Androgen receptor genotypes predict response to endocrine treatment in breast cancer patients.

Background:The androgen receptor (AR) is frequently expressed in breast cancers. The AR genotype may affect disease-free survival and response to endocrine therapy.Methods:In all, 634 women undergoing breast cancer surgery between 2002 and 2008 were followed until 30 June 2010. Six haplotype-tagging single-nucleotide polymorphisms in the AR, and the resulting AR diplotypes, were examined in relation to breast cancer patient characteristics, tumour characteristics, disease-free survival, and response to endocrine treatment.Results:Five common AR diplotypes were found. Seventeen rare variants were combined into a composite group. The resulting six AR diplotype groups were clustered into two subgroups, groups A (n=128) and B (n=499), with three diplotypes in each. Patients in group B had larger total breast volume (P=0.024), higher body mass index (BMI) (P=0.050), more axillary lymph node involvement (P(trend)=0.020), and higher histological grade (P(trend)=0.031). There were 59 breast cancer events in the 569 patients with invasive cancers and no preoperative treatment. Patients in group B also had shorter disease-free survival (P=0.037) than patients in group A. Among patients in group B with oestrogen receptor α positive tumours, tamoxifen (TAM) treatment was associated with longer disease-free survival (P=0.008), while treatment with aromatase inhibitors (AIs) was not (P=0.94). Response to endocrine treatment could not be predicted based on BMI, suggesting that the effect of AR diplotypes went beyond that of a higher BMI.Conclusion:A marker for a group of patients who responded to TAM, but not to AIs, was identified. If this finding is confirmed, AR genotyping may provide useful information for selection of endocrine treatment of breast cancer patients.British Journal of Cancer advance online publication, 27 October 2011; doi:10.1038/bjc.2011.441 www.bjcancer.com

Given breast cancer, does breast size matter? Data from a prospective breast cancer cohort.

PURPOSE: Body mass index (BMI), waist-to-hip ratio (WHR), and tumor characteristics affect disease-free survival. Larger breast size may increase breast cancer risk, but its influence on disease-free survival is unclear. The purpose of this study was to elucidate whether breast size independently influenced disease-free survival in breast cancer patients. METHODS: Body measurements were obtained preoperatively from 772 breast cancer patients in a population-based ongoing cohort from southern Sweden. The research nurse measured breast volumes with plastic cups used by plastic surgeons doing breast reductions. Clinical data were obtained from patient charts and pathology reports. RESULTS: Patients with a BMI ≥ 25 kg/m(2) had larger tumors (p 0.85 had larger tumors (p = 0.013), more advanced histological grade (p = 0.0016), and more axillary nodal involvement (p = 0.012). Patients with right + left breast volume ≥ 850 mL were more likely to have larger tumor sizes (p = 0.018), more advanced histological grade (p = 0.031), and more axillary nodal involvement (p = 0.025). There were 62 breast cancer events during the 7-year follow-up. Breast volume ≥ 850 mL was associated with shorter disease-free survival (p = 0.004) and distant metastasis-free survival (p = 0.001) in patients with estrogen receptor (ER)-positive tumors independent of other anthropometric measurements and age. In patients with ER-positive tumors, breast size was an independent predictor of shorter disease-free (HR 3.64; 95 % CI 1.42-9.35) and distant metastasis-free survival (HR 6.33; 95 %CI 1.36-29.43), adjusted for tumor characteristics, BMI, age, and treatment. CONCLUSION: A simple and cheap anthropometric measurement with standardized tools may help identify a subgroup of patients in need of tailored breast cancer therapy

Fungal succession in decomposing ash leaves colonized by the ash dieback pathogen Hymenoscyphus fraxineus or its harmless relative Hymenoscyphus albidus

