Mutational analysis of mechanosensitive ion channels in the carnivorous Venus flytrap plant.

How the Venus flytrap (Dionaea muscipula) evolved the remarkable ability to sense, capture, and digest animal prey for nutrients has long puzzled the scientific community.1 Recent genome and transcriptome sequencing studies have provided clues to the genes thought to play a role in these tasks.2,3,4,5 However, proving a causal link between these and any aspect of the plant's hunting behavior has been challenging due to the genetic intractability of this non-model organism. Here, we use CRISPR-Cas9 methods to generate targeted modifications in the Venus flytrap genome. The plant detects prey using touch-sensitive trigger hairs located on its bilobed leaves.6 Upon bending, these hairs convert mechanical touch signals into changes in the membrane potential of sensory cells, leading to rapid closure of the leaf lobes to ensnare the animal.7 Here, we generate mutations in trigger-hair-expressed MscS-like (MSL)-family mechanosensitive ion channel genes FLYCATCHER1 (FLYC1) and FLYCATCHER2 (FLYC2)5 and find that double-mutant plants have a reduced leaf-closing response to mechanical ultrasound stimulation. While we cannot exclude off-target effects of the CRISPR-Cas9 system, our genetic analysis is consistent with these and other functionally redundant mechanosensitive ion channels acting together to generate the sensory system necessary for prey detection.

The mutational dynamics of short tandem repeats in large, multigenerational families.

BACKGROUND: Short tandem repeats (STRs) compose approximately 3% of the genome, and mutations at STR loci have been linked to dozens of human diseases including amyotrophic lateral sclerosis, Friedreich ataxia, Huntington disease, and fragile X syndrome. Improving our understanding of these mutations would increase our knowledge of the mutational dynamics of the genome and may uncover additional loci that contribute to disease. To estimate the genome-wide pattern of mutations at STR loci, we analyze blood-derived whole-genome sequencing data for 544 individuals from 29 three-generation CEPH pedigrees. These pedigrees contain both sets of grandparents, the parents, and an average of 9 grandchildren per family. RESULTS: We use HipSTR to identify de novo STR mutations in the 2nd generation of these pedigrees and require transmission to the third generation for validation. Analyzing approximately 1.6 million STR loci, we estimate the empirical de novo STR mutation rate to be 5.24 × 10-5 mutations per locus per generation. Perfect repeats mutate about 2 × more often than imperfect repeats. De novo STRs are significantly enriched in Alu elements. CONCLUSIONS: Approximately 30% of new STR mutations occur within Alu elements, which compose only 11% of the genome, but only 10% are found in LINE-1 insertions, which compose 17% of the genome. Phasing these mutations to the parent of origin shows that parental transmission biases vary among families. We estimate the average number of de novo genome-wide STR mutations per individual to be approximately 85, which is similar to the average number of observed de novo single nucleotide variants.

Leaf cell-specific and single-cell transcriptional profiling reveals a role for the palisade layer in UV light protection.

Like other complex multicellular organisms, plants are composed of different cell types with specialized shapes and functions. For example, most laminar leaves consist of multiple photosynthetic cell types. These cell types include the palisade mesophyll, which typically forms one or more cell layers on the adaxial side of the leaf. Despite their importance for photosynthesis, we know little about how palisade cells differ at the molecular level from other photosynthetic cell types. To this end, we have used a combination of cell-specific profiling using fluorescence-activated cell sorting and single-cell RNA-sequencing methods to generate a transcriptional blueprint of the palisade mesophyll in Arabidopsis thaliana leaves. We find that despite their unique morphology, palisade cells are otherwise transcriptionally similar to other photosynthetic cell types. Nevertheless, we show that some genes in the phenylpropanoid biosynthesis pathway have both palisade-enriched expression and are light-regulated. Phenylpropanoid gene activity in the palisade was required for production of the ultraviolet (UV)-B protectant sinapoylmalate, which may protect the palisade and/or other leaf cells against damaging UV light. These findings improve our understanding of how different photosynthetic cell types in the leaf can function uniquely to optimize leaf performance, despite their transcriptional similarities.

