The motivation of breast cancer patients to participate in a national randomized control trial.

PURPOSE: Clinical trials are essential for development of better cancer care. Therefore, patient willingness to participate in these trials is important. The aim of this study was to assess motivation and thoughts of breast cancer patients concerning participation in a clinical trial. METHODS: Twenty-one patients participated in two semi-structed interviews about participating in a clinical trial testing the efficacy of cryotherapy for the prevention of chemotherapy-induced peripheral neuropathy in breast cancer patients treated with paclitaxel. The interviews took place before and after the intervention and were coded and categorized following the steps in Braun & Clarke's thematic analysis to identify motivational factors and experiential themes. RESULTS: Four overarching themes were identified: (1) reasons to participate in the trial, (2) personal resources, (3) safety, and (4) experience of the randomization. The most frequent reason for participating in the trial was to support research and help others, but many also participated hoping to receive the intervention treatment. The study showed that a surplus of personal resources played an important role when the patients decided to participate in the trial. Differences were found between patients belonging to the intervention and the control group in relation to these themes. Finally, both groups experienced the extra examinations received during the trial as an additional source of safety. CONCLUSION: This qualitative study found different factors influencing the experience of participating in a clinical trial, e.g., intervention-status, personal resources, and safety. This knowledge can be valuable when planning future clinical trials involving breast cancer patients.

Conidiobolus lunulus, a new entomophthoralean species isolated from leafcutter ants.

Entomophthoralean fungi with pathogenic abilities to infect social insects are rare. Here, we describe a fungus isolated from leafcutter ants. Morphologically, the fungus has spherical primary conidia and two types of microconidia: one with the same shape as the primary conidia and another with an elliptical to half-moon shape. The fungus also produces villose conidia known previously only from Conidiobolus coronatus. A multilocus phylogenetic analysis was performed with nuc rDNA sequences from three regions (28S, 18S, and internal transcribed spacer [ITS]). Our isolates are distinguished as a new species, described here as Conidiobolus lunulus, and is more closely related to C. brefeldianus than to C. coronatus, despite the greater morphological resemblance to the latter. Morphological differences, unique phylogenetic placement, and isolation from an altogether new host support this finding. This is the first record of an entomophthoralean species isolated from leafcutter ants.

Fluorescence or X-ray cholangiography in elective laparoscopic cholecystectomy: a randomized clinical trial.

BACKGROUND: Safe laparoscopic cholecystectomy may necessitate biliary imaging, and non-invasive fluorescence cholangiography may have advantages over contrast X-ray cholangiography. This trial compared fluorescence and X-ray cholangiography for visualization of the critical junction between the cystic, common hepatic and common bile ducts. METHODS: This non-inferiority blinded RCT included patients who had either intraoperative fluorescence cholangiography using 0·05 mg/kg indocyanine green or X-ray cholangiography during elective laparoscopic cholecystectomy. RESULTS: Between March 2015 and August 2018, a total of 120 patients were randomized (60 in each group). There were no drop-outs and 30-day follow-up data were available for all patients. In intention-to-treat analysis, there was no difference between the fluorescence and X-ray cholangiography groups in ability to visualize the critical junction (49 of 60 versus 51 of 60 respectively; P = 0·230). Fluorescence cholangiography was faster by a few minutes: median 2·0 (range 0·5-5·0) versus 4·8 (1·3-17·6) min (P < 0·001). CONCLUSION: Fluorescence cholangiography was confirmed to be non-inferior to X-ray cholangiography in visualizing the critical junction during laparoscopic cholecystectomy. Registration number: NCT02344654 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La práctica de una colecistectomía laparoscópica segura puede requerir imágenes de la vía biliar, en las cuales la colangiografía con fluorescencia no invasiva puede tener ventajas sobre la colangiografía con contraste con rayos X. Este ensayo comparó la colangiografía con fluorescencia con la colangiografía con rayos X para la visualización de la unión crítica entre el conducto cístico, el conducto hepático común y los conductos biliares comunes. MÉTODOS: Ensayo clínico aleatorizado, ciego, de no inferioridad que incluyó a 120 pacientes en los que durante la colecistectomía laparoscópica electiva se practicó una colangiografía con fluorescencia intraoperatoria utilizando 0,05 mg/kg de verde de indocianina o una colangiografía con rayos X. RESULTADOS: De marzo de 2015 a agosto de 2018, se aleatorizaron un total de 120 pacientes (6 en cada grupo), en los que no hubo abandonos y con datos de seguimiento de 30 días disponibles en todos ellos. Basado en un análisis por intención de tratamiento, la capacidad de visualizar la unión crítica fue igual entre los dos grupos (49/60 versus 51/60, P = 0,23). La colangiografía con fluorescencia fue más rápida de realizar, en unos pocos minutos (mediana 2 min (rango 0,5-5,0) versus 5 min (rango 5,2-17,6), P < 0,001). CONCLUSIÓN: Se confirmó que la colangiografía con fluorescencia no fue inferior a la colangiografía con rayos X para visualizar la unión crítica durante la colecistectomía laparoscópica.

