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J L Collins

Publications and source records attributed to J L Collins.

At least 19 recordsLinked to original sources

Surveillance for characteristics of health education among secondary schools--school health education profiles, 1998.

PROBLEM/CONDITION: School health education (e.g., classroom instruction) is an essential component of school health programs; such education promotes the health of youth and improves overall public health. REPORTING PERIOD: February-May 1998. DESCRIPTION OF SYSTEM: The School Health Education Profiles monitor characteristics of health education in middle or junior high schools and senior high schools in the United States. The Profiles are school-based surveys conducted by state and local education agencies. This report summarizes results from 36 state surveys and 10 local surveys conducted among representative samples of school principals and lead health education teachers. The lead health education teacher coordinates health education policies and programs within a middle/junior high school or senior high school. RESULTS: During the study period, most schools in states and cities that conducted Profiles required health education in grades 6-12. Of these, a median of 91.0% of schools in states and 86.2% of schools in cities taught a separate health education course. The median percentage of schools in each state and city that tried to increase student knowledge in selected topics (i.e., prevention of tobacco use, alcohol and other drug use, pregnancy, human immunodeficiency virus [HIV] infection, other sexually transmitted diseases, violence, or suicide; dietary behaviors and nutrition; and physical activity and fitness) was >73% for each of these topics. The median percentage of schools with a health education teacher who coordinated health education was 38.7% across states and 37.6% across cities. A median of 41.8% of schools across states and a median of 31.0% of schools across cities had a lead health education teacher with professional preparation in health and physical education, whereas a median of 6.0% of schools across states and a median of 5.5% of schools across cities had a lead health education teacher with professional preparation in health education only. A median of 19.3% of schools across states and 21.2% of schools across cities had a school health advisory council. The median percentage of schools with a written school or school district policy on HIV-infected students or school staff members was 69.7% across states and 84.4% across cities. INTERPRETATION: Many middle/junior high schools and senior high schools require health education to help provide students with knowledge and skills needed for adoption of a healthy lifestyle. However, these schools might not be covering all important topic areas or skills sufficiently. The number of lead health education teachers who are academically prepared in health education and the number of schools with school health advisory councils needs to increase. PUBLIC HEALTH ACTION: The Profiles data are used by state and local education officials to improve school health education.

Health Education↗

St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor.

St. John's wort (Hypericum perforatum) is an herbal remedy used widely for the treatment of depression. Recent clinical studies demonstrate that hypericum extracts increase the metabolism of various drugs, including combined oral contraceptives, cyclosporin, and indinavir. In this report, we show that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand (K(i) = 27 nM) for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Treatment of primary human hepatocytes with hypericum extracts or hyperforin results in a marked induction of CYP3A4 expression. Because CYP3A4 is involved in the oxidative metabolism of >50% of all drugs, our findings provide a molecular mechanism for the interaction of St. John's wort with drugs and suggest that hypericum extracts are likely to interact with many more drugs than previously had been realized.

Bridged Bicyclo Compounds↗

Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands.

Xenobiotics induce the transcription of cytochromes P450 (CYPs) 2B and 3A through the constitutive androstane receptor (CAR; NR1I3) and pregnane X receptor (PXR; NR1I2), respectively. In this report, we have systematically compared a series of xenobiotics and natural steroids for their effects on mouse and human CAR and PXR. Our results demonstrate dual regulation of PXR and CAR by a subset of compounds that affect CYP expression. Moreover, there are marked pharmacological differences between the mouse (m) and human (h) orthologs of both CAR and PXR. For example, the planar hydrocarbon 1, 4-bis[2-(3,5-dichloropyridyl-oxy)]benzene activates mCAR and hPXR but has little or no activity on hCAR and mPXR. In contrast, the CAR deactivator androstanol activates both mouse and human PXR. Similarly, the PXR activator clotrimazole is a potent deactivator of hCAR. Using radioligand binding and fluorescence resonance energy transfer assays, we demonstrate that several of the compounds that regulate mouse and human CAR, including natural steroids, bind directly to the receptors. Our results suggest that CAR, like PXR, is a steroid receptor that is capable of recognizing structurally diverse compounds. Moreover, our findings underscore the complexity in the physiologic response to xenobiotics.

