An exploration of neural predictors of treatment compliance in cognitive-behavioral group therapy for hoarding disorder.

A persistent and influential barrier to effective cognitive-behavioral therapy (CBT) for patients with hoarding disorder (HD) is treatment retention and compliance. Recent research has suggested that HD patients have abnormal brain activity identified by functional magnetic resonance (fMRI) in regions often engaged for executive functioning (e.g., right superior frontal gyrus, anterior insula, and anterior cingulate), which raises questions about whether these abnormalities could relate to patients' ability to attend, understand, and engage in HD treatment. We examined data from 74 HD-diagnosed adults who completed fMRI-measured brain activity during a discarding task designed to elicit symptom-related brain dysfunction, exploring which regions' activity might predict treatment compliance variables, including treatment engagement (within-session compliance), homework completion (between-session compliance), and treatment attendance. Brain activity that was significantly related to within- and between-session compliance was found largely in insula, parietal, and premotor areas. No brain regions were associated with treatment attendance. The results add to findings from prior research that have found prefrontal, cingulate, and insula activity abnormalities in HD by suggesting that some aspects of HD brain dysfunction might play a role in preventing the engagement needed for therapeutic benefit.

A randomized clinical trial to evaluate feasibility, tolerability, and preliminary target engagement for a novel executive working memory training in adolescents with ADHD.

OBJECTIVE: Working memory training for Attention-Deficit/Hyperactivity Disorder (ADHD) has focused on increasing working memory capacity, with inconclusive evidence for its effectiveness. Alternative training targets are executive working memory (EWM) processes that promote flexibility or bolster stability of working memory contents to guide behavior via selective attention. This randomized, placebo-controlled study was designed to assess feasibility, tolerability, and behavioral target engagement of a novel EWM training for ADHD. METHOD: 62 ADHD-diagnosed adolescents (12-18 years) were randomized to EWM training or placebo arms for 20 remotely coached sessions conducted over 4-5 weeks. Primary outcome measures were behavioral changes on EWM tasks. Secondary outcomes were intervention tolerability, trial retention, and responsiveness to adaptive training difficulty manipulations. RESULTS: Linear regression analyses found intervention participants showed medium effect size improvements, many of which were statistically significant, on Shifting and Filtering EWM task accuracy and Shifting and Updating reaction time measures. Intervention participants maintained strong self-rated motivation, mood, and engagement and progressed through the adaptive difficulty measures, which was further reflected in high trial retention. CONCLUSIONS: The results suggest that these EWM processes show promise as training targets for ADHD. The subsequent NIMH R33-funded extension clinical trial will seek to replicate and extend these findings.

Diblock bottlebrush polymer in a non-polar medium: Self-assembly, surface forces, and superlubricity.

Whilst bottlebrush polymers have been studied in aqueous media for their conjectured role in biolubrication, surface forces and friction mediated by bottlebrush polymers in non-polar media have not been previously reported. Here, small-angle neutron scattering (SANS) showed that a diblock bottlebrush copolymer (oligoethyleneglycol acrylate/ethylhexyl acrylate; OEGA/EHA) formed spherical core-shell aggregates in n-dodecane (a model oil) in the polymer concentration range 0.1-2.0 wt%, with a radius of gyration Rg âˆ¼ 7 nm, comprising 40-65 polymer molecules per aggregate. The surface force apparatus (SFA) measurements revealed purely repulsive forces between surfaces bearing inhomogeneous polymer layers of thickness L âˆ¼ 13-23 nm, attributed to adsorption of a mixture of polymer chains and surface-deformed micelles. Despite the surface inhomogeneity, the polymer layers could mediate effective lubrication, demonstrating superlubricity with the friction coefficient as low as µ ∼ 0.003. The analysis of velocity-dependence of friction using the Eyring model shed light on the mechanism of the frictional process. That is, the friction mediation was consistent with the presence of nanoscopic surface aggregates, with possible contributions from a gel-like network formed by the polymer chains on the surface. These unprecedented results, correlating self-assembled polymer micelle structure with the surface forces and friction the polymer layers mediate, highlight the potential of polymers with the diblock bottlebrush architecture widespread in biological living systems, in tailoring desired surface interactions in non-polar media.

Growth in children with homozygous sickle cell disease 0-5 years: comparison with a control population - abstract

