Interactions between sleep disorders and oral diseases

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106655/1/odi12152.pd

Dietary fat increases solid tumor growth and metastasis of 4T1 murine mammary carcinoma cells and mortality in obesity-resistant BALB/c mice

Introduction High-fat diets (HFDs) are known to cause obesity and are associated with breast cancer progression and metastasis. Because obesity is associated with breast cancer progression, it is important to determine whether dietary fat per se stimulates breast cancer progression in the absence of obesity. This study investigated whether an HFD increases breast cancer growth and metastasis, as well as mortality, in obesity-resistant BALB/c mice. Methods The 4-week-old, female BALB/c mice were fed HFD (60% kcal fat) or control diet (CD, 10% kcal fat) for 16 weeks. Subsequently, 4T1 mammary carcinoma cells were injected into the inguinal mammary fat pads of mice fed continuously on their respective diets. Cell-cycle progression, angiogenesis, and immune cells in tumor tissues, proteases and adhesion molecules in the lungs, and serum cytokine levels were analyzed with immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). In vitro studies were also conducted to evaluate the effects of cytokines on 4T1 cell viability, migration, and adhesion. Results Spleen and gonadal fat-pad weights, tumor weight, the number and volume of tumor nodules in the lung and liver, and tumor-associated mortality were increased in the HFD group, with only slight increases in energy intake and body weight. HF feeding increased macrophage infiltration into adipose tissues, the number of lipid vacuoles and the expression of cyclin-dependent kinase (CDK)2, cyclin D1, cyclin A, Ki67, CD31, CD45, and CD68 in the tumor tissues, and elevated serum levels of complement fragment 5a (C5a), interleukin (IL)-16, macrophage colony-stimulating factor (M-CSF), soluble intercellular adhesion molecule (sICAM)-1, tissue inhibitors of metalloproteinase (TIMP)-1, leptin, and triggering receptor expressed on myeloid cells (TREM)-1. Protein levels of the urokinase-type plasminogen activator, ICAM-1, and vascular cell adhesion molecule-1 were increased, but plasminogen activator inhibitor-1 levels were decreased in the lungs of the HFD group. In vitro assays using 4T1 cells showed that sICAM-1 increased viability; TREM-1, TIMP-1, M-CSF, and sICAM-1 increased migration; and C5a, sICAM-1, IL-16, M-CSF, TIMP-1, and TREM-1 increased adhesion. Conclusions Dietary fat increases mammary tumor growth and metastasis, thereby increasing mortality in obesity-resistant mice

Attitudes towards Human Papillomavirus vaccination among African parents in a city in the north of England: A qualitative study.

Background: Human papillomavirus (HPV) is sexually transmitted and has been conclusively linked to cervical cancer and genital warts. Cervical cancer is attributed to approximately 1100 deaths annually in UK, and is the second most common female cancer globally. It has been suggested that black African women are more predisposed to HPV infection and cervical cancer. A vaccine has been developed to reduce HPV infection, and in the UK, has been offered to 12-13 year old adolescent girls through schools as part of their childhood immunization programme since 2008. Upon programme initiation, it was noted that vaccine uptake was lower in schools where girls from ethnic minority groups were proportionately higher. Objectives: The study’s objectives were to explore factors influencing UK based African parents’ acceptance or decline of the HPV vaccine, whether fathers and mothers share similar views pertaining to vaccination and any interfamily tensions resulting from differing views. Methodology: A qualitative study was conducted with five African couples residing in north England. Face to face semi-structured interviews were carried out. Participants were parents to at least one daughter aged between 8 and 14 years. Recruitment was done through purposive sampling using snowballing. Results: HPV and cervical cancer awareness was generally low, with awareness lower in fathers. HPV vaccination was generally unacceptable among the participants, with fear of promiscuity, infertility and concerns that it’s still a new vaccine with yet unknown side effects cited as reasons for vaccine decline. There was HPV risk denial 3 as religion and good cultural upbringing seemed to result in low risk perceptions, with HPV and cervical cancer generally perceived as a white person’s disease. Religious values and cultural norms influenced vaccine decision-making, with fathers acting as the ultimate decision makers. Current information about why the vaccine is necessary was generally misunderstood. Conclusion: Tailored information addressing religious and cultural concerns may improve vaccine acceptability in African parents

