Is the Aligning Prism Measured with the Mallett Unit Correlated with Fusional Vergence Reserves?

Background

The Mallett Unit is a clinical test designed to detect the fixation disparity that is most likely to occur in the presence of a decompensated heterophoria. It measures the associated phoria, which is the “aligning prism” needed to nullify the subjective disparity. The technique has gained widespread acceptance within professions such as optometry, for investigating suspected cases of decompensating heterophoria; it is, however, rarely used by orthoptists and ophthalmologists. The aim of this study was to investigate whether fusional vergence reserves, measured routinely by both orthoptists and ophthalmologists to detect heterophoria decompensation, were correlated with aligning prism (associated phoria) in a normal clinical population.

Methodology/Principal Findings

Aligning prism (using the Mallett Unit) and fusional vergence reserves (using a prism bar) were measured in 500 participants (mean 41.63 years; standard deviation 11.86 years) at 40 cm and 6 m. At 40 cm a strong correlation (p<0.001) between base in aligning prism (Exo FD) and positive fusional reserves was found. Of the participants with zero aligning prism 30% had reduced fusional reserves. At 6 m a weak correlation between base out aligning prism (Eso FD) and negative fusional reserves was found to break (p = 0.01) and to recovery (p = 0.048). Of the participants with zero aligning prism 12% reported reduced fusional reserves.

Conclusions/Significance

For near vision testing, the strong inverse correlation between base in aligning prism (Exo FD) and fusional vergence reserves supports the notion that both measures are indicators of decompensation of heterophoria. For distance vision testing and for those patients reporting zero aligning prism further research is required to determine why the relationship appears to be weak/non-existent?     

Is the money following the clients with learning disabilities?

For the past decade patients with learning disabilities living in long stay mental handicap hospitals have been resettled in the community. Local authorities have also taken on the care of new patients who would once have been long stay residents. The imperfect data that are available suggest that in England about half the residents in mental handicap hospitals in 1981 are now the responsibility of local authorities; the figures for Wales and Northern Ireland are 38% and 33%. Data on revenue suggest that the savings to the health service are much less--perhaps 9% in Northern Ireland and 3.6% in England, although there have also been capital gains through the sale of hospitals. Existing methods of transferring money from health to local authorities--joint finance and "dowries" for individual patients--do not seem adequately to have compensated local authorities. Moreover, as patients still to be transferred are more severely disabled local authorities will require larger sums--about 26 000 pounds per patient per year plus 39 200 pounds in capital. If the government chooses not to transfer these resources from health authorities it will be switching funds away from learning disabled people to other care groups.     

Working with living krill – the people and the places

The fascination of Antarctic scientists with Antarctic krill and their capabilities has a long and varied history, and prompted many scientists to maintain and manipulate krill under laboratory conditions. Starting in the Discovery era with Mackintosh at the King Edward Point labs on South Georgia, 1930, scientists have collected krill from sailing vessels, small boats, inflatable zodiacs and large ice-breaking vessels. Krill have been maintained in small and large jars, deep rectangular tanks, large round tanks and in flow-through and recycling systems. They have been maintained both on board research vessels and in laboratories, in flowing seawater systems at ambient conditions and in temperature-controlled environmental rooms. A few researchers have transported living krill back to their home laboratories, for example tropical laboratories in Japan (Murano) and Australia (Ikeda), temperate laboratories (Nicol) in Australia, a northern European laboratory in Germany (Marschall) and a sunny maritime laboratory in California (Ross and Quetin). The goals have been varied: short-term experiments to understand in situ physiological rates, long-term experiments to test the effects of manipulations or controlled changes in environmental conditions, and behavioral responses. We take you on a brief historical tour as we trace the lineage of modern day research on living Antarctic krill.     

Insulin analogues with modifications in the β-turn of the B-chain

The β-turn formed by the amino acid residues 20–23 of the B-chain of insulin has been implicated as an important structural feature of the molecule. In other biologically active peptides, stabilization of β-turns has resulted in increases in activity. We have synthesized three insulin analogues containing modifications which would be expected to increase the stability of the β-turn. In two analogues, we have substituted α-aminoisobutyric acid (Aib) for the Glu residue normally present in position B21 or for the Arg residue normally present in position B22; in a third compound, we have replaced the Glu residue with its D-isomer. Biological evaluation of these compounds showed that [B21 Aib]insulin displays a potencyca. one-fourth that of natural insulin, while [B22 Aib]insulin is less than 10% as potent. In contrast, [B21 D-Glu]insulin is equipotent with natural insulin. We conclude that the β-turn region of the insulin molecule normally possesses considerable flexibility, which may be necessary for it to assume a conformation commensurate with high biological activity. If this is the case, [B21 D-Glu]insulin may exhibit a stabilized geometry similar to that of natural insulin when bound to the insulin receptor.     

