Age-period-cohort analysis of oral cancer mortality in Europe: the end of an epidemic?

Over the last decade, mortality from oral and pharyngeal cancer has been declining in most European countries, but it had been increasing substantially in Hungary, Slovakia and a few other countries of central Europe, reaching rates comparable to those of lung cancer in several western European countries in males. To update trends in oral cancer mortality and further analyse the recent epidemic in central Europe, official death certifications for oral and pharyngeal cancer for 37 European countries were derived over the period 1970-2007, and an age-period-cohort model was fitted for selected countries. Male oral cancer mortality continued to decline in most European countries, including the Russian Federation, and, more importantly, it also started to decline in some of the countries with the highest male rates, i.e. Hungary and Slovakia; persisting rises were, however, observed in Belarus, Bulgaria and Romania. Oral cancer mortality rates for women were lower than in men and showed no appreciable trend over recent periods in the EU overall. Estimates from the age-period-cohort analysis for most selected countries showed a fall in effects for the cohorts born after the 1950s. For the period effect displayed a rise for the earlier periods, an inversion in the 1990s and a continuous fall up to the last studied period. Only some former non-market economy countries, like Romania, Ukraine and Lithuania, had rising cohort effect trends up to most recent generations. The major finding of this updated analysis of oral cancer mortality is the leveling of the epidemic for men in most European countries, including Hungary and other central European countries, where mortality from this cancer was exceedingly high. These trends essentially reflect the changes in alcohol and tobacco consumption in various populations.

Theoretical estimates of consumable food and probability of acquiring food in larvae of Chrysomya putoria (Diptera: Calliphoridae)

An indirect estimate of consumable food and probability of acquiring food in a blowfly species, Chrysomya putoria, is presented. This alternative procedure combines three distinct models to estimate consumable food in the context of the exploitative competition experienced by immature individuals in blowfly populations. The relevant parameters are derived from data for pupal weight and survival and estimates of density-independent larval mortality in twenty different larval densities. As part of this procedure, the probability of acquiring food per unit of time and the time taken to exhaust the food supply are also calculated. The procedure employed here may be valuable for estimations in insects whose immature stages develop inside the food substrate, where it is difficult to partial out confounding effects such as separation of faeces. This procedure also has the advantage of taking into account the population dynamics of immatures living under crowded conditions, which are particularly characteristic of blowflies and other insects as well.

A two years study on vectors of cutaneous leishmaniasis: Evidence for sylvatic transmission cycle in the State of Campeche, Mexico

Vectors of cutaneous leishmaniasis in the State of Campeche were studied in relation to the transmission cycle of Leishmania (Le.) mexicana. To determine how transmission of leishmaniasis occurs, we collected phlebotomine sand flies for two years. In the first year (October 1990 to November 1991) the collections were made with CDC light traps, Shannon traps and direct captures at natural shelters around the village (<200 m) of La Libertad. In the second year (February 1993 to January 1994) the catches were performed at 8 km southeast of La Libertad in the forest. Female sand flies were examined for Leishmania. During the first year, 347 sand flies of nine species were collected, most of which were Lutzomyia deleoni (61.3%). When all nine species were considered, more females than males were captured. Low densities of anthropophillic species of sand flies around the village indicated that sylvatic transmission was taking place. For the second year, 1484 sand flies of 16 species were caught. The most common were L. olmeca olmeca (21.7%), L. cruciata (19.2%) and L. ovallesi (14.1%). Similarly, more females were caught than males. Thirty-five females of five species were found infected with flagellates believed to be Leishmania sp. The highest infection rate was found in L. olmeca olmeca (7.1%) followed by L. cruciata (4.5%) and L. ovallesi (1.1%). These data plus other evidence on the epidemiology of human cases and results from reservoir studies are discussed in relation to the sylvatic transmission cycle.

History matters: relating paths and rates of landscape change to butterfly species decline

Western European landscapes have drastically changed since the 1950s, with agricultural intensifications and the spread of urban settlements considered the most important drivers of this land-use/land-cover change. Losses of habitat for fauna and flora have been a direct consequence of this development. In the present study, we relate butterfly occurrence to land-use/land-cover changes over five decades between 1951 and 2000. The study area covers the entire Swiss territory. The 10 explanatory variables originate from agricultural statistics and censuses. Both state as well as rate was used as explanatory variables. Species distribution data were obtained from natural history collections. We selected eight butterfly species: four species occur on wetlands and four occur on dry grasslands. We used cluster analysis to track land-use/land-cover changes and to group communes based on similar trajectories of change. Generalized linear models were applied to identify factors that were significantly correlated with the persistence or disappearance of butterfly species. Results showed that decreasing agricultural areas and densities of farms with more than 10 ha of cultivated land are significantly related with wetland species decline, and increasing densities of livestock seem to have favored disappearance of dry grassland species. Moreover, we show that species declines are not only dependent on land-use/land-cover states but also on the rates of change; that is, the higher the transformation rate from small to large farms, the higher the loss of dry grassland species. We suggest that more attention should be paid to the rates of landscape change as feasible drivers of species change and derive some management suggestions.

