Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.

Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5-4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known.

Factors associated with determinants of sexual functioning in midlife women.

OBJECTIVES: The present study was conducted to assess the associations between a woman's passionate love for her partner and sexual satisfaction and demographic factors, health and life-style characteristics, menopausal status, and menopausal symptoms. METHODS: A cross-sectional study was conducted among women (40-60 years) residing in Maryland (n = 846). chi(2)-tests were performed to evaluate the associations between each of the outcome variables (sexual satisfaction and passionate love for the partner) and predictor/independent variables. Logistic regression analysis was performed to determine whether significant associations from chi(2) analyses remained significant after adjustment for confounders. RESULTS: Older age (adjusted odds ratio (OR) 1.04; 95% confidence interval (CI) 1.01, 1.07), higher education (OR 1.47; 95% CI 1.09, 1.99), and alcohol intake (OR 1.42; 95% CI 1.03, 1.95) were associated with low passion for the partner. Older age was also a significant predictor of low sexual satisfaction (OR 1.04; 95% CI 1.01, 1.07). Women experiencing vaginal dryness had higher odds of low passion for partner (OR 1.67; 95% CI 1.21, 1.31) and low sexual satisfaction (OR 1.58; 95% CI 1.14, 2.20) than women not experiencing vaginal dryness. CONCLUSIONS: Older age, higher education, alcohol intake, and vaginal dryness are significantly associated with lower levels of passionate love for the partner, while older age and vaginal dryness are significantly associated with lower levels of sexual satisfaction in midlife women.

Do football helmets reduce acceleration of impact in blunt head injuries?

UNLABELLED: Several recent studies suggest that acceleration of the head at impact during sporting activities may have a detrimental effect on cognitive function. Reducing acceleration of impact in these sports could reduce neurologic sequelae. OBJECTIVE: To measure the effectiveness of a regulation football helmet to reduce acceleration of impact for both low- and moderate-force impacts. METHODS: An experimental paired study design was used. Male volunteers between 16 and 30 years of age headed soccer balls traveling approximately 35 miles per hour bareheaded and with a helmet. An intraoral accelerometer worn inside a plastic mouthpiece measured acceleration of the head. The helmet also had an accelerometer placed inside the padding. For more forceful impacts, cadaver heads, both with and without helmets, were instrumented with intraoral (IO) and intracranial (IC) accelerometers and struck with a pendulum device. Simultaneous IO and IC accelerations were measured and compared between helmeted and unhelmeted cadaver heads. The main outcome was mean peak acceleration of the head and/or brain associated with low- and moderate-force impacts with and without protective headgear. RESULTS: Mean peak Gs, measured by the mouthpiece accelerometer, were significantly reduced when the participants heading soccer balls were wearing a helmet (7.7 Gs with vs 19.2 Gs without, p = 0.01). Wearing a helmet also significantly lowered the peak Gs measured intraorally and intracranially in cadavers subjected to moderate-force pendulum impacts: 28.7 Gs with vs 62.6 Gs without, p < 0.001; and 56.4 Gs with vs 81.6 Gs without, p < 0.001, respectively. CONCLUSIONS: A regulation football helmet substantially reduced the peak Gs associated with "heading" a soccer ball traveling at moderately high velocities. A helmet was also effective in reducing the peak acceleration both intraorally and intracranially for impacts significantly more forceful than heading a soccer ball.

Factors influencing condom use and STD acquisition among African American college women.

To identify factors that influence condom use and the risk of acquiring sexually transmitted diseases (STDs) among African American college women, the authors surveyed a sample of 123 sexually experienced undergraduate women at a state university. The college women who were older, had initiated sex earlier, or had more recent sexual partners were more likely than others in the study to report a history of an STD. The findings have implications for prevention and intervention programs for African American college women.

Structural evidence for a common zinc binding domain in archaeal and eukaryal transcription factor IIB proteins.

X-ray absorption spectroscopy has been used to compare the metal coordination of the N-terminal zinc binding domain of eukaryal human transcription factor (TF) IIB to the previously reported structure of archaeal Pyrococcus furiosus (Pf) TFB. Full length and N-terminal fragments for both PfTFB and human TFIIB were cloned, expressed, and purified. The [C10H] variant of PfTFB was constructed to resemble the metal binding motif of higher eukaryal TFIIB proteins by mutating the second cysteine ligand to a histidine. All five proteins bind zinc in a 1:1 ratio. Zn X-ray absorption spectroscopy of human TFIIB and [C10H]PfTFB mutant are consistent with ZnS3(N,O) ligation, and further suggest that the N/O ligand is an imidazole.