A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1).

STUDY AIM: Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). METHODS: Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). Patients with nadir leukopenia grade 0-2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75-90 mg/m2, C 900-1200 mg/m2) or fixed treatment with 6 standard FEC. Patients with grade 3-4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). RESULTS: The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC (N = 524) or standard FEC (N = 528), whereas 401 patients with leukopenia grade 3-4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67-1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57-1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. CONCLUSIONS: The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment.

Psychosocial predictors of posttreatment pain after nonmetastatic breast cancer treatment: a systematic review and meta-analysis of prospective studies.

BACKGROUND: The search for risk factors of pain after breast cancer, which affects a considerable proportion of the women, has primarily focused on clinical factors. The aim of this meta-analysis was to explore the less well-studied psychosocial predictors of pain after breast cancer treatment. METHODS: Two independent searches were conducted in PubMed, PsycINFO, Web of Science, and CINAHL. Eligible studies were prospective, observational studies of women aged ≥18 years, diagnosed and treated for nonmetastatic breast cancer ≥3 months previously. Additional inclusion criteria were that studies had assessed at least one pain outcome and at least one psychosocial predictor. The psychosocial predictors investigated included: 1) psychological-behavioral states, 2) psychological traits, and 3) social support. Effect size correlations (ESr) were chosen as the effect size and pooled using a random effects model. We also explored a number of study characteristics as possible moderators of the effect with meta-regression. RESULTS: Of the total of 13 eligible studies identified, most studies measured psychosocial predictors at presurgery. Neither psychological-behavioral states (ESr: 0.05; p=0.13; K=11) nor psychological traits (ESr: 0.02; p=0.48; K=6) emerged as statistically significant predictors of pain. In contrast, higher levels of social support were statistically significantly associated with less pain (ESr: -0.24; p<0.001; K=4). In studies of psychological-behavioral states, longer follow-up was associated with smaller effect sizes (p=0.023). Furthermore, older mean sample age was associated with larger effect sizes for both psychological-behavioral states (p=0.0004) and psychological traits (p=0.035). CONCLUSION: The results of this meta-analysis suggest that psychosocial factors measured at presurgery may only be of modest predictive value in identifying women at risk of developing pain after breast cancer treatment. While speculative, psychosocial factors may play a larger role in the postsurgery trajectory, which could be valuable to investigate in future studies.

Mindfulness-based cognitive therapy (MBCT) is cost-effective compared to a wait-list control for persistent pain in women treated for primary breast cancer-Results from a randomized controlled trial.

