Family history of cancer and the risk of laryngeal cancer: a case-control study from Italy and Switzerland.

Only limited data is available on the relationship between family history of laryngeal and other neoplasms and laryngeal cancer risk. We investigated the issue using data from a multicentre case-control study conducted in Italy and Switzerland between 1992 and 2009 including 852 cases with histologically confirmed laryngeal cancer and 1970 controls admitted to hospital for acute, non neoplastic conditions. Unconditional logistic regression models adjusted for age, sex, study center, education, tobacco smoking, alcohol drinking and number of siblings were used to estimate the odds ratios (ORs) of laryngeal cancer. The multivariate OR was 2.8 (95% confidence interval [CI], 1.5-5.3) in subjects reporting a first-degree relative with laryngeal cancer, as compared to subjects with no family history. The OR was higher when the relative was diagnosed before 60 years of age (OR = 3.5, 95% CI 1.4-8.8). As compared to subjects without family history, non-smokers, and moderate drinkers, the OR was 37.1 (95% CI 9.9-139.4) for current smokers, heavy drinkers, with family history of laryngeal cancer. Family history of colorectal (OR = 1.5, 95% CI 1.0-2.3) and kidney (OR = 3.8, 95% CI 1.2-12.1) cancer were also associated to an increased risk of laryngeal cancer, while no significant increase in risk was found for family history of cancer at all sites, excluding the larynx (OR = 1.1).

Quantitative antibiogram as a typing method for the prospective epidemiological surveillance and control of MRSA: comparison with molecular typing.

OBJECTIVE: Evaluation of the quantitative antibiogram as an epidemiological tool for the prospective typing of methicillin-resistant Staphylococcus aureus (MRSA), and comparison with ribotyping. METHODS: The method is based on the multivariate analysis of inhibition zone diameters of antibiotics in disk diffusion tests. Five antibiotics were used (erythromycin, clindamycin, cotrimoxazole, gentamicin, and ciprofloxacin). Ribotyping was performed using seven restriction enzymes (EcoRV, HindIII, KpnI, PstI, EcoRI, SfuI, and BamHI). SETTING: 1,000-bed tertiary university medical center. RESULTS: During a 1-year period, 31 patients were found to be infected or colonized with MRSA. Cluster analysis of antibiogram data showed nine distinct antibiotypes. Four antibiotypes were isolated from multiple patients (2, 4, 7, and 13, respectively). Five additional antibiotypes were isolated from the remaining five patients. When analyzed with respect to the epidemiological data, the method was found to be equivalent to ribotyping. Among 206 staff members who were screened, six were carriers of MRSA. Both typing methods identified concordant of MRSA types in staff members and in the patients under their care. CONCLUSIONS: The quantitative antibiogram was found to be equivalent to ribotyping as an epidemiological tool for typing of MRSA in our setting. Thus, this simple, rapid, and readily available method appears to be suitable for the prospective surveillance and control of MRSA for hospitals that do not have molecular typing facilities and in which MRSA isolates are not uniformly resistant or susceptible to the antibiotics tested.

Estimating and explaining the effect of education and income on head and neck cancer risk : INHANCE consortium pooled analysis of 31 case-control studies from 27 countries

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region, and calendar time, and to explain the association in terms of behavioural risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2·50; 95%CI 2·02- 3·09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviours; and it remained elevated among never users of tobacco and non-drinkers (OR = 1·61; 95%CI 1·13 - 2·31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviours: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America, and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low vs high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioural risk factors for these cancers, and which varies across cancer sites, sexes, countries, and country income inequality levels. © 2014 Wiley Periodicals, Inc.

Control of transepithelial Na+ transport and Na-K-ATPase by oxytocin and aldosterone.

