Rewiring of Aminoacyl-tRNA Synthetase Localization and Interactions in Plants With Extensive Mitochondrial tRNA Gene Loss.

The number of tRNAs encoded in plant mitochondrial genomes varies considerably. Ongoing loss of bacterial-like mitochondrial tRNA genes in many lineages necessitates the import of nuclear-encoded counterparts that share little sequence similarity. Because tRNAs are involved in highly specific molecular interactions, this replacement process raises questions about the identity and trafficking of enzymes necessary for the maturation and function of newly imported tRNAs. In particular, the aminoacyl-tRNA synthetases (aaRSs) that charge tRNAs are usually divided into distinct classes that specialize on either organellar (mitochondrial and plastid) or nuclear-encoded (cytosolic) tRNAs. Here, we investigate the evolution of aaRS subcellular localization in a plant lineage (Sileneae) that has experienced extensive and rapid mitochondrial tRNA loss. By analyzing full-length mRNA transcripts (PacBio Iso-Seq), we found predicted retargeting of many ancestrally cytosolic aaRSs to the mitochondrion and confirmed these results with colocalization microscopy assays. However, we also found cases where aaRS localization does not appear to change despite functional tRNA replacement, suggesting evolution of novel interactions and charging relationships. Therefore, the history of repeated tRNA replacement in Sileneae mitochondria reveals that differing constraints on tRNA/aaRS interactions may determine which of these alternative coevolutionary paths is used to maintain organellar translation in plant cells.

Prevalence of pain in a sample of long-term survivors of head and neck cancer.

PURPOSE: The experience of long-term pain in head and neck cancer (HNC) survivors is important but has received less attention in the HNC literature. The present study sought to examine the prevalence of pain from 2 to 5 years postdiagnosis and its association with HNC-specific health-related quality of life. MATERIALS & METHODS: Prospective observational study at a single-institution tertiary care center. Pain was measured using a single item ranging from 0 to 10 with 0 representing no pain and 10 representing worst pain possible at 2 through 5 years postdiagnosis. HNC-specific HRQOL was measured using the Head and Neck Cancer Inventory (HNCI). RESULTS: Pain reports were consistent across time. At 2 years postdiagnosis (N = 581), 27.6 % experienced at least some pain with 14.3 % reporting moderate or severe pain. At 3 years postdiagnosis (N = 417), 21.4 % experienced at least some pain with 14.2 % indicating moderate or severe pain. At 4 years postdiagnosis (N = 334), 26.7 % experienced at least some pain with 15.9 % reporting moderate or severe pain. At 5 years postdiagnosis (N = 399), 30.5 % experienced at least some pain with 17.5 % indicating moderate or severe pain. In general, across all four HNCI domains, those in the moderate and severe pain categories largely failed to reach 70 which is indicative of high functioning on the HNCI. CONCLUSIONS: Pain is a considerable issue in long-term HNC survivors up to 5 years postdiagnosis. More research is needed to understand correlates of pain after treatment, including opportunities for screening and intervention, to improve outcomes and optimize recovery in HNC.

Prevalence and persistence of depressive symptoms during the first year postdiagnosis in a large sample of patients with head and neck cancer.

PURPOSE: The experience of persistent depressive symptomatology during the first year postdiagnosis has implications for recovery and adjustment by one year postdiagnosis. The present descriptive study sought to examine the prevalence and persistence of mild to moderate-severe depressive symptomology and associated disease-specific health-related quality of life (HRQOL) in patients with HNC. MATERIALS & METHODS: This study was a prospective observational study at a single-institution tertiary cancer center. Depressive symptomatology was measured using the Beck Depression Inventory (BDI), captured at diagnosis and 3-, 6-, 9-, and 12-months postdiagnosis. HNC-specific HRQOL was measured using the Head and Neck Cancer Inventory (HNCI). Four subgroups were defined by BDI scores over time: persistent-moderate/severe subgroup, persistent-mild subgroup, transient subgroup, and resilient subgroup. RESULTS: The distribution of patients (N = 946) was 65 (6.9 %) in the persistent-moderate/severe subgroup, 190 (20.1 %) in the persistent-mild subgroup, 186 (19.7 %) in the transient subgroup, and 505 (53.3 %) in the resilient subgroup. Across all four HNCI domains, patients in the persistent-moderate/severe subgroup failed to reach a score of 70 by 12-months postdiagnosis which is indicative of high functioning on the HNCI (aesthetics: M = 42.32, SD = 28.7; eating: M = 32.08, SD = 25.7; speech: M = 47.67, SD = 25.3; social disruption: M = 52.39, SD = 24.3). Patients in the persistent-mild subgroup failed to reach 70 in three of four domains. Patients in the resilient subgroup reached, on average, >70 on all HNCI domains. CONCLUSIONS: Depression is a considerable issue during the first year postdiagnosis. Avenues for screening and intervention should be incorporated into HNC patient care per clinical practice guidelines to optimize recovery and HRQOL.

