Background: Breast cancer may be classified into distinct molecular subtypes based on gene expression profiling and/or immunophenotypic characteristics. Aim of the study was to investigate ...prevalence, clinicopathologic features and overall survival (OS) of molecular subtypes, in a large European population-based study. Patients and methods: All invasive breast cancers from 2003 to 2007 were selected from the files of Ticino Cancer Registry. Molecular subtypes were defined by immunohistochemical markers. Clinicopathological characteristics and short-term OS were analyzed. Results: Of 1214 invasive breast cancers, 73.2% were luminal A subtype, 13.8% luminal B, 7.4% basal like and 5.6% Her2/neu. Basal like presented largely in premenopausal women and displayed aggressive features, such as large tumor size, poorly differentiated cancers, high Ki-67 proliferation index and the worst 24-month OS. Luminal A included the highest percentage of patients >70, the highest proportion of stage I tumors and well/moderately differentiated lesions. Her2/neu was more frequent in postmenopausal women and showed the highest percentage of positive lymph nodes and stage IV cases. Conclusion: This is a comprehensive European population-based study on breast cancer molecular subtypes. We provide strong evidence that the molecular classification is useful for clinical management and superior to World Health Organization classification in terms of short-term prognostic value.
The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people ...with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy.
We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods.
Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population.
Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.
The following species are described and illustrated for the listed countries: Stenistoderus ibadan sp. n. (Nigeria), S. abnormis sp. n. (Nigeria), Agoreina tanzanica sp. n. (Tanzania), Neoxantholinus ...camerunensis sp. n. (Cameroon), Nudobius lomaensis sp. n. (Sierra Leone), N. capitatus sp. n. (Kenya), and N. occasus sp. n. (Kenya).
More people than ever before are currently living with a diagnosis of cancer and the number of people concerned is likely to continue to rise. Cancer survivors are at risk of developing a second ...primary cancer (SPC). This study aims to investigate the risk of SPC in Switzerland.
The study cohort included all patients with a first primary cancer recorded in 9 Swiss population-based cancer registries 1981-2009 who had a minimum survival of 6 months, and a potential follow-up until the end of 2014. We calculated standardized incidence ratios (SIR) to estimate relative risks (RR) of SPC in cancer survivors compared with the cancer risk of the general population. SIR were stratified by type of first cancer, sex, age and period of first diagnosis, survival period and site of SPC.
A total of 33,793 SPC were observed in 310,113 cancer patients. Both male (SIR 1.18, 95%CI 1.16-1.19) and female (SIR 1.20, 95%CI 1.18-1.22) cancer survivors had an elevated risk of developing a SPC. Risk estimates varied substantially according to type of first cancer and were highest in patients initially diagnosed with cancer of the oral cavity and pharynx, Hodgkin lymphoma, laryngeal, oesophageal, or lung cancer. Age-stratified analyses revealed a tendency towards higher RR in patients first diagnosed at younger ages. Stratified by survival period, risk estimates showed a rising trend with increasing time from the initial diagnosis. We observed strong associations between particular types of first and SPC, i.e. cancer types sharing common risk factors such as smoking or alcohol consumption (e.g. repeated cancer of the oral cavity and pharynx (SIR
20.12, 95%CI 17.91-22.33; SIR
37.87, 95%CI 30.27-45.48).
Swiss cancer survivors have an increased risk of developing a SPC compared to the general population, particularly patients first diagnosed before age 50 and those surviving more than 10 years. Cancer patients should remain under continued surveillance not only for recurrent cancers but also for new cancers. Some first and SPCs share lifestyle associated risk factors making it important to promote healthier lifestyles in both the general population and cancer survivors.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The analysis of Gravity Recovery and Climate Experiment (GRACE) Level 2 data time series from the Center for Space Research (CSR) and GeoForschungsZentrum (GFZ) allows us to extract a new estimate of ...the co‐seismic gravity signal due to the 2004 Sumatran earthquake. Owing to compressible self‐gravitating Earth models, including sea level feedback in a new self‐consistent way and designed to compute gravitational perturbations due to volume changes separately, we are able to prove that the asymmetry in the co‐seismic gravity pattern, in which the north–eastern negative anomaly is twice as large as the south–western positive anomaly, is not due to the previously overestimated dilatation in the crust. The overestimate was due to a large dilatation localized at the fault discontinuity, the gravitational effect of which is compensated by an opposite contribution from topography due to the uplifted crust. After this localized dilatation is removed, we instead predict compression in the footwall and dilatation in the hanging wall. The overall anomaly is then mainly due to the additional gravitational effects of the ocean after water is displaced away from the uplifted crust, as first indicated by de Linage et al. (2009). We also detail the differences between compressible and incompressible material properties. By focusing on the most robust estimates from GRACE data, consisting of the peak‐to‐peak gravity anomaly and an asymmetry coefficient, that is given by the ratio of the negative gravity anomaly over the positive anomaly, we show that they are quite sensitive to seismic source depths and dip angles. This allows us to exploit space gravity data for the first time to help constraining centroid‐momentum‐tensor (CMT) source analyses of the 2004 Sumatran earthquake and to conclude that the seismic moment has been released mainly in the lower crust rather than the lithospheric mantle. Thus, GRACE data and CMT source analyses, as well as geodetic slip distributions aided by GPS, complement each other for a robust inference of the seismic source of large earthquakes. Particular care is devoted to the spatial filtering of the gravity anomalies estimated both from observations and models to make their comparison significant.