A tRNA modifying enzyme as a tunable regulatory nexus for bacterial stress responses and virulence.

Post-transcriptional modifications can impact the stability and functionality of many different classes of RNA molecules and are an especially important aspect of tRNA regulation. It is hypothesized that cells can orchestrate rapid responses to changing environmental conditions by adjusting the specific types and levels of tRNA modifications. We uncovered strong evidence in support of this tRNA global regulation hypothesis by examining effects of the well-conserved tRNA modifying enzyme MiaA in extraintestinal pathogenic Escherichia coli (ExPEC), a major cause of urinary tract and bloodstream infections. MiaA mediates the prenylation of adenosine-37 within tRNAs that decode UNN codons, and we found it to be crucial to the fitness and virulence of ExPEC. MiaA levels shifted in response to stress via a post-transcriptional mechanism, resulting in marked changes in the amounts of fully modified MiaA substrates. Both ablation and forced overproduction of MiaA stimulated translational frameshifting and profoundly altered the ExPEC proteome, with variable effects attributable to UNN content, changes in the catalytic activity of MiaA, or availability of metabolic precursors. Cumulatively, these data indicate that balanced input from MiaA is critical for optimizing cellular responses, with MiaA acting much like a rheostat that can be used to realign global protein expression patterns.

Engaging family caregivers and health system partners in exploring how multi-level contexts in primary care practices affect case management functions and outcomes of patients and family caregivers at end of life: a realist synthesis.

BACKGROUND: An upstream approach to palliative care in the last 12 months of life delivered by primary care practices is often referred to as Primary Palliative Care (PPC). Implementing case management functions can support delivery of PPC and help patients and their families navigate health, social and fiscal environments that become more complex at end-of-life. A realist synthesis was conducted to understand how multi-level contexts affect case management functions related to initiating end-of-life conversations, assessing patient and caregiver needs, and patient/family centred planning in primary care practices to improve outcomes. The synthesis also explored how these functions aligned with critical community resources identified by patients/families dealing with end-of-life. METHODS: A realist synthesis is theory driven and iterative, involving the investigation of proposed program theories of how particular contexts catalyze mechanisms (program resources and individual reactions to resources) to generate improved outcomes. To assess whether program theories were supported and plausible, two librarian-assisted and several researcher-initiated purposive searches of the literature were conducted, then extracted data were analyzed and synthesized. To assess relevancy, health system partners and family advisors informed the review process. RESULTS: Twenty-eight articles were identified as being relevant and evidence was consolidated into two final program theories: 1) Making end-of-life discussions comfortable, and 2) Creating plans that reflect needs and values. Theories were explored in depth to assess the effect of multi-level contexts on primary care practices implementing tools or frameworks, strategies for improving end-of-life communications, or facilitators that could improve advance care planning by primary care practitioners. CONCLUSIONS: Primary care practitioners' use of tools to assess patients/families' needs facilitated discussions and planning for end-of-life issues without specifically discussing death. Also, receiving training on how to better communicate increased practitioner confidence for initiating end-of-life discussions. Practitioner attitudes toward death and prior education or training in end-of-life care affected their ability to initiate end-of-life conversations and plan with patients/families. Recognizing and seizing opportunities when patients are aware of the need to plan for their end-of-life care, such as in contexts when patients experience transitions can increase readiness for end-of-life discussions and planning. Ultimately conversations and planning can improve patients/families' outcomes.

Acute Effects of Cheddar Cheese Consumption on Circulating Amino Acids and Human Skeletal Muscle.

