Determination and application of immunodominant regions of SARS coronavirus spike and nucleocapsid proteins recognized by sera from different animal species

Knowledge of immunodominant regions in major viral antigens is important for rational design of effective vaccines and diagnostic tests. Although there have been many reports of such work done for SARS-CoV, these were mainly focused on the immune responses of humans and mice. In this study, we aim to search for and compare immunodominant regions of the spike (S) and nucleocapsid (N) proteins which are recognized by sera from different animal species, including mouse, rat, rabbit, civet, pig and horse. Twelve overlapping recombinant protein fragments were produced in Escherichia coli, six each for the S and N proteins, which covered the entire coding region of the two proteins. Using a membrane-strip based Western blot approach, the reactivity of each antigen fragment against a panel of animal sera was determined. Immunodominant regions containing linear epitopes, which reacted with sera from all the species tested, were identified for both proteins. The S3 fragment (aa 402-622) and the N4 fragment (aa 220-336) were the most immunodominant among the six S and N fragments, respectively. Antibodies raised against the S3 fragment were able to block the binding of a panel of S-specific monoclonal antibodies (mAb) to SARS-CoV in ELISA, further demonstrating the immunodominance of this region. Based on these findings, one-step competition ELISAs were established which were able to detect SARS-CoV antibodies from human and at least seven different animal species. Considering that a large number of animal species are known to be susceptible to SARS-CoV, these assays will be a useful tool to trace the origin and transmission of SARS-CoV and to minimise the risk of animal-to-human transmission.     

Internet-based health information consumer skills intervention for people living with HIV/AIDS

Medical information can improve health, and there is an enormous amount of health information available on the Internet. A randomized clinical trial tested the effectiveness of an intervention based on social- cognitive theory to improve information use among people living with HIV/AIDS. Men and women (N = 448) were placed in either (a) an 8-session intervention that focused on Internet information consumer skills or (b) a time-matched support group and were followed to 9 months postintervention. The Internet skills group demonstrated greater Internet use for health, information coping, and social support compared with the control group. The authors conclude that people with HIV infection may benefit from increased access to health information on the Internet and that vulnerability to misinformation and fraud can be reduced through behavioral interventions.     

Age-related probability of contralateral processus vaginalis patency in children with unilateral inguinal hernia

Purpose

Contralateral groin exploration with closure of a patent processus vaginalis (PPV) in children with a unilateral inguinal hernia remains controversial. We aimed to generate precise, age-related probabilities of patency of the contralateral processus vaginalis (PV) in infants with a unilateral inguinal hernia to guide practice.

Methods

Retrospective review of all unilateral laparoscopic inguinal hernia repairs in 5?years to determine patency of contralateral PV. Using logistic binomial regression, age-adjusted odds ratio (OR), probability of contralateral PPV and number needed to explore (NNE) in order to close all PPVs were estimated.

Results

Data from 331 children [262 male, median 3.8?months corrected gestational age (CGA)] were analysed; 160 (48?%) had a contralateral PPV. In the regression model, CGA is linearly related to log[OR] such that for each month increase in CGA, the log[OR] of having a contralateral PPV decreased by 0.017?±?0.006 (mean?±?SEM; p?=?0.005). Gender and side of hernia had no significant effect. The probability of contralateral PPV is 50?% (NNE?=?2) at 8?m CGA, 33?% (NNE?=?3) at 49?m and 25?% (NNE?=?4) at 72?m.

Conclusions

These data contribute to our knowledge of the natural history of the PV and may help guide the need for contralateral groin exploration in infants with inguinal hernia.     

Clinical use of the abiomed BVS 5000 as a pulsatile extracorporeal membrane oxygenation unit

The traditional extracorporeal membrane oxygenation circuit uses a centrifugal pump. These pumps require close monitoring and are subject to complications. In addition, they do not take advantage of the potential benefits of pulsatile flow. These extracorporeal membrane oxygenation circuits use a single pump with an inline oxygenator. If cardiac failure persists after respiratory recovery has occurred, removal of the oxygenator requires an additional procedure to convert the patient to biventricular support. This report describes a circuit in which an oxygenator is connected to a pulsatile ventricular assist device. Single and dual circuit configurations are illustrated. Recommendations for pulmonary care during support are also described.     

