Lack of seasonal variation in cardiovascular mortality in a country near the equator

Introduction: Mortality from cardiovascular disease (CVD) varies according to seasons in countries that are located far away from the equator, likely linked to concomitant seasonal variation in underlying CVD risk factors. We assessed temporal variation in CVD mortality in the Seychelles, a small island state situated near the equator and where the climate is virtually constant throughout the year. Seychelles is one of the few countries located near the equator where all deaths are registered. Methods: We recoded all deaths along broad causes, including CVD (n=5643), stroke (2112) and myocardial infarction (MI, 804). Stroke and MI were considered as the cause of death if the diagnosis appeared in any of the four fields for underlying causes of death in the death certificates. In view of the small size of the population, we pooled all deaths (n=13'163) between 1989 and 2010. Results: Mortality for all CVD, stroke and MI did not systematically vary according to month or season (chi square >0.05). A lack of variation was also observed within sex and age categories. Conclusion: The lack of seasonal variation in CVD mortality in a country located near the equator is consistent with the hypothesis that seasonal variation in CVD decreases along decreasing a country's latitude.

Les variations du développement sexuel: «La différence au grand jour»

Contexte : Hermaphrodisme, pseudohermaphrodisme, intersexe ou encore troubles du développement du sexe (Disorders of Sex Development) : autant de termes désignant des pathologies concernant une proportion non-négligeable de la population. Dans une société où le développement génital et l'identité sexuelle sont à la fois tabous et mal connus, le corps médical a un rôle clé à jouer dans la prise en charge à long terme ainsi que dans le soutien des patients intersexués et de leur entourage proche. Cette prise en charge commence par une information complète et transparente des parents et des enfants touchés. Objectifs : Elaborer un document capable de décrire de la manière la plus complète et compréhensible possible le thème de l'intersexualité. Il sera à la fois basé sur les connaissances médicales actuelles, mais également sur les témoignages de patients, parents et groupes de soutien aux intersexes. Il sera finalement destiné à l'information des parents ainsi que de leurs enfants intersexués à différentes étapes de leur développement. Méthode : Une compréhension approfondie de la thématique de l'intersexualité sur le plan médical, impliquant une approche multidisciplinaire, est une première étape cruciale. Agrémentée de témoignages de patients, de parents et des divers groupes de soutient actifs sur ce sujet, nous obtiendrons les bases nécessaires pour concevoir un document d'information à la fois le plus complet et le plus proche possible des attentes des patients et des parents. Résultat escompté : Répondre aux attentes formulées par les différents acteurs de la thématique de l'intersexualité et ainsi promouvoir une meilleure compréhension des mécanismes et des enjeux qui la caractérisent. Obtenir un feedback positif des groupes de soutien aux intersexes sur la qualité de l'information donnée dans ce document.

Circadian Variations of Ischemic Burden Among Patients with Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Introduction Le rythmes circadiens influencent différents paramètres de la physiologie et de la physiopathologie cardiovasculaire. Récemment, une relation entre la taille d'un infarctus et l'heure du jour à laquelle il se produit a été suggérée dans des modèles expérimentaux d'infarctus du myocarde. Le but de cette étude a été de déterminer si les rythmes circadiens pouvaient influencer la gravité d'un infarctus en terme de taille et de mortalité chez les patients hospitalisés pour un infarctus du myocarde avec sus-décalage du segment ST (STEMI) ayant bénéficié d'une intervention coronarienne percutanée primaire (ICPP). Méthode Chez 353 patients consécutifs admis avec un STEMI et traités par ICPP, l'heure à la survenue des symptômes, le pic de créatine kinase (reflet de la taille d'un infarctus) et le suivi à 30 jours ont été collectés. Les patients ont été répartis en 4 groupes en fonction de l'heure de survenue de leurs symptômes (00 :00 - 05h59, 06:00 - 11 59 12 00-17h59 et 18h00-23h59). Résultats Aucune différence statistiquement significative n'a été retrouvée entre les différents groupes en ce qui concerne les caractéristiques des patients ou de leur prise en charge. Après analyse multivariée, nous avons mis en évidence une différence statistiquement significative entre les pics de créatine kinase chez les patients avec survenue des symptômes entre 00 :00 et 05:59, qui étaient plus élevés que les pics de créatine kinase chez les patients avec survenue des symptômes à tout autre moment de la journée (augmentation moyenne de 38,4%, ρ <0.05). A 30 jours, la mortalité des patients avec survenue des symptômes entre 00 :00 et 05:59 était également significativement plus élevé que celle des patients avec survenue à tout autre moment de la journée (p <0.05). Conclusion Notre étude démontre une corrélation indépendante entre la taille d'un infarctus STEMI traité par ICPP et le moment de la journée où les symptômes apparaissent. Ces résultats suggèrent que ce moment devrait être un paramètre important à prendre en compte pour évaluer le pronostic des patients.

