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Age associated differences in postural equilibrium control: a comparison between EQscore and minimum time to contact (TTC(min)).

Increased postural instability and the subsequent elevation in fall incidence with increasing age are important contributors for hip fractures and developing frailty. When testing for such instability, most studies characterize balance in terms of center-of-mass (COM) deviation from a finite point, the "equilibrium point", located at the center of a subject's stance. For example, the clinically accepted equilibrium score (EQscore) represents instability as the maximum peak-to-peak sway about the "equilibrium point". An alternative theory views balance as being controlled within a "stability margin" in which all corrective actions are based on the time to contact (TTC) of the body's COM with that margin. This study examines the differences offered by evaluating balance control using the EQscore and TTC approach across several age groups and sessions. Consenting subjects from the Baltimore Longitudinal Study of Aging were recruited (N=155) from each age decade (20s-80s) who were generally healthy and free from neurological diagnoses. Results showed TTC tests detected significant variations in eyes open versus eyes closed testing that were unpredictable by EQscore. Further, TTC produced differences in age-related stability threats not seen using EQscore. The TTC data also provided a discriminating difference between subjects who fell in the difficult tests and those who maintained posture. Overall, these data suggest EQscore might not sufficiently account for dynamic control components the body may be using to maintain balance. TTC may offer a more accurate estimate of postural stability (functional ability) than EQscore based on its inclusion of a velocity component to detect dynamic changes.

Accidental Falls↗

Algorithms for articular cartilage repair.

The treatment of cartilage lesions in the knee joint is still controversial. There are many approaches for restoration of diseased cartilage, but no single procedure is universally accepted for each kind of lesion and every patient. The goal of any reconstructive or regenerative procedure is to relieve the symptoms of the cartilage defect and restore joint function. Most current approaches to cartilage repair accomplish this objective. However, it is clear that there is no "gold standard" in the treatment of cartilage defects and the choice of treatment is the key element. The patient with knee joint pain undergoes a detailed history and clinical examination. It is important to evaluate the factors like the nature of the cartilage failure, the joint findings, leg alignment, and muscle balance, as well as patient's activity level, expectations, and ability to follow the rehabilitation regimen. This study sought to create a clinical algorithm for management of diseased articular knee joint cartilage that was suitable for patients with traumatic full-depth lesions.

Adolescent↗

Mechanism of aerobic biological destabilisation of wool scour effluent emulsions.

Wool scouring effluent is a highly polluted industrial wastewater in which the main pollutant, wool wax, is held in a stable oil-in-water emulsion by non-ionic detergent. The use of microbial action to cause emulsion destabilisation has been proposed as a new treatment strategy for this effluent stream. This strategy aims at improving aerobic treatment performance by physically removing the high-COD, slowly bio-degradable wool wax from the system without bio-degradation. The mechanism by which an aerobic-mixed culture destabilises the wool scouring effluent emulsion was investigated. Our results show that destabilisation is due to partial bio-degradation of both the scouring detergent and the wool wax. Cleavage of the wool wax esters was the first stage in wax degradation, when 40-50% of wax was de-emulsified. Over the same period, detergent degradation was low, at 7-21%. With further incubation, detergent degradation increased, aiding further breakdown of the emulsion. The degradation of the detergent, a nonylphenol ethoxylate, resulted in both a reduction in molar concentration (of up to 82%) and a shortening of the ethoxylate chain length. The latter reduced the hydrophile-lipophile balance (HLB) from 12 to approximately 7, thereby reducing the ability of the residual detergent to stabilise the emulsion. Analysis of the emulsified and de-emulsified wax fractions could not identify a group of compounds that were preferentially de-emulsified based on molecular weight or polarity. These findings will assist in using a de-emulsification strategy in both existing and new treatment systems in order to save on aeration costs and treatment times for biological treatment of this highly polluted wastewater.

Animals↗

Modulation of concentration fluctuations in phase-separated lipid membranes by polypeptide insertion.

