Filling In: Family Member Support for Nonrelative Residents in Long-Term Care Homes.

BACKGROUND AND OBJECTIVES: Past research about family involvement in long-term care (LTC) homes mainly focuses on family members' involvement with their own relative, interactions with staff, and collective activities such as Family Councils. Our research provides novel insights into family member's involvement in the care of residents who are not their relatives, an area that has not previously been explored. RESEARCH DESIGN AND METHODS: This critical ethnographic study examined ways that family members negotiate and navigate their roles within LTC homes. Data collection and analysis took place at 3 LTC homes in British Columbia, Canada, between 2014 and 2018. Data were collected through participant observation and semistructured interviews. Eleven family member participants shared experiences of caring for residents who were not their relatives. RESULTS: The umbrella theme was "filling in," which takes place in a care environment that is understaffed and underresourced. The subthemes reflect the various ways that families are "filling in": responding to resident's needs, supporting staff to respond to resident needs, and filling in for residents' families. DISCUSSION AND IMPLICATIONS: Caring for residents who are not their relatives is facet of family involvement in LTC homes that has not been previously explored. Many family members have expertise in providing person-centered care and they extend this expertise to residents who are not their relatives. Policies and legislation are needed to formalize family involvement in caring for nonrelative residents as it is a component of quality of care for all residents.

Disruptions in Relational Continuity: The Impact of Pandemic Public Health Measures on Families in Long-Term Care.

Although the value of family caregivers' involvement with relatives in long-term care (LTC) is well recognized, tensions remain regarding their role. Such tensions were exacerbated during the COVID-19 pandemic as strict public health measures restricted family access to LTC homes. Using interpretive description, we examined the impact of visitation restrictions on family caregivers' experiences caring for a relative in LTC between March 2020 and June 2021. In-depth interviews were conducted with 14 family caregivers (five spouses and nine adult daughters) and two key themes were identified. The first theme, "seeking to maintain relational continuity," illustrates how caregivers sought to sustain connections with residents prior to and during the pandemic. The second theme, "disrupted relational continuity," highlights the impact of severed relational connections on caregivers' sense of self and ongoing feelings of loss and anger. Findings call for a trauma-informed approach that recognizes the pervasiveness of trauma for family caregivers and the avoidance of re-traumatization.

Exploring the Impacts of COVID-19 Public Health Measures on Community-Dwelling People Living With Dementia and Their Family Caregivers: A Longitudinal, Qualitative Study.

Since the onset of the COVID-19 pandemic, community-dwelling people living with dementia and their family caregivers have experienced many challenges. The unanticipated consequences of public health measures have impacted these families in a myriad of ways. In this interpretive policy analysis, which used a longitudinal, qualitative methodology, we purposively recruited 12 families in British Columbia, Canada, to explore the impacts of pandemic public health measures over time. Semi-structured interviews were conducted every 3 months and participants completed diary entries. Twenty-eight interviews and 34 diary entries were thematically analyzed. The findings explore ways that families adopted and adapted to public health measures, loss of supports, both formal and informal, and the subsequent consequences for their mental and physical well-being. Within the ongoing context of the pandemic, as well as potential future wide-spread emergencies, it is imperative that programs and supports are restarted and maintained to avoid further harm to these families.

Not Just How Many but Who Is on Shift: The Impact of Workplace Incivility and Bullying on Care Delivery in Nursing Homes.

BACKGROUND AND OBJECTIVES: Much of the literature examining the staffing-care quality link in long-term care (LTC) homes focuses on staffing ratios; that is, how many staff are on shift. Far less attention is devoted to exploring the impact of staff members' workplace relationships, or who is on shift. As part of our work exploring workplace incivility and bullying among residential care aides (RCAs), we examined how RCAs' workplace relationships are shaped by peer incivility and bullying and the impact on care delivery. RESEARCH DESIGN AND METHODS: Using critical ethnography, we conducted 100 hr of participant observation and 33 semistructured interviews with RCAs, licensed practical nurses, support staff, and management in 2 nonprofit LTC homes in British Columbia, Canada. RESULTS: Three key themes illustrate the power relations underpinning RCAs' encounters with incivility and bullying that, in turn, shaped care delivery. Requesting Help highlights how exposure to incivility and bullying made RCAs reluctant to seek help from their coworkers. Receiving Help focuses on how power relations and notions of worthiness and reciprocity impacted RCAs' receipt of help from coworkers. Resisting Help/ing outlines how workplace relationships imbued with power relations led some RCAs to refuse assistance from their coworkers, led longer-tenured RCAs to resist helping newer RCAs, and dictated the extent to which RCAs provided care to residents for whom another RCA was responsible. DISCUSSION AND IMPLICATIONS: Findings highlight "who" is on shift warrants as much attention as "how many" are on shift, offering additional insight into the staffing-care quality link.