In July 1973 the Medical Research Council Laboratories initiated a cohort study, based on cord blood screening at the Victoria Jubilee Hospital, Kingston, in order to study the natural history of sickle cell disease in childhood. Two controls (AA genotype) were selected for each child with homozygous sickle cell (SS) disease until January, 1976 when 250 AA controls had been recruited, which was considered adequate. All children were requested to attend routinely at regular intervals and strenuous efforts were made to trace defaulters. At each attendance measurements of weight (by lever balance scale) and height (by stadiometer) were made. In August, 1979 the measurements of 233 SS and 250 AA children were used in this analysis. The data was analyzed cross-sectionally at age points between birth and five years, and the results presented in two parts. (1) Growth in AA children. These data represent the most recent available for Jamaican pre-school children. The results showed: (i) no significant sex difference in birth weight but, during the first year of life, males were consistently and significantly heavier and longer than females. Thereafter there was no significant difference between the sexes. (ii) comparison with a previous study of an urban Jamaican population (McGregor, 1972) showed that growth in both height and weight was very similar in both studies. (iii) comparison with a rural Jamaican population (Desai et al, 1969) showed consistently better growth at all ages in the cohort group, for both height and weight. (iv) comparison with the most recent WHO growth standards (WHO, 1978) showed weight in both sexes to be well maintained near the mean during the first six months, subsequently falling away towards a deficit of - 1 S.D. at 5 years. Height tended to follow a similar pattern although the deficit was less. (2) - Growth in SS Children. - By the age of 1 year SS children of both sexes were significantly lighter than the AA controls. In boys this difference was sustained to 3 years while in girls the trend was maintained but did not achieve significance. In both sexes there was a trend for weight to fall further behind the controls with increasing age. SS children were slightly but consistently shorter after the first year. These effects were confirmed by the observation that mean weight for height tended to increasingly deviate with age below that of the controls. This may represent the development of the slender habitus seen in older SS patients. Male - female differences in the SS group were of the same order as those seen in the controls (AU)

The development of cardiomegaly in homozygous sickle cell disease

Cardiomegaly is a feature of the physiological adaptation to chronic anaemia and is characteristic of many patients with sickle cell disease. This study documents that significant cardiomegaly develops in children with homozygous sickle cell(SS) disease before the age of one year. No correlation was found between the degree of cardiomegaly and the severity of aneamia. Abnormal cardiac signs are common in very young children with SS disease and do not necessarily imply cardiac dysfunction. (AU)

Body shape in young children with homozygous sickle cell disease

Body shape, defined by detailed anthropometric measurement, was compared in 64 children with homozygous sickle cell (SS) disease, and in 123 children with a normal hemoglobin (AA) genotype, aged 4 to 6 years. Children with homozygous sickle cell disease showed an average reduction in weight, height, sitting height, limb length, interacromial and intercristal diameters, and skinfold thickness. They showed increased anteroposterior chest diameter ratio. This report establishes that the effect of homozygous sickle cell disease on growth patterns in childhood is apparent before the age of 6 years. The relationship to changes in body shape, seen during adolescence and in affected adults, and their possible determinants, are discussed.(AU)

Impaired pituitary responsiveness to luteinizing hormone-thyrotropin releasing hormone: a possible sickle-cell disease - abstract

Homozygous sickle-cell(SS) disease is associated with delayed development and reduced fertility in both men and women. The results of an initial pilot study indicated significantly lower (p<0.01) serum levels of testosterone in male SS patients. This study is a further attempt to evaluate pituitary responsiveness to exogenous administration of luteinizing-thyrotropin releasing hormone (LHRH-TRH) in a group of 10 male SS patients, each matched with a brother without SS disease to determine whether a defect exists in the central regulation of pituitary secretions in these patients. The mean serum testosterone levels were significantly lower (p < 0.025), whereas basal levels of luteinizing hormone (LH) and thyrotropin (TSH) were significantly higher (p < 0.05) at 20 minutes in the SS patients. Mean LH responses were consistently higher in SS patients but the differences only reached significantly (p<0.05) at 120 minutes after LHRH-TRH administration. We concluded that subnormal levels of serum testosterone in SS disease are not solely attributable to primary testicular failure, but also result from defect(s) in LH-negative feed back operation (AU)

Fetal haemoglobin and clinical severity of homozygous sickle cell disease in early childhood

The relationship of the clinical features of homozygous sickle cell disease in the first two years of life to the level of fetal hemoglobin at 6 months was investigated. Mean HgbF levels were significantly lower in children manifesting early palpable splenomegaly, dactylitis, acute splenic sequestration, and in those who died. The risks of dactylitis and ASS were significantly greater in patients with lower HgbF levels. Since early splenomegaly itself may increase the risks of ASS, infection, and death, the relationship of HgbF to these features was further analyzed within the early splenomegaly group.The results suggest that a low HgbF may have a direct effect on the etiology of ASS, but any effect on infection or death is probably mediated via its relationship with the appearance of a palpable spleen. A protective effect of a high HgbF on the risk of dactylitis was demonstrated coincident with the accepted theory of its pathogenesis. Early HgbF determinations may be of value in identifying patients at high risk of serious complications during infancy (AU)

Skinfold thickness and nutritional status in young Jamaican children

Height, weight, and mid-upper arm circumference and skin-fold thickness at four sites (triceps, biceps, subscapular, and supra-iliac) were measured in a representative sample of 121 Jamaican children of predominantly African origin, aged 4-6 years. Subscapular skinfold thickness was slightly below standards based on white children, but triceps skinfold thickness was substancially smaller, suggesting ethnic differences in the distribution of subcutaneous body fat. Sum skinfold thickness explained less than half the variance in corrected weight, an estimate of weight for height and an accepted index of acute malnutrition. Sum skinfold thickness correlated with corected weight more closely among girls (r=0.72) than boys (r=0.48). Mid-upper arm circumference explained 64 percent of the variability in corrected weight and sex differences were less marked. Among populations of African origin, mid-upper arm circumference may be a more reliable index of nutritional status than triceps skinfold thickness which gives misleading results, especially in boys (AU)

