The Tutor of Resilience Program with Children Who Have Experienced Maltreatment: Mothers' Involvement Matters.

Resilience is a dynamic process involving the presence and interaction of personal and environmental factors that modify the impact of adversity. Resilience-building interventions are therefore important for improving trauma-related outcomes in children and caregivers exposed to adversity. This study examines the impact of the Tutor of Resilience (TOR) program on beneficiaries' trauma-related symptoms and on mother-child interactions in a group of children exposed to maltreatment (N = 186; mean age = 11.95; SD = 2.50). Assessments were completed at baseline and post-intervention. RM-ANOVAs indicated significant improvements for most trauma symptoms (anxiety, anger, post-traumatic stress, and disassociation, but not depression) in the intervention group relative to a control group (N = 88; mean age = 10.76; SD = 2.57), and indicated further improvements to anxiety and dissociation for the intervention group when mothers were involved. Mother-child interactions also improved over time, as did their overall trauma symptoms and distress. Findings support the effectiveness of the ToR, especially when involving mothers.

Bioactive ryanoids from nucleophilic additions to 4,12-seco-4,12-dioxoryanodine.

Ryanoids are the most potent inhibitors known for the calcium-release channel (ryanodine receptor), and they are also botanical insecticides. Twenty-two new ryanoids are described in which the C-4, C-12 bond is ruptured or replaced with an oxygen bridge and in which substituents at C-4 and C-12 are modified to have a wide range of polarities. They are obtained by nucleophilic additions to the 4,12-seco-4,12-dioxo compounds or diketones prepared from ryanodine and dehydroryanodine by periodate oxidation. Structures of the new compounds are distinguished by changes in NMR chemical shifts of 13C and 1H nuclei in the regions of C-4 and C-12. The new ryanoids are compared with ryanodine as inhibitors of [3H]ryanodine binding using a rabbit muscle sarcoplasmic reticulum preparation alone or with ATP and a mouse brain receptor with ATP. They are also examined as knockdown agents for houseflies pretreated with a cytochrome P450 oxidase inhibitor to suppress detoxification and then injection with the ryanoid. The diketones have very weak binding activity in the receptor assays and very low toxicity to flies. Activity approaching that of ryanodine in both the receptor and fly assays is obtained for ketals with small groups at C-12 and polar substituents such as OH or NHOH at C-4. The oximes range from low to moderate potency. Addition of thiols to the vinyl group of dehydroryanodine gives three thioethers all of low biological activity. With most ryanoids addition of ATP to the muscle system increases its sensitivity to near that found for the brain receptor with ATP; possible exceptions are compounds with phenyl substituents. Activity at the calcium-release channel generally follows housefly toxicity although the hydrazine and hydroxyamine adducts are much weaker than expected perhaps due to dissociation under the assay conditions.

Ryanodine action at calcium release channels. 1. importance of hydroxyl substituents.

Ryanodine (1) and dehydroryanodine (2) have a polar face formed by cis-hydroxyls at C-2, C-4, C-6, and C-12. The importance of the hydroxyls to the action of 1 and 2 at the ryanodine receptor (ryr) of calcium release channels is examined at [3H]-1 binding sites in brain and skeletal muscle and in heart membranes relative to cardiac contractility, a pharmacologic response which appears to be mediated by the ryr. Five types of changes are considered: blocking the 4- and 6-hydroxyls as cyclic borates and boronates; blocking the 10- and 12-hydroxyls as cyclic phosphates, phosphonates, and phosphoramidates; methylation at nitrogen or hydroxyls at C-4 and C-10; dehydration of the C-2 hydroxyl; additional data for a 4,12-oxygen-bridged series. The first change has little effect on potency possibly due to the lability of the boron protective groups whereas the cyclic phosphorus compounds have reduced activity. Methylation reduces potency the least at nitrogen and the C-4 hydroxyl. Dehydration of 1 to 2-deoxy-2(13)-dehydro-1 allows the restoration of oxygen at C-2 by conversion to epoxides or a diol. One of the epoxides and 2-deoxy-2(13)-dehydro-2 retain 8-31% of ryanodine's potency in the ryr assays and 81% in the cardiac contractility system. In the 4,12-oxygen-bridged series, high potency at the receptor and cardiac muscle is retained in the 4-hydroxy ketal.

Ryanodine action at calcium release channels. 2. relation to substituents of the cyclohexane ring.