Animals↗

Physical activity, food choice, and weight management goals and practices among US college students.

INTRODUCTION: Physical activity and a healthy diet have been recommended to help reverse the increasing prevalence of overweight among adolescents and adults in the United States. METHODS: Data is from the 1995 National College Health Risk Behavior Survey. A representative sample of US undergraduate college students (n = 4609) were analyzed to examine associations of physical activity and food choice with weight management goals and practices. RESULTS: Based on self-reported height and weight, 35% of students were overweight or obese (body mass index > or = 25.0). Nearly half (46%) of all students reported they were trying to lose weight. Female students were less likely than male students to be overweight, but more likely to be trying to lose weight. Among female and male students, using logistic regression to control for demographics, trying to lose weight was associated with participation in vigorous physical activity and strengthening exercises, and consumption of < or = 2 servings/ day of high-fat foods. Female and male students who reported using exercise to lose weight or to keep from gaining weight were more likely than those who did not to participate in vigorous, strengthening, and moderate physical activity, and were more likely to eat > or = 5 servings/day of fruits and vegetables and < or = 2 servings/day of high-fat foods. Among students who were trying to lose weight, only 54% of females and 41% of males used both exercise and diet for weight control. CONCLUSION: Colleges should implement programs to increase student awareness of healthy weight management methods and the importance of physical activity combined with a healthy diet.

Adult↗

Contextual influences on school provision of health services.

PURPOSE: To examine contextual factors that may facilitate or impede the provision of school health services. METHODS: Using a composite database derived primarily from the National Longitudinal Study of Adolescent Health, we used logistic regression to examine how selected characteristics of communities, schools, and state-level policies are related to the provision of specific health services by high schools. RESULTS: Schools whose students experienced more health risks were generally more likely to provide related services than schools whose students experienced fewer risks. State policies and requirements for health-related programs and services were associated with greater school-based provision of services. Availability of health care services within the community was associated with a reduced likelihood that schools provided similar services on-site; however, for some health services, the reverse was true. In general, more affluent communities were more likely to provide school health services than less affluent communities. Public schools were more likely to offer health services than private schools. CONCLUSIONS: Certain characteristics of communities, schools, and state-level policies are associated with the provision of school health services. These contextual factors appear to operate by creating a demand for services and by creating the opportunity for schools to provide health services.

Adolescent↗

Use of birth control pills, condoms, and withdrawal among U.S. high school students.

PURPOSE: To examine the use of contraception at last sexual intercourse among currently sexually active adolescents. METHODS: We analyzed data from national school-based Youth Risk Behavior Surveys (YRBS) conducted in 1991, 1993, 1995, and 1997. The YRBS is a self-administered, anonymous survey which uses a national probability sample of U.S. students in public and private schools from grades 9 through 12. RESULTS: From 1991 to 1997, condom use significantly increased (from 46% to 57%), birth control pill use decreased (from 21% to 17%), and use of withdrawal significantly decreased (from 18% to 13%). In 1997, although more students were using condoms, 13% reported using withdrawal and 15% reported using no method to prevent pregnancy at last sexual intercourse. In 1997, condom use among females was significantly lower in the 9th grade than in the 12th grade (p <.001), whereas birth control pill use was higher (p <.001) and use of withdrawal remained stable. Among males, condom use and withdrawal use remained stable from 9th to 12th grade, whereas birth control pill use by their partner increased (p <.001). CONCLUSIONS: Inadequate contraceptive use among sexually active adolescents continues to be a major public health problem in the United States. For young people who will not remain sexually abstinent, families, health care providers, schools, and other influential societal institutions should promote the correct and continued use of condoms as essential protection against sexually transmitted diseases and human immunodeficiency virus infection.

Adolescent↗

Youth risk behavior surveillance. National Alternative High School Youth Risk Behavior Survey, United States, 1998.

Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. The reporting period is February-May 1998. In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes. During the 30 days preceding the survey, 51.9% had ridden with a driver who had been drinking alcohol, 25.1% had driven a vehicle after drinking alcohol, 32.9% had carried a weapon, 64.5% had drunk alcohol, and 53.0% had used marijuana. During the 12 months preceding the survey, 15.7% had attempted suicide, and 29.0% had rarely or never worn a seat belt. Substantial morbidity among school-aged youth and young adults also results from unintended pregnancies and STDs, including HIV infection. ALT-YRBS results indicate that in 1998, a total of 87.8% of students at alternative high schools had had sexual intercourse, 54.1% of sexually active students had not used a condom at last sexual intercourse, and 5.7% had ever injected an illegal drug. Among adults aged > or = 25 years, 66.5% of all deaths result from two causes--cardiovascular disease and cancer. Most risk behaviors associated with these causes of death are initiated during adolescence. In 1998, a total of 64.1% of students at alternative high schools had smoked cigarettes during the 30 days preceding the survey, 38.3% had smoked a cigar during the 30 days preceding the survey, 71.2% had not eaten > or = 5 servings of fruits and vegetables during the day preceding the survey, and 81.0% had not attended physical education (PE) class daily. Comparing ALT-YRBS results with 1997 national YRBS results demonstrates that the prevalence of most risk behaviors is higher among students attending alternative high schools compared with students at regular high schools. Some risk behaviors are more common among certain sex and racial/ethnic subgroups of students. ALT-YRBS data can be used nationwide by health and education officials to improve policies and programs designed to reduce risk behaviors associated with the leading causes of morbidity and mortality among students attending alternative high schools.

Adolescent↗

Youth Risk Behavior Surveillance--National Alternative High School Youth Risk Behavior Survey, United States, 1998.

PROBLEM/CONDITION: Alternative high schools serve approximately 280,000 students nationwide who are at high risk for failing or dropping out of regular high school or who have been expelled from regular high school because of illegal activity or behavioral problems. Such settings provide important opportunities for delivering health promotion education and services to these youth and young adults. However, before this survey, the prevalence of health-risk behaviors among students attending alternative high schools nationwide was unknown. REPORTING PERIOD: February-May 1998. DESCRIPTION OF SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors the following six categories of priority health-risk behaviors among youth and young adults: behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The national Alternative High School Youth Risk Behavior Survey (ALT-YRBS) is one component of the YRBSS; it was conducted in 1998 to measure priority health-risk behaviors among students at alternative high schools. The 1998 ALT-YRBS used a three-stage cluster sample design to produce a nationally representative sample of students in grades 9-12 in the United States who attend alternative high schools. The school response rate was 81.0%, and the student response rate was 81.9%, resulting in an overall response rate of 66.3%. This report summarizes results from the 1998 ALT-YRBS. RESULTS AND INTERPRETATION: In the United States, 73.6% of all deaths among youth and young adults aged 10-24 years results from only four causes--motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the 1998 ALT-YRBS demonstrate that many students at alternative high schools engage in behaviors that increase their likelihood of death from these four causes. During the 30 days preceding the survey, 51.9% had ridden with a driver who had been drinking alcohol, 25.1% had driven a vehicle after drinking alcohol, 32.9% had carried a weapon, 64.5% had drunk alcohol, and 53.0% had used marijuana. During the 12 months preceding the survey, 15.7% had attempted suicide, and 29.0% had rarely or never worn a seat belt. Substantial morbidity among school-aged youth and young adults also results from unintended pregnancies and STDs, including HIV infection. ALT-YRBS results indicate that in 1998, a total of 87.8% of students at alternative high schools had had sexual intercourse, 54.1% of sexually active students had not used a condom at last sexual intercourse, and 5.7% had ever injected an illegal drug. Among adults aged > or =25 years, 66.5% of all deaths result from two causes--cardiovascular disease and cancer. Most risk behaviors associated with these causes of death are initiated during adolescence. In 1998, a total of 64.1% of students at alternative high schools had smoked cigarettes during the 30 days preceding the survey, 38.3% had smoked a cigar during the 30 days preceding the survey, 71.2% had not eaten > or =5 servings of fruits and vegetables during the day preceding the survey, and 81.0% had not attended physical education (PE) class daily. Comparing ALT-YRBS results with 1997 national YRBS results demonstrates that the prevalence of most risk behaviors is higher among students attending alternative high schools compared with students at regular high schools. Some risk behaviors are more common among certain sex and racial/ethnic subgroups of students. PUBLIC HEALTH ACTION: ALT-YRBS data can be used nationwide by health and education officials to improve policies and programs designed to reduce risk behaviors associated with the leading causes of morbidity and mortality among students attending alternative high schools.

