Evolution of Exchangeable Copper and Relative Exchangeable Copper through the Course of Wilson's Disease in the Long Evans Cinnamon Rat

Background

Wilson''s disease (WD) is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC) has recently been described as a reliable serum diagnostic marker for WD.

Methodology/Principal Findings

The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC), total serum copper and REC) and acute liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat under normal food developed acute liver failure (ALF), with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats.

Conclusions/Significance

REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload.     

Relevance of blood groups in transfusion of sickle cell disease patients

Blood groups are clinically significant in sickle cell disease (SCD) as transfusion remains a key treatment in this pathology. The occurrence of a delayed haemolytic transfusion reaction (DHTR) is not rare and is a life-threatening event. The main cause of DHTR is the production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in SCD patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, DHTR in SCD patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of DHTR, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available.     

A white side of black Britain: The concept of racial literacy

Opposition to transracial adoption on both sides of the Atlantic, has been based, in part, on the assumption that white parents cannot understand race or racism and thus cannot properly prepare children of multiracial heritage to cope with racism. In this article I draw on a seven-year ethnographic study to offer an intensive case study of white transracial birth parents that counters this racial logic. I draw on a subset of data collected from field research and in-depth interviews with 102 members of black-white interracial families in England. I provide an analysis of three practices that I discovered among white transracial birth parents who were attempting to cultivate ‘black’ identities in their children of multiracial heritage. I offer the concept of ‘racial literacy’ to theorize their parental labour as a type of anti-racist project that remains under the radar of conventional sociological analyses of racism and anti-racist social movements.     

Importance of the methyl-citrate cycle on glycerol metabolism in the yeast Yarrowia lipolytica

A novel approach to trigger lipid accumulation and/or citrate production in vivo through the inactivation of the 2-methyl-citrate dehydratase in Yarrowia lipolytica was developed. In nitrogen-limited cultures with biodiesel-derived glycerol utilized as substrate, the Δphd1 mutant (JMY1203) produced 57.7 g/L of total citrate, 1.6-fold more than the wild-type strain, with a concomitant glycerol to citrate yield of 0.91 g/g. Storage lipid in cells increased at the early growth stages, suggesting that inactivation of the 2-methyl-citrate dehydratase would mimic nitrogen limitation. Thus, a trial of JMY1203 strain was performed with glycerol under nitrogen-excess conditions. Compared with the equivalent nitrogen-limited culture, significant quantities of lipid (up to ∼31% w/w in dry weight, 1.6-fold higher than the nitrogen-limited experiment) were produced. Also, non-negligible quantities of citric acid (up to ∼26 g/L, though 0.57-fold lower than the nitrogen-limited experiment) were produced, despite remarkable nitrogen presence into the medium, indicating the construction of phenotype that constitutively accumulated lipid and secreted citrate in Y. lipolytica during growth on waste glycerol utilized as substrate.     

Impact of DECISION + 2 on patient and physician assessment of shared decision making implementation in the context of antibiotics use for acute respiratory infections

Background

DECISION?+?2, a training program for physicians, is designed to implement shared decision making (SDM) in the context of antibiotics use for acute respiratory tract infections (ARTIs). We evaluated the impact of DECISION?+?2 on SDM implementation as assessed by patients and physicians, and on physicians’ intention to engage in SDM.

Methods

From 2010 to 2011, a multi-center, two-arm, parallel randomized clustered trial appraised the effects of DECISION?+?2 on the decision to use antibiotics for patients consulting for ARTIs. We randomized 12 family practice teaching units (FPTUs) to either DECISION?+?2 or usual care. After the consultation, both physicians and patients independently completed questionnaires based on the D-Option scale regarding SDM behaviors during the consultation. Patients also answered items assessing the role they assumed during the consultation (active/collaborative/passive). Before and after the intervention, physicians completed a questionnaire based on the Theory of Planned Behavior to measure their intention to engage in SDM. To account for the cluster design, we used generalized estimating equations and generalized linear mixed models to assess the impact of DECISION?+?2 on the outcomes of interest.