Key Points
GRACE data help constraining seismic models of the 2004 Sumatran earthquake
In Western countries the dietary guidance emphasizes the need to decrease the intake of saturated fatty acids and to replace them with polyunsaturated fatty acids (PUFA), particularly long chain n-3 ...PUFA (LC-PUFA). The production of poultry meat having a lower fat content and healthier fatty acid (FA) profile is a hot topic for the poultry industry, and the possibility to identify genotypes able to produce meat with a higher LC-PUFA content deserves attention. The aims of the present study were to evidence in chicken (i) a genotype-related different expression of the desaturating enzymes delta-6 (Δ6, EC 1.14.99.25), delta-5 (Δ5, EC 1.14.19.) and delta-9 (Δ9, EC 1.14.19.1); (ii) the impact of the hypothesized different expression on the meat FA composition; (iii) the distribution of desaturase products in the different lipid classes. Slow (SG), medium (MG) and fast (FG) growing chickens fed the same diet were evaluated either for the relative expression of FADS1, FADS2 and SCD1 genes in liver (by q-PCR), or for the FA composition of breast meat. MG and particularly SG birds showed a greater expression of FADS2 and FADS1 genes, a higher Δ6 and Δ5 activity (estimated using desaturase indices), and consequently a higher LC-PUFA content in the breast meat than FG birds. The relationship between genotype and desaturating ability was demonstrated, with a significant impact on the PUFA content of breast meat. Due to the high consumption rate of avian meat, the identification of the best genotypes for meat production could represent an important goal not only for the food industry, but also for the improvement of human nutrition.
Some food bioactives potentially exert anti-obesity effects. Anthocyanins (ACN), catechins, β-glucan (BG) and n-3 long chain PUFA (LCPUFA) are among the most promising candidates and have been ...considered as a strategy for the development of functional foods counteracting body weight gain. At present, clinical trials, reviews and meta-analyses addressing anti-obesity effects of various bioactives or bioactive-rich foods show contradictory results. Abdominal obesity is an important criterion for metabolic syndrome (MetS) diagnosis along with glucose intolerance, dyslipidaemia and hypertension. Food bioactives are supposed to exert beneficial effects on these parameters, therefore representing alternative therapy approaches for the treatment of MetS. This review summarises outcomes on MetS biomarkers in recent clinical trials supplementing ACN, catechins, BG and n-3 LCPUFA, focusing mainly on anti-obesity effects. Overall, it is clear that the level of evidence for the effectiveness varies not only among the different bioactives but also among the different putative health benefits suggested for the same bioactive. Limited evidence may be due to the low number of controlled intervention trials or to inconsistencies in trial design, i.e. duration, dose and/or the method of bioactive supplementation (extracts, supplements, rich or enriched food). At present, the question 'Are bioactives effective in weight management and prevention of metabolic syndrome?' remains inconclusive. Thus, a common effort to harmonise the study design of intervention trials focusing on the most promising bioactive molecules is urgently needed to strengthen the evidence of their potential in the treatment of obesity, MetS and related diseases.
Aims
Pompe disease is an autosomal recessive lysosomal storage disorder resulting from deficiency of acid α‐glucosidase (GAA) enzyme. Histopathological hallmarks in skeletal muscle tissue are fibre ...vacuolization and autophagy. Since 2006, enzyme replacement therapy (ERT) is the only approved treatment with human recombinant GAA alglucosidase alfa. We designed a study to examine ERT‐related skeletal muscle changes in 18 modestly to moderately affected late onset Pompe disease (LOPD) patients along with the relationship between morphological/biochemical changes and clinical outcomes. Treatment duration was short‐to‐long term.
Methods
We examined muscle biopsies from 18 LOPD patients at both histopathological and biochemical level. All patients underwent two muscle biopsies, before and after ERT administration respectively. The study is partially retrospective because the first biopsies were taken before the study was designed, whereas the second biopsy was always performed after at least 6 months of ERT administration.
Results
After ERT, 15 out of 18 patients showed improved 6‐min walking test (6MWT; P = 0.0007) and most of them achieved respiratory stabilization. Pretreatment muscle biopsies disclosed marked histopathological variability, ranging from an almost normal pattern to a severe vacuolar myopathy. After treatment, we detected morphological improvement in 15 patients and worsening in three patients.
Post‐ERT GAA enzymatic activity was mildly increased compared with pretreatment levels in all patients. Protein levels of the mature enzyme increased in 14 of the 18 patients (mean increase = +35%; P < 0.05). Additional studies demonstrated an improved autophagic flux after ERT in some patients.
Conclusions
ERT positively modified skeletal muscle pathology as well as motor and respiratory outcomes in the majority of LOPD patients.
Neurotoxicity due to the accumulation of mutant proteins is thought to drive pathogenesis in neurodegenerative diseases. Mutations in superoxide dismutase 1 (SOD1) are linked to familial amyotrophic ...lateral sclerosis (fALS); these mutations result in progressive motor neuron death through one or more acquired toxicities. Interestingly, SOD1 is not only responsible for fALS but may also play a significant role in sporadic ALS; therefore, SOD1 represents a promising therapeutic target. Here, we report slowed disease progression, improved neuromuscular function, and increased survival in an in vivo ALS model following therapeutic delivery of morpholino oligonucleotides (MOs) designed to reduce the synthesis of human SOD1. Neuropathological analysis demonstrated increased motor neuron and axon numbers and a remarkable reduction in astrogliosis and microgliosis. To test this strategy in a human model, we treated human fALS induced pluripotent stem cell (iPSC)-derived motor neurons with MOs; these cells exhibited increased survival and reduced expression of apoptotic markers. Our data demonstrated the efficacy of MO-mediated therapy in mouse and human ALS models, setting the stage for human clinical trials.
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