Introduction: The ascomycete Hymenoscyphus fraxineus, originating from Asia, is currently threatening common ash (Fraxinus excelsior) in Europe, massive ascospore production from the saprotrophic phase being a key determinant of its invasiveness. Methods: To consider whether fungal diversity and succession in decomposing leaf litter are affected by this invader, we used ITS-1 metabarcoding to profile changes in fungal community composition during overwintering. The subjected ash leaf petioles, collected from a diseased forest and a healthy ash stand hosting the harmless ash endophyte Hymenoscyphus albidus, were incubated in the forest floor of the diseased stand between October 2017 and June 2018 and harvested at 2–3-month intervals. Results: Total fungal DNA level showed a 3-fold increase during overwintering as estimated by FungiQuant qPCR. Petioles from the healthy site showed pronounced changes during overwintering; ascomycetes of the class Dothideomycetes were predominant after leaf shed, but the basidiomycete genus Mycena (class Agaricomycetes) became predominant by April, whereas H. albidus showed low prevalence. Petioles from the diseased site showed little change during overwintering; H. fraxineus was predominant, while Mycena spp. showed increased read proportion by June. Discussion: The low species richness and evenness in petioles from the diseased site in comparison to petioles from the healthy site were obviously related to tremendous infection pressure of H. fraxineus in diseased forests. Changes in leaf litter quality, owing to accumulation of host defense phenolics in the pathogen challenged leaves, and strong saprophytic competence of H. fraxineus are other factors that probably influence fungal succession. For additional comparison, we examined fungal community structure in petioles collected in the healthy stand in August 2013 and showing H. albidus ascomata. This species was similarly predominant in these petioles as H. fraxineus was in petioles from the diseased site, suggesting that both fungi have similar suppressive effects on fungal richness in petiole/rachis segments they have secured for completion of their life cycle. However, the ability of H. fraxineus to secure the entire leaf nerve system in diseased forests, in opposite to H. albidus, impacts the general diversity and successional trajectory of fungi in decomposing ash petioles.publishedVersio

Triage and urgent dental care for COVID-19 patients in the Hospital District of Helsinki and Uusimaa

Objective This paper describes and reports the patient-specific characteristics of an urgent dental care clinic for COVID-19 infected, suspected, exposed or quarantined patients from March to December 2020 in the Hospital District of Helsinki and Uusimaa, Finland. Material and methods The triage and the treatment protocol were established based on the scientific data. Patient files were evaluated from the hospital district's electronic medical record system. IBM SPSS software was used for statistical analysis. Results There were 1114 consultations and 257 visits at the clinic. Most of the patients were generally healthy with mean age of 35, had toothache and were suspected to be SARS-CoV-2 positive. Seventeen of the patients received positive tests for COVID-19 infection. The main treatment was tooth extraction, mostly due to caries. Statistically significant differences between COVID-19 infected and other patients occurred in age (45 vs 34 years-of-age, p = .009) and number of teeth (25 vs 28, p = .031). No SARS-CoV-2 infection transmission chains were traced to the clinic. Conclusion During the challenging pandemic time, patients were carefully screened by specialists in clinical dentistry and treated safely and effectively. Patient-specific characteristics revealed no differences between COVID-19 infected and other patients in terms of symptoms or treatment needs.Peer reviewe

Sex difference in brain CB1 receptor availability in man

none12The endocannabinoid system (ECS) has a widespread neuromodulatory function in the central nervous system and is involved in important aspects of brain function including brain development, cortical rhythms, plasticity, reward, and stress sensitivity. Many of these effects are mediated via the cannabinoid CB1 receptor (CB1R) subtype. Animal studies convincingly show an interaction between the ECS and sex hormones, as well as a sex difference of higher brain CB1R in males. Human in vivo studies of sex difference have yielded discrepant findings. Gender differences in CB1R availability were investigated in vivo in 11 male and 11 female healthy volunteers using a specific CB1R tracer [18F]FMPEP-d2 and positron emission tomography (PET). Regional [18F]FMPEP-d2 distribution volume was used as a proxy for CB1R availability. In addition, we explored whether CB1R availability is linked to neuropsychological functioning. Relative to females, CB1R availability was on average 41% higher in males (p = 0.002) with a regionally specific effect larger in the posterior cingulate and retrosplenial cortices (p = 0.001). Inter-subject variability in CB1R availability was similar in both groups. Voxel-based analyses revealed an inverse association between CB1R availability and visuospatial working memory task performance in both groups (p noneLaurikainen, Heikki; Tuominen, Lauri; Tikka, Maria; Merisaari, Harri; Armio, Reetta-Liina; Sormunen, Elina; Borgan, Faith; Veronese, Mattia; Howes, Oliver; Haaparanta-Solin, Merja; Solin, Olof; Hietala, JarmoLaurikainen, Heikki; Tuominen, Lauri; Tikka, Maria; Merisaari, Harri; Armio, Reetta-Liina; Sormunen, Elina; Borgan, Faith; Veronese, Mattia; Howes, Oliver; Haaparanta-Solin, Merja; Solin, Olof; Hietala, Jarm

Promoting healthy dietary behaviour through personalised nutrition: technology push or technology pull?

