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PubMed1983

An experimental study of social isolation of elderly people: psychoendocrine and metabolic effects.

Psychoendocrine and metabolic effects of social isolation and understimulation in real life were examined in a controlled study of 60 elderly people representative of their age group. Together with the staff and the elderly, a social activation program was formed at a senior citizen apartment building. Half of the elderly were part of this activation program (experimental group). The other half constituted the control group. Blood sampling and psychosocial testing were performed immediately before and after 3 and 6 months of social activation. Social activation increased threefold in the experimental group. Height decreased in the control group compared to the experimental subjects. Plasma levels of testosterone, dehydroepiandrosterone, and estradiol increased significantly in the experimental group over the 6-month period compared to the control group. The most pronounced increase took place during the initial 3 months. Hemoglobin A1c decreased significantly in the experimental group over the 6-month period compared to the control group. In this preliminary study it is concluded that social isolation and understimulation may be associated with a wide range of psychophysiologic effects in elderly people.

Aged↗
PubMed1978

Tuftsin (an Ig-associated tetrapeptide) triggers the immunogenic function of macrophages: implications for activation of programmed cells.

The immunoglobulin heavy-chain-associated tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-specific, macrophage-dependent education of T lymphocytes. The investigation of stereospecific characteristics of the tetrapeptide, by use of structural analogs with different modifications, revealed strict structural requirements for eliciting the immunogenic activity of macrophages. It was found that the most important moiety for its activity is the dipeptide Pro-Arg. This finding is of interest in view of the appearance of this particular dipeptide in other bioregulatory peptides, including many of the peptide hormones. The significance of the appearance of a common structure in such molecules, which may act through specific receptors on different target cells, is discussed.

Amino Acid Sequence↗
PubMed1988

A community outreach training program for pediatric residents and medical students.

In 1982 the Division of Community Pediatrics of the University of North Carolina at Chapel Hill began a new training program for all first-year pediatrics residents and fourth-year medical students taking an ambulatory pediatrics elective. The program was designed to introduce the trainees to community resources for children and increase their knowledge of the factors affecting children's development. During their regular hospital clinic rotations, the trainees spend approximately one-third of their time in program activities that involve 25 community agencies. Educational packets (consisting of books, journal articles, films, slides, videotapes, self-instruction materials, manuals for developmental tests, and/or agency materials) are provided for each program component. At the end of each one-month rotation of program activities, the trainees meet individually with the program director and coordinator to discuss the trainee's experiences and reactions and to identify strengths and weaknesses of the program components.

Child↗
PubMed1991

[Lateral instability of the ankle joint (2). Active training programs can prevent surgery].

One hundred consecutive patients with chronic lateral functional instability of the ankle were treated non-operatively with physiotherapy (active range-of-motion training, strengthening exercises and co-ordination training with a tilt-board). All patients were evaluated functionally with a special rating scale, and radiologically with standardised stress radiographs measuring anterior talar translation (ATT) and talar tilt (TT). Excellent or good functional results were obtained in 49 of the patients, fair or poor in the remainder. The outcome was better in those with painful functional instability or mild mechanical instability, while those with more pronounced mechanical instability required further treatment (i e, reconstructive surgery). Of 10 patients with generalised joint laxity, only fair or poor results were obtained in seven, all of whom had mechanical instability.

Adult↗
PubMedDate not supplied

Use of process evaluation to guide health education in Forsyth County's project to prevent cervical cancer.

The Forsyth County, NC, Cervical Cancer Prevention Project is a 5-year public health education program designed to increase the proportion of black women in the county who are appropriately screened for cervical cancer. In this paper, the authors report on process evaluation--the procedures used to monitor the intervention and to insure that the target population was reached with a high quality, community-based health education program. A system that encompasses documentation of program activities, interviews with women in waiting rooms of primary care providers, semiannual interviews with a panel of approximately 100 women from the target population, and telephone followup with participants in direct education workshops was designed and implemented. Through October 1990, more than 2,100 interviews had been conducted. Data from these activities have facilitated continued development and refinement of educational materials, provided guidance for developing new strategies for reaching the target population, and provided continuous feedback to program managers to allow monitoring the impact of all program activities.