Avoiding epigenetic variations in transgene expression with genetic insulators

Gene transfer that relies on integrating vectors often suffers from epigenetic or regulatory effects that influence the expression of the therapeutic gene and=or of cellular genes located near the vector integration site in the chromosome. Insulator elements act to block gene activation by enhancers, while chromatin domain boundary or barrier sequences prevent gene-silencing effects. At present, the modes of action of insulator and barriers are poorly understood, and their use in the context of gene therapies remains to be documented. Using combinations of reporter genes coding for indicator fluorescent proteins, we constructed assay systems that allow the quantification of the insulator or of the barrier activities of genetic elements in individual cells. This presentation will illustrate how these assay systems were used to identify short DNA elements that can insulate nearby genes from activation by viral vector enhancer elements, and=or that can block the propagation of a silent chromatin structure that leads to gene silencing. We will show that small elements of the order of 100-400 nucleotides can be designed to achieve both insulator and boundary function, as needed for safer integrating viral vectors.

Seasonal patterns op biomass variation of Ruppia cirrhosa (Petagna) Grande and Potamageton pectinatus L. in a coastal logoon

Coastal lagoons where salinity varies within a wide range during the year are colonized by euryhaline macrophytes which can develop extensive beds. Seasonal changes in biomass of Ruppia cirrhosa and Potamogeton pectinatus were studied in Tancada Lagoon (Ebro Delta, NE Spain) in order to reveal the environmental factors controlling their population development. Ruppia cirrhosa occupy a larger area of the lagoon than Potarnogeton pectinatus. Their maximum above ground biomasses are also different (495 g m-2 and 351 g m-2 ash free dry weight, respectively). Below ground biomass of Ruppia cirrhosa is between 9 and 53 % of the above ground biomass, while it is 3-40 % for Potamogeton pectinatus. Chlorophyll a contents show fluctuations similar to biomass. Low salinity and high turbidity caused by freshwater inflows favour Potamogeton expansion, while Ruppia development is favoured by high salinity and transparent water.

Effects on blood pressure and cardiovascular risk of variations in patients' adherence to prescribed antihypertensive drugs: role of duration of drug action.

P>Aim: To determine the effects of imperfect adherence (i.e. occasionally missing prescribed doses), and the influence of rate of loss of antihypertensive effect during treatment interruption, on the predicted clinical effectiveness of antihypertensive drugs in reducing mean systolic blood pressure (SBP) and cardiovascular disease (CVD) risk.Method:The effects of imperfect adherence to antihypertensive treatment regimens were estimated using published patterns of missed doses, and taking into account the rate of loss of antihypertensive effect when doses are missed (loss of BP reduction in mmHg/day; the off-rate), which varies between drugs. Outcome measures were the predicted mean SBP reduction and CVD risk, determined from the Framingham Risk Equation for CVD.Results:In patients taking 75% of prescribed doses (typical of clinical practice), only long-acting drugs with an off-rate of similar to 1 mmHg/day were predicted to maintain almost the full mean SBP-lowering effect throughout the modelled period. In such patients, using shorter-acting drugs (e.g. an off-rate of similar to 5-6 mmHg/day) was predicted to lead to a clinically relevant loss of mean SBP reduction of > 2 mmHg. This change also influenced the predicted CVD risk reduction; in patients with a baseline 10-year CVD risk of 27.0% and who were taking 75% of prescribed doses, a difference in off-rate from 1 to 5 mmHg/day led to a predicted 0.5% absolute increase in 10-year CVD risk.Conclusions:In patients who occasionally miss doses of antihypertensives, modest differences in the rate of loss of antihypertensive effect following treatment interruption may have a clinically relevant impact on SBP reduction and CVD risk. While clinicians must make every effort to counsel and encourage each of their patients to adhere to their prescribed medication, it may also be prudent to prescribe drugs with a low off-rate to mitigate the potential consequences of missing doses.