The Potential for Dispersal of Onchocerciasis in Ecuador in Relation to the Distribution of the Vector Simulium exiguum (Diptera:Simuliidae)

The future dispersal of onchocerciasis in Ecuador is dependent on the distribution of cytotypes of the vector species complex Simulium exiguum. Over the last 14 years, collections of larvae have been made from over 25 rivers, between 80-1600 m altitude, from various sites on both sides of the Andes. Analysis of larval polytene chromosomes was used to determine the distributions of each cytotype. On the western side of the Andes, the Cayapa cytotype (the only cytotype directly incriminated as a vector) has a distribution from Santo Domingo de los Colorados northwards. The Quevedo and Bucay cytotypes occur from Santo Domingo de los Colorados southwards. On the eastern side of the Andes, the Aguarico cytotype occurs in the Rio Aguarico and a new cytotype is present in the tributaries of the Rio Napo. Whether the disease will spread south of Santo Domingo and on the eastern side of the Andes depends on vector capacity of the cytotypes and the dispersal patterns of individuals infected with onchocerciasis. At present the Aguarico, Bucay and Quevedo cytotypes are known to be efficient hosts, but their biting preferences and biting densities have not yet been evaluated

Density-dependent pollen limitation and reproductive assurance in a wind-pollinated herb with contrasting sexual systems

1. Wind pollination is thought to have evolved in response to selection for mechanisms to promote pollination success, when animal pollinators become scarce or unreliable. We might thus expect wind-pollinated plants to be less prone to pollen limitation than their insect-pollinated counterparts. Yet, if pollen loads on stigmas of wind-pollinated species decline with distance from pollen donors, seed set might nevertheless be pollen-limited in populations of plants that cannot self-fertilize their progeny, but not in self-compatible hermaphroditic populations.2. Here, we test this hypothesis by comparing pollen limitation between dioecious and hermaphroditic (monoecious) populations of the wind-pollinated herb Mercurialis annua.3. In natural populations, seed set was pollen-limited in low-density patches of dioecious, but not hermaphroditic, M. annua, a finding consistent with patterns of distance-dependent seed set by females in an experimental array. Nevertheless, seed set was incomplete in both dioecious and hermaphroditic populations, even at high local densities. Further, both factors limited the seed set of females and hermaphrodites, after we manipulated pollen and resource availability in a common garden experiment.4. Synthesis. Our results are consistent with the idea that pollen limitation plays a role in the evolution of combined vs. separate sexes in M. annua. Taken together, they point to the potential importance of pollen transfer between flowers on the same plant (geitonogamy) by wind as a mechanism of reproductive assurance and to the dual roles played by pollen and resource availability in limiting seed set. Thus, seed set can be pollen-limited in sparse populations of a wind-pollinated species, where mates are rare or absent, having potentially important demographic and evolutionary implications.

Gender-role alternation in the simultaneously hermaphroditic freshwater snail Physa acuta: not with the same partner

In simultaneous hermaphrodites, gender conflicts that arise from two potential mates sharing the same gender preference may be solved through conditional reciprocity (or gamete trading). Conditional reciprocity had initially been considered widespread, but recent studies suggest that its real occurrence may have been overestimated, possibly because most mating observations have been performed on isolated pairs of individuals. Some resulting patterns (e. g., non-random alternation of sexual roles) were indeed compatible with conditional reciprocity but could also have stemmed from the two partners independently executing their own mating strategy and being experimentally enforced to do so with the same partner. Non-random alternation of gender roles was recently documented in the simultaneously hermaphroditic freshwater snail Physa acuta. To distinguish between conditional and unconditional gender alternations, we observed copulations of individually marked snails reared at three contrasted densities. We showed that density affected the overall frequency of copulations during the first 2 days of the experiment with high-density boxes showing more copulations than low density boxes, but it did not affect gender alternation patterns. A change in gender role was observed more often than expected by chance over two successive copulations by the same individual, confirming previous studies. However, gender switches did not preferentially occur with the same partner. We conclude that gender alternation is not due to conditional reciprocity in P. acuta. It may rather stem from each individual having a preference for gender alternation. We finally discuss the mechanisms and the potential extent of this unconditional reciprocity.