Short- and long-term effect of oxytocin on Na+ transport and Na-K-ATPase biosynthesis in the toad bladder, and the potential interaction of this hormone with aldosterone have been studied, leading to the following observations. An early Na+ transport response (oxytocin, 50 mU/ml) peaked at 10-15 min of hormone addition. At maximal stimulation a three- to fourfold increase in Na+ transport was observed, a sustained Na+ transport response (about two-fold control base line) was observed as long as the hormone was present in the medium and for up to 20 h of incubation. Pretreatment for 30 min with actinomycin D (2 micrograms/ml) did not inhibit the early response, but significantly impaired the sustained response, suggesting that de novo protein synthesis was required. The simultaneous addition of the two hormones led within 60 min to a marked potentiation of the action on Na+ transport. This synergism could be mimicked by exogenous cyclic adenosine monophosphate (cAMP). Oxytocin alone (18 h exposure, 50 mU/ml) increased the relative rate of synthesis of both alpha and beta subunits of Na-K-ATPase (1.9- and 1.6-fold, respectively; P less than 0.05), whereas aldosterone (80 nM) increased the relative rate of synthesis of the same subunits (2.6- and 2.2-fold, respectively; P less than 0.02). Finally, in contrast to what was observed at the physiological level, the interaction of oxytocin and aldosterone did not lead to a similar potentiation at the biochemical level, i.e., induction of Na-K-ATPase biosynthesis (2.7- and 2.9-fold, for alpha and beta subunits, respectively; P less than 0.025).

Periodic forcing of scroll rings and control of Winfree turbulence in excitable media

By simulations of the Barkley model, action of uniform periodic nonresonant forcing on scroll rings and wave turbulence in three-dimensional excitable media is investigated. Sufficiently strong rapid forcing converts expanding scroll rings into the collapsing ones and suppresses the Winfree turbulence caused by the negative tension of wave filaments. Slow strong forcing has an opposite effect, leading to expansion of scroll rings and induction of the turbulence. These effects are explained in the framework of the phenomenological kinematic theory of scroll waves.

Alpha1b-adrenergic receptors control locomotor and rewarding effects of psychostimulants and opiates.

Drugs of abuse, such as psychostimulants and opiates, are generally considered as exerting their locomotor and rewarding effects through an increased dopaminergic transmission in the nucleus accumbens. Noradrenergic transmission may also be implicated because most psychostimulants increase norepinephrine (NE) release, and numerous studies have indicated interactions between noradrenergic and dopaminergic neurons through alpha1-adrenergic receptors. However, analysis of the effects of psychostimulants after either destruction of noradrenergic neurons or pharmacological blockade of alpha1-adrenergic receptors led to conflicting results. Here we show that the locomotor hyperactivities induced by d-amphetamine (1-3 mg/kg), cocaine (5-20 mg/kg), or morphine (5-10 mg/kg) in mice lacking the alpha1b subtype of adrenergic receptors were dramatically decreased when compared with wild-type littermates. Moreover, behavioral sensitizations induced by d-amphetamine (1-2 mg/kg), cocaine (5-15 mg/kg), or morphine (7.5 mg/kg) were also decreased in knock-out mice when compared with wild-type. Ruling out a neurological deficit in knock-out mice, both strains reacted similarly to novelty, to intraperitoneal saline, or to the administration of scopolamine (1 mg/kg), an anti-muscarinic agent. Finally, rewarding properties could not be observed in knock-out mice in an oral preference test (cocaine and morphine) and conditioned place preference (morphine) paradigm. Because catecholamine tissue levels, autoradiography of D1 and D2 dopaminergic receptors, and of dopamine reuptake sites and locomotor response to a D1 agonist showed that basal dopaminergic transmission was similar in knock-out and wild-type mice, our data indicate a critical role of alpha1b-adrenergic receptors and noradrenergic transmission in the vulnerability to addiction.

Circadian control of tissue homeostasis and adult stem cells.

The circadian timekeeping mechanism adapts physiology to the 24-hour light/dark cycle. However, how the outputs of the circadian clock in different peripheral tissues communicate and synchronize each other is still not fully understood. The circadian clock has been implicated in the regulation of numerous processes, including metabolism, the cell cycle, cell differentiation, immune responses, redox homeostasis, and tissue repair. Accordingly, perturbation of the machinery that generates circadian rhythms is associated with metabolic disorders, premature ageing, and various diseases including cancer. Importantly, it is now possible to target circadian rhythms through systemic or local delivery of time cues or compounds. Here, we summarize recent findings in peripheral tissues that link the circadian clock machinery to tissue-specific functions and diseases.