Consistent assignment in long-term care homes: Avoiding the pitfalls to capitalise on the promises.

BACKGROUND: Consistent assignment (CA) is the practice within long-term care (LTC) by which care staff work with the same residents almost every shift for an indefinite period of time. CA is considered by many to be essential to person-centred care. OBJECTIVES: This paper explores how staff assignment practices impact the caregiving experience from the perspectives of resident care aides (RCAs), residents and family members and, by doing so, describe the nuanced conditions under which CA may or may not be beneficial to all, and why. METHODS: Data are drawn from 40 in-depth interviews conducted as part of a larger institutional ethnography exploring the social organisation of care in three purposively selected LTC homes in Western Canada. Data analysis was based on the principles of constant comparison. RESULTS: RCAs, residents and family members described the primary benefit of CA as being able to 'get to know' each other well and form meaningful relationships. However, the RCAs also indicated that CA can contribute to feelings of isolation, which has negative effects on worker comfort and satisfaction, care team dynamics and communication, and resident care. CONCLUSIONS: Management initiatives are needed to ensure that the implementation of CA does not result in the unintended consequences of decreasing RCAs' experience of teamwork, decreasing RCAs' exchange of individualised resident care information, or negatively impacting RCAs' ability and desire to care for each other as well as the residents. IMPLICATIONS FOR PRACTICE: The staffing practice of consistent assignment in long-term care homes provides increased opportunities for the development of stronger staff-resident and staff-family member relationships. Findings from this study enable us to offer several, evidenced-based recommendations for ensuring the successful implementation of consistent assignment, such that it may be beneficial to all.

EFab domain substitution as a solution to the light-chain pairing problem of bispecific antibodies.

Bispecific antibody therapeutics can expand the functionality of a conventional monoclonal antibody drug because they can bind multiple antigens. However, their great potential is counterbalanced by the challenges faced in their production. The classic asymmetric bispecific containing an Fc requires the expression of four unique chains - two light chains and two heavy chains; each light chain must pair with its correct heavy chain, which then must heterodimerize to form the full bispecific. The light-chain pairing problem has several solutions, some of which require engineering and optimization for each bispecific pair. Here, we introduce a technology called EFab Domain Substitution, which replaces the Cε2 of IgE for one of the CL/CH1 domains into one arm of an asymmetric bispecific to encourage the correct pairing of the light chains. EFab Domain Substitution provides very robust correct pairing while maintaining antibody function and is effective for many variable domains. We report its effect on the biophysical properties of an antibody and the crystal structure of the EFab domain substituted into the adalimumab Fab (PDB ID 6CR1).

Staff personhood in dementia care settings: "Do they care about me?"

AIMS AND OBJECTIVES: This article aims to examine RCAs' own experiences of personhood in dementia care settings. BACKGROUND: Conceptually, person-centred care entails fostering the personhood of residents and the residential care aides (RCAs) who provide much of their hands-on care. To date, however, staff personhood has been overlooked in the empirical literature. DESIGN: The study was part of a larger focused ethnographic project exploring how the organisational care environment impedes or facilitates the provision of quality dementia care. METHODS: Semi-structured interviews with 23 RCAs and more than 230 hours of participant observation were conducted in two nursing homes with specialised dementia units in British Columbia, Canada. RESULTS: Two overarching themes, "personhood undermined-management-staff relations" and "personhood undermined-workplace policies and practices" emerged, illustrating how, despite exposure to features believed beneficial to their working environment (e.g., favourable staffing ratios, relatively good remuneration), RCAs encountered repeated affronts to their personhood. The first theme encompasses the importance of being known (i.e., as persons and of their job demands) and valued (i.e., appreciated for their work in non-monetary terms). The second highlights the salience of work-life balance, full-staffing coverage and supportive human resource practices. CONCLUSIONS: RCAs' experiences reveal how the ongoing search for cost-efficiencies, cost-containment and cost-accountability overshadows their individuality, indicating a key disconnect between conceptual ideals and workplace realities. IMPLICATIONS FOR PRACTICE: Organisations are encouraged to consider creating person-centred management and workplace practices that provide tangible evidence that RCAs, and their work, matter.

