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PubMed1990

Simulations of dynamical properties of a Michaelis complex: porcine pancreatic elastase and the hexapeptide, Thr-Pro-n Val-Leu-Tyr-Thr.

Molecular dynamic simulations (30ps) of the Michaelis complex of hexapeptide (Thr-Pro-nVal-Leu-Tyr-Thr) bound to porcine pancreatic elastase (PPE) hydrated by about 2000 water molecules have been performed using the AMBER 3.0 program package. Dynamical properties of the conformation of the active site have been examined. A comparison with previously reported simulations of native PPE shows that after the substrate is bound, the catalytically crucial H-bond between O gamma-H group of (Ser 195) and nitrogen N epsilon (His 57) is more readily formed. These results show, however, that the H-bond does not adopt the most favorable conformation. The O gamma-H group of Ser 195 has a statistical preference for an attractive interaction with the O = C carbonyl (Ser 214) rather than the nitrogen N epsilon (His 57).

Amino Acid Sequence↗
PubMed1981

The adolescent and contraception: issues and controversies.

Issues relating to adolescent sexuality and high fertility in the U.S. are reviewed briefly. Similar issues in the developing world are discussed, with emphasis placed on the limited data on the subject currently available in most developing countries. The contraceptive options available for the sexually active teenager are presented, together with a discussion of the very difficult decisions and controversies that result from the lack of an ideal or even preferable method of contraception at present.

Adolescent↗
PubMed1993

Contraceptive delivery in the developing world.

A strong demand for family planning exists in most developing countries and family size is falling rapidly in many of them. Effective family planning programmes offer a world-wide range of choices (including voluntary sterilisation and abortion) through a variety of distribution channels. Universal access to voluntary family planning can be achieved easily and cheaply by the turn of the century, but only if conservative medical policies are overcome and funding is greatly expanded. The international community faces a genuine choice: if it responds to current opportunities the global population will stabilize at approximately 10 billion or fewer; if it fails, population may grow to 14 billion or more. The difference between these two projections (approximately equal to the present world population of 5.4 billion) may well determine the future of the planet.

Contraception↗
PubMed2026

Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small-Cell Lung Cancer.

BACKGROUND: Small-cell lung cancer (SCLC) is characterized by pervasive chromosomal instability (CIN) and remains largely refractory to targeted therapies. KIF18A, a motor protein that regulates chromosome alignment during mitosis, has emerged as a selective dependency in CIN-high tumors. Whether this dependency extends to SCLC, a prototypical CIN-high cancer, has not been established, and biomarkers predicting response to KIF18A inhibition, currently in clinical trials, are lacking. METHODS: We integrated analyses of patient tumor datasets, neuroendocrine (NE) and non- NE SCLC cell lines, and functional perturbation models to define the determinants of response to KIF18A inhibition. Chromosomal instability metrics, transcriptional programs, mitotic dynamics, and spindle assembly checkpoint (SAC) function were assessed using genomic profiling, live-cell imaging, genetic perturbation, and pharmacologic inhibition. RESULTS: KIF18A expression was elevated in SCLC tumors and correlated with CIN-associated transcriptional programs, proliferative markers, and NE status; however, these features did not predict sensitivity to KIF18A inhibition. Instead, response was determined by the functional integrity of the SAC. SAC-proficient SCLC cells underwent sustained mitotic arrest followed by apoptotic cell death upon KIF18A inhibition, whereas SAC-defective cells failed to maintain checkpoint activation and survived. Mechanistically, resistant cells exhibited impaired kinetochore recruitment of core SAC components, including MAD1 and BUBR1. Importantly, transient induction of acute CIN through MPS1 inhibition partially restored sensitivity to KIF18A inhibition in resistant models. CONCLUSIONS: This study provides the first mechanistic characterization of KIF18A dependency in SCLC, identifying SAC competency as the primary determinant of response. These findings establish a biologically informed framework for patient stratification and rational combination strategies. TRANSLATIONAL RELEVANCE: Small-cell lung cancer (SCLC) is an aggressive malignancy with few effective targeted therapies and marked chromosomal instability. KIF18A has emerged as a potential therapeutic target in genomically unstable cancers, but biomarkers predicting response to KIF18A inhibition are lacking. We demonstrate that sensitivity to KIF18A inhibition in SCLC is determined not by KIF18A expression, neuroendocrine subtype, or baseline chromosomal instability, but by the functional integrity of the spindle assembly checkpoint (SAC). SCLC cells with intact SAC signaling undergo sustained mitotic arrest and apoptosis upon KIF18A inhibition, whereas SAC-defective cells bypass checkpoint activation and survive aberrant mitosis. Notably, transient induction of acute chromosomal instability through MPS1 inhibition partially restores sensitivity in resistant models. Together, these findings identify mitotic checkpoint competency as a mechanistic determinant and candidate predictive biomarker for KIF18A-targeted therapies, providing a biologically informed framework for patient stratification and rational combination strategies relevant to ongoing KIF18A inhibitor clinical trials.

Journal Article↗
PubMedDate not supplied

First family planning visits by young women.