OBJECTIVE: To investigate the cost-effectiveness of mindfulness-based cognitive therapy (MBCT) compared to a wait-list control group for pain in women treated for breast cancer. METHODS: A total of 129 women were randomly allocated to MBCT or a wait-list control group. The primary outcome was the minimal clinically important difference (MCID) on pain intensity (≥2 point reduction on an 11-point Numeric Rating Scale). Analyses were conducted from the health care system perspective and included data on health care utilization and pain medication retrieved from national registries for the period from baseline (T1) to 6 months postintervention (T4). Bootstrap simulations were used to estimate confidence intervals for the incremental cost and effect measures, and cost-effectiveness acceptability curves. In sensitivity analyses, we replaced dropouts with last-observation-carried-forward and tested consequences of higher costs of the intervention. RESULTS: The intervention cost was 240€ per participant. The average total cost from T1 to T4 in the MBCT group was 1706€ compared with 2436€ in the control group (mean difference: 729€, P = .07). More women in the MBCT group (N:19/36; 52.8%) than in the control group (N:14/48; 29.2%) achieved an MCID in pain intensity (OR=2.71, P = .03). The MBCT was cost-effective with a probability of 85% with a value of an additional women achieving MCID set to zero remained cost-effective with a probability of 70% to 82% when smaller effect and higher MBCT costs were assumed. CONCLUSIONS: Our results suggest that MBCT is a cost-effective pain intervention for women treated for breast cancer. Future studies could include utility measures, indirect costs, and active control groups to increase the generalizability and pragmatic value of the results.

Clinical and psychological moderators of the effect of mindfulness-based cognitive therapy on persistent pain in women treated for primary breast cancer - explorative analyses from a randomized controlled trial.

BACKGROUND: Mindfulness-based intervention has been found efficacious in reducing persistent pain in women treated for breast cancer. Little, however, is known about possible moderators of the effect. We explored clinical and psychological moderators of the effect on pain intensity previously found in a randomized controlled trial of mindfulness-based cognitive therapy (MBCT) with women treated for breast cancer with persistent pain. MATERIAL AND METHODS: A total of 129 women treated for breast cancer reporting persistent pain were randomized to MBCT or a wait-list control. The primary outcome of pain intensity (11-point numeric rating scale) was measured at baseline, post-intervention, three, and six months follow-up. Proposed clinical moderators included age, axillary lymph node dissection (ALND), radiotherapy, and endocrine treatment. Psychological moderators included psychological distress [the Hospital Anxiety and Depression Scale (HADS)], the adult attachment dimensions anxiety and avoidance [the Experiences in Close Relationships Short Form (the ECR-SF)], and alexithymia [the Toronto Alexithymia Scale (TAS-20)]. Multi-level models were used to test moderation effects over time, i.e. time × group × moderator. RESULTS: Only attachment avoidance (p = 0.03, d = 0.36) emerged as a statistically significant moderator. Higher levels of attachment avoidance predicted a larger effect of MBCT in reducing pain intensity compared with lower levels attachment avoidance. None of the remaining psychological or clinical moderators reached statistical significance. However, based on the effect size, radiotherapy (p = 0.075, d = 0.49) was indicated as a possible clinical moderator of the effect, with radiotherapy being associated with a smaller effect of MBCT on pain intensity over time compared with no radiotherapy. CONCLUSION: Attachment avoidance, and potentially radiotherapy, may be clinically relevant factors for identifying the patients who may benefit most from MBCT as a pain intervention. Due to the exploratory nature of the analyses, the results should be considered preliminary.

Evaluation of different sampling methods and criteria for diagnosing canine urinary tract infection by quantitative bacterial culture.

