Newborn insula gray matter volume is prospectively associated with early life adiposity gain.

BACKGROUND: The importance of energy homeostasis brain circuitry in the context of obesity is well established, however, the developmental ontogeny of this circuitry in humans is currently unknown. Here, we investigate the prospective association between newborn gray matter (GM) volume in the insula, a key brain region underlying energy homeostasis, and change in percent body fat accrual over the first six months of postnatal life, an outcome that represents among the most reliable infant predictors of childhood obesity risk. METHODS: A total of 52 infants (29 male, 23 female, gestational age at birth=39(1.5) weeks) were assessed using structural MRI shortly after birth (postnatal age at MRI scan=25.9(12.2) days), and serial Dual X-Ray Absorptiometry shortly after birth (postnatal age at DXA scan 1=24.6(11.4) days) and at six months of age (postnatal age at DXA scan 2=26.7(3.3) weeks). RESULTS: Insula GM volume was inversely associated with change in percent body fat from birth to six-months postnatal age and accounted for 19% of its variance (ß=-3.6%/S.D., P=0.001). This association was driven by the central-posterior portion of the insula, a region of particular importance for gustation and interoception. The direction of this effect is in concordance with observations in adults, and the results remained statistically significant after adjusting for relevant covariates and potential confounding variables. CONCLUSIONS: Altogether, these findings suggest an underlying neural basis of childhood obesity that precedes the influence of the postnatal environment. The identification of plausible brain-related biomarkers of childhood obesity risk that predate the influence of the postnatal obesogenic environment may contribute to an improved understanding of propensity for obesity, early identification of at-risk individuals, and intervention targets for primary prevention.

Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.

The profile of brain structural abnormalities in schizophrenia is still not fully understood, despite decades of research using brain scans. To validate a prospective meta-analysis approach to analyzing multicenter neuroimaging data, we analyzed brain MRI scans from 2028 schizophrenia patients and 2540 healthy controls, assessed with standardized methods at 15 centers worldwide. We identified subcortical brain volumes that differentiated patients from controls, and ranked them according to their effect sizes. Compared with healthy controls, patients with schizophrenia had smaller hippocampus (Cohen's d=-0.46), amygdala (d=-0.31), thalamus (d=-0.31), accumbens (d=-0.25) and intracranial volumes (d=-0.12), as well as larger pallidum (d=0.21) and lateral ventricle volumes (d=0.37). Putamen and pallidum volume augmentations were positively associated with duration of illness and hippocampal deficits scaled with the proportion of unmedicated patients. Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities in schizophrenia, which is consistent with that based on traditional meta-analytic approaches. This first ENIGMA Schizophrenia Working Group study validates that collaborative data analyses can readily be used across brain phenotypes and disorders and encourages analysis and data sharing efforts to further our understanding of severe mental illness.

Prospective association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity.

BACKGROUND: Mitochondria are multifunctional energy-producing and signaling organelles that support life and contribute to stress adaptation. There is a growing understanding of the dynamic relationship between stress exposure and mitochondrial biology; however, the influence of stress on key domains of mitochondrial biology during early-life, particularly the earliest phases of intra-uterine/prenatal period remains largely unknown. Thus, the goal of this study was to examine the impact of fetal exposure to stress (modeled as the biological construct allostatic load) upon mitochondrial biology in early childhood. METHODS: In n = 30 children (range: 3.5-6 years, 53% male), we quantified mitochondrial content via citrate synthase (CS) activity and mtDNA copy number (mtDNAcn), and measured mitochondrial bioenergetic capacity via respiratory chain enzyme activities (complexes I (CI), II (CII), and IV (CIV)) in platelet-depleted peripheral blood mononuclear cells (PBMCs). In a cohort of healthy pregnant women, maternal allostatic load was operationalized as a latent variable (sum of z-scores) representing an aggregation of early-, mid- and late-gestation measures of neuroendocrine (cortisol), immune (interleukin-6, C-reactive protein), metabolic (homeostasis model assessment of insulin resistance, free fatty acids), and cardiovascular (aggregate systolic and diastolic blood pressure) systems, as well as an anthropometric indicator (pre-pregnancy body mass index [BMI]). RESULTS: An interquartile increase in maternal allostatic load during pregnancy was associated with higher mitochondrial content (24% and 15% higher CS and mtDNAcn), and a higher mitochondrial bioenergetic capacity (16%, 23%, and 25% higher CI, CII and CIV enzymatic activities) in child leukocytes. The positive association between maternal allostatic load during pregnancy and child mitochondrial content and bioenergetic capacity remained significant after accounting for the effects of key pre- and post-natal maternal and child covariates (p's < 0.05, except CI p = 0.073). CONCLUSION: We report evidence that prenatal biological stress exposure, modeled as allostatic load, was associated with elevated child mitochondrial content and bioenergetic capacity in early childhood. This higher mitochondrial content and bioenergetic capacity (per leukocyte) may reflect increased energetic demands at the immune or organism level, and thus contribute to wear-and-tear and pathophysiology, and/or programmed pro-inflammatory phenotypes. These findings provide potential mechanistic insight into the cellular processes underlying developmental programming, and support the potential role that changes in mitochondrial content and bioenergetic functional capacity may play in altering life-long susceptibility for health and disease.

