Non-standard management of breast cancer increases with age in the UK: a population based cohort of women ⩾65 years

Evidence suggests that compared to younger women, older women are less likely to receive standard management for breast cancer. Whether this disparity persists once differences in tumour characteristics have been adjusted for has not been investigated in the UK. A retrospective cohort study involving case note review was undertaken, based on the North Western Cancer Registry database of women aged ⩾65 years, resident in Greater Manchester with invasive breast cancer registered over a 1-year period (n=480). Adjusting for tumour characteristics associated with age by logistic regression analyses, older women were less likely to receive standard management than younger women for all indicators investigated. Compared to women aged 65–69 years, women aged ⩾80 years with operable (stage 1–3a) breast cancer have increased odds of not receiving triple assessment (OR=5.5, 95% confidence interval (CI): 2.1–14.5), not receiving primary surgery (OR=43.0, 95% CI: 9.7–191.3), not undergoing axillary node surgery (OR=27.6, 95% CI: 5.6–135.9) and not undergoing tests for steroid receptors (OR=3.0, 95% CI: 1.7–5.5). Women aged 75–79 years have increased odds of not receiving radiotherapy following breast-conserving surgery compared to women aged 65–69 years (OR=11.0, 95% CI: 2.0–61.6). These results demonstrate that older women in the UK are less likely to receive standard management for breast cancer, compared to younger women and this disparity cannot be explained by differences in tumour characteristics

Comparison of airway measurements during influenza-induced tachypnea in infant and adult cotton rats

<p>Abstract</p> <p>Background</p> <p>Increased respiratory rate (tachypnea) is frequently observed as a clinical sign of influenza pneumonia in pediatric patients admitted to the hospital. We previously demonstrated that influenza infection of adult cotton rats (<it>Sigmodon hispidus</it>) also results in tachypnea and wanted to establish whether this clinical sign was observed in infected infant cotton rats. We hypothesized that age-dependent differences in lung mechanics result in differences in ventilatory characteristics following influenza infection.</p> <p>Methods</p> <p>Lung tidal volume, dynamic elastance, resistance, and pleural pressure were measured in a resistance and compliance system on mechanically-ventilated anesthestized young (14–28 day old) and adult (6–12 week old) cotton rats. Animals at the same age were infected with influenza virus, and breathing rates and other respiratory measurements were recorded using a whole body flow plethysmograph.</p> <p>Results</p> <p>Adult cotton rats had significantly greater tidal volume (TV), and lower resistance and elastance than young animals. To evaluate the impact of this increased lung capacity and stiffening on respiratory disease, young and adult animals were infected intra-nasally with influenza A/Wuhan/359/95. Both age groups had increased respiratory rate and enhanced pause (<it>Penh</it>) during infection, suggesting lower airway obstruction. However, in spite of significant tachypnea, the infant (unlike the adult) cotton rats maintained the same tidal volume, resulting in an increased minute volume. In addition, the parameters that contribute to <it>Penh </it>were different: while relaxation time between breaths and time of expiration was decreased in both age groups, a disproportionate increase in peak inspiratory and expiratory flow contributed to the increase in <it>Penh </it>in infant animals.</p> <p>Conclusion</p> <p>While respiratory rate is increased in both adult and infant influenza-infected cotton rats, the volume of air exchanged per minute (minute volume) is increased in the infant animals only. This is likely to be a consequence of greater lung elastance in the very young animals. This model replicates many respiratory features of humans and consequently may be a useful tool to investigate new strategies to treat respiratory disease in influenza-infected infants.</p

Simulation Modifies Prehension: Evidence for a Conjoined Representation of the Graspable Features of an Object and the Action of Grasping It

Movement formulas, engrams, kinesthetic images and internal models of the body in action are notions derived mostly from clinical observations of brain-damaged subjects. They also suggest that the prehensile geometry of an object is integrated in the neural circuits and includes the object's graspable characteristics as well as its semantic properties. In order to determine whether there is a conjoined representation of the graspable characteristics of an object in relation to the actual grasping, it is necessary to separate the graspable (low-level) from the semantic (high-level) properties of the object. Right-handed subjects were asked to grasp and lift a smooth 300-g cylinder with one hand, before and after judging the level of difficulty of a “grasping for pouring” action, involving a smaller cylinder and using the opposite hand. The results showed that simulated grasps with the right hand exert a direct influence on actual motor acts with the left hand. These observations add to the evidence that there is a conjoined representation of the graspable characteristics of the object and the biomechanical constraints of the arm

A haplotype variation affecting the mitochondrial transportation of hMYH protein could be a risk factor for colorectal cancer in Chinese