The use of voided urine specimens for bacteriological culture in dogs is discouraged because contamination from external genitalia could lead to misinterpretation of laboratory results. Quantitative culturing and defining significant bacteriuria could increase the usefulness of voided specimens. However, limited evidence exists for the cut-offs currently recommended. The aim of this study was to evaluate the accuracy of current veterinary cut-off values for significant bacteriuria in voided canine urine. A secondary aim was to investigate if accuracy improved when applying qualitative criteria used in humans. Paired urine specimens were collected by both cystocentesis and voiding, and quantitative bacteriological cultures were performed within the same day. Cystocentesis was used as the reference standard with a cut-off for significant bacteriuria of ≥1000 colony forming units (CFU)/mL. Voided specimens were compared to cystocentesis using: (1) the veterinary cut-off of ≥100,000 CFU/mL; and (2) various cut-offs depending on qualitative criteria (sex, clinical signs and complicating factors), adapted from human guidelines. Ninety-four dogs with suspected urinary tract infection (UTI) were included for analysis. The veterinary cut-off yielded an accuracy of 94% with a sensitivity and specificity of 94% (95% confidence intervals [CI] 0.81, 0.99) and 94% (95% CI 0.86, 0.98), respectively. Applying the human guidelines did not improve overall accuracy (89%), and yielded a sensitivity and specificity of 97% (95% CI 0.86, 1.00) and 86% (95% CI 0.77, 0.92), respectively. The veterinary cut-off value of ≥100,000 CFU/mL for voided urine is appropriate for determining significant bacteriuria in the majority of dogs with suspected UTI if specimens are refrigerated and cultured on the day of collection.

Relative Effects of Temperature, Light, and Humidity on Clinging Behavior of Metacercariae-Infected Ants.

The lancet fluke, Dicrocoelium dendriticum, is perhaps the best-known example of parasite manipulation of host behavior, which is manifested by a radically changed behavior that leaves infected ants attached to vegetation at times when transmission to an herbivore host is optimal. Despite the publicity surrounding this parasite, curiously little is known about factors inducing and maintaining behavioral changes in its ant intermediate host. This study examined the importance of 3 environmental factors on the clinging behavior of red wood ants, Formica polyctena , infected with D. dendriticum . This behavior, hypothesized to involve cramping of the mandibular muscles in a state of tetany, was observed in naturally infected F. polyctena under controlled temperature, light, and humidity conditions. We found that low temperature significantly stimulated and maintained tetany in infected ants while light, humidity, ant size, and infection intensity had no influence on this behavior. Under none of the experimental conditions did uninfected ants attach to vegetation, demonstrating that tetany was induced by D. dendriticum . Temperature likely has a direct impact on the initiation of clinging behavior, but it may also serve as a simple but reliable indicator of the encounter rate between infected ants and ruminant definitive hosts. In addition, temperature-sensitive behavior manipulation may protect infected ants from exposure to temperatures in the upper thermal range of the host.

Utilizing Genomics to Study Entomopathogenicity in the Fungal Phylum Entomophthoromycota: A Review of Current Genetic Resources.

The order Entomophthorales, which formerly contained c.280 species, has recently been recognized as a separate phylum, Entomophthoromycota, consisting of three recognized classes and six families. Many genera in this group contain obligate insect-pathogenic species with narrow host ranges, capable of producing epizootics in natural insect populations. Available sequence information from the phylum Entomophthoromycota can be classified into three main categories: first, partial gene regions (exons+introns) used for phylogenetic inference; second, protein coding gene regions obtained using degenerate primers, expressed sequence tag methodology or de novo transcriptome sequencing with molecular function inferred by homology analysis; and third, primarily forthcoming whole-genome sequencing data sets. Here we summarize the current genetic resources for Entomophthoromycota and identify research areas that are likely to be significantly advanced from the availability of new whole-genome resources.

Assessment of acute oxaliplatin-induced cold allodynia: a pilot study.

BACKGROUND: Following oxaliplatin treatment, acute neurotoxicity symptoms are suggested to be correlated with both the development and degree of chronic neuropathy. AIMS: The aim of this clinical commentary was to examine different methods to assess acute cold allodynia and dysesthesia in patients treated with adjuvant oxaliplatin. METHODS: Nine patients over the age of 18 years scheduled for standard adjuvant treatment with capecitabine and oxaliplatin were included. Patients were asked to come for two visits: a baseline visit before and a follow-up visit within 5 days after treatment. Patients were examined with questionnaires, thermal tests, and the thermal grill. RESULTS: All patients reported neurotoxicity, and they all had abnormal cold sensitivity. The only significant changes observed were increased ratings of pain, unpleasantness, and pricking sensations to holding a ~8°C metal cylinder for 10 s and an increased intensity of unpleasantness and pricking sensation to the 20-s contact with the 10°C plates of the thermal grill on the palmar hand. CONCLUSIONS: he results showed that the palm of the hand is the most sensitive part of the body when detecting oxaliplatin-induced cold allodynia, and the use of a cold metal cylinder seems as a promising sensitive method.

