A study of the killer cell immunoglobulin-like receptor gene KIR2DS1 in a Caucasoid Brazilian population with psoriasis vulgaris

Psoriasis is a chronic inflammatory skin disease whose pathogenesis and genetic background remain unclear. Considering that previous studies have suggested an association of psoriasis vulgaris (PV) and killer cell immunoglobulin-like receptors (KIRs), we typed 15 KIR genes and human leukocyte antigen (HLA)-Cw in 79 Brazilian Caucasoid patients with PV and 110 healthy controls by polymerase chain reaction (PCR) using sequence-specific oligonucleotides and sequence-specific primers. We did not observe a relevant increase in the frequency of the activating KIR2DS1 gene in the PV group [KIR2DS1, 46 of 79 cases (58.2%) vs 40 of 110 controls (36.4%)]. However, an association of KIR2DS1 with Cw*0602+ in 26.5% of PV patients was observed, while it was present in only 5.4% of controls. These results suggest that activating KIR2DS1 gene may not confer susceptibility to PV, and an association of KIR2DS1 gene with the HLA-Cw*0602+ was observed in these patients.     

The c.797 G>A (p.R266K) cystathionine β‐synthase mutation causes homocystinuria by affecting protein stability

Mutations in the cystathionine beta‐synthase (CBS) gene are the cause of classical homocystinuria, the most common inborn error in sulfur metabolism. The c.797 G>A (p.R266K) mutation in CBS was originally described in several Norwegian pyridoxine responsive CBS deficient patients, and heterologous gene expression studies have shown that the protein has near wild‐type levels of enzyme activity. Here, we characterize a transgenic mouse lacking endogenous Cbs and expressing p.R266K human CBS protein from a zinc inducible metallothionein promoter (Tg‐R266K Cbs^‐/‐). Unlike mice expressing other mutant CBS alleles, the Tg‐R266K transgene is unable to efficiently rescue neonatal lethality of Cbs^‐/‐ on a C57BL/6J background. On a C3H/HeJ background, zinc‐induced Tg‐R266K Cbs^‐/‐ mice express CBS mRNA, but have very low levels of CBS protein and enzyme activity, resulting in extreme elevations in serum total homocysteine (tHcy). Treatment with pyridoxine did not have any appreciable effect on tHcy, indicating this allele is not pyridoxine responsive in mice. However, treatment with the proteasome inhibitor bortezomib resulted in an 97% reduction in tHcy and a 2381% increase in liver CBS activity. These studies show that the p.R266K mutation causes increased proteasomal degradation in vivo, and that treatments that stabilize the protein can be used to reverse its effect.     

Undertaking midwifery studies: Commencing students’ views

Objective

to explore the motivations and beliefs of commencing midwifery students against a background of high course demand and high student attrition.

Design

a qualitative analysis of student reflective essays.

Setting

Melbourne, Australia.

Participants

all commencing midwifery students, in 2008, were invited to participate (n=41).

Measurements and findings

three primary motivations for choosing midwifery were identified, including: notions of altruism (wanting to help), a fascination with pregnancy and birth, and a view of midwifery as a personally satisfying career.

Key conclusions and implications for practice

Bachelor of Midwifery programmes attract students with idealised views about midwifery practice. Such views may lead to student disillusionment, tensions with educators and clinicians, and higher rates of student attrition. Students need greater support to examine their views about midwifery practice. More meaningful support may assist the students' successful socialisation into clinical practice.     

PERCEPTIONS OF PROCEDURAL JUSTICE MEDIATE THE RELATIONSHIP BETWEEN LOCAL VIOLENT CRIME DENSITY AND CRIME REPORTING INTENTIONS

Community attitudes toward the police are of increasing concern to scholars and practitioners. Although it is widely accepted that perceptions of procedural justice are influential in shaping citizens’ attitudes toward police, prior studies have not considered its relationship to crime density. To address this gap, we examined the relationship between crime density, perceptions of procedural justice, and intentions to report crimes to police using data from a demographically representative survey in an urban center widely known for exhibiting extremely high violent crime rates. We created a path model predicting perceptions of procedural justice, the likelihood of contacting police to report a crime, and the likelihood of socially interacting with police other than in relation to crime. The results indicate that independent of race and educational background, community members’ trust in police mediates the relationship between local crime density and their intentions report crimes to and otherwise interact with the police.     

