it will become possible to provide the information needed for regeneration exogenously in the form of an engineered extracellular matrix that is a biomimetic of the endogenous information. Since growth factors (morphogens) can control pattern formation, an engineered grid could be based on spatially organized patterns of sulfation of glycosaminoglycans that control the behavior of cells by modulating morphogen activity. Progress in engineering the positional information grid for regeneration will necessitate learning the sulfation codes associated with successful regeneration in animals such as salamanders.

The relationship between growth and pattern formation.

Successful development depends on the creation of spatial gradients of transcription factors within developing fields, and images of graded distributions of gene products populate the pages of developmental biology journals. Therefore the challenge is to understand how the graded levels of intracellular transcription factors are generated across fields of cells. We propose that transcription factor gradients are generated as a result of an underlying gradient of cell cycle lengths. Very long cell cycles will permit accumulation of a high level of a gene product encoded by a large transcription unit, whereas shorter cell cycles will permit progressively fewer transcripts to be completed due to gating of transcription by the cell cycle. We also propose that the gradients of cell cycle lengths are generated by gradients of extracellular morphogens/growth factors. The model of cell cycle gated transcriptional regulation brings focus back to the functional role of morphogens as cell cycle regulators, and proposes a specific and testable mechanism by which morphogens, in their roles as growth factors (how they were originally discovered), also determine cell fate.

Cancer Patients' Experiences of Using Mistletoe (Viscum album): A Qualitative Systematic Review and Synthesis.

OBJECTIVE: Systematic reviews of mistletoe therapy (MT) trials in cancer show promising results in improvement of patients' quality of life during chemotherapy and reduction of fatigue. However, patients' experiences of side effects and the acceptability, tolerability, and perceived benefits of MT have not been systematically reviewed. The aim of this study was to systematically review and synthesise the results of qualitative studies of cancer patients' experiences of using MT. DESIGN: A systematic search was conducted in MEDLINE, Embase, PsychLIT, CINAHL, and AMED to identify qualitative studies of MT. Articles were screened independently by two reviewers and critically appraised using the Critical Appraisal Skills Programme tool. A thematic synthesis of the findings was carried out. RESULTS: One hundred and seventy-three papers were identified; 156 were excluded at initial screening. Seventeen papers were read in full, 14 of which were excluded. Three articles about patients' experiences of MT alongside conventional treatment were included in the synthesis, either as a monotherapy (two articles) or as part of a package of anthroposophic treatment (one article). Patients reported demonstrable changes to their physical, emotional, and psychosocial well-being following MT, as well as a reduction in chemotherapy side effects. Self-reported side effects from MT were few, and the studies suggest good adherence to the therapy. Self-injection gave patients a sense of empowerment through involvement in their own treatment. CONCLUSIONS: A systematic search revealed a small number of qualitative studies of MT in cancer. These were effectively combined to provide a detailed overview of patients' experiences in order to complement the developing evidence base from trials. Given the variation in context of MT delivery across the articles, it is not possible to ascribe changes in patients' quality of life specifically to MT. The results of this review will help in the design of outcome measures that more fully capture patients' experiences. It is essential to embed qualitative research of patients' experiences of MT and other CAM therapies within future trials.

The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods.

The axolotl is one of the few tetrapods that are capable of regenerating complicated biological structures, such as complete limbs, throughout adulthood. Upon injury the axolotl generates a population of regeneration-competent limb progenitor cells known as the blastema, which will grow, establish pattern, and differentiate into the missing limb structures. In this review we focus on the crucial early events that occur during wound healing, the neural-epithelial interactions that drive the formation of the early blastema, and how these mechanisms differ from those of other species that have restricted regenerative potential, such as humans. We also discuss how the presence of cells from the different axes of the limb is required for the continued growth and establishment of pattern in the blastema as described in the polar coordinate model, and how this positional information is reprogrammed in blastema cells during regeneration. Multiple cell types from the mature limb stump contribute to the blastema at different stages of regeneration, and we discuss the contribution of these types to the regenerate with reference to whether they are "pattern-forming" or "pattern-following" cells. Lastly, we explain how an engineering approach will help resolve unanswered questions in limb regeneration, with the goal of translating these concepts to developing better human regenerative therapies.

Positional information in axolotl and mouse limb extracellular matrix is mediated via heparan sulfate and fibroblast growth factor during limb regeneration in the axolotl (Ambystoma mexicanum).

