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Coronal and sagittal balance in surgically treated adolescent idiopathic scoliosis with the King II curve pattern. A review of 67 consecutive cases having selective thoracic arthrodesis.

STUDY DESIGN: A retrospective study by an independent observer of a consecutive series of 67 cases of adolescent idiopathic scoliosis presenting with a King II curve pattern. OBJECTIVES: To demonstrate the validity of a selective thoracic fusion as a treatment of King II curves with special attention to immediate postoperative and long-term trunk balance in the coronal and sagittal planes. SUMMARY OF THE BACKGROUND DATA: The literature has been fairly controversial in terms of the recommended treatment of King II curve patterns in adolescent idiopathic scoliosis. The main confusion appears to be whether the thoracic curve alone or both curves should be instrumented and fused. METHODS: Sixty-seven patients were identified as having had a selective posterior thoracic spine fusion with instrumentation between 1961 and 1994. None of these cases had a fusion of the lumbar spine. Preoperative radiographs were analyzed for determination of the appropriate fusion level using the criteria of the stable and neutral vertebra. Follow-up radiographs were evaluated for balance in the coronal and sagittal planes using the central sacral line on posteroanterior radiograph and the C7 sacral promontory line on lateral film. RESULTS: At 2-year or greater follow-up, the unfused lumbar curve remained equal to or less than the corrected thoracic curve in 63 patients (94%). No patient required extension of fusion. Frontal plane balance analysis showed that 47 of the 67 patients had the T1 plumb line within 2 cm of the midline for an average decompensation of 8.7 mm. In no patient was the loss of balance greater than 3.8 cm. Sagittal plane balance analysis showed that only one patient had inferior junctional kyphosis greater than 10 degrees. This did not require extension of fusion. There were no cases of superior junctional kyphosis. CONCLUSIONS: The concept of selective thoracic fusion in the King II curve pattern appears to be valid. These findings suggest that arthrodesis of the lumbar spine can be avoided when this pattern is properly diagnosed and appropriately treated. Proper identification of the stable and neutral vertebra and of the appropriate level of fusion are important to achieve good postoperative balance. Successful preservation of lumbar motion segments is important to long-term satisfactory outcome in adolescent idiopathic scoliosis.

Adolescent↗

Application of visual signal detection concepts to clinical decision analysis.

The performance of both clinical diagnostic and mass screening tests is commonly measured in terms of the two basic parameters, sensitivity and specificity. Selection of cut-off points, balancing the sensitivity-specificity trade-off, and comparison with alternative tests are often a matter of arbitrary decisions and are frequently made without consideration of outcome. Some of the concepts used in the analysis of visual signal detection systems can be helpful in this aspect of screening test selection and evaluation. A simplified version of these concepts is developed and its application to clinical and public health optometry is illustrated.

Cost-Benefit Analysis↗

Use of gene expression microarrays for evaluating environmental stress tolerance at the cellular level in cattle.

Selecting domestic animals for tolerance to thermal stress (TS) has been counterproductive, because acclimation involves reducing or diverting metabolizable energy from production to balance heat gain and loss. Ideally, simultaneous selection for increased production and improved thermotolerance is desirable, but to accomplish this at the genomic level the genes associated with acclimation, adaptation, and thermo-tolerance need to be identified. We evaluated the effects of TS on mammary development and gene expression in vitro using a bovine mammary epithelial cell collagen gel culture system. Acute TS was characterized by inhibition and regression of the ductal branches. Gene expression profiling revealed an overall upregulation of genes associated with the stress response and protein repair. In contrast, genes associated with cellular and mammary epithelial cell-specific biosynthesis, metabolism, and morphogenesis were generally downregulated by TS. Future studies will examine the impact of acclimation and adaptation on gene expression to identify those genes associated with acquisition of thermal tolerance.

Animals↗

Population evolution on a multiplicative single-peak fitness landscape.