Black or African American↗
PubMedDate not supplied

Activation of programmed cell death by anticancer agents: cisplatin as a model system.

The anticancer drug cisplatin exerts its action as a consequence of interaction with DNA. Cell cycle progression facilitates sensitivity to the drug, but inhibition of DNA synthesis is not necessarily the critical step. Lethally damaged cells can progress to and arrest for several days in the G2 phase of the cell cycle before dying. Certain features of cisplatin-induced cell death, such as chromatin condensation and the activation of a DNA endonuclease, are reminiscent of apoptosis, or programmed cell death. Many other anticancer drugs produce the same phenotypic effects, suggesting that these agents may all interact with the same signal transduction pathway leading to cell death.

Cell Cycle↗
PubMed2025

Boolean matrix logic programming for active learning of gene functions in genome-scale metabolic network models.

Reasoning about hypotheses and updating knowledge through empirical observations are central to scientific discovery. In this work, we applied logic-based machine learning methods to drive biological discovery by guiding experimentation. Genome-scale metabolic network models (GEMs) - comprehensive representations of metabolic genes and reactions - are widely used to evaluate genetic engineering of biological systems. However, GEMs often fail to accurately predict the behaviour of genetically engineered cells, primarily due to incomplete annotations of gene interactions. The task of learning the intricate genetic interactions within GEMs presents computational and empirical challenges. To efficiently predict using GEM, we describe a novel approach called Boolean Matrix Logic Programming (BMLP) by leveraging Boolean matrices to evaluate large logic programs. We developed a new system, [Formula: see text], which guides cost-effective experimentation and uses interpretable logic programs to encode a state-of-the-art GEM of a model bacterial organism. Notably, [Formula: see text] successfully learned the interaction between a gene pair with fewer training examples than random experimentation, overcoming the increase in experimental design space. [Formula: see text] enables rapid optimisation of metabolic models to reliably engineer biological systems for producing useful compounds. It offers a realistic approach to creating a self-driving lab for biological discovery, which would then facilitate microbial engineering for practical applications.

Active learning↗
PubMed1983

Physical activity and the healthy mind.

Physicians should seek to enhance the quality rather than the quantity of human life. Physical activity programs can increase life satisfaction through an immediate increase of arousal and a long-term enhancement of self-esteem and body image. In the young child competition can cause excessive arousal, but long-term adverse effects are rare. In the adult a reduction of anxiety and stress and a general feeling of well-being reduce the frequency of minor medical complaints, generating important economic benefits. Physical activity programs also help to correct the reactive depression that accompanies conditions such as myocardial infarction. Interest in physical activity should be stimulated from the earliest years of primary school. The allocation of curricular time to physical education does not hamper academic achievement. Rather, through its impact on psychomotor learning, it enhances the total process of intellectual and psychomotor development.

Aged↗
PubMed1992

Correlation of calcineurin phosphatase activity and programmed cell death in murine T cell hybridomas.

Ligation of T cell receptor/CD3 complexes induces programmed cell death, or apoptosis, in immature thymocytes and many T cell hybridomas. While it has been demonstrated that T cell receptor-mediated apoptosis requires an increase in intracellular calcium concentration, the specific calcium-dependent signalling events leading to cell death are poorly defined. We have previously shown that T cell receptor/CD3-mediated induction of apoptosis in a murine T cell hybridoma is inhibited by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Recently, it has been determined that these agents inhibit the activity of calcineurin, a calcium- and calmodulin-dependent serine/threonine phosphatase. Using an assay which measures calcineurin activity in cell lysates, we find that calcineurin-dependent dephosphorylation of a phosphopeptide substrate is potently inhibited in hybridomas treated with CsA or FK506. Drug dose-response analyses indicate that the level of cellular calcineurin activity correlates closely with the ability of these cells to undergo apoptosis. Thus, calcineurin appears to be a critical mediator of T cell receptor/CD3 signalling leading to programmed cell death in T cell hybridomas.

