Prognostic implications of immunohistochemically detected YKL-40 expression in breast cancer

BACKGROUND: YKL-40 has been implicated as a mediator of collagen synthesis and extracellular matrix re-modeling as well as mitogenesis. Elevated serum levels of YKL-40 have been associated with worse survival in a variety of malignancies including breast cancer. We wished to determine if immunohistochemically detected expression had prognostic implications in breast cancer. METHODS: A prospectively collected database of breast cancer patients treated at the University Hospital of Newark was used for analysis. Immunohistochemistry was performed on archived tumor tissue from 109 patients for whom full clinical information and follow up was available. RESULTS: YKL-40 expression was noted in 37 patients (34%). YKL-40 immunoreactivity significantly correlated with larger tumor size, poorer tumor differentiation, and a greater likelihood of being estrogen and/or progesterone receptor negative. No significant correlation was demonstrated between YKL-40 status and nodal stage. At a mean follow up of 3.2 years, disease-free survival was significantly worse in the subset of patients whose tumors demonstrated YKL-40 expression compared to the non-expressors. In multivariate analysis, YKL-40 status was independent of T-stage and N-stage in predicting disease recurrence. CONCLUSION: Immunoreactivity for YKL-40 was a significant predictor of breast cancer relapse in this subset of patients. This was independent of T or N-stage and suggests that tumor immunohistochemistry for this protein may be a valuable prognostic marker in breast cancer

Ultrafast valley-resolved carrier dynamics in group IV semiconductors

Attosecond transient absorption spectroscopy at the M4,5-edge of Ge following ultrafast photoexcitation reveals valley-resolved hot electron and hole relaxation, carrier recombination and trapping in Ge and Si-Ge alloy in unprecedented clarity and simultaneously

Diabetes related risk factors did not explain the increased risk for urinary incontinence among women with diabetes. The Norwegian HUNT/EPINCONT study

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown an association between diabetes mellitus (DM) and urinary incontinence (UI) in women, especially severe UI. The purpose of this study was to investigate whether diabetes related variables could explain this association.</p> <p>Methods</p> <p>The study is part of the EPINCONT study, which is based on the large Nord-Trøndelag Health Study 2 (HUNT 2), performed in the county of Nord-Trøndelag, Norway, during the years 1995 - 1997. Questions on diabetes and UI were answered by a total of 21 057 women aged 20 years and older. Of these 685 were identified as having diabetes, and thus comprise the population of our study. A variety of clinical and biochemical variables were recorded from the participants.</p> <p>Results</p> <p>Blood-glucose, HbA1c, albumine:creatinine ratio (ACR), duration of diabetes, diabetes treatment, type of diabetes, cholesterol and triglycerides did not significantly differ in women with and without UI in crude analyses. However, the diabetic women with UI had more hospitalizations during the last 12 months, more homecare, and a higher prevalence of angina and use of oestrogene treatment (both local and oral/patch). After adjusting for age, BMI, parity and smoking, there were statistically significant associations between any UI and angina (OR 1.89; 95% CI: 1.22 - 2.93), homecare (OR 1.72; 95% CI: 1.02 - 2.89), and hospitalization during the last 12 months (OR 1.67; 95% CI: 1.18 - 2.38). In adjusted analyses severe UI was also significantly associated with the same variables, and also with diabetes drug treatment (OR 2.10; 95% CI: 1.07 - 4.10) and stroke (OR 2.47; 95% CI: 1.09 - 5.59).</p> <p>Conclusion</p> <p>No single diabetes related risk factor seems to explain the increased risk for UI among women with diabetes. However, we found associations between UI and some clinical correlates of diabetes.</p

Successful treatment with azithromycin and rifampicin of penicillin and cephalosporin insensitive pneumococcal osteomyelitis in a child with HIV infection: a case report

Pneumococcal infection is common in children with HIV infection, but osteomyelits is unusual. The best treatment for bone and joint infection due to antibiotic resistant pneumococci is not known, especially in immunocompromised children

ELF5 modulates the estrogen receptor cistrome in breast cancer.

