Inhibition of mouse hepatocyte intercellular communication by phthalate monoesters

A series of straight and branched chain phthalate monoesters were examined for their effects on hepatocyte intercellular communication in male B6C3F1 mouse hepatocytes. Intercellular communication was determined autoradiographically following the passage and incorporation of [5-3H]uridine nucleotides from pre-labelled hepatocytes into non-labelled hepatocytes. Intercellular communication was evaluated in hepatocytes after 8 h treatment of straight and branched chain phthalate esters at sublethal concentrations. Straight chain phthalate monoesters (mono(ethyl)phthalate, mono(n-butyl) phthalate, mono(n-hexyl)phthalate, mono(n-octyl)phthalate, mono(n-nonyl)phthalate and mono(isononyl)phthalate) had no effect on hepatocyte intercellular communication. Branched chain phthalate monoesters that contained an ethylalkyl moiety (i.e. mono(2-ethylpropyl) phthalate, mono(2-ethylbutyl)phthalate, mono(2-ethylpentyl)-phthalate and mono(2-ethylhexyl)phthalate) inhibited intercellular communication. These results show a structure-activity relationship in the ability of phthalate monoesters to inhibit intercellular communication in mouse hepatocytes. Based upon previous correlations between inhibition of intercellular communication in hepatocytes and hepatocarcinogenicity, these data suggest that branched chain phthalate esters may be liver carcinogens in male B6C3F1 mice.     

Passive transfer of antibody to Ehrlichia risticii protects mice from ehrlichiosis.

Mice that recovered from Ehrlichia risticii infection were immune to a challenge dose of 100 50% lethal doses. Immune or normal mouse serum was passively transferred to mice challenged with E. risticii. Clinical signs of ehrlichiosis were completely prevented in 22 of 24 recipients of immune serum, and the onset of signs of illness was delayed in the remaining two mice compared with the onset of illness in 24 of 24 recipients of nonimmune serum. Purified immunoglobulin G (IgG) was used to passively protect mice from infection with E. risticii. All 15 mice that received IgG from normal serum but none of the 15 mice that received IgG from immune serum developed clinical signs of illness. Antibodies in immune mouse serum immunoprecipitated [35S]methionine metabolically labeled E. risticii proteins with apparent molecular masses ranging from 14 to 90 kDa. The major antigens recognized by dilute immune serum in immunoblot analysis had molecular masses of 62, 53, 40, 33, 27, and 25 kDa, and the 62- and 27-kDa antigens were prominent in immunoprecipitations with dilute antibody. Antigens with molecular masses of 62, 53, 40, 33, and 27 kDa are likely surface exposed, as determined by immunoprecipitation of 125I-labeled organisms with immune mouse serum.     

Reflexiveness: structural principle for a course on values

This article describes an attempt to integrate the cognitive and affective domains in a course on values for allied health students by using reflexiveness as the course's structural principle. This course's reflexive structure included opportunities for the students to reflect critically on value questions, an interconnected system of educational stages, and a synthesis of traditional curricular elements. Each of the educational stages (conceptual, dialogue, and affective analysis and application) incorporated and developed the information and affective skills gained by the students in the previous stages. Even the evaluation instruments were designed as learning exercises to reflect the goal of the course. Reflexiveness thus provided a curricular pattern or strategy for a systematic approach to the study of the moral dimensions of health care by allied health professionals.     

Overseas Gonorrhea Screening Among Newly Arrived Refugees During 2018

Journal of Immigrant and Minority Health - We assessed the overseas gonorrhea results reported in the CDC’s Electronic Disease Notification (EDN) system among...     

Increased adhesive properties of neutrophils and inflammatory markers in venous thromboembolism patients with residual vein occlusion and high D-dimer levels

Background

Venous thromboembolism (VTE) develops via a multicellular process on the endothelial surface. Although widely recognized, the relationship between inflammation and thrombosis, this relationship has been mostly explored in clinical studies by measuring circulating levels of inflammatory cytokines. However, the role of inflammatory cells, such as neutrophils, in the pathogenesis of VTE is not clear in humans.

Aims

To evaluate the adhesive properties of neutrophils, erythrocytes and platelets in VTE patients and to correlate findings with inflammatory and hypercoagulability marker levels.

Methods

Study group consisted of twenty-nine VTE patients and controls matched according to age, gender and ethnic background. Adhesive properties of neutrophils, erythrocytes and platelets were determined using a static adhesion assay. Neutrophil adhesion molecules expressions were evaluated by flow cytometry. Inflammatory and hypercoagulability marker levels were evaluated by standard methods. Residual vein occlusion (RVO) was evaluated by Doppler ultrasound.

Results

No significant difference could be observed in platelet and erythrocyte adhesion between VTE patients and controls. Interestingly, VTE patients with high levels of D-dimer and RVO, demonstrated a significant increase in neutrophil adhesion, compared to controls and remaining patients. Inflammatory markers (IL-6, IL-8, TNF-α) were also significantly elevated in this subgroup, compared to other VTE patients. Adhesive properties of neutrophils correlated with IL-6 and D-dimer levels. Neutrophils adhesion molecules (CD11a, CD11b and CD18) were not altered in any of the groups.

