Recombinant congenic strains of mice from B10.D2 and DBA/2: Their contribution to behavior genetic research and application to audiogenic seizures

Recombinant congenic strains (RCS) represent a series of related strains, each of which carries a small fraction of the genome of one strain (donor strain) on the genetic background of another strain (background strain). Recombinant inbred strains (RIS) are commonly used to identify major gene segregation and linkage and associations between behavior and quantitative trait loci, whereas recombinant congenic strains (RCS) open other complementary leads. The variability in the reactivity of RCS to a trait is thus the expression of few minor-effect genes originating from the donor strain, because the probability that major genes are present in any one RCS is low. Unlike RIS in which minor-effect genes are often masked by major genes, RCS enable the effects of minor genes to be studied. With our method, for a given trait, an estimate can be made of the gene strength distribution as well as an estimate of the minimal number of genes involved having a certain strength.This study was supported by the Centre National de la Recherche Scientifique (URA 1924 and CSEAL-UPS 44, CNRS), Université René-Descartes, Paris V UFR Biomédicale, and the Fondation pour la Recherche Médicale.     

In vivo efficacy of cefotaxime and amoxicillin against penicillin-susceptible, penicillin-resistant and penicillin-cephalosporin-resistant strains of Streptococcus pneumoniae in a mouse pneumonia model

Objective: To compare cefotaxime (CTX) to amoxicillin (AMO) (usually considered the definitive therapy for penicillinsusceptible Streptococcus pneumoniae infections) in an immunocompromised mouse pneumonia model.
Methods: Three S. pneumoniae clinical isolates were used: two serotype 19 strains, a penicillin-susceptible (P^s) strain (penicillin MIC = 0.03 μ/mL) and a highly penicillin-resistant (P^r) strain (penicillin MIC = 4 μ/mL), and one serotype 23F strain, a penicillin-cephalosporin-resistant (CFTR) strain (CTX MIC = 4 μ/mL).
Results: CTX activity in this mouse model of pneumonia induced by the highly penicillin-resistant strain of S. pneumoniae was lower than expected from its low MIC against this organism. Furthermore, AMO had greater efficacy than CTX against a CFTR S. pneumoniae strain.
Conclusion: Our data suggest that there is no major difference in the in vivo efficacy of the two agents, cefotaxime and amoxicillin, against penicillin-resistant and penicillin-cephalosporin-resistant S. pneumoniae.     

Cytotoxic properties of a new synthetic demethylpodophyllotoxin derivative,BN 58705, against human tumor cell lines

The in vitro cytotoxic properties of a newly synthesized demethylpodophyllotoxin derivative, 4-o-butanoyl-4-demethylpodophyllotoxin (BN 58705), were determined by using several human tumor cell lines of different histological origin and of different sensitivity to conventional chemotherapeutic drugs (Adriamycin andcis-diammine-dichloride platinum). BN 58705 is shown to be cytotoxic against various human tumor cell lines as assessed by the MTT assay. Furthermore, BN 58705 is shown to be cytotoxic against several drug-resistant tumor cell lines. BN 58705 is cytotoxic at concentrations 100- to 1000-fold lower than those of Adriamycin orcis-diammine-dichloride platinum required to achieve similar cytotoxicity. BN 58705 did not mediate DNA fragmentation of target cells, whereas the epipodophyllotoxin-like etoposide induced DNA cleavage by stabilizing the DNA-enzyme intermediate. Like vinca alkaloids, BN 58705 induced a block in the mitotic phase of the cell cycle. By comparison, BN 58705 exerted a stronger cytotoxic activity in vitro than did either etoposide, an epipodophyllotoxin, or vincristine, a vinca alkaloid. When BN 58705 was applied in vivo in mice, it resulted in low toxicity (50% lethal dose, 150 mg/kg). These results demonstrate than BN 58705 is cytotoxic to drug-resistant human tumor cell lines and is manyfold more potent than conventional drugs. The cytotoxic potency and low toxicity of BN 58705 are important criteria to establish its potential chemotherapeutic efficacy in vivo.Abbreviations cpm counts per minute - BN 58705 4-o-butanoyl-4-demethylpodophyllotoxin - MTT 3-(4,5-dimethyl-thiazoyl-2-yl)-2,5-diphenyl-tetrazolium bromide - OD optical density - TRIS TRIS (hydroxymethyl) aminomethane - EDTA ethylenediaminetetraacetic acid - FITC fluoresceinisothiocyanate - PI propidium iodide This work was supported by a grant from Institut Henri Beaufour, France     

Wagner vitreoretinal degeneration with genetic linkage refinement on chromosome 5q13-q14