The lateral membrane organization and phase behavior of the binary lipid mixture DMPC (1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine) - DSPC (1,2-distearoyl-sn-glycero-3-phosphatidylcholine) without and with incorporated gramicidin D (GD) as a model biomembrane polypeptide was studied by small-angle neutron scattering, Fourier-transform infrared spectroscopy, and by two-photon excitation fluorescence microscopy on giant unilamellar vesicles. The small-angle neutron scattering method allows the detection of concentration fluctuations in the range from 1 to 200 nm. Fluorescence microscopy was used for direct visualization of the lateral lipid organization and domain shapes on a micrometer length scale including information of the lipid phase state. In the fluid-gel coexistence region of the pure binary lipid system, large-scale concentration fluctuations appear. Infrared spectral parameters were used to determine the peptide conformation adopted in the different lipid phases. The data show that the structure of the temperature-dependent lipid phases is significantly altered by the insertion of 2 to 5 mol% GD. At temperatures corresponding to the gel-fluid phase coexistence region the concentration fluctuations drastically decrease, and we observe domains in the giant unilamellar vesicles, which mainly disappear by the incorporation of 2 to 5 mol% GD. Further, the lipid matrix has the ability to modulate the conformation of the inserted polypeptide. The balance between double-helical and helical dimer structures of GD depends on the phospholipid chain length and phase state. A large hydrophobic mismatch, such as in gel phase one-component DSPC bilayers, leads to an increase in population of double-helical structures. Using an effective molecular sorting mechanism, a large hydrophobic mismatch can be avoided in the DMPC-DSPC lipid mixture, which leads to significant changes in the heterogeneous lipid structure and in polypeptide conformation.

Anti-Bacterial Agents↗

Modular augments in revision total knee arthroplasty.

Modularity in total knee arthroplasty is extremely helpful in the management of patients with complex primary and revision total knee arthroplasties. Modularity allows selective augmentation to deal with bone deficiencies on the distal and posterior femur. The ability to selectively augment the femur is very helpful in balancing the soft tissues and providing stability. Selective augmentation of the femur allows restoration of the joint line and more normal patellar and collateral ligament kinematics. Selective modular augments on the tibia allow dealing with bone deficiency without the concerns of bone graft incorporation. Modular extended intramedullary stems allow the option of either press-fit or cement fixation of the stem, entailing the stem diameter length to the given patient.

Arthroplasty, Replacement, Knee↗

Complement in Alzheimer's disease: opportunities for modulating protective and pathogenic events.

The complement system is a critical element of the innate immune system recognizing and killing, or targeting for destruction, otherwise pathogenic organisms. In addition to triggering the generation of a membranolytic complex, complement proteins interact with cell surface receptors to promote a local inflammatory response that contributes to the protection and healing of the host. Compelling evidence has been reported that in Alzheimer's Disease complement activation occurs in the brain, and that this contributes to the development of a local inflammatory state that is correlated with cognitive dysfunction. However, recent data suggest that at least some of the complement components have the ability to contribute to neuroprotective pathways. Thus, it is the balance of these seemingly competing events that influences the ultimate state of neuronal function. Knowledge of the unique molecular interactions that occur in the development of Alzheimer's Disease, the functional consequences of those interactions, and the proportional contribution of each element to this disorder, should facilitate the design of effective therapeutic strategies for this disease.

Alzheimer Disease↗

Capturing error rates and reporting significant data.

Programs that embrace sound outcomes, process, and structure assessment complemented by systematic inquiry and improvement serve as protectors of quality during an era of dramatic cost reduction. Outcome data presented alongside process and structural methods enable a clear understanding of quality, balancing the scales between societal cost and individual health. The ability to change a system through the generation and use of powerful data reporting mechanisms takes on increased significance as we strive to improve the safety of US health care. The NQF's work is just the tip of the iceberg; health care organizations must accept the inevitable: Practice standardization and delineation of concrete, nationwide quality benchmarks are the future of US health care.

Benchmarking↗

Peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase. 3. In vitro and in vivo potency of a series of peptidyl alpha-ketobenzoxazoles.