The Influence of the Physical Environment on Residents With Dementia in Long-Term Care Settings: A Review of the Empirical Literature.

Background and Objectives: The physical environment in long-term care facilities has an important role in the care of residents with dementia. This paper presents a literature review focusing on recent empirical research in this area and situates the research with therapeutic goals related to the physical environment. Research Design and Methods: A comprehensive literature search was conducted in Ageline, PsychINFO, CINAHL, Medline and Google Scholar databases to identify relevant articles. A narrative approach was used to review the literature. Results: A total of 103 full-text items were reviewed, including 94 empirical studies and 9 reviews. There is substantial evidence on the influence of unit size, spatial layout, homelike character, sensory stimulation, and environmental characteristics of social spaces on residents' behaviors and well-being in care facilities. However, research in this area is primarily cross-sectional and based on relatively small and homogenous samples. Discussion and Implications: Given the increasing body of empirical evidence, greater recognition is warranted for creating physical environments appropriate and responsive to residents' cognitive abilities and functioning. Future research needs to place greater emphasis on environmental intervention-based studies, diverse sample populations, inclusion of residents in different stages and with multiple types of dementia, and on longitudinal study design.

Practice Change Interventions in Long-Term Care Facilities: What Works, and Why?

Over the past three decades, there has been a notable increase in studies of practice change interventions in long-term care (LTC) settings. This review, based on a modified realist approach, addresses the following questions: What practice change intervention characteristics work? And, in what circumstances do they work and why? A modified realist approach was applied to identify and explain the interactions among context, mechanism, and outcome. We searched electronic databases and published literature for empirical studies of practice change interventions that (a) were conducted in LTC settings, (b) involved formal care staff members, and (c) reported a formal evaluation. Ninety-four articles met the inclusion criteria. Interventions that included only predisposing factors were least likely to be effective. Interventions that included reinforcing factors were most likely to produce sustained outcomes. We concluded that interventions aimed at practice change in LTC settings should include feasible and effective enabling and reinforcing factors.

An examination of the psychometric properties and efficacy of Dementia Care Mapping.

This paper offers a critique of Dementia Care Mapping (DCM) as a practice development and research tool by examining the psychometric properties and efficacy of DCM as a method for evaluating and enhancing care quality and quality of life. Based on a review and analysis of the published empirical studies utilizing DCM, it becomes apparent that there is mixed support for the tool's validity and reliability. More importantly, there is a need for additional studies specifically examining the range of related assessments to provide conclusive evidence for DCM's relevance, applicability and reliability as a practice and research tool in dementia care. The paper identifies methodological issues of implementation and use of DCM, i.e., coding practices, mapping duration. Also, a summary of the tool's strengths and limitations in practice and research settings, areas for improvement and future research avenues is provided.

Influence of individual and contextual characteristics on the provision of individualized care in long-term care facilities.

PURPOSE: Previous research examining improved provision of individualized care (I-Care) in long-term care (LTC) facilities has primarily considered contextual influences. Using Kanter's theory of structural empowerment, this study explored the relationship among contextual-level characteristics, individual-level characteristics, and access to empowerment structures on LTC staffs' perceived ability to provide I-Care. METHODS: Multilevel models were used to examine 567 staffs' (registered nurse [RN], licensed practical nurses [LPN], care aides) reported ability to provide I-Care, nested within 41 LTC facilities. I-Care was first modeled as a function of within-person (e.g., age, job classification, experience) and between-context (e.g., facility ownership status, culture change models) variables. Independent of these predictors, we then assessed the influence of staffs' access to empowerment structures (information, support, opportunities, resources, informal power, and formal power) on reported ability to provide I-Care. RESULTS: The intraclass correlation coefficient indicated that 91.7% of the total variance in perceived ability to provide I-Care reflected within- versus between-person differences, with the 6 empowerment variables accounting for 31% of this within-person variance independent of the other context- and person-level covariates. In the final model, only informal power (i.e., quality of interprofessional relationships) and resources (i.e., adequate time and supplies) uniquely predicted I-Care. Notably, access to resources also attenuated the significant effect of support, suggesting a possible mediating effect. IMPLICATIONS: These findings suggest that both contextual- and individual-level factors exert considerably less influence on I-Care than factors associated to staffs' perceptions of empowerment. Consequently, interventions aimed at increasing I-Care in LTC settings should carefully consider staffs' access to structural empowerment.