· Background: It has been previously described that Wagner disease is linked to chromosome 5q13-q14. This study was carried out to describe the ophthalmological aspects and report the results of genetic linkage analysis in a large pedigree affected by Wagner disease. · Methods: Fourty members of one same family agreed to be examined. · Results: Twenty patients presented vitreoretinal degeneration in both eyes without any extra-ocular abnormalities. In young patients, visual acuity was usually normal after correction of frequent mild myopia. Presenile cataracts progressed by the third decade and required removal for visual rehabilitation. The primary disorder involved an abnormal vitreous. A few avascular vitreous bands were usually the only optical feature in the mostly empty vitreous cavity. A circumferential vitreous condensation formed in contact with the retina on many spots. Less common retinal findings included retinal detachment, abnormal retinal pigmentation, progressive atrophy of the RPE simulating choroideremia and lattice degeneration. Genetic analysis revealed a highly significant linkage (lod score >5.0) between the disease and 10 markers of the chromosome 5q13-q14 region. Two recombination events allowed us to refine the linked interval to 20 cM between the D5S650 and D5S618 markers. · Conclusion: Ophthalmological aspects of Wagner’s disease appear to progress with age. Regular ophthalmological examination is important for detecting retinal abnormalities. The gene involved in Wagner’s disease lies in a 20 cM interval on chromosome 5q13-q14. Received: 30 June 1998 Revised version received: 5 October 1998 Accepted: 6 October 1998     

Prevalence of depression in coronary heart disease in China: a systematic review and meta-analysis

Background Coronary heart diseases （CHD） have been identified as one of topmost diseases affecting the Chinese population.However,depression in CHD has not been reported and there are limited high quality empirical studies in China focused on the prevalence of the comorbidity.This study aimed to estimate the pooled prevalence of depression with CHD in China.Methods Systematic review and meta-analysis of published epidemiologic studies on the depression in CHD patients in China were conducted.The research findings dated before 30 September 2013 were obtained from Ovid Medline,EMBASE and two Chinese electronic publication libraries WANFANG and CNKI.We used ＂cardiovascular disease＂,＂depression＂ and ＂China＂ as the search themes in Ovid Medline and EMBASE and ＂cardiovascular disease＂ and ＂depression＂ in WANFANG and CNKI.Random-effects meta-analysis was used to estimate the prevalence of depression in CHD patients.Results Twenty-seven studies were included in the review.Twenty-three studies had 5 236 participants who were hospitalized and four studies had 1 353 participants from community.The overall prevalence of depression in CHD from hospital was 51% （95% CI：0.43,0.58; Ⅰ-squared=97%,P=-0.000）.The prevalence of depression in CHD from community ranged between 34.6% to 45.8%,and the severe depression was found ranging between 3.1% to 11.2%.Conclusions On comparing data with other countries,the prevalence of depression in CHD among admitted patients in China was found to be high.The physicians and healthcare providers should pay more attention to the ＂physical-mental＂ health of the CHD patients.     

从澳大利亚护理实践的演变看中国社区护理的发展(二)——中国社区护理的发展和挑战

目的从历史纵深角度,探讨我国护理的发展沿革及社区护理面临的严峻挑战,揭示阻碍社区护理发展的历史和文化渊源,从而为制定发展社区护理的政策,迎接老龄化社区卫生服务挑战,提供有意义的依据。方法以文献研究和政策分析作为主要的研究手段。结果中国的护士源于鸦片战争后医学传教士带来的西医技术医学体系,从传统的家庭护理一步跨入医院为中心的护理。然而机构内护理与东方文化传统的矛盾,医护比例的严重倒置,以及护理培训制度不健全,不但影响了医院护理质量,也使得社区护理资源奇缺。社区护理教育边缘化和人力发展严重滞后,是困扰我国社区卫生服务发展的主要障碍。结论大力发展社区护理是保证社区协调发展和满足人群健康需要的关键战略。我国的社区护理发展与其他国家一样,受到历史传承因素的影响,面临迅速增长的社区需要与发育不良的社区护理之间的矛盾,医学界和政府都应该从历史和文化的角度理解这个问题的背景,并从中获得启迪。     

Identifying Counseling Needs of Nulliparous Adolescent Intrauterine Contraceptive Users: A Qualitative Approach

PurposeTo describe the intrauterine contraception (IUC) adoption process among nulliparous adolescents and to identify the role of the medical provider in this trajectory.MethodsWe conducted semistructured interviews with a clinic-based sample of 20 nulliparous adolescents (aged 15–24 years) with a history of IUC use. Interviews were analyzed using modified grounded theory and cross-case analysis to reveal a process model for IUC adoption, with a focus on the role of the medical provider.ResultsThe model includes the following stages: first awareness, initial reaction, information gathering, adoption, and adjustment and reassessment. It is influenced by personal preferences and experiences, friends, family, sexual partner(s), and medical providers. Interactions with medical providers that study participants found helpful in navigating the adoption process included the use of visuals; tailored counseling to address specific contraceptive needs; assurance that IUC discontinuation was an option; information on a wide range of side effects; medical provider self-disclosure regarding use of IUC; and addressing and validating concerns, both before and after IUC insertion.ConclusionsNulliparous adolescents in this study described a complex IUC adoption process in which the medical provider plays a substantial supportive role. Findings from this study may be used to counsel and support future nulliparous adolescents regarding IUC use.     