Comparison of SNR and CNR for in vivo mouse brain imaging at 3 and 7 T using well matched scanner configurations.

Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) for magnetic resonance microimaging were measured using two nearly identical magnetic resonance imaging (MRI) scanners operating at field strengths of 3 and 7 T. Six mice were scanned using two imaging protocols commonly applied for in vivo imaging of small animal brain: RARE and FLASH. An accounting was made of the field dependence of relaxation times as well as a small number of hardware disparities between scanner systems. Standard methods for relaxometry were utilized to measure T1 and T2 for two white matter (WM) and two gray matter (GM) regions in the mouse brain. An average increase in T1 between 3 and 7 T of 28% was observed in the brain. T2 was found to decrease by 27% at 7 T in agreement with theoretical models. The SNR was found to be uniform throughout the mouse brain, increasing at higher field by a factor statistically indistinguishable from the ratio of Larmor frequencies when imaging with either method. The CNR between GM and WM structures was found to adhere to the expected field dependence for the RARE imaging sequence. Improvement in the CNR for the FLASH imaging sequence between 3 and 7 T was observed to be greater than the Larmor ratio, reflecting a greater susceptibility to partial volume effects at the lower SNR values at 3 T. Imaging at 7 T versus 3 T in small animals clearly provides advantages with respect to the CNR, even beyond the Larmor ratio, especially in lower SNR regimes. This careful multifaceted assessment of the benefits of higher static field is instructive for those newly embarking on small animal imaging. Currently the number of 7 T MRI scanners in use for research in human subjects is increasing at a rapid pace with approximately 30 systems deployed worldwide in 2008. The data presented in this article verify that if system performance and radio frequency uniformity is optimized at 7 T, it should be possible to realize the expected improvements in the CNR and SNR compared with MRI at 3 T.

Separation of human peripheral blood monocytes on continuous density gradients of polyvinylpyrrolidone-coated silica gel (Percoll).

A standardized, reproducible two-step method for separation of human peripheral blood monocytes on continuous Percoll gradients has been developed. The first step involves separation of mononuclear cell on Percoll of density 1.075 g/ml and the second step separation of monocytes from lymphocytes on a continuous Percoll gradient with a starting density of 1.075 g/ml for the formation of the gradient. The average yield during a 10 month period of daily routine use has been 74 +/- 17% (mean +/- 1 S.D.), and the average purity 63 +/- 10%. Ninety to 95% of the monocytes are viable after separation as judged from trypan blue exclusion and by ingestion of latex particles and sensitized sheep erythrocytes. The separation takes about 3 h and the total number of monocytes obtained from 40 ml of blood is in the range of 10-15 x 106. The procedure has been reliable with 3-4% separation failures, mainly due to bacterial or fungal growth in Percoll suspension or media. The contaminating cells are exclusively lymphocytes, predominantly T-lymphocytes (90-95%), when citrate is used as anticoagulant. Heparin can not be used as anticoagulant, as there appears to be a dose-dependent formation of thrombocyte aggregates which contaminate the monocytes, and result in poor separation.

