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Determination of functional aerobic capacity using the microcomputer.

The general interest in the application of exercise testing to evaluate the work capacity or change in the functional ability of individuals has resulted in the development of a variety of non-invasive tests and test protocols such as the Bruce Treadmill Protocol. This paper presents a computer program written in BASIC that determines an individuals functional work capacity and functional age from minutes completed during a Bruce Treadmill incremental exercise test. Results are summarized in tabular as well as graphical format. The use of the Bruce Treadmill protocol in conjunction with this computer program provides another means of efficiently determining the exercise capability and functional status of a patient.

Computer Systems↗

p53-dependent apoptosis modulates the cytotoxicity of anticancer agents.

Although the primary cellular targets of many anticancer agents have been identified, less is known about the processes leading to the selective cell death of cancer cells or the molecular basis of drug resistance. p53-deficient mouse embryonic fibroblasts were used to examine systematically the requirement for p53 in cellular sensitivity and resistance to a diverse group of anticancer agents. These results demonstrate that an oncogene, specifically the adenovirus E1A gene, can sensitize fibroblasts to apoptosis induced by ionizing radiation, 5-fluorouracil, etoposide, and adriamycin. Furthermore, the p53 tumor suppressor is required for efficient execution of the death program. These data reinforce the notion that the cytotoxic action of many anticancer agents involves processes subsequent to the interaction between drug and cellular target and indicate that divergent stimuli can activate a common cell death program. Consequently, the involvement of p53 in the apoptotic response suggests a mechanism whereby tumor cells can acquire cross-resistance to anticancer agents.

Adenovirus E1A Proteins↗

Regulation of estrous cycles in dairy cattle: A review.

Artificial insemination has allowed rapid genetic progress in dairy cattle through the use of semen from genetically superior sires. Detection of estrus and proper timing of insemination remain as major problems limiting reproductive efficiency in dairy herds. Numerous programs for regulating estrous cycles have been examined in this review. While several programs appear promising, results remain variable and the need for accurate detection of estrus has not been eliminated. Nulliparous heifers seem to respond more consistently than lactating cows. Further research is required to develop a successful program that will consistently produce a precise synchrony of estrus and ovulation with normal fertility and be cost effective.

Journal Article↗

A comparison of two radiological path length algorithms.

Most radiation therapy dose calculation methods require the determination of the effective path length of the primary radiation from the radiation source to the point at which the dose is calculated. This usually involves representing the patient anatomy as a set of polygons (contours) as approximations to plane curves. Several algorithms are known for determining the length of a segment or segments on a ray through a planar contour, that are interior to the contour. We have implemented two of these algorithms in a test program to benchmark their relative efficiency. One algorithm uses a linear search over all the contour segments, and the other method represents the contour as a binary tree of "strips," of successively increasing resolution. In general, the tree search should give times proportional to log(n) where n is the number of contour segments, and the linear search time should be proportional to n. Thus, one might expect the tree search to run faster once the number of segments reaches some sufficiently large value. We found that this value is a number of contour points far in excess of that typical for contours representing radiation therapy patient anatomy. Therefore, for this application the linear search method is more efficient.

Algorithms↗

The influence of dose constraint point placement on optimized radiation therapy treatment planning.

To efficiently use linear and quadratic programming for treatment planning optimization on a routine basis, automated methods are needed for placing dose constraint points. We have investigated, for linear programming optimization, the minimum number of constraint points needed to achieve an acceptable approximation to the desired (ideal) solution. Seven different constraint point placement algorithms were evaluated for a given objective function. One of these algorithms was chosen for routine clinical use at our institution. This algorithm places constraint points on the perimeter of the target volume and on the perimeter and in the interior of each normal structure. Additional points are placed on the perimeter of a constant thickness buffer region surrounding the target volume. Excellent optimization results are obtained with 40-70 constraint points per treatment planning slice.

Computer Simulation↗

Do neuroleptics impair learning in schizophrenic patients?

