The twin arginine translocation system is essential for virulence of Yersinia pseudotuberculosis

Yersinia species pathogenic to humans have been extensively characterized with respect to type III secretion and its essential role in virulence. This study concerns the twin arginine translocation (Tat) pathway utilized by gram-negative bacteria to secrete folded proteins across the bacterial inner membrane into the periplasmic compartment. We have shown that the Yersinia Tat system is functional and required for motility and contributes to acid resistance. A Yersinia pseudotuberculosis mutant strain with a disrupted Tat system (tatC) was, however, not affected in in vitro growth or more susceptible to high osmolarity, oxidative stress, or high temperature, nor was it impaired in type III secretion. Interestingly, the tatC mutant was severely attenuated via both the oral and intraperitoneal routes in the systemic mouse infection model and highly impaired in colonization of lymphoid organs like Peyer's patches and the spleen. Our work highlights that Tat secretion plays a key role in the virulence of Y. pseudotuberculosis.     

Environmental assessment of Norwegian priority pharmaceuticals based on the EMEA guideline

An environmental risk assessment of eleven pharmaceuticals according to the guideline recommended by the European Medicines Evaluation Agency (EMEA) was performed. Cefuroxime, ciprofloxacin, cyclophosphamide, diclofenac, ethinylestradiol, ibuprofen, metoprolol, paracetamol, sulfamethoxazole, tetracycline and trimethoprim were selected for assessment by the Norwegian Pollution Control Authority. Predicted environmental concentrations (PECs) were calculated according to both the EMEA guideline and a conventional model for comparison and ranged from 0.0002 to 45 microg/L. Available acute and chronic toxicity data were collected from the literature, although no data were available for cyclophosphamide. Toxicity tests showed cyclophosphamide to have relatively low acute toxicity with an EC50 for Pseudokirchneriella subcapitata >100 mg/L and a Daphnia magna reproduction NOEC of 56 mg/L. These and the literature data were used to derive predicted no effect concentrations (PNEC). Risk quotients (PEC/PNEC) were then calculated for all 11 pharmaceutical compounds. Risk quotients greater than 1 were obtained for ciprofloxacin, diclofenac, ethinylestradiol, sulfamethoxazole and tetracycline according to the EMEA guideline. Measured environmental concentrations (MECs) confirmed that the release of ciprofloxacin from wastewater treatment works may potentially be of environmental concern in Norway.     

Risk of violence among patients in psychiatric treatment: results from a national census

Background: Adverse media coverage of isolated incidents affects the public perception of the risk of violent behavior among people with mental illness. However, the risk of violence is studied most frequently among inpatients, which falsely exaggerates the prevalence of people with mental illness because the majority of individuals receive treatment as outpatients.

Aim: To estimate the prevalence of the risk of violence among inpatients and outpatients in psychiatric treatment, as well as the associations with gender, age, socio-economic status and co-morbid substance use disorders in all major diagnostic categories.

Methods: We conducted a national census of patients in specialist mental health services in Norway, which included 65% of all inpatients (N?=?2,358) and 60% of all outpatients (N?=?23,124).

Results: The prevalence of the risk of violence was 32% among inpatients and 8% among outpatients, where 80% of the patients in specialist mental health services were outpatients. If we weight the prevalence rates accordingly, less than 2% of the patients in specialist mental health services had a high risk of violent behavior.

Conclusions: The stigma attached to those with mental illness is not consistent with the absence or low to modest risk of violent behavior in 98% of the patient group. Substance use disorders must be given priority in the treatment of all patient groups. Mental health care in general and interventions that target violent behavior in particular should address the problems and needs of these patients better, especially those who are unemployed, have a low level of education and have a background of being a refugee or an immigrant.     

Prospective trial comparing full-field digital mammography (FFDM) versus combined FFDM and tomosynthesis in a population-based screening programme using independent double reading with arbitration

Objectives

To compare double readings when interpreting full field digital mammography (2D) and tomosynthesis (3D) during mammographic screening.