Seasonal growth of "algodão-bravo" (Ipomoea carnea spp. fistulosa)

Ipomoea carnea spp. fistulosa, a native woody perennial, is capable of spreading rapidly over seasonally flooded grassland in the Brazilian Pantanal, South America's largest wetland, thus conflicting with the local cattle ranching. I. carnea is controlled by mowing at the onset of the rainy season, as close as possible before the seasonal flooding. Often, however, flooding begins after the plant has had enough time to re-sprout enabling it to survive. The objective of this study was to verify if Ipomoea carnea plant's production follows a seasonal cycle, and, if so, at which point in this cycle, the plant is most vulnerable to mechanical control measures. Seasonal dynamics of stem and leaf production of I. carnea were studied. The results showed that growth of I. carnea is fastest at the onset of the rainy season in November/December. Production declines when seasonal flooding commences in January/February and almost ceases towards the begin of the dry season in May/June. This leads to the proposal that I. carnea could be controlled more effectively if the weed were mown in the early dry season when its production and its capability to re-sprout is lowest, and if any new sprouts were cut by hand when the seasonal flooding starts.

Lack of EGFR-activating mutations in European patients with triple-negative breast cancer could emphasise geographic and ethnic variations in breast cancer mutation profiles.

INTRODUCTION: Triple-negative breast cancers (TNBCs) are characterised by lack of expression of hormone receptors and epidermal growth factor receptor 2 (HER-2). As they frequently express epidermal growth factor receptors (EGFRs), anti-EGFR therapies are currently assessed for this breast cancer subtype as an alternative to treatments that target HER-2 or hormone receptors. Recently, EGFR-activating mutations have been reported in TNBC specimens in an East Asian population. Because variations in the frequency of EGFR-activating mutations in East Asians and other patients with lung cancer have been described, we evaluated the EGFR mutational profile in tumour samples from European patients with TNBC. METHODS: We selected from a DNA tumour bank 229 DNA samples isolated from frozen, histologically proven and macrodissected invasive TNBC specimens from European patients. PCR and high-resolution melting (HRM) analyses were used to detect mutations in exons 19 and 21 of EGFR. The results were then confirmed by bidirectional sequencing of all samples. RESULTS: HRM analysis allowed the detection of three EGFR exon 21 mutations, but no exon 19 mutations. There was 100% concordance between the HRM and sequencing results. The three patients with EGFR exon 21 abnormal HRM profiles harboured the rare R836R SNP, but no EGFR-activating mutation was identified. CONCLUSIONS: This study highlights variations in the prevalence of EGFR mutations in TNBC. These variations have crucial implications for the design of clinical trials involving anti-EGFR treatments in TNBC and for identifying the potential target population.

Variations of the carcinoembryonic antigen level in the plasma of patients with gynecologie cancers during therapy

In 63 patients with histologically proved gynecologie carcinoma, circulating carcinoembryonic antigen (CEA) was determined by radioimmunoassay before and at two intervals after treatment. Thirty-one patients of 63 had CEA values over 2.5 ng. per milliliter before treatment. In general, the CEA levels were low compared to those found in endodermal carcinoma. The percentage of elevated CEA values was slightly higher in cases of carcinoma of the cervix and corpus uteri than in those of carcinoma of the ovary. All patients with CEA levels greater than 2.5 ng. per milliliter treated by complete surgical resection of tumor showed a drop of CEA levels to below 2.5 ng. per milliliter seven weeks after operation. In contrast, patients with palliative therapy showed no change in CEA values. About half of the patients treated with a complete course of internal and external radiotherapy showed a drop of CEA levels to below 2.5 ng. per milliliter, whereas the other patients showed fluctuating CEA values. No correlation between clinical status and evolution of CEA levels in these patients could be drawn at the present time. The CEA test seems to be of little value for the earl of diagnosis of gynecologie carcinoma but appears to be interesting for the evaluation of therapy and the follow-up of patients with diagnosed cases.