Comparison of impact data in hockey, football, and soccer.

PURPOSE: To compare accelerational forces to the head in high school-level football, hockey, and soccer athletes. METHODS: Acceleration of impact was measured within the helmet of high school hockey and football players during actual game play. A triaxial accelerometer was placed at the vertex of the helmet immediately adjacent to the players head. Peak acceleration (in g's) was measured and the Gadd Severity Index and Head Injury Criterion score calculated during actual play periods in several games over four seasons. We also recorded acceleration of head impacts in high school-level soccer players who headed a soccer ball while equipped with a football helmet instrumented identically to the helmet used to record during football games. RESULTS: Peak accelerations inside the helmet for football averaged 29.2 g compared with 35 g for hockey (p = .004). There were no incidents of concussion or other traumatic brain injury during the recorded periods. In contrast, the peak accelerations associated with heading a soccer ball was 54.7 g (p = 2 x 10(-5) vs. hockey). CONCLUSION: Peak accelerations as measured at the surface of the head were 160 to 180% greater from heading a soccer ball than from routine (noninjurious) impacts during hockey or football, respectively. The effect of cumulative impacts at this level may lead to neurologic sequelae.

Attitudes regarding vaccinations of STDs and other diseases.

The purpose of this study was to examine, among 2 groups of individuals with different risk profiles, the similarity of their attitudes towards vaccines for sexually transmitted diseases (STDs) and non-STDs. Subjects were recruited from an undergraduate psychology class at an urban university (n=518) or were participants in genital herpes vaccine trials (n=87). The participants were asked to complete a questionnaire regarding their attitudes about vaccines for selected diseases. The results of this study revealed that, in general, both groups supported vaccination for most diseases. There were differences, however, between groups regarding 3 diseases: measles, genital warts, and chlamydia. The vaccine trial participants were more likely to accept vaccines for measles and the college students were more likely to accept vaccines for chlamydia and genital warts. The results of this study suggest that negative attitudes regarding vaccination to control STDs may not be a significant barrier to use.

College students' knowledge and perceptions of genital herpes.

Given the rising prevalence of herpes simplex virus type 2 (HSV-2) and the lack of accurate information about STDs in general, it is important to understand specific aspects of knowledge and attitudes regarding genital herpes acquisition among college students. This study examined the knowledge and attitudes regarding HSV-2 among college students by recruiting subjects (n=518) from an undergraduate psychology class to complete a questionnaire. The percentage of students answering individual knowledge items correctly ranged from 67% to 99%. The media was a common source of information, and almost one-third of the students anticipated that their care provider would think negatively of them should they acquire the disease. There were gender differences in care-seeking behaviour, knowledge, and attitudes, with females having a more negative view of themselves if they acquired the disease. This study pointed to the challenges in ensuring accurate knowledge about genital herpes that will encourage preventive behaviours without causing undue alarm or shame.

College students' attitudes regarding vaccination to prevent genital herpes.

BACKGROUND AND OBJECTIVES: Vaccines represent an important strategy for the control of infectious diseases but are only effective if accepted by the public. Unique attitudinal issues may affect usage of vaccines to control sexually transmitted diseases (STDs). The object of this study was to examine among college students factors that may influence acceptance of a vaccine against genital herpes. GOALS: To examine attitudes regarding acceptance of vaccination for genital herpes by college students using aspects of health behavior theories. STUDY DESIGN: Subjects were recruited from an undergraduate psychology class to complete a questionnaire regarding attitudes and beliefs about receiving a potential genital herpes vaccine. RESULTS: Of the 518 subjects, 100 would not get the vaccine, 207 would, and 211 were unsure. In the final models, factors that influenced acceptance were low cost and an opinion that the vaccine should be recommended for everyone. Those who were unsure were more likely to be influenced by an opinion that the vaccine would be unsuccessful. While not remaining in the final models, those who believed they were at low risk of acquiring genital herpes were unlikely to accept a genital herpes vaccine. CONCLUSIONS: Our results indicate that most college students would not reject vaccination, a priori, against genital herpes. Vaccine acceptance may be maximized if vaccine cost is low, the public is educated regarding risk of acquiring genital herpes, and public health policy encourages universal vaccination.

Locus of control for general health and STD acquisition among adolescent girls.