Mapping Patients' Perceived Facilitators and Barriers to In-Center Hemodialysis Attendance to the Health Belief Model: Insights from a Qualitative Study.

BACKGROUND: Previous research has shown that deliberate withdrawal, skipping, and/or shortening hemodialysis sessions has become a major health problem associated with poor clinical outcomes and early mortality in patients with end-stage renal disease (ESRD). However, patients' experiences with this treatment remain largely unexplored. This study aimed to explore patients' perceived facilitators and barriers to in-center hemodialysis attendance and map these findings to the Health Belief Model. METHODS: A qualitative exploratory study was conducted with a purposive sample. Semi-structured interviews were conducted and submitted to thematic analysis. RESULTS: Twenty-four patients (66.2 ± 12.3 years old; length of time on hemodialysis: 35.2 ± 51.5 months) were interviewed. Five major facilitators (social support, perceived benefits, self-efficacy, time on dialysis, and risk/susceptibility perception) and two barriers (lack of knowledge about ESRD and hemodialysis, and psychosocial costs) were identified. CONCLUSION: Adherence to the prescribed regimen of hemodialysis attendance is a complex and multidimensional phenomenon that involves an interaction between modifying factors (social support, disease and treatment knowledge, time on dialysis) and patients' perceived benefits, perceived risks, self-efficacy, and treatment costs. This study findings expand knowledge by suggesting that perceiving health benefits from the beginning of treatment, self-efficacy to deal with dialysis demands, and purpose in life are important facilitators of adherence to in-center hemodialysis sessions. Furthermore, it suggests that the impact of the hemodialysis regimen on the emotional well-being of family members is an important barrier. Future interventions should focus on skills training to promote self-efficacy and family coping with the demands of in-center hemodialysis, improve disease and treatment knowledge, and help balance perceived benefits with dialysis costs.

A dedicated flavin-dependent monooxygenase catalyzes the hydroxylation of demethoxyubiquinone into ubiquinone (coenzyme Q) in Arabidopsis.

Ubiquinone (Coenzyme Q) is a vital respiratory cofactor and liposoluble antioxidant. In plants, it is not known how the C-6 hydroxylation of demethoxyubiquinone, the penultimate step in ubiquinone biosynthesis, is catalyzed. The combination of cross-species gene network modeling along with mining of embryo-defective mutant databases of Arabidopsis thaliana identified the embryo lethal locus EMB2421 (At1g24340) as a top candidate for the missing plant demethoxyubiquinone hydroxylase. In marked contrast with prototypical eukaryotic demethoxyubiquinone hydroxylases, the catalytic mechanism of which depends on a carboxylate-bridged di-iron domain, At1g24340 is homologous to FAD-dependent oxidoreductases that instead use NAD(P)H as an electron donor. Complementation assays in Saccharomyces cerevisiae and Escherichia coli demonstrated that At1g24340 encodes a functional demethoxyubiquinone hydroxylase and that the enzyme displays strict specificity for the C-6 position of the benzoquinone ring. Laser-scanning confocal microscopy also showed that GFP-tagged At1g24340 is targeted to mitochondria. Silencing of At1g24340 resulted in 40 to 74% decrease in ubiquinone content and de novo ubiquinone biosynthesis. Consistent with the role of At1g24340 as a benzenoid ring modification enzyme, this metabolic blockage could not be bypassed by supplementation with 4-hydroxybenzoate, the immediate precursor of ubiquinone's ring. Unlike in yeast, in Arabidopsis overexpression of demethoxyubiquinone hydroxylase did not boost ubiquinone content. Phylogenetic reconstructions indicated that plant demethoxyubiquinone hydroxylase is most closely related to prokaryotic monooxygenases that act on halogenated aromatics and likely descends from an event of horizontal gene transfer between a green alga and a bacterium.