Mutual control of membrane fission and fusion proteins.

Membrane fusion and fission are antagonistic reactions controlled by different proteins. Dynamins promote membrane fission by GTP-driven changes of conformation and polymerization state, while SNAREs fuse membranes by forming complexes between t- and v-SNAREs from apposed vesicles. Here, we describe a role of the dynamin-like GTPase Vps1p in fusion of yeast vacuoles. Vps1p forms polymers that couple several t-SNAREs together. At the onset of fusion, the SNARE-activating ATPase Sec18p/NSF and the t-SNARE depolymerize Vps1p and release it from the membrane. This activity is independent of the SNARE coactivator Sec17p/alpha-SNAP and of the v-SNARE. Vps1p release liberates the t-SNAREs for initiating fusion and at the same time disrupts fission activity. We propose that reciprocal control between fusion and fission components exists, which may prevent futile cycles of fission and fusion.

City of Oakville public assistance grants independent auditor’s reports, schedule of expenditures of federal awards, schedule of findings and questioned costs, year ended june 30, 2009.

Audit report on the City of Oakville, Iowa for the year ended June 30, 2009.

Immunologic and virologic characterization of an ART-treated HIV-I patients cohort with long-term control of viremia

Background Long-term treatment of primary HIV-1 infection (PHI) may allow the immune reconstitution of responses lost during the acute viremic phase and decrease of peripheral reservoirs. This in turn may represent the best setting for the use of therapeutic vaccines in order to lower the viral set-point or control of viral rebound upon ART discontinuation. Methods We investigated a cohort of 16 patients who started ART at PHI, with treatment duration of ≥4 years and persistent aviremia (<50 HIV-1 copies/ml). The cohort was characterized in terms of viral subtype, cell-associated RNA, proviral DNA and HLA genotype. Secretion of IFN-γ, IL-2 and TNF-α by CD8 T-cells was analysed by polychromatic flowcytometry using a panel of 192 HIV-1-derived epitopes. Results This cohort is highly homogenous in terms of viral subtype: 81% clade B. We identified 44 epitope-specific responses: all patients had detectable responses to >1 epitope and the mean number of responding epitopes per patient was 3. The mean frequency of cytokines-secreting CD8 T-cells was 0.32%. CD8 T-cells secreting simultaneously IFN-γ, IL-2 and TNF-α made up for about 40% of the response and cells secreting at least 2 cytokines for about 80%, consistent with a highly polyfunctional CD8 T-cell profile. There was no difference in term of polyfunctionality when HLA restriction, or recognized viral regions and epitopes were considered. Proviral DNA was detectable in all patients but at low levels (mean = 108 copies/1 million PBMCs) while cell-associated mRNA was not detectable in 19% of patients (mean = 11 copies/1 million PBMCs when detectable). Conclusion Patients with sustained virological suppression after initiation of ART at PHI show polyfunctional CD8 T-cell and low levels of proviral DNA with an absence of residual replication in a substantial percentage of patients. The use of therapeutic vaccines in this population may promote low level of rebound viremia or control of viral replication upon ART cessation.

A circuit-based gatekeeper for adult neural stem cell proliferation: Parvalbumin-expressing interneurons of the dentate gyrus control the activation and proliferation of quiescent adult neural stem cells.

Newborn neurons are generated in the adult hippocampus from a pool of self-renewing stem cells located in the subgranular zone (SGZ) of the dentate gyrus. Their activation, proliferation, and maturation depend on a host of environmental and cellular factors but, until recently, the contribution of local neuronal circuitry to this process was relatively unknown. In their recent publication, Song and colleagues have uncovered a novel circuit-based mechanism by which release of the neurotransmitter, γ-aminobutyric acid (GABA), from parvalbumin-expressing (PV) interneurons, can hold radial glia-like (RGL) stem cells of the adult SGZ in a quiescent state. This tonic GABAergic signal, dependent upon the activation of γ(2) subunit-containing GABA(A) receptors of RGL stem cells, can thus prevent their proliferation and subsequent maturation or return them to quiescence if previously activated. PV interneurons are thus capable of suppressing neurogenesis during periods of high network activity and facilitating neurogenesis when network activity is low.

