Dynamics of modulation of biochemical programs in cancer cells.
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Animals↗
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Results for “Dynamic Programming”
Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.
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Impact of user fees on attendance at a referral centre for sexually transmitted diseases in Kenya.
We investigated the impact of a short-lived policy of charging fees to patients attending public-sector outpatient health facilities in Kenya by collecting data on attendance at Nairobi's Special Treatment Clinic for sexually transmitted diseases (STDs) before (23 months), during (9 months), and after (15 months) the user-charge period. During the user-charge period, the seasonally adjusted total mean monthly attendance of men decreased significantly to 40% (95% CI 36-45) of that before fees were levied. Attendance rose in the post-user-charge period, but reached only 64% (59-68) of the pre-user-charge level. For women, the adjusted total mean monthly attendance during the user-charge period was reduced significantly to 65% (55-77) of the pre-user-charge level. Mean monthly attendance by women rose in the post-user-charge period to 22% (9-37) above the pre-user-charge level. There was no evidence of an increase in attendance over the course of the user-charge period among either men or women. The introduction of user fees probably increased the number of untreated STDs in the population, with potentially serious long-term health implications. The user-fee experience in Kenya should be carefully evaluated before similar measures are introduced elsewhere.
Community Health Centers↗
Conceptions and misconceptions. Decisions about pregnancy.
Induced abortion has been practiced in every known society and in every era of history. Psychological concomitants of abortion are as much a product of the social and interpersonal context as of the process itself. Though abortion results in the loss of a potential human life, it is not associated with significant psychiatric morbidity, and, in fact, represents for many women--and men--a significant milestone in which they assume responsibility for the direction of their lives for the first time. However, assertions that abortion is psychologically damaging have characterized much of the recent bitter debate over the legality and availability of abortion. It is important that mental health professionals are knowledgeable about the subject of abortion so that they can discuss policy with their patients.
Abortion, Induced↗
The clinical advantages of I-125 seeds as a substitute for Ir-192 seeds in temporary plastic tube implants.
In August of 1986 at William Beaumont Hospital, Iodine-125 (I-125) seeds were introduced in the clinical practice as a substitute for Iridium-192 (Ir-192) seeds in patients undergoing temporary plastic tube interstitial implants. Through February 1988, 108 I-125 implants were performed in 105 patients. Acute and chronic toxicity was indistinguishable from Ir-192. However, improved radiation safety and a dynamic dosimetric program have resulted from this endeavor. Because of the multiple clinical advantages of I-125, we feel that this should be considered the isotope of choice in temporary interstitial plastic tube implants.
Brachytherapy↗
Early dynamic splinting for extensor tendon injuries.
Extensor tendon injuries are traditionally splinted with no motion for 3 to 4 weeks after repair. This may result in limitation of flexion because of extensor tenodesis at the site of repair. To prevent this, we used a dynamic splinting program opposite to the one that is used for flexor tendon repair, with an outrigger splint holding the fingers in extension and allowing full active flexion. Fifty-two patients who had extensor tendon repairs in the area from the wrist to the middle of the proximal phalanx were treated. Motion was begun 2 to 5 days after repair and was continued for approximately 5 weeks. No tendon ruptures occurred, and all patients recovered full flexion.
Adult↗
Photon beam compensation design: dose optimization in 3D volume for parallel opposed beams.
Most existing methods for photon beam compensation design is based on the dose optimization in a 2D plane through the treatment volume for each individual beam. These approaches do not, however, optimize the dose uniformity in the dimension along the beam path (hence not in the 3D volume). In this work, the author presents a practical compensation design algorithm for 3D dose optimization. In contrast to existing methods, the present algorithm simultaneously calculates the desired cross-beam transmission factor map of the compensation device for each pair of parallel opposed beams. By using computed tomography scans, the patient's external shape and the internal inhomogeneous tissue density are also taken into account. The result is used to construct beam-attenuating compensators or to program a dynamic beam delivery scheme. The algorithm is presented in a form easily adaptable to different dose calculation systems. Compared to other methods, superior dose uniformity is achieved via the present approach.
Humans↗
Feeding the epigenome: EZH2 as a metabolic integrator of cell fate in development and cancer.