Cheddar cheese is a protein-dense whole food and high in leucine content. However, no information is known about the acute blood amino acid kinetics and protein anabolic effects in skeletal muscle in healthy adults. Therefore, we conducted a crossover study in which men and women (n = 24; ~27 years, ~23 kg/m2) consumed cheese (20 g protein) or an isonitrogenous amount of milk. Blood and skeletal muscle biopsies were taken before and during the post absorptive period following ingestion. We evaluated circulating essential and non-essential amino acids, insulin, and free fatty acids and examined skeletal muscle anabolism by mTORC1 cellular localization, intracellular signaling, and ribosomal profiling. We found that cheese ingestion had a slower yet more sustained branched-chain amino acid circulation appearance over the postprandial period peaking at ~120 min. Cheese also modestly stimulated mTORC1 signaling and increased membrane localization. Using ribosomal profiling we found that, though both milk and cheese stimulated a muscle anabolic program associated with mTORC1 signaling that was more evident with milk, mTORC1 signaling persisted with cheese while also inducing a lower insulinogenic response. We conclude that Cheddar cheese induced a sustained blood amino acid and moderate muscle mTORC1 response yet had a lower glycemic profile compared to milk.

De novo structural mutation rates and gamete-of-origin biases revealed through genome sequencing of 2,396 families.

Each human genome includes de novo mutations that arose during gametogenesis. While these germline mutations represent a fundamental source of new genetic diversity, they can also create deleterious alleles that impact fitness. Whereas the rate and patterns of point mutations in the human germline are now well understood, far less is known about the frequency and features that impact de novo structural variants (dnSVs). We report a family-based study of germline mutations among 9,599 human genomes from 33 multigenerational CEPH-Utah families and 2,384 families from the Simons Foundation Autism Research Initiative. We find that de novo structural mutations detected by alignment-based, short-read WGS occur at an overall rate of at least 0.160 events per genome in unaffected individuals, and we observe a significantly higher rate (0.206 per genome) in ASD-affected individuals. In both probands and unaffected samples, nearly 73% of de novo structural mutations arose in paternal gametes, and we predict most de novo structural mutations to be caused by mutational mechanisms that do not require sequence homology. After multiple testing correction, we did not observe a statistically significant correlation between parental age and the rate of de novo structural variation in offspring. These results highlight that a spectrum of mutational mechanisms contribute to germline structural mutations and that these mechanisms most likely have markedly different rates and selective pressures than those leading to point mutations.

Reduced Physical Activity Alters the Leucine-Stimulated Translatome in Aged Skeletal Muscle.

Periods of inactivity experienced by older adults induce nutrient anabolic resistance creating a cascade of skeletal muscle transcriptional and translational aberrations contributing to muscle dysfunction. The purpose of this study was to identify how inactivity alters leucine-stimulated translation of molecules and pathways within the skeletal muscle of older adults. We performed ribosomal profiling alongside RNA sequencing from skeletal muscle biopsies taken from older adults (n = 8; ~72 years; 6 F/2 M) in response to a leucine bolus before (Active) and after (Reduced Activity) 2 weeks of reduced physical activity. At both visits, muscle biopsies were taken at baseline, 60 minutes (early response), and 180 minutes (late response) after leucine ingestion. Previously identified inactivity-related gene transcription changes (PFKFB3, GADD45A, NMRK2) were heightened by leucine with corresponding changes in translation. In contrast, leucine also stimulated translational efficiency of several transcripts in a manner not explained by corresponding changes in mRNA abundance ("uncoupled translation"). Inactivity eliminated this uncoupled translational response for several transcripts, and reduced the translation of most mRNAs encoding for ribosomal proteins. Ingenuity Pathway Analysis identified discordant circadian translation and transcription as a result of inactivity such as translation changes to PER2 and PER3 despite unchanged transcription. We demonstrate inactivity alters leucine-stimulated "uncoupled translation" of ribosomal proteins and circadian regulators otherwise not detectable by traditional RNA sequencing. Innovative techniques such as ribosomal profiling continues to further our understanding of how physical activity mediates translational regulation, and will set a path toward therapies that can restore optimal protein synthesis on the transcript-specific level to combat negative consequences of inactivity on aging muscle.

Stretch-activated ion channels identified in the touch-sensitive structures of carnivorous Droseraceae plants.