A theory for evolution of either gene sequences or molecular sequences must take into account that a population consists of a finite number of individuals with related sequences. Such a population will not behave in the deterministic way expected for an infinite population, nor will it behave as in adaptive walk models, where the whole of the population is represented by a single sequence. Here we study a model for evolution of population in a fitness landscape with a single fitness peak. This landscape is simple enough for finite size population effects to be studied in detail. Each of the N individuals in the population is represented by a sequence of L genes which may either be advantageous or disadvantageous. The fitness of an individual with k disadvantageous genes is Wk = (1-s)k, where s determines the strength of selection. In the limit L-->infinity, the model reduces to the problem of Muller's Ratchet: the population moves away from the fitness peak at a constant rate due to the accumulation of disadvantageous mutations. For finite length sequences, a population placed initially at the fitness peak will evolve away from the peak until a balance is reached between mutation and selection. From then on the population will wander through a spherical shell in sequence space at a constant mean Hamming distance from the optimum sequence. We give an approximate theory for the way depends on N, L, s, and the mutation rate u. This is found to agree well with numerical simulation. Selection is less effective on small populations, so increases as N decreases. Our simulations also show that the mean overlap between gene sequences separated by a time of t generations is of the form Q(t) = Q infinity + (Q0-Q infinity)exp(-2ut), which means that the rate of evolution within the spherical shell is independent of the selection strength. We give a simplified model which can be solved exactly for which Q(t) has precisely this form. We then consider the limit L-->infinity keeping U = uL constant. We suppose that each mutation may be favourable with probability p, or unfavourable with probability 1-p. We show that for p less than a critical value pc, the population decreases in fitness for all values of U, whereas for pc < p < 1/2, the population increases in fitness for small U and decreases in fitness for large U. In this case there is an optimum non-zero value of U at which the fitness increases most rapidly, and natural selection will favour species with non-zero mutation rates.

Animals↗

Static balance and developmental coordination disorder.

The development of static balance is a basic characteristic of normal motor development. Most of the developmental motor tests include a measure of static balance. Children with a developmental coordination disorder (DCD) often fail this item. Twenty-four children at risk for DCD with balance problems (DCD-BP) and 24 matched control children in the age range of 6-12 years participated in a detailed study of balance control. Additional groups of children (6-7 years, N=25; 10-11 years, n=16; with M-ABC scores >15th percentile) were selected randomly to study developmental changes in balance control in the age range of interest. Three experiments were conducted to examine developmental and clinical differences in the control of static balance. In the first, we measured the excursion of the centre of pressure (force-plate) in conditions with and without vision while standing still on one or two legs for 20 s. In the second experiment, EMGs were measured while standing on one leg. In the third experiment, in which only a subgroup of the DCD-BP and matched control children participated, a short unexpected force in the back lightly perturbed normal standing and EMG and force-plate responses were measured during balance recovery. In conditions of one-leg stance, children were not always able to maintain balance. Only epochs of stable postural control (7.5-20 s) were analysed. The results showed improvement of static balance with age, but only subtle differences between the DCD and control groups. Centre of pressure measures differed in the more difficult conditions. DCD-BP children had more difficulty standing on one leg with eyes closed. While standing on the non-preferred leg the EMGs of the DCD-BP children showed slightly more co-activation of the muscles of lower and upper leg. Perturbation of standing resulted in longer duration of recovery in the first trial in this group. Apparently DCD children learn to compensate for the perturbation within a few trials as well as control children do. The clear improvement with age shows that our measures of balance control are sensitive to detect changes. The general conclusion that may be drawn from this study is that under normal conditions static balance control is not a problem for children with DCD. Only in difficult or novel situations they seem to suffer from increased postural sway as a result of non-optimal balance control.

Child↗

Balance control in the elderly: implications for clinical assessment and rehabilitation.

Deterioration of balance control system with age results in a higher incidence of falls. To assess the performance of the balance control system we need to select appropriate body posture and/or motion, decide on the type and level of perturbation and study the response using selected measures. The guidelines we should use to determine the task, perturbation and measures is the focus of this article. Our work on the elderly is used to provide support for the various criteria put forward. The tasks evaluated for stability should include specific postures and movements which are part of the normal repertoire and challenge the balance control system. Variety of perturbations are necessary to get insights into the working of the system. The level of perturbation that can be handled should be specified. The response measures should be able to identify deterioration in the system performance, provide diagnostic information and insights into how the system has adapted to the age-related changes. These guidelines are critical if balance tests are to be used for clinical assessment and rehabilitation.

Aged↗

Sequential feeding of whole wheat to growing broiler chickens.

