Termination of pregnancy due to Thalassemia major, Hemophilia, and Down's Syndrome: the views of Iranian physicians

<p>Abstract</p> <p>Background</p> <p>Genetic disorders due to <b>kindred </b>marriages are common medical conditions in Iran; however, the legal aspects of abortion remain controversial. This study was undertaken to determine physicians' opinions regarding the termination of pregnancy for three genetic diseases: thalassemia major, hemophilia, and Down's syndrome.</p> <p>Methods</p> <p>A questionnaire was administered to selected physicians by stratified random sampling to determine the following: age, gender, knowledge about prenatal diagnosis of diseases in high risk pregnancies, agreement with abortion, recommended gestational age for abortion, and, if opposed to abortion, the reason.</p> <p>Results</p> <p>Of 323 physicians, who participated in the study, 91.3(295), 40.6(131), and 78.6%(254) were in agreement and 8.7(28), 59.4(192), and 21.4%(69) were opposed to abortion for thalassemia major, hemophilia, and Down's syndrome, respectively. Among 289 physicians opposed to abortion in respect of each of all three conditions, the following reasons were cited: religion, 18; emotional, 10; quality of care, 23; hope to find a new treatment option in the future, 103; miscellaneous reasons, 6; and a combination of these reasons, 129. Among 680 physicians in agreement with abortion in relation to all of the diseases, 4.6%(31) were agreed with abortion in less than 12 weeks gestation, 79.2%(538) in less than 16 weeks gestation, 5.6%(38) in less than 20 weeks gestation, 2.2%(15) in less than 24 weeks gestation, and 8.4%(58) were agreed with beyond the 24 weeks of gestational age.</p> <p>Conclusion</p> <p>The majority of physicians were in agreement with abortion for thalassemia major and Down's syndrome because of the overall prognosis, but opposed to abortion for hemophilia.</p

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Health care seeking among pulmonary tuberculosis suspects and patients in rural Ethiopia: a community-based study

<p>Abstract</p> <p>Background</p> <p>Health care seeking is a dynamic process that is influenced by socio-demographic, cultural and other factors. In Ethiopia, there are limited studies regarding the health seeking behaviour of tuberculosis (TB) suspects and TB patients. However, a thorough understanding of patients' motivation and actions is crucial to understanding TB and the treatment of disease. Such insights would conceivably help to reduce delay in diagnosis, improve treatment adherence and thereby reduce transmission of TB in the community. The objective of this study was to describe and analyze health care seeking among TB suspects and pulmonary TB (PTB) cases in a rural district of the Amhara Region in Ethiopia.</p> <p>Methods</p> <p>Study <it>kebeles </it>were randomly selected in a cross-sectional study design. House-to-house visits were conducted in which individuals aged 15 years and above in all households of the <it>kebeles </it>were included. Subjects with symptoms suggestive of TB were interviewed about their health seeking behaviour, socio-demographic and clinical factors using a semi-structured questionnaire. Logistics regression analysis was employed to assess associations between the independent and outcome variables.</p> <p>Results</p> <p>The majority, 787 (78%), TB suspects and 33 (82.5%) PTB cases had taken health care actions for symptoms from sources outside their homes. The median delay before the first action was 30 days. In logistics regression, women (AOR 0.8, 95% CI 0.6, 0.9) were found to be less likely to visit a medical health provider than men. Those with a long duration of cough (AOR 1.5, 95% CI 1.03, 2.1) and those with a previous history of TB (AOR 1.5, 95% CI 1.03, 2.3) were more likely to visit a medical health provider compared to those with a shorter duration of cough and with no history of TB.</p> <p>Conclusion</p> <p>The majority of TB suspects and PTB cases had already taken health care actions for their symptoms at the time of the survey. The availability of a simple and rapid diagnostic TB test for use at the lowest level of health care and the involvement of all health providers in case finding activities are imperative for early TB case detection.</p

The Mid-IR spatially resolved environment of OH26.5+0.6 at maximum luminosity

We present observations of the famous OH/IR star OH26.5+0.6 obtained using the Mid-Infrared Interferometric Instrument MIDI at the European Southern Observatory (ESO) Very Large Telescope Interferometer VLTI. The emission of the dusty envelope, spectrally dispersed at a resolution of 30 from 8 to 13.5 micron, appears resolved by a single dish UT telescope. In particular the angular diameter increases strongly within the silicate absorption band. Moreover an acquisition image taken at 8.7 micron exhibits, after deconvolution, a strong asymmetry. The axis ratio is 0.75+/-0.07 with the FWHM of the major and minor axis which are 286mas and 214mas respectively. The measured PA angle, 95 degrees +/-6 degrees is reminiscent of the asymmetry in the OH maser emission detected at 1612MHz by Bowers & Johnston (1990) for this star. In interferometric mode the UT1-UT3 102m baseline was employed to detect the presence of the star. No fringes have been found with a detection threshold estimated to be of the order of 1% of the total flux of the source, i.e. 5-8 Jy. These observations were carried out during the phase of maximum luminosity of the star, when the dust shell is more diluted and therefore the chance to detect the central source maximized. We modeled the dusty environment based on the work of Justannont et al. (1996). In particular, the failure to detect fringes provides strong constraints on the opacities in the inner regions of the dust shell or in the close vicinity of the star.Comment: Accepted in A&