A series of peptidyl alpha-ketobenzoxazoles were synthesized and evaluated for their in vitro and in vivo inhibition of human neutrophil elastase (HNE). These compounds inhibit HNE by forming both a covalent bond between the ketone carbonyl carbon atom and the hydroxyl group of Ser-195 and a hydrogen bond between the benzoxazole nitrogen atom and His-57. Appending to the parent benzoxazole ring a variety of substituents which spanned a range of physicochemical properties had only a modest effect on in vitro potency (Ki = 3-0.4 nM). This apparent lack of a significant effect is believed to result from the fact that any increased ketone carbonyl activation by the ring substituent is counter balanced by a corresponding decrease in the hydrogen-bonding ability of the benzoxazole nitrogen atom. In contrast to the results in vitro, maximizing in vivo activity was critically dependent upon the choice of the benzoxazole ring substituent. Several substituted peptidyl alpha-ketobenzoxazoles effectively inhibited HNE-induced lung injury when administered intratracheally 24 h prior to the enzyme.

Amino Acid Sequence↗

The furoxan system as a useful tool for balancing "hybrids" with mixed alpha 1-antagonist and NO-like vasodilator activities.

The design of new vasodilator derivatives in which two different pharmacophoric groups are present in a single molecule has been pursued by substitution of NO-prodrug furoxan moieties for the furanylcarbonyl function in Prazosin, a well-known alpha 1-receptor antagonist. The aim was to obtain new antihypertensive agents in which two vasodilation mechanisms, alpha 1-antagonist and NO-mediated, can operate in an appropriate balance. The alpha 1-antagonist activity was assessed on rat aortic strips in the presence and in the absence of oxyhemoglobin (HbO2), a well-known scavenger of nitric oxide. The resulting hybrids displayed different pharmacological behaviors. When the 4-furoxanylcarbonyl system, bearing an ester or an amide function at the 3-position, was present (derivatives 7a,b), hybrids with predominant alpha 1-antagonist activity were obtained. By contrast, in the derivative 7c, in which the nitrile function is linked to the 3-position of the furoxan ring, the NO-mediated vasodilating properties are predominant. Finally, the (furoxanylsulfonyl)piperidine derivatives 13a,b showed NO vasodilation and alpha 1-antagonist activities in an appropriate balance. For the furoxan derivatives, the NO-dependent vasodilating ability, assessed on the K(+)-depolarized aortic strip, and the NO release features under the action of thiol cofactors are also discussed.

Adrenergic alpha-Antagonists↗

Modification and ablation for inappropriate sinus tachycardia: current status.

Inappropriate sinus tachycardia is an ill-defined clinical syndrome with diverse clinical manifestations. Clinical symptoms can range from intermittent palpitations to multisystem complaints. Although there is a general consensus that when the heartbeat exceeds 100 beats per minute at rest or with minimal physiologic challenge, it is considered "inappropriate," this quantitative differentiation is quite arbitrary, while validation of the reproducibility of the heart rate/activity correlation can be challenging. Once the clinical diagnosis of inappropriate sinus tachycardia is expected, other supraventricular tachyarrhythmias and medical conditions causing sinus tachycardia should be excluded. The underlying mechanism of inappropriate sinus tachycardia is not well understood. "Intracardiac" mechanisms such as enhanced intrinsic automaticity, enhanced sympathetic tone, increased sympathetic receptor sensitivity, and blunted parasympathetic tone have been proposed. Evidences for "extracardiac" mechanisms such as length-dependent autonomic neuropathy, excessive venous pooling, beta-receptor hypersensitivity, alpha-receptor hyposensitivity, altered sympathovagal balance, and brainstem dysregulation have also been reported. Currently, our ability to differentiate primary (intracardiac) from secondary (extracardiac) mechanisms of inappropriate sinus tachycardia is limited. It has been reported that ablative therapy of sinus node is effective in treating patients with symptomatic inappropriate sinus tachycardia. Acute success of sinus node modification/ablation can be accomplished in 70%-100% of the various study populations. Although long-term successful outcome may be accomplished in a few patients, symptoms of palpitations and autonomic characteristics frequently persist. Identification and differentiation of patients who are suitable for ablative therapy versus medical therapy should be one of the central clinical research issues in this patient population. This brief review first considers the clinical and electrophysiologic diagnosis of inappropriate tachycardia and then summarizes the mechanisms of inappropriate sinus tachycardia and related syndromes such as postural orthostatic tachycardia syndrome. Techniques of mapping and ablation of sinus node are discussed briefly. A critical review of the acute and long-term clinical outcomes following sinus node ablation and modification is updated. In conclusion, the precise role of sinus node modification in patients with inappropriate sinus tachycardia remains to be determined. Sinus node modification could be considered in patients with inappropriate sinus tachycardia with persistently increased heart rate in the absence of any autonomic abnormalities. Autonomic laboratory testing should be performed to exclude any evidence of autonomic dysregulation. Clinical research on the pathophysiology of inappropriate sinus tachycardia should be pursued vigorously.