Acquired resistance to endocrine therapy is responsible for half of the therapeutic failures in the treatment of breast cancer. Recent findings have implicated increased expression of the ETS transcription factor ELF5 as a potential modulator of estrogen action and driver of endocrine resistance, and here we provide the first insight into the mechanisms by which ELF5 modulates estrogen sensitivity. Using chromatin immunoprecipitation sequencing we found that ELF5 binding overlapped with FOXA1 and ER at super enhancers, enhancers and promoters, and when elevated, caused FOXA1 and ER to bind to new regions of the genome, in a pattern that replicated the alterations to the ER/FOXA1 cistrome caused by the acquisition of resistance to endocrine therapy. RNA sequencing demonstrated that these changes altered estrogen-driven patterns of gene expression, the expression of ER transcription-complex members, and 6 genes known to be involved in driving the acquisition of endocrine resistance. Using rapid immunoprecipitation mass spectrometry of endogenous proteins, and proximity ligation assays, we found that ELF5 interacted physically with members of the ER transcription complex, such as DNA-PKcs. We found 2 cases of endocrine-resistant brain metastases where ELF5 levels were greatly increased and ELF5 patterns of gene expression were enriched, compared to the matched primary tumour. Thus ELF5 alters ER-driven gene expression by modulating the ER/FOXA1 cistrome, by interacting with it, and by modulating the expression of members of the ER transcriptional complex, providing multiple mechanisms by which ELF5 can drive endocrine resistance

Missed Opportunities: Family History and Behavioral Risk Factors in Breast Cancer Risk Assessment Among a Multiethnic Group of Women

BACKGROUND: Clinician’s knowledge of a woman’s cancer family history (CFH) and counseling about health-related behaviors (HRB) is necessary for appropriate breast cancer care. OBJECTIVE: To evaluate whether clinicians solicit CFH and counsel women on HRB; to assess relationship of well visits and patient risk perception or worry with clinician’s behavior. DESIGN: Cross-sectional population-based telephone survey. PARTICIPANTS: Multiethnic sample; 1,700 women from San Francisco Mammography Registry with a screening mammogram in 2001–2002. MEASUREMENTS: Predictors: well visit in prior year, self-perception of 10-year breast cancer risk, worry scale. Outcomes: Patient report of clinician asking about CFH in prior year, or ever counseling about HRB in relation to breast cancer risk. Multivariate models included age, ethnicity, education, language of interview, insurance/mammography facility, well visit, ever having a breast biopsy/follow-up mammography, Gail-Model risk, Jewish heritage, and body mass index. RESULTS: 58% reported clinicians asked about CFH; 33% reported clinicians ever discussed HRB. In multivariate analysis, regardless of actual risk, perceived risk, or level of worry, having had a well visit in prior year was associated with increased odds (OR = 2.3; 95% CI 1.6, 3.3) that a clinician asked about CFH. Regardless of actual risk of breast cancer, a higher level of worry (OR = 1.9; 95% CI 1.4, 2.6) was associated with increased odds that a clinician ever discussed HRB. CONCLUSIONS: Clinicians are missing opportunities to elicit family cancer histories and counsel about health-related behaviors and breast cancer risk. Preventive health visits offer opportunities for clinicians to address family history, risk behaviors, and patients’ worries about breast cancer

Platelet-derived growth factor-B gene delivery sustains gingival fibroblast signal transduction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65871/1/j.1600-0765.2008.01089.x.pd

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

Flavor of quiver-like realizations of effective supersymmetry

We present a class of supersymmetric models which address the flavor puzzle and have an inverted hierarchy of sfermions. Their construction involves quiver-like models with link fields in generic representations. The magnitude of Standard-Model parameters is obtained naturally and a relatively heavy Higgs boson is allowed without fine tuning. Collider signatures of such models are possibly within the reach of LHC in the near future.Comment: LaTeX, 17 pages, 3 figures. V2: reference adde