Ultimate test bench for pediatric biventricular assist device based on artificial muscles.

Ventricular assist devices (VADs) are used in treatment for terminal heart failure or as a bridge to transplantation. We created biVAD using the artificial muscles (AMs) that supports both ventricles at the same time. We developed the test bench (TB) as the in vitro evaluating system to enable the measurement of performance. The biVAD exerts different pressure between left and right ventricle like the heart physiologically does. The heart model based on child's heart was constructed in silicone. This model was fitted with the biVAD. Two pipettes containing water with an ultrasonic sensor placed on top of each and attached to ventricles reproduced the preload and the after load of each ventricle by the real-time measurement of the fluid height variation proportionally to the exerted pressure. The LabVIEW software extrapolated the displaced volume and the pressure generated by each side of our biVAD. The development of a standardized protocol permitted the validation of the TB for in vitro evaluation, measurement of the performances of the AM biVAD herein, and reproducibility of data.

Development of glycopeptide-intermediate resistance by Staphylococcus aureus leads to attenuated infectivity in a rat model of endocarditis.

Glycopeptide-intermediate resistant Staphylococcus aureus (GISA) are characterized by multiple changes in the cell wall and an altered expression of global virulence regulators. We investigated whether GISA are affected in their infectivity in a rat model of experimental endocarditis. The glycopeptide-susceptible, methicillin-resistant S. aureus M1V2 and its laboratory-derived GISA M1V16 were examined for their ability to (i) adhere to fibrinogen and fibronectin in vitro, (ii) persist in the bloodstream after intravenous inoculation, (iii) colonize aortic vegetations in rats, and (iv) compete for valve colonization by co-inoculation. Both GISA M1V16 and M1V2 adhered similarly to fibrinogen and fibronectin in vitro. In rats, GISA M1V16 was cleared faster from the blood (P < 0.05) and required 100-times more bacteria than parent M1V2 (10(6) versus 10(4)CFU) to infect 90% of vegetations. GISA M1V16 also had 100 to 1000-times lower bacterial densities in vegetations. Moreover, after co-inoculation with GISA M1V16 and M1V2Rif, a rifampin-resistant variant of M1V2 to discriminate them in organ cultures, GISA M1V16 was out-competed by the glycopeptide-susceptible counterpart. Thus, in rats with experimental endocarditis, GISA showed an attenuated virulence, likely due to a faster clearance from the blood and a reduced fitness in cardiac vegetations. The GISA phenotype appeared globally detrimental to infectivity.

Population pharmacokinetics and clinical response for artemether-lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Tanzania.

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response (P = 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.

Changes in the Sexual Dimorphism of Triatominae in the Transition from Natural to Artificial Habitats

A shift from large to small average sizes was observed in Triatoma infestans and Rhodnius domesticus between field and domestic (or laboratory) conditions of life. It was more pronounced in the female specimens, leading to a subsequent reduction of sexual size dimorphism. This feature is discussed in terms of genetic and populational changes occurring from natural to artificial habitats, in particular those related to population densities. Sexual size dimorphism is then recommended as a new character to be used in the study of species of Triatominae adapting to domestic ecotopes.

Transcriptional control of the hydrogen cyanide biosynthetic genes hcnABC by the anaerobic regulator ANR and the quorum-sensing regulators LasR and RhlR in Pseudomonas aeruginosa.

Virulence factors of Pseudomonas aeruginosa include hydrogen cyanide (HCN). This secondary metabolite is maximally produced at low oxygen tension and high cell densities during the transition from exponential to stationary growth phase. The hcnABC genes encoding HCN synthase were identified on a genomic fragment complementing an HCN-deficient mutant of P. aeruginosa PAO1. The hcnA promoter was found to be controlled by the FNR-like anaerobic regulator ANR and by the quorum-sensing regulators LasR and RhlR. Primer extension analysis revealed two transcription starts, T1 and T2, separated by 29 bp. Their function was confirmed by transcriptional lacZ fusions. The promoter sequence displayed an FNR/ANR box at -42.5 bp upstream of T2 and a lux box centered around -42.5 bp upstream of T1. Expression of the hcn genes was completely abolished when this lux box was deleted or inactivated by two point mutations in conserved nucleotides. The lux box was recognized by both LasR [activated by N-(oxododecanoyl)-homoserine lactone] and RhlR (activated by N-butanoyl-homoserine lactone), as shown by expression experiments performed in quorum-sensing-defective P. aeruginosa mutants and in the N-acyl-homoserine lactone-negative heterologous host P. fluorescens CHA0. A second, less conserved lux box lying 160 bp upstream of T1 seems to account for enhanced quorum-sensing-dependent expression. Without LasR and RhlR, ANR could not activate the hcn promoter. Together, these data indicate that expression of the hcn promoter from T1 can occur under quorum-sensing control alone. Enhanced expression from T2 appears to rely on a synergistic action between LasR, RhlR, and ANR.