An international comparison of the Ohio department of aging-resident satisfaction survey: applicability in a U.S. and Canadian sample.

PURPOSE OF THE STUDY: The majority of resident satisfaction surveys available for use in assisted living settings have been developed in the United States; however, empirical assessment of their measurement properties remains limited and sporadic, as does knowledge regarding their applicability for use in settings outside of the United States. This study further examines the psychometric properties of the Ohio Department of Aging-Resident Satisfaction Survey (ODA-RSS) and explores its applicability within a sample of Canadian assisted living facilities. DESIGN AND METHODS: Data were collected from 9,739 residential care facility (RCF) residents in Ohio, United States and 938 assisted-living residents in British Columbia, Canada. Confirmatory factor analysis was used to assess the instrument's psychometric properties within the 2 samples. RESULTS: Although the ODA-RSS appears well suited for assessing resident satisfaction in Ohio RCFs, it is less so in British Columbia assisted living settings. Adequate reliability and validity were observed for all 8 measurable instrument domains in the Ohio sample, but only 4 (Care and Services, Employee Relations, Employee Responsiveness, and Communications) in the British Columbia sample. IMPLICATIONS: The ODA-RSS performs best in an environment that encompasses a wide range of RCF types. In settings where greater uniformity and standardization exist, more nuanced questions may be required to detect variation between facilities. It is not sufficient to assume that rigorous development and empirical testing of a tool ensures its applicability in states or countries other than that in which it was initially developed.

Synthesis of methylphosphonic acid by marine microbes: a source for methane in the aerobic ocean.

Relative to the atmosphere, much of the aerobic ocean is supersaturated with methane; however, the source of this important greenhouse gas remains enigmatic. Catabolism of methylphosphonic acid by phosphorus-starved marine microbes, with concomitant release of methane, has been suggested to explain this phenomenon, yet methylphosphonate is not a known natural product, nor has it been detected in natural systems. Further, its synthesis from known natural products would require unknown biochemistry. Here we show that the marine archaeon Nitrosopumilus maritimus encodes a pathway for methylphosphonate biosynthesis and that it produces cell-associated methylphosphonate esters. The abundance of a key gene in this pathway in metagenomic data sets suggests that methylphosphonate biosynthesis is relatively common in marine microbes, providing a plausible explanation for the methane paradox.

Mechanistic investigation of methylphosphonate synthase, a non-heme iron-dependent oxygenase.

Methylphosphonate synthase is a non-heme iron-dependent oxygenase that converts 2-hydroxyethylphosphonate (2-HEP) to methylphosphonate. On the basis of experiments with two enantiomers of a substrate analog, 2-hydroxypropylphosphonate, catalysis is proposed to commence with stereospecific abstraction of the pro-S hydrogen on C2 of the substrate. Experiments with isotopologues of 2-HEP indicate stereospecific hydrogen transfer of the pro-R hydrogen at C2 of the substrate to the methyl group of methylphosphonate. Kinetic studies with these substrate isotopologues reveal that neither hydrogen transfer is rate limiting under saturating substrate conditions. A mechanism is proposed that is consistent with the available data.

Mechanism and substrate recognition of 2-hydroxyethylphosphonate dioxygenase.

HEPD belongs to the superfamily of 2-His-1-carboxylate non-heme iron-dependent dioxygenases. It converts 2-hydroxyethylphosphonate (2-HEP) to hydroxymethylphosphonate (HMP) and formate. Previously postulated mechanisms for the reaction catalyzed by HEPD cannot explain its conversion of 1-HEP to acetylphosphate. Alternative mechanisms that involve either phosphite or methylphosphonate as intermediates, which potentially explain all experimental studies including isotope labeling experiments and use of substrate analogues, were investigated. The results of these studies reveal that these alternative mechanisms are not correct. Site-directed mutagenesis studies of Lys16, Arg90, and Tyr98 support roles of these residues in binding of 2-HEP. Mutation of Lys16 to Ala resulted in an inactive enzyme, whereas mutation of Arg90 to Ala or Tyr98 to Phe greatly decreased k(cat)/K(m,2-HEP). Furthermore, the latter mutants could not be saturated in O(2). These results suggest that proper binding of 2-HEP is important for O(2) activation and that the enzyme uses a compulsory binding order with 2-HEP binding before O(2). The Y98F mutant produces methylphosphonate as a minor side product providing indirect support for the proposal that the last step during catalysis involves a ferric hydroxide reacting with a methylphosphonate radical.