<p>Abstract</p> <p>Background</p> <p>The human MutY homolog (<it>hMYH</it>), a DNA glycolsylase involved in the excision repair of oxidative DNA damage, is currently studied in colorectal cancer (CRC). We previously demonstrated a haplotype variant c.53C>T/c.74G>A of <it>hMYH </it>(T/A) increasing the risk for gastric cancer in Chinese. However, most investigations on correlation between <it>hMYH </it>and CRC are conducted in Western countries and the underlying mechanism has been poorly understood.</p> <p>Methods</p> <p>To determine whether the haplotype T/A variant of <it>hMYH </it>was related to colorectal carcinogenesis, we performed a case-control study in 138 colorectal cancer (CRC) patients and 343 healthy controls in a Chinese population. Furthermore, the C/G for wild-type, C/A or T/G for single base variant and T/A for haplotype variant <it>hMYH </it>cDNAs with a flag epitope tag were cloned into pcDNA3.1+ vector and transfected into cos-7 cell line. Their subcellular localizations were determined by immunofluorescence assay.</p> <p>Results</p> <p>It was found that the frequency of haplotype variant allele was statistically higher in CRC patients than that in controls (<it>P </it>= 0.02, odds ratio = 5.06, 95% confidence interval = 1.26 – 20.4). Similarly, significant difference of heterozygote frequency was indicated between the two groups (<it>P </it>= 0.019), while no homozygote was found. In addition, immunofluorescence analysis showed that hMYH protein with haplotype T/A variation presented in both nucleus and mitochondria, in contrast to the wild-type protein only converging in mitochondria. However, neither of the single missense mutations alone changed the protein subcelluar localization.</p> <p>Conclusion</p> <p>Although preliminarily, these results suggest that: the haplotype variant allele of <it>hMYH </it>leads to a missense protein, which partly affects the protein mitochondrial transportation and results as nuclear localization. This observation might be responsible for the increased susceptibility to cancers, including CRC, in Chinese.</p

Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in ulcerative colitis

We recently reported that oxidative stress elicited by chronic inflammation increases the mutation of mitochondrial DNA (mtDNA) and possibly correlates with precancerous status. Since severe oxidative stress is elicited in the colorectal mucosa of individuals with ulcerative colitis (UC), the possible occurrence of an mtDNA mutation in the inflammatory colorectal mucosa and colitic cancer was investigated. Colorectal mucosal specimens were obtained from individuals with UC with and without colitic cancer and from control subjects. The frequency of mtDNA mutations was higher in colorectal mucosal specimens from patients with UC than that from control subjects. The levels of 8-hydroxy-2′-deoxyguanosine, a DNA adduct by reactive oxygen species, were significantly higher in UC than in control. Specimens from patients with colitic cancer contained a significantly higher number of mtDNA mutations. The present observations suggest that the injury followed by the regeneration of colorectal mucosal cells associated with chronic inflammation causes accumulation of mtDNA mutations. The increased instability of genes, including those on the mtDNA, is consistent with the high and multicentric incidence of colorectal cancer in individuals with UC. Thus, analysis of mtDNA could provide a new criterion for the therapeutic evaluation, and may be useful for the prediction of risk of carcinogenesis

Atividade física, qualidade de vida e depressão durante a gravidez

This study examines physical activity patterns among women, from pre-pregnancy to the second trimester of pregnancy, and the relationship between physical activity status based on physical activity guidelines and health-related quality of life (HRQoL) and depression over pregnancy. 56 healthy pregnant women self reported physical activity, HRQoL and depression at 10-15 and 19-24 weeks of pregnancy and physical activity before pregnancy. Whereas vigorous leisure physical activity decreased after conception, moderate leisure physical activity and work related physical activity remained stable over time. The prevalence of recommended physical activity was 39.3% and 12.5% in the 1st and 2nd trimesters of pregnancy respectively, and 14.3% pre-pregnancy. From the 1st to the 2nd pregnancy trimester, most physical HRQoL dimensions scores decreased and only mental component increased, independently of physical activity status. No changes in mean depression scores were observed. These data suggest that physical activity patterns change with pregnancy and that physical and mental components are differentially affected by pregnancy course, independently of physical activity status.Este estudo examina os padrões de atividade física antes da concepção até o segundo trimestre de gravidez e a relação entre o nível de atividade física, com base nas recomendações de atividade física, a qualidade de vida relacionada à saúde (QVRS) e depressão ao longo da gravidez. Cinquenta e seis grávidas saudáveis reportaram nível de atividade física, QVRS e depressão às 10-15 e 19-24 semanas de gravidez, além de atividade física antes da concepção. Enquanto a atividade física vigorosa no lazer diminuiu depois da concepção, as atividades físicas moderadas no lazer e no trabalho mantiveram-se estáveis. A prevalência de atividade fí- sica recomendada foi de 39,3%, 12,5% e 14,3% antes, no primeiro e no segundo trimestres de gravidez, respectivamente. Independentemente do estatuto de atividade física, a maior parte dos escores nas dimensões físicas da QVRS diminui do primeiro para o segundo trimestre de gestação, e apenas o componente mental aumenta. Não se verificaram alterações nos escores médios de depressão. Estes dados sugerem que, com a gravidez, há alteração nos padrões de atividade física; além disso, os componentes físico e mental são diferentemente afetados pelo curso da gestação, independentemente do nível de atividade física