Dopamine (DA) has been shown to be involved in reward-related (incentive) learning but not stimulus-stimulus (s-s) associative learning. Schizophrenic individuals receive neuroleptics (DA receptor blockers) for therapy and therefore may have impaired incentive learning. To test this hypothesis, in experiment 1, schizophrenic outpatients receiving haloperidol or flupenthixol and matched controls were tested on tasks involving incentive or s-s learning. Patients were also given the Brief Psychiatric Rating Scale (BPRS). Results showed the patients to be significantly impaired in every task. However, only impairments of s-s learning were correlated with psychiatric state. Thus, deficits on the tasks involving incentive learning were interpreted as resulting from neuroleptic drugs rather than psychiatric state. Experiment 2 tested 26 schizophrenic inpatients receiving a variety of neuroleptics (converted to chloropromazine equivalency (CPZEQ)) on the same tasks. A blood sample was collected from the patients and from age-matched controls and prolactin levels were found to be significantly higher in the patients. Multiple regression analysis was used on patient data to determine whether prolactin level or CPZEQ were related to performance. It was found that incentive learning but not s-s associative learning was significantly predicted by one of these two indexes of neuroleptic drug dose. The results of these experiments provide some support for the hypothesis that neuroleptics might impair incentive but not s-s associative learning in schizophrenics. The observation that neuroleptics affect human incentive learning might lead to more efficient use of behavior modification programs in the treatment of schizophrenia.

Adult↗

Assessing the status of infection control programs in small rural hospitals in the western United States.

BACKGROUND: Organized infection control (IC) interventions have been successful in reducing the acquisition of hospital-associated infections. Rural community hospitals, although contributing significantly to the US health care system, have rarely been assessed regarding the nature and quality of their IC programs. METHODS: A sample of 77 small rural hospitals in Idaho, Nevada, Utah, and eastern Washington completed a written survey in 2000 regarding IC staffing, infrastructure support, surveillance of nosocomial infections, and IC policies and practices. RESULTS: Almost all hospitals (65 of 67, 97%) had one infection control practitioner (ICP), and 29 of 61 hospitals (47.5%) reported a designated physician with IC oversight. Most ICPs (62 of 64, 96.9%) were also employed for other activities outside of IC. The median number of ICP hours per week for IC activities was 10 (1-40), equating to a median of 1.56 (0.30-21.9) full-time ICPs per 250 hospital beds. Most hospitals performed total house surveillance for nosocomial infections (66 of 73, 90.4%) utilizing Centers for Disease Control and Prevention (CDC) definitions (69 of 74, 93.2%). Most also monitored employee bloodborne exposures (69 of 73, 94.5%). All hospitals had a written bloodborne pathogen exposure plan and isolation policies. CDC guidelines were typically followed when developing IC policies. Access to medical literature and online resources appeared to be limited for many ICPs. CONCLUSIONS: Most rural hospitals surveyed have expended reasonable resources to develop IC programs that are patterned after those seen in larger hospitals and conform to recommendations of consensus expert panels. Given these hospitals' small patient census, short length of stay, and low infection rates, further studies are needed to evaluate necessary components of effective IC programs in these settings that efficiently utilize limited resources without compromising patient care.

Centers for Disease Control and Prevention, U.S.↗

Consideration of age at admission for selective screening to identify methicillin-resistant Staphylococcus aureus carriers to control dissemination in a medical ward.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly important pathogen responsible for hospital-acquired infections. Our study was to evaluate the efficiency of our selective screening program for methicillin-resistant Staphylococcus aureus (MRSA) carriers at admission to nonintensive care units. METHODS: During 6 months, all patients were screened at admission to an internal medicine ward, at which time they were classified as patients at risk of carriage (PRC) and those with no known risk factor. The amplitude of cross transmission was estimated using various indicators during this universal screening period and during the same calendar period of the preceding year (selective screening). RESULTS: The prevalence of MRSA carriage at admission was 5.5%. Among the 22 carriers identified, only 10 were PRC. Age >80 years was significantly associated with MRSA carriage upon admission (OR, 3.5; P < .01). All estimation indicators of MRSA dissemination amplitude were significantly lower during universal screening (relative risks varied from 2.79 to 26.4 according to indicators), demonstrating the need to broaden our criteria defining PRC. CONCLUSION: Adding patients >80 years of age to our PRC definition would increase screening sensitivity (15 carriers identified for 128 patients sampled) and would enable early implementation of barrier precautions for the additional carriers identified.

