Potential novel candidate polymorphisms identified in genome-wide association study for breast cancer susceptibility

Previous genome-wide association studies (GWAS) have shown several risk alleles to be associated with breast cancer. However, the variants identified so far contribute to only a small proportion of disease risk. The objective of our GWAS was to identify additional novel breast cancer susceptibility variants and to replicate these findings in an independent cohort. We performed a two-stage association study in a cohort of 3,064 women from Alberta, Canada. In Stage I, we interrogated 906,600 single nucleotide polymorphisms (SNPs) on Affymetrix SNP 6.0 arrays using 348 breast cancer cases and 348 controls. We used single-locus association tests to determine statistical significance for the observed differences in allele frequencies between cases and controls. In Stage II, we attempted to replicate 35 significant markers identified in Stage I in an independent study of 1,153 cases and 1,215 controls. Genotyping of Stage II samples was done using Sequenom Mass-ARRAY iPlex platform. Six loci from four different gene regions (chromosomes 4, 5, 16 and 19) showed statistically significant differences between cases and controls in both Stage I and Stage II testing, and also in joint analysis. The identified variants were from EDNRA, ROPN1L, C16orf61 and ZNF577 gene regions. The presented joint analyses from the two-stage study design were not significant after genome-wide correction. The SNPs identified in this study may serve as potential candidate loci for breast cancer risk in a further replication study in Stage III from Alberta population or independent validation in Caucasian cohorts elsewhere.     

Assimilation of water and dietary ions by the gastrointestinal tract during digestion in seawater-acclimated rainbow trout

Recent studies focusing on the consequences of feeding for ion and water balance in freshwater fish have revealed the need for similar comparative studies in seawater fish. A detailed time course sampling of gastrointestinal (GI) tract contents following the ingestion of a single meal of a commercial diet revealed the assimilation of both water and dietary ions (Na⁺, Cl^?, K⁺, Ca²⁺, Mg²⁺) along the GI tract of seawater-acclimated rainbow trout (Oncorhynchus mykiss) which had been fasted for 1 week. Consumption of the meal did not change the drinking rate. There was a large secretion of fluid into the anterior intestine and caecae (presumably bile and/or pancreatic secretions). As a result, net assimilation (63%) of the ingested water along the GI tract was lower than generally reported for fasted trout. Mg²⁺ was neither secreted into nor absorbed from the GI tract on a net basis. Only K⁺ (93% assimilated) and Ca²⁺ (43% assimilated) were absorbed in amounts in excess of those provided by ingested seawater, suggesting that dietary sources of K⁺ and Ca²⁺ may be important to seawater teleosts. The oesophagus–stomach served as a major site of absorption for Na⁺, Cl^?, K⁺, Ca²⁺, and Mg²⁺, and the anterior intestine and caecae as a major site of net secretion for all of these ions, except Cl^?. Despite large absorptive fluxes of these ions, the ionic composition of the plasma was maintained during the digestion of the meal. The results of the present study were compared with previous work on freshwater-acclimated rainbow trout, highlighting some important differences, but also several similarities on the assimilation of water and ions along the gastrointestinal tract during digestion. This study highlights the complicated array of ion and water transport that occurs in the intestine during digestion while revealing the importance of dietary K⁺ and Ca²⁺ to seawater-acclimated rainbow trout. Additionally, this study reveals that digestion in seawater-acclimated rainbow trout appears to compromise intestinal water absorption.     

Multiple effects of the cellular prion protein on tooth development

The role of the prion protein (PrP) in transmissible spongiform encephalopathies has been the focus of intense investigation. However, less is known about the physiological function of normal cellular PrP (PrP(C)). In adult human teeth, PrP(C) has been identified in odontoblasts, cementoblasts and epithelial remnants of Malassez. In this study, we have localized PrP(C) in developing human and mouse teeth, and investigated the function of PrP using a PrP-knockout (Prnp(0/0) ) mouse model. PrP(C) was detected in developing human and mouse ameloblasts and odontoblasts. In vitro, undifferentiated dental mesenchymal cells from embryonic day 18 (E18) Prnp(0/0) mouse molars proliferated much more rapidly compared to age-matched, wild-type (wt) mouse molar dental mesenchymal cells. Histochemistry and immunohistochemical analyses showed a subtle but measurable phenotype, with the absence of PrP resulting in earlier initiation of both dentin and enamel formation. Consistent with this finding, laser microdissected odontoblasts from newborn Prnp(0/0) mouse incisors had a reduced proliferation rate, as measured by the expression of proliferating cell nuclear antigen (PCNA), and increased type 1 collagen mRNA expression. Dentin microhardness of the fully erupted molars was reduced and incisal enamel mineralization was delayed in Prnp(0/0) compared to age-matched wt mouse teeth. Taken together, these results suggest that PrP(C) affects multiple processes involved in tooth formation, through regulating the differentiation of ameloblasts and odontoblasts.     