Conclusion

These findings not only support the hypothesis of an association between inflammation and hypercoagulability, but more importantly, highlight the role of neutrophils in this process.     

Validation of the Intelligibility in Context Scale as a screening tool for preschoolers in Hong Kong

The Intelligibility in Context Scale (ICS) is a parent report questionnaire for assessing children’s speech intelligibility. The original version was developed in English and was based on Environmental Factors identified within the International Classification of Functioning, Disability and Health-Children and Youth Version (ICF-CY). The ICS has been translated into over 30 languages, including Traditional Chinese (ICS-TC). The aims of the current study were to examine the psychometric properties of the ICS-TC with Cantonese-speaking parent--child dyads and to identify speech measures that were more sensitive to the ICS-TC ratings. A total of 72 Cantonese-speaking preschoolers with (n?=?39) and without speech sound disorders (SSD; n?=?33) were recruited. Native Cantonese-speaking parents completed the ICS-TC independently. The measure showed good internal consistency and test–retest reliability. Correlations with speech performance on the Hong Kong Cantonese Articulation Test (HKCAT), and significant difference in ICS-TC mean scores between the two groups provided preliminary support for the validity of ICS-TC and suggested that ICS-TC can differentiate between children with and without SSD with a large effect size of d?=?0.74. The optimal cutoff was estimated using Receiver Operative Characteristic (ROC) curve analysis, giving a sensitivity of 0.70 and specificity of 0.59. ICS-TC mean scores showed a positive correlation with the percentage of initial consonants correct and negative correlation with frequency of atypical errors, and both were moderate in strength. Given the satisfactory psychometric properties of ICS-TC, it may be a valuable clinical tool for screening Cantonese-speaking preschool children’s intelligibility.     

The Effect of Seatbelt Use on Injury Patterns, Disposition, and Hospital Charges for Elders

OBJECTIVE: To study the relationships between seatbelt use and injury patterns, hospital charges, morbidity, and mortality in elder motor vehicle crash victims. METHODS: A retrospective review of individuals at least 65 years old presenting to an urban emergency department (ED) after a motor vehicle crash. RESULTS: Over a two-year period, 339 patients had documentation of seatbelt use or non-use at the time of the crash. Of these, 241 (71%) patients had been wearing a seatbelt and 98 (29%) had not. Elders not using seatbelts were more likely to require hospitalization (29% unbelted vs. 17% belted) and had a higher mortality rate. Injury patterns were different in the two groups. Emergency department charges were significantly different between belted and unbelted elders ($351 vs. $451, p = 0.01) and head computed tomography (CT) utilization was higher in the unbelted group (25.6% vs 12.7%, p = 0.005). CONCLUSIONS: Improved seatbelt compliance in elders can reduce injuries, hospitalization rates, ED charges, and mortality resulting from motor vehicle crashes.     

Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer

The folate derivatives folic acid (FA) and folinic acid (FNA) decrease the in vivo and in vitro activities of antifolate drugs in Plasmodium falciparum. However, the effects of 5-methyl-tetrahydrofolate (5-Me-THF) and tetrahydrofolate (THF), the two dominant circulating folate forms in humans, have not been explored yet. We have investigated the effects of FA, FNA, 5-Me-THF, and THF on the in vitro activity of the antimalarial antifolates pyrimethamine and chlorcycloguanil and the anticancer antifolates methotrexate (MTX), aminopterin, and trimetrexate (TMX), against P. falciparum. The results indicate that these anticancers are potent against P. falciparum, with IC₅₀ < 50 nM. 5-Me-THF does not significantly decrease the activity of all tested drugs, and none of the tested folate derivatives significantly decrease the activity of these anticancers. Thus, malaria folate metabolism has features different from those in human, and the exploitation of this difference could lead to the discovery of new drugs to treat malaria. For instance, the combination of 5-Me-THF with a low dose of TMX could be used to treat malaria. In addition, the safety of a low dose of MTX in the treatment of arthritis indicates that this drug could be used alone to treat malaria. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. This study was supported by Pfizer-Royal Society Award, UK (to AN), the EU Commission under Framework 6 as part of the AntiMal Integrated Project 018834, and the European & Developing Countries Clinical Trials Partnership (EDCPT).     

Social Determinants of Mental Health: Where We Are and Where We Need to Go

Purpose of Review

The present review synthesizes recent literature on social determinants and mental health outcomes and provides recommendations for how to advance the field. We summarize current studies related to changes in the conceptualization of social determinants, how social determinants impact mental health, what we have learned from social determinant interventions, and new methods to collect, use, and analyze social determinant data.

Recent Findings

Recent research has increasingly focused on interactions between multiple social determinants, interventions to address upstream causes of mental health challenges, and use of simulation models to represent complex systems. However, methodological challenges and inconsistent findings prevent a definitive understanding of which social determinants should be addressed to improve mental health, and within what populations these interventions may be most effective.

Summary

Recent advances in strategies to collect, evaluate, and analyze social determinants suggest the potential to better appraise their impact and to implement relevant interventions.