Social networks in the single cell.

This article comments on: Chustecki JM, Etherington RD, Gibbs DJ, Johnston IG. 2022. Altered collective mitochondrial dynamics in the Arabidopsis msh1 mutant compromising organelle DNA maintenance. Journal of Experimental Botany 73, 5428-5439. Plant mitochondrial DNA (mtDNA) can become damaged in many ways. A major repair mechanism is homologous recombination, which requires an undamaged DNA template. Presumably, this template comes from a different mitochondrion in the same cell. Plant mitochondria undergo fission and fusion to form transient networks which could allow the exchange of genetic information. To test this hypothesis, Chustecki et al. (2022) used msh1 mutants with defective DNA repair, and showed that mitochondrial interactions increased, revealing a link between the physical and genetic behavior of mitochondria.

Problem alcohol and tobacco use in head and neck cancer patients at diagnosis: associations with health-related quality of life.

PURPOSE: Problem alcohol and tobacco use in patients with head and neck cancer (HNC) frequently co-occur and each are associated with poor outcomes including health-related quality of life (HRQOL). The purpose of this descriptive exploratory study was to identify the prevalence of these co-occurring behaviors and associations with HNC-specific HRQOL within the first year of diagnosis in a large sample of patients with HNC. METHODS: Cross-sectional study examined prevalence of co-occurring problem alcohol and tobacco use at diagnosis in a large sample of patients with HNC (N = 1327). Problem alcohol use was assessed using the Short Michigan Alcoholism Screening Test (SMAST); patients were classified as current/previous/never smokers based on self-reported tobacco use. HNC-specific HRQOL was assessed using the Head and Neck Cancer Inventory (HNCI), measured at diagnosis and 3 and 12 months postdiagnosis. RESULTS: Three hundred twenty-five of 1327 (24.5%) scored 3 + on the SMAST at diagnosis, suggesting problem alcohol use and nearly 30% (28.4%) were current smokers. Of those with problem alcohol use, 173 (53.2%) were also current smokers. In total, 173 of 1327 (13.0%) exhibited both behaviors at diagnosis. Covariate-adjusted mean HNCI scores suggest that patients classified as both problem drinkers and current smokers have lower HRQOL scores during the first year postdiagnosis in multiple HNC-specific domains. CONCLUSION: HNC patients should be screened for alcohol and tobacco use at diagnosis. Multimodal behavioral health interventions may provide one avenue for improved access and outcomes, particularly for patients at distance, and deserve further study in HNC.

Disparities in dialysis modality decision-making using a social-ecological lens: a qualitative approach.

BACKGROUND: Patients with end-stage kidney disease (ESKD) may choose to undergo dialysis in-center or at home, but uptake of home dialysis in the US has been minimal despite its benefits over in-center dialysis. Factors that may have led patients to select home dialysis over in-center dialysis are poorly understood in the literature, and interventions to improve selection of home dialysis have focused on patient knowledge and shared decision-making processes between patients and providers. The purpose of this study was to explore micro- and macro-level factors surrounding dialysis modality decision-making among patients undergoing in-center and home dialysis, and explore what leads patients to select home dialysis over in-center dialysis. METHODS: Semi-structured qualitative interviews were conducted in a dialysis clinic at a large Midwestern research hospital, from September 2019 to December 2020. Participants were 18 years or older, undergoing dialysis for ESKD, and had the cognitive ability to provide consent. Surveys assessing demographic and clinical information were administered to participants following their interviews. RESULTS: Forty patients completed interviews and surveys (20 [50%] in-center dialysis, 17 [43%] female, mean [SD] age, 59 [15.99] years). Qualitative findings suggested that healthcare access and engagement before entering nephrology care, after entering nephrology care, and following dialysis initiation influenced patients' awareness regarding their kidney disease status, progression toward ESKD, and dialysis options. Potential modifiers of these outcomes include race, ethnicity, and language barriers. Most participants adopted a passive-approach during decision-making. Finally, fatigue, concerns regarding one's dialyzing schedule, and problems with fistula/catheter access sites contributed to overall satisfaction with one's dialysis modality. CONCLUSIONS: Findings point to broader factors affecting dialysis selection, including healthcare access and racial/ethnic inequities. Providing dialysis information before entering nephrology and after dialysis initiation may improve patient agency in decision-making. Additional resources should be prioritized for patients of underrepresented backgrounds. Dialysis decision-making may be appropriately modeled under the social-ecological framework to inform future interventions.