Methods

A prospective, Ethical Committee approved screening study is underway. During the first year 12,621 consenting women underwent both 2D and 3D imaging. Each examination was independently interpreted by four radiologists under four reading modes: Arm A—2D; Arm B—2D?+?CAD; Arm C—2D?+?3D; Arm D—synthesised 2D?+?3D. Examinations with a positive score by at least one reader were discussed at an arbitration meeting before a final management decision. Paired double reading of 2D (Arm A?+?B) and 2D?+?3D (Arm C?+?D) were analysed. Performance measures were compared using generalised linear mixed models, accounting for inter-reader performance heterogeneity (P?<?0.05).

Results

Pre-arbitration false-positive scores were 10.3 % (1,286/12,501) and 8.5 % (1,057/12,501) for 2D and 2D?+?3D, respectively (P?<?0.001). Recall rates were 2.9 % (365/12,621) and 3.7 % (463/12,621), respectively (P?=?0.005). Cancer detection was 7.1 (90/12,621) and 9.4 (119/12,621) per 1,000 examinations, respectively (30 % increase, P?<?0.001); positive predictive values (detected cancer patients per 100 recalls) were 24.7 % and 25.5 %, respectively (P?=?0.97). Using 2D?+?3D, double-reading radiologists detected 27 additional invasive cancers (P?<?0.001).

Conclusion

Double reading of 2D?+?3D significantly improves the cancer detection rate in mammography screening.

Key Points

? Tomosynthesis-based screening was successfully implemented in a large prospective screening trial. ? Double reading of tomosynthesis-based examinations significantly reduced false-positive interpretations. ? Double reading of tomosynthesis significantly increased the detection of invasive cancers.     

THROMBOTIC EFFECTS OF ASPARAGINASE IN TWO ACUTE LYMPHOBLASTIC LEUKEMIA PROTOCOLS (NOPHO ALL-1992 VERSUS NOPHO ALL-2000): A Single-Institution Study

Asparaginase is essential in the treatment of lymphoproliferative malignancies, but it is associated with several side effects. The objective of this study was to compare asparaginase-induced alterations of the coagulation inhibitors and the impact on central line-associated thrombosis in children treated according to 2 different asparaginase regimens. The study enrolled 30 children treated for acute lymphoblastic leukemia, and they were divided into 2 groups with respect to asparaginase preparation and protocol (NOPHO ALL-1992 versus NOPHO ALL-2000). The coagulation inhibitors antithrombin, protein C, and proteins S were measured prior to and during asparaginase therapy, and incidence of central line-associated thromboses was compared to evaluate the protocols' thrombogenicity. Thirteen children received Erwinia asparaginase and 17 children received E. coli asparaginase. Independent of protocol, the coagulation inhibitors were significantly reduced during asparaginase therapy (p < .001), and central line-associated thromboses were frequent. Four children developed thrombosis in the course of asparaginase therapy, and there was a correlation between asparaginase-induced fall of antithrombin and occurrence of new thromboses (p = .01).     