Are Cancer Patients' Socioeconomic and Cultural Factors Associated with Contact to General Practitioners in the Last Phase of Life?

Introduction. General practitioners (GPs) play an important role in end of life care, which should be offered regardless of socioeconomic position and cultural factors. The aim was to analyse associations between GP contacts at the end of life and socioeconomic and cultural characteristics of Danish cancer patients. Method. Population-based study identifying 599 adults who died of cancer from March to November 2006, in Aarhus County, Denmark. Associations between health register-based data on "total GP face-to-face contacts" and "GP home visits" during the last 90 days of life and patients' socioeconomic and cultural characteristics were calculated. Results. Having low income (RR: 1.18 (95% CI: 1.03; 1.35)) and being immigrants or descendants of immigrants (RR: 1.17 (95% CI: 1.02; 1.35)) were associated with GP face-to-face contacts. However, patients living in large municipalities had lower likelihood of having both GP face-to-face contacts in general (RR: 0.85 (95% CI: 0.77;0.95)) and GP home visits (RR: 0.89 (95% CI: 0.80; 0.99)). Conclusion. This study indicates higher proportion of GP contacts to economically deprived patients and immigrants/descendants of immigrants. These subgroups were, however, small and results should be looked upon with caution. Furthermore, palliative needs were not included and together with urban/rural the underlying causes need further investigation.

Socio-demographic, treatment-related, and health behavioral predictors of persistent pain 15 months and 7-9 years after surgery: a nationwide prospective study of women treated for primary breast cancer.

The purpose of this study was to investigate and report prevalence and risk factors for persistent pain in breast cancer patients at 15 months and 7-9 years post surgery. A nationwide inception cohort study including 3343 women treated for primary breast cancer between 2001 and 2004, who returned a questionnaire 3 months post surgery. Socio-demographic and clinical information was obtained from registries. Questionnaire data on pain and health behaviors were obtained 15 months and 7-9 years post surgery. A total of 1905 women were eligible for analysis. At 15-month post surgery, 32.7 % reported pain "almost every day" or more frequently. At 7-9 years post surgery, the prevalence decreased to 20.4 %. Socio-demographic (young age, lower education, lower income, lower occupational status), treatment-related (being lymph node positive, axillary lymph node dissection (ALND), post-menopausal endocrine treatment), and health behavioral factors (smoking ≥ 10 cigarettes/day, obesity (BMI ≥ 30 and < 35), comorbidity, poor physical function) were significantly associated with pain at 15 months. Being physically active and moderate alcohol intake (<3 units/day) were negatively associated with pain. At 7-9 years post surgery, only ALND (OR:1.41, p = 0.03), post-menopausal endocrine treatment (OR:1.62, p = 0.01), poorer physical function (ORs:2.00-2.40, p = 0.003), and weight training (h/week) at 15 months (OR:1.10, p = 0.008) were significant predictors of pain when adjusting for age and pain 15 months post surgery. No socio-demographic predictors remained statistically significant. Younger age, lower socio-economic status, more invasive surgery, endocrine treatment, and adverse health behaviors emerged as risk factors for persistent pain. The influence of risk factors changed over time, suggesting a complex course of pain development and maintenance.

Long-term subjective cognitive functioning following adjuvant systemic treatment: 7-9 years follow-up of a nationwide cohort of women treated for primary breast cancer.