PURPOSE: To examine adolescent girls' perception of control over general health and sexually transmitted disease (STD) acquisition. METHODS: Adolescents participating in a longitudinal study were asked questions regarding their perception of their locus of control. These questions, adopted from a previous measure, focused on six loci: internal control, control by parents, partners, peers, and health care providers, and chance. RESULTS: There were 128 girls (mean age, 17 years; range, 14.5 to 18.8); 82% were black and 18% white. Statistically significant associations were found between control of general health and STD acquisition for each locus of control subscale, with the exception of partner control. However, the girls reported significantly less control over STD acquisition than over general health for health care providers, parents, and by chance, and significantly more partner and internal control over STD acquisition than general health. The correlations between parental control over general health and over STD acquisition were inversely correlated with age. Partner control was positively related to current condom use, but internal control was not. CONCLUSIONS: The degree of the locus of control was specific for STD acquisition. Girls who believe they should be able to control STD acquisition may not be using condoms. The view of partners as having control over STD acquisition may represent joint communication or coercion. However, in general these findings support the development of female-controlled methods for STD prevention, such as topical microbicides.

Adolescents' views regarding sexual history taking.

To address the health needs of adolescents, health care providers need to understand adolescent perceptions of the sexual history taking process. Adolescents (n = 113) were recruited from two sources of health care to complete a questionnaire regarding sexual history taking issues. The results revealed that there were differences in demographics, practice characteristics, and communication strategies between the private office and the hospital clinic. Attitudes and beliefs related to the discussion of sensitive issues were similar. Most adolescents would like health care providers to discuss sensitive topics directly. It is important for health care providers to feel comfortable initiating discussion of sensitive issues directly.

PIP: This study described adolescents' perception of their sexual history taken by health care providers. There were two stages of data collection. The first included focus group discussion, while the second was the administration of a sexual history-taking questionnaire. Adolescents were recruited from three locations (private pediatric practice, adolescent clinic setting, or a Job Corps Center) and were of a mean age of 16 years. Findings revealed differences in demographics and practice characteristics, as well as in strategies used when communicating with the care provider. However, there were similarities in attitudes and beliefs related to the discussion of sensitive issues. The majority of the adolescents believed that issues related to sexuality were important for their health care provider to discuss. Moreover, they preferred that their care provider address sexuality issues within a generally caring context; however, they also favored a direct approach.

Seroprevalence of herpes simplex virus-type 2 in African-American college women.

This study examines the relationship between sexual behaviors and prevalence of herpes simplex virus-type 2 (HSV-2) among African-American college women. Subjects (n = 138) were recruited randomly from a state university to participate in a study regarding sexual attitudes and behaviors and to have their blood drawn for type-specific HSV seroprevalence. Sera were analyzed for 96 college women with a mean age of 21 years. Of the 96 women, 29 (30%) were HSV-2 seropositive. The results of this study revealed that a history of sexually transmitted disease was predictive of HSV-2 infection. Number of lifetime partners, however, was not related to HSV-2 seropositivity. Four (31%) of the 13 women who reported only one lifetime partner were seropositive. These findings indicate that for young African-American college women, the risk of being infected with HSV-2 is high even with only one lifetime partner. Behavioral strategies focused on decreasing the number of sexual partners are not likely to be sufficient in preventing the spread of HSV-2 infection among young African-American women. The development and use of alternative approaches to prevent the spread of HSV-2 among young African Americans should be considered.

Research fundamentals: I. Getting from hypothesis to manuscript: an overview of the skills required for success in research.

This is the first in a series of articles developed by members of the Society for Academic Emergency Medicine (SAEM) Research Committee. The purpose of this series is to describe a stepwise approach to research, from the inception of a hypothesis to the final publication of a report. This series is written for junior academic emergency physicians (EPs), as well as nonacademic physicians who have an interest in research. This first article presents an overview of the steps involved in performing research and publishing the results, emphasizing the initial steps and the importance of collaboration.

Collaboration in emergency medicine research: a consensus statement.

The role of collaboration in medical research and how it applies to emergency medicine (EM) research are discussed. The guidance of the Division of Health Sciences Policy of the Institute of Medicine is reviewed. Application of the principles of collaborative efforts and recognition of each individual's contribution are overviewed. Emergency physicians can and should be invaluable contributors to collaborative research. Collaborative research relationships, whether established at individual institutions or through national clinical trials, must be developed deliberately. The specialty of EM must make the necessary commitment of time and resources to ensure that these occur.

Collaboration in emergency medicine research: a consensus statement.

The role of collaboration in medical research and how it applies to emergency medicine research are discussed. The guidance of the Division of Health Sciences Policy of the Institute of Medicine is reviewed. Application of the principles of collaborative efforts and recognition of each individual's contribution are overviewed. Emergency physicians can and should be invaluable contributors to collaborative research. Collaborative research relationships, whether established at individual institutions or through national clinical trials, must be developed deliberately. The specialty of emergency medicine must take the necessary commitment of time and resources to ensure that these occur.

