Chromosomal DNA damage measured using the cytokinesis‐block micronucleus cytome assay is significantly associated with cognitive impairment in South Australians

Loss of genome integrity may be associated with increased risk for neurodegenerative disease. The aim of this study was to investigate whether mild cognitive impairment (MCI) or Alzheimer's disease (AD) individuals have increased DNA damage relative to age‐ and gender‐ matched controls using the cytokinesis‐block micronucleus cytome (CBMN‐Cyt) assay. DNA damage was measured as micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear buds (NBUD) in binucleated cells. The assay was performed on blood samples from 80 participants consisting of (i) MCI cases (N = 20) and age‐ and gender‐ matched controls (N = 20), and (ii) AD cases (N = 20) and age‐ and gender‐ matched controls (N = 20). There was a significant increase in MCI NBUD frequency (P = 0.006) relative to controls, which was also observed in male (P = 0.03) and female (P = 0.04) subgroups. For AD cases, there were no significant differences in assay biomarkers relative to controls. There was a significant negative correlation between Mini Mental State Examination (MMSE) and (i) MN in all controls, (R = ?0.3, P = 0.04), and AD cases (R = ?0.4, P = 0.03), (ii) NPB in all controls, (R = ?0.4, P = 0.006) and AD cases (R = ?0.5, P = 0.01), and (iii) NBUD in MCI cases (R = ?0.5, P = 0.007) and AD cases (R = ?0.7, P = 0.0002). The results suggest that an increase in lymphocyte CBMN‐Cyt DNA damage biomarkers may be associated with cognitive decline. Environ. Mol. Mutagen. 56:32–40, 2015. © 2014 Wiley Periodicals, Inc.     

Polypharmacy among patients with multiple sclerosis: a qualitative systematic review

ABSTRACT

Objectives: The consequences of polypharmacy (intake of ≥ 5 drugs) are diverse, including drug interactions, rising costs and side effects. Risk groups for polypharmacy are multimorbid and chronically ill people, such as patients with multiple sclerosis (MS). MS is the most common neuroimmunological disease in young adults worldwide. We aimed to provide a systematic overview of the current research status regarding frequency and predictors of polypharmacy in MS patients.

Methods: A systematic literature search in the databases PubMed, Cochrane Library and Scopus was carried out according to the PRISMA guidelines. English and German original research articles were included.

Results: Seven studies fulfilled the inclusion criteria of this review, while the research objectives and methods were very heterogenous. The polypharmacy rates in these studies ranged from 15% to 59%. Polypharmacy correlated with comorbidities, increased disability, cognitive deficits, increased hospitalization, higher relapse rate and lower quality of life.

Conclusions: In MS patients, polypharmacy is common and closely associated with health issues. There is a great need for research in this area, especially regarding longitudinal changes in drug utilization. Effective networks between physicians and pharmacists are needed to optimize medication management for patients and to achieve the best possible therapy results.     

Adenocarcinoma metastatic to the temporomandibular joint

There are many causes for painful limitation of the temporomandibular joint. Among the rarer conditions that must be considered is a metastatic tumor. A case is presented in which progressively worsening limitation and increasing pain lead to a biopsy and diagnosis of metastatic adenocarcinoma of the TMJ.     

Trans-hiatal herniation following esophagectomy or gastrectomy: retrospective single-center experiences with a potential surgical emergency

Hernia - Trans-hiatal herniation after esophago-gastric surgery is a potentially severe complication due to the risk of bowel incarceration and cardiac or respiratory complaints. However, measures...     

Interferon β-1a and β-1b for patients with multiple sclerosis: updates to current knowledge

Introduction: Although multiple sclerosis (MS) remains incurable, interferon beta (IFNβ) has been at the forefront of treatment for many years. Different formulations of IFNβ allow for different levels of exposure: low-dose/frequency with some agents, and high-dose/frequency with others.

Areas covered: This review article discusses existing and emerging efficacy and safety data for IFNβ in MS. Clinical evidence of IFNβ efficacy has been generated and accumulated over many decades. During this time, key clinical trials have demonstrated the benefits of high-dose and/or high-frequency dosing of IFNβ-1a or β-1b, compared with lower levels of exposure, on outcome measures such as relapse rates, disability progression, disease progression and magnetic resonance imaging lesion outcomes.

IFNβ therapy is well tolerated and has one of the best characterized safety profiles of all first line therapies. The overall severity of adverse events (AEs) does not appear to be affected by different IFNβ exposures. Typical AEs that patients may experience with IFNβ are mild, reversible and manageable.