Ryanodine (1) and dehydroryanodine (2) are equipotent probes for the ryanodine receptor (ryr) of calcium release channels and differ only in 9eq-methyl for 1 and 9,21-methylene for 2. Ryanoids 1 and 2 are used here to prepare novel modifications of the cyclohexane substituents to determine their effects on ryr activity and selectivity. 10-Oxo-1 when reacted with carbonyl and other reagents gave 13 C-10 derivatives including the epi-amine and epi-4-azidobenzoyl hydrazide as a candidate affinity probe. Four derivatives of 2 including the delta 8-10-hydroxy and delta 8-10-oxo compounds. Defunctionalization of the cyclohexane ring of 2 or its 4,6-ethylboronate was achieved in part by controlled periodate oxidation of the 9,21-diol to the 21-nor-9-oxo compounds. These in turn provided access to the 9ax- and 9eq-hydroxy derivatives and to the 21-nor-10-deoxy-9-oxo compound which was converted to 21-nor-10-deoxy-1 and 10-deoxy-2 along with the epimeric 10-deoxy-9-hydroxy compounds. Ryanoids of similar potency to 1 as inhibitors of [3H]-1 binding in mouse brain, rabbit skeletal muscle, and canine ventricle ryr preparations and in rat cardiac contractility assay (inhibition of mechanical response to electrical stimulation) are epi-1 and the 10-epi-amino, 10-epi-methoxyamino, and 10-epi-azidobenzoyl hydrazide derivatives and 10-deoxydehydroryanodine. With a few exceptions the potency of the ryanoids at the cardiac ryr correlates well with their inhibition of cardiac contractility, indicating that the activity is associated with stabilizing the calcium release channel in a subconducting state, thereby uncoupling the excitation-contraction process.

Dialkylquinoneimine metabolites of chloroacetanilide herbicides induce sister chromatid exchanges in cultured human lymphocytes.

Some of the most widely-used herbicides are the chloroacetanilides exemplified by alachlor and butachlor (derived from 2,6-diethylaniline) and metolachlor and acetochlor (synthesized from 2-ethyl-6-methylaniline). This investigation tests the hypothesis that the previously-observed oncogenicity of these herbicides is due to genotoxic intermediates such as diethylbenzoquinoneimine, a purported alachlor metabolite. Syntheses are reported here for the corresponding 2,6-dialkylbenzoquinoneimines, selected chloroacetyldialkylbenzoquinoneimines and several other candidate or known metabolites. The possible mutagenicity of diethylbenzoquinoneimine was tested in Salmonella typhimurium strains TA98 and TA100 with a weakly-positive response in the TA100 strain indicating induction of base-pair substitution mutations. The frequency of sister chromatid exchange (SCE) in Chinese hamster ovary cells was increased by alachlor at 10 microM and diethylaniline but not ethylmethylaniline at 30 and 3 microM. Isolated and cultured peripheral lymphocytes (mostly T cells) were used from two human donors to study the effects of the chloroacetanilides and their metabolites on primary human cells. In tests at 10 microM, the SCE frequency was increased by alachlor and possibly acetochlor but not by butachlor, metolachlor, dimethachlor (a 2,6-dimethyl analog) and dimethenamid (an analog based on 2,4-dimethyl-3-thienylamine). At 0.3 microM in cultured human lymphocytes, alachlor, the corresponding chloroacetanilide (N-dealkyl-alachlor) and aniline metabolites (and their 4-hydroxy derivatives), and diethylbenzoquinone were inactive or active in only one of the two donors whereas at 0.1-0.3 microM the SCE ratio for treated cells divided by the controls was always higher for diethylbenzoquinoneimine than for ethylmethyl- and dimethylbenzoquinoneimines. All the tested compounds were toxic to lymphocytes, but the depression of the mitotic index and increased duration of the cell cycle were not directly linked with SCE induction. Previous investigations have suggested that chloroacetanilide herbicides such as alachlor derived from 2,6-dialkylanilines are metabolized to 2,6-dialkylbenzoquinoneimines and the present study provides the first direct evidence that these metabolites are genotoxic in human lymphocytes.

Deterministic dynamics in the minority game.

The minority game (MG) behaves as a stochastically disturbed deterministic system due to the coin toss invoked to resolve tied strategies. Averaging over this stochasticity yields a description of the MG's deterministic dynamics via mapping equations for the strategy score and global information. The strategy-score map contains both restoring-force and bias terms, whose magnitudes depend on the game's quenched disorder. Approximate analytical expressions are obtained and the effect of "market impact" is discussed. The global-information map represents a trajectory on a de Bruijn graph. For small quenched disorder, a Eulerian trail represents a stable attractor. It is shown analytically how antipersistence arises. The response to perturbations and different initial conditions is also discussed.

Generalized strategies in the minority game.

We show analytically how the fluctuations (i.e., standard deviation sigma) in the minority game can decrease below the random coin-toss limit if the agents use more general, stochastic strategies. This suppression of sigma results from a cancellation between the actions of a crowd, in which agents act collectively and make the same decision, and those of an anticrowd, in which agents act collectively by making the opposite decision to the crowd.

An unusual ciliary body tumour: a haemangioblastoma.

A 23-year-old woman who presented with blurred vision in her right eye from increasing astigmatism had a vascular ciliary body tumour. After slow growth was documented over a 15-month period the tumour was excised with an iridocyclectomy. Microscopically the tumour consisted of sheets of large polygonal cells with round nuclei and foamy cytoplasm, separated by numerous capillaries, findings consistent with a diagnosis of a haemangioblastoma. Haemangioblastomas occur in the retina in von Hippel's disease and this occurrence in the ciliary body is a rare event. Investigation of the patient with a CT of the head and an abdominal ultrasound revealed no systemic lesions suggestive of systemic angiomatosis or von Hippel-Lindau disease.