Heterosexual romantic relationships and sexual behaviors of young adolescent girls.

PURPOSE: To compare the heterosexual romantic relationships of a cohort sexually experienced and sexually inexperienced adolescent girls, to describe the perceptions of the appropriateness of the age of first intercourse, and to evaluate the reasons why sexually experienced girls chose to have sexual intercourse the first and the most recent times they had sexual intercourse. METHODS: Girls (n = 174) with a mean age of 14.5 years were recruited from an urban-based adolescent clinic to participate in a longitudinal study of psychosexual development. The subjects were interviewed regarding their views about relationships and sexual behaviors. For the purposes of this study, data were analyzed from the first wave of data collection. RESULTS AND CONCLUSIONS: The results of this study revealed that sexually experienced girls were more likely than sexually inexperienced ones to share unique information and spend time with their boyfriends, and to anticipate that their relationships would last longer. Regardless of sexual experience, 35% of their relationships were not mutually exclusive, which places the sexually experienced girls at risk for sexually transmitted infections. Most of the girls felt that they had been "too young" at the time of first intercourse. The reasons the adolescent girls gave for having intercourse the first time and the most recent time were correlated. It would be useful to incorporate the results of this study into subsequent research which identifies strategies to aid girls to postpone the initiation of intercourse, and maintain exclusive sexual relationships. Helping sexually experienced girls to consider why they have had intercourse in the past can aid future decision-making.

Can urinary nitrite results be used to guide antimicrobial choice for urinary tract infection?

Enterococcus is unable to reduce nitrates and is also considered clinically resistant to trimethoprim/sulfamethoxazole (TMP/SMX), the drug of choice for uncomplicated urinary tract infection (UTI). The purpose of this study was to determine whether urinalysis nitrite results can be used to guide antimicrobial therapy when treating UTI in the emergency department (ED). A retrospective chart review examined 159 university hospital ED outpatients who had signs or symptoms of UTI and had a urinalysis with positive culture. Patients were categorized into two groups based on nitrite results. The proportion of isolates sensitive to TMP/SMX in each group was compared by using a two-sample z-test. Eighty-six urinalyses were nitrite positive: 67 (78%) contained TMP/SMX-sensitive isolates. Seventy-three urinalyses were nitrite negative; 60 (82%) contained sensitive isolates. There was no statistically significant difference in the proportion of isolates sensitive to TMP/SMX. Thus, we conclude that emergency physicians should not adjust antibiotic therapy for UTI based on nitrite results.

Adolescent girls' perceived prevalence of sexually transmitted diseases and condom use.

Little is known concerning sexually experienced and inexperienced adolescent girls' perceptions of the prevalence of condom use and sexually transmitted diseases (STDs). Girls (n = 174; 41% sexually experienced) rated the prevalence of condom use among friends and STDs among male and female friends and adolescents in general. Girls perceive the prevalence of STDs similarly across both gender and level of familiarity. For the most part, however, the girls perceived the prevalence among boys and girls more similarly than among friends and adolescents in general. No significant differences were found between sexually experienced and inexperienced girls in perceptions of condom use prevalence, but girls with a history of STD perceived condoms as used less frequently. Girls with an STD history perceived STDs as the most prevalent, followed by sexually inexperienced girls and then sexually experienced girls without a history of an STD. After an adolescent girl initiates sexual intercourse, STD experience could be a key variable in affecting her perceptions. Prevention programs can incorporate an understanding of patients' perceptions of condom use and STDs.

Do wrist guards protect against fractures?

STUDY OBJECTIVE: To determine whether wrist guards increase the fracture threshold for wrist and forearm fractures. METHODS: We conducted a controlled, blinded experimental study using matched cadaveric arms-one fitted with a wrist guard-dropped with the use of a device designed to simulate a fall. We measured the mean number of drops before the occurrence of fracture, mean height and velocity change to fracture, mean kinetic energy, mean peak acceleration (in Gs), and summed impulse [weight (kilograms) x delta velocity (meters/second)] to fracture with and without wrist guards. Fracture severity was compared with the use of an ordinal ranking system and analyzed with the Mann-Whitney rank-sum test. RESULTS: Wrist guards were associated with a statistically significant increase in the number of drops, mean drop height, mean kinetic energy, and summed impulse required to cause a fracture. Fractures also tended to be less severe when wrist guards were used. CONCLUSION: The biomechanical evidence of a protective effect of wrist guards against wrist fractures seen in this study, coupled with previous epidemiologic evidence, is strong enough to warrant pediatricians, family practitioners, and emergency physicians to counsel skaters to use these devices when using roller skates, skateboards, or in-line skates.