Epigenetic regulation is intimately linked to cellular metabolism, enabling environmental and nutritional cues to shape gene expression programs through dynamic modifications of chromatin structure. This metabolism-epigenetics interface is mediated, in part, by the dependence of chromatin-modifying enzymes on key metabolites, including S-adenosylmethionine (SAM), acetyl-CoA, UDP-GlcNAc, and α-ketoglutarate, which serve as substrates or cofactors for DNA and histone modifications. Among these regulators, EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), has emerged as a key mediator linking metabolic state to epigenetic regulation by translating metabolic inputs into changes in chromatin architecture and gene expression. EZH2 governs developmental cell fate through H3K27me3-mediated gene repression and is frequently dysregulated in cancer, where it promotes dedifferentiation, tumor progression, and metabolic reprogramming. Importantly, EZH2 activity is itself modulated by cellular metabolic status through posttranslational modifications, including phosphorylation, acetylation, methylation, ubiquitination, and O-GlcNAcylation, which influence its stability, catalytic activity, and chromatin-binding capacity. These modifications are responsive to nutrient availability and signaling pathways involving glucose, SAM, NAD+, and other metabolic intermediates. Consequently, disruption of this finely tuned regulatory network can contribute to developmental abnormalities, metabolic dysfunction, and oncogenesis. In this review, we examine the molecular mechanisms governing EZH2 regulation and discuss how metabolic control of EZH2 shapes chromatin dynamics, cell fate decisions, and disease pathogenesis. Elucidating how metabolic signals modulate EZH2 activity will advance our understanding of development and disease while uncovering potential therapeutic opportunities to target metabolism-driven epigenetic dysregulation.
Humans↗
Married women's dissatisfaction with tubal sterilization and vasectomy at first-year follow-up: effects of perceived spousal dominance.
Examination of first-year follow-up data obtained from 234 tubal ligation women and 154 vasectomy wives indicated a very low incidence of actual regret in both groups. However, use of a broader measure of satisfaction/dissatisfaction indicated that tubal ligation women had significantly more positive feelings about the sterilization decision than did vasectomy wives. Results of a series of multivariate statistical analyses demonstrated that group differences in satisfaction were related to (1) the disproportionate prevalence of perceived male control (particularly extensive control) over reproductive decisions among vasectomy wives and the negative effect it had upon subjects in both groups and (2) the disproportionate prevalence of female control over reproductive decision-making among tubal ligation women and the positive effect it had among subjects in this group. Study results point to the importance of couple counseling and exercising control over one's own body.
Adult↗
Smoking and reproduction.
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Birth Weight↗
Nonoperative management of multilevel lumbar disk herniations in an adolescent athlete.
Herniated lumbar nucleus pulposus is rare in the pediatric age-group; for surgically proven cases, the estimated prevalence is between 0.8 and 3.2%. Most of the current literature indicates that herniated nucleus pulposus in pediatric patients differs from that in adult patients in epidemiologic characteristics, clinical manifestations, and frequency of associated neurologic findings. To our knowledge, the current case is the first published report of lumbar disk herniations at three levels in a 15-year-old male adolescent, whose abnormalities were verified by computed tomography and myelography. Most investigators recommend surgical treatment; however, our patient had good results with nonoperative management that consisted of nonsteroid anti-inflammatory drugs, passive extension, lumbar traction, segmental mobilization, and a progressive program of dynamic lumbar stabilization exercises. The patient is now asymptomatic and able to participate in selected limited contact sports and most farm activities; however, contact sports are prohibited for 1 year. If follow-up computed tomographic imaging of the lumbar spine demonstrates no progression of the disk abnormalities and if the patient remains asymptomatic, he could consider participation in contact sports after necessary conditioning.
Adolescent↗
Mortality and morbidity from malaria in Gambian children after introduction of an impregnated bednet programme.
After the success of a controlled trial of insecticide-treated bednets in lowering child mortality, The Gambia initiated a National Insecticide Impregnated Bednet Programme (NIBP) in 1992 with the objective of introducing this form of malaria control into all large villages in The Gambia. Five areas (population 115,895) were chosen as sentinel sites for evaluation of the NIBP. During the first year of intervention a 25% reduction was achieved in all-cause mortality in children 1-9 years old living in treated villages (rate ratio 0.75 [95% CI 0.57-0.98], p = 0.04). If one area where the programme was ineffective was excluded, the reduction was 38% (0.62 [0.46-0.83), p = 0.001). A decrease in rates of parasitaemia and high-density parasitaemia, an increase in mean packed-cell volume (rate ratio 0.75 [95% CI 0.59-0.98], p = 0.04) and an improvement in the nutritional status of children living in treated villages were also detected. In a country such as The Gambia, where nets were widely used and which has a good primary health care system, it is possible to achieve insecticide-treatment of bednets at a national level with a significant reduction in child mortality; but at a cost which the country cannot afford.
Bedding and Linens↗
A preliminary evaluation of education material prepared for the Safe Motherhood Initiative Educational Project.
Maternal death is a tragedy which is all too familiar in much of the world. As part of the Safe Motherhood Initiative the World Health Organization is developing and producing a learning package designed specifically for midwives. Through a modular system of learning incorporating aspects of community, prevention, treatment and follow-up the package seeks to address the five main causes of maternal mortality. In this paper the first pre-testing of the educational material in an African country is described. The extent of the evaluation is limited at this early stage but the initial analysis of the results is encouraging and have led to modifications of the original package. The evaluation has confirmed that a tool such as this package can be a valuable resource for midwife teachers attempting to improve the relevance of education for their midwifery students. The midwifery students whilst being 'with woman' in childbirth are also grappling with the realities of death in their everyday practice. The educational package has also reinforced the sense of urgency fundamental to completing this extensive project so that it can be made available to midwives throughout the developing world at the earliest opportunity.