Trace Elements and Carbon and Nitrogen Stable Isotopes in Organisms from a Tropical Coastal Lagoon

Trace elements (Fe, Mn, Al, Zn, Cr, Cu, Ni, Pb, Cd, Hg, and As) and stable isotope ratios (δ13C and δ15N) were analyzed in sediments, invertebrates, and fishes from a tropical coastal lagoon influenced by iron ore mining and processing activities to assess the differences in trace element accumulation patterns among species and to investigate relations with trophic levels of the organisms involved. Overall significant negative relations between trophic level (given by 15N) and trace element concentrations in gastropods and crustaceans showed differences in internal controls of trace element accumulation among the species of different trophic positions, leading to trace element dilution. Generally, no significant relation between δ15N and trace element concentrations was observed among fish species, probably due to omnivory in a number of species as well as fast growth. Trace element accumulation was observed in the fish tissues, with higher levels of most trace elements found in liver compared with muscle and gill. Levels of Fe, Mn, Al, and Hg in invertebrates, and Fe and Cu in fish livers, were comparable with levels in organisms and tissues from other contaminated areas. Trace element levels in fish muscle were below the international safety baseline standards for human consumption

Polymorphism in Gag Gene Cleavage Sites of HIV-1 Non-B Subtype and Virological Outcome of a First-Line Lopinavir/Ritonavir Single Drug Regimen

Virological failure on a boosted-protease inhibitor (PI/r) first-line triple combination is usually not associated with the detection of resistance mutations in the protease gene. Thus, other resistance pathways are being investigated. First-line PI/r monotherapy is the best model to investigate in vivo if the presence of mutations in the cleavage sites (CS) of gag gene prior to any antiretroviral treatment might influence PI/r efficacy. 83 patients were assigned to initiate antiretroviral treatment with first-line lopinavir/r monotherapy in the randomised Monark trial. We compared baseline sequence of gag CS between patients harbouring B or non-B HIV-1 subtype, and between those who achieved viral suppression and those who experienced virological failure while on LPV/r monotherapy up to Week 96. Baseline sequence of gag CS was available for 82/83 isolates; 81/82 carried at least one substitution in gag CS compared to HXB2 sequence. At baseline, non-B subtype isolates were significantly more likely to harbour mutations in gag CS than B subtype isolates (p<0.0001). Twenty-three patients experienced virological failure while on lopinavir/r monotherapy. The presence of more than two substitutions in p2/NC site at baseline significantly predicted virological failure (p = 0.0479), non-B subtype isolates being more likely to harbour more than two substitutions in this specific site. In conclusion, gag cleavage site was highly polymorphic in antiretroviral-naive patients harbouring a non-B HIV-1 strain. We show that pre-therapy mutations in gag cleavage site sequence were significantly associated with the virological outcome of a first-line LPV/r single drug regimen in the Monark trial

Absence of pathogenic mitochondrial DNA mutations in mouse brain tumors

BACKGROUND: Somatic mutations in the mitochondrial genome occur in numerous tumor types including brain tumors. These mutations are generally found in the hypervariable regions I and II of the displacement loop and unlikely alter mitochondrial function. Two hypervariable regions of mononucleotide repeats occur in the mouse mitochondrial genome, i.e., the origin of replication of the light strand (O(L)) and the Arg tRNA. METHODS: In this study we examined the entire mitochondrial genome in a series of chemically induced brain tumors in the C57BL/6J strain and spontaneous brain tumors in the VM mouse strain. The tumor mtDNA was compared to that of mtDNA in brain mitochondrial populations from the corresponding syngeneic mouse host strain. RESULTS: Direct sequencing revealed a few homoplasmic base pair insertions, deletions, and substitutions in the tumor cells mainly in regions of mononucleotide repeats. A heteroplasmic mutation in the 16srRNA gene was detected in a spontaneous metastatic VM brain tumor. CONCLUSION: None of the mutations were considered pathogenic, indicating that mtDNA somatic mutations do not likely contribute to the initiation or progression of these diverse mouse brain tumors