Results

A total of 270 physicians (66% women) participated in the study. After DECISION?+?2, patients’ D-Option scores were 80.1?±?1.1 out of 100 in the intervention group and 74.9?±?1.1 in the control group (p?=?0.001). Physicians’ D-Option scores were 79.7?±?1.8 in the intervention group and 76.3?±?1.9 in the control group (p?=?0.2). However, subgroup analyses showed that teacher physicians D-Option scores were 79.7?±?1.5 and 73.0?±?1.4 respectively (p?=?0.001). More patients reported assuming an active or collaborative role in the intervention group (67.1%), than in the control group (49.2%) (p?=?0.04). There was a significant relation between patients’ and physicians’ D-Option scores (p?<?0.01) and also between patient-reported assumed roles and both D-Option scores (as assessed by patients, p?<?0.01; and physicians, p?=?0.01). DECISION?+?2 had no impact on the intention of physicians to engage in SDM.

Conclusion

DECISION?+?2 positively influenced SDM behaviors as assessed by patients and teacher physicians. Physicians’ intention to engage in SDM was not affected by DECISION?+?2.

Trial registration

ClinicalTrials.gov trials register no. NCT01116076.

     

Organizational readiness for knowledge translation in chronic care: a review of theoretical components

Background

With the persistent gaps between research and practice in healthcare systems, knowledge translation (KT) has gained significance and importance. Also, in most industrialized countries, there is an increasing emphasis on managing chronic health conditions with the best available evidence. Yet, organizations aiming to improve chronic care (CC) require an adequate level of organizational readiness (OR) for KT.Objectives: The purpose of this study is to review and synthesize the existing evidence on conceptual models/frameworks of Organizational Readiness for Change (ORC) in healthcare as the basis for the development of a comprehensive framework of OR for KT in the context of CC.

Data sources

We conducted a systematic review of the literature on OR for KT in CC using Pubmed, Embase, CINAHL, PsychINFO, Web of Sciences (SCI and SSCI), and others. Search terms included readiness; commitment and change; preparedness; willing to change; organization and administration; and health and social services.Study selection: The search was limited to studies that had been published between the starting date of each bibliographic database (e.g., 1964 for PubMed) and November 1, 2012. Only papers that refer to a theory, a theoretical component from any framework or model on OR that were applicable to the healthcare domain were considered. We analyzed data using conceptual mapping.Data extraction: Pairs of authors independently screened the published literature by reviewing their titles and abstracts. Then, the two same reviewers appraised the full text of each study independently.

Results

Overall, we found and synthesized 10 theories, theoretical models and conceptual frameworks relevant to ORC in healthcare described in 38 publications. We identified five core concepts, namely organizational dynamics, change process, innovation readiness, institutional readiness, and personal readiness. We extracted 17 dimensions and 59 sub-dimensions related to these 5 concepts.

Conclusion

Our findings provide a useful overview for researchers interested in ORC and aims to create a consensus on the core theoretical components of ORC in general and of OR for KT in CC in particular. However, more work is needed to define and validate the core elements of a framework that could help to assess OR for KT in CC.

     

Understanding Providers’ Offering and Patients’ Acceptance of HIV Screening in Emergency Departments: A Multilevel Analysis. ANRS 95008, Paris,France

Objective

We assessed the EDs’ characteristics associated with the offer and acceptance rates of a nontargeted HIV rapid-test screening in 29 Emergency Departments (EDs) in the metropolitan Paris region (11.7 million inhabitants), where half of France’s new HIV cases are diagnosed annually.

Methods

EDs nurses offered testing to all patients 18–64-year-old, able to provide consent, either with or without supplemental staff (hybrid staff model or indigenous staff model). The EDS’ characteristics collected included structural characteristics (location, type, size), daily workload (patients’ number and severity, length of stay in hours), staff’s participation (training, support to the intervention, leadership), type of week day (weekends vs weekdays) and time (in days). Associations between these variables and the staff model, the offer and acceptance rates were studied using multilevel modeling.