An anatomical study of retinal arteriovenous crossings and their role in the pathogenesis of retinal branch vein occlusions.

To elucidate the anatomical features which predispose artery over vein (AV) crossings to be the preferential sites for retinal branch vein occlusions (RBVO), 11 AV and six vein over artery (VA) crossings in 12 eyes from non-hypertensive donors who were aged 35 to 82 years, were studied by light and electron microscopy. At AV crossings the veins were often observed to abruptly alter direction to pass under the artery. Here focal stratification of the vein basement membrane opposite the point of contact with the artery was seen. A focal reduction in the vein lumen occurred at three of 11 AV crossings. In contrast, deviation of the vein, focal basement membrane stratification or focal narrowing was not seen at VA crossings. Both types of crossings had a common adventitial sheath when each vessel was of large calibre. This study demonstrated anatomical features which predispose AV crossings to be the preferential site for venous occlusion.

Efficient photochemical formation of 1 alpha-hydroxyprevitamin D3.

Control of the band width of the irradiating light between 280 and 310 nm and of the temperature of the reaction permits formation of 1 alpha-hydroxyprevitamin D3 in yields of over 80%, at 40-60% conversion of the 1 alpha-hydroxyprovitamin D3. The procedures developed permit doubling the photochemical yield of the 1 alpha-hydroxyvitamin D3 compounds which are the major circulatory forms of vitamin D3.

Ryanodyl 3-(pyridine-3-carboxylate): a novel ryanoid from Ryania insecticide.

Ryanodyl 3-(pyridine-3-carboxylate) was isolated as a minor component from the wet CHCl3 extract of Ryania insecticide, and its structure was assigned by chemical and spectroscopic methods. This compound is essentially inactive compared with ryanodine for insecticidal activity against Musca domestica adults and Tribolium castaneum larvae, for toxicity to mice, and for competition with [3H]ryanodine at the Ca(2+)-ryanodine receptor complex of skeletal muscle.

Radiation hazards during cobalt 60 plaque therapy for choroidal melanoma.

Prompted by the concerns of the staff and patients, radiation hazards from Cobalt 60 (Co 60) plaque therapy for choroidal melanoma were recently assessed when two patients were concurrently treated at Christchurch Hospital. The risks from radiation to the attending medical staff, nursing personnel from the operating theatre and ward, and the patients' visitors were investigated. The radiation dose for all staff and visitors involved with the two patients was found to be well below the recommended weekly limits set by the International Commission on Radiological Protection. Our department code of practice to minimise radiation hazard during plaque therapy has been revised.

Dialkylquinonimines validated as in vivo metabolites of alachlor, acetochlor, and metolachlor herbicides in rats.

The oncogenicity of chloroacetanilide herbicides (1-5) is proposed to involve bioactivation to 2,6-dialkylbenzoquinonimines (quinonimines, 9) based on two earlier observations: (1) in vitro conversion of the alachlor (1) metabolite diethylaniline (7Et2) to 2, 6-diethylquinonimine (9Et2) which reacts readily with GSH and (2) induction of sister chromatid exchanges in human lymphocytes for the parent herbicides and their purported 9 metabolites. This hypothesis lacks in vivo evidence for 9 formation which might be provided by analysis of urine and tissue for thiol adducts of 9. Accordingly, two mercapturates (10Et2 and 10Me2) and a cysteine conjugate (11Me2) were prepared by addition of N-acetylcysteine or cysteine to 9Et2 and the 2,6-dimethyl homologue (9Me2). Mercapturate 10Et2 was characterized by HPLC using the urine of rats treated ip with hydroxyaniline 8Et2, and both mercapturate 10Me2 and cysteine conjugate 11Me2 were found in the urine of mice administered hydroxyaniline 8Me2. The mercapturates were then converted to the N, N-dimethyl-2,6-dialkyl-4-methoxy-3-(methylthio)anilines (12Et2, 12EtMe, and 12Me2) by alkaline permethylation, thereby providing a method for analysis of 9-derived thiol adducts in urine and liver as the 12 derivatives by GC/MS with selected ion monitoring. The urine of rats 0-6 h after ip treatment with 1, butachlor (2), acetochlor (3), metolachlor (4), and dimethachlor (5) at 0.74 mmol/kg yields permethylated derivatives which are definitively diagnostic for the 9 intermediates from each of the herbicides in amounts of 3-24-fold above the minimum detectable limit, as well as 1 and 2 orders of magnitude higher from the corresponding anilines (7) and hydroxyanilines (8), respectively. Similar liver analyses reveal tissue thiol adducts of 9 6 h after treatment with 7 and 8 but not with the parent herbicides. The yields of urinary 9 derivatives from the parent herbicides are higher from the 2,6-diethyl series (1 and 2) and the 2-ethyl-6-methyl derivatives (3 and 4) than from the 2, 6-dimethyl analogue (5). These findings provide direct evidence in vivo that quinonimines are metabolites of 1-5 in rats.