Time-related expression profiles for heat shock protein gene transcripts (HSP40, HSP70) in the central nervous system of Lymnaea stagnalis exposed to thermal stress

Organisms exposed to environmental stressors respond by rapidly synthesising a suite of highly conserved proteins called heat shock proteins (HSPs). Environmental stress can also enhance and/or block memory formation, with longterm memory formation requiring gene activation and protein synthesis. Thermal stress in the pond snail Lymnaea stagnalis can enhance memory formation, and, in this study, the effect of thermal stress on HSP gene expression in the nervous system was investigated. Time-related expression profiles for HSP40 and HSP70 indicated rapid (100 fold and expression did not return to control levels within 8 h

North Atlantic ocean circulation and abrupt climate change during the last glaciation.

The most recent ice age was characterized by rapid and hemispherically asynchronous climate oscillations, whose origin remains unresolved. Variations in oceanic meridional heat transport may contribute to these repeated climate changes, which were most pronounced during marine isotope stage 3, the glacial interval 25 thousand to 60 thousand years ago. We examined climate and ocean circulation proxies throughout this interval at high resolution in a deep North Atlantic sediment core, combining the kinematic tracer protactinium/thorium (Pa/Th) with the deep water-mass tracer, epibenthic δ(13)C. These indicators suggest reduced Atlantic overturning circulation during every cool northern stadial, with the greatest reductions during episodic Hudson Strait iceberg discharges, while sharp northern warming followed reinvigorated overturning. These results provide direct evidence for the ocean's persistent, central role in abrupt glacial climate change

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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Argument Schemes for Reasoning with Legal Cases Using Values

ABSTRACT Argument schemes can provide a means of explicitly describing reasoning methods in a form that lends itself to computation. The reasoning required to distinguish cases in the manner of CATO has been previously captured as a set of argument schemes. Here we present argument schemes that encapsulate another way of reasoning with cases: using preferences between social values revealed in past decisions to decide cases which have no exact matching precedents when the cases are described in terms of factors. We provide a set of schemes, with variations to capture different ways of comparing sets and varying degrees of promotion of values; we formalise these schemes; and we illustrate them with some examples

Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case–control study

The aromatase inhibitor (AI)-associated musculoskeletal syndrome (AIMSS) occurs in approximately 50% of AI-treated patients. Inflammatory mediators are associated with oestrogen signalling and may change with oestrogen depletion. We hypothesised that AIMSS may be associated with changes in circulating inflammatory markers

Endocrine therapy and related issues in hormone receptor-positive early breast cancer: a roundtable discussion by the breast cancer therapy expert group (BCTEG)

Purpose: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient’s comorbid conditions, actual versus perceived benefit of treatments, patient’s compliance as well as financial/reimbursement issues, and long-term tolerability of therapy. Methods: A meeting of global oncology experts was convened in January 2017 with the belief that there is a gap in clinical practice guidance on several fundamental issues in breast cancer care, particularly in the community setting, where oncologists may encounter multiple tumor types. The goal was to discuss some of the most important questions in this area and provide some guidance for practicing oncologists. Results: Topics addressed included risk of contralateral breast cancer recurrence in patients with estrogen receptor-positive early breast cancer who have undergone 5 years of adjuvant endocrine therapy, adverse events associated with endocrine therapy and their management, emergent data on adjuvant bisphosphonate therapy and its apparent benefit in reducing breast cancer recurrence, recent findings of extended adjuvant endocrine therapy trials, and the use of currently available genomic biomarker tests as a means of further informing treatment decisions. Conclusions: A summary of the discussion on these topics and several ‘expert opinion statements’ are provided herein in an effort to convey the collective insights of the panel as it relates to current standard practice

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes

Collection of Epithelial Cells from Rodent Mammary Gland Via Laser Capture Microdissection Yielding High-Quality RNA Suitable for Microarray Analysis

Laser capture microdissection (LCM) enables collection of cell populations highly enriched for specific cell types that have the potential of yielding critical information about physiological and pathophysiological processes. One use of cells collected by LCM is for gene expression profiling. Samples intended for transcript analyses should be of the highest quality possible. RNA degradation is an ever-present concern in molecular biological assays, and LCM is no exception. This paper identifies issues related to preparation, collection, and processing in a lipid-rich tissue, rodent mammary gland, in which the epithelial to stromal cell ratio is low and the stromal component is primarily adipocytes, a situation that presents numerous technical challenges for high-quality RNA isolation. Our goal was to improve the procedure so that a greater probe set present call rate would be obtained when isolated RNA was evaluated using Affymetrix microarrays. The results showed that the quality of RNA isolated from epithelial cells of both mammary gland and mammary adenocarcinomas was high with a probe set present call rate of 65% and a high signal-to-noise ratio

Influence of the incremental step size in work rate on exercise response and gas exchange in patients with pulmonary hypertension

<p>Abstract</p> <p>Background</p> <p>Cardiopulmonary exercise testing (CPET) has become increasingly important as a routine procedure in daily clinical work. So far, it is generally accepted that an individualized exercise protocol with exercise duration of 6 to 12 minutes is preferable to assess maximal exercise performance. The aim of this study was to compare an individualized NYHA adapted exercise protocol with a fixed standard protocol in patients with severe pulmonary arterial hypertension.</p> <p>Methods</p> <p>Twenty-two patients (17 female, 5 male; mean age 49 ± 14 yrs) underwent symptom limited CPET on a bicycle. On two consecutive days each subject performed a stepwise CPET according to a modified Jones protocol (16 Watt per minute stages) as well as an individualized NYHA adapted protocol with 5 or 10 Watt/min stages in a randomized order. Oxygen uptake at peak exercise (peakVO₂) and anaerobic threshold (VO₂AT), maximal ventilation (VE), breathing reserve (VE/MVV), ventilatory efficiency (VE vs. VCO₂slope), exercise time, maximal power and work rate were assessed and compared between both protocols.</p> <p>Results</p> <p>Comparing both, adapted NYHA protocol and standardized Jones protocol, we found significant differences in maximal power (56.7 ± 19 W vs. 74 ± 18 W; p < 0.001) and exercise time (332 ± 107 sec. vs. 248 ± 72 sec.; p < 0.001). In contrast, no significant differences were obvious comparing both protocols concerning work rate, VE, VE/MVV, peakVO₂, VO₂AT and VE vs. VCO₂slope.</p> <p>Conclusion</p> <p>Variations of incremental step size during CPET significantly affect exercise time and maximal power, whereas relevant parameters for clinical judgement and prognosis such as oxygen uptake, ventilation and ventilatory efficiency remain unchanged. These findings have practical implications for the exercise evaluation of patients with pulmonary hypertension. To reach maximal results for ventilation, oxygen uptake and gas exchange an individualization of incremental step size appears not to be mandatory.</p