Genomic insights into cancer-associated aberrant CpG island hypermethylation

Carcinogenesis is thought to occur through a combination of mutational and epimutational events that disrupt key pathways regulating cellular growth and division. The DNA methylomes of cancer cells can exhibit two striking differences from normal cells; a global reduction of DNA methylation levels and the aberrant hypermethylation of some sequences, particularly CpG islands (CGIs). This aberrant hypermethylation is often invoked as a mechanism causing the transcriptional inactivation of tumour suppressor genes that directly drives the carcinogenic process. Here, we review our current understanding of this phenomenon, focusing on how global analysis of cancer methylomes indicates that most affected CGI genes are already silenced prior to aberrant hypermethylation during cancer development. We also discuss how genome-scale analyses of both normal and cancer cells have refined our understanding of the elusive mechanism(s) that may underpin aberrant CGI hypermethylation

Validated scattering kernels for triphenylmethane at cryogenic temperatures

Cold neutrons are widely used in different fields of research such as the study of the structure and dynamics of solids and liquids, the investigation of magnetic materials, biological systems, polymer science, and a rapidly growing area of industrial applications. In a pulsed neutron source where the pulse width is an important parameter to be considered, hydrogenated materials are often used because of their high energy transfer in each collision. The preliminary scattering kernel for triphenylmethane, a material of great potential interest for cold neutron production, had been presented at the ND2016 conference. Here, a new model for the generation of the scattering kernels for this material, together with experimental results on its total cross section measured at the VESUVIO instrument (ISIS Neutron and Muon Source, United Kingdom) is presented. The thermal scattering kernel was generated by means of the NJOY Nuclear Data Processing system, using as input the vibrational modes obtained by density functional theory techniques (DFT). The agreement between measurements and our model validates the scattering kernel construction and the cross section library generated in ENDF and ACE formats

Experimental validation of the temperature behavior of the ENDF/B-VIII.0 thermal scattering kernel for light water

The Neutron Physics Department at Centro Atómico Bariloche developed new models for the interaction of thermal neutrons with water which have been validated against experimental data, including new thermal scattering experiments, and were adopted for the release of ENDF/B-VIII.0. Although the older models are, in general, good for most applications, some discrepancies had appeared in the case of heavy water, and this motivated new measurements that validated the new model. In the case of light water, the new model predicts a reduction of the total cross section around 0.025 eV when the temperature is increased from room temperature. This reduction, that is not predicted by the existing models, and potentially affects the calculation of temperature reactivity coefficients in nuclear reactors, has been traced to a shift in the vibrational frequency spectrum of liquid water. The only experimental data previously available is from an experiment performed at the Demokritos reactor in the ’60s at 293 K and 473 K, which validates the new model when the cross section ratios are computed. In order to verify this effect at a lower temperature range, a transmission experiment was carried out at the VESUVIO spectrometer in the ISIS facility in the UK in June 2018, measuring the total neutron cross section in the range from 283 K to 353 K. Here, we present this new experimental data and its comparison with the models

SARC025 arms 1 and 2: A phase 1 study of the poly(ADP‐ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma

BACKGROUND: In preclinical Ewing sarcoma (ES) models, poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors were identified as a potential therapeutic strategy with synergy in combination with cytotoxic agents. This study evaluated the safety and dosing of the PARP1/2 inhibitor niraparib (NIR) with temozolomide (TMZ; arm 1) or irinotecan (IRN; arm 2) in patients with pretreated ES. METHODS: Eligible patients in arm 1 received continuous NIR daily and escalating TMZ (days 2-6 [D2-6]) in cohort A. Subsequent patients received intermittent NIR dosing (cohort B), with TMZ re-escalation in cohort C. In arm 2, patients were assigned to NIR (days 1-7 [D1-7]) and escalating doses of IRN (D2-6). RESULTS: From July 2014 to May 2018, 29 eligible patients (23 males and 6 females) were enrolled in arms 1 and 2, which had 7 dose levels combined. Five patients experienced at least 1 dose-limiting toxicity (DLT) in arm 1 (grade 4 [G4] neutropenia for >7 days or G4 thrombocytopenia), and 3 patients experienced at least 1 DLT in arm 2 (grade 3 [G3] colitis, G3 anorexia, or G3 alanine aminotransferase elevation). The maximum tolerated dose was NIR at 200 mg every day on D1-7 plus TMZ at 30 mg/m2 every day on D2-6 (arm 1) or NIR at 100 mg every day on D1-7 plus IRN at 20 mg/m2 every day on D2-6 (arm 2). One confirmed partial response was observed in arm 2; the median progression-free survival was 9.0 weeks (95% CI, 7.0-10.1 weeks) and 16.3 weeks (95% CI, 5.1-69.7 weeks) in arms 1 and 2, respectively. The median decrease in tumor poly(ADP-ribose) activity was 89% (range, 83%-98%). CONCLUSIONS: The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple-combination study of NIR, IRN, and TMZ has commenced