Characterization of the state transition in the cyanobacterium synechococcus sp. 7002 and a phycobilisome-less Mutant

ABSTRACT Photosynthetic state transitions were investigated in the cyanobacterium Synechococcus sp. PCC 7002 in both wild-type cells and mutant cells lacking phycobilisomes. Preillumination in the presence of DCMU (3(3,4 dichlorophenyl) 1,1 dimethyl urea) induced state 1 and dark adaptation induced state 2 in both wild-type and mutant cells as determined by 77K fluorescence emission spectroscopy. Light-induced transitions were observed in the wildtype after preferential excitation of phycocyanin (state 2) or preferential excitation of chlorophyll .a. (state 1). The state 1 and 2 transitions in the wild-type had half-times of approximately 10 seconds. Cytochrome f and P-700 oxidation kinetics could not be correlated with any current state transition model as cells in state 1 showed faster oxidation kinetics regardless of excitation wavelength. Light-induced transitions were also observed in the phycobilisomeless mutant after preferential excitation of short wavelength chlorophyll !l. (state 2) or carotenoids and long wavelength chlorophyll it (state 1). One-dimensional electrophoresis revealed no significant differences in phosphorylation patterns of resolved proteins between wild-type cells in state 1 and state 2. It is concluded that the mechanism of the light state transition in cyanobacteria does not require the presence of the phycobilisome. The results contradict proposed models for the state transition which require an active role for the phycobilisome

The WISHED Trial: implementation of an interactive health communication application for patients with chronic kidney disease

Background: Despite many advantages over facility-based therapies, less than 25 % of prevalent dialysis patients in Ontario are on a home therapy. Interactive health communication applications, web-based packages for patients, have been shown to have a beneficial effect on knowledge, social support, self-efficacy, and behavioral and clinical outcomes but have not been evaluated in patients with chronic kidney disease (CKD). Web-based tools designed for patients with CKD exist but to our knowledge have not been assessed in their ability to influence dialysis modality decision-making. Objective: To determine if a web-based tool increases utilization of a home-based therapy in patients with CKD starting dialysis. Design: This is a multi-centered randomized controlled study. Setting: Participants will be recruited from sites in Canada. Participants: Two hundred and sixty-four consenting patients with an estimated glomerular filtration rate (eGFR) less than 20 ml/min/1.73 m 2 who have received modality education will be enrolled in the study. Measurements: The primary outcome will be the proportion of participants who are on dialysis using a home-based therapy within 3 months of dialysis initiation. Secondary outcomes will include the proportion of patients intending to perform a home-based modality and measures of dialysis knowledge, decision conflict, and social support. Methods: The between-group differences in frequencies will be expressed as either absolute risk differences and/or by calculating the odds ratio and its associated 95 % confidence interval. Conclusions: This study will assess whether access to a website dedicated to supporting and promoting home-based dialysis therapies will increase the proportion of patients with CKD who initiate a home-based dialysis therapy. Trial registration: ClinicalTrials.gov #NCT01403454, registration date: July 21, 2011

Waist-to-Hip Ratio, Cardiovascular Outcomes, and Death in Peritoneal Dialysis Patients

Objectives. The primary objective of this study was to determine the relationship between waist-to-hip ratio (WHR), cardiovascular (CV) events, and mortality in peritoneal dialysis (PD) patients. A secondary objective was to investigate the association between abdominal obesity and systemic inflammatory markers. Methods. This is a prospective study of 22 prevalent PD patients. WHR was measured at baseline. C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Main outcomes were first CV event and death from all causes. Survival analysis was used to examine the relationship between anthropomorphic measures and clinical outcomes. Results. Mean follow-up period was 3.1 years. In Kaplan-Meier analysis, survival was lower in those with higher WHR (P = .002). In Cox regression, WHR independently predicted mortality and first CV event after adjustment for known ischemic heart disease (hazard ratio [HR] 1.17, confidence interval [CI] 1.05–1.30 for death; HR 1.13, CI 1.01–1.26 for CV event). WHR correlated with serum TNF-α (r = 0.45; P = .05). Conclusion. The results of this study suggest WHR may be a risk factor for increased CV events and mortality in PD patients. Abdominal obesity is also associated with inflammatory markers. Larger studies are warranted to confirm these findings

Quality of Chronic Kidney Disease Management in Canadian Primary Care.