Botswana↗
Infant and child mortality in rural Egypt.
This research examines determinants of infant and child mortality in rural Egypt, primarily the effects of household economic status and the availability of health services. Certain features of the health service environment affect survival in the neonatal period. In early childhood, survival chances improve markedly as income increases and if the household depends almost exclusively on employment income. In infancy and in early childhood, mortality is strongly associated with region of residence and maternal demographic characteristics, and is weakly associated with parental schooling.
Child, Preschool↗
High-resolution solution structure of the EGF-like domain of heregulin-alpha.
The solution structure of the 63-residue heregulin-alpha (HRG-alpha) epidermal growth factor (EGF)-like domain, corresponding to residues 177-239 of HRG-alpha, has been determined to high resolution using data from two-dimensional and three-dimensional homo- and heteronuclear NMR spectroscopy. The structure is based on a total of 887 internuclear distance and dihedral restraints derived from data obtained using unlabeled and uniformly 15N-labeled protein samples, at pH 4.5, 20 degrees C. A total of 20 structures were calculated using a hybrid distance geometry-simulated annealing approach with the program DGII, followed by restrained molecular dynamics using the program DISCOVER. The average maximum violations are 0.12 +/- 0.01 angstroms and 1.4 +/- 0.3 degrees for distance and dihedral restraints, respectively. The backbone (N,C(alpha),C) atomic rms distribution about the mean coordinates for residues 3-23 and 31-49 is 0.29 +/- 0/07 angstroms. The N-and C-terminal residues (1-2 and 50-63) and 24-30 are disordered. Comparison of the HRG-alpha EGF-like domain structure with the previously determined structure of human EGF [Hommel et al. (1992) J. Mol. Biol. 227, 271-282] reveals a high degree of structural similarity; excluding the N-terminal region (residues 1-13), the disordered phi-loop region (residues 24-30) that contains a three-residue insertion in HRG-alpha relative to hEGF, and the disordered C-terminal region (residues 50-63), the C(alpha) alignment between the HRG-alpha and hEGF minimized mean structures has a rms difference of approximately 1 angstrom. In HRG-alpha the N-terminal residues 2-6 form a well-defined beta strand rather than being disordered as found for hEGF. This structural difference correlates with functional data which suggest that the N-terminal region of the HRG-alpha EGF-like domain is responsible for the observed receptor specificity differences between HRG-alpha and EGF.
Amino Acid Sequence↗
Counseling adolescents with problem pregnancies.
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Abortion, Induced↗
Genomic and structural analysis of dacB variants associated with cephalosporin resistance in Pseudomonas aeruginosa.
The rise of resistance to fourth-generation cephalosporin in Pseudomonas aeruginosa (P. aeruginosa) is a global concern. The resistance is largely driven by variants of chromosomally encoded AmpC β-lactamase, known as Pseudomonas-derived cephalosporinase (PDC), which arise from the mutations in the ampC gene. In addition, alteration in dacB, which encode the penicillin-binding protein 4 (PBP4), can lead to the overexpression of ampC, thereby contributing to β-lactam resistance. Present work analyzed 208 clinical isolates of P. aeruginosa using whole-genome sequencing (WGS) and detected multiple nonsynonymous single nucleotide polymorphisms (nsSNPs), such as Y264C, G444D, and a double mutation (A394P-T428P). All nsSNPs were predicted to be deleterious by several prediction program. Molecular dynamics (MD) simulations suggested that these substitutions destabilize PBP4, increase structural flexibility, and contribute to the resistance mechanism, which favored their selection. To determine the effective therapeutics against these mutations, molecular docking was conducted with various antibiotics. Cefoperazone exhibited the highest binding affinity (-7.3 kcal/mol) among multiple PBP4 variants. The Molecular dynamics (MD) simulations and Molecular Mechanics Poisson Boltzmann Surface Area calculations (MMPBSA) further confirmed the favorable interactions between cefoperazone and PBP4 variants. In vitro MIC analyses supported these findings, indicating that cefoperazone displayed significant activity against clinical dacB mutants of P. aeruginosa. The study offers structural insight of dacB variants leading to antibiotic resistance and emphasizes the need to prioritize specific antibiotics to address the challenges arising from protein mutations.
Pseudomonas aeruginosa↗
Female circumcision as a public health issue.
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Child↗
Contraception for the adolescent.
The primary care physician is in an excellent position to counsel adolescents about contraception. However, an adequate understanding of the biologic and psychosocial development of this particular age-group is imperative. In addition, communication skills are necessary to advise adolescents on use of contraceptives. The goal in counseling the adolescent about sexuality is to instill a sense of sexual responsibility and to provide individualized instruction in selecting the appropriate birth control method. General factors to remember in selecting the proper method include motivation, moral-ethical responsibility, frequency of intercourse, side effects of the various contraceptive methods, and patient's preference.
Adolescent↗