The alternative reality of plant mitochondrial DNA: One ring does not rule them all.

Plant mitochondrial genomes are usually assembled and displayed as circular maps based on the widely-held view across the broad community of life scientists that circular genome-sized molecules are the primary form of plant mitochondrial DNA, despite the understanding by plant mitochondrial researchers that this is an inaccurate and outdated concept. Many plant mitochondrial genomes have one or more pairs of large repeats that can act as sites for inter- or intramolecular recombination, leading to multiple alternative arrangements (isoforms). Most mitochondrial genomes have been assembled using methods unable to capture the complete spectrum of isoforms within a species, leading to an incomplete inference of their structure and recombinational activity. To document and investigate underlying reasons for structural diversity in plant mitochondrial DNA, we used long-read (PacBio) and short-read (Illumina) sequencing data to assemble and compare mitochondrial genomes of domesticated (Lactuca sativa) and wild (L. saligna and L. serriola) lettuce species. We characterized a comprehensive, complex set of isoforms within each species and compared genome structures between species. Physical analysis of L. sativa mtDNA molecules by fluorescence microscopy revealed a variety of linear, branched, and circular structures. The mitochondrial genomes for L. sativa and L. serriola were identical in sequence and arrangement and differed substantially from L. saligna, indicating that the mitochondrial genome structure did not change during domestication. From the isoforms in our data, we infer that recombination occurs at repeats of all sizes at variable frequencies. The differences in genome structure between L. saligna and the two other Lactuca species can be largely explained by rare recombination events that rearranged the structure. Our data demonstrate that representations of plant mitochondrial genomes as simple, circular molecules are not accurate descriptions of their true nature and that in reality plant mitochondrial DNA is a complex, dynamic mixture of forms.

Caring for parents with end-stage renal disease: What do adult children face and how do they cope?

AIM: This study aimed to explore the stressors and coping strategies of adult children who care for their parents with end-stage renal disease (ESRD) undergoing in-centre haemodialysis. BACKGROUND: Given the growing number of older patients with ESRD, adult children are increasingly providing more care and assistance to their parents with this condition. However, little is still known about the experiences of caring for a parent undergoing haemodialysis. DESIGN: A qualitative exploratory study was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. METHODS: Semi-structured face-to-face interviews with nineteen adult children (44.9 ± 11.7 years old) were carried out. Data were transcribed verbatim and subjected to thematic analysis. RESULTS: Four stressors (managing disease and treatment-related requirements, patients' reaction to treatment, lack of support from family members, and additional challenges to personal and family life) and five coping strategies (active coping and planning, seeking social support for emotional use, accepting the situation as it is, venting emotions, and maintaining interests outside caring) were identified. CONCLUSION: Caring for a parent undergoing haemodialysis is an experience with several challenges, marked by educational needs, emotional distress, lack of support from close relatives and the need to manage multiple responsibilities. RELEVANCE TO CLINICAL PRACTICE: Findings highlight the importance of developing interdisciplinary educational and supportive interventions to support this group of caregivers. These interventions should facilitate access to disease and treatment-related information, provide emotional support, and train coping skills to prevent burden and promote healthy adjustment to the demands of ESRD care.

Association of depressive symptomatology with problem alcohol use in rural head and neck cancer patients at diagnosis.