In response to touch, some carnivorous plants such as the Venus flytrap have evolved spectacular movements to capture animals for nutrient acquisition. However, the molecules that confer this sensitivity remain unknown. We used comparative transcriptomics to show that expression of three genes encoding homologs of the MscS-Like (MSL) and OSCA/TMEM63 family of mechanosensitive ion channels are localized to touch-sensitive trigger hairs of Venus flytrap. We focus here on the candidate with the most enriched expression in trigger hairs, the MSL homolog FLYCATCHER1 (FLYC1). We show that FLYC1 transcripts are localized to mechanosensory cells within the trigger hair, transfecting FLYC1 induces chloride-permeable stretch-activated currents in naïve cells, and transcripts coding for FLYC1 homologs are expressed in touch-sensing cells of Cape sundew, a related carnivorous plant of the Droseraceae family. Our data suggest that the mechanism of prey recognition in carnivorous Droseraceae evolved by co-opting ancestral mechanosensitive ion channels to sense touch.

Germline mutation rates in young adults predict longevity and reproductive lifespan.

Ageing may be due to mutation accumulation across the lifespan, leading to tissue dysfunction, disease, and death. We tested whether germline autosomal mutation rates in young adults predict their remaining survival, and, for women, their reproductive lifespans. Age-adjusted mutation rates (AAMRs) in 61 women and 61 men from the Utah CEPH (Centre d'Etude du Polymorphisme Humain) families were determined. Age at death, cause of death, all-site cancer incidence, and reproductive histories were provided by the Utah Population Database, Utah Cancer Registry, and Utah Genetic Reference Project. Higher AAMRs were significantly associated with higher all-cause mortality in both sexes combined. Subjects in the top quartile of AAMRs experienced more than twice the mortality of bottom quartile subjects (hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.21-3.56; p = 0.008; median survival difference = 4.7 years). Fertility analyses were restricted to women whose age at last birth (ALB) was ≥ 30 years, the age when fertility begins to decline. Women with higher AAMRs had significantly fewer live births and a younger ALB. Adult germline mutation accumulation rates are established in adolescence, and later menarche in women is associated with delayed mutation accumulation. We conclude that germline mutation rates in healthy young adults may provide a measure of both reproductive and systemic ageing. Puberty may induce the establishment of adult mutation accumulation rates, just when DNA repair systems begin their lifelong decline.

Capacity building and mentorship among pan-Canadian early career researchers in community-based primary health care.

AIM: To describe activities and outcomes of a cross-team capacity building strategy that took place over a five-year funding period within the broader context of 12 community-based primary health care (CBPHC) teams. BACKGROUND: In 2013, the Canadian Institutes of Health Research funded 12 CBPHC Teams (12-Teams) to conduct innovative cross-jurisdictional research to improve the delivery of high-quality CBPHC to Canadians. This signature initiative also aimed to enhance CBPHC research capacity among an interdisciplinary group of trainees, facilitated by a collaboration between a capacity building committee led by senior researchers and a trainee-led working group. METHODS: After the committee and working group were established, capacity building activities were organized based on needs and interests identified by trainees of the CBPHC Teams. This paper presents a summary of the activities accomplished, as well as the outcomes reported through an online semistructured survey completed by the trainees toward the end of the five-year funding period. This survey was designed to capture the capacity building and mentorship activities that trainees either had experienced or would like to experience in the future. Descriptive and thematic analyses were conducted based on survey responses, and these findings were compared with the existing core competencies in the literature. FINDINGS: Since 2013, nine webinars and three online workshops were hosted by trainees and senior researchers, respectively. Many of the CBPHC Teams provided exposure for trainees to innovative methods, CBPHC content, and showcased trainee research. A total of 27 trainees from 10 of the 12-Teams responded to the survey (41.5%). Trainees identified key areas of benefit from their involvement in this initiative: skills training, networking opportunities, and academic productivity. Trainees identified gaps in research and professional skill development, indicating areas for further improvement in capacity building programs, particularly for trainees to play a more active role in their education and preparation.

The complexity of caregiving for community-living older adults with multiple chronic conditions: A qualitative study.