Data from the 1982 National Survey of Family Growth indicate that among sexually active women aged 15-24, friends and parents are the main sources of referral for first family planning visits. Friends are the leading referral source for women who attend clinics, and parents are the leading referral source for those who go to private doctors. Despite the importance of confidentiality to many teenagers, women who make their first family planning visit before the age of 17 are more likely to be referred by their parents than are those whose first visit occurs when they are 17 or older. Race, age at first visit and income influence women's choice of a provider (clinic or private doctor). Black women, low-income women and younger women are considerably more likely than their counterparts to use a clinic at first family planning visit. At their first visit, sixty-seven percent of women receive birth control counseling, and only 50 percent begin using a contraceptive method. Among clinic users, white women are more likely than black women to begin a birth control method (50 percent vs. 40 percent). Women whose first visit takes place before their first conception (including those who have never been pregnant) are much more likely than women whose first visit occurs after their first pregnancy ends to begin a method. Women who make their first visit during their first pregnancy are more likely than those who are not pregnant to receive a pregnancy test or counseling on matters other than birth control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2002

Reducing the risk of falls through proprioceptive dynamic posture training in osteoporotic women with kyphotic posturing: a randomized pilot study.

OBJECTIVE: To assess the effect of a proprioceptive dynamic posture training program on balance in osteoporotic women with kyphotic posture. DESIGN: Subjects were randomly assigned to either a proprioceptive dynamic posture training program or exercise only group. Anthropometric measurements, muscle strength, level of physical activity, computerized dynamic posturography, and spine radiography were performed at baseline and 1 mo. RESULTS: At the 1-mo follow-up, three groups were formed on the basis of the baseline computerized dynamic posturography results. In general, groups 1 and 2 had no significant change at 1 mo, whereas group 3 improved balance significantly at 1 mo. CONCLUSION: The subjects who had abnormal balance and used the proprioceptive dynamic posture training program had the most significant improvement in balance. Improved balance could reduce the risk of falls.

Accidental Falls↗
PubMed1984

Computer-assisted instruction and diagnosis of radiographic findings.

Recent advances in computer technology, including high bit-density storage, digital imaging, and the ability to interface microprocessors with videodisk, create enormous opportunities in the field of medical education. This program, utilizing a personal computer, videodisk, BASIC language, a linked textfile system, and a triangulation approach to the interpretation of radiographs developed by Dr. W. L. Thompson, can enable the user to engage in a user-friendly, dynamic teaching program in radiology, applicable to various levels of expertise. Advantages include a relatively more compact and inexpensive system with rapid access and ease of revision which requires little instruction to the user.

Computer-Assisted Instruction↗
PubMed1987

Influence of family planning counseling in an adolescent clinic on sexual activity and contraceptive use.

We evaluated whether family planning counseling (FPC) in an adolescent clinic promoted the onset of sexual activity among the non-sexually active teens and/or increased contraceptive use among the sexually active teens. The FPC focused on the teens' establishing sexual values, the right to say "no," abstinence and alternate forms of intimacy, consequences of intercourse, and the various contraceptive methods. Data for one year were collected on the adolescents' first and subsequent visits to a medically oriented, municipal outpatient adolescent clinic. There were 383 teenagers who qualified for the study. Of these, 35% (134) reported premarital sexual activity. During the study period, 3% (8) of the 249 nonsexually active teens reported becoming sexually active. Among the 134 sexually active teens at clinic entry, 27% reported using a contraceptive method at their most recent sexual encounter. Among the 142 sexually active adolescents at the conclusion of the study, 76% reported contraceptive use at their most recent sexual encounter (p less than 0.001). We conclude that the provision of FPC to nonsexually active and sexually active teens does not appear to promote the onset of sexual activity significantly among the non-sexually active group, although it significantly increases contraceptive use among the sexually active group.

Adolescent↗
PubMedDate not supplied

Fetal loss and contraceptive acceptance among the Bhopal gas victims.

The rates of fetal loss and family planning acceptance among Bhopal gas victims from 1984 to 1989 were compared to those of a control group. In all, 136 eligible women in the affected area and 139 women in the control area were interviewed. Care was taken to ensure that these women had conceived at least once during the previous five years. The The fetal loss rate among the gas-affected women was abnormally high (26.3 per cent) compared to that of women in the control area (7.8 per cent). Family planning acceptance in both areas was similar, with most women using permanent methods. In the case of temporary methods, the percentage of use was higher in the gas-affected area.

Abortion, Spontaneous↗
PubMed1999

Women's fears and men's anxieties: the impact of family planning on gender relations in northern Ghana.

The Navrongo experiment, a family planning and health project in northern Ghana, has demonstrated that an appropriately designed, community-based family planning program can produce a change in contraceptive practice that had been considered unattainable in such a setting. Simultaneously, however, evidence suggests that newly introduced family planning services and contraceptive availability can activate tension in gender relations. In this society, where payment of bridewealth signifies a woman's requirement to bear children, there are deeply ingrained expectations about women's reproductive obligations. Physical abuse and reprisals from the extended family pose substantial threats to women; men are anxious that women who practice contraception might be unfaithful. Data from focus-group discussions with men and women are examined in this report and highlight the strains on gender relations resulting from contraceptive use. The measures taken to address this problem and methods of minimizing the risk of adverse social consequences are discussed.

Adult↗