Ochroconis humicola Coexisting with Esthesioneuroblastoma: An Incidental Coloniser or Allergen?

Ochroconis humicola, a fish pathogen, is rarely reported to cause disease in human. We report its first isolation from nasal tissue of a human immunodeficiency virus-positive young female patient. Histopathologically, the nasal mass was diagnosed as esthesioneuroblastoma. She presented with right-sided nasal obstruction and bleeding for two and half months. Computed tomography scan showed the nasal mass filling the whole right nasal cavity, maxillary, ethmoid and sphenoid sinuses. The direct microscopy of the nasal tissue and mucin demonstrated the presence of septate hyphae. On culture, O. humicola was isolated from the same tissue and the fungus was identified by morphologic, physiologic and molecular data including sequencing of ITS and 28S rDNA regions. No antifungal was prescribed, and the whole mass was resected out by endoscopic surgery. The patient was treated further by radical radiotherapy. After 1 year of follow-up, patient is stable with no recurrence of tumour. The role of this fungus was not clear, as it may be bystander or producing allergic fungal rhinosinusitis.     

nMAT4, a maturase factor required for nad1 pre‐mRNA processing and maturation,is essential for holocomplex I biogenesis in Arabidopsis mitochondria

Group II introns are large catalytic RNAs that are found in bacteria and organellar genomes of lower eukaryotes, but are particularly prevalent within mitochondria in plants, where they are present in many critical genes. The excision of plant mitochondrial introns is essential for respiratory functions, and is facilitated in vivo by various protein cofactors. Typical group II introns are classified as mobile genetic elements, consisting of the self‐splicing ribozyme and its own intron‐encoded maturase protein. A hallmark of maturases is that they are intron‐specific, acting as cofactors that bind their intron‐containing pre‐RNAs to facilitate splicing. However, the degeneracy of the mitochondrial introns in plants and the absence of cognate intron‐encoded maturase open reading frames suggest that their splicing in vivo is assisted by ‘trans’‐acting protein factors. Interestingly, angiosperms harbor several nuclear‐encoded maturase‐related (nMat) genes that contain N‐terminal mitochondrial localization signals. Recently, we established the roles of two of these paralogs in Arabidopsis, nMAT1 and nMAT2, in the splicing of mitochondrial introns. Here we show that nMAT4 (At1g74350) is required for RNA processing and maturation of nad1 introns 1, 3 and 4 in Arabidopsis mitochondria. Seed germination, seedling establishment and development are strongly affected in homozygous nmat4 mutants, which also show modified respiration phenotypes that are tightly associated with complex I defects.     

Television Viewing Time in Hong Kong Adult Population: Associations with Body Mass Index and Obesity

Background

Obesity is increasing dramatically in the Asia-Pacific region particularly China. The population of Hong Kong was exposed to modernization far earlier than the rest of China, reflecting conditions that are likely to be replicated as other Chinese cities undergo rapid change. This study examined the relationship between television viewing and obesity in a Hong Kong sample. Information about the relationship between a key sedentary behavior, TV viewing, and obesity, and its moderation by demographic characteristics may identify sectors of the population at highest risk for excess weight.

Methods

Data were from Hong Kong Family and Health Information Trends Survey (2009–2010), a population-based survey on the public''s use of media for health information and family communication by telephone interviews with 3,016 Hong Kong adults (age≥18 years). TV viewing time, body mass index (BMI), physical activity and other lifestyle variables were analyzed.

Results

Viewing time was longer in women, increased with age but decreased with education level and vigorous physical activity (all P<0.01). Longer TV viewing time was significantly associated with higher BMI (Coefficients B = 0.17, 95% CI: 0.11, 0.24) after adjusting for age, gender, employment status, marital status, education level, smoking activity and vigorous physical activity. This association was stronger in women than men (Coefficients B: 0.19 versus 0.15) and strongest in those aged 18 to 34 years (Coefficients B = 0.35). Furthermore, an hour increase in daily TV viewing was associated with 10% greater odds of being obese.

Conclusions

A significant socioeconomic gradient in television viewing time was observed. TV viewing time positively associated with BMI and obesity. The TV viewing – BMI associations were strongest in women and young adults, suggesting vulnerable groups to target for obesity prevention by decreasing TV viewing.     

Rhodiola Rosea for Mental and Physical Fatigue in Nursing Students: A Randomized Controlled Trial

Background

Fatigue is one of many unintended consequences of shift work in the nursing profession. Natural health products (NHPs) for fatigue are becoming an increasingly popular topic of clinical study; one such NHP is Rhodiola rosea. A well-designed, rigorously conducted randomized controlled trial is required before therapeutic claims for this product can be made.

