Quality of life measurement in women with cervical cancer: implications for Chinese cervical cancer survivors

<p>Abstract</p> <p>Background</p> <p>Women with cervical cancer now have relatively good 5-year survival rates. Better survival rates have driven the paradigm in cancer care from a medical illness model to a wellness model, which is concerned with the quality of women's lives as well as the length of survival. Thus, the assessment of quality of life among cervical cancer survivors is increasingly paramount for healthcare professionals. The purposes of this review were to describe existing validated quality of life instruments used in cervical cancer survivors, and to reveal the implications of quality of life measurement for Chinese cervical cancer survivors.</p> <p>Methods</p> <p>A literature search of five electronic databases was conducted using the terms <it>cervical/cervix cancer</it>, <it>quality of life</it>, <it>survivors</it>, <it>survivorship</it>, <it>measurement</it>, and <it>instruments</it>. Articles published in either English or Chinese from January 2000 to June 2009 were searched. Only those adopting an established quality of life instrument for use in cervical cancer survivors were included.</p> <p>Results</p> <p>A total of 11 validated multidimensional quality of life instruments were identified from 41 articles. These instruments could be classified into four categories: generic, cancer-specific, cancer site-specific and cancer survivor-specific instruments. With internal consistency varying from 0.68-0.99, the test-retest reliability ranged from 0.60-0.95 based on the test of the Pearson coefficient. One or more types of validity supported the construct validity. Although all these instruments met the minimum requirements of reliability and validity, the original versions of these instruments were mainly in English.</p> <p>Conclusion</p> <p>Selection of an instrument should consider the purpose of investigation, take its psychometric properties into account, and consider the instrument's origin and comprehensiveness. As quality of life can be affected by culture, studies assessing the quality of life of cervical cancer survivors in China or other non-English speaking countries should choose or develop instruments relevant to their own cultural context. There is a need to develop a comprehensive quality of life instrument for Chinese cervical cancer survivors across the whole survivorship, including immediately after diagnosis and for short- (less than 5 years) and long-term (more than 5 years) survivorship.</p

Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation

Pairing of a given E3 ubiquitin ligase with different E2s allows synthesis of ubiquitin conjugates of different topologies. While this phenomenon contributes to functional diversity, it remains largely unknown how a single E3 ubiquitin ligase recognizes multiple E2s, and whether identical structural requirements determine their respective interactions. The E3 ubiquitin ligase RNF8 that plays a critically important role in transducing DNA damage signals, interacts with E2s UBCH8 and UBC13, and catalyzes both K48- and K63-linked ubiquitin chains. Interestingly, we report here that a single-point mutation (I405A) on the RNF8 polypeptide uncouples its ability in catalyzing K48- and K63-linked ubiquitin chain formation. Accordingly, while RNF8 interacted with E2s UBCH8 and UBC13, its I405A mutation selectively disrupted its functional interaction with UBCH8, and impaired K48-based poly-ubiquitylation reactions. In contrast, RNF8 I405A preserved its interaction with UBC13, synthesized K63-linked ubiquitin chains, and assembled BRCA1 and 53BP1 at sites of DNA breaks. Together, our data suggest that RNF8 regulates K48- and K63-linked poly-ubiquitylation via differential RING-dependent interactions with its E2s UBCH8 and UBC13, respectively.published_or_final_versio

Ferulic Acid Induces Th1 Responses by Modulating the Function of Dendritic Cells and Ameliorates Th2-Mediated Allergic Airway Inflammation in Mice

This study investigated the immunomodulatory effects of ferulic acid (FA) on antigen-presenting dendritic cells (DCs) in vitro and its antiallergic effects against ovalbumin- (OVA-) induced Th2-mediated allergic asthma in mice. The activation of FA-treated bone marrow-derived DCs by lipopolysaccharide (LPS) stimulation induced a high level of interleukin- (IL-) 12 but reduced the expression levels of the proinflammatory cytokines IL-1β, IL-6, and tumor necrosis factor- (TNF-) α. Compared to control-treated DCs, FA significantly enhanced the expressions of Notch ligand Delta-like 4 (Dll4), MHC class II, and CD40 molecules by these DCs. Furthermore, these FA-treated DCs enhanced T-cell proliferation and Th1 cell polarization. In animal experiments, oral administration of FA reduced the levels of OVA-specific immunoglobulin E (IgE) and IgG1 and enhanced IgG2a antibody production in serum. It also ameliorated airway hyperresponsiveness and attenuated eosinophilic pulmonary infiltration in dose-dependent manners. In addition, FA treatment inhibited the production of eotaxin, Th2 cytokines (IL-4, IL-5, and IL-13), and proinflammatory cytokines but promoted the Th1 cytokine interferon- (IFN-) γ production in bronchoalveolar lavage fluid (BALF) and the culture supernatant of spleen cells. These findings suggest that FA exhibits an antiallergic effect via restoring Th1/Th2 imbalance by modulating DCs function in an asthmatic mouse model