Body Surface Potential Mapping↗

Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands.

Potassium channels are essential for maintaining a normal ionic balance across cell membranes. Central to this function is the ability of such channels to support transmembrane ion conduction at nearly diffusion-limited rates while discriminating for K+ over Na+ by more than a thousand-fold. This selectivity arises because the transfer of the K+ ion into the channel pore is energetically favoured, a feature commonly attributed to a structurally precise fit between the K+ ion and carbonyl groups lining the rigid and narrow pore. But proteins are relatively flexible structures that undergo rapid thermal atomic fluctuations larger than the small difference in ionic radius between K+ and Na+. Here we present molecular dynamics simulations for the potassium channel KcsA, which show that the carbonyl groups coordinating the ion in the narrow pore are indeed very dynamic ('liquid-like') and that their intrinsic electrostatic properties control ion selectivity. This finding highlights the importance of the classical concept of field strength. Selectivity for K+ is seen to emerge as a robust feature of a flexible fluctuating pore lined by carbonyl groups.

Bacterial Proteins↗

Early development of protein metabolic perturbations in the liver and skeletal muscle of tumour-bearing rats. A model system for cancer cachexia.

In rats into which a fast-growing ascites hepatoma (Yoshida AH-130) had been transplanted, tumour growth elicited a marked loss of body weight until the animal's death in about 2 weeks. Overall tissue protein metabolism was simultaneously studied in vivo in the gastrocnemius muscle and liver after labelling with [14C]bicarbonate. Early and progressive atrophy developed in the gastrocnemius muscle, the underlying metabolic imbalance being expressed by an elevation in the apparent protein-degradation rate, with no changes in the apparent synthesis rate. A transient hyperplastic response preceded waste in the liver, both states being associated with alterations in protein-degradation rate: an initial decrease during liver growth, then an acceleration as liver regressed. Protein-synthesis rates, virtually unchanged during liver growth, were elevated in the subsequent phase, although not sufficient to balance the enhanced breakdown. Thus, in the tumour host tissues examined, altered states of protein turnover appeared to result mostly from changes in rates of protein breakdown. In sharp contrast with the negative protein balance in the host, the ascites hepatoma cells had the ability to grow or at least, in advanced stages, to maintain a stationary state.

Animals↗

Weaning from mechanical ventilation.

Patients that require positive pressure ventilation to maintain sufficient alveolar ventilation or pulmonary gas exchange may eventually reach a point in the course of their care wherein mechanical ventilation is no longer necessary. This process of transferring the work of breathing from the ventilator back to the patient is referred to as ventilator weaning. The term "ventilator weaning" may be used to refer to all methods by which this transfer of workload may be accomplished. In many patients, particularly those with short-lasting or readily correctable causes of respiratory insufficiency (e.g., general anesthesia), the discontinuation of positive pressure ventilation may be easily achieved. Indeed, in patients awakening from general anesthesia, the axiom "awake enough to blink, awake enough to breath" may prove to be a sufficient guideline. However, in those patients requiring long-term mechanical ventilatory support, the process can prove to be both frustrating and exceptionally challenging. It is of crucial importance to identify those patients that may be successfully weaned because of both the financial impact of prolonged intensive care unit hospitalization and the risks imposed on the patient by the process of positive pressure ventilation. To be able to predict which patients may be ready to be weaned from the ventilator requires an understanding of the balance between the work of breathing (ventilatory load) and the ability of the patient's respiratory pump to meet those needs (ventilatory capacity). The management of patients experiencing difficulty during the weaning process requires that the clinician recognize imbalances between ventilatory load and capacity and to correct these imbalances once identified.

