The R18 Polyarginine Peptide Is More Effective Than the TAT-NR2B9c (NA-1) Peptide When Administered 60 Minutes after Permanent Middle Cerebral Artery Occlusion in the Rat.

We examined the dose responsiveness of polyarginine R18 (100, 300, and 1000 nmol/kg) when administered 60 minutes after permanent middle cerebral artery occlusion (MCAO). The TAT-NR2B9c peptide, which is known to be neuroprotective in rodent and nonhuman primate stroke models, served as a positive control. At 24 hours after MCAO, there was reduced total infarct volume in R18 treated animals at all doses, but this reduction only reached statistical significance at doses of 100 and 1000 nmol/kg. The TAT-NR2B9c peptide reduced infarct volume at doses of 300 and 1000 nmol/kg, but not to a statistically significant extent, while the 100 nmol/kg dose was ineffective. The reduction in infarct volume with R18 and TAT-NR2B9c peptide treatments was mirrored by improvements in one or more functional outcomes (namely, neurological score, adhesive tape removal, and rota-rod), but not to a statistically significant extent. These findings further confirm the neuroprotective properties of polyarginine peptides and for R18 extend its therapeutic time window and dose range, as well as demonstrating its greater efficacy compared to TAT-NR2B9c in a severe stroke model. The superior neuroprotective efficacy of R18 over TAT-NR2B9c highlights the potential of this polyarginine peptide as a lead candidate for studies in human stroke.

The Norwich Patellar Instability Score: Validity, internal consistency and responsiveness for people conservatively-managed following first-time patellar dislocation.

BACKGROUND: This paper assessed the validity, internal consistency, responsiveness and floor-ceiling effects of the Norwich Patellar Instability (NPI) Score for a cohort of conservatively managed people following first-time patellar dislocation (FTPD). METHODS: Fifty patients were recruited, providing 130 completed datasets over 12 months. The NPI Score, Lysholm Knee Score, Tegner Level of Activity Score and isometric knee extension strength were assessed at baseline, six weeks, six and 12 months post-injury. RESULTS: There was high convergent validity with a statistically significant correlation between the NPI Score and the Lysholm Knee Score (p<0.001), Tegner Level of Activity Score (p<0.001) and isometric knee extension strength (p<0.002). Principal component analysis revealed that the NPI Score demonstrated good concurrent validity with four components account for 70.4% of the variability. Whilst the NPI Score demonstrated a flooring-effect for 13 of the 19 items, no ceiling effect was reported. There was high internal consistency with a Cronbach Alpha value of 0.93 (95% CI: 0.91 to 0.93). The NPI Score was responsive to change over the 12 months period with an effect size of 1.04 from baseline to 12 months post-injury. CONCLUSIONS: The NPI Score is a valid tool to assess patellar instability symptoms in people conservatively managed following FTPD. LEVEL OF EVIDENCE: Level II.

Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.

Data from massively parallel sequencing or 'Next Generation Sequencing' of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes, we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening.

Modes of Neuronal Calcium Entry and Homeostasis following Cerebral Ischemia.

One of the major instigators leading to neuronal cell death and brain damage following cerebral ischemia is calcium dysregulation. The neuron's inability to maintain calcium homeostasis is believed to be a result of increased calcium influx and impaired calcium extrusion across the plasma membrane. The need to better understand the cellular and biochemical mechanisms of calcium dysregulation contributing to neuronal loss following stroke/cerebral ischemia is essential for the development of new treatments in order to reduce ischemic brain injury. The aim of this paper is to provide a concise overview of the various calcium influx pathways in response to ischemia and how neuronal cells attempts to overcome this calcium overload.

Helical computed tomography and three-dimensional reconstruction of a bipedicular developmental anomaly of the C2 vertebra.

STUDY DESIGN: A case of bilateral failure of fusion of the C2 neural arch resembling a bipedicular fracture in a 9-year-old boy involved in a motor vehicle accident. OBJECTIVES: To describe the use of helical computed tomography and three-dimensional reconstruction images to identify the defect as congenital. SUMMARY OF BACKGROUND DATA: Congenital defects in the C2 neural arch are rare. Diagnostic difficulties arise when they are discovered during the assessment of patients after trauma, when they may resemble C2 arch fractures. METHODS: Lateral cervical spine radiograph, transverse section computed tomography, and three-dimensional reconstruction images were used to delineate the anatomy of the defect. RESULTS: The three-dimensional reconstruction views showed that normal alignment of the vertebrae was maintained, despite the pedicle defects. CONCLUSIONS: Differentiation of a C2 fracture from a congenital defect may be difficult. Reconstruction in three dimensions from helical computed tomography is a useful adjunct to conventional computed tomography in the evaluation of such patients.

Job stress and preeclampsia.

We conducted a case-control study to determine whether job strain (or stress) during pregnancy resulted in an increased risk of preeclampsia. We compared 110 nulliparous Caucasian and African-American women who had preeclampsia with 115 healthy nulliparous controls. All subjects gave birth between 1984 and 1987 in Chapel Hill, NC. Occupation was ascertained during a telephone interview. We assigned each job title a strain (or stress) score in accordance with the occupational database developed by Karasek. Overall, 54 (49%) of the control women worked during pregnancy, 14 in high-stress jobs. Logistic regression analysis indicated a 3.1-fold [95% confidence interval (CI) = 1.2-7.8] increased risk of preeclampsia for women employed in high-stress jobs (high psychological demand, low decision latitude) and an odds ratio of 2.0 (95% CI = 1.0-4.3) for low-stress jobs compared with nonworking women, while simultaneously adjusting for age, race, family history of preeclampsia, history of hypertension in the subject's mother, gravidity, smoking during pregnancy, timing of the first prenatal visit, and type of birth control used by the couple before the pregnancy. Furthermore, working women had 2.3 times the risk of developing preeclampsia (95% CI = 1.2-4.6) compared with nonworking women. Work-related psychosocial strain increased the risk of preeclampsia in our study.

Physician satisfaction with human immunodeficiency virus type 1 and hepatitis B virus testing in San Diego County.

Physician satisfaction with the laboratory testing process is one indicator of the physician's perception of the quality of laboratory testing and the effectiveness of the communication of the laboratory results. This study compares the level of satisfaction of physicians reporting their experience with human immunodeficiency virus type 1 (HIV-1) testing with the satisfaction levels of those physicians reporting their experience with hepatitis B virus (HBV) testing. By mail, 6,570 licensed San Diego County physicians were surveyed. Among those who tested for HIV-1 or HBV, their satisfaction with four different HIV-1 or HBV testing parameters was assessed: 1) specimen submission process, 2) test accuracy, 3) clarity of test report, and 4) turnaround time. Overall, physician satisfaction with both HIV-1 and HBV testing was high, particularly for test accuracy (means of 2.79 and 2.84, respectively on a 3-point scale), although slightly lower for turnaround time (means of 2.40 and 2.43, respectively). Mean satisfaction with the specimen submission process and test accuracy were higher for physicians who ordered HBV tests than for those who ordered HIV-1 tests. Satisfaction with the four HIV-1 testing process parameters varied significantly by physician specialty, practice type, and type of laboratory used. For HBV testing, significant differences were observed only for turnaround time. For both HIV-1 and HBV testing, those who received a final interpretation of laboratory results were more satisfied with test report clarity than those who did not. Although physician satisfaction with HIV-1 and HBV testing is high, this study identifies the least satisfied groups and specific areas in the testing process than may need improvement.