Molecular biology of baculovirus and its use in biological control in Brazil

Baculoviruses are insect viruses found mainly in Lepidoptera. The family Baculoviridae is taxonomically divided in two genera, Nucleopolyhedrovirus and Granulovirus, which differ by occlusion body morphology. NPVs (Nucleopolyhedroviruses) have polyhedrical inclusion bodies (PIBs) containing multiple viral particles, while GVs (Granuloviruses) appear to be generally single particles occluded in oval shaped occlusion bodies. During the life cycle, two different viral progenies are produced: BV (Budded Virus) and PDV (Polyhedra Derived Virus), which are essential for the infectious process and virus propagation in host cells. Baculoviruses are being used for pest control and they are especially safe due to their specificity and invertebrate-restricted host range. Baculoviruses have been used as vectors for high level protein expression ofheterologous genes from prokaryotic and eukaryotic organisms. Also, recombinant DNA techniques have allowed the production of genetically modified viral insecticides. This study is a review on the taxonomy, structure, replication and molecular biology of baculoviruses, as well as their use as bioinsecticides in Brazil.

Tumor-host interactions Part 1: Stromal signatures of breast and prostate cancer Part 2: GLG1 and the control of the secretory pathway in tumor cells

Tumor-host interaction is a key determinant during cancer progression, from primary tumor growth to metastatic dissemination. At each step, tumor cells have to adapt to and subvert different types of microenvironment, leading to major phenotypic and genotypic alterations that affect both tumor and surrounding stromal compartments. Understanding the molecular mechanisms that govern tumor-host interplay may be essential for better comprehension of tumorigenesis in an effort to improve current anti-cancer therapies. The present work is composed of two projects that address tumor-host interactions from two different perspectives, the first focusing on the characterization of tumor-associated stroma and the second on membrane trafficking in tumor cells. Part 1. To selectively address stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to analyze the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Comparison showed that invasive breast and prostate cancer elicit distinct, tumor-specific stromal responses, with a limited panel of shared induced and/or repressed genes. Both breast and prostate tumor-specific deregulated stromal gene sets displayed statistically significant survival-predictive ability for their respective tumor type. By contrast, a stromal gene signature common to both tumor types did not display prognostic value, although expression of two individual genes within this common signature was found to be associated with patient survival. Part 2. GLG1 is known as an E-selectin ligand and an intracellular FGF receptor, depending on cell type and context. Immunohistochemical and immunofluorescence analyses showed that GLG1 is primarily localized in the Golgi of human tumor cells, a central location in the biosynthetic/secretory pathways. GLG1 has been shown to interact with and to recruit the ARF GEF BIGI to the Golgi membrane. Depletion of GLG1 or BIGI markedly reduced ARF3 membrane localization and activation, and altered the Golgi structure. Interestingly, these perturbations did not impair constitutive secretion in general, but rather seemed to impair secretion of a specific subset of proteins that includes MMP-9. Thus, GLG1 coordinates ARF3 activation by recruiting BIGI to the Golgi membrane, thereby affecting secretion of specific molecules. - Les interactions tumeur-hôte constituent un élément essentiel à la progression tumorale, de la croissance de la tumeur primaire à la dissémination des métastases. A chaque étape, les cellules tumorales doivent s'adapter à différents types de microenvironnement et les détourner à leur propre avantage, donnant lieu à des altérations phénotypiques et génotypiques majeures qui affectent aussi bien la tumeur elle-même que le compartiment stromal environnant. L'étude des mécanismes moléculaires qui régissent les interactions tumeur-hôte constitue une étape essentielle pour une meilleure compréhension du processus