BACKGROUND: There is growing concern among breast cancer (BC) patients and survivors about cognitive impairment following systemic treatments. The aim of the present study was to investigate the long-term effects of standard systemic adjuvant therapies on subjective cognitive impairment (SCI) in a large nationwide cohort of BC survivors 7-9 years after primary surgery. METHODS: Participants were recruited from the nationwide Psychosocial Factors and Breast Cancer inception cohort of Danish women treated for primary BC. SCI was assessed with the Cognitive Failures Questionnaire and women allocated to systemic treatment according to nationwide standard protocols were compared with women who had not received any systemic treatments. RESULTS: A total of 1889 recurrence-free survivors were eligible for analysis. No difference in SCI was found between survivors across standardized systemic treatment protocols when analyses were stratified by menopausal status and adjusted for possible sociodemographic and treatment-related confounders. The frequency of significant SCI in a subgroup of survivors in the age range 65-74 years was ∼7%. CONCLUSIONS: No differences in long-term SCI at 7-9 years post surgery were found between women who had received systemic therapies and those who had not. Furthermore, the observed proportion of survivors with significant SCI was comparable to normative data. These results are important to communicate to patients, survivors, and clinicians alike, especially in the light of increasing concern about cognitive impairment following systemic therapies.

New selective inhibitors of calcium-activated chloride channels - T16A(inh) -A01, CaCC(inh) -A01 and MONNA - what do they inhibit?

BACKGROUND AND PURPOSE: T16A(inh)-A01, CaCC(inh)-A01 and MONNA are identified as selective inhibitors of the TMEM16A calcium-activated chloride channel (CaCC). The aim of this study was to examine the chloride-specificity of these compounds on isolated resistance arteries in the presence and absence (±) of extracellular chloride. EXPERIMENTAL APPROACH: Isolated resistance arteries were maintained in a myograph and tension recorded, in some instances combined with microelectrode impalement for membrane potential measurements or intracellular calcium monitoring using fura-2. Voltage-dependent calcium currents (VDCC) were measured in A7r5 cells with voltage-clamp electrophysiology using barium as a charge carrier. KEY RESULTS: Rodent arteries preconstricted with noradrenaline or U46619 were concentration-dependently relaxed by T16A(inh) -A01 (0.1-10 µM): IC50 and maximum relaxation were equivalent in ±chloride (30 min aspartate substitution) and the T16A(inh) -A01-induced vasorelaxation ±chloride were accompanied by membrane hyperpolarization and lowering of intracellular calcium. However, agonist concentration-response curves ±chloride, with 10 µM T16A(inh) -A01 present, achieved similar maximum constrictions although agonist-sensitivity decreased. Contractions induced by elevated extracellular potassium were concentration-dependently relaxed by T16A(inh)-A01 ±chloride. Moreover, T16A(inh) -A01 inhibited VDCCs in A7r5 cells in a concentration-dependent manner. CaCC(inh) -A01 and MONNA (0.1-10 µM) induced vasorelaxation ±chloride and both compounds lowered maximum contractility. MONNA, 10 µM, induced substantial membrane hyperpolarization under resting conditions. CONCLUSIONS AND IMPLICATIONS: T16A(inh) -A01, CaCC(inh) -A01 and MONNA concentration-dependently relax rodent resistance arteries, but an equivalent vasorelaxation occurs when the transmembrane chloride gradient is abolished with an impermeant anion. These compounds therefore display poor selectivity for TMEM16A and inhibition of CaCC in vascular tissue in the concentration range that inhibits the isolated conductance.

Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly.

Genetic diversity, virulence and fitness evolution in an obligate fungal parasite of bees.