BACKGROUND: Older adults with multiple chronic conditions (MCC) rely heavily on caregivers for assistance with care. However, we know little about their psychosocial experiences and their needs for support in managing MCC. The purpose of this study was to explore the experiences of caregivers of older adults living in the community with MCC. METHODS: This qualitative study was a secondary analysis of previously collected data from caregivers in Ontario and Alberta, Canada. Participants included caregivers of older adults (65 years and older) with three or more chronic conditions. Data were collected through in-depth, semi-structured interviews. Interview transcripts were coded and analyzed using Thorne's interpretive description approach. RESULTS: Most of the 47 caregiver participants were female (76.6%), aged 65 years of age or older (61.7%), married (87.2%) and were spouses to the care recipient (68.1%). Caregivers' experiences of caring for community-living older adults with MCC were complex and included: (a) dealing with the demands of caregiving; (b) prioritizing chronic conditions; (c) living with my own health limitations; (d) feeling socially isolated and constrained; (e) remaining committed to caring; and (f) reaping the rewards of caregiving. CONCLUSIONS: Healthcare providers can play key roles in supporting caregivers of older adults with MCC by providing education and support on managing MCC, actively engaging them in goal setting and care planning, and linking them to appropriate community health and social support services. Communities can create environments that support caregivers in areas such as social participation, social inclusion, and community support and health services.

Healthcare providers' experiences in supporting community-living older adults to manage multiple chronic conditions: a qualitative study.

BACKGROUND: Living with multiple chronic conditions (MCC), the coexistence of two or more chronic conditions, is becoming more prevalent as the population ages. Primary care and home care providers play key roles in caring for older adults with MCC such as facilitating complex care decisions, shared decision-making, and access to community health and support services. While there is some research on the perceptions and experiences of these providers in caring for this population, much of this literature is focused specifically on family physicians. Little is known about the experiences of other primary care and home care providers from multiple disciplines who care for this vulnerable group. The purpose of this study was to explore the experiences of primary and home care healthcare providers in supporting the care of older adults with MCC living in the community, and identify ways of improving care delivery and outcomes for this group. METHODS: The study used an interpretive descriptive design. A total of 42 healthcare providers from two provinces in Canada (Ontario and Alberta) participated in individual semi-structured, face-to-face 60-min interviews. Participants represented diverse disciplines from primary care and home care settings. Inductive thematic analysis was used for data analysis. RESULTS: The experiences and recommendations of healthcare providers managing care for older adults with MCC were organized into six major themes: (1) managing complexity associated with MCC, (2) implementing person-centred care, (3), supporting caregivers, (4) using a team approach for holistic care delivery, (5) encountering challenges and rewards, and (6) recommending ways to address the challenges of the healthcare system. Healthcare providers identified the need for a more comprehensive, integrated system of care to improve the delivery of care and outcomes for older adults with MCC and their family caregivers. CONCLUSIONS: Study findings suggest that community-based healthcare providers are using many relevant and appropriate strategies to support older adults living with the complexity of MCC, such as implementing person-centred care, supporting caregivers, working collaboratively with other providers, and addressing social determinants of health. However, they also identified the need for a more comprehensive, integrated system of care.

Pedigree-based estimation of human mobile element retrotransposition rates.

Germline mutation rates in humans have been estimated for a variety of mutation types, including single-nucleotide and large structural variants. Here, we directly measure the germline retrotransposition rate for the three active retrotransposon elements: L1, Alu, and SVA. We used three tools for calling mobile element insertions (MEIs) (MELT, RUFUS, and TranSurVeyor) on blood-derived whole-genome sequence (WGS) data from 599 CEPH individuals, comprising 33 three-generation pedigrees. We identified 26 de novo MEIs in 437 births. The retrotransposition rate estimates for Alu elements, one in 40 births, is roughly half the rate estimated using phylogenetic analyses, a difference in magnitude similar to that observed for single-nucleotide variants. The L1 retrotransposition rate is one in 63 births and is within range of previous estimates (1:20-1:200 births). The SVA retrotransposition rate, one in 63 births, is much higher than the previous estimate of one in 900 births. Our large, three-generation pedigrees allowed us to assess parent-of-origin effects and the timing of insertion events in either gametogenesis or early embryonic development. We find a statistically significant paternal bias in Alu retrotransposition. Our study represents the first in-depth analysis of the rate and dynamics of human retrotransposition from WGS data in three-generation human pedigrees.

