The influence of external factors on bacteriophages—review

The ability of bacteriophages to survive under unfavorable conditions is highly diversified. We summarize the influence of different external physical and chemical factors, such as temperature, acidity, and ions, on phage persistence. The relationships between a phage’s morphology and its survival abilities suggested by some authors are also discussed. A better understanding of the complex problem of phage sensitivity to external factors may be useful not only for those interested in pharmaceutical and agricultural applications of bacteriophages, but also for others working with phages

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

The benefits of strength training on musculoskeletal system health: practical applications for interdisciplinary care

Global health organizations have provided recommendations regarding exercise for the general population. Strength training has been included in several position statements due to its multi-systemic benefits. In this narrative review, we examine the available literature, first explaining how specific mechanical loading is converted into positive cellular responses. Secondly, benefits related to specific musculoskeletal tissues are discussed, with practical applications and training programmes clearly outlined for both common musculoskeletal disorders and primary prevention strategies

An exploratory study of host polymorphisms in genes that clinically characterize breast cancer tumors and pretreatment cognitive performance in breast cancer survivors

Theresa A Koleck,1,2 Catherine M Bender,1 Beth Z Clark,3,4 Christopher M Ryan,5,6 Puja Ghotkar,1 Adam Brufsky,4,7,8 Priscilla F McAuliffe,4,8,9 Priya Rastogi,4,7 Susan M Sereika,1,10,11 Yvette P Conley,1,12 1School of Nursing, University of Pittsburgh, Pittsburgh, PA, 2School of Nursing, Columbia University, New York, NY, 3Division of Gynecologic Pathology, Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC), 4School of Medicine, 5Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 6Department of Psychiatry, University of California San Francisco, San Francisco, CA, 7Division of Hematology/Oncology, Magee-Womens Hospital of UPMC, 8University of Pittsburgh Cancer Institute, 9Division of Breast Surgical Oncology, Magee-Womens Hospital of UPMC, 10Department of Biostatistics, 11Department of Epidemiology, 12Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA Purpose: Inspired by the hypothesis that heterogeneity in the biology of breast cancers at the cellular level may account for cognitive dysfunction symptom variability in survivors, the current study explored relationships between host single-nucleotide polymorphisms (SNPs) in 25 breast cancer-related candidate genes (AURKA, BAG1, BCL2, BIRC5, CCNB1, CD68, CENPA, CMC2, CTSL2, DIAPH3, ERBB2, ESR1, GRB7, GSTM1, MELK, MKI67, MMP11, MYBL2, NDC80, ORC6, PGR, RACGAP1, RFC4, RRM2, and SCUBE2), identified from clinically relevant prognostic multigene-expression profiles for breast cancer, and pretreatment cognitive performance.Patients and methods: The sample (n=220) was comprised of 138 postmenopausal women newly diagnosed with early stage breast cancer and 82 postmenopausal age- and education-matched healthy controls without breast cancer. Cognitive performance was assessed after primary surgery but prior to initiation of adjuvant chemotherapy and/or hormonal therapy using a comprehensive battery of neuropsychological tests encompassing eight cognitive function composite domains: attention, concentration, executive function, mental flexibility, psychomotor speed, verbal memory, visual memory, and visual working memory. In total, 131 SNPs were included in the analysis. Standard and robust multiple linear regression modeling was used to examine relationships between each domain and the presence or absence of one or more minor alleles for each SNP. Genetic risk/protection scores (GRSs) were calculated for each domain to evaluate the collective effect of possession of multiple risk/protective alleles.Results: With the exception of CMC2, MMP11, and RACGAP1, significant (P<0.05) SNP main effect and/or SNP by future prescribed treatment group interactions were observed for every gene between at least one domain and one or more SNPs. All GRSs were found to be significantly (P<0.001) associated with each respective domain score.Conclusion: Associations between host SNPs and computed GRSs and variability in pretreatment cognitive function performance support the study hypothesis, and warrant further investigations to identify biomarkers for breast cancer-related cognitive dysfunction. Keywords: breast neoplasms, genetics, cognition, biomarker

Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease) after laparoscopic Roux-en-Y gastric bypass for morbid obesity: a case report

<p>Abstract</p> <p>Introduction</p> <p>Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a rare, benign, autoimmune condition characterized by lymphadenopathy, fever and neutropenia. It is a self-limited condition of unknown etiology.</p> <p>Case presentation</p> <p>We report the case of a 45-year-old Caucasian man with the first known case of Kikuchi disease associated with dramatic weight loss after bariatric surgery.</p> <p>Conclusion</p> <p>Although the association between Kikuchi disease and bariatric surgery may be entirely coincidental, we speculate whether the immune dysfunction associated with weight loss may have played an etiologic role in this process.</p

Mechanisms of estrogen-independent breast cancer growth driven by low estrogen concentrations are unique versus complete estrogen deprivation

Despite the success of the aromatase inhibitors (AIs) in treating estrogen receptor positive breast cancer, 15–20 % of patients receiving adjuvant AIs will relapse within 5–10 years of treatment initiation. Long-term estrogen deprivation (LTED) of breast cancer cells in culture mimics AI-induced estrogen depletion to dissect mechanisms of AI resistance. However, we hypothesized that a subset of patients receiving AI therapy may maintain low circulating concentrations of estrogens that influence the development of endocrine resistance. We expanded established LTED models to account for incomplete suppression of estrogen synthesis during AI therapy. MCF-7 cells were grown in medium with charcoal-stripped serum supplemented with defined concentrations of 17β-estradiol (E2) or the estrogenic androgen metabolite 5α-androstane-3β,17β-diol (3βAdiol), an endogenous selective estrogen receptor modulator. Cells were selected in concentrations of E2 or 3βAdiol that induce 10 or 90 percent of maximal proliferation (EC(10) and EC(90), respectively), or estrogen deprived. Estrogen independence was evaluated during selection by assessing cell growth in the absence or presence of E2 or 3βAdiol. Following >7 months of selection, estrogen independence developed in estrogen-deprived cells and EC(10)-selected cells. Functional analyses demonstrated that estrogen-deprived and EC(10)-selected cells developed estrogen independence via unique mechanisms, ERα-independent and dependent, respectively. Estrogen-independent proliferation in EC(10)-selected cells could be blocked by kinase inhibitors. However, these cells were resistant to kinase inhibition in the presence of low steroid concentrations. These data demonstrate that further understanding of the total estrogen environment in patients on AI therapy who experience recurrence is necessary to effectively treat endocrine-resistant disease