Semen parameters in a fertile versus subfertile population: a need for change in the interpretation of semen testing

This prospectively designed study was conducted to compare a fertile and a subfertile population so as to define normal values for different semen parameters. Semen analyses were performed according to the World Health Organization (WHO) guidelines, except for sperm morphology (strict criteria). In the fertile population (n = 144), all patients had recently achieved pregnancy, within 12 months of unprotected coitus. As subfertile controls we examined semen samples from 143 consecutive men attending our infertility clinic during the same study period. Couples with tubal factor infertility and/or ovulatory disorders were excluded from our study. Using receiver operating characteristic (ROC) curve analysis we determined the diagnostic potential and cut-off values for single and combined sperm parameters. Sperm morphology scored best, with a value of 78% (area under the ROC curve). Summary statistics showed a shift towards abnormality for most semen parameters in the subfertile population. Using the 10th percentile of the fertile population as the cut-off value, the following results were obtained: 14.3 x 10(6)/ml for sperm concentration, 28% for progressive motility and 5% for sperm morphology. Using ROC analysis, cut-off values were 34 x 10(6)/ml, 45% and 10% respectively. Cut-off values for normality were different from those described in the WHO guidelines. Routine bacterial and non- bacterial cultures turned out to be of little prognostic value.      

Measurement of half-value layer in x-ray CT: a comparison of two noninvasive techniques

The purpose of this paper is to determine the accuracy and reproducibility of two noninvasive methods of measuring half-value layer (HVL), ring and localization, compared with an invasive technique (suspending tube rotation). The ring method uses concentric aluminum rings about a CTDI ionization chamber at isocenter. Data were acquired using axial CT protocols (rotating x-ray tube, stationary patient table). The localization technique uses square aluminum sheets secured to the gantry shroud to filter the radiation beam, and a CTDI chamber suspended externally at isocenter. Data were acquired using localization image protocols (stationary x-ray tube, moving patient table). The invasive technique was similar to the localization technique except that the ion chamber was placed on the patient table and the tube rotation disabled using service software. Data for all techniques were collected on the same CT system. Independent data sets were collected to determine reproducibility. Sensitivity to ionization chamber lateral displacement from isocenter was investigated. Measured HVLs (mm aluminum, mean+/-std, n=4) were 7.19+/-0.03 (ring); 7.17+/-0.04 (localization); and 7.24+/-0.02 (service mode), which were not significantly different (p = 0.05). Displacing the chamber from isocenter changes the HVL, depending on the bow-tie filter, by as much as 5 mm aluminum. Aluminum filter to ion chamber distances of 25-35 cm provided accurate results. Both noninvasive techniques were accurate and reproducible at isocenter. However, the measured HVL was dependent upon the bow-tie filter and the lateral displacement of the ionization chamber with respect to isocenter. Greater than 2 cm off of isocenter, the ring technique did not provide accurate HVL measurements.     

Defining the valid hemizona assay: accounting for binding variability within zonae pellucidae and within semen samples from fertile males.

OBJECTIVE: To achieve a better understanding of the variability in sperm and oocyte binding capacities will optimize use of the hemizona assay (HZA) as a predictor of sperm function. DESIGN: Limitations of the HZA were more clearly delineated by current studies: (1) variability of sperm binding capacity of men over a 90-day interval; (2) variability of sperm binding using different oocytes; and (3) lower limits of the number of sperm bound from the fertile control in two laboratories. PATIENTS: Semen was obtained from proven fertile men and one subfertile individual. MAIN OUTCOME MEASURE: The number of sperm tightly bound to the hemizona were measured and compared. RESULTS: In the initial study, 6 fertile control men exhibited a similar degree of variability in zona binding when studied over a 90-day interval. Average sperm binding for individuals ranged from 68 to 127. Second, 3 of the 15 simultaneous assays showed very low numbers of sperm bound, indicating that 20% of the zonae had poor binding. Third, from 18 men who had 0% fertilization in an in vitro fertilization system using mature oocytes, evaluation of their sperm by HZA was performed. The sperm bound poorly and the 95% confidence interval was 20 sperm bound. Thus, the fertile controls should bind greater than 20 sperm to distinguish them from the infertile group in the HZA system resulting in a valid assay. CONCLUSIONS: With these guidelines, applications of the HZA may be made with greater reassurance of a valid bioassay of sperm fertilizing potential.     

Predictive value of abnormal sperm morphology in in vitro fertilization

In patients with acceptable sperm count and motility, two patterns of abnormal morphology, judged with strict criteria, were identified and described. Patients with less than 4% normal forms and less than 30% morphology index (summation of normal and slightly amorphous forms) had a fertilization rate of 7.6% of the oocytes (P pattern, poor prognosis). Patients with normal morphology between 4 and 14% had a significantly better fertilization rate of 63.9% of the oocytes (P less than 0.0001). Cases with greater than 14% normal forms fertilized within the normal range for the laboratory. By evaluating sperm morphology with the proposed strict criteria, its predictive value in in vitro fertilization is enhanced.