Objective

To compare the efficacy of R. rosea with placebo for reducing fatigue in nursing students on shift work.

Design

A parallel-group randomized, double-blinded, placebo-controlled trial of 18–55 year old students from the Faculty of Nursing from the University of Alberta, participating in clinical rotations between January 2011 and September 2011.

Interventions

Participants were randomized to take 364 mg of either R. rosea or identical placebo at the start of their wakeful period and up to one additional capsule within the following four hours on a daily basis over a 42-day period.

Outcomes

The primary outcome was reduction in fatigue over the 42-day trial period measured using the Vitality-subscale of the RAND-36, cross-validated by the visual analogue scale for fatigue (VAS-F). Secondary outcomes included health-related quality of life, individualized outcomes assessment, and adverse events.

Results

A total of 48 participants were randomized to R. rosea (n = 24) or placebo (n = 24). The mean change in scores on the Vitality-subscale was significantly different between the study groups at day 42 in favor of placebo (−17.3 (95% CI −30.6, −3.9), p = 0.011), The mean change in scores on the VAS-F was also significantly difference between study groups at day 42 in favour of placebo (1.9 (95% CI 0.4, 3.5), p = 0.015). Total number of adverse events did not differ between R. rosea and placebo groups.

Conclusion

This study indicates that among nursing students on shift work, a 42-day course of R. Rosea compared with placebo worsened fatigue; however, the results should be interpreted with caution.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01278992","term_id":"NCT01278992"}}NCT01278992     

Self-Administered Tuberculosis Treatment Outcomes in a Tribal Population on the Indo-Myanmar Border,Nagaland, India

Background

Multiple strategies are being adopted by national tuberculosis (TB) programmes to achieve universal coverage of tuberculosis treatment. However, populations living in ‘hard-to-reach’ areas of north-east India have poor access to health services. Our study aimed to detail treatment outcomes in TB program supported by Médecins Sans Frontières (MSF) and using an alternative model of TB treatment delivery in Mon district, Nagaland, India.

Methods

This was a retrospective cohort study of TB patients, initiated on self-administered therapy (SAT) through Mon District Hospital, Nagaland, India between April 2012 and March 2013.

Results

A total of 238 tuberculosis patients had final TB treatment outcomes during the study period, including 82 and 156 from semi-urban and rural areas respectively. The majority of patients (62%, 147/238) were suffering from pulmonary, smear-positive tuberculosis. Overall, 74% of patients (175/238) had successful outcomes, being cured or having completed their treatment. Females (81%), pulmonary TB patients (75%) and those on a Category I regimen (79%) had better treatment success rates than males (67%), extra-pulmonary TB patients (62%) and patients on a Category II regimen (61%). The univariate and bivariate analyses found age, sex and TB treatment regimen significantly associated with unsuccessful TB treatment outcomes (defined as death, loss-to-follow-up and failure). However, only older age showed significance in a multivariate binary logistic regression model.

Conclusion

Our study suggests that self-administered TB treatment is feasible for patients living in areas with limited or no access to health services. The relatively low number of patients with adverse outcomes suggests that SAT models are safe; other advantages include the need for fewer resources and less frequent movements by patients. National TB programmes should consider allowing SAT strategies for delivery of TB treatment to ‘hard-to-reach’ populations, which could in turn help to achieve universal coverage and contribute to global TB elimination by 2050.     

Effect of bioaugmentation and nitrogen supplementation on composting of paddy straw

A composting experiment was conducted to evaluate the effect of a hyperlignocellulolytic fungal consortium and different nitrogen amendments on paddy straw composting in terms of changes in physicochemical and biological parameters. A fungal consortium comprising four lignocellulolytic mesophilic fungal cultures was used as inoculum for bioaugmentation of paddy straw in perforated pits. The comparative effect of farmyard manure (FYM), soybean trash, poultry litter and urea on the composting process was evaluated at monthly intervals in terms of physicochemical (pH, EC, available P, C:N ratio and humus content) and biological (enzymatic and microbial activity) parameters. The compost prepared from bioaugmented paddy straw composting mixture, with poultry manure as nitrogen supplement attained desirable C:N ratio in 1 month and displayed least phytotoxicity levels along with higher production of β-1,4-Exoglucanase. The combined activity of the autochthonous composting microbiota as well as the externally applied fungal inoculum accelerated the composting process of paddy straw. Supplementation of paddy straw with poultry manure in 8:1 ratio was identified as the best treatment to hasten the composting process. This study highlights the importance of application of fungal inoculum and an appropriate N-amendment such as poultry manure for preparation of compost using a substrate having high C:N ratio, such as paddy straw.