Probing the active site of MIO-dependent aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites.

The tyrosine aminomutase SgTAM produces (S)-ss-tyrosine from L-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form alpha,ss-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been limited reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the alpha,ss-unsaturated intermediates to form ss-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray cocrystal structure of the SgTAM mutant of the catalytic base with L-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis.

Molecular basis of substrate promiscuity for the SAM-dependent O-methyltransferase NcsB1, involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.

The small molecule component of chromoprotein enediyne antitumor antibiotics is biosynthesized through a convergent route, incorporating amino acid, polyketide, and carbohydrate building blocks around a central enediyne hydrocarbon core. The naphthoic acid moiety of the enediyne neocarzinostatin plays key roles in the biological activity of the natural product by interacting with both the carrier protein and duplex DNA at the site of action. We have previously described the in vitro characterization of an S-adenosylmethionine-dependent O-methyltransferase (NcsB1) in the neocarzinostatin biosynthetic pathway [Luo, Y., Lin, S., Zhang, J., Cooke, H. A., Bruner, S. D., and Shen, B. (2008) J. Biol. Chem. 283, 14694-14702]. Here we provide a structural basis for NcsB1 activity, illustrating that the enzyme shares an overall architecture with a large family of S-adenosylmethionine-dependent proteins. In addition, NcsB1 represents the first enzyme to be structurally characterized in the biosynthetic pathway of neocarzinostatin. By cocrystallizing the enzyme with various combinations of the cofactor and substrate analogues, details of the active site structure have been established. Changes in subdomain orientation were observed via comparison of structures in the presence and absence of substrate, suggesting that reorientation of the enzyme is involved in binding of the substrate. In addition, residues important for substrate discrimination were predicted and probed through site-directed mutagenesis and in vitro biochemical characterization.

Structure and chemistry of 4-methylideneimidazole-5-one containing enzymes.

The prosthetic group 4-methylideneimidazole-5-one (MIO) is the catalytic component of the ammonia lyase class of enzymes. This family is responsible for the processing of amino acids in a variety of metabolic pathways through the elimination of ammonia to form unsaturated products. Recently, new chemistry has been attributed to this family with the discovery of MIO-based aminomutases. The mechanism of electrophilic chemistry catalyzed by MIO-based enzymes has been investigated for several decades. Recent X-ray crystal structures of members of the family have provided novel insight into the molecular basis for catalysis and substrate recognition. In addition, the inclusion of aminomutases in natural product biosynthetic pathways has spurned recent advances toward rational engineering and chemoenzymatic applications.

Regiospecific O-methylation of naphthoic acids catalyzed by NcsB1, an O-methyltransferase involved in the biosynthesis of the enediyne antitumor antibiotic neocarzinostatin.

Neocarzinostatin, a clinical anticancer drug, is the archetypal member of the chromoprotein family of enediyne antitumor antibiotics that are composed of a nonprotein chromophore and an apoprotein. The neocarzinostatin chromophore consists of a nine-membered enediyne core, a deoxyaminosugar, and a naphthoic acid moiety. We have previously cloned and sequenced the neocarzinostatin biosynthetic gene cluster and proposed that the biosynthesis of the naphthoic acid moiety and its incorporation into the neocarzinostatin chromophore are catalyzed by five enzymes NcsB, NcsB1, NcsB2, NcsB3, and NcsB4. Here we report the biochemical characterization of NcsB1, unveiling that: (i) NcsB1 is an S-adenosyl-L-methionine-dependent O-methyltransferase; (ii) NcsB1 catalyzes regiospecific methylation at the 7-hydroxy group of its native substrate, 2,7-dihydroxy-5-methyl-1-naphthoic acid; (iii) NcsB1 also recognizes other dihydroxynaphthoic acids as substrates and catalyzes regiospecific O-methylation; and (iv) the carboxylate and its ortho-hydroxy groups of the substrate appear to be crucial for NcsB1 substrate recognition and binding, and O-methylation takes place only at the free hydroxy group of these dihydroxynaphthoic acids. These findings establish that NcsB1 catalyzes the third step in the biosynthesis of the naphthoic acid moiety of the neocarzinostatin chromophore and further support the early proposal for the biosynthesis of the naphthoic acid and its incorporation into the neocarzinostatin chromophore with free naphthoic acids serving as intermediates. NcsB1 represents another opportunity that can now be exploited to produce novel neocarzinostatin analogs by engineering neocarzinostatin biosynthesis or applying directed biosynthesis strategies.