1. Four broiler feeding trials were performed to examine the suitability of a whole wheat sequential feeding regimen for commercial broiler production. The sequential feeding programme gave a continuous cycle of ad libitum access to only whole wheat followed by the same time of access to only a pelleted diet. The pelleted diet provided a concentration of nutrients to balance that provided by the whole wheat. This was called a balancer diet. 2. The first trial used 144 cage-reared broilers from 28 to 49 d of age. Four different times of access (4, 8, 12 and 24 h) to the two alternate foods were compared. A whole wheat choice-feeding treatment and a complete single diet treatment were also compared. Whole wheat accounted for over 40% of the broilers' total food intakes when they were given the sequential feeding treatments of 8 h or greater. The whole wheat intakes of the birds given the 4 h sequential feeding and the choice-feeding were only 20 and 5% respectively. There was a non linear relationship between the weight gains of the broilers and the length of the sequential feeding period (P < 0.01). The growth rates of the broilers given sequential feeding were lowest (P < 0.05) in the 4-h feeding periods but highest (P < 0.05) in the 8-h periods. Weight gains decreased (P < 0.01) linearly as the sequential feeding periods were increased above 8 h. 3. A second trial, using 144 cage-reared broilers, examined the effect of different balancer compositions or different wheat varieties in 8-h sequential feeding. The broilers selected more whole wheat in their diet when they were given balancers with increased cereal contents. However, these broilers did not eat enough whole wheat to compensate for the reduced cereal content of the balancers and their overall diets had lower energy:protein ratios. The two different wheat samples did not result in any differences (P > 0.05) in the proportion of whole wheat selected by the broilers. 4. A third trial compared the diet selections, weight gains, food intakes and water excretions of 72 cage-reared broilers given whole wheat feeding regimens. The growth rates of the broilers given a loose mix of whole wheat and a pelleted balancer diet were similar (P > 0.05) to broilers given a complete single diet. The growth rates of these two groups were 7% greater (P < 0.05) than broilers given choice-feeding or 8-h sequential feeding.(ABSTRACT TRUNCATED AT 400 WORDS)

Animal Feed↗

Dopamine-1 and dopamine-2 mechanisms in the control of renal function.

Dopamine (DA), a catecholamine produced in the kidney, is a renal vasodilator and natriuretic substance, but its action at dopamine-1 (DA-1), dopamine-2 (DA-2) and alpha- and beta-adrenergic receptors limits its effectiveness as a heuristic tool and pharmacologic agent. We have studied the effects of highly selective DA-1 and DA-2 receptor agonists and antagonists in normal human subjects and experimental animals to determine the precise physiological role of renal dopamine at DA-1 and DA-2 receptors within the kidney. We studied fenoldopam, a selective DA-1 agonist, in normal human subjects in metabolic balances at high (300 mEq/day) and low (10 mEq/day) sodium (Na) intake. Selective DA-1 receptor stimulation during high Na intake resulted in renal vasodilation, natriuresis and diuresis in a sustained manner for 3 hours. The natriuresis was mediated by a reduction in Na reabsorption at both proximal and distal tubular sites. In contrast, during low Na intake, DA-1 receptor stimulation did not engender a natriuretic or diuretic response. Thus, sodium depletion may inhibit the function of renal tubular cells in response to DA-1 stimulation. DA-1 receptors are present in the medial layer of the renal vasculature, proximal tubule and cortical collecting duct; DA-2 receptors are localized to the glomerulus, the renal nerves surrounding renal blood vessels and possibly the renal vascular endothelium. We have performed studies in conscious dogs with indwelling renal arterial catheters to identify the physiological role of renal DA to DA-1 and DA-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Interchromosomal biased gene conversion, mutation and selection in a multigene family.

A mathematical model of the effects of interchromosomal biased gene conversion, mutation and natural selection on a multigene family is developed and analyzed. The model assumes two allelic states at each of n loci. The effects of genetic drift are ignored. The model is developed under the assumption of no recombination, but the analysis shows that, at equilibrium, there is no linkage disequilibrium, which implies that the conclusions are valid for arbitrary recombination among loci. At equilibrium, the balance between mutation, gene conversion and selection depends on the ratio of the mutation rates to the quantity [s + g(2 alpha - 1)/n], where s is the increment or decrement in relative fitness with each additional copy of one of the alleles, g is the conversion rate, and alpha is a measure of the bias in favor of one of the alleles. When this quantity is large relative to the mutation rates, the allele that has the net advantage, combining the effects of selection and conversion, will be nearly fixed in the multigene family. A comparison of these results with those from a comparable model of intrachromosomal biased conversion shows that biased interchromosomal conversion leads to approximately the same equilibrium copy number as does intrachromosomal conversion of the same strength. Interchromosomal conversion is much more effective in causing the substitution of one allele by another. The relative frequencies of interchromosomal and intrachromosomal conversion is indicated by the extent of the linkage disequilibrium among the loci in a multigene family.

Alleles↗

Processing of second-order motion stimuli in primate middle temporal area and medial superior temporal area.

