A Review of the Evidence Supporting the Taste of Non‐esterified Fatty Acids in Humans

Dietary fats contribute to the flavor of foods by multiple mechanisms. A role for their taste has only recently gained credence. Current evidence indicates non‐esterified fatty acids (NEFA) are the effective stimuli for the taste component. CD36 and GPR120 are putative receptors, but may not fully account for the totality of the range of sensations elicited by fatty acids. The sensory quality of long‐chain NEFA is not adequately characterized by commonly accepted taste primary qualities and has been termed oleogustus. There is marked individual variability in sensitivity to the taste of NEFA prompting hypotheses of genetic and environmental determinants. Though an association with BMI has been proposed, the preponderance of evidence is not supportive. The importance of oleogustus has not been fully established, but likely contributes to flavor, which influences food choice as well as lipid metabolism and chronic disease risk. A better understanding of oleogustus may provide insights useful for product formulation

Risk factors for delay in symptomatic presentation: a survey of cancer patients

Background: Delay in symptomatic presentation leading to advanced stage at diagnosis may contribute to poor cancer survival. To inform public health approaches to promoting early symptomatic presentation, we aimed to identify risk factors for delay in presentation across several cancers. Methods: We surveyed 2371 patients with 15 cancers about nature and duration of symptoms using a postal questionnaire. We calculated relative risks for delay in presentation (time from symptom onset to first presentation >3 months) by cancer, symptoms leading to diagnosis and reasons for putting off going to the doctor, controlling for age, sex and deprivation group. Results: Among 1999 cancer patients reporting symptoms, 21% delayed presentation for >3 months. Delay was associated with greater socioeconomic deprivation but not age or sex. Patients with prostate (44%) and rectal cancer (37%) were most likely to delay and patients with breast cancer least likely to delay (8%). Urinary difficulties, change of bowel habit, systemic symptoms (fatigue, weight loss and loss of appetite) and skin symptoms were all common and associated with delay. Overall, patients with bleeding symptoms were no more likely to delay presentation than patients who did not have bleeding symptoms. However, within the group of patients with bleeding symptoms, there were significant differences in risk of delay by source of bleeding: 35% of patients with rectal bleeding delayed presentation, but only 9% of patients with urinary bleeding. A lump was a common symptom but not associated with delay in presentation. Twenty-eight percent had not recognised their symptoms as serious and this was associated with a doubling in risk of delay. Embarrassment, worry about what the doctor might find, being too busy to go to the doctor and worry about wasting the doctor’s time were also strong risk factors for delay, but were much less commonly reported (<6%). Interpretation: Approaches to promote early presentation should aim to increase awareness of the significance of cancer symptoms and should be designed to work for people of the lowest socioeconomic status. In particular, awareness that rectal bleeding is a possible symptom of cancer should be raised

On finite monoids of cellular automata.

For any group G and set A, a cellular automaton over G and A is a transformation τ:AG→AGτ:AG→AG defined via a finite neighbourhood S⊆GS⊆G (called a memory set of ττ) and a local function μ:AS→Aμ:AS→A. In this paper, we assume that G and A are both finite and study various algebraic properties of the finite monoid CA(G,A)CA(G,A) consisting of all cellular automata over G and A. Let ICA(G;A)ICA(G;A) be the group of invertible cellular automata over G and A. In the first part, using information on the conjugacy classes of subgroups of G, we give a detailed description of the structure of ICA(G;A)ICA(G;A) in terms of direct and wreath products. In the second part, we study generating sets of CA(G;A)CA(G;A). In particular, we prove that CA(G,A)CA(G,A) cannot be generated by cellular automata with small memory set, and, when G is finite abelian, we determine the minimal size of a set V⊆CA(G;A)V⊆CA(G;A) such that CA(G;A)=⟨ICA(G;A)∪V⟩CA(G;A)=⟨ICA(G;A)∪V⟩

The influence on survival of delay in the presentation and treatment of symptomatic breast cancer

The aim of this study was to examine the possible influence on survival of delays prior to presentation and/or treatment among women with breast cancer. Duration of symptoms prior to hospital referral was recorded for 2964 women who presented with any stage of breast cancer to Guy's Hospital between 1975 and 1990. Median follow-up is 12.5 years. The impact of delay (defined as having symptoms for 12 or more weeks) on survival was measured from the date of diagnosis and from the date when the patient first noticed symptoms to control for lead-time bias. Thirty-two per cent (942/2964) of patients had symptoms for 12 or more weeks before their first hospital visit and 32% (302/942) of patients with delays of 12 or more weeks had locally advanced or metastatic disease, compared with only 10% (210/2022) of those with delays of less than 12 weeks (P< 0.0001). Survival measured both from the date of diagnosis (P< 0.001) and from the onset of the patient's symptoms (P= 0.003) was worse among women with longer delays. Ten years after the onset of symptoms, survival was 52% for women with delays less than 12 weeks and 47% for those with longer delays. At 20 years the survival rates were 34% and 24% respectively. Furthermore, patients with delays of 12–26 weeks had significantly worse survival rates than those with delays of less than 12 weeks. Multivariate analyses indicated that the adverse impact of delay in presentation on survival was attributable to an association between longer delays and more advanced stage. However, within individual stages, longer delay had no adverse impact on survival. Analyses based on ‘total delay’ (i.e. the interval between a patient first noticing symptoms and starting treatment) yielded very similar results in terms of survival to those based on delay to first hospital visit (delay in presentation). © 1999 Cancer Research Campaig

