Hsp21potentiates antifungal drug tolerance in Candida albicans

Peer reviewedPublisher PD

Compliance with guidelines is related to better local recurrence-free survival in ductal carcinoma in situ

The aim was to study the effect of compliance with guidelines on local recurrence (LR)-free survival in patients treated for ductal carcinoma in situ (DCIS). From January 1992 to December 2003, 251 consecutive patients had been treated for DCIS in two hospitals in the North Netherlands. Every case in this two-hospital sample was reviewed in retrospect for its clinical and pathological parameters. It was determined whether treatment had been carried out according to clinical guidelines, and outcomes in follow-up were assessed. In addition, all patients treated for DCIS in this region (n=1389) were studied regarding clinical parameters, in order to determine whether the two-hospital sample was representative of the entire region. In the two-hospital sample, 31.4% (n=79) of the patients had not been treated according to the guidelines. Positive margins were associated with LR (hazard ratio (HR)=4.790, 95% confidence interval (CI) 1.696–13.531). Breast-conserving surgery and deviation from the guidelines were independent predictors of LR (HR=7.842, 95% CI 2.126–28.926; HR=2.778, 95% CI 0.982–6.781, respectively). Although the guidelines changed over time, time was not a significant factor in predicting LRs (HR=1.254, 95% CI 0.272–5.776 for time period 1992–1995 and HR=1.976, 95% CI 0.526–7.421 for time period 1996–1999). Clinical guidelines for the treatment of patients with DCIS have been developed and updated from existing literature and best evidence. Compliance with the guidelines was an independent predictor of disease-free survival. These findings support the application of guidelines in the treatment of DCIS

No effect of short-term amino acid supplementation on variables related to skeletal muscle damage in 100 km ultra-runners - a randomized controlled trial

Background: The purpose of this study was to investigate the effect of short-term supplementation of amino acids before and during a 100 km ultra-marathon on variables of skeletal muscle damage and muscle soreness. We hypothesized that the supplementation of amino acids before and during an ultra-marathon would lead to a reduction in the variables of skeletal muscle damage, a decrease in muscle soreness and an improved performance. Methods: Twenty-eight experienced male ultra-runners were divided into two groups, one with amino acid supplementation and the other as a control group. The amino acid group was supplemented a total of 52.5 g of an amino acid concentrate before and during the 100 km ultra-marathon. Pre- and post-race, creatine kinase, urea and myoglobin were determined. At the same time, the athletes were asked for subjective feelings of muscle soreness. Results: Race time was not different between the groups when controlled for personal best time in a 100 km ultra-marathon. The increases in creatine kinase, urea and myoglobin were not different in both groups. Subjective feelings of skeletal muscle soreness were not different between the groups. Conclusions: We concluded that short-term supplementation of amino acids before and during a 100 km ultra-marathon had no effect on variables of skeletal muscle damage and muscle soreness

Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery

BACKGROUND: After the availability of the results of validation studies, the sentinel lymph node biopsy (SLNB) has replaced routine axillary dissection (AD) as the new standard of care in early unifocal breast cancers. Multifocal (MF) and multicentric (MC) tumors have been considered a contraindication for this technique due to the possible incidence of a higher false-negative rate. This prospective study evaluates the lymphatic drainage from different tumoral foci of the breast and assesses the accuracy of SLNB in MF-MC breast cancer. PATIENTS AND METHODS: Patients with preoperative diagnosis of MF or MC infiltrating and clinically node-negative (cN0) breast carcinoma were enrolled in this study. Two consecutive groups of patients underwent SLN mapping using a different site of injection of the radioisotope tracer: a) "2ID" Group received two intradermal (ID) injections over the site of the two dominant neoplastic nodules. A lymphoscintigraphic study was performed after each injection to evaluate the route of lymphatic spreading from different sites of the breast. b) "A" Group had periareolar (A) injection followed by a conventional lymphoscintigraphy. At surgery, both radioguided SLNB (with frozen section exam) and subsequent AD were planned, regardless the SLN status. RESULTS: A total 31 patients with MF (n = 12) or MC (n = 19) invasive, cN0 cancer of the breast fulfil the selection criteria. In 2 ID Group (n = 15) the lymphoscintigraphic study showed the lymphatic pathways from two different sites of the breast which converged into one major lymphatic trunk affering to the same SLN(s) in 14 (93.3%) cases. In one (6.7%) MC cancer two different pathways were found, each of them affering to a different SLN. In A Group (n = 16) lymphoscintigraphy showed one (93.7%) or two (6.3%) lymphatic channels, each connecting areola with one or more SLN(s). Identification rate of SLN was 100% in both Groups. Accuracy of frozen section exam on SLN was 96.8% (1 case of micrometastasis was missed). SLN was positive in 13 (41.9%) of 31 patients, including 4 cases (30.7%) of micrometastasis. In 7 of 13 (53.8%) patients the SLN was the only site of axillary metastasis. SLNB accuracy was 96.8% (30 of 31), sensitivity 92.8 (13 of 14), and false-negative rate 7.1% (1 of 14). Since the case of skip metastasis was identified by the surgeon intraoperatively, it would have been no impact in the clinical practice. CONCLUSION: Our lymphoscintigraphic study shows that axillary SLN represents the whole breast regardless of tumor location within the parenchyma. The high accuracy of SLNB in MF and MC breast cancer demonstrates, according with the results of other series published in the literature, that both MF and MC tumors do not represent a contraindication for SLNB anymore