Importance: Although patients with chronic kidney disease (CKD) are routinely managed in primary care settings, no nationally representative study has assessed the quality of care received by these patients in Canada. Objective: To evaluate the current state of CKD management in Canadian primary care practices to identify care gaps to guide development and implementation of national quality improvement initiatives. Design, Setting, and Participants: This cross-sectional study leveraged Canadian Primary Care Sentinel Surveillance Network data from January 1, 2010, to December 31, 2015, to develop a cohort of 46 162 patients with CKD managed in primary care practices. Data analysis was performed from August 8, 2018, to July 31, 2019. Main Outcomes and Measures: The study examined the proportion of patients with CKD who met a set of 12 quality indicators in 6 domains: (1) detection and recognition of CKD, (2) testing and monitoring of kidney function, (3) use of recommended medications, (4) monitoring after initiation of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), (5) management of blood pressure, and (6) monitoring for glycemic control in those with diabetes and CKD. The study also analyzed associations of divergence from these quality indicators. Results: The cohort comprised 46 162 patients (mean [SD] age, 69.2 [14.0] years; 25 855 [56.0%] female) with stage 3 to 5 CKD. Only 4 of 12 quality indicators were met by 75% or more of the study cohort. These indicators were receipt of an outpatient serum creatinine test within 18 months after confirmation of CKD, receipt of blood pressure measurement at any time during follow-up, achieving a target blood pressure of 140/90 mm Hg or lower, and receiving a hemoglobin A1c test for monitoring diabetes during follow-up. Indicators in the domains of detection and recognition of CKD, testing and monitoring of kidney function (specifically, urine albumin to creatinine ratio testing), use of recommended medications, and appropriate monitoring after initiation of treatment with ACEIs or ARBs were not met. Only 6529 patients (18.4%) with CKD received a urine albumin test within 6 months of CKD diagnosis, and 3954 (39.4%) had a second measurement within 6 months of an abnormal baseline urine albumin level. Older age (≥85 years) and CKD stage 5 were significantly associated with not satisfying the criteria for the quality indicators across all domains. Across age categories, younger patients (aged 18-49 years) and older patients (≥75 years) were less likely to be tested for albuminuria (314 of 1689 patients aged 18-49 years [18.5%], 1983 of 11 919 patients aged 75-84 years [61.6%], and 614 of 5237 patients aged ≥85 years [11.7%] received the urine albumin to creatinine ratio test within 6 months of initial estimated glomerular filtration rate <60 mL/min per 1.73 m2; P < .001). Patients aged 18 to 49 years were less commonly prescribed recommended medications (222 of 2881 [7.7%]), whereas patients aged 75 to 84 years were prescribed ACEIs or ARBs most frequently (2328 of 5262 [44.2%]; P < .001). Conclusions and Relevance: The findings suggest that management of CKD across primary care practices in Canada varies according to quality indicator. This study revealed potential priority areas for quality improvement initiatives in Canadian primary care practices

Prevalence of polypharmacy and associated adverse health outcomes in adult patients with chronic kidney disease: protocol for a systematic review and meta-analysis