Interaction of IgG immunoglobulins with the guinea pig peritoneal macrophage Fcγ receptors. Effect on the association of the receptors with the membrane skeleton and the cytoskeleton

Binding of ligands to cell surface receptors may induce an interaction of the receptors with the cytoskeleton and/or membrane skeleton and decrease the solubility of the receptors in nonionic detergents. Cytochalasins, reagents affecting the structure of microfilaments, inhibit some cell functions induced by cross-linking of the receptors with ligands. Information concerning the function of the cytoskeleton in insolubilization of Fcγ receptors (FcγR) and in FcγR-mediated signal transmission is rather limited. The aim of this work was to investigate the effect of binding of homologous (guinea pig IgG1 and IgG2) and heterologous (rabbit IgG) immunoglobulins to guinea pig peritoneal macrophages on association of the macrophage Fcγ receptors with the membrane skeleton and cytoskeleton. Cross-linking the macrophage Fcγ receptors with immunoglobulin ligands induced insolubilization of the receptors in nonionic detergents suggesting association of the receptors with the membrane skeleton and the cytoskeleton. The ligands showed differential effects depending on a subclass and origin of the IgG used. The process of association of the Fcγ receptors with the skeletons was fast and did not depend on temperature. Treatment of insoluble complexes with cytochalasin D, DNAse I or colchicine showed that actin microfilaments and microtubules play a role, at least partially, in insolubilization of the cross-linked macrophage Fcγ receptors. Inhibition of insolubilization of the macrophage Fcγ receptors by genistein indicated that tyrosine kinases are involved in the process of insolubilization. The association with the skeletons might be a part of the process of transduction of a signal which depended on the subclass and origin of IgG used and on the type of the Fcγ receptor.     

On the aggregation properties of FMRP--a link with the FXTAS syndrome?

Fragile X mental retardation protein (FMRP) is an RNA binding protein necessary for correct spatiotemporal control of neuronal gene expression in humans. Lack of functional FMRP causes fragile X mental retardation, which is the most common inherited neurodevelopmental disorder in humans. In a previous study, we described the biochemical and biophysical aggregation properties of constructs spanning the conserved region of FMRP and of two other human fragile X related (FXR) proteins, FXR1P and FXR2P. Here, we show that the same regions have an intrinsic tendency to aggregate and spontaneously misfold towards β-rich structures, also under non-destabilizing conditions. These findings pave the way to future studies of the mechanism of formation of FXR-containing ribonucleoprotein granules and suggest a possible link with the as yet poorly understood FXR proteins' associated pathologies.     

Is the treatment with psychostimulants in children and adolescents with attention deficit hyperactivity disorder harmful for the dopaminergic system?

A major concern regarding psychostimulant medication (amphetamine and methylphenidate) in the treatment of children and adolescents with attention deficit/hyperactivity disorder (ADHD) are the potential adverse effects to the developing brain, particularly in regard to dopaminergic brain function. The present review focuses on the pharmacology of these psychostimulants, their mode of action in the human brain and their potential neurotoxic effects to the developing brain in animals, particularly concerning DA brain function. The potential clinical significance of these findings for the treatment of ADHD in children and adolescents is discussed. Studies on sensitization to psychostimulants’ rewarding effects, which is a process expected to increase the risk of substance abuse in humans, are not included. The available findings in non-human primates support the notion that the administration of amphetamine and methylphenidate with procedures simulating clinical treatment conditions does not lead to long-term adverse effects in regard to development, neurobiology or behaviour as related to the central dopaminergic system.     

Fighting with the enemy's weapons? the role of costimulatory molecules in HIV

HIV infection is characterized by a number of abnormalities in several components of the immune system. For example, during HIV infection, a massive decrease of CD4(+) T cells is observed, as well as a progressive depletion of na?ve CD8(+) T cells. Furthermore, elevated numbers of apoptotic B and T cells are present in HIV-infected patients, and a systemic immune activation results in T-cell exhaustion. Finally, HIV infection is characterized by the presence of functionally impaired dendritic cells, with decreased expression of maturation markers, decreased secretion of cytokines and defects in antigen processing and presentation. All these characteristics result in the occurrence of non-functional cytotoxic T lymphocytes, that fail to control HIV-replication in most individuals during progressive disease. Costimulatory and co-inhibitory molecules are involved in the activation, differentiation and survival of several cell-types of the immune system. Each costimulatory receptor (generally expressed on effector cells) can conjugate with one or more specific ligands (expressed on antigen-presenting cells), which leads to an activation of intracellular signaling pathways inside the cells on which they are expressed. HIV infection is characterized by an aberrant expression of these molecules on cells of the immune system. Many of the immune deficiencies mentioned in the previous paragraph can be explained by abnormal expression of costimulatory molecules, and could consequently be overcome by interfering with their interactions. In this review, we give an overview of the functions and expression patterns of the receptor/ligand pairs of the tumor necrosis factor and the B7 super-families of costimulatory and co-inhibitory molecules in HIV-infected patients. We will also discuss possibilities for manipulating their signaling as a therapeutic anti-HIV tool.     