PURPOSE: Problem alcohol use is a risk factor for the development of head and neck cancer (HNC) and continued use is associated with poor outcomes; depressive symptoms may be associated with this behavior. DESIGN: Exploratory cross-sectional study examined depressive symptoms as a correlate of self-reported problem alcohol use at diagnosis. SAMPLE/METHODS: Multivariable linear regression examined depressive symptoms as a correlate of problem alcohol use in a sample of rural HNC patients (N = 249). FINDINGS: Over half (55.2%) of rural patients with potentially problem alcohol use exhibited mild to moderate depressive symptomatology. Regression models controlling for age, cancer site, stage, sex, tobacco use, and treatment modality indicated that depressive symptoms at diagnosis were associated with self-reported problem alcohol use scores at diagnosis (ß = .186, sr2 = .031, p < .01). Follow-up subgroup analyses demonstrated that depressive symptoms at diagnosis were significantly associated with self-reported problem alcohol use in male patients, those with advanced stage disease, and of older age. CONCLUSIONS/IMPLICATIONS: HNC patients should be screened for alcohol use and depression at diagnosis. Access to behavioral health treatment and/or referral options may be lacking in rural areas thus additional ways of connecting rural patients to specialty care should be explored. These may include telehealth and multimodal interventions to address complex behavioral health cases. Additional research in important patient subgroups such as older patients and those presenting with advanced disease is also warranted.

Plant Mitochondria are a Riddle Wrapped in a Mystery Inside an Enigma.

A fundamental paradox motivates the study of plant mitochondrial genomics: the mutation rate is very low (lower than in the nucleus) but the rearrangement rate is high. A landmark paper published in Journal of Molecular Evolution in 1988 established these facts and revealed the paradox. Jeffrey Palmer and Laura Herbon did a prodigious amount of work in the pre-genome sequencing era to identify both the high frequency of rearrangements between closely related species, and the low frequency of mutations, observations that have now been confirmed many times by sequencing. This paper was also the first to use molecular data on rearrangements as a phylogenetic trait to build a parsimonious tree. The work was a technical tour-de-force, its findings are still at the heart of plant mitochondrial genomics, and the underlying molecular mechanisms that produce this paradox are still not completely understood.

Problem alcohol use among rural head and neck cancer patients at diagnosis: Associations with health-related quality of life.

OBJECTIVE: Problem alcohol use in persons with head and neck cancer (HNC) is associated with poor outcomes, including survival. Some evidence suggests that individuals living in rural areas may be at greater risk of problem alcohol use. The present exploratory cross-sectional study sought to examine problem alcohol use at diagnosis in a sample of HNC patients by rural versus urban status. METHODS: Self-reported problem alcohol use as measured by the Short Michigan Alcoholism Screening Test (SMAST) was examined in rural and urban HNC patients at diagnosis (N = 454). Multivariable linear regression analysis was conducted to examine correlates of problem alcohol use. Subgroup analyses examined HNC-specific health-related quality of life (HRQOL) by problem drinking status at diagnosis and 3- and 12-month postdiagnosis in rural patients. RESULTS: Multivariable linear regression analysis controlling for age, cancer site, cancer stage, depressive symptoms at diagnosis, and tobacco use at diagnosis indicated that rural residence was significantly associated with SMAST scores at diagnosis such that rural patients were more likely to report higher scores (ß = 0.095, sr2  = 0.010, p = 0.04). Covariate-adjusted subgroup analyses suggest that rural patients with self-reported problem alcohol use may exhibit deficits in HNC-specific HRQOL at diagnosis and 3- and 12-month postdiagnosis. CONCLUSIONS: HNC patients should be screened for problem alcohol use at diagnosis and counseled regarding the deleterious effects of continued drinking during treatment and beyond. Because access to treatment and referral options may be lacking in rural areas, additional ways of connecting rural patients to specialty care should be explored.

Exploring the Relationship Between Patient Activation, Treatment Satisfaction, and Decisional Conflict in Patients Approaching End-Stage Renal Disease.

