508 research outputs found
Unilateral vs. bilateral squat training for strength, sprints and agility in academy rugby players
Two highly divergent alcohol dehydrogenases of melon exhibit fruit ripening-specific expression and distinct biochemical characteristics
Alcohol dehydrogenases (ADH) participate in
the biosynthetic pathway of aroma volatiles in fruit by
interconverting aldehydes to alcohols and providing substrates
for the formation of esters. Two highly divergent
ADH genes (15% identity at the amino acid level) of
Cantaloupe Charentais melon (Cucumis melo var. Cantalupensis)
have been isolated. Cm-ADH1 belongs to the
medium-chain zinc-binding type of ADHs and is highly
similar to all ADH genes expressed in fruit isolated so far.
Cm-ADH2 belongs to the short-chain type of ADHs. The
two encoded proteins are enzymatically active upon
expression in yeast. Cm-ADH1 has strong preference for
NAPDH as a co-factor, whereas Cm-ADH2 preferentially
uses NADH. Both Cm-ADH proteins are much more active
as reductases with Kms 10–20 times lower for the conversion
of aldehydes to alcohols than for the dehydrogenation
of alcohols to aldehydes. They both show strong preference
for aliphatic aldehydes but Cm-ADH1 is capable of
reducing branched aldehydes such as 3-methylbutyraldehyde,
whereas Cm-ADH2 cannot. Both Cm-ADH genes are
expressed specifically in fruit and up-regulated during
ripening. Gene expression as well as total ADH activity are
strongly inhibited in antisense ACC oxidase melons and in
melon fruit treated with the ethylene antagonist 1-methylcyclopropene
(1-MCP), indicating a positive regulation by
ethylene. These data suggest that each of the Cm-ADH
protein plays a specific role in the regulation of aroma
biosynthesis in melon fruit
Analysis of the ATR-Chk1 and ATM-Chk2 pathways in male breast cancer revealed the prognostic significance of ATR expression
The ATR-Chk1 and ATM-Chk2 pathways are central in DNA damage repair (DDR) and their over-activation may confer aggressive molecular features, being an adaptive response to endogenous DNA damage and oncogene-induced replication stress. Herein we investigated the ATR-Chk1 and ATM-Chk2 signalings in male breast cancer (MBC). The expression of DDR kinases (pATR, pATM, pChk1, pChk2, and pWee1) and DNA damage markers (pRPA32 and γ-H2AX) was evaluated by immunohistochemistry in 289 MBC samples to assess their association. Survival analyses were carried out in 112 patients. Survival curves were estimated with the Kaplan-Meier method and compared by log-rank test. Cox proportional regression models were generated to identify variables impacting survival outcomes. The expression of pATR conferred poorer survival outcomes (log rank p = 0.013, p = 0.007 and p = 0.010 for overall, 15- and 10-year survival, respectively). Multivariate Cox models of 10-year survival and overall indicated that pATR expression, alone or combined with pChk2, was an independent predictor of adverse outcomes (10-year survival: pATR: HR 2.74, 95% CI: 1.23–6.10; pATR/pChk2: HR 2.92, 95% CI: 1.35–6.33; overall survival: pATR: HR 2.58, 95% CI: 1.20–5.53; pATR/pChk2: HR 2.89, 95% CI: 1.37–6.12). Overall, the ATR/ATM-initiated molecular cascade seems to be active in a fraction of MBC patients and may represent a negative prognostic factor
Effects of intrauterine exposure to synthetic glucocorticoids on fetal, newborn, and infant hypothalamic-pituitary-adrenal axis function in humans : a systematic review
BACKGROUND: Synthetic glucocorticoids are commonly used in reproductive medicine. Fetal organ systems are highly sensitive to changes in the intrauterine environment, including overexposure to glucocorticoids. Structural and functional alterations resulting from such changes may persist throughout life and have been associated with diverse diseases. One system that could be particularly sensitive to fetal glucocorticoid overexposure is the hypothalamic-pituitary-adrenal (hpa) axis. Many human studies have investigated this possibility, but a systematic review to identify consistent, emergent findings is lacking. METHODS: We systematically review 49 human studies, assessing the effects of intrauterine exposure to synthetic glucocorticoids on fetal, neonate, and infant hpa function. RESULTS: Study quality varied considerably, but the main findings held true after restricting the analyses to higher-quality studies: intrauterine exposure to synthetic glucocorticoids reduces offspring hpa activity under unstimulated conditions after pain but not pharmacological challenge. Although reduced unstimulated hpa function appears to recover within the first 2 wk postpartum, blunted hpa reactivity to pain is likely to persist throughout the first 4 months of life. There is some evidence that the magnitude of the effects is correlated with the total amount of glucocorticoids administered and varies with the time interval between glucocorticoid exposure and hpa assessment. CONCLUSIONS: This systematic review has allowed the demonstration of the way in which intrauterine exposure to various regimens of synthetic glucocorticoids affects various forms of hpa function. As such, it guides future studies in terms of which variables need to be focused on in order to further strengthen the understanding of such therapy, whilst continuing to profit from its clinical benefits
Male breast cancer
Male breast cancer (MBC) is a rare disease representing less than 1% of all breast cancers (BC) and less than 1% of cancers in men. Age at presentation is mostly in the late 60s. MBC is recognized as an estrogen-driven disease, specifically related to hyperestrogenism. About 20% of MBC patients have family history for BC. Mutations in BRCA1 and, predominantly, BRCA2, account for approximately 10% of MBC cases.