Ovarian cancer symptom awareness and anticipated delayed presentation in a population sample

Background: While ovarian cancer is recognised as having identifiable early symptoms, understanding of the key determinants of symptom awareness and early presentation is limited. A population-based survey of ovarian cancer awareness and anticipated delayed presentation with symptoms was conducted as part of the International Cancer Benchmarking Partnership (ICBP). Methods: Women aged over 50 years were recruited using random probability sampling (n = 1043). Computer-assisted telephone interviews were used to administer measures including ovarian cancer symptom recognition, anticipated time to presentation with ovarian symptoms, health beliefs (perceived risk, perceived benefits/barriers to early presentation, confidence in symptom detection, ovarian cancer worry), and demographic variables. Logistic regression analysis was used to identify the contribution of independent variables to anticipated presentation (categorised as < 3 weeks or ≥ 3 weeks). Results: The most well-recognised symptoms of ovarian cancer were post-menopausal bleeding (87.4%), and persistent pelvic (79.0%) and abdominal (85.0%) pain. Symptoms associated with eating difficulties and changes in bladder/bowel habits were recognised by less than half the sample. Lower symptom awareness was significantly associated with older age (p ≤ 0.001), being single (p ≤ 0.001), lower education (p ≤ 0.01), and lack of personal experience of ovarian cancer (p ≤ 0.01). The odds of anticipating a delay in time to presentation of ≥ 3 weeks were significantly increased in women educated to degree level (OR = 2.64, 95% CI 1.61 – 4.33, p ≤ 0.001), women who reported more practical barriers (OR = 1.60, 95% CI 1.34 – 1.91, p ≤ 0.001) and more emotional barriers (OR = 1.21, 95% CI 1.06 – 1.40, p ≤ 0.01), and those less confident in symptom detection (OR = 0.56, 95% CI 0.42 – 0.73, p ≤ 0.001), but not in those who reported lower symptom awareness (OR = 0.99, 95% CI 0.91 – 1.07, p = 0.74). Conclusions: Many symptoms of ovarian cancer are not well-recognised by women in the general population. Evidence-based interventions are needed not only to improve public awareness but also to overcome the barriers to recognising and acting on ovarian symptoms, if delays in presentation are to be minimised

A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF– strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression

H-Ras Expression in Immortalized Keratinocytes Produces an Invasive Epithelium in Cultured Skin Equivalents

Ras proteins affect both proliferation and expression of collagen-degrading enzymes, two important processes in cancer progression. Normal skin architecture is dependent both on the coordinated proliferation and stratification of keratinocytes, as well as the maintenance of a collagen-rich basement membrane. In the present studies we sought to determine whether expression of H-ras in skin keratinocytes would affect these parameters during the establishment and maintenance of an in vitro skin equivalent.Previously described cdk4 and hTERT immortalized foreskin keratinocytes were engineered to express ectopically introduced H-ras. Skin equivalents, composed of normal fibroblast-contracted collagen gels overlaid with keratinocytes (immortal or immortal expressing H-ras), were prepared and incubated for 3 weeks. Harvested tissues were processed and sectioned for histology and antibody staining. Antigens specific to differentiation (involucrin, keratin-14, p63), basement-membrane formation (collagen IV, laminin-5), and epithelial to mesenchymal transition (EMT; e-cadherin, vimentin) were studied. Results showed that H-ras keratinocytes produced an invasive, disorganized epithelium most apparent in the lower strata while immortalized keratinocytes fully stratified without invasive properties. The superficial strata retained morphologically normal characteristics. Vimentin and p63 co-localization increased with H-ras overexpression, similar to basal wound-healing keratinocytes. In contrast, the cdk4 and hTERT immortalized keratinocytes differentiated similarly to normal unimmortalized keratinocytes.The use of isogenic derivatives of stable immortalized keratinocytes with specified genetic alterations may be helpful in developing more robust in vitro models of cancer progression

Losartan therapy in adults with Marfan syndrome: study protocol of the multi-center randomized controlled COMPARE trial

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