Urodele amphibians are unique among adult vertebrates in their ability to regenerate complex body structures after traumatic injury. In salamander regeneration, the cells maintain a memory of their original position and use this positional information to recreate the missing pattern. We used an in vivo gain-of-function assay to determine whether components of the extracellular matrix (ECM) have positional information required to induce formation of new limb pattern during regeneration. We discovered that salamander limb ECM has a position-specific ability to either inhibit regeneration or induce de novo limb structure, and that this difference is dependent on heparan sulfates that are associated with differential expression of heparan sulfate sulfotransferases. We also discovered that an artificial ECM containing only heparan sulfate was sufficient to induce de novo limb pattern in salamander limb regeneration. Finally, ECM from mouse limbs is capable of inducing limb pattern in axolotl blastemas in a position-specific, developmental-stage-specific, and heparan sulfate-dependent manner. This study demonstrates a mechanism for positional information in regeneration and establishes a crucial functional link between salamander regeneration and mammals.

Using Simulation to Introduce Nursing Students to Caring for Victims of Elder Abuse and Intimate Partner Violence.

Learning experiences about domestic violence may not be readily available to nursing students at their traditional clinical sites. Faculty at an associate degree nursing program developed and implemented elder abuse and intimate partner violence simulation scenarios for a Health Systems Concepts course. Learning objectives focused on assessment, safety, communication, education, and legal responsibilities for nurses. After the simulation, students participated in debriefing, completed student evaluations, and responded to three questions about the experience in their reflective journals. Faculty and students expressed satisfaction with this method of learning about domestic violence.

Evaluation of different recruitment and randomisation methods in a trial of general practitioner-led interventions to increase physical activity: a randomised controlled feasibility study with factorial design.

BACKGROUND: Interventions promoting physical activity by General Practitioners (GPs) lack a strong evidence base. Recruiting participants to trials in primary care is challenging. We investigated the feasibility of (i) delivering three interventions to promote physical activity in inactive participants and (ii) different methods of participant recruitment and randomised allocation. METHODS: We recruited general practices from Devon, Bristol and Coventry. We used a 2-by-2 factorial design for participant recruitment and randomisation. Recruitment strategies were either opportunistic (approaching patients attending their GP surgery) or systematic (selecting patients from practice lists and approaching them by letter). Randomisation strategies were either individual or by practice cluster. Feasibility outcomes included time taken to recruit the target number of participants within each practice. Participants were randomly allocated to one of three interventions: (i) written advice (control); (ii) brief GP advice (written advice plus GP advice on physical activity), and (iii) brief GP advice plus a pedometer to self-monitor physical activity during the trial. Participants allocated to written advice or brief advice each received a sealed pedometer to record their physical activity, and were instructed not to unseal the pedometer before the scheduled day of data collection. Participant level outcomes were reported descriptively and included the mean number of pedometer steps over a 7-day period, and European Quality of Life (EuroQoL)-5 dimensions (EQ-5D) scores, recorded at 12 weeks' follow-up. RESULTS: We recruited 24 practices (12 using each recruitment method; 18 randomising by cluster, 6 randomising by individual participant), encompassing 131 participants. Opportunistic recruitment was associated with less time to target recruitment compared with systematic (mean difference (days) -54.9, 95% confidence interval (CI) -103.6; -6.2) but with greater loss to follow up (28.8% versus. 6.9%; mean difference 21.9% (95% CI 9.6%; 34.1%)). There were differences in the socio-demographic characteristics of participants according to recruitment method. There was no clear pattern of change in participant level outcomes from baseline to 12 weeks across the three arms. CONCLUSIONS: Delivering and trialling GP-led interventions to promote physical activity is feasible, but trial design influences time to participant recruitment, participant withdrawal, and possibly, the socio-demographic characteristics of participants. TRIAL REGISTRATION NUMBER: ISRCTN73725618.

Clinically relevant dimensions of 3-rooted maxillary premolars obtained via high-resolution computed tomography.

