High levels of women's satisfaction and compliance with transdermal contraception: results from a European multinational, 6-month study

Objective. To investigate compliance, satisfaction, and preference in women using a transdermal contraceptive patch. Methods. Women (18–46 years) from eight European countries used contraceptive patches (norelgestromin 6 mg, ethinylestradiol 600 mg) for six, 4-week treatment cycles. Compliance, satisfaction, and preference were assessed after 3 and 6 cycles and study completion using self-report methods. Results. Of the 778 participants, 36.8 % (n 287) used no contraception at baseline. The most common methods were oral contraceptives (67.9%, n 334) and barrier methods (21.5%, n 106). Of oral contraception users, 63.5 % (n 212) were satisfied or very satisfied with their previous method, but compliance was poor with 77.8 % (n 260) reporting missed doses. After 3 and 6 cycles,480 % of all included women were satisfied or very satisfied with the patch. At study completion, most participants (73.7%) reported a preference for the patch compared to their previous method. Of 4107 cycles, 3718 (90.5%) were completed with perfect compliance. Two pregnancies occurred during this study, representing a Pearl Index of 0.63. No new safety issues were identified and the patch was well tolerated. Conclusion. Women were highly satisfied with transdermal contraception and preferred this form of family planning over their previous method. Transdermal contraception represents a valuable addition to contraceptive options with potential t

Adult Congenital Heart Disease Investigated with Cardiac Catheterization Over A 20-Year Period

BACKGROUND: Recent advances in diagnosis and treatment have increased the life expectancy of patients with congenital heart disease. METHODS: To investigate the prevalence of adult congenital heart disease (ACHD) in a large registry of patients over a 20-year period, we retrospectively assessed data of 14,012 males and 4,461 females who underwent clinically indicated cardiac catheterization from 1984 to 2003. RESULTS: ACHD was recorded in 234 subjects aged from 18 to 66 years, [95 males (40.7%) and 139 females (59.3%)]. Females were more likely to present with ACHD than males (p<0.001). Atrial septal defect was the most common defect (43.3%) followed by partial anomalous pulmonary venous return (12.0%), pulmonary valve stenosis (11.3%) ventricular septal defect (8.0%), coarctation of aorta (5.5%) patent ductus arteriosus (4.0%) and Fallot's tetralogy (3.3%). Atrial septal defect was more common in females (p<0.01), while pulmonary valve stenosis was more frequent in males (p<0.05). No difference across sexes was found in the other forms of ACHD. Females with ACHD were significantly older than males at the time of catheterization (median age 41 years, interquartile range 26 to 53 years vs. median age 35 years, interquartile range 22 to 48 years, p<0.05). CONCLUSIONS: In adulthood ACHD is found more commonly in females and is diagnosed later in life than in males. Atrial septal defect is the most prevalent form of ACHD and occurs most commonly in females

Genomic analysis of the function of the transcription factor gata3 during development of the Mammalian inner ear

We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKB beta, a dramatic increase in Akt1/PKB alpha protein and relocation of Akt1/PKB alpha from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27(kip1), a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome

Adhesion Molecules Associated with Female Genital Tract Infection

Altres ajuts: Marie Curie Career Integration Grant i una beca Fundació Dexeus Salut de la DonaEfforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut). Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes

Severe Pandemic H1N1 2009 Infection Is Associated with Transient NK and T Deficiency and Aberrant CD8 Responses

BACKGROUND: It is unclear why the severity of influenza varies in healthy adults or why the burden of severe influenza shifts to young adults when pandemic strains emerge. One possibility is that cross-protective T cell responses wane in this age group in the absence of recent infection. We therefore compared the acute cellular immune response in previously healthy adults with severe versus mild pandemic H1N1 infection. METHODS AND PRINCIPAL FINDINGS: 49 previously healthy adults admitted to the National Hospital of Tropical Diseases, Viet Nam with RT-PCR-confirmed 2009 H1N1 infection were prospectively enrolled. 39 recovered quickly whereas 10 developed severe symptoms requiring supplemental oxygen and prolonged hospitalization. Peripheral blood lymphocyte subset counts and activation (HLADR, CD38) and differentiation (CD27, CD28) marker expression were determined on days 0, 2, 5, 10, 14 and 28 by flow cytometry. NK, CD4 and CD8 lymphopenia developed in 100%, 90% and 60% of severe cases versus 13% (p<0.001), 28%, (p = 0.001) and 18% (p = 0.014) of mild cases. CD4 and NK counts normalized following recovery. B cell counts were not significantly associated with severity. CD8 activation peaked 6-8 days after mild influenza onset, when 13% (6-22%) were HLADR+CD38+, and was accompanied by a significant loss of resting/CD27+CD28+ cells without accumulation of CD27+CD28- or CD27-CD28- cells. In severe influenza CD8 activation peaked more than 9 days post-onset, and/or was excessive (30-90% HLADR+CD38+) in association with accumulation of CD27+CD28- cells and maintenance of CD8 counts. CONCLUSION: Severe influenza is associated with transient T and NK cell deficiency. CD8 phenotype changes during mild influenza are consistent with a rapidly resolving memory response whereas in severe influenza activation is either delayed or excessive, and partially differentiated cells accumulate within blood indicating that recruitment of effector cells to the lung could be impaired

Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

The SUN Protein Mps3 Is Required for Spindle Pole Body Insertion into the Nuclear Membrane and Nuclear Envelope Homeostasis

The budding yeast spindle pole body (SPB) is anchored in the nuclear envelope so that it can simultaneously nucleate both nuclear and cytoplasmic microtubules. During SPB duplication, the newly formed SPB is inserted into the nuclear membrane. The mechanism of SPB insertion is poorly understood but likely involves the action of integral membrane proteins to mediate changes in the nuclear envelope itself, such as fusion of the inner and outer nuclear membranes. Analysis of the functional domains of the budding yeast SUN protein and SPB component Mps3 revealed that most regions are not essential for growth or SPB duplication under wild-type conditions. However, a novel dominant allele in the P-loop region, MPS3-G186K, displays defects in multiple steps in SPB duplication, including SPB insertion, indicating a previously unknown role for Mps3 in this step of SPB assembly. Characterization of the MPS3-G186K mutant by electron microscopy revealed severe over-proliferation of the inner nuclear membrane, which could be rescued by altering the characteristics of the nuclear envelope using both chemical and genetic methods. Lipid profiling revealed that cells lacking MPS3 contain abnormal amounts of certain types of polar and neutral lipids, and deletion or mutation of MPS3 can suppress growth defects associated with inhibition of sterol biosynthesis, suggesting that Mps3 directly affects lipid homeostasis. Therefore, we propose that Mps3 facilitates insertion of SPBs in the nuclear membrane by modulating nuclear envelope composition

Discrimination in lexical decision.

In this study we present a novel set of discrimination-based indicators of language processing derived from Naive Discriminative Learning (ndl) theory. We compare the effectiveness of these new measures with classical lexical-distributional measures-in particular, frequency counts and form similarity measures-to predict lexical decision latencies when a complete morphological segmentation of masked primes is or is not possible. Data derive from a re-analysis of a large subset of decision latencies from the English Lexicon Project, as well as from the results of two new masked priming studies. Results demonstrate the superiority of discrimination-based predictors over lexical-distributional predictors alone, across both the simple and primed lexical decision tasks. Comparable priming after masked corner and cornea type primes, across two experiments, fails to support early obligatory segmentation into morphemes as predicted by the morpho-orthographic account of reading. Results fit well with ndl theory, which, in conformity with Word and Paradigm theory, rejects the morpheme as a relevant unit of analysis. Furthermore, results indicate that readers with greater spelling proficiency and larger vocabularies make better use of orthographic priors and handle lexical competition more efficiently

MR fluoroscopy in vascular and cardiac interventions (review)

Vascular and cardiac disease remains a leading cause of morbidity and mortality in developed and emerging countries. Vascular and cardiac interventions require extensive fluoroscopic guidance to navigate endovascular catheters. X-ray fluoroscopy is considered the current modality for real time imaging. It provides excellent spatial and temporal resolution, but is limited by exposure of patients and staff to ionizing radiation, poor soft tissue characterization and lack of quantitative physiologic information. MR fluoroscopy has been introduced with substantial progress during the last decade. Clinical and experimental studies performed under MR fluoroscopy have indicated the suitability of this modality for: delivery of ASD closure, aortic valves, and endovascular stents (aortic, carotid, iliac, renal arteries, inferior vena cava). It aids in performing ablation, creation of hepatic shunts and local delivery of therapies. Development of more MR compatible equipment and devices will widen the applications of MR-guided procedures. At post-intervention, MR imaging aids in assessing the efficacy of therapies, success of interventions. It also provides information on vascular flow and cardiac morphology, function, perfusion and viability. MR fluoroscopy has the potential to form the basis for minimally invasive image–guided surgeries that offer improved patient management and cost effectiveness