Biocontrol ability of fluorescent pseudomonads genetically dissected: importance of positive feedback regulation.

Root diseases caused by fungal pathogens can be suppressed by certain rhizobacteria that effectively colonize the roots and produce extracellular antifungal compounds. To be effective, biocontrol bacteria need to be present at sufficiently high cell densities. These conditions favor the operation of positive feedback mechanisms that control the production of antifungal compounds in biocontrol strains of fluorescent pseudomonads, via both transcriptional and post-transcriptional mechanisms.

Gene expression mapping in neuropathic pain : molecular plasticity in nociceptors and superficial dorsal horn

RESUME : La douleur neuropathique est le résultat d'une lésion ou d'un dysfonctionnement du système nerveux. Les symptômes qui suivent la douleur neuropathique sont sévères et leur traitement inefficace. Une meilleure approche thérapeutique peut être proposée en se basant sur les mécanismes pathologiques de la douleur neuropathique. Lors d'une lésion périphérique une douleur neuropathique peut se développer et affecter le territoire des nerfs lésés mais aussi les territoires adjacents des nerfs non-lésés. Une hyperexcitabilité des neurones apparaît au niveau des ganglions spinaux (DRG) et de la corne dorsale (DH) de la moelle épinière. Le but de ce travail consiste à mettre en évidence les modifications moléculaires associées aux nocicepteurs lésés et non-lésés au niveau des DRG et des laminae I et II de la corne dorsale, là où l'information nociceptive est intégrée. Pour étudier les changements moléculaires liés à la douleur neuropathique nous utilisons le modèle animal d'épargne du nerf sural (spared nerve injury model, SNI) une semaine après la lésion. Pour la sélection du tissu d'intérêt nous avons employé la technique de la microdissection au laser, afin de sélectionner une sous-population spécifique de cellules (notamment les nocicepteurs lésés ou non-lésés) mais également de prélever le tissu correspondant dans les laminae superficielles. Ce travail est couplé à l'analyse à large spectre du transcriptome par puce ADN (microarray). Par ailleurs, nous avons étudié les courants électriques et les propriétés biophysiques des canaux sodiques (Na,,ls) dans les neurones lésés et non-lésés des DRG. Aussi bien dans le système nerveux périphérique, entre les neurones lésés et non-lésés, qu'au niveau central avec les aires recevant les projections des nocicepteurs lésés ou non-lésés, l'analyse du transcriptome montre des différences de profil d'expression. En effet, nous avons constaté des changements transcriptionnels importants dans les nocicepteurs lésés (1561 gènes, > 1.5x et pairwise comparaison > 77%) ainsi que dans les laminae correspondantes (618 gènes), alors que ces modifications transcriptionelles sont mineures au niveau des nocicepteurs non-lésés (60 gènes), mais important dans leurs laminae de projection (459 gènes). Au niveau des nocicepteurs, en utilisant la classification par groupes fonctionnels (Gene Ontology), nous avons observé que plusieurs processus biologiques sont modifiés. Ainsi des fonctions telles que la traduction des signaux cellulaires, l'organisation du cytosquelette ainsi que les mécanismes de réponse au stress sont affectés. Par contre dans les neurones non-lésés seuls les processus biologiques liés au métabolisme et au développement sont modifiés. Au niveau de la corne dorsale de la moelle, nous avons observé des modifications importantes des processus immuno-inflammatoires dans l'aire affectée par les nerfs lésés et des changements associés à l'organisation et la transmission synaptique au niveau de l'aire des nerfs non-lésés. L'analyse approfondie des canaux sodiques a démontré plusieurs changements d'expression, principalement dans les neurones lésés. Les analyses fonctionnelles n'indiquent aucune différence entre les densités de courant tétrodotoxine-sensible (TTX-S) dans les neurones lésés et non-lésés même si les niveaux d'expression des ARNm des sous-unités TTX-S sont modifiés dans les neurones lésés. L'inactivation basale dépendante du voltage des canaux tétrodotoxine-insensible (TTX-R) est déplacée vers des potentiels positifs dans les cellules lésées et non-lésées. En revanche la vitesse de récupération des courants TTX-S et TTX-R après inactivation est accélérée dans les neurones lésés. Ces changements pourraient être à l'origine de l'altération de l'activité électrique des neurones sensoriels dans le contexte des douleurs neuropathiques. En résumé, ces résultats suggèrent l'existence de mécanismes