Age Factors↗

The use of hormonal treatments to improve reproductive performance of anestrous beef cattle in tropical climates.

Most of the world's bovine herd is found in tropical regions. Bos indicus predominates, due to their adaptation to the climate and management conditions. Anestrous is the main factor that negatively affects reproductive performance of animals bred in these regions of the globe. Several factors affect postpartum anestrous, including suckling and maternal-offspring bond, and pre- and postpartum nutritional status. The short duration of estrus and the tendency to show estrus during the night, greatly affect the efficiency of artificial insemination (AI) programs in B. indicus cattle managed in tropical areas. Several restricted suckling or weaning procedures (temporary or permanent), and hormonal treatments have been used to induce ovulation and cyclicity in postpartum cows. Most hormonal treatments are based on progesterone/progestogen (P4) releasing devices associated with estradiol benzoate (EB), or a combination of GnRH/PGF(2alpha)/GnRH (Ovsynch). Treatments with GnRH/PGF(2alpha)/GnRH has presented inconsistent results, probably due to the variable number of cows in anestrous. Treatments using P4 devices and EB have resulted in apparently more consistent results than Ovsynch programs in B. indicus cattle; however, pregnancy rates are low in herds presenting high anestrous rates and moderate to low body condition. The addition of an eCG treatment at the time of device removal, which increased plasma progesterone concentrations and pregnancy rates in anestrous postpartum suckled B. indicus cows, may be useful to improve reproductive performance of beef cattle in tropical climates.

Anestrus↗

Blood management: issues and options.

Blood management in the perioperative period of the total joint arthroplasty procedure has evolved over the last 3 decades. Strategies have changed and are changing based on a better understanding of blood loss and blood replacement options in this patient population. Patient-specific options based on preoperative hemoglobin levels and patient comorbidities as well as anticipated blood loss have been developed and studied. Patient-specific blood management programs have provided cost-efficient care with low morbidity.

Algorithms↗

A randomized controlled trial of an internet-based treatment for chronic headache.

Chronic headache is a significant public health problem in Western nations. Although controlled trials demonstrate the efficacy and cost-effectiveness of face-to-face behavioral therapy, most headache sufferers have limited access to these treatments. Delivery of behavioral interventions using Internet technology has the potential to reach a larger number of headache sufferers and reduce the burden of disease. This randomized controlled study evaluated an Internet-delivered behavioral regimen composed of progressive relaxation, limited biofeedback with autogenic training, and stress management versus a symptom monitoring waitlist control. Treatment led to a significantly greater decrease in headache activity than symptom monitoring alone. Thirty-nine percent of treated individuals showed clinically significant improvement on self-report measures of headache symptoms at post-treatment. At two-month follow-up, 47% of participants maintained improvement. Treatment had a significant impact on general headache symptoms and headache-related disability. There was a 35% within-group reduction of medication usage among the treated subjects. The Internet program was more time-efficient than traditional clinical treatment. Treatment and follow-up dropout rates, 38.1% and 64.8%, respectively, were typical of behavioral self-help studies. This approach to self-management of headache is promising; however, several methodological and ethical challenges need to be addressed.

Adult↗

Long-term persistence of a nonintegrated lentiviral vector in mouse hematopoietic stem cells.