Influence of Friends on Children’s Physical Activity: A Review

We examined evidence for friendship influences on children''s physical activity (PA) through systematic searches of online databases in May 2012. We identified 106 studies (25 qualitative) published in English since 2000 that analyzed indicators of friendship influences (e.g., communication about PA, friends’ PA, and PA with friends) among persons younger than 19 years.Children''s PA was positively associated with encouragement from friends (43 of 55 studies indicating a positive relationship), friends'' own PA (30/35), and engagement with friends in PA (9/10). These findings are consistent with friends influencing PA, but most studies did not isolate influence from other factors that could explain similarity.Understanding friendship influences in childhood can facilitate the promotion of lifelong healthy habits. PA with friends should be considered in health promotion programs.Extensive research has linked physical activity to health and inactivity to poor health, especially to obesity and other cardiometabolic problems such as diabetes and cardiovascular disease.1–3 Increases in overweight, obesity, diabetes, and metabolic syndrome among children and adolescents over the past few decades4–7 have stimulated a surge of research into possible contributing factors, including insufficient physical activity.8–10In spite of its health benefits, physical activity is declining around the world.11 In the United States, levels of physical activity in children and adolescents are not sufficient to promote optimal health.12 The Centers for Disease Control and Prevention recommends that children and adolescents be active for at least 60 minutes per day, but in 2009, only 18.4% of adolescents reported this much physical activity and 23.1% of adolescents reported not participating in 60 minutes of physical activity on any day.13,14A factor that may affect health behaviors that has received increasing attention in recent years is social influence. Research has suggested that family, friends, and peers can guide behaviors such as smoking, sexual initiation, and eating behaviors.15–19 Influences from these close contacts can occur through social pressure, social modeling and imitation, social comparison, and behavior approximation.20 However, not all social relations are equally important: the closer and stronger the connection, the broader and stronger the possibilities for influence.21,22 Information transmitted from friends is generally more clearly understood and more likely to be internalized than is information from others, meaning that friends may be more influential than other social contacts,23–26 such as cliques and peer groups.24,27,28Although social influences on physical activity can occur throughout life, they are particularly important to study in children and adolescents, for several reasons. First, childhood and adolescence are a formative period when friends are a primary point of reference29,30 in deciding which behaviors, values, and attitudes are desirable and which activities warrant effort.31–34 Friends have been shown to affect timing of first sexual intercourse, drug use, delinquency, and educational attainment among adolescents.31,32,35–42 Second, physical activity tracks across life: activity levels during adolescence predict adult levels, and active children and adolescents are more likely to become active adults.43 Third, physical activity often decreases during adolescence, so children and adolescents may be the most important age groups to target for interventions to establish lifelong activity levels.44 Finally, the development of successful interventions to increase physical activity in children and adolescents requires an understanding of the unique determinants of physical activity at these ages.Quantifying the extent to which friends can promote or discourage physical activity is critical for understanding why physical activity levels are decreasing and for developing strategies to promote active lifestyles. We reviewed the literature to determine the role of friends in shaping physical activity among children and adolescents.     

Mammographic Density and Intake of Selected Nutrients and Vitamins in Norwegian Women

Investigating the association between dietary factors and mammographic density (MD) could shed light on the relationship between diet and breast cancer risk. We took advantage of a national mammographic screening program to study the association between intake of nutrients and MD. In this study, we analyzed data of 2,252 postmenopausal women aged 50–69 yr who participated in the Norwegian Breast Cancer Screening Program in 2004. MD was assessed on digitized mammograms using a computer-assisted method. We used multivariate linear regression models to determine least square means of percent and absolute MD. Overall, we observed no associations between MD and intake of total calories, protein, carbohydrates, cholesterol, and dietary fiber. There was a positive borderline statistically significant association between absolute MD and total fat intake (P = 0.10) and between percent MD and intake of saturated fat (P = 0.06). There was no association between MD and intake of calcium, retinol, vitamins A, B12, C, or D, or combined intake of vitamin D and calcium. This study provides some evidence of an association between MD and dietary intake. Our study highlights the importance of adequate adjustments for BMI in studies of diet and MD.     

Life satisfaction in early rheumatoid arthritis: A prospective study

The aim of this study was to describe life satisfaction prospectively in patients with early rheumatoid arthritis (RA) and to investigate its correlation with disease activity. The early RA group was compared with RA patients with longstanding disease and with a reference group. Gender differences were also compared. Patients with early RA, treated by a multidisciplinary team, reported their life satisfaction by completing a questionnaire. Disease activity score, patient global assessment, and pain were scored at onset of disease and after two years. The patients with early RA were less satisfied with life as a whole at disease onset compared with the reference group, as was a cohort of patients with longstanding disease. Patients with early RA also reported low levels of satisfaction with self-care activities, work, and sexual life. The women reported themselves more satisfied than men. After two years, a slight increase in the reported levels of satisfaction could be seen for life as a whole and for five of the eight domains. No correlation was found between disease activity variables and satisfaction with life as a whole. There were, however, positive correlations between disease activity and satisfaction both with partnership and with family life after two years, i.e. the higher disease activity the higher satisfaction with partnership relation and family life. In contrast, patients with greater disease activity were less satisfied with self-care activities. The results of this study indicate that greater effort is needed to assist patients with early RA to cope with problems concerning self-care activities, sexual life, and work.