YesThe notion of educating the public through generic healthy eating messages has pervaded dietary health promotion efforts over the years and continues to do so through various media, despite little evidence for any enduring impact upon eating behaviour. There is growing evidence, however, that tailored interventions such as those that could be delivered online can be effective in bringing about healthy dietary behaviour change. The present paper brings together evidence from qualitative and quantitative studies that have considered the public perspective of genomics, nutrigenomics and personalised nutrition, including those conducted as part of the EU-funded Food4Me project. Such studies have consistently indicated that although the public hold positive views about nutrigenomics and personalised nutrition, they have reservations about the service providers’ ability to ensure the secure handling of health data. Technological innovation has driven the concept of personalised nutrition forward and now a further technological leap is required to ensure the privacy of online service delivery systems and to protect data gathered in the process of designing personalised nutrition therapies

Response of macroinvertebrates to experimental nutrient and fish additions in European localities at different latitudes

The sedimentary and plant-associated macroinvertebrate communities have been examined in a series of mesocosm experiments carried out in five locations, in Finland, Sweden, UK, Northwest Spain and Mediterranean Spain (the International Mesocosm Experiment). The experiments were designed to investigate how shallow lake ecosystems respond to the addition of nutrients and planktivorous fish along a climate gradient. Nutrient additions increased sedimentary benthos densities and total biomass to a plateau at intermediate levels of nutrients. The effect was greater in the warmest localities. Beyond the saturation point a further increase in nutrient loading had different effects depending on locality. Only in the southernmost site (in Mediterranean Spain), did it induce a shift to a turbid phase and macrophyte disappearance. Thus there are breakpoints in the relationship with nutrients, leading to alternative sediment communities subsequent to the water alternative states. Presence of fish increased the densities and biomass of sediment macroinvertebrates, more clearly in the more southern locality, where the fish Gambusia did not prey in the bottom animals. A stabilising role of macrophytes was observed by cutting them, samples taken three weeks after cutting indicated a higher effect of fish on the sediment community when macrophytes were not present. Nutrients tended also to increase densities of plant associated macroinvertebrates at low levels with a flattening of response at intermediate levels and a decline at high levels. At high fish level the numbers and biomass of plant-associated macroinvertebrates were lowered in all cases, because of increased predation. However fish addition at low level in most cases had the opposite effect, because their predation pressure was not high and regeneration of nutrients through their activities might increase food availability and control invertebrate predators. Fish influenced especially community composition, because they prey selectively. Addition of fish at low densities increased macroinvertebrate diversity. A diel migratory cycle was observed in plant-associated macroinvertebrates, but only in the southerly locations. Latitudinal influences on the structure of the macroinvertebrate communities occur but that they operate indirectly. There was a prominent effect of nutrients on these communities so that starting trophy is very important. Fish effects are layered on these and depend to a large extent on the particular range of diet of the species involved.Se ha estudiado la comunidad de macroinvertebrados bentónicos del sedimento así como la de los asociados a los macrófitos en una serie de mesocosmos concebidos para un experimento múltiple simultáneo llevado a cabo en cinco localidades europeas: Finlandia, Suecia, Reino Unido (UK), Noroeste de España y Levante Español. El experimento fue diseñado para investigar como responden los ecosistemas de lagos someros a los aportes de nutrientes y a la abundancia de peces planctívoros a lo largo de un gradiente climático. La adición de nutrientes incrementó la densidad del bentos del sedimento y su biomasa hasta estabilizarse a niveles intermedios de nutrientes, siendo este efecto mayor en las latitudes más bajas y cálidas. Más allá del punto de saturación, un aumento adicional de la carga de nutrientes tuvo efectos diferentes dependiendo de la localidad y solo en el lugar de menor latitud, (en el Levante Español) indujo el cambio hacia una fase turbia, con desaparición de los macrófitos, esto es, hay puntos de ruptura relacionados con la carga de nutrientes que conducen a comunidades alternativas en el sedimento, subsiguientes a los mencionados estados alternativos en las aguas someras. La presencia de peces aumentó la densidad y biomasa de los macroinvertebrados del sedimento, ello también más claramente en la localidad situada más al Sur, ya que el pez planctívoro ensayado (Gambusia) por lo general no depreda en los animales del sedimento. Se observó también el papel estabilizador de los macrófitos comparando las muestras tomadas antes y después de que estos fueran cortados, por ejemplo se observó un efecto mayor de los peces en las comunidades del sedimento cuando los macrófitos no estaban presentes. Los nutrientes tendieron también a incrementar las densidades de los macroinvertebrados asociados a los macrófitos cuando se aportan a bajos niveles, con una estabilización de la respuesta para los valores intermedios y un declive para los valores más altos. Cuando se adicionaron densidades altas de peces, el número y biomasa de los macroinvertebrados asociados a los macrófitos descendieron en todos los casos, como resultado del aumento de la depredación. Sin embargo, las adiciones a baja densidad de peces, en la mayoría de los casos, tuvo el efecto contrario, ya que su presión de depredación no es alta y pueden contribuir a la regeneración de los nutrientes a través de la vía detrítica que incrementa la disponibilidad de alimento, así como al control de otros invertebrados depredadores. La presencia de peces influenció especialmente la composición de la comunidad, ya que su depredación es selectiva. La adición de peces en bajas densidades aumentó la diversidad de los macroinvertebrados. También fue observado que el ciclo diario de migración en los macroinvertebrados asociados a los macrófitos, es más importante en las localidades ubicadas en las latitudes de más al Sur. Las influencias latitudinales en la estructura de las comunidades de macroinvertebrados, si bien sucede, opera indirectamente. Hay un efecto dominante de los nutrientes en estas comunidades, y el nivel trófico de las condiciones iniciales es muy importante. Los efectos de los peces se subordinan al de los nutrientes y dependen en gran medida de la dieta de las especies involucradas