Adolescent↗

A peroxisome proliferator-activated receptor gamma ligand inhibits adipocyte differentiation.

The peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that regulate glucose and lipid homeostasis. The PPARgamma subtype plays a central role in the regulation of adipogenesis and is the molecular target for the 2, 4-thiazolidinedione class of antidiabetic drugs. Structural studies have revealed that agonist ligands activate the PPARs through direct interactions with the C-terminal region of the ligand-binding domain, which includes the activation function 2 helix. GW0072 was identified as a high-affinity PPARgamma ligand that was a weak partial agonist of PPARgamma transactivation. X-ray crystallography revealed that GW0072 occupied the ligand-binding pocket by using different epitopes than the known PPAR agonists and did not interact with the activation function 2 helix. In cell culture, GW0072 was a potent antagonist of adipocyte differentiation. These results establish an approach to the design of PPAR ligands with modified biological activities.

Adipocytes↗

Estimates of mouse oviductal fluid tonicity based on osmotic responses of embryos.

Zygotes and early cleavage-stage embryos are very sensitive to increased osmolality in vitro, although the tonicity of their in vivo environment, oviductal fluid, is unknown. A preference for low osmolality in vitro might imply similar conditions in vivo or be specific to culture. Previous electron probe x-ray microanalysis measurements of total ion content predicted oviductal fluid osmolalities of 310-360 mOs/kg, higher than osmolalities tolerated by mouse zygotes in vitro. However, such indirect estimates may not reflect the tonicity experienced by embryos. We have now used embryos themselves as osmosensors to determine the tonicity of mouse oviductal fluid. In one method, we measured the mean volume of zygotes in undiluted oviductal fluid and compared this to the mean volumes measured for zygotes in media spanning a range of osmolalities. The osmolality corresponding to the measured mean volume in oviductal fluid was taken to be isotonic. In another, independent method, the sizes of zygotes and two-cell embryos were measured as a function of time beginning immediately after removal from oviducts. The osmolality in which the embryos neither swelled nor shrank was taken to be isotonic. Both methods yielded approximately the same range for the tonicity of oviductal fluid: around 290-300 mOs/kg.

Animals↗

School violence, substance use, and availability of illegal drugs on school property among US high school students.

To determine if school violence is associated with substance use and availability of illegal drugs at school, this study examined data from the 1995 Youth Risk Behavior Survey, a nationally representative sample of 10,904 high school students. Adjusted odds ratios were calculated to describe the associations of tobacco, alcohol, and marijuana use (on and off school property), and availability of illegal drugs at school with five indicators of school violence--weapon-carrying, physical fighting, having property stolen or damaged, being threatened or injured, and being absent from school because of feeling unsafe. School violence indicators increased with the number of substances used and the location of use (on school property vs. off school property). School violence was associated with availability of illegal drugs at school, even among students who did not use substances. These findings suggest a need for coordinated violence and substance use prevention programs for youth in school and community settings.

Adolescent↗

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.