Urea kinetics in adults with homozygous sickle cell disease

The kinetics of urea metabolism were measured in four adults with homozyguous sickle cell disease (HbSS). On a dietary intake of 1.2 to 2.7g protein /kg/d. A relatively small proportion of the urea was excreted in the urine (40 per cent), with a high fixed rate of hydrolysis in the bowel, 145 mg nitrogen /kg/d. Although 50 per cent of the nitrogen from hydrolysed urea was resynthesized to urea, and a further 10 per cent may have been lost in the stool, it is estimated that 58 mg nitrogen /kg/d was available for synthetic metabolic activity. Urea kinetics in sickle cell disease subjects are markedly different from normals, and this may be a reflection of the metabolic demands for increased red cell synthesis. (AU)

Sickle cell-Hb Lepore Boston syndrome: uncommon differential diagnosis to homozygous sickle cell disease

Two siblings assumed on the basis of clinical and hematological evidence to have homozygous sickle cell (SS) disease were found to have a mother without sickle hemoglobin. Subsequent investigation and hemoglobin structural studies indicated the diagnosis to be sickle cell-Hb Lepore Boston syndrome. This syndrome generally manifests clinically significant sickle cell disease, and this genotype should be borne in mind in apparent SS disease where a parent without sickle hemoglobin is discovered.(AU)

The mechanism of low testosterone levels in homozygous sickle-cell disease

Significantly lower testosterone levels are common in male patients with homozygous sickle-cell (SS) disease and have been attributed to either abnormalities of the hypothalamo-pituitary axis or primary testicular failure. The mechanism has now been investigated by observing the response to gonadrotropin-thytotropin releasing hormones (GnRH-TRH) in 10 male patients with SS disease and in 10 matched male sibling controls without sickle-cell disease. Mean basal levels of luteninizing hormone (LH) follicular stimulating hormone (FSH) and thyrotropin (TSH) were significantly elevated but prolactin (RL) levels were within the normal range in the SS group. All hormones increased following GnRH-TRH, and proportionate increases over baseline were similar for FSH and TSH in SS and AA subjects, but SS patients showed a lesser percentage increase in LH at 30 minutes, and a higher percentage increase in PRL at 60 minutes. These observations are more consistent with primary testicular failure than with adnormalities of the hypothalmic-pituitaty-testicular axis (AU)

Abnormal thyroid hormone and thyrotropin levels in homozygous sickle cell disease

Male patients with SS disease had significantly lower T3 and higher TSH levels than a comparison group. Stimulation with TRH in 10 male sibling pairs showed highly significant increases in T3 and TSH in both patients and sibling controls although the increase in TSH was significantly greater in SS disease. The interpretation of these findings unclear although the thyroid indices indicate an abnormal pituitary-thyroid axis most consistent with a modest primary thyroid failure

Haematological change in sickle cell-haemoglobin C disease and in sickle cell-beta thalassaemia: a cohort study from birth

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell-haemoglobin C (SC) disease, sickle cell-á+ thalassaemia, and in sickle cell-á Thalassaemia. Most haematological indices in SC disease were intermediate between previously published values in SS disease and in AA controls, generally being closer to values in normal children, Eceptions were microcytosis which may be genetically determined and a striking elevation of mean cell haemoglobin cocentration from age 2 months to 4 years. The combination of a raised MCHC and a lowered MCV is unusual and may be characteristic of SC disease. Features in sickle cell-á thalassaemaia generally differed accordingly to the type of á thalassaemia gene. Sickle cell-B degree thalassaemia had lower levels of haemoglobin, MCHC, red cell count, MCV, and higher reticulocytes, most differences being significant before 1 year. No differences between SB degree thalassaemia and Sá+ thalassaemia were apparent in HbF levels (which resembled those in SS disease) or in HbA2 levels (which exceeded those in SS disease by 1 year of age).(AU)

Alpha thalassemia and the hematology of homozygous sickle cell disease in childhood

Alpha thalassemia modifies the gematolic expression of homozygous sickle cell (SS) disease, resulting in increased total hemoglobin and HbA2 and decreased HbF, mean cell volume, reticulocytes, irreversibly sickled cells, and biliru-bin levels. The age at which these changes develop in children with SS disease is unknown. Ascertainment of globin gene status in a large representative sample of study the gematologic indices in nine children homozygous for Alpha thalassemia 2 (two-gene group), 90 children heterozygous for Alpha thalassemia 2 (three-gene group), and 167 children with a normal Alpha globin gene complement (four-gene group). The two-gene group had significantly lower mean cell volumes from birth, higher red cell counts from one month, lower reticulocytes from three months, and higher HbA2 levels from one year, as compared with the four-gene group. Children with three genes had intermediate indices but resembled more closely the four-gene group. Differences in total hemoglobin or in fetal hemoglobin between the groups were not apparent by eight years of age. The most characteristic differences of the two-gene group were the raised proportional HbA2 level and low mean cell volume, the latter having some predictive value for Alpha thalassemia status at birth.(AU)