Effects of voluntary running on plasma levels of neurotrophins, hippocampal cell proliferation and learning and memory in stressed rats

Previous studies have shown that a 2-week treatment with 40mg/kg corticosterone (CORT) in rats suppresses hippocampal neurogenesis and decreases hippocampal brain-derived neurotrophic factor (BDNF) levels and impairs spatial learning, all of which could be counteracted by voluntary wheel running. BDNF and insulin-like growth factor (IGF-1) have been suggested to mediate physical exercise-enhanced hippocampal neurogenesis and cognition. Here we examined whether such running-elicited benefits were accompanied by corresponding changes of peripheral BDNF and IGF-1 levels in a rat model of stress. We examined the effects of acute (5days) and chronic (4weeks) treatment with CORT and/or wheel running on (1) hippocampal cell proliferation, (2) spatial learning and memory and (3) plasma levels of BDNF and IGF-1. Acute CORT treatment improved spatial learning without altered cell proliferation compared to vehicle treatment. Acute CORT-treated non-runners showed an increased trend in plasma BDNF levels together with a significant increase in hippocampal BDNF levels. Acute running showed no effect on cognition, cell proliferation and peripheral BDNF and IGF-1 levels. Conversely, chronic CORT treatment in non-runners significantly impaired spatial learning and suppressed cell proliferation in association with a decreased trend in plasma BDNF level and a significant increase in hippocampal BDNF levels. Running counteracted cognitive deficit and restored hippocampal cell proliferation following chronic CORT treatment; but without corresponding changes in plasma BDNF and IGF-1 levels. The results suggest that the beneficial effects of acute stress on cognitive improvement may be mediated by BDNF-enhanced synaptic plasticity that is hippocampal cell proliferation-independent, whereas chronic stress may impair cognition by decreasing hippocampal cell proliferation and BDNF levels. Furthermore, the results indicate a trend in changes of plasma BDNF levels associated with a significant alteration in hippocampal levels, suggesting that treatment with running/CORT for 4 weeks may induce a change in central levels of hippocampal BDNF level, which may not lead to a significant change in peripheral levels.postprin

Prevalence and impact of clinical violence towards nursing students in Hong Kong: a cross-sectional study

Objectives: Studies of violence towards nursing students (NSs) have been scattered mainly in the West and Middle East, but to date there have been no studies in Eastern countries. Differences in nursing education systems and cultures might have contributed to variations in incidences of clinical violence. The purpose of this study was to investigate the prevalence, associated factors and impact of clinical violence to NSs.Methods: This was a cross-sectional survey study. Convenience sampling was used to recruit university NSs from March to June 2012 in classroom settings in Hong Kong. A valid and reliable questionnaire was used to collect the data. 1297 questionnaires were distributed and 1017 NSs completed questionnaires, with a response rate of 78.41%.Results: Of the 1017 NSs, 37.3% (n=379) reported having experienced clinical violence during their nursing studies. The prevalence of verbal abuse (30.6%) was significantly greater than that of physical violence (16.5%). The perpetrators of verbal abuse were predominantly patients (66.8%), hospital staff (29.7%), university supervisors (13.4%) and patients’ relatives (13.2%). Patients (91.0%) were the greatest source of physically violent assaults. Compared with those who had experienced physical violence, the NSs who had experienced verbal abuse were more likely not to take action, and not to stop or report the incident, but were also more likely to tell their friends/families. Although the negative effects on emotions, clinical performance and the extent to which they were disturbed by the violence were significantly greater for verbal abuse than that for physical violence, their intention to leave the nursing profession after experiencing either verbal or physical violence was significantly higher after than before the experience (p<0.001).Conclusions: Our results found a moderately high prevalence of clinical violence among NSs. Provision and/or reinforcement of appropriate training about clinical violence in the nursing curricula is necessary

Profiling occupational therapists’ preference for an international master’s program in occupational therapy : a needs analysis study.

Background: To advance occupational therapy knowledge and practice in Southeast Asia, it is pivotal that quality master’s degree programs in occupational therapy are in place. Such a program must respond to the needs of the region in terms of occupational therapy education, practice, and scholarship. By recognizing the diversity of the occupational therapy education and training in the region, it has become possible to consider alternatives in establishing a graduate program in occupational therapy through partnerships and consortia. In order to make an informed decision to decide whether co-creating a master’s program in occupational therapy through an international consortium within the region is possible or not, a needs assessment is warranted. Objectives: To describe the profile of occupational therapists living and working in the Southeast Asian region who would like to pursue a master’s degree in occupational therapy via an international consortium. Materials and methods: An online survey design was used to produce data that would be used to inform the co-creation of an international master’s program in occupational therapy. The survey questionnaire was designed specifically for this study and included three sections: 1) information and consent form; 2) demographic information; and 3) information about the need for and preferences on a master’s program in occupational therapy. Participants were recruited through professional organizations and various social media platforms of national and international occupational therapy groups. Results: Eighty-five final-year occupational therapy students and 143 occupational therapists from the Philippines, Indonesia, Thailand, and other countries completed the survey. Majority (62%) of the respondents was interested in pursuing a master’s degree in occupational therapy because they perceived that an advanced degree can enable specialization in practice, promote personal and professional development, and help generate new knowledge for the field. The characteristics of the envisaged international master’s program must be: 1) completed ideally in 1.5 to 2 years, 2) taken by part-time students who are also working practicing, 3) delivered via a hybrid arrangement (i.e., online and face-to-face) with a fixed weekly schedule, and 4) matriculated for USD 1,000 per semester. Conclusion: While this cross-sectional survey cannot encapsulate the totality of occupational therapists’ needs in terms of their professional development, the survey provided an empirical basis to inform decisions in the creation of a master’s program in occupational therapy jointly offered by an international consortium of Southeast Asian universities