We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified as a structurally novel PPARgamma agonist. Structure-activity relationships identified the 2-aminobenzophenone moiety as a suitable isostere for the chemically labile enaminone moiety in compound 2, affording 2-((2-benzoylphenyl)amino)-3-(4-(benzyloxy)phenyl)propionic acid (9). Replacement of the benzyl group in 9 with substituents known to confer in vivo potency in the thiazolidinedione (TZD) class of antidiabetic agents provided a dramatic increase in the in vitro functional potency and affinity at PPARgamma, affording a series of potent and selective PPARgamma agonists exemplified by (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(methylpyridin-2-ylamino+ ++)ethoxy ]phenyl¿propionic acid (18), 3-¿4-[2-(benzoxazol-2-ylmethylamino)ethoxy]phenyl¿-(2S)-((2- benzoylph enyl)amino)propanoic acid (19), and (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propanoic acid (20). Compounds 18 and 20 show potent antihyperglycemic and antihyperlipidemic activity when given orally in two rodent models of type 2 diabetes. In addition, these analogues are readily prepared in chiral nonracemic fashion from L-tyrosine and do not show a propensity to undergo racemization in vitro. The increased potency of these PPARgamma agonists relative to troglitazone may translate into superior clinical efficacy for the treatment of type 2 diabetes.

Administration, Oral↗

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 2. Structure-activity relationship and optimization of the phenyl alkyl ether moiety.

We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propanoic acid (2) (PPARgamma pKi = 8.94, PPARgamma pEC50 = 9.47) as a potent and selective PPARgamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPARgamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-pyridin-4-yloxazol+ ++- 4-yl)ethoxy]phenyl¿propionic acid (16) (PPARgamma pKi = 8.85, PPARgamma pEC50 = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-¿2-[5-methyl-2-(4-methylpiperazin+ ++- 1-yl)thiazol-4-yl]ethoxy¿phenyl)propionic acid (24) (PPARgamma pKi = 8.66, PPARgamma pEC50 = 8.89) provided two potent and selective PPARgamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPARgamma ligands (PPARgamma pKi's 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPARgamma binding, functional activity, selectivity, and aqueous solubility.

Adipocytes↗

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 3. Structure-activity relationship and optimization of the N-aryl substituent.

3-¿4-[2-(Benzoxazol-2-ylmethylamino)ethoxy]phenyl¿-(2S)-((2- benzoylph enyl)amino)propionic acid (1) and (2S)-((2-benzoylphenyl)amino)-3-¿4-[2-(5-methyl-2-phenyloxazol-4-y l)e thoxy]phenyl¿propionic acid (2) are peroxisome proliferator-activated receptor gamma (PPARgamma) agonists and have antidiabetic activity in rodent models of type 2 diabetes. As part of an effort to develop the SAR of the N-2-benzoylphenyl moiety of 1 and 2, a series of novel carboxylic acid analogues, 23-66, modified only in the N-2-benzoylphenyl moiety were synthesized from L-tyrosine and evaluated as PPARgamma agonists. In general, only modest changes in the N-2-benzoylphenyl moiety of 1 and 2 are tolerated. More specifically, the best changes involve bioisosteric replacement of one of the two phenyl rings of this moiety. Addition of substituents to this moiety generally produced compounds that are less active in the cell-based functional assays of PPARgamma activity although binding affinity to PPARgamma may be maintained. A particularly promising set of analogues is the anthranilic acid esters 63-66 in which the phenyl ring in the 2-benzoyl group of 1 and 2 has been replaced by an alkoxy group. In particular, (S)-2-(1-carboxy-2-¿4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phen yl¿ ethylamino)benzoic acid methyl ester (63) has a pKi of 8.43 in the binding assay using human PPARgamma ligand binding domain and a pEC50 of 9.21 in the in vitro murine lipogenesis functional assay of PPARgamma activity. Finally, 63 was found to normalize glycemia when dosed at 3 mg/kg bid po in the Zucker diabetic fatty rat model of type 2 diabetes.

Administration, Oral↗

Heterotopic neurogenesis in a rat with cortical heterotopia.

