[R74W;R1070W;D1270N]: a new complex allele responsible for cystic fibrosis.

Since the beginning of population screening for CF carriers, it has become apparent that complex CFTR alleles are not uncommon. Deciphering their impact in disease pathogenesis remains a challenge for both clinicians and researchers. We report the observation of a new complex allele p.[R74W+R1070W+D1270N] found in trans with a type 1 mutation and associated with clinical diagnosis of cystic fibrosis in a one year-old Moroccan patient. This case underlines the difficulties in counseling patients with uncommon mutations and the necessity of functional studies to evaluate the structure-function relationships, since the association of several variations in cis can dramatically alter CFTR function.

Wing geometry as a tool for studying the Lutzomyia longipalpis (Diptera: Psychodidae) complex

Toro Toro (T) and Yungas (Y) have been described as genetically well differentiated populations of the Lutzomyia longipalpis (Lutz & Neiva, 1912) complex in Bolivia. Here we use geometric morphometrics to compare samples from these populations and new populations (Bolivia and Nicaragua), representing distant geographical origins, qualitative morphological variation ("one-spot" or "two-spots" phenotypes), ecologically distinct traits (peridomestic and silvatic populations), and possibly different epidemiological roles (transmitting or nor transmitting Leishmania chagasi). The Nicaragua (N) (Somotillo) sample was "one-spot" phenotype and a possible peridomestic vector. The Bolivian sample of the Y was also "one-spot" phenotype and a demonstrated peridomestic vector of visceral leishmaniasis (VL). The three remaining samples were silvatic, "two-spots" phenotypes. Two of them (Uyuni and T) were collected in the highlands of Bolivian where VL never has been reported. The last one (Robore, R) came from the lowlands of Bolivia, where human cases of VL are sporadically reported. The decomposition of metric variation into size and shape by geometric morphometric techniques suggests the existence of two groups (N/Y/R, and U/T). Several arguments indicate that such subdivision of Lu. longipalpis could correspond to different evolutionary units.

Secretory IgA's complex roles in immunity and mucosal homeostasis in the gut.

Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms. Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence composition of the intestinal microbiota by Fab-dependent and Fab-independent mechanisms, promote retro-transport of antigens across the intestinal epithelium to dendritic cell subsets in gut-associated lymphoid tissue, and, finally, to downregulate proinflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships with immunity and intestinal homeostasis.

Perfusion-CT guided intravenous thrombolysis in patients with unknown-onset stroke: a randomized, double-blind, placebo-controlled, pilot feasibility trial.

INTRODUCTION: Patients with unknown stroke onset are generally excluded from acute recanalisation treatments. We designed a pilot study to assess feasibility of a trial of perfusion computed tomography (PCT)-guided thrombolysis in patients with ischemic tissue at risk of infarction and unknown stroke onset. METHODS: Patients with a supratentorial stroke of unknown onset in the middle cerebral artery territory and significant volume of at-risk tissue on PCT were randomized to intravenous thrombolysis with alteplase (0.9 mg/kg) or placebo. Feasibility endpoints were randomization and blinded treatment of patients within 2 h after hospital arrival, and the correct application (estimation) of the perfusion imaging criteria. RESULTS: At baseline, there was a trend towards older age [69.5 (57-78) vs. 49 (44-78) years] in the thrombolysis group (n = 6) compared to placebo (n = 6). Regarding feasibility, hospital arrival to treatment delay was above the allowed 2 h in three patients (25%). There were two protocol violations (17%) regarding PCT, both underestimating the predicted infarct in patients randomized in the placebo group. No symptomatic hemorrhage or death occurred during the first 7 days. Three of the four (75%) and one of the five (20%) patients were recanalized in the thrombolysis and placebo group respectively. The volume of non-infarcted at-risk tissue was 84 (44-206) cm(3) in the treatment arm and 29 (8-105) cm(3) in the placebo arm. CONCLUSIONS: This pilot study shows that a randomized PCT-guided thrombolysis trial in patients with stroke of unknown onset may be feasible if issues such as treatment delays and reliable identification of tissue at risk of infarction tissue are resolved. Safety and efficiency of such an approach need to be established.

Standardization of Stroke Perfusion CT for Reperfusion Therapy

With the advances in terms of perfusion imaging, the "time is brain" approach used for acute reperfusion therapy in ischemic stroke patients is slowly being replaced by a "penumbra is brain" or "imaging is brain" approach. But the concept of penumbra-guided reperfusion therapy has not been validated. The lack of standardization in penumbral imaging is one of the main contributing factors for this absence of validation. This article reviews the issues underlying the lack of standardization of perfusion-CT for penumbra imaging, and offers avenues to remedy this situation

Analyzing complex rock slope deformation at Stampa, western Norway, by integrating geomorphology, kinematics and numerical modeling