INTRODUCTION: This study aimed to characterize the dimensions of a selection of 3-rooted maxillary premolars through high-resolution computed tomographic analysis considering measures of clinical interest for root canal treatment, such as root wall thickness, canal diameters, and distances between 2 canals in fused roots and between the root apex and foramen. METHODS: Fifteen 3-rooted human maxillary premolars extracted for therapeutic reasons were individually scanned using a high-resolution desktop high-resolution computed tomographic system. Starting from the apical foramen, the selected cross-sectional images corresponding to each millimeter of the roots were evaluated. Measures of clinical interest were determined using Image J software (version 1.41; National Institutes of Health, Bethesda, MD). RESULTS: Root wall thickness as thin as 0.4 and 0.6 mm was detected in the apical portion of buccal and palatal roots, respectively. In the cervical portion, buccal roots had narrower root walls (0.817-1.670 mm) compared with palatal roots (1.361-2.720 mm). In all thirds, the palatal canal was wider compared with the mesiobuccal and distobuccal canals. In the buccopalatal direction, all roots had thicker root walls toward the furcation, whereas in the mesiodistal direction the mesiobuccal and distobuccal roots had the thinnest walls along their distal and mesial aspects, respectively. Both buccal canals revealed dentin apposition 2 mm from the canal orifice, resulting in cervical constriction. Generally, the distance between the root apex and the foramen was greater in distobuccal roots in comparison with the others with a tendency for foramina to be eccentric. CONCLUSIONS: Three-rooted premolars are a clinical challenge not just because of their low frequency and difficulties regarding diagnosis and root canals access but also because of their fragile roots. These phenomena are critical in terms of the amount of dentin removed during the preparation of root canals and during post space preparation.

Three-rooted premolar analyzed by high-resolution and cone beam CT.

OBJECTIVES: The aim of this study was to analyze the variations in canal and root cross-sectional area in three-rooted maxillary premolars between high-resolution computed tomography (µCT) and cone beam computed tomography (CBCT). MATERIALS AND METHODS: Sixteen extracted maxillary premolars with three distinct roots and fully formed apices were scanned using µCT and CBCT. Photoshop CS software was used to measure root and canal cross-sectional areas at the most cervical and the most apical points of each root third in images obtained using the two tomographic computed (CT) techniques, and at 30 root sections equidistant from both root ends using µCT images. Canal and root areas were compared between each method using the Student t test for paired samples and 95 % confidence intervals. RESULTS: Images using µCT were sharper than those obtained using CBCT. There were statistically significant differences in mean area measurements of roots and canals between the µCT and CBCT techniques (P < 0.05). Root and canal areas had similar variations in cross-sectional µCT images and became proportionally smaller in a cervical to apical direction as the cementodentinal junction was approached, from where the area then increased apically. CONCLUSION: Although variation was similar in the roots and canals under study, CBCT produced poorer image details than µCT. CLINICAL RELEVANCE: Although CBCT is a strong diagnosis tool, it still needs improvement to provide accuracy in details of the root canal system, especially in cases with anatomical variations, such as the three-rooted maxillary premolars.

Green tea and green tea catechin extracts: an overview of the clinical evidence.

BACKGROUND: Tea leaves contain varying amounts of polyphenols of which the majority are catechins. There has been a sizable amount of research on the potential effect of green tea catechins for cancer risk, cardiovascular disease risk and weight loss; all conditions that are relevant to mid-life health. The aim was to produce an overview of the evidence for green tea for these three important health conditions. METHODS: The databases Medline (& Medline in process) and Embase, were searched for systematic reviews and meta-analyses using customised search strategies performed up until April 2012. Assessment of Multiple Systematic Reviews criteria were used to assess the quality of the included reviews. Relevant data were extracted into predefined tables. The results are described and discussed narratively. RESULTS: We included eight systematic reviews and meta-analyses covering the topics of cancer risk (n=2), cardiovascular risk (n=4) and weight loss (n=2). CONCLUSIONS: The evidence for green tea and cancer risk is inadequate and inconclusive. However there is some positive evidence for risk reduction of breast, prostate, ovarian and endometrial cancers with green tea. RCTs of green tea and cardiovascular risk factors suggest that green tea may reduce low-density lipoproteins and total cholesterol, although studies are of short duration. There is no robust evidence to support a reduction in coronary artery disease risk in green tea drinkers. There are a considerable number of RCTs to suggest that green tea does reduce body weight in the short term, but this not likely to be of clinical relevance.

Retrotransposon long interspersed nucleotide element-1 (LINE-1) is activated during salamander limb regeneration.