Within-host competition is predicted to drive the evolution of virulence in parasites, but the precise outcomes of such interactions are often unpredictable due to many factors including the biology of the host and the parasite, stochastic events and co-evolutionary interactions. Here, we use a serial passage experiment (SPE) with three strains of a heterothallic fungal parasite (Ascosphaera apis) of the Honey bee (Apis mellifera) to assess how evolving under increasing competitive pressure affects parasite virulence and fitness evolution. The results show an increase in virulence after successive generations of selection and consequently faster production of spores. This faster sporulation, however, did not translate into more spores being produced during this longer window of sporulation; rather, it appeared to induce a loss of fitness in terms of total spore production. There was no evidence to suggest that a greater diversity of competing strains was a driver of this increased virulence and subsequent fitness cost, but rather that strain-specific competitive interactions influenced the evolutionary outcomes of mixed infections. It is possible that the parasite may have evolved to avoid competition with multiple strains because of its heterothallic mode of reproduction, which highlights the importance of understanding parasite biology when predicting disease dynamics.

Glucocorticoid prescriptions and breast cancer recurrence: a Danish nationwide prospective cohort study.

BACKGROUND: Treatment with synthetic glucocorticoids (GCs) depresses the immune response and may therefore modify cancer outcomes. We investigated the association between GC use and breast cancer recurrence. MATERIALS AND METHODS: We conducted a population-based cohort study to examine the risk of breast cancer recurrence associated with GC use among incident stage I-III female breast cancer patients aged >18 years diagnosed 1996-2003 in Denmark. Data on patients, clinical and treatment factors, recurrence, and comorbidities as well as data on GC prescriptions and potential confounders were obtained from Danish population-based medical registries. GCs were categorized according to administrative route: systemic, inhaled, or intestinal. Women were followed for up to 10 years or until 31 December 2008. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) to evaluate the association between GC use and recurrence. Time-varying drug exposures were lagged by 1 year. RESULTS: We included 18 251 breast cancer patients. Median recurrence follow-up was 6.9 years; 3408 women developed recurrence during follow-up. Four thousand six hundred two women filled at least one GC prescription after diagnosis. In unadjusted models, no association was observed among users of systemic, inhaled, and intestinal GCs (HRsystemic = 1.1, 95% CI 0.9-1.3; HRinhaled = 0.9, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.9-1.2) versus nonusers. In adjusted models, the results were also near null (HRsystemic = 1.1, 95% CI 0.9-1.2; HRinhaled = 0.8, 95% CI 0.7-1.0; and HRintestinal = 1.0, 95% CI 0.8-1.2). CONCLUSION: We found no evidence of an effect of GC use on breast cancer recurrence.

The significance of elevated placental PHLDA2 in human growth restricted pregnancies.

In utero growth restriction is the failure of a fetus to achieve its genetic growth potential during gestation. Elevated expression of the maternally expressed imprinted gene PHLDA2, has been reported in the human placenta of growth restricted pregnancies. A mouse modelling this alteration has been generated and also displays fetal growth restriction suggesting that increased expression of PHLDA2 is not an effect but rather a cause of growth restriction in human pregnancies. Here we review the current data linking PHLDA2 to growth restriction and the data from human and animal model studies suggesting that placental PHLDA2 expression may be responsive to environmental stimuli such as maternal lifestyle. Further investigation is warranted in larger studies of human placentas with the aim of determining whether placental PHLDA2 expression could be used as a diagnostic tool to identify or sub-classify growth restricted infants and to inform more effective interventions and treatment for IUGR in the future.

Imprinted genes in mouse placental development and the regulation of fetal energy stores.

Imprinted genes, which are preferentially expressed from one or other parental chromosome as a consequence of epigenetic events in the germline, are known to functionally converge on biological processes that enable in utero development in mammals. Over 100 imprinted genes have been identified in the mouse, the majority of which are both expressed and imprinted in the placenta. The purpose of this review is to provide a summary of the current knowledge regarding imprinted gene function in the mouse placenta. Few imprinted genes have been assessed with respect to their dosage-related action in the placenta. Nonetheless, current data indicate that imprinted genes converge on two key functions of the placenta, nutrient transport and placental signalling. Murine studies may provide a greater understanding of certain human pathologies, including low birth weight and the programming of metabolic diseases in the adult, and complications of pregnancy, such as pre-eclampsia and gestational diabetes, resulting from fetuses carrying abnormal imprints.