Large, three-generation human families reveal post-zygotic mosaicism and variability in germline mutation accumulation.

The number of de novo mutations (DNMs) found in an offspring's genome increases with both paternal and maternal age. But does the rate of mutation accumulation in human gametes differ across families? Using sequencing data from 33 large, three-generation CEPH families, we observed significant variability in parental age effects on DNM counts across families, ranging from 0.19 to 3.24 DNMs per year. Additionally, we found that ~3% of DNMs originated following primordial germ cell specification in a parent, and differed from non-mosaic germline DNMs in their mutational spectra. We also discovered that nearly 10% of candidate DNMs in the second generation were post-zygotic, and present in both somatic and germ cells; these gonosomal mutations occurred at equivalent frequencies on both parental haplotypes. Our results demonstrate that rates of germline mutation accumulation vary among families with similar ancestry, and confirm that post-zygotic mosaicism is a substantial source of human DNM.

Optimizing osteoporosis care in a rural primary health care center: Findings of a research study aimed to support seniors.

BACKGROUND: Osteoporosis is one of the most under-diagnosed and under-treated health conditions in Canada. This study questioned whether an invitation to self-refer for osteoporosis risk evaluation would improve the number of patients who were tested for bone mineral density (BMD) at a rural Primary Health Care Center (PHCC). PURPOSE: The purpose of this study is to improve osteoporosis care and decrease bone fracture risk in a population of patients 65 years of age and older. METHODOLOGY: A quasi-experimental research design was used to review screening rates of BMD testing and identified patients in this population who were at low, moderate, and high risk for developing osteoporosis. Screening rates at the PHCC were compared to screening rates at another rural PHCC in the province. CONCLUSION: The self-referral program for BMD testing and a nurse-led intervention resulted in an increased number of people who were BMD tested at the study PHCC compared with the control PHCC, and identified more male patients 65 years of age and older who were at risk for osteoporosis and bone fractures. Recommendations suggest future research in other provincial PHCCs that may encourage self-referral programs for BMD testing and improved osteoporosis care for patients 65 years of age and older.

Factors That Influence Home Care Case Managers' Work and Workload.

BACKGROUND: Home care services are increasing across Canada and in other developed nations. There has been increased pressure on home care programs to not only accept more clients more rapidly but also work more efficiently. Case management is an approach through which clients access and receive home care. With both rising numbers of clients and growing complexity among them, case managers' work and workload are also increasing. The demands on case managers and expansion in caseloads are happening without an increase in resources or funding. With case manager work increasing steadily, an understanding of the factors that influence their work and workload is vital. PURPOSE: The purpose of this study was to explore what factors influence case managers' work and workload. METHODS: This study used an ethnographic approach. It took place in Alberta, Canada, in 3 home care offices in urban and suburban geographic areas. Purposive sampling was used, and participants included 28 home care case managers with predominantly long-term clients (>3 months on home care), 3 site managers, and 1 project lead. Data collection methods included semistructured interviews, nonparticipant observation, participant journaling, and focus groups. RESULTS: Case manager works were portrayed in 2 key ways: the number and type of tasks a case manager was required to complete and the amount of time and energy needed to complete a task. The factors that influence case manager work and workload fall into 3 overarching categories: structural, operational, or individual factors. DISCUSSION: The 3 overarching categories, as well as interactions between various factors, contribute to what is known about case managers' work and workload. Participants found it difficult to discuss the factors in isolation because the interaction and "messiness" of the factors were inherent in their actions and stories about their work and workload. Workload includes not only the easily captured work such as direct care and specific activities such as assessment but also diverse forms of invisible work such as problem solving, rapport building, and caseload management, as well as emotional work such as coping, stress management, and team support. IMPLICATIONS FOR CASE MANAGEMENT: Case managers' work and workload in home care are important phenomena. In a climate of budgetary restraint and an aging population, which seemingly prefer home care as much as the system desires to provide it as a main option for care, it is important to capture, recognize, and legitimize an understanding of case managers' work and workload. Increased knowledge in this area could, in turn, transforms both home care and case management.