Because of its rarity, MBC is often compared with female BC (FBC). Based on age-frequency distribution, age-specific incidence rate patterns and prognostic factors profiles, MBC is considered similar to late-onset, postmenopausal estrogen/progesterone receptor positive (ER+/PR+) FBC. However, clinical and pathological characteristics of MBC do not exactly overlap FBC. Compared with FBC, MBC has been reported to occur later in life, present at a higher stage, and display lower histologic grade, with a higher proportion of ER+ and PR+ tumors.
Although rare, MBC remains a substantial cause for morbidity and mortality in men, probably because of its occurrence in advanced age and delayed diagnosis. Diagnosis and treatment of MBC generally is similar to that of FBC. Men tend to be treated with mastectomy rather than breast-conserving surgery. The backbone of adjuvant therapy or palliative treatment for advanced disease is endocrine, mostly tamoxifen.
Use of FBC-based therapy led to the observation that treatment outcomes for MBC are worse and that survival rates for MBC do not improve like FBC. These different outcomes may suggest a non-appropriate utilization of treatments and that different underlying pathogenetic mechanisms may exist between male and female BC
Male breast cancer: a report of 127 cases at a Moroccan institution
Background: Male breast cancer (MBC) is a rare disease representing less than 1% of all malignancies in men and
only 1% of all incident breast cancers. Our study details clinico-pathological features, treatments and prognostic
factors in a large Moroccan cohort.
Findings: One hundred and twenty-seven patients were collected from 1985 to 2007 at the National Institute of
Oncology in Rabat, Morocco.
Median age was 62 years and median time for consultation 28 months. The main clinical complaint was a mass
beneath the areola in 93, 5% of the cases. Most patients have an advanced disease. Ninety-one percent of tumors
were ductal carcinomas.
Management consisted especially of radical mastectomy; followed by adjuvant radiotherapy and hormonal therapy
with or without chemotherapy. The median of follow-up was 30 months. The evolution has been characterized by
local recurrence; in twenty two cases (17% of all patients). Metastasis occurred in 41 cases (32% of all patients). The
site of metastasis was the bone in twenty cases; lung in twelve cases; liver in seven case; liver and skin in one case
and pleura and skin in one case.
Conclusion: Male breast cancer has many similarities to breast cancer in women, but there are distinct features
that should be appreciated. Future research for better understanding of this disease at national or international
level are needed to improve the management and prognosis of male patients
Expert Status and Performance
Expert judgements are essential when time and resources are stretched or we face novel dilemmas requiring fast solutions. Good advice can save lives and large sums of money. Typically, experts are defined by their qualifications, track record and experience [1], [2]. The social expectation hypothesis argues that more highly regarded and more experienced experts will give better advice. We asked experts to predict how they will perform, and how their peers will perform, on sets of questions. The results indicate that the way experts regard each other is consistent, but unfortunately, ranks are a poor guide to actual performance. Expert advice will be more accurate if technical decisions routinely use broadly-defined expert groups, structured question protocols and feedback
PbSe Nanorod Field-Effect Transistors:Room- and Low-Temperature Performance
Lead chalcogenides with large exciton Bohr radius display strong quantum confinement, which make them applicable in a wide range of optoelectronic devices such as solar cells and photodetectors. Especially, 1D PbSe nanocrystals attract much attention with their potential for multiple exciton generation. However, very little is known on their charge transport properties. In this study well performing field-effect transistors based on PbSe nanorods with an inorganic iodide-based ligand are presented for the first time. The transistors at room temperature display ambipolar characteristics with electron mobility of approximate to 0.1 cm(2) V-1 s(-1) and hole mobility of 1.1 x 10(-4) cm(2) V-1 s(-1) in the ultraclean environment. Low temperature investigation reveals a transition around 200 K between nearest-neighbor and variable-range hopping mechanism. Below 200 K, the transport properties are dominated by the severe disorder
Evaluation of applying IHC4 as a prognostic model in the translational study of Intergroup Exemestane Study (IES): PathIES
Background: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2–3 years from tamoxifen to exemestane. This PathIES aimed to assess the role of immunohistochemical (IHC)4 score in determining the relative sensitivity to either tamoxifen or sequential treatment with tamoxifen and exemestane. Patients and methods: Primary tumour samples were available for 1274 patients (27% of IES population). Only patients for whom the IHC4 score could be calculated (based on oestrogen receptor, progesterone receptor, HER2 and Ki67) were included in this analysis (N = 430 patients). The clinical score (C) was based on age, grade, tumour size and nodal status. The association of clinicopathological parameters, IHC4(+C) scores and treatment effect with time to distant recurrence-free survival (TTDR) was assessed in univariable and multivariable Cox regression analyses. A modified clinical score (PathIEscore) (N = 350) was also estimated. Results: Our results confirm the prognostic importance of the original IHC4, alone and in conjunction with clinical scores, but no significant difference with treatment effects was observed. The combined IHC4 + Clinical PathIES score was prognostic for TTDR (P < 0.001) with a hazard ratio (HR) of 5.54 (95% CI 1.29–23.70) for a change from 1st quartile (Q1) to Q1–Q3 and HR of 15.54 (95% CI 3.70–65.24) for a change from Q1 to Q4. Conclusion: In the PathIES population, the IHC4 score is useful in predicting long-term relapse in patients who remain disease-free after 2–3 years. This is a first trial to suggest the extending use of IHC4+C score for prognostic indication for patients who have switched endocrine therapies at 2–3 years and who remain disease-free after 2–3 years
Inverse relationship between ER-β and SRC-1 predicts outcome in endocrine-resistant breast cancer
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