Amino Acid Sequence↗
PubMed1992

The effect of graded activity on patients with subacute low back pain: a randomized prospective clinical study with an operant-conditioning behavioral approach.

The aim of this study was to determine whether graded activity restored occupational function in industrial blue-collar workers who were sick-listed for 8 weeks because of subacute, nonspecific, mechanical low back pain (LBP). Patients with LBP, who had been examined by an orthopedic surgeon and a social worker, were randomly assigned to either an activity group (n = 51) or a control group (n = 52). Patients with defined orthopedic, medical, or psychiatric diagnoses were excluded before randomization. The graded activity program consisted of four parts: (1) measurements of functional capacity; (2) a work-place visit; (3) back school education; and (4) an individual, submaximal, gradually increased exercise program, with an operant-conditioning behavioral approach, based on the results of the tests and the demands of the patient's work. Records of the amount of sick leave taken over a 3-year period (ie, the 1-year periods before, during, and after intervention) were obtained from each patient's Social Insurance Office. The patients in the activity group returned to work significantly earlier than did the patients in the control group. The median number of physical therapist appointments before return to work was 5, and the average number of appointments was 10.7 (SD = 12.3). The average duration of sick leave attributable to LBP during the second follow-up year was 12.1 weeks (SD = 18.4) in the activity group and 19.6 weeks (SD = 20.7) in the control group. Four patients in the control group and 1 patient in the activity group received permanent disability pensions. The graded activity program made the patients occupationally functional again, as measured by return to work and significantly reduced long-term sick leave.

Absenteeism↗
PubMed1975

Evaluation by objectives: A systematic approach to the evaluation of educational programs and activities in dental education.

In response to the need for more effective utilization of resources, many institutions of higher learning are beginning to use corporate management methods. These methods, MBO being the most familiar example, center on the common comprehension at all levels of the goals of the corporation. However, institutions of higher learning uniformly lack a cohesiveness of purpose that extends from the level of president to that of teaching faculty. It is a mistake to assume that institutional educational goals are understood and supported by appropriate educational objectives at the department and program level. The evaluation-by-objective format is a concise graphical way to identify areas of support and confusion. It can be applied at each level of the institution and transmitted upward so that personnel at each administrative level can see the way in which its goals and objectives are perceived at lower levels. The proposed format facilitates grouping of educational objectives into programs, providing a framework for the estimation of effort and of needed resources. Since perceptions of effort and required resources will differ depending upon perspective, important issues will be identified, a most significant benefit of the system. The format leads to the formulation of an action plan, which should be reviewed periodically. The first step toward scientific management in institutions of higher learning must be a clear understanding of institutional and subunit goals, along with a set of education objectives that will accomplish these goals. The evaluation-by-objective format directs itself to exactly that concern.

Education, Dental↗
PubMed2025

Transcriptional activation of regenerative hematopoiesis via microenvironmental sensing.

Transition between activation and quiescence states in hematopoietic stem and progenitor cells (HSPCs) is tightly governed by cell-intrinsic means and microenvironmental co-adaptation. Although this balance is fundamental for lifelong hematopoiesis and immunity, the underlying molecular mechanisms remain poorly defined. Multimodal analysis divulging differential transcriptional activity between distinct HSPC states indicates the presence of Fli-1 transcription factor binding motif in activated hematopoietic stem cells. We reveal that Fli-1 activity is essential during regenerative hematopoiesis in mice. Fli-1 directs activation programs while priming cellular sensory and output machineries, enabling HSPCs co-adoptability with a stimulated vascular niche through propagation of niche-derived angiocrine Notch1 signaling. Constitutively induced Notch1 signaling is sufficient to recuperate functional hematopoietic stem cells impairments in the absence of Fli-1, without leukemic transformation. Applying FLI-1 transient modified-mRNA transduction into latent adult human mobilized HSPCs, enables their niche-mediated expansion and superior engraftment capacities. Thus, decryption of stem cell activation programs offers valuable insights for immunological regenerative medicine.