Early cellular development was studied in the neocortex of the tish rat. This neurological mutant is seizure-prone and displays cortical heterotopia similar to those observed in certain epileptic patients. The present study demonstrates that a single cortical preplate is formed in a typical superficial position of the developing tish neocortex. In contrast, two cortical plates are formed: one in a normotopic position and a second in a heterotopic position in the intermediate zone. As the normotopic cortical plate is formed, it characteristically separates the subplate cells from the superficial Cajal-Retzius cells. In contrast, the heterotopic cortical plate is not intercalated between the preplate cells because of its deeper position in the developing cortex. Cellular proliferation occurs in two zones of the developing tish cortex. One proliferative zone is located in a typical position in the ventricular/subventricular zone. A second proliferative zone is located in a heterotopic position in the superficial intermediate zone, i.e., between the two cortical plates. This misplaced proliferative zone may contribute cells to both the normotopic and heterotopic cortical plates. Taken together, these findings indicate that misplaced cortical plate cells, but not preplate cells, comprise the heterotopia of the tish cortex. Heterotopic neurogenesis is an early developmental event that is initiated before the migration of most cortical plate cells. It is concluded that misplaced cellular proliferation, in addition to disturbed neuronal migration, can play a key role in the formation of large cortical heterotopia.

Animals↗

Characteristics of health education among secondary schools--School Health Education Profiles, 1996.

PROBLEM/CONDITION: School health education (e.g., classroom training) is an essential component of school health programs; such education promotes the health of youth and improves overall public health. REPORTING PERIOD: February-May 1996. DESCRIPTION OF SYSTEM: The School Health Education Profiles monitor characteristics of health education in middle or junior high schools and senior high schools. The Profiles are school-based surveys conducted by state and local education agencies. This report summarizes results from 35 state surveys and 13 local surveys conducted among representative samples of school principals and lead health education teachers. The lead health education teacher is the person who coordinates health education policies and programs within a middle or junior high school and senior high school. RESULTS: During the study period, almost all schools in states and cities required health education in grades 6-12; of these, a median of 87.6% of states and 75.8% of cities taught a separate health education course. The median percentage of schools that tried to increase student knowledge on certain topics (i.e., prevention of tobacco use, alcohol and other drug use, pregnancy, human immunodeficiency virus [HIV] infection, other sexually transmitted diseases, violence, or suicide; dietary behaviors and nutrition; and physical activity and fitness) was > 72% for each of these topics. The median percentage of schools that tried to improve certain student skills (i.e., communication, decision making, goal setting, resisting social pressures, nonviolent conflict resolution, stress management, and analysis of media messages) was > 69% for each of these skills. The median percentage of schools that had a health education teacher coordinate health education was 33.0% across states and 26.8% across cities. Almost all schools taught HIV education as part of a required health education course (state median: 94.3%; local median: 98.1%), and more than half (state median: 69.5%; local median: 82.5%) had a written policy on HIV infection among students and school staff. A median of 41.0% of schools across states and a median of 25.8% of schools across cities had a lead health education teacher with professional preparation in health and physical education, and < 25% of schools across states or cities had a lead health education teacher with professional preparation in health education only. Across states, the median percentage of schools, whose lead health education teacher had received in-service training on certain health education topics, ranged from 15.6% for suicide prevention to 51.4% for HIV prevention; across cities, the median percentage ranged from 26.2% for suicide prevention to 76.1% for HIV prevention. A median of 19.7% of schools across states and 18.1% of schools across cities had a school health advisory council. Of the schools that received parental feedback (state median: 59.1%; local median: 54.2%), > 78% reported receiving positive feedback. INTERPRETATION: More than 75% of schools have a required course in health education to help provide students with the knowledge and skills they need to adopt healthy lifestyles. ACTIONS TAKEN: The School Health Education Profiles data are being used by state and local education officials to improve school health education and HIV education.

Adolescent↗

Youth risk behavior surveillance--United States, 1997.