BACKGROUND: Patients approaching end-stage renal disease (ESRD) experience a high level of decisional conflict because they are often not provided with sufficient support and information regarding different treatment options prior to renal failure. Decisional conflict is an important correlate of treatment satisfaction, as it is associated with disease- and treatment-related knowledge that can inform decision-making. Patient activation, the willingness and ability to independently manage one's own health and healthcare, is an individual difference factor that may have important mitigating effects on decisional conflict. PURPOSE: To identify modifiable factors that may enhance the decision-making process in patients approaching ESRD by exploring potential mediational effects between decisional conflict, treatment satisfaction, and patient activation. METHODS: Sixty-four patients approaching ESRD completed self-report measures (32% response rate). Measures included the Decisional Conflict Scale, the Kidney Disease Treatment Questionnaire, and the Patient Activation Measure Short Form. RESULTS: There was a high level of self-reported decisional conflict in this sample. Linear regressions revealed main effects among treatment satisfaction, patient activation, and decisional conflict. These variables were entered into PROCESS to assess a mediational pattern. Results showed that higher chronic kidney disease-related treatment satisfaction predicted lower decisional conflict through higher patient activation in a statistical mediational relationship. CONCLUSIONS: While the link between treatment satisfaction and decision-making is well established, these results suggest this relationship might be partially explained by patient activation, a potentially modifiable process in patients approaching ESRD. Therefore, interventions that encourage patients to become actively involved in their care could also reduce decisional conflict among patients approaching ESRD.

Looking back, looking forward: forty years of the Journal of Behavioral Medicine.

The inception, development, and rise of the Journal of Behavioral Medicine (JOBM) has paralleled that of the field of behavioral medicine. Under the leadership of founding editor, W. Doyle Gentry, published its first issue in 1978. The subsequent 40 years have seen JOBM progress to the level of a top tier journal publishing inter-disciplinary work devoted to furthering understanding of physical health and illness through the theories and methodologies of behavioral science. In recent years, JOBM has become a prominent international platform for scientific communication in the field of behavioral medicine. The present article examines many of the important milestones JOBM has achieved and examines the scope and impact of the most highly cited papers in the journal's history. As Stephen Weiss and Gary Schwartz predicted 40 years ago, behavioral medicine is in a unique and powerful position to address a broad range of issues surrounding individual, community, and population health. It is the hope of the current editorial team that in the next 40 years the journal will facilitate a broadening of the clinical and public health contexts that the science and practice of behavioral medicine addresses and informs.

Effect of a Behavioral Self-Regulation Intervention on Patient Adherence to Fluid-Intake Restrictions in Hemodialysis: a Randomized Controlled Trial.

OBJECTIVE: The purpose of this study is to evaluate the efficacy of a behavioral self-regulation intervention vs. active control condition using a parallel-group randomized clinical trial with a sample of center hemodialysis patients with chronic kidney disease. METHOD: Participants were recruited from 8 hemodialysis treatment centers in the Midwest. Eligible patients were (a) fluid nonadherent as defined by an interdialytic weight gain >2.5 kg over a 4-week period, (b) >18 years of age, (c) English-speaking without severe cognitive impairment, (d) treated with center-based hemodialysis for >3 months, and (e) not living in a care facility in which meals were managed. Medical records were used to identify eligible patients. Patients were randomly assigned to either a behavioral self-regulation intervention or active control condition in which groups of 3-8 patients met for hour-long, weekly sessions for 7 weeks at their usual hemodialysis clinic. Primary analyses were intention-to-treat. RESULTS: Sixty-one patients were randomized to the intervention while 58 were assigned to the attention-placebo support and discussion control. Covariate-adjusted between-subjects analyses demonstrated no unique intervention effect for the primary outcome, interdialytic weight gain (ß = 0.13, p = 0.48). Significant within-subjects improvement over time was observed for the intervention group (ß = -0.32, p = 0.014). CONCLUSIONS: The present study found that participation in a behavioral self-regulation intervention resulted in no unique intervention effect on a key indicator of adherence for those with severe chronic kidney disease. There was, however, modest within-subjects improvement in interdialytic weight gain for the intervention group which meshes with other evidence showing the utility of behavioral interventions in this patient population. ClinicalTrials.gov Identifier: NCT01066949.

Are Synonymous Substitutions in Flowering Plant Mitochondria Neutral?