OBJECTIVE: Lentiviral transduction is an established method for efficiently modifying the gene expression program of primary cells, but the ability of the introduced construct to persist as an episome has not been well studied. MATERIAL AND METHODS: Here we investigated this issue in lethally irradiated female mice injected with 300 or 3000 doubly sorted male lin(neg), Sca-1(high), c-kit(high), Thy-1.1(low) mouse bone marrow cells that had been exposed in vitro to self-inactivating lentivirus vector encoding a green fluorescence protein (GFP) cDNA. Seven to sixteen months later, bone marrow cells from primary mice were injected into secondary female recipients and another 8 months later into tertiary female recipients. Integration study was performed on individual spleen colonies by Southern blot analysis. Inverse polymerase chain reaction (PCR) and sequence of amplified vector-derived DNA was used to verify Southern blot results. RESULTS: Spleen colony-forming cell study revealed that a small fraction of the spleen colonies contained integrated provirus as shown by Southern blot analysis. Unexpectedly, many spleen colonies were found to contain a nonintegrated episomal form of the provirus, which was confirmed by an inverse PCR analysis. In some of the spleen colonies containing only the episomal form, GFP-expressing cells were also detected. Lentiviral sequences were present in hematopoietic tissues of primary mice but not in other tissues. CONCLUSIONS: These results demonstrate that lentiviral vectors produce episomal circles in hematopoietic stem cells that can be transferred through many cell generations and expressed in their progeny.

Animals↗

Rendering of quantum topological atoms and bonds.

In this article, we describe and apply an algorithm that visualizes atoms and bonds in molecules and van der Waals complexes, based on the topology of the electron density. The theory of quantum chemical topology defines both atoms and bonds via a single consistent procedure, and enables the association of an atomic shape with an atomic property (charge, dipole moment, volume, ...). Special attention is paid to the bridging of gaps arising in interatomic surfaces, in the presence of ring critical points or high ellipticity. This algorithm, in conjunction with the graphical user interface of the computer program MORPHY enables robust and efficient rendering of complicated interatomic surfaces, as found in larger systems.

Adamantane↗

Cues for apoptotic cell engulfment: eat-me, don't eat-me and come-get-me signals.

Efficient elimination of cells undergoing programmed cell death is crucial for normal tissue homeostasis and for the regulation of immune responses. This review examines unique signals presented by apoptotic cells and the mechanisms by which phagocytes recognize and respond to these signals to orchestrate the selective and rapid removal of apoptotic cells. Such unique signals include direct and indirect 'eat-me' markers on the apoptotic cell surface, the absence of 'don't eat-me' markers normally found on living cells and soluble 'come-get-me' signals secreted by apoptotic cells to attract phagocytes to sites of apoptotic cell death. Once apoptotic cells are identified, their uptake by phagocytes further depends on the molecular machinery highly conserved from Caenorhabditis elegans to mammals.

Animals↗

The generation and persistence of genetic variation in foot-and-mouth disease virus.

Genetic variation in foot-and-mouth disease virus (FMDV) is of interest for at least two reasons. First, changes to the genes encoding capsid proteins results in antigenic variation, and affects vaccine efficiency and effectiveness of vaccination programs; second, genetic changes can lead to important insights into the transport of virus between countries, regions, herds, and even possibly individuals. Current estimates of RNA virus mutation rates suggest that an average of about one base mis-incorporation is likely to occur each time a single FMDV genome replicates. This should result in the introduction of every possible 1-step mutation from the progenitor genotype into the viraemia of a single infected animal many times a day. In the absence of purifying selection, a single infected animal should therefore generate a genetically very diverse population of virus.Viral-capsid sequences obtained from infected animals sampled over long-term FMDV epidemics suggest that these genetic changes accrue in a remarkably linear 'clock-like' fashion and at rates of around 1% change per year. While such a rate is generally regarded as quite high, it is actually somewhat lower than one might expect based on the rate at which viral diversity could be generated within a single animal. The difference might be explained in a variety of possible ways: (1) the mutation rate has been overestimated; (2) purifying selection is stronger than predicted; (3) only a restricted subset of excreted virus is actually infectious; (4) infected animals only excrete virus from a small partitioned subset of amplified virus, and that most of the generated viral diversity is unable to exit the animal; or (5) only a small fraction of all infected animals participate in the actual disease-transmission process.

Animals↗

Health status and work burden of Alzheimer patients' informal caregivers: comparisons of five different care programs in the European Union.