In Vivo Complementation of ureB Restores the Ability of Helicobacter pylori To Colonize

The objective of this study was to determine (i) if complementation of ureB-negative Helicobacter pylori restores colonization and (ii) if urease is a useful reporter for promoter activity in vivo. Strains used were M6, M6DeltaureB, and 10 recombinant derivatives of M6 or M6DeltaureB in which urease expression was under the control of different H. pylori promoters. Mice were orally inoculated with either the wild type or one of the mutant strains, and colonization, in vivo urease activity, and extent of gastritis were determined. Of eight M6DeltaureB recombinants tested, four colonized mice. Of those, three had the highest in vitro urease activity of any of the recombinants, significantly different from that of the noncolonizing mutants. The fourth colonizing recombinant, with ureB under control of the cag-15 promoter, had in vitro urease activity which did not differ significantly from the noncolonizing strains. In vivo, urease activities of the four colonizing transformants and the wild-type control were indistinguishable. There were no differences in gastritis or epithelial lesions between mice infected with M6 and those infected with the transformants. These results demonstrate that recovery of urease activity can restore colonizing ability to urease-negative H. pylori. They also suggest that cag-15 is upregulated in vivo, as was previously suggested by demonstrating that it is upregulated upon contact with epithelial cells. Finally, our results suggest that total urease activity and colonization density do not contribute to gastritis due to H. pylori.     

Integration of new genetic diseases into statewide newborn screening: New England experience

Heavy alcohol exposure can have serious and long-lasting effects on the developing fetal brain. In the last decade, researchers have utilized quantitative structural magnetic resonance imaging (MRI) to examine the brains of living children and adults with histories of heavy prenatal alcohol exposure. In addition to microcephaly, these studies indicated structural abnormalities in various regions of the brain, including the cerebellum, corpus callosum, and the basal ganglia. Most recently, we have utilized novel imaging and analytic techniques to study the brain as a whole in an effort to elucidate more subtle differences than was possible with earlier techniques. Results indicated displacements in the corpus callosum, increased gray matter densities in both hemispheres in the perisylvian regions, and altered gray matter asymmetry in portions of the temporal lobes in the brains of alcohol-exposed subjects. In addition, prominent shape abnormalities were observed in the brains of these subjects, with narrowing in the temporal region and reduced brain growth in portions of the frontal lobe. These results imply that brain growth continues to be adversely affected long after the prenatal insult and that the brain regions most affected may be consistent with the neurocognitive deficits characteristic of individuals prenatally exposed to alcohol.     

The longitudinal relationship between personality disorder dimensions and global functioning in a community-residing population

BACKGROUND: Little is known about the long-term outcome of personality disorder traits. The purpose of this study was to investigate, in a community-residing population, the longitudinal relationship between psychiatrist-assessed personality disorder scores and global functioning 13-18 years later. METHOD: A stratified random sample of residents of east Baltimore were examined by psychiatrists in 1981 and asssessed for DSM-III personality disorders using a semi-structured instrument, the Standardized Psychiatric Examination. A total of 292 persons were re-examined by different psychiatrists during 1994-1999 using the Schedules for the Assessment of Neuropsychiatry (SCAN). After completion of the SCAN, the subjects' functional status was evaluated using the Global Assessment of Functioning (GAF). The relationships between personality dimensions and follow-up GAF scores were evaluated using linear regression models. RESULTS: All of the personality disorder scales measured in 1981 were inversely related to functioning 13-18 years later, with the exception of narcissistic and compulsive scales. After controlling for Axis I disorders diagnosed contemporaneously with GAF assessment, schizoid, antisocial, borderline, histrionic, and avoidant personality disorder scores significantly predicted GAF scores. CONCLUSIONS: Most dimensions of DSM-III personality disorder traits were significantly associated with global functioning after an interval of 15 years. However, only schizoid, antisocial, borderline, histrionic, and avoidant personality disorder traits had long-term effects on functioning when Axis I disorders at follow-up were controlled. This suggests that the functional effect of the other personality disorder traits may be mediated through their relationship with Axis I disorders. Future research is needed using more specific and sensitive outcome measures.     

Role of vacuolating cytotoxin in gastritis due to Helicobacter pylori in gnotobiotic piglets.

To investigate the role of the Helicobacter pylori cytotoxin in the pathogenesis of gastritis, gnotobiotic piglets were colonized with either toxigenic H. pylori or a nontoxigenic isogenic mutant. Only piglets given the toxigenic strain developed toxin-neutralizing antibodies (indicating that toxin is expressed in vivo), but there was no difference in bacterial colonization, epithelial vacuolation, or gastritis between the two groups of piglets.     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.