différenciés affectant les neurones lésés et les neurones adjacents non-lésés lors de la mise en place la douleur neuropathique. De plus, les changements centraux au niveau de la moelle épinière qui surviennent après lésion sont probablement intégrés différemment selon la perception de signaux des neurones périphériques lésés ou non-lésés. En conclusion, ces modulations complexes et distinctes sont probablement des acteurs essentiels impliqués dans la genèse et la persistance des douleurs neuropathiques. ABSTRACT : Neuropathic pain (NP) results from damage or dysfunction of the peripheral or central nervous system. Symptoms associated with NP are severe and difficult to treat. Targeting NP mechanisms and their translation into symptoms may offer a better therapeutic approach.Hyperexcitability of the peripheral and central nervous system occurs in the dorsal root ganglia (DRG) and the dorsal horn (DH) of the spinal cord. We aimed to identify transcriptional variations in injured and in adjacent non-injured nociceptors as well as in corresponding laminae I and II of DH receiving their inputs.We investigated changes one week after the injury induced by the spared nerve injury model of NP. We employed the laser capture microdissection (LCM) for the procurement of specific cell-types (enrichment in nociceptors of injured/non-injured neurons) and laminae in combination with transcriptional analysis by microarray. In addition, we studied functionál properties and currents of sodium channels (Nav1s) in injured and neighboring non-injured DRG neurons.Microarray analysis at the periphery between injured and non-injured DRG neurons and centrally between the area of central projections from injured and non-injured neurons show significant and differential expression patterns. We reported changes in injured nociceptors (1561 genes, > 1.5 fold, >77% pairwise comparison) and in corresponding DH laminae (618 genes), while less modifications occurred in non-injured nociceptors (60 genes) and in corresponding DH laminae (459 genes). At the periphery, we observed by Gene Ontology the involvement of multiple biological processes in injured neurons such as signal transduction, cytoskeleton organization or stress responses. On contrast, functional overrepresentations in non-injured neurons were noted only in metabolic or developmentally related mechanisms. At the level of superficial laminae of the dorsal horn, we reported changes of immune and inflammatory processes in injured-related DH and changes associated with synaptic organization and transmission in DH corresponding to non-injured neurons. Further transcriptional analysis of Nav1s indicated several changes in injured neurons. Functional analyses of Nav1s have established no difference in tetrodotoxin-sensitive (TTX-S) current densities in both injured and non-injured neurons, despite changes in TTX-S Nav1s subunit mRNA levels. The tetrodotoxin-resistant (TTX-R) voltage dependence of steady state inactivation was shifted to more positive potentials in both injured and non-injured neurons, and the rate of recovery from inactivation of TTX-S and TTX-R currents was accelerated in injured neurons. These changes may lead to alterations in neuronal electrogenesis. Taken together, these findings suggest different mechanisms occurring in the injured neurons and the adjacent non-injured ones. Moreover, central changes after injury are probably driven in a different manner if they receive inputs from injured or non-injured neurons. Together, these distinct and complex modulations may contribute to NP.

Reconstructing the origins of high-alpine niches and cushion life form in the genus Androsace S.L. (Primulaceae).

Relatively, few species have been able to colonize extremely cold alpine environments. We investigate the role played by the cushion life form in the evolution of climatic niches in the plant genus Androsace s.l., which spreads across the mountain ranges of the Northern Hemisphere. Using robust methods that account for phylogenetic uncertainty, intraspecific variability of climatic requirements and different life-history evolution scenarios, we show that climatic niches of Androsace s.l. exhibit low phylogenetic signal and that they evolved relatively recently and punctually. Models of niche evolution fitted onto phylogenies show that the cushion life form has been a key innovation providing the opportunity to occupy extremely cold environments, thus contributing to rapid climatic niche diversification in the genus Androsace s.l. We then propose a plausible scenario for the adaptation of plants to alpine habitats.