Two rhesus monkeys were subjects in a direction-discrimination task involving moving stimuli defined by either first- or second-order motion. Two different second-order motion stimuli were used: drift-balanced motion consisting of a rectangular field of stationary dots and theta motion consisting of the same rectangular field with dots moving in the direction opposite to that of the object. The two types of stimuli involved different segmentation cues between the moving object and the background: temporal structure of the luminance (flicker) in the case of drift-balanced motion and opposed motion in the case of the theta-motion stimulus. Our monkeys were able to correctly report the direction of each stimulus. Single-unit recordings from the middle temporal (MT) and medial superior temporal (MST) areas revealed that 16 out of 38 neurons (41%) from area MT and 34 out of 68 neurons (50%) from area MST responded in a directionally selective manner to the drift-balanced stimulus. The movement of an object defined by theta motion is not explicitly encoded in the neuronal activity in areas MT or MST. Our results do not support the hypothesis that the neuronal activity in these areas codes for the direction of stimulus movement independent of specific stimulus parameters. Furthermore, our results emphasize the relevance of different segmentation cues between figure and background. Therefore the notion that there are multiple sites responsible for the processing of second-order motion is strongly supported.

Animals↗

A review of balance instruments for older adults.

OBJECTIVE: The purpose of this article is to review balance instruments developed within the past 10 years that can be used in the clinic or home environment. The use of such instruments may assist in identifying older adults who are at risk for falling, a major problem that can result in impaired function and loss of independence. METHOD: Six instruments were reviewed: the Berg Balance Scale (Berg), the Clinical Test of Sensory Interaction and Balance (CTSIB), the Functional Reach Test, the Tinetti Balance Test of the Performance-Oriented Assessment of Mobility Problems (Tinetti), the Timed "Up and Go" Test (TU&GT), and the Physical Performance Test (PPT). Considered were what aspects of balance are assessed, time needed to administer the instrument, tools or equipment needed, evidence of reliability and validity, advantages and disadvantages, and the target population. RESULTS: The Berg, Tinetti, and PPT measure a variety of aspects of balance, whereas the Functional Reach, TU&GT, and CTSIB measure more narrow aspects of balance. All six instruments have been used with older adults and do not require much equipment. The instruments differ in their reliability and validity. CONCLUSION: Familiarity with balance instruments can be helpful in selecting the one most appropriate for clinical setting and clients in order to institute appropriate prevention programs, such as environmental modifications and lifestyle adaptations.

Accidental Falls↗

Trade-off mediated effects on the genetics of human survival caused by increasingly benign living conditions.

It is sometimes suggested that modern life, with its planned fertility and medically assisted compensation for genetic disadvantage, has greatly reduced the power of natural selection to produce significant further human evolution. However, this overlooks the very recent and dramatic changes that have occurred in the patterns of human mortality, driven by the development of increasingly benign living conditions. Where the genetics of survival are significantly influenced by life history trade-offs, as is now thought to be the case for ageing and longevity, a change in the environment can shift the optimal balance that was established through natural selection under previous conditions. We examine this possibility in the context of the dramatic recent change in the mortality pressure exerted by infectious disease using a model of a hypothetical immunogenetic trade-off that weighs survival against fecundity. Our results predict that such a change might have a significant effect on population genetics over relatively short-timescales, and they may also resolve the paradox of genes that impair fertility in present-day populations by showing how such genes might be a legacy from a powerful trade-off that has acted until very recently.

Biological Evolution↗

Visual destabilisation of posture in normal subjects.

A new and simple method of assessing reliance on vision for postural control was evaluated in 41 normal subjects. Left-right reversal of peripheral vision induced by a head-mounted mirror device caused an initial dramatic instability in approximately half the subjects, when standing on foam to reduce the value of proprioception. Lateral reversal of central vision by means of a prism device evoked similar responses. Sensitivity to vision reversal was significantly correlated with motion sickness susceptibility. Despite some rapid habituation (partially retained over several weeks) sway remained as great as with eye closure in the anterior-posterior as well as lateral direction, indicating complete suppression of the visual input. Balancing with vision reversal caused a selective decrement in performance of a visuo-spatial memory task, suggesting that coping with misleading visual input may place continuous demands on cortical spatial processing.

Adult↗

Natural selection and the frequency distributions of "silent" DNA polymorphism in Drosophila.