Three-dimensional modelling of the shock-turbulence interaction

The complex interaction between shocks and plasma turbulence is extremely important to address crucial features of energy conversion in a broad range of astrophysical systems. We study the interaction between a supercritical, perpendicular shock and pre-existing, fully-developed plasma turbulence, employing a novel combination of magnetohydrodynamic (MHD) and small-scale, hybrid-kinetic simulations where a shock is propagating through a turbulent medium. The variability of the shock front in the unperturbed case and for two levels of upstream fluctuations is addressed.We find that the behaviour of shock ripples, i.e., shock surface fluctuations with short (a few ion skin depths, $d_i$) wavelengths, is modified by the presence of pre-existing turbulence, which also induces strong corrugations of the shock front at larger scales. We link this complex behaviour of the shock front and the shock downstream structuring with the proton temperature anisotropies produced in the shock-turbulence system. Finally, we put our modelling effort in the context of spacecraft observations, elucidating the role of novel cross-scale, multi-spacecraft measurements in resolving shock front irregularities at different scales. These results are relevant for a broad range of astrophysical systems characterised by the presence of shock waves interacting with plasma turbulence.Comment: Submitted to MNRA

Cold shock proteins: A minireview with special emphasis on Csp-family of enteropathogenic Yersinia

Bacteria have evolved a number of mechanisms for coping with stress and adapting to changing environmental conditions. Many bacteria produce small cold shock proteins (Csp) as a response to rapid temperature downshift (cold shock). During cold shock, the cell membrane fluidity and enzyme activity decrease, and the efficiency of transcription and translation is reduced due to stabilization of nucleic acid secondary structures. Moreover, protein folding is inefficient and ribosome function is hampered. Csps are thought to counteract these harmful effects by serving as nucleic acid chaperons that may prevent the formation of secondary structures in mRNA at low temperature and thus facilitate the initiation of translation. However, some Csps are non-cold inducible and they are reported to be involved in various cellular processes to promote normal growth and stress adaptation responses. Csps have been shown to contribute to osmotic, oxidative, starvation, pH and ethanol stress tolerance as well as to host cell invasion. Therefore, Csps seem to have a wider role in stress tolerance of bacteria than previously assumed. Yersinia enterocolitica and Yersinia pseudotuberculosis are enteropathogens that can spread through foodstuffs and cause an enteric infection called yersiniosis. Enteropathogenic Yersinia are psychrotrophs that are able to grow at temperatures close to 0 degrees C and thus they set great challenges for the modern food industry. To be able to efficiently control psychrotrophic Yersinia during food production and storage, it is essential to understand the functions and roles of Csps in stress response of enteropathogenic Yersinia.Peer reviewe

SNCA mutation p.Ala53Glu is derived from a common founder in the Finnish population

Peer reviewe