Dietary patterns and risk for Crohn's disease in children

BACKGROUND: Some dietary foods are considered protective (vegetables and fruits), whereas others (fatty foods) are thought to enhance the risk for Crohn's disease (CD). The evidence, however, is inconsistent. METHODS: We postulated that specific dietary patterns may influence the risk for CD. A case-control study was carried out. Newly diagnosed CD cases with population and/or hospital-based controls < or =20 years were selected from 3 tertiary hospitals across Canada. Pre-disease diet was assessed using a validated food frequency questionnaire (FFQ) administered within 1 month of diagnosis. Factor analyses and unconditional logistic regression (adjusted) was used to determine gender-specific dietary patterns and assess associated risks for CD. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were estimated. RESULTS: A total of 149 cases and 251 controls were included. The mean age (range) of the cases was 13.3 (2.6-20 years). There were more boys (61.1%). Four dietary patterns each were observed among both boys and girls. Pattern 1 in girls, characterized by meats, fatty foods, and desserts, was positively associated with CD (OR 4.7, 95% CI 1.6-14.2). Pattern 2, common to both boys and girls, was characterized by vegetables, fruits, olive oil, fish, grains, and nuts and was inversely associated with CD in both genders (girls: OR 0.3, 95% CI 0.1-0.9; boys: OR 0.2, 95% CI 0.1-0.5). CONCLUSIONS: Our results suggest that specific dietary patterns could be associated with higher or lower risks for CD in children. Larger prospective studies are required to confirm these findings.     

Association of Roadway Proximity with Fasting Plasma Glucose and Metabolic Risk Factors for Cardiovascular Disease in a Cross-Sectional Study of Cardiac Catheterization Patients

Background

The relationship between traffic-related air pollution (TRAP) and risk factors for cardiovascular disease needs to be better understood in order to address the adverse impact of air pollution on human health.

Objective

We examined associations between roadway proximity and traffic exposure zones, as markers of TRAP exposure, and metabolic biomarkers for cardiovascular disease risk in a cohort of patients undergoing cardiac catheterization.

Methods

We performed a cross-sectional study of 2,124 individuals residing in North Carolina (USA). Roadway proximity was assessed via distance to primary and secondary roadways, and we used residence in traffic exposure zones (TEZs) as a proxy for TRAP. Two categories of metabolic outcomes were studied: measures associated with glucose control, and measures associated with lipid metabolism. Statistical models were adjusted for race, sex, smoking, body mass index, and socioeconomic status (SES).

Results

An interquartile-range (990 m) decrease in distance to roadways was associated with higher fasting plasma glucose (β = 2.17 mg/dL; 95% CI: –0.24, 4.59), and the association appeared to be limited to women (β = 5.16 mg/dL; 95% CI: 1.48, 8.84 compared with β = 0.14 mg/dL; 95% CI: –3.04, 3.33 in men). Residence in TEZ 5 (high-speed traffic) and TEZ 6 (stop-and-go traffic), the two traffic zones assumed to have the highest levels of TRAP, was positively associated with high-density lipoprotein cholesterol (HDL-C; β = 8.36; 95% CI: –0.15, 16.9 and β = 5.98; 95% CI: –3.96, 15.9, for TEZ 5 and 6, respectively).

Conclusion

Proxy measures of TRAP exposure were associated with intermediate metabolic traits associated with cardiovascular disease, including fasting plasma glucose and possibly HDL-C.

Citation

Ward-Caviness CK, Kraus WE, Blach C, Haynes CS, Dowdy E, Miranda ML, Devlin RB, Diaz-Sanchez D, Cascio WE, Mukerjee S, Stallings C, Smith LA, Gregory SG, Shah SH, Hauser ER, Neas LM. 2015. Association of roadway proximity with fasting plasma glucose and metabolic risk factors for cardiovascular disease in a cross-sectional study of cardiac catheterization patients. Environ Health Perspect 123:1007–1014; http://dx.doi.org/10.1289/ehp.1306980