Expert commentary: IFNβ is one of the best characterized treatments for MS, with a large body of clinical and real-world evidence supporting the risk-benefit profile. High-dose/frequency regimens may provide better long-term outcomes.     

Postural education and behavior among students in a city in southern Brazil: student postural education and behavior

[Purpose] The aim of the present study was to assess the knowledge of the spine and posture among adolescent female students and to determine if they had access to postural education in or outside school. [Subjects and Methods] This was an epidemiological survey of a representative sample of 495 female students aged 14 to 18 years attending a regular secondary school in São Leopoldo, RS, Brazil. Data were collected through a questionnaire. [Results] The results showed that 16.8% of teens did not know what a spine was, 8.3% had no knowledge of posture, and 61% reported receiving no posture education. Posture awareness was associated only with posture while using a computer, while having postural education class was not associated with any postural behavior. [Conclusion] The results showed that, although most students are familiar with the spine and posture, a sizable group is not, and over half had no postural education. These findings suggest that inclusion of postural education programs in schools should be encouraged in order to promote health and prevent diseases related to the spine.Key words: Posture, Adolescent health, School health     

Plasminogen activator induction and platelet aggregation by phorbol and some of its derivatives: Correlation with skin irritancy and tumor-promoting activity

Summary Phorbol and eight of its derivatives were investigated for their ability to stimulate the synthesis of the enzyme plasminogen activator in cultured chick embryo fibroblasts and to aggregate human blood platelets and have been assayed for tumor, promoting and skin, irritant activities. Over a range of concentrations, elevation in the levels of plasminogen activator activity induced by phorbol derivatives correlates well with their promoting and irritant properties. In the platelet aggregation assay however, the parallelism between the activities measured in different biological assays was less complete. While strong promoters, such as TPA, are potent aggregating agents, and weak promoters, such as PDA, are poor or ineffective inducers of aggregation, two derivatives, PDD and PDB, deviate from this general result. Platelets must be exposed to PDD in relatively high concentrations before they will aggregate, and PDB was found to be the most potent aggregating agent of all the derivatives tested.

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Abbreviations TPA 12-O-tetradecanoylphorbol-13-acetate - PDD phorbol-12,13-didecanoate - TPA--oxide 12-O-tetradecanoylphorbol-13-acetate-6,7-oxide - PDB phorbol-12,13-dibenzoate - PDA phorbol-12,13-diacetate - 4-OMe-TPA 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate - 1,2-dihydro-TPA--oxide 1,2-dihydro-12-O-tetradecanoylphorbol-13-acetate-6,7-oxide - 4-PDD 4-phorbol-12,13-didecanoate This work was supported by a Grant-in-Aid from the American Heart Association and with funds contributed in part by the Suffolk Heart Association (Grant 78 747), the National Cancer Institute (Grants CA08290 and CA00118), and the American Cancer Society (Grant PDT1)     

Discriminating between latent and active tuberculosis with multiple biomarker responses

We sought to identify biomarker responses to tuberculosis specific antigens which could 1) improve the diagnosis of tuberculosis infection and 2) allow the differentiation of active and latent infections. Seventy subjects with active tuberculosis (N = 12), latent tuberculosis (N = 32), or no evidence of tuberculosis infection (N = 26) were evaluated. We used the Luminex Multiplexed Bead Array platform to simultaneously evaluate 25 biomarkers in the supernatant of whole blood samples following overnight stimulation using the Quantiferon(?) Gold In-Tube kit. We defined the response to stimulation as the difference (within an individual patient) between the response to the pooled tuberculosis antigens and the negative control. IP-10 response was significantly higher in tuberculosis-infected (active or latent) subjects compared to the uninfected group (p < 0.0001). Among the 25 parameters, expression levels of IL-15 and MCP-1 were found to be significantly higher in the active tuberculosis group compared to the latent tuberculosis group (p = 0.0006 and 0.0030, respectively). When combined, IL-15 and MCP-1 accurately identified 83% of active and 88% of latent infections. The combination of IL-15 and MCP-1 responses was accurate in distinguishing persons with active tuberculosis from persons with latent tuberculosis in this study.     

Toxicity of Aqueous l-Selenomethionine Exposure to Early Life-Stages of the Fathead Minnow (Pimephales promelas)

Bulletin of Environmental Contamination and Toxicology - Aqueous exposures to selenomethionine (SeMet), the major form of selenium (Se) in the diet, represent a rapid and simplified method for...