Angiosperm mitochondrial genes appear to have very low mutation rates, while non-gene regions expand, diverge, and rearrange quickly. One possible explanation for this disparity is that synonymous substitutions in plant mitochondrial genes are not truly neutral and selection keeps their occurrence low. If this were true, the explanation for the disparity in mutation rates in genes and non-genes needs to consider selection as well as mechanisms of DNA repair. Rps14 is co-transcribed with cob and rpl5 in most plant mitochondrial genomes, but in some genomes, rps14 has been duplicated to the nucleus leaving a pseudogene in the mitochondria. This provides an opportunity to compare neutral substitution rates in pseudogenes with synonymous substitution rates in the orthologs. Genes and pseudogenes of rps14 have been aligned among different species and the mutation rates have been calculated. Neutral substitution rates in pseudogenes and synonymous substitution rates in genes are significantly different, providing evidence that synonymous substitutions in plant mitochondrial genes are not completely neutral. The non-neutrality is not sufficient to completely explain the exceptionally low mutation rates in land plant mitochondrial genomes, but selective forces appear to play a small role.

Effect of a care transition intervention by pharmacists: an RCT.

BACKGROUND: Pharmacists may improve medication-related outcomes during transitions of care. The aim of the Iowa Continuity of Care Study was to determine if a pharmacist case manager (PCM) providing a faxed discharge medication care plan from a tertiary care institution to primary care could improve medication appropriateness and reduce adverse events, rehospitalization and emergency department visits. METHODS: Design. Randomized, controlled trial of 945 participants assigned to enhanced, minimal and usual care groups conducted 2007 to 2012. Subjects. Participants with cardiovascular-related conditions and/or asthma or chronic obstructive pulmonary disease were recruited from the University of Iowa Hospital and Clinics following admission to general medicine, family medicine, cardiology or orthopedics. Intervention. The minimal group received admission history, medication reconciliation, patient education, discharge medication list and medication recommendations to inpatient team. The enhanced group also received a faxed medication care plan to their community physician and pharmacy and telephone call 3-5 days post-discharge. Participants were followed for 90 days post-discharge. Main Outcomes and Measures. Medication appropriateness index (MAI), adverse events, adverse drug events and post-discharge healthcare utilization were compared by study group using linear and logistic regression, as models accommodating random effects due to pharmacists indicated little clustering. RESULTS: Study groups were similar at baseline and the intervention fidelity was high. There were no statistically significant differences by study group in medication appropriateness, adverse events or adverse drug events at discharge, 30-day and 90-day post-discharge. The average MAI per medication as 0.53 at discharge and increased to 0.75 at 90 days, and this was true across all study groups. Post-discharge, about 16% of all participants experienced an adverse event, and this did not differ by study group (p > 0.05). Almost one-third of all participants had any type of healthcare utilization within 30 days post-discharge, where 15% of all participants had a 30-day readmission. Healthcare utilization post-discharge was not statistically significant different at 30 or 90 days by study group. CONCLUSION: The pharmacist case manager did not affect medication use outcomes post-discharge perhaps because quality of care measures were high in all study groups. TRIAL REGISTRATION: Clinicaltrials.gov registration: NCT00513903, August 7, 2007.

Evaluating the Psychometric Properties of Patient-Reported Outcome Measures for Assessing Symptoms in Hemodialysis: A Systematic Review Using COSMIN Guidelines.

CONTEXT: Patient-reported outcome measures (PROMs) may have an important role in screening and monitoring for unpleasant symptoms in kidney failure. However, there is still little evidence on the psychometric properties of the measures available to assess physical and psychological symptoms in people on hemodialysis. This gap makes it difficult to decide which measure is the most appropriate for use in clinical practice and research with this population. OBJECTIVES: This systematic review aimed to critically appraise, compare, and summarize the quality of the measurement properties of PROMs used to assess symptoms in adults on hemodialysis. METHODS: The protocol for this review was registered in PROSPERO (CRD42023393441). The last database search update was performed on November 25, 2022. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines informed methodological quality assessment, data extraction, analysis, and synthesis. RESULTS: Twenty-seven primary studies reported the measurement properties of 16 PROMs used to assess physical and psychological symptoms in adults on hemodialysis. Results showed that most measures lacked the necessary psychometric evidence to attest their suitability for this study population, and few underwent rigorous validation procedures. Overall, caveats were found on methodological quality and evidence of content validity and structural validity, and little data was available on responsiveness, measurement error, and cross-cultural validity. CONCLUSION: The current systematic review provides the basis for identifying PROMs with potential utility for assessing symptoms in hemodialysis care. Several recommendations are presented to help guide future research aimed at improving the rigor of validation and/or translation procedures of existing (and future) measures using COSMIN guidelines.