Animals↗
PubMed1984

Programmed electromyographic activity and negative incremental muscle stiffness in monkeys jumping downward.

We trained monkeys to jump down from different heights, and recorded electromyograms (e.m.g.s) in arm muscles, and ground reaction forces. The landing movements were also recorded by high-speed cinematography. The e.m.g. of the triceps began about 80 ms before landing. The initial burst lasted until about 20 ms after ground contact and was succeeded by bursts of gradually declining amplitude. These discharges were not of reflex origin, because when the monkey was deceived by a collapsible platform, they were time-locked to the expected, not to the true landing. The amplitude of the e.m.g. in the triceps increased with the height of the jump, indicating adaptive control. The timing of the e.m.g. pattern was assumed to be programmed before take off, because it was unaffected by extinction of the light during the fall. The vertical ground reaction force produced by the arms had an inflexion on its rising phase which arose from the very rapid stretch of the muscles which control the wrist. Then came a sharp peak produced mainly by stretch of the triceps. The inflexion and the sharp peak were probably produced by short-range stiffness of the muscles of the upper arm. The torque acting on the elbow joint, and the elbow joint stiffness were calculated from the ground reaction forces and the movement of the arm. The torque was high at impact and gradually declined during the landing. The force produced by the triceps increased sharply, then decreased while it continued to lengthen. Thus, the elbow joint showed high initial stiffness, which then decreased, and finally became negative. This dynamic relation between length and tension was very different from the static length-tension characteristic of skeletal muscles. The observed behaviour of the muscles presumably takes advantage of the resistance of the musculo-skeletal system to transient forces. The observed negative stiffness occurs only during submaximal contractions. We propose that the segmented pattern in the e.m.g. produces submaximal contractions in both slow and fast fibres in spite of a high excitatory drive.

Animals↗
PubMed1990

Activation of programmed cell death (apoptosis) by cisplatin, other anticancer drugs, toxins and hyperthermia.

Cell death induced by cisplatin was studied in Chinese hamster ovary cell lines, one proficient and the other deficient (100-fold sensitive) in DNA excision repair. Previous experiments demonstrated that cells progressed to and arrested in the G2 phase of the cell cycle before dying. DNA double-strand breaks were detected following G2 arrest and prior to loss of membrane integrity. These DNA breaks have been studied in more detail. DNA fragments were observed consisting of multimers of approximately 180 base pairs. These fragments are consistent with internucleosomal cleavage of chromatin by an endonuclease. At LC90 concentrations, DNA digestion began 48 hr cisplatin treatment followed by loss of membrane integrity and cell shrinkage 24 hr later. High concentrations of cisplatin (170 logs of kill) induced DNA digestion 12 hr after drug treatment but loss of membrane integrity occurred 12 hr later. Both cell death and DNA fragmentation were inhibited by cycloheximide, suggesting the requirement for new protein synthesis. Cells incubated with many other agents demonstrated the same characteristic pattern of DNA degradation. At 90% lethal conditions, DNA digestion was induced within 30 min by hyperthermia, 18 hr by methotrexate, and 48-72 hr by all other agents tested. DNA digestion always preceded loss of membrane integrity and cell shrinkage. These observations are consistent with cell death occurring by the process of apoptosis, or prorammed cell death, and demonstrate the importance of DNA digestion as an early and presumably essential step in cell death. The results suggest that, irrespective of the primary site of action of a drug, cell death by most pharmacologic agents is mediated by activation of the signal transduction pathway for apoptosis. The results also suggest two signal pathways for apoptosis, one directly associated with drug action and a second that requires cell cycle-related events.

Animals↗