PROBLEM/CONDITION: Priority health-risk behaviors, which contribute to the leading causes of mortality and morbidity among youth and adults, often are established during youth, extend into adulthood, and are interrelated. REPORTING PERIOD: February-May 1997. DESCRIPTION OF THE SYSTEM: The Youth Risk Behavior Surveillance System (YRBSS) monitors six categories of priority health-risk behaviors among youth and young adults--behaviors that contribute to unintentional and intentional injuries; tobacco use; alcohol and other drug use; sexual behaviors that contribute to unintended pregnancy and sexually transmitted diseases (STDs) (including human immunodeficiency virus [HIV] infection); unhealthy dietary behaviors; and physical inactivity. The YRBSS includes a national school-based survey conducted by CDC as well as state, territorial, and local school-based surveys conducted by education and health agencies. This report summarizes results from the national survey, 33 state surveys, 3 territorial surveys, and 17 local surveys conducted among high school students from February through May 1997. RESULTS AND INTERPRETATION: In the United States, 73% of all deaths among youth and young adults 10-24 years of age result from only four causes: motor vehicle crashes, other unintentional injuries, homicide, and suicide. Results from the national 1997 YRBSS demonstrate that many high school students engage in behaviors that increase their likelihood of death from these four causes--19.3% had rarely or never worn a seat belt; during the 30 days preceding the survey, 36.6% had ridden with a driver who had been drinking alcohol; 18.3% had carried a weapon during the 30 days preceding the survey; 50.8% had drunk alcohol during the 30 days preceding the survey; 26.2% had used marijuana during the 30 days preceding the survey; and 7.7% had attempted suicide during the 12 months preceding the survey. Substantial morbidity among school-age youth, young adults, and their children also result from unintended pregnancies and STDs, including HIV infection. YRBSS results indicate that in 1997, 48.4% of high school students had ever had sexual intercourse; 43.2% of sexually active students had not used a condom at last sexual intercourse; and 2.1% had ever injected an illegal drug. Of all deaths and substantial morbidity among adults > or = 25 years of age, 67% result from two causes--cardiovascular disease and cancer. Most of the risk behaviors associated with these causes of death are initiated during adolescence. In 1997, 36.4% of high school students had smoked cigarettes during the 30 days preceding the survey; 70.7% had not eaten five or more servings of fruits and vegetables during the day preceding the survey; and 72.6% had not attended physical education class daily. ACTIONS TAKEN: These YRBSS data are already being used by health and education officials to improve national, state, and local policies and programs to reduce risks associated with the leading causes of morbidity and mortality. YRBSS data also are being used to measure progress toward achieving 21 national health objectives and 1 of the 8 National Education Goals.

Accidents↗

N-Phenylamidines as selective inhibitors of human neuronal nitric oxide synthase: structure-activity studies and demonstration of in vivo activity.

Selective inhibition of the neuronal isoform of nitric oxide synthase (NOS) compared to the endothelial and inducible isoforms may be required for treatment of neurological disorders caused by excessive production of nitric oxide. Recently, we described N-(3-(aminomethyl)benzyl)acetamidine (13) as a slow, tight-binding inhibitor, highly selective for human inducible nitric oxide synthase (iNOS). Removal of a single methylene bridge between the amidine nitrogen and phenyl ring to give N-(3-(aminomethyl)phenyl)acetamidine (14) dramatically altered the selectivity to give a neuronal selective nitric oxide synthase (nNOS) inhibitor. Part of this large shift in selectivity was due to 14 being a rapidly reversible inhibitor of iNOS in contrast to the essentially irreversible inhibition of iNOS observed with 13. Structure-activity studies revealed that a basic amine functionality tethered to an aromatic ring and a sterically compact amidine are key pharmacophores for this class of NOS inhibitors. Maximal nNOS inhibition potency was achieved with N-(3-(aminomethyl)phenyl)-2-furanylamidine (77) (Ki-nNOS = 0.006 microM; Ki-eNOS = 0.35 microM; Ki-iNOS = 0.16 microM). Finally, alpha-fluoro-N-(3-(aminomethyl)phenyl)acetamidine (74) (Ki-nNOS = 0. 011 microM; Ki-eNOS = 1.1 microM; Ki-iNOS = 0.48 microM) had excellent brain penetration and inhibited nNOS in a rat brain slice assay as well as in the rat brain (cerebellum) in vivo. Thus, N-phenylamidines should be useful in validating the role of nNOS in neurological disorders.

Amidines↗