Salamanders possess an extraordinary capacity for tissue and organ regeneration when compared to mammals. In our effort to characterize the unique transcriptional fingerprint emerging during the early phase of salamander limb regeneration, we identified transcriptional activation of some germline-specific genes within the Mexican axolotl (Ambystoma mexicanum) that is indicative of cellular reprogramming of differentiated cells into a germline-like state. In this work, we focus on one of these genes, the long interspersed nucleotide element-1 (LINE-1) retrotransposon, which is usually active in germ cells and silent in most of the somatic tissues in other organisms. LINE-1 was found to be dramatically upregulated during regeneration. In addition, higher genomic LINE-1 content was also detected in the limb regenerate when compared to that before amputation indicating that LINE-1 retrotransposition is indeed active during regeneration. Active LINE-1 retrotransposition has been suggested to have a potentially deleterious impact on genomic integrity. Silencing of activated LINE-1 by small RNAs has been reported to be part of the machinery aiming to maintain genomic integrity. Indeed, we were able to identify putative LINE-1-related piRNAs in the limb blastema. Transposable element-related piRNAs have been identified frequently in the germline in other organisms. Thus, we present here a scenario in which a unique germline-like state is established during axolotl limb regeneration, and the re-activation of LINE-1 may serve as a marker for cellular dedifferentiation in the early-stage of limb regeneration.

Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl.

The capacity for tissue and organ regeneration in humans is dwarfed by comparison to that of salamanders. Emerging evidence suggests that mechanisms learned from the early phase of salamander limb regeneration-wound healing, cellular dedifferentiation and blastemal formation-will reveal therapeutic approaches for tissue regeneration in humans. Here we describe a unique transcriptional fingerprint of regenerating limb tissue in the Mexican axolotl (Ambystoma mexicanum) that is indicative of cellular reprogramming of differentiated cells to a germline-like state. Two genes that are required for self-renewal of germ cells in mice and flies, Piwi-like 1 (PL1) and Piwi-like 2 (PL2), are expressed in limb blastemal cells, the basal layer keratinocytes and the thickened apical epithelial cap in the wound epidermis in the regenerating limb. Depletion of PL1 and PL2 by morpholino oligonucleotides decreased cell proliferation and increased cell death in the blastema leading to a significant retardation of regeneration. Examination of key molecules that are known to be required for limb development or regeneration further revealed that FGF8 is transcriptionally downregulated in the presence of the morpholino oligos, indicating PL1 and PL2 might participate in FGF signaling during limb regeneration. Given the requirement for FGF signaling in limb development and regeneration, the results suggest that PL1 and PL2 function to establish a unique germline-like state that is associated with successful regeneration.

Nerve signaling regulates basal keratinocyte proliferation in the blastema apical epithelial cap in the axolotl (Ambystoma mexicanum).

The ability of adult vertebrates to repair tissue damage is widespread and impressive; however, the ability to regenerate structurally complex organs such as the limb is limited largely to the salamanders. The fact that most of the tissues of the limb can regenerate has led investigators to question and identify the barriers to organ regeneration. From studies in the salamander, it is known that one of the earliest steps required for successful regeneration involves signaling between nerves and the wound epithelium/apical epithelial cap (AEC). In this study we confirm an earlier report that the keratinocytes of the AEC acquire their function coincident with exiting the cell cycle. We have discovered that this unique, coordinated behavior is regulated by nerve signaling and is associated with the presence of gap junctions between the basal keratinocytes of the AEC. Disruption of nerve signaling results in a loss of gap junction protein, the reentry of the cells into the cell cycle, and regenerative failure. Finally, coordinated exit from the cell cycle appears to be a conserved behavior of populations of cells that function as signaling centers during both development and regeneration.

Regulation of proximal-distal intercalation during limb regeneration in the axolotl (Ambystoma mexicanum).

Intercalation is the process whereby cells located at the boundary of a wound interact to stimulate proliferation and the restoration of the structures between the boundaries that were lost during wounding. Thus, intercalation is widely considered to be the mechanism of regeneration. When a salamander limb is amputated, the entire cascade of regeneration events is activated, and the missing limb segments and their boundaries (joints) as well as the structures within each segment are regenerated. Therefore, in an amputated limb it is not possible to distinguish between intersegmental regeneration (formation of new segments/joints) and intrasegmental regeneration (formation of structures within a given segment), and it is not possible to study the differential regulation of these two processes. We have used two models for regeneration that allow us to study these two processes independently, and report that inter- and intrasegmental regeneration are different processes regulated by different signaling pathways. New limb segments/joints can be regenerated from cells that dedifferentiate to form blastema cells in response to signaling that is mediated in part by fibroblast growth factor.