Algorithms↗

Immunopathology of antibodies as effectors of orthotopic liver allograft rejection.

We have come a long way in our understanding of antibodies as effectors of liver graft damage, but we still have much to learn. Animal heterografts provided the first evidence that livers are susceptible to antibody-mediated damage. The pathophysiologic events are similar to those of extrahepatic organ grafts, but the liver is relatively resistant and rapidity of graft destruction is slower, if it occurs at all. Nevertheless, the ABO isoagglutinins can predictably cause human liver allograft failure, often in a quickened, but rarely a hyperacute fashion. The liver is more resistant to lymphocytotoxins, and in many cases will suffer no apparent damage. However, when present, a spectrum of graft pathologic changes can be seen. Early manifestations include hemorrhagic necrosis and lesions mimicking "preservation" injury. Later on, ischemic biliary necrosis and small bile duct loss may be seen. The variability is likely related to a balance between destructive antibody class, specificity, and titers and the ability of the liver to withstand the assault. More precise characterization of lymphocytotoxic antibodies is needed in clinical practice. In addition, antigen distribution in the graft, release of soluble MHC antigens, the role of Kupffer cells and other mechanisms of liver resistance are likely areas of fruitful investigation.

ABO Blood-Group System↗

[Functional disorder of the hypothalamic osmoreceptor as the cause of excessive hypernatremia in a girl with absence epilepsy].

BACKGROUND: Chronic hypernatremia is a rare disorder in childhood and normally results from impairment of the water homeostasis. In some cases, chronic hypernatremia is caused by decreased intake of water based on impaired thirst perception. CASE REPORT: We report a girl with microcephaly, partial agenesis of the corpus callosum, mild midface hypoplasia and absence seizures, who presented with severe hypernatremia (serum sodium concentration 189 mmol/l). Though serum osmolality was increased up to 382 mOsm/kg, the girl showed no signs of thirst. After normalization by intravenous fluid therapy, serum osmolality and serum sodium concentration remained in the normal range with an oral water intake of at least 1500 ml/d. Polyuria was never present, the ability to concentrate urine was preserved. CONCLUSIONS: In summary, we speculate that the chronic hypernatremia in our patient is caused by a selective hypothalamic osmoreceptor dysfunction associated with mild dysplasia of the midline structures. Only very few similar cases have been documented in the literature.

Agenesis of Corpus Callosum↗

[Digestive function of the residual pancreas after partial duodenopancreatectomy for chronic pancreatitis (author's transl)].

Forty-eight patients with chronic recurrent pancreatitis treated by resection of the head of the pancreas were restudied more than a year post-operatively. In addition to general features such as symptoms, alcohol consumption and work ability, faecal weight, its fat content, fat and fatty acid balance and faecal chymotrypsin were measured. According to the patients' own estimate, late results were good or very good in 70-90%. Faecal fat content and balance indicated high-grade exocrine pancreatic insufficiency in 80 and 90%, respectively. But it was easily controlled by drugs. In a third of the cases there was the need to supplement the diet with medium-chain triglycerides. Its components are satisfactorily absorbed even when the fat utilisation is severely abnormal.

Chronic Disease↗

PMF: a stereo correspondence algorithm using a disparity gradient limit.

The advantages of solving the stereo correspondence problem by imposing a limit on the magnitude of allowable disparity gradients are examined. It is shown how the imposition of such a limit can provide a suitable balance between the twin requirements of disambiguating power and the ability to deal with a wide range of surfaces. Next, the design of a very simple stereo algorithm called PMF is described. In conjunction with certain other constraints used in many other stereo algorithms, PMF employs a limit on allowable disparity gradients of 1, a value that coincides with that reported for human stereoscopic vision. The excellent performance of PMF is illustrated on a series of natural and artificial stereograms. Finally, the differences between the theoretical justification for the use of disparity gradients for solving the stereo correspondence problems presented in the paper and others that exist in the stereo algorithm literature are discussed.

Depth Perception↗