Enchytraeus albidus Microarray: Enrichment, Design, Annotation and Database (EnchyBASE)

Enchytraeus albidus (Oligochaeta) is an ecologically relevant species used as standard test organisms for risk assessment. Effects of stressors in this species are commonly determined at the population level using reproduction and survival as endpoints. The assessment of transcriptomic responses can be very useful e.g. to understand underlying mechanisms of toxicity with gene expression fingerprinting. In the present paper the following is being addressed: 1) development of suppressive subtractive hybridization (SSH) libraries enriched for differentially expressed genes after metal and pesticide exposures; 2) sequencing and characterization of all generated cDNA inserts; 3) development of a publicly available genomic database on E. albidus. A total of 2100 Expressed Sequence Tags (ESTs) were isolated, sequenced and assembled into 1124 clusters (947 singletons and 177 contigs). From these sequences, 41% matched known proteins in GenBank (BLASTX, e-value≤10-5) and 37% had at least one Gene Ontology (GO) term assigned. In total, 5.5% of the sequences were assigned to a metabolic pathway, based on KEGG. With this new sequencing information, an Agilent custom oligonucleotide microarray was designed, representing a potential tool for transcriptomic studies. EnchyBASE (http://bioinformatics.ua.pt/enchybase/) was developed as a web freely available database containing genomic information on E. albidus and will be further extended in the near future for other enchytraeid species. The database so far includes all ESTs generated for E. albidus from three cDNA libraries. This information can be downloaded and applied in functional genomics and transcription studies

The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO) to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH.Methods/design: This trial is designed as a multicentre trial in which 400 infants (200 in each arm) will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension.Discussion: To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity.Trial registration: Netherlands Trial Register (NTR): NTR1310

It Takes Two to Tango: Defining an Essential Second Active Site in Pyridoxal 5′-Phosphate Synthase

The prevalent de novo biosynthetic pathway of vitamin B6 involves only two enzymes (Pdx1 and Pdx2) that form an ornate multisubunit complex functioning as a glutamine amidotransferase. The synthase subunit, Pdx1, utilizes ribose 5-phosphate and glyceraldehyde 3-phosphate, as well as ammonia derived from the glutaminase activity of Pdx2 to directly form the cofactor vitamer, pyridoxal 5′-phosphate. Given the fact that a single enzyme performs the majority of the chemistry behind this reaction, a complicated mechanism is anticipated. Recently, the individual steps along the reaction co-ordinate are beginning to be unraveled. In particular, the binding of the pentose substrate and the first steps of the reaction have been elucidated but it is not known if the latter part of the chemistry, involving the triose sugar, takes place in the same or a disparate site. Here, we demonstrate through the use of enzyme assays, enzyme kinetics, and mutagenesis studies that indeed a second site is involved in binding the triose sugar and moreover, is the location of the final vitamin product, pyridoxal 5′-phosphate. Furthermore, we show that product release is triggered by the presence of a PLP-dependent enzyme. Finally, we provide evidence that a single arginine residue of the C terminus of Pdx1 is responsible for coordinating co-operativity in this elaborate protein machinery

Externalizing behaviors in preadolescents: familial risk to externalizing behaviors and perceived parenting styles

The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10–12 years who participated in TRAILS, a large prospective population-based cohort study in the Netherlands (N = 2,230). Regression analyses were used to determine the relative contribution of FR-EXT and perceived parenting styles to parent and teacher ratings of externalizing behaviors. FR-EXT was based on lifetime parental externalizing psychopathology and the different parenting styles (emotional warmth, rejection, and overprotection) were based on the child’s perspective. We also investigated whether different dimensions of perceived parenting styles had different effects on subdomains of externalizing behavior. We found main effects for FR-EXT (vs. no FR-EXT), emotional warmth, rejection, and overprotection that were fairly consistent across rater and outcome measures. More specific, emotional warmth was the most consistent predictor of all outcome measures, and rejection was a stronger predictor of aggression and delinquency than of inattention. Interaction effects were found for FR-EXT and perceived parental rejection and overprotection; other interactions between FR-EXT and parenting styles were not significant. Correlations between FR-EXT and perceived parenting styles were absent or very low and were without clinical significance. Predominantly main effects of FR-EXT and perceived parenting styles independently contribute to externalizing behaviors in preadolescents, suggesting FR-EXT and parenting styles to be two separate areas of causality. The relative lack of gene–environment interactions may be due to the epidemiological nature of the study, the preadolescent age of the subjects, the measurement level of parenting and the measurement level of FR-EXT, which might be a consequence of both genetic and environmental factors