Background Polypharmacy, often defined as the concomitant use of ≥ 5 medications, has been identified as a significant global public health threat. Aging and multimorbidity are key drivers of polypharmacy and have been linked to a broad range of adverse health outcomes and mortality. Patients with chronic kidney disease (CKD) are particularly at high risk of polypharmacy and use of potentially inappropriate medications given the numerous risk factors and complications associated with CKD. The aim of this systematic review will be to assess the prevalence of polypharmacy among adult patients with CKD, and the potential association between polypharmacy and adverse health outcomes within this population. Methods/design We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL, Web of Science, and PsycINFO and grey literature from inception onwards (with no language restrictions) for observational studies (e.g., cross-sectional or cohort studies) reporting the prevalence of polypharmacy in adult patients with CKD (all stages including dialysis). Two reviewers will independently screen all citations, full-text articles, and extract data. Potential conflicts will be resolved through discussion. The study methodological quality will be appraised using an appropriate tool. The primary outcome will be the prevalence of polypharmacy. Secondary outcomes will include any adverse health outcomes (e.g., worsening kidney function) in association with polypharmacy. If appropriate, we will conduct random effects meta-analysis of observational data to summarize the pooled prevalence of polypharmacy and the associations between polypharmacy and adverse outcomes. Statistical heterogeneity will be estimated using Cochran’s Q and I2 index. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., sex, kidney replacement therapy, multimorbidity). Discussion Given that polypharmacy is a major and a growing public health issue, our findings will highlight the prevalence of polypharmacy, hazards associated with it, and medication thresholds associated with adverse outcomes in patients with CKD. Our study will also draw attention to the prognostic importance of improving medication practices as a key priority area to help minimize the use of inappropriate medications in patients with CKD. Systematic review registration PROSPERO registration number: [ CRD42020206514 ]

Prevalence and Demographics of CKD in Canadian Primary Care Practices: A Cross-sectional Study.

INTRODUCTION: Surveillance systems enable optimal care delivery and appropriate resource allocation, yet Canada lacks a dedicated surveillance system for chronic kidney disease (CKD). Using data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), a national chronic disease surveillance system, this study describes the geographic, sociodemographic, and clinical variations in CKD prevalence in the Canadian primary care context. METHODS: This cross-sectional study included 559,745 adults in primary care in 5 provinces across Canada from 2010 through 2015. Data were analyzed by geographic (urban or rural residence), sociodemographic (age, sex, deprivation index), and clinical (medications prescribed, comorbid conditions) factors, using data from CPCSSN and the Canadian Deprivation Index. CKD stage 3 or higher was defined as 2 estimated glomerular filtration rate (eGFR) values of <60 ml/min per 1.73 m2 more than 90 days apart as of January 1, 2015. RESULTS: Prevalence of CKD was 71.9 per 1000 individuals and varied by geography, with the highest prevalence in rural settings compared with urban settings (86.2 vs. 68.4 per 1000). CKD was highly prevalent among individuals with 3 or more other chronic diseases (281.7 per 1000). Period prevalence of CKD indicated a slight decline over the study duration, from 53.4 per 1000 in 2010 to 46.5 per 1000 in 2014. CONCLUSION: This is the first study to estimate the prevalence of CKD in primary care in Canada at a national level. Results may facilitate further research, prioritization of care, and quality improvement activities to identify gaps and improvement in CKD care

Gene Expression Profile of Neuronal Progenitor Cells Derived from hESCs: Activation of Chromosome 11p15.5 and Comparison to Human Dopaminergic Neurons

BACKGROUND: We initiated differentiation of human embryonic stem cells (hESCs) into dopamine neurons, obtained a purified population of neuronal precursor cells by cell sorting, and determined patterns of gene transcription. METHODOLOGY: Dopaminergic differentiation of hESCs was initiated by culturing hESCs with a feeder layer of PA6 cells. Differentiating cells were then sorted to obtain a pure population of PSA-NCAM-expressing neuronal precursors, which were then analyzed for gene expression using Massive Parallel Signature Sequencing (MPSS). Individual genes as well as regions of the genome which were activated were determined. PRINCIPAL FINDINGS: A number of genes known to be involved in the specification of dopaminergic neurons, including MSX1, CDKN1C, Pitx1 and Pitx2, as well as several novel genes not previously associated with dopaminergic differentiation, were expressed. Notably, we found that a specific region of the genome located on chromosome 11p15.5 was highly activated. This region contains several genes which have previously been associated with the function of dopaminergic neurons, including the gene for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, IGF2, and CDKN1C, which cooperates with Nurr1 in directing the differentiation of dopaminergic neurons. Other genes in this region not previously recognized as being involved in the functions of dopaminergic neurons were also activated, including H19, TSSC4, and HBG2. IGF2 and CDKN1C were also found to be highly expressed in mature human TH-positive dopamine neurons isolated from human brain samples by laser capture. CONCLUSIONS: The present data suggest that the H19-IGF2 imprinting region on chromosome 11p15.5 is involved in the process through which undifferentiated cells are specified to become neuronal precursors and/or dopaminergic neurons