The unstable rock slope, Stampa, above the village of Flåm, Norway, shows signs of both active and postglacial gravitational deformation over an area of 11 km2. Detailed structural field mapping, annual differential Global Navigation Satellite System (GNSS) surveys, as well as geomorphic analysis of high-resolution digital elevation models based on airborne and terrestrial laser scanning indicate that slope deformation is complex and spatially variable. Numerical modeling was used to investigate the influence of former rockslide activity and to better understand the failure mechanism. Field observations, kinematic analysis and numerical modeling indicate a strong structural control of the unstable area. Based on the integration of the above analyses, we propose that the failure mechanism is dominated by (1) a toppling component, (2) subsiding bilinear wedge failure and (3) planar sliding along the foliation at the toe of the unstable slope. Using differential GNSS, 18 points were measured annually over a period of up to 6 years. Two of these points have an average yearly movement of around 10 mm/year. They are located at the frontal cliff on almost completely detached blocks with volumes smaller than 300,000 m3. Large fractures indicate deep-seated gravitational deformation of volumes reaching several 100 million m3, but the movement rates in these areas are below 2 mm/year. Two different lobes of prehistoric rock slope failures were dated with terrestrial cosmogenic nuclides. While the northern lobe gave an average age of 4,300 years BP, the southern one resulted in two different ages (2,400 and 12,000 years BP), which represent most likely multiple rockfall events. This reflects the currently observable deformation style with unstable blocks in the northern part in between Joasete and Furekamben and no distinct blocks but a high rockfall activity around Ramnanosi in the south. With a relative susceptibility analysis it is concluded that small collapses of blocks along the frontal cliff will be more frequent. Larger collapses of free-standing blocks along the cliff with volumes > 100,000 m3, thus large enough to reach the fjord, cannot be ruled out. A larger collapse involving several million m3 is presently considered of very low likelihood.

Evalución con pet/ct 11c-colina de recidivas bioquímicas ocultas de carcinoma de próstata.

Introducció. Material y mètodes. El nostre objectiu és valorar la utilitat del PET/CT 11C-Colina a la recidiva bioquímica oculta del carcinoma de pròstata. Es van estudiar retrospectivament 58 pacients amb aument de PSA posttractament. La interpretació de les imatges fou visual. Resultats: El PET/CT fou positiu en 39 pacients (67%) (PSA mitjà: 11.7). Es van dividir els malats en 4 grups segons el valor del PSA (sensibilitat%): &1ng/ml:50% 1ng/ml -3ng/ml:60% 3ng/ml-5ng/ml:86% & a 5ng/ml:91% . Conclusió: La PET/CT 11C-Colina mostra una alta capacitat de detecció per valors de PSA superiors a 5ng/ml i pot ser útil en valors superiors a 1ng/ml.

Perfusion ct based thrombolysis in acute ischaemic stroke

Background Despite use in clinical practice and trials of thrombolysis, a non-contrast CT is not sensitive for identifying penumbral tissue in acute stroke. This study evaluated how it compares with physiological imaging using CT perfusion.Methods 40 imaging datasets with non-contrast CT (NCCT) and perfusion CT (CTP) were retrospectively identified. 2 sets of observers (n¼6) and a neuroradiologist made a blind evaluation of the images. Inter-observer agreement was calculated for identifying ischaemic change on NCCT, and abnormalities on cerebral blood flow, time to peak and cerebral blood volume maps. A prospective cohort of 73 patients with anterior circulation cortical strokes were thrombolysed based on qualitative assessment of penumbral tissue on CTP within 3 h of stroke onset. Functional outcome was assessed at 3 months.Results Inter-rater agreement was moderate (k¼0.54) for early ischaemic change on NCCT. Perfusion maps improved this to substantial for deficit in cerebral blood volume (k¼0.67) and almost perfect for time to peak and cerebral blood flow (both k¼0.87). In the prospective arm, 58.9% of patients with cortical strokes were thrombolysed. There was no significant difference in attainment of complete recovery (p¼0.184) between the thrombolysed and nonthrombolysed group.Conclusions We demonstrate how perfusion CT aids clinical decision- making in acute stroke. Good functional outcomes from thrombolysis can be safely achieved using this physiologically informed approach.

Sequencing of simple sequence repeat anchored polymerase chain reaction amplification products of Biomphalaria glabrata

Simple sequence repeat anchored polymerase chain reaction amplification (SSR-PCR) is a genetic typing technique based on primers anchored at the 5' or 3' ends of microsatellites, at high primer annealing temperatures. This technique has already been used in studies of genetic variability of several organisms, using different primer designs. In order to conduct a detailed study of the SSR-PCR genomic targets, we cloned and sequenced 20 unique amplification products of two commonly used primers, CAA(CT)6 and (CA)8RY, using Biomphalaria glabrata genomic DNA as template. The sequences obtained were novel B. glabrata genomic sequences. It was observed that 15 clones contained microsatellites between priming sites. Out of 40 clones, seven contained complex sequence repetitions. One of the repeats that appeared in six of the amplified fragments generated a single band in Southern analysis, indicating that the sequence was not widespread in the genome. Most of the annealing sites for the CAA(CT)6 primer contained only the six repeats found within the primer sequence. In conclusion, SSR-PCR is a useful genotyping technique. However, the premise of the SSR-PCR technique, verified with the CAA(CT)6 primer, could not be supported since the amplification products did not result necessarily from microsatellite loci amplification.