Emerging Two-Dimensional Crystallization of Cucurbit[8]uril Complexes: From Supramolecular Polymers to Nanofibers.

The binding of imidazolium salts to cucurbit[8]uril, CB[8], triggers a stepwise self-assembly process with semiflexible polymer chains and crystalline nanostructures as early- and late-stage species, respectively. In such a process, which involves the crystallization of the host-guest complexes, the guest plays a critical role in directing self-assembly toward desirable morphologies. These include platelet-like aggregates and two-dimensional (2D) fibers, which, moreover, exhibit viscoelastic and lyotropic properties. Our observations provide a deeper understanding of the self-assembly of CB[8] complexes, with fundamental implications in the design of functional 2D systems and crystalline materials.EPSRC (reference no. EP/ G060649/1), ERC Starting Investigator Grant (project no. 240629, ASPiRe) Next Generation Fellowship from the Walters-Kundert Foundation. MINE- CO, the FSE and the FEDER for funding through projects RYC-2015-18471 (Ramoń y Cajal program) and CTQ2017- 84087-R. Royal Society University Research Fellowship UF160152. EPSRC CDT in Nanoscience and Nanotechnology (NanoDTC), grant number EP/L015978/1

Inferring who-infected-whom-where in the 2016 Zika outbreak in Singapore-a spatio-temporal model.

Singapore experienced its first known Zika outbreak in 2016. Given the lack of herd immunity, the suitability of the climate for pathogen transmission, and the year-round presence of the vector- Aedes aegypti-Zika had the potential to become endemic, like dengue. Guillain-Barré syndrome and microcephaly are severe complications associated elsewhere with Zika and the risk of these complications makes understanding its spread imperative. We investigated the spatio-temporal spread of locally transmitted Zika in Singapore and assessed the relevance of non-residential transmission of Zika virus infections, by inferring the possible infection tree (i.e. who-infected-whom-where) and comparing inferences using geographically resolved data on cases' home, their work, or their home and work. We developed a spatio-temporal model using time of onset and both addresses of the Zika-confirmed cases between July and September 2016 to estimate the infection tree using Bayesian data augmentation. Workplaces were involved in a considerable fraction (64.2%) of infections, and homes and workplaces may be distant relative to the scale of transmission, allowing ambulant infected persons may act as the 'vector' infecting distant parts of the country. Contact tracing is a challenge for mosquito-borne diseases, but inferring the geographically structured transmission tree sheds light on the spatial transmission of Zika to immunologically naive regions of the country

Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren’s Syndrome

We have previously isolated several IgG rheumatoid factors (RFs) from patients with both rheumatoid arthritis and idiopathic thrombocytopenia purpura using phage display system. To study IgG RFs in patients with other autoimmune diseases, phage display antibody libraries from a hepatitis C virus infected patient with Sjögren’s syndrome were constructed. After panning, a specific clone RFL11 was isolated for characterization in advance. The binding activity and specificity of RFL11 to IgG Fc fragment were comparable to those of RFs previously isolated. The analysis with existed RF-Fc complex structures indicated the homology model of RFL11 is similar to IgM RF61 complex with high binding affinity of about 6×10-8 M. This effect resulted from longer complementarity-determining region (CDR) combining key somatic mutations. In the RFL11-Fc interfaces, the CDR-H3 loop forms a finger-like structure extending into the bottom of Fc pocket and resulting in strong ion and cation-pi interactions. Moreover, a process of antigen-driven maturation was proven by somatically mutated VH residues on H2 and H3 CDR loops in the interfaces. Taken together, these results suggested that high affinity IgG RFs can be generated in patients with Sjögren’s syndrome and may play an important role in the pathogenesis of this autoimmune disease

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women

Background: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. Methods and Results: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T→C (rs799908:T→C), c.-2265C→T (rs11655505:C→T), c.-2004A→G (rs799906:A→G) and c.-1896(ACA) 1→(ACA) 2 (rs8176071:(ACA) 1→(ACA) 2) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% Cl 0.69 to 0.93; p = 0.003) which was more evident among women aged ≥45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% Cl 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged ≥45 years without a family history of breast cancer (OR = 0.64, 95% Cl 0.46 to 0.89; p = 0.008). Conclusion: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C→T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.published_or_final_versio