Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

<p>Abstract</p> <p>Background</p> <p>Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT.</p> <p>Methods</p> <p>We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN.</p> <p>Results</p> <p>We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months.</p> <p>Conclusions</p> <p>LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence.</p

Health-seeking behaviors and self-care practices of Dominican women with lymphoedema of the leg: implications for lymphoedema management programs

BACKGROUND: In the Dominican Republic, a Latin American country with filariasis-endemic areas, more than 63,000 people have lymphatic filariasis and more than 400,000 people are at risk of future infection. In this paper, we explore the health beliefs, health-seeking behaviors and self-care practices of women with lymphoedema in filariasis-endemic areas to better understand the needs of women when developing lymphoedema morbidity control programs. METHODS: Qualitative data were collected through semi-structured interviews of 28 women, 3 focus group discussions with 28 women, field notes and photographs. RESULTS: Women described exhaustive and expensive attempts at seeking a cure for their lymphoedema. Family members were influential in providing women with initial care seeking referrals to indigenous healers credited with influence over physical, mental, spiritual and supernatural properties of illness. When indigenous treatments proved to be ineffectual, the women sought care from trained healthcare providers. Most healthcare providers incorrectly diagnosed the edema, failed to adequately treat and meet the needs of women and were viewed as expensive. Most women resorted to self-prescribing injectable, oral, or topical antibiotics along with oral analgesics as a standard practice of self-care. CONCLUSION: Healthcare providers must understand a woman's cultural perspectives of illness, her natural networks of support and referral, her behavioural practices of care-seeking and self-care and the financial burden of seeking care. In the culture of the Dominican Republic family members and traditional healthcare providers are influential advisors on initial health-seeking behaviors and self-care practices. For this reason family-oriented interventions, support groups for women and their families, community education and training on simple, low cost lymphoedema management techniques for indigenous healers are viable ways to influence the early detection, diagnosis and treatment of women with lymphoedema. The extensive use of injectable, oral and topical antibiotics by indigenous healers and women without medical supervision suggests a need for health education messages related to the risks of such practices

Sociodemographic correlates of food habits among school adolescents (12–15 year) in north Gaza Strip

Background: There is little information about meal patterns and food consumption of adolescents in Palestine. The objective of this study was to describe the association between sociodemographic factors and food intake, and meal patterns among Palestinian school adolescents (12–15 year) in North Gaza Strip. Methods: A cross-sectional study was conducted in 2002 comprising 944 subjects in 10 schools in Gaza city, Jabalia village and Jabalia refugee camp. Self-administered questionnaires were filled in by students and parents to obtain data on frequency of meals, food intake and sociodemographic characteristics. Results: High household socioeconomic status (SES) was associated with the increased number of meals and the increased intakes of many nutritious foods such as; animal food items, fruits and vegetables and dairy foods. The percentage of adolescents having breakfast daily of high and low SES was 74.5% vs 55% in boys and 65.6% vs 45% in girls. The percentage of girls with refugee status who had lunch was higher (90.2%) compared to the local citizen girls (83.9%), (p = 0.03). Girls were less likely to skip daily lunch (OR = 0.55, 95% CI = 0.36–0.87, p = 0.01) compared to boys. Risk of skipping lunch was three times higher among adolescents living in the village compared to Gaza well-off area (OR = 3.3, 95% CI = 1.72–6.31, p < 0.001). Adolescents who were having lunch daily were less likely to skip breakfast or dinner. Only 11.6% of boys and 16.2% of girls consumed fruits daily. In multivariate analysis, SES was positively associated with food frequency intake scores in both genders. Boys from the refugee camp and the village had a significant higher consumption of fruits and vegetables than boys from high and low income area in Gaza City, while it was the opposite in girls. Conclusion: Meal skipping is common, particularly among those of low SES and the intakes of many nutritious foods such as animal food items, fruits and vegetables and dairy foods seem to be low among adolescents of low SES. The results of this study could be used as an important baseline for future monitoring of the nutritional situation of adolescents.Abdallah H Abudayya, Hein Stigum, Zumin Shi, Yehia Abed and Gerd Holmboe-Ottese

A Role for Polyploidy in the Tumorigenicity of Pim-1-Expressing Human Prostate and Mammary Epithelial Cells

Polyploidy is a prominent feature of many human cancers, and it has long been hypothesized that polyploidy may contribute to tumorigenesis by promoting genomic instability. In this study, we investigated whether polyploidy per se induced by a relevant oncogene can promote genomic instability and tumorigenicity in human epithelial cells.When the oncogenic serine-threonine kinase Pim-1 is overexpressed in immortalized, non-tumorigenic human prostate and mammary epithelial cells, these cells gradually converted to polyploidy and became tumorigenic. To assess the contribution of polyploidy to tumorigenicity, we obtained sorted, matched populations of diploid and polyploid cells expressing equivalent levels of the Pim-1 protein. Spectral karyotyping revealed evidence of emerging numerical and structural chromosomal abnormalities in polyploid cells, supporting the proposition that polyploidy promotes chromosomal instability. Polyploid cells displayed an intact p53/p21 pathway, indicating that the viability of polyploid cells in this system is not dependent on the inactivation of the p53 signaling pathway. Remarkably, only the sorted polyploid cells were tumorigenic in vitro and in vivo.Our results support the notion that polyploidy can promote chromosomal instability and the initiation of tumorigenesis in human epithelial cells

A Research Agenda for Helminth Diseases of Humans: Basic Research and Enabling Technologies to Support Control and Elimination of Helminthiases

Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host–parasite interactions and immunopathology; and 4) (invertebrate) host–parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases

Energy limitation of cyanophage development : implications for marine carbon cycling

RJP was in receipt of a Natural Environment Research Council (NERC) PhD studentship and a Warwick University IAS Fellowship. This work was also supported in part by NERC grant NE/N003241/1 and Leverhulme Trust grant RPG-2014-354 to A.D.M., D.J.E., and D.J.S.Marine cyanobacteria are responsible for ~25% of the fixed carbon that enters the ocean biosphere. It is thought that abundant co-occurring viruses play an important role in regulating population dynamics of cyanobacteria and thus the cycling of carbon in the oceans. Despite this, little is known about how viral infections ‘play-out’ in the environment, particularly whether infections are resource or energy limited. Photoautotrophic organisms represent an ideal model to test this since available energy is modulated by the incoming light intensity through photophosphorylation. Therefore, we exploited phototrophy of the environmentally relevant marine cyanobacterium Synechococcus and monitored growth of a cyanobacterial virus (cyanophage). We found that light intensity has a marked effect on cyanophage infection dynamics, but that this is not manifest by a change in DNA synthesis. Instead, cyanophage development appears energy limited for the synthesis of proteins required during late infection. We posit that acquisition of auxiliary metabolic genes (AMGs) involved in light-dependent photosynthetic reactions acts to overcome this limitation. We show that cyanophages actively modulate expression of these AMGs in response to light intensity and provide evidence that such regulation may be facilitated by a novel mechanism involving light-dependent splicing of a group I intron in a photosynthetic AMG. Altogether, our data offers a mechanistic link between diurnal changes in irradiance and observed community level responses in metabolism, i.e., through an irradiance-dependent, viral-induced release of dissolved organic matter (DOM).Publisher PDFPeer reviewe