Tunable thermal expansion in framework materials through redox intercalation

Thermal expansion properties of solids are of fundamental interest and control of thermal expansion is important for practical applications but can be difficult to achieve. Many framework-type materials show negative thermal expansion when internal cages are empty but positive thermal expansion when additional atoms or molecules fill internal voids present. Here we show that redox intercalation offers an effective method to control thermal expansion from positive to zero to negative by insertion of Li ions into the simple negative thermal expansion framework material ScF3, doped with 10% Fe to enable reduction. The small concentration of intercalated Li ions has a strong influence through steric hindrance of transverse fluoride ion vibrations, which directly controls the thermal expansion. Redox intercalation of guest ions is thus likely to be a general and effective method for controlling thermal expansion in the many known framework materials with phonon-driven negative thermal expansion

Duration of adjuvant chemotherapy for breast cancer: a joint analysis of two randomised trials investigating three versus six courses of CMF

Cyclophosphamide, methotrexate and fluorouracil adjuvant combination chemotherapy for breast cancer is currently used for the duration of six monthly courses. We performed a joint analysis of two studies on the duration of adjuvant cyclophosphamide, methotrexate and fluorouracil in patients with node-positive breast cancer to investigate whether three courses of cyclophosphamide, methotrexate and fluorouracil might suffice. The International Breast Cancer Study Group Trial VI randomly assigned 735 pre- and perimenopausal patients to receive ‘classical’ cyclophosphamide, methotrexate and fluorouracil for three consecutive cycles, or the same chemotherapy for six consecutive cycles. The German Breast Cancer Study Group randomised 289 patients to receive either three or six cycles of i.v. cyclophosphamide, methotrexate and fluorouracil day 1, 8. Treatment effects were estimated using Cox regression analysis stratified by clinical trial without further adjustment for covariates. The 5-year disease-free survival per cents (±s.e.) were 54±2% for three cycles and 55±2% for six cycles (n=1024; risk ratio (risk ratio: CMF×3/CMF×6), 1.00; 95% confidence interval, 0.85 to 1.18; P=0.99). Use of three rather than six cycles was demonstrated to be adequate in both studies for patients at least 40-years-old with oestrogen-receptor-positive tumours (n=594; risk ratio, 0.86; 95% confidence interval, 0.68 to 1.08; P=0.19). In fact, results slightly favoured three cycles over six for this subgroup, and the 95% confidence interval excluded an adverse effect of more than 2% with respect to absolute 5-year survival. In contrast, three cycles appeared to be possibly inferior to six cycles for women less than 40-years-old (n=190; risk ratio, 1.25; 95% confidence interval, 0.87 to 1.80; P=0.22) and for women with oestrogen-receptor-negative tumours (n=302; risk ratio, 1.15; 95% confidence interval, 0.85 to 1.57; P=0.37). Thus, three initial cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil chemotherapy were as effective as six cycles for older patients (40-years-old) with oestrogen-receptor-positive tumours, while six cycles of adjuvant cyclophosphamide, methotrexate and fluorouracil might still be required for other cohorts. Because endocrine therapy with tamoxifen and GnRH analogues is now available for younger women with oestrogen-receptor-positive tumours, the need for six cycles of cyclophosphamide, methotrexate and fluorouracil is unclear and requires further investigation

Estimating Dengue Transmission Intensity from Sero-Prevalence Surveys in Multiple Countries

BACKGROUND:Estimates of dengue transmission intensity remain ambiguous. Since the majority of infections are asymptomatic, surveillance systems substantially underestimate true rates of infection. With advances in the development of novel control measures, obtaining robust estimates of average dengue transmission intensity is key for assessing both the burden of disease from dengue and the likely impact of interventions. METHODOLOGY/PRINCIPAL FINDINGS:The force of infection (λ) and corresponding basic reproduction numbers (R0) for dengue were estimated from non-serotype (IgG) and serotype-specific (PRNT) age-stratified seroprevalence surveys identified from the literature. The majority of R0 estimates ranged from 1-4. Assuming that two heterologous infections result in complete immunity produced up to two-fold higher estimates of R0 than when tertiary and quaternary infections were included. λ estimated from IgG data were comparable to the sum of serotype-specific forces of infection derived from PRNT data, particularly when inter-serotype interactions were allowed for. CONCLUSIONS/SIGNIFICANCE:Our analysis highlights the highly heterogeneous nature of dengue transmission. How underlying assumptions about serotype interactions and immunity affect the relationship between the force of infection and R0 will have implications for control planning. While PRNT data provides the maximum information, our study shows that even the much cheaper ELISA-based assays would provide comparable baseline estimates of overall transmission intensity which will be an important consideration in resource-constrained settings