Experiences of community-dwelling older adults living with multiple chronic conditions: a qualitative study.

OBJECTIVES: The aim of the study was to understand the experiences of living with multiple chronic conditions (MCC) from the perspective of community-living older adults with MCC. DESIGN: A qualitative study using an interpretive description approach. SETTING: Participants were recruited from southern Ontario, Canada. PARTICIPANTS: 21 community-living, older adults (≥65 years) with an average of 7.4 chronic conditions including one of diabetes, dementia or stroke. METHODS: Data were collected through digitally-recorded, in-depth, semi-structured in-person interviews. Interview transcripts were analysed and coded using Thorne's interpretive description approach. RESULTS: Five themes were identified representing older adults' experiences of living with MCC: (a) trying to stay healthy while living with MCC, (b) depending on family caregivers for support with just about everything, (c) paying the high costs of living with MCC, (d) making healthcare decisions by proxy and (e) receiving healthcare services that do not address the complex needs of persons living with MCC. CONCLUSIONS: The experience of living with MCC in the community was complex and multi-faceted. The need for a person-centred and family-centred approach to care in the community, which includes the coordination of health and social services that are tailored to the needs of older adults and their informal caregivers, was underscored. Such an approach would facilitate improved information-sharing and discussion of care management options between health professionals and their patients, enable older adults with MCC to actively engage in priority-setting and decision-making and may result in improved health and quality of life for older adults with MCC.

Conceptualization of the Chronic Care Model: Implications for Home Care Case Manager Practice.

One of the greatest challenges for healthcare systems is the management and prevention of chronic diseases. Wagner's Chronic Care Model aims to transform the daily care of patients with chronic illnesses from acute and reactive to proactive, planned, and population-based. The purpose of this article is to provide a review of the available research relating to the Chronic Care Model and consider the implications for Home Care Case Management practice. A total of 18 research studies (5 qualitative and 13 quantitative) were reviewed. A thematic content analysis approach was used. The findings included three themes: Chronic Care Model and positive chronic illness health behaviors and outcomes; Chronic Care Model and delivery of quality chronic illness care; and the importance of the supportive role of the home care nurse in the role of Home Care Case Management. Gaps and limitations of the Chronic Care Model in relation to Home Care Case Management were identified and discussed in relationship to partnership building and reciprocal trust between patients, family caregivers, and the Home Care Case Manager. Finally, implications for the use of the Chronic Care Model in Home Care Case Manager practice, policy development, and future research were presented.

Overexpression of the Sorghum bicolor SbCCoAOMT alters cell wall associated hydroxycinnamoyl groups.

Sorghum (Sorghum bicolor) is a drought tolerant crop, which is being developed as a bioenergy feedstock. The monolignol biosynthesis pathway is a major focus for altering the abundance and composition of lignin. Caffeoyl coenzyme-A O-methyltransferase (CCoAOMT) is an S-adenosyl methionine (SAM)-dependent O-methyltransferase that methylates caffeoyl-CoA to generate feruloyl-CoA, an intermediate required for the biosynthesis of both G- and S-lignin. SbCCoAOMT was overexpressed to assess the impact of increasing the amount of this enzyme on biomass composition. SbCCoAOMT overexpression increased both soluble and cell wall-bound (esterified) ferulic and sinapic acids, however lignin concentration and its composition (S/G ratio) remained unaffected. This increased deposition of hydroxycinnamic acids in these lines led to an increase in total energy content of the stover. In stalk and leaf midribs, the increased histochemical staining and autofluorescence in the cell walls of the SbCCoAOMT overexpression lines also indicate increased phenolic deposition within cell walls, which is consistent with the chemical analyses of soluble and wall-bound hydroxycinnamic acids. The growth and development of overexpression lines were similar to wild-type plants. Likewise, RNA-seq and metabolite profiling showed that global gene expression and metabolite levels in overexpression lines were also relatively similar to wild-type plants. Our results demonstrate that SbCCoAOMT overexpression significantly altered cell wall composition through increases in cell wall associated hydroxycinnamic acids without altering lignin concentration or affecting plant growth and development.