de tumorigenèse dans le but d'améliorer les thérapies anti cancer existantes. Le travail présenté ici est composé de deux projets qui abordent la problématique des interactions tumeur-hôte selon différentes perspectives, le premier se concentrant sur la caractérisation du stroma tumoral et le second sur le trafic intracellulaire des cellules tumorales. Partie 1. Pour examiner les changements d'expression des gènes dans le stroma en réponse à la progression du cancer, des puces à ADN Affymetrix ont été utilisées afin d'analyser les transcriptomes des cellules stromales issues de carcinomes invasifs du sein et de la prostate et collectées par microdissection au laser. L'analyse comparative a montré que les cancers invasifs du sein et de la prostate provoquent des réponses stromales spécifiques à chaque type de tumeur, et présentent peu de gènes induits ou réprimés de façon similaire. L'ensemble des gènes dérégulés dans le stroma associé au cancer du sein, ou à celui de la prostate, présente une valeur pronostique pour les patients atteints d'un cancer du sein, respectivement de la prostate. En revanche, la signature stromale commune aux deux types de cancer n'a aucune valeur prédictive, malgré le fait que l'expression de deux gènes présents dans cette liste soit liée à la survie des patients. Partie 2. GLG1 est connu comme un ligand des sélectines E ainsi que comme récepteur intracellulaire pour des facteurs de croissances FGFs selon le type de cellule dans lequel il est exprimé. Des analyses immunohistochimiques et d'immunofluorescence ont montré que dans les cellules tumorales, GLG1 est principalement localisé au niveau de l'appareil de Golgi, une place centrale dans la voie biosynthétique et sécrétoire. Nous avons montré que GLG1 interagit avec la protéine BIGI et participe à son recrutement à la membrane du Golgi. L'absence de GLG1 ou de BIGI réduit drastiquement le pool d'ARF3 associé aux membranes ainsi que la quantité d'ARF3 activés, et modifie la structure de l'appareil de Golgi. Il est particulièrement intéressant de constater que ces perturbations n'ont pas d'effet sur la sécrétion constitutive en général, mais semblent plutôt affecter la sécrétion spécifique d'un sous-groupe défini de protéines comprenant MMP-9. GLG1 coordonne donc l'activation de ARF3 en recrutant BIGI à la membrane du Golgi, agissant par ce moyen sur la sécrétion de molécules spécifiques.

Prevalence, awareness and control of diabetes in the Seychelles and relationship with excess body weight.

BACKGROUND: The evidence for a "diabesity" epidemic is accumulating worldwide but population-based data are still scarce in the African region. We assessed the prevalence, awareness and control of diabetes (DM) in the Seychelles, a rapidly developing country in the African region. We also examined the relationship between body mass index, fasting serum insulin and DM. METHODS: Examination survey in a sample representative of the entire population aged 25-64 of the Seychelles, attended by 1255 persons (participation rate of 80.2%). An oral glucose tolerance test (OGTT) was performed in individuals with fasting blood glucose between 5.6 and 6.9 mmol/l. Diabetes mellitus (DM), impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were defined along criteria of the ADA. Prevalence estimates were standardized for age. RESULTS: The prevalence of DM was 11.5% and 54% of persons with DM were aware of having DM. Less than a quarter of all diabetic persons under treatment were well controlled for glycemia (HbA1c), blood pressure or LDL-cholesterol. The prevalence of IGT and IFG were respectively 10.4% and 24.2%. The prevalence of excess weight (BMI > or = 25 kg/m2) and obesity (BMI > or = 30 kg/m2) was respectively 60.1% and 25.0%. Half of all DM cases in the population could be attributed to excess weight. CONCLUSION: We found a high prevalence of DM and pre-diabetes in a rapidly developing country in the African region. The strong association between overweight and DM emphasizes the importance of weight control measures to reduce the incidence of DM in the population. High rates of diabetic persons not aware of having DM in the population and insufficient cardiometabolic control among persons treated for DM stress the need for intensifying health care for diabetes.