Primary care provider perceptions of enablers and barriers to following guideline-recommended laboratory tests to confirm chronic kidney disease: a qualitative descriptive study

Abstract Background Patients should receive follow-up serum creatinine tests after an initial abnormal result to diagnose chronic kidney disease. However, half of the time this fails to occur in primary care. We interviewed primary care providers to better understand their perceptions of enablers and barriers to following this guideline-recommended care. Methods We performed a qualitative descriptive study guided by the Theoretical Domains Framework (TDF), a framework for behavioural change. We used purposeful sampling to recruit primary care providers (physicians and nurse practitioners) based on provider and practice characteristics (rural, solo versus team practice, etc.) from Ontario, Canada. We completed one-on-one interviews with providers using a semi-structured and open-ended interview guide based on the 14 TDF domains. We alternated between data collection and analysis, where we used directed content analysis to identify frequent, important, and conflicting enablers and barriers. Results We completed 13 interviews with nine primary care physicians and four nurse practitioners. Nine themes related to the TDF emerged from the data: 1) environmental context and resources, 2) knowledge, 3) memory, attention, and decision processes, 4) beliefs about consequences, 5) goals, 6) social or professional role, 7) behavioural regulation, 8) skills, and 9) optimism. Within these themes, we identified 16 enablers and five barriers. Some enablers included, providers’ knowledge on appropriate testing, their motivation to order these tests, and their use of tools and resources to help order follow-up serum creatinine tests. However, providers perceived some barriers including that ordering confirmatory laboratory tests for chronic kidney disease was not always a priority in regards to other care they wish to provide. Providers also noted that a perceived barrier is patients not going to the laboratory to complete the test. Conclusions We identified novel enablers and barriers to primary care providers completing guideline recommended repeat testing for the diagnosis of chronic kidney disease. Similar research is needed to understand the views of patients. These research findings can be used to inform strategies to improve the quality of care

Risk Factors for Unplanned Dialysis Initiation: A Systematic Review of the Literature

Background: Unplanned dialysis initiation is common in patients with chronic kidney disease (CKD). Objective: To determine common definitions and patient risk factors for unplanned dialysis. Design: Systematic review. Setting: MEDLINE, EMBASE, and the Cochrane Library were searched from inception to February 2018. Patients: Studies that included incident chronic dialysis patients or patients with CKD that cited a definition or examined risk factors for unplanned dialysis were included. Measurements: Definitions and criteria for unplanned dialysis reported across studies. Patient characteristics associated with unplanned dialysis. Methods: Two reviewers independently extracted data using a standardized data abstraction form and assessed study quality using a modified New Castle Ottawa Scale. Results: From 2797 citations, 48 met eligibility criteria. Reported definitions for unplanned dialysis were variable. Most publications cited dialysis initiation under emergency conditions and/or with a central venous catheter. The association of patient characteristics with unplanned dialysis was reported in 26 studies, 18 were retrospective and 21 included incident dialysis patients. The most common risk factors in univariate analyses were (number of studies) increased age (n = 7), cause of kidney disease (n = 6), presence of cardiovascular disease (n = 7), lower serum hemoglobin (n = 9), lower serum albumin (n = 10), higher serum phosphate (n = 6), higher serum creatinine or lower estimated glomerular filtration rate (eGFR) at dialysis initiation (n = 7), late referral (n = 5), lack of dialysis education (n = 6), and lack of follow-up in a predialysis clinic prior to dialysis initiation (n = 5). A minority of studies performed multivariable analyses (n = 10); the most common risk factors were increased age (n = 4), increased comorbidity score (n = 3), late referral (n = 5), and lower eGFR at dialysis initiation (n = 3). Limitations: Comparison of results across studies was limited by inconsistent definitions for unplanned dialysis. High-quality data on patient risk factors for unplanned dialysis are lacking. Conclusions: Well-designed prospective studies to determine modifiable risk factors are needed. The lack of a consensus definition for unplanned dialysis makes research and quality improvement initiatives in this area more challenging