Results

Indigenous staff model was more frequent in EDs with a lower daily patient flow and a higher staff support score to the intervention. In indigenous-model EDs, the offer rate was associated with the patient flow (OR = 0.838, 95% CI = 0.773–0.908), was lower during weekends (OR = 0.623, 95% CI = 0.581–0.667) and decreased over time (OR = 0.978, 95% CI = 0.975–0.981). Similar results were found in hybrid-model EDs. Acceptance was poorly associated with EDs characteristics in indigenous-model EDs while in hybrid-model EDs it was lower during weekends (OR = 0.713, 95% CI = 0.623–0.816) and increased after the first positive test (OR = 1.526, 95% CI = 1.142–2.038).The EDs’ characteristics explained respectively 38.5% and 15% of the total variance in the offer rate across indigenous model-EDs and hybrid model-EDs vs 12% and 1% for the acceptance rate.

Conclusion

Our findings suggest the need for taking into account EDs’ characteristics while considering the implementation of an ED-based HIV screening program. Strategies allowing the optimization of human resources’ utilization such as HIV targeted screening in the EDs might be privileged.     

Abrupt Decline in Tuberculosis among Foreign-Born Persons in the United States

While the number of reported tuberculosis (TB) cases in the United States has declined over the past two decades, TB morbidity among foreign-born persons has remained persistently elevated. A recent unexpected decline in reported TB cases among foreign-born persons beginning in 2007 provided an opportunity to examine contributing factors and inform future TB control strategies. We investigated the relative influence of three factors on the decline: 1) changes in the size of the foreign-born population through immigration and emigration, 2) changes in distribution of country of origin among foreign-born persons, and 3) changes in the TB case rates among foreign-born subpopulations. Using data from the U.S. National Tuberculosis Surveillance System and the American Community Survey, we examined TB case counts, TB case rates, and population estimates, stratified by years since U.S. entry and country of origin. Regression modeling was used to assess statistically significant changes in trend. Among foreign-born recent entrants (<3 years since U.S. entry), we found a 39.5% decline (-1,013 cases) beginning in 2007 (P<0.05 compared to 2000–2007) and ending in 2011 (P<0.05 compared to 2011–2014). Among recent entrants from Mexico, 80.7% of the decline was attributable to a decrease in population, while the declines among recent entrants from the Philippines, India, Vietnam, and China were almost exclusively (95.5%–100%) the result of decreases in TB case rates. Among foreign-born non-recent entrants (≥3 years since U.S. entry), we found an 8.9% decline (-443 cases) that resulted entirely (100%) from a decrease in the TB case rate. Both recent and non-recent entrants contributed to the decline in TB cases; factors contributing to the decline among recent entrants varied by country of origin. Strategies that impact both recent and non-recent entrants (e.g., investment in overseas TB control) as well as those that focus on non-recent entrants (e.g., expanded targeted testing of high-risk subgroups among non-recent entrants) will be necessary to achieve further declines in TB morbidity among foreign-born persons.     

Sperm number assessed by flow cytometry in species of Daphnia (Crustacea,Cladocera)

Daphnia magna and Daphnia pulex are two important model species in ecotoxicology. In daphniids, studies of the effects of contaminants have mostly focused on female life history traits, yet it would also be important to examine male reproductive traits, particularly in relation to endocrine disruptors. In this study, we developed a protocol that uses flow cytometry to measure sperm number in individual males of different species of Daphnia. We tested our protocol on 114 males from several clones of three common species of Daphnia. Sperm count varied widely among individuals and reached high numbers (up to 1.45 × 10⁵). Positive relationships between male length and sperm number were observed in D. pulex and Daphnia pulicaria, but not in D. magna. Important inter‐clonal differences in sperm production were observed in all species, with some clones producing very little sperm. Duplicated sperm samples showed on average only 6% difference in sperm counts. Sperm counts were stable at least over a 2‐hr period and up to 5 hr for most samples. This sperm isolation protocol and flow cytometric enumeration approach will be of major interest to ecotoxicologists.