BACKGROUND: In 1998, a research study was conducted to compare existing programs in the European Union providing both care to people with senile dementia of the Alzheimer type, and support to their informal caregiver. METHOD: Five programs were selected in seven centres. Home social services (Denmark), Day centres (Germany), Expert Centres (Belgium, Spain), Group Living/Cantou (Sweden, France), Respite hospitalization (France). In each centre, 50 patients were randomly selected. The questionnaire addressed informal caregivers (or referents). It included the Nottingham Health Profile (NHP), the Zarit Scale, and it collected data on age, sex and position (spouse or child) of the informal caregiver, as well as age, level of mental deterioration and disabilities of the patient. RESULTS: (n=322 subjects) Comparatively with caregivers of Respite hospitalization patients chosen as the reference, caregivers of patients cared by Group living/Cantou and Home social services experienced a significantly lower burden. The benefit from the Expert centre program concerned emotional reactions (depression) (odds ratio=0.32; P=0.02) and work burden (Zarit) (OR=0.32; P=0.04). The main benefit for caregivers who received Day centre help was the important reduction of feelings of social isolation (OR=0.13; P=0.0003). CONCLUSIONS: The Group Living/Cantou program appeared as the most efficient way to reduce informal caregiver burden, independently from the country considered.

Aged↗

Fertility estimation: a review of past experience and future prospects.

Fertility has many components and stages which require that males and females be functionally capable of carrying out all critical stages if each generational reproductive cycle is to be completed. To accomplish this, the male must produce and ejaculate normal fertile sperm. The female must produce, store and ovulate normal fertilizable oocytes. Furthermore, the female must provide a reproductive system compatible with sperm transport, capacitation, and fertilization of the oocytes, embryo and fetal development, and finally birth of healthy young. Reproductive success or failure at several of these points can be estimated quantitatively on a population basis, and in a few situations on an individual basis. It is important that fertility estimates be determined accurately and with precision to be most useful to researchers and managers of animal enterprises. Many studies have underestimated the biological relationship of fertility to other traits because the estimates lacked precision. Many in vitro manipulations of sperm in artificial insemination, of gametes in various assisted reproductive technologies, and of embryos in embryo transfer are utilized in animal breeding programs. Accurate estimation of reproductive efficiency of these in vitro procedures also is important. Conditions surrounding different sets of fertility estimates almost certainly will be different. These conditions should be described as precisely as possible, and appropriate controls included in all experiments. When possible, experiments should be replicated over time and place to determine the repeatability of the various criteria used to estimate fertility and reproductive efficiency. Advances in genomic information and molecular biology should facilitate characterizing more fully inherent potential fertility of animals at birth. In vitro tests will improve, and automated techniques will facilitate making multiple determinations possible on a large scale. Reliability of fertility estimates will increase, with the potential for enhanced animal reproductive performance through more accurate selection, genetic engineering, and enlightened animal care. Simultaneously, it is important to recognize that prediction of future fertility is more hazardous than estimating fertility, as a completely new set of circumstances may occur which are not predictable. Because fertility estimation may be applied under a myriad of conditions, principles and factors affecting fertility will be emphasized in this review as being more useful than a compilation of numerical examples.

Animals↗

Microglia promote the death of developing Purkinje cells.

The loss of neuronal cells, a prominent event in the development of the nervous system, involves regulated triggering of programmed cell death, followed by efficient removal of cell corpses. Professional phagocytes, such as microglia, contribute to the elimination of dead cells. Here we provide evidence that, in addition to their phagocytic activity, microglia promote the death of developing neurons engaged in synaptogenesis. In the developing mouse cerebellum, Purkinje cells die, and 60% of these neurons that already expressed activated caspase-3 were engulfed or contacted by spreading processes emitted by microglial cells. Apoptosis of Purkinje cells in cerebellar slices was strongly reduced by selective elimination of microglia. Superoxide ions produced by microglial respiratory bursts played a major role in this Purkinje cell death. Our study illustrates a mammalian form of engulfment-promoted cell death that links the execution of neuron death to the scavenging of dead cells.

Animals↗