In Escherichia coli, Saccharomyces cerevisiae, and Drosophila melanogaster, codon bias may be maintained by a balance among mutation pressure, genetic drift, and natural selection favoring translationally superior codons. Under such an evolutionary model, silent mutations fall into two fitness categories: preferred mutations that increase codon bias and unpreferred changes in the opposite direction. This prediction can be tested by comparing the frequency spectra of synonymous changes segregating within populations; natural selection will elevate the frequencies of advantageous mutations relative to that of deleterious changes. The frequency distributions of preferred and unpreferred mutations differ in the predicted direction among 99 alleles of two D. pseudoobscura genes and five alleles of eight D. simulans genes. This result confirms the existence of fitness classes of silent mutations. Maximum likelihood estimates suggest that selection intensity at silent sites is, on average, very weak in both D. pseudoobscura and D. simulans (magnitude of NS approximately 1). Inference of evolutionary processes from within-species sequence variation is often hindered by the assumption of a stationary frequency distribution. This assumption can be avoided when identifying the action of selection and tested when estimating selection intensity.

Animals↗

Inhibition of the self-renewal capacity of blast progenitors from acute myeloblastic leukemia patients by site-selective 8-chloroadenosine 3',5'-cyclic monophosphate.

The physiologic balance between the two regulatory subunit isoforms, RI and RII, of cAMP-dependent protein kinase is disrupted in cancer cells; growth arrest and differentiation of malignant cells can be achieved when the normal ratio of these intracellular signal transducers of cAMP is restored by the use of site-selective cAMP analogs. In this study we evaluated the effects of the site-selective cAMP analog 8-chloroadenosine 3',5'-cyclic monophosphate (8-Cl-cAMP) on clonogenic growth of blast progenitors from 15 patients with acute myeloblastic leukemia and 3 patients affected by advanced myelodysplastic syndrome. Leukemic blast progenitors undergo terminal divisions, giving rise to colonies in methylcellulose. The self-renewal capacity of blast progenitors is conversely reflected in a secondary methylcellulose assay after exponential growth of clonogenic cells in suspension cultures. In all the samples tested, 8-Cl-cAMP, at micromolar concentrations (0.1-50 microM), suppressed in a dose-dependent manner both primary colony formation in methylcellulose and the recovery of clonogenic cells from suspension culture. Strikingly, in the samples from the entire group of patients, 8-Cl-cAMP was more effective in inhibiting the self-renewing clonogenic cells than the terminally dividing blast cells (P = 0.005). In addition, in four out of six cases studied, 8-Cl-cAMP was able to induce a morphologic and/or immunophenotypic maturation of leukemic blasts. An evident reduction of RI levels in fresh leukemic cells after exposure to 8-Cl-cAMP was also detected. Our results showing that 8-Cl-cAMP is a powerful inhibitor of clonogenic growth of leukemic blast progenitors by primarily suppressing their self-renewal capacity indicate that this site-selective cAMP analog represents a promising biological agent for acute myeloblastic leukemia therapy in humans.

8-Bromo Cyclic Adenosine Monophosphate↗

Inhibition of proteasome activity by selected amino acids.

Cellular protein homeostasis is a balance between synthesis and degradation. Protein degradation is regulated by hormones (eg, insulin) and nutrients (eg, amino acids). Certain amino acids are capable of decreasing cellular protein degradation, with evidence that this is mediated through altered lysosomal function. However, proteasomes, the major cytosolic protein degrading machinery, are being shown to play a central role in the control of protein turnover in the cell. In this study we show that the amino acids, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, lysine, and arginine are capable of inhibiting the chymotrypsin-like activity of the proteasome in a dose-dependent manner. Leucine, tyrosine, and phenylalanine have a substantial effect at normal serum concentrations. The effect was greater in a proteasome preparation derived from muscle compared to a similar preparation from liver. On the assumption that amino acid-induced alterations in cellular protein degradation reflect the inhibitory changes in proteasomal activity shown here, we may conclude that amino acid control of cellular protein degradation is mediated, at least in part, through proteasomes.

Amino Acids↗

Quality assurance system must balance functionality with data security.

The evaluation and selection of a QA system should include scrutiny of its security mechanisms. When the system is implemented, evaluate access by all users, establish security policies, and, most importantly, enforce them. Security features should not overburden the system to the point that it becomes cumbersome. As many security features as possible should be inherent in its day-to-day operations. After all, automation is intended to provide access to clinical and financial information easily and quickly. QA professionals must weigh security issues against the need for patient and physician-specific performance information. Finally, include medical staff in the early stages of system implementation so they are aware of the security precautions you have taken. They will be assured that you are protecting confidential information while meeting the needs of both the medical staff and the quality management team.

Confidentiality↗