Immediate breast reconstruction with saline-filled implants: no interference with the oncologic outcome?

The possible adverse effects on cancer control due to immediate breast reconstruction have been addressed recently for both silicone-filled implants and flap reconstruction. To evaluate those possible effects after immediate breast reconstruction with saline-filled implants, 49 patients reconstructed with saline-filled breast implants at the Jules Bordet Cancer Institute were studied. Selection was only based on the possibility to find a matched patient. These patients were matched with a control group of 49 matched women with breast cancer treated in the same center by mastectomy without any type of breast reconstruction. The two groups were comparable according to age at diagnosis (within 3 years), year of diagnosis (same year), stage of the tumor, histology, and nodal status. The only difference between the two groups was that radiation therapy was applied to some of the patients who were not reconstructed (due to tumor location). The results show, in terms of local recurrences, distant metastasis, and deaths, no significant difference between the two groups, even for the irradiated patients, within a mean follow-up period of 72 months (range, 24 to 108) months.     

Back to the future with the AGP–Ca2+ flux capacitor

Background

Arabinogalactan proteins (AGPs) are ubiquitous in green plants. AGPs comprise a widely varied group of hydroxyproline (Hyp)-rich cell surface glycoproteins (HRGPs). However, the more narrowly defined classical AGPs massively predominate and cover the plasma membrane. Extensive glycosylation by pendant polysaccharides O-linked to numerous Hyp residues like beads of a necklace creates a unique ionic compartment essential to a wide range of physiological processes including germination, cell extension and fertilization. The vital clue to a precise molecular function remained elusive until the recent isolation of small Hyp–arabinogalactan polysaccharide subunits; their structural elucidation by nuclear magentic resonance imaging, molecular simulations and direct experiment identified a 15-residue consensus subunit as a β-1,3-linked galactose trisaccharide with two short branched sidechains each with a single glucuronic acid residue that binds Ca²⁺ when paired with its adjacent sidechain.

Scope

AGPs bind Ca²⁺ (K_d ∼ 6 μm) at the plasma membrane (PM) at pH ∼5·5 but release it when auxin-dependent PM H⁺-ATPase generates a low periplasmic pH that dissociates AGP–Ca²⁺ carboxylates (pk_a ∼3); the consequential large increase in free Ca²⁺ drives entry into the cytosol via Ca²⁺ channels that may be voltage gated. AGPs are thus arguably the primary source of cytosolic oscillatory Ca²⁺ waves. This differs markedly from animals, in which cytosolic Ca²⁺ originates mostly from internal stores such as the sarcoplasmic reticulum. In contrast, we propose that external dynamic Ca²⁺ storage by a periplasmic AGP capacitor co-ordinates plant growth, typically involving exocytosis of AGPs and recycled Ca²⁺, hence an AGP–Ca²⁺ oscillator.

Conclusions

The novel concept of dynamic Ca²⁺ recycling by an AGP–Ca²⁺ oscillator solves the long-standing problem of a molecular-level function for classical AGPs and thus integrates three fields: AGPs, Ca²⁺ signalling and auxin. This accounts for the involvement of AGPs in plant morphogenesis, including tropic and nastic movements.     

Induction of parturition in the bitch with the progesterone-receptor blocker aglépristone

The triggering mechanism for parturition in the bitch remains unclear. Consequently, the development of drugs to successfully induce parturition in the dog has been difficult. The aim of this study was to evaluate the efficacy of the progesterone-receptor blocker aglépristone for the induction of parturition in beagle bitches. The course of parturition was therefore investigated in six parturitions induced by aglépristone and in six spontaneous parturitions. In addition, data were collected on pup survival and growth rates. Aglépristone was administered twice with a 9h interval on day 58 of pregnancy. If parturition did not proceed a standard intervention protocol was applied. Expulsion of the first pup occurred between 32 and 56 h after the first treatment with aglépristone, at which time the plasma progesterone concentration was still elevated. Accordingly, the gestation length of the bitches in the induced group (59.5+/-0.2 days) was significantly shorter than that of the spontaneously whelping bitches (62.2+/-0.5 days). The expulsion phase length, the inter-pup interval, the number of puppies born dead, and the number of clinical interventions needed during parturition did not significantly differ between the spontaneously whelping and the induced group. Pup survival and mean birth weights in the two groups did not differ significantly and aglépristone treatment had no significant influence on the growth rates. The results of this study show that aglépristone is an effective drug which can be used safely for the induction of parturition in the dog.