Partial characterization of circulating macromolecular beta 2-microglobulin complexes by density gradient ultracentrifugation and page-blotting.

beta 2-microglobulin (beta 2m)-containing, rapidly sedimenting peaks were seen when sera of patients with 3% polyethylene glycol (PEG)-insoluble beta 2m were fractionated by sucrose density gradient ultracentrifugation. No such material was found in serum of a healthy volunteer without 3% PEG-insoluble beta 2m. MW of beta 2m-containing high molecular weight fractions ranged from 1.6 X 10(5) to 2.1 X 10(6). When some fractions were recentrifuged a majority of beta 2m was recovered at the original sedimentation position. Analysis of high molecular weight beta 2m-containing peaks by SDS-PAGE followed by electroblotting revealed only monomeric beta 2m indicating that beta 2m was not covalently bound in the high molecular weight material.

Enhanced binding of immune complexes processed by erythrocyte CR1 (CD 35) receptors to purified CR2 (CD 21) receptors from tonsillar mononuclear cells.

The binding of immune complexes (IC) opsonized by serum complement (C) and IC processed by CR1 (CD 35) receptors on human erythrocytes (E) to purified CR2 (CD 21) receptors was compared. Soluble CR2 was prepared from tonsillar mononuclear cells and purified by antibody affinity chromatography. Solid phase CR2 as well as CR2 subjected to PAGE and blotted onto nitro-cellulose membranes bound 125I-labelled BSA anti-BSA IC which had been opsonized by C and processed by CR1 up to ten times more efficiently than IC reacted with serum only. Radiolabelled monomeric C3d also bound to solid phase CR2. The binding of IC to purified and solid phase bound CR2 could be inhibited by anti-CR2 antibodies or by preincubation of the IC with polyclonal antibodies reacting with C3d or C3b/iC3b. Thus, both C3dg and iC3b appeared to mediate binding of IC to CR2. Preincubation of solid phase CR2 with purified monomeric C3d did not inhibit the subsequent binding of E-CR1 processed IC. The data indicate that E-CR1 have an important role in generating IC which bind effectively to CR2 receptors on B lymphocytes.

Simultaneous quantitation of free haptoglobin and haemoglobin-haptoglobin (HbHp) complexes by double-decker rocket immunoelectrophoresis.

Existing immunochemical methods for haptoglobin (Hp) determination are incapable of distinguishing between free haptoglobin and haemoglobin-haptoglobin (HbHp) complexes. A one-dimensional double-decker rocket immunoelectrophoretic method (DD-RIE) for simultaneous quantitation of free Hp and Hp bound as HbHp complexes was therefore developed. The DD-RIE can be used for quantitative in vitro studies of the Hb-Hp interactions, for quantitation of Hp's Hb binding capacity and for investigations of haemolytic episodes in patients. The clinical value of the method is illustrated by an investigation of a patient with a gradual accumulation of HbHp complexes in plasma, a steady rise in total Hp and a fall in free Hp during haemolysis. A proposed receptor-mediated clearance of the complexes by the reticuloendothelial system (RES) could not be substantiated, as HbHp receptors were not demonstrable on human blood monocytes.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. I. Disease manifestations and analyses of clinical subsets.

A Danish multicentre study was undertaken of the manifestations, infections, thrombotic events, survival and predictive factors of survival in 513 Danish patients with systemic lupus erythematosus (SLE) according to the 1982 classification criteria of the American College of Rheumatology. The mean duration of follow-up was 8.2 years from diagnosis and 12.8 years from first symptom. This paper describes the most common clinical and laboratory manifestations and their relationship to sex and age at the time of onset and diagnosis. Cluster analysis revealed three clinically defined clusters at the time of disease onset. Cluster 1 (57% of patients) consisted of relatively elderly patients without nephropathy or malar rash, but with a high prevalence of discoid lesions. Cluster 2 (18%) consisted of patients with nephropathy, a third of whom also developed serositis and lymphopenia. The patients of the third cluster (25%) all had malar rash and half were photosensitive. Follow-up showed that the patients of cluster 2 developed azotaemia, large proteinuria, arterial hypertension and myositis significantly more often than did the rest of the patients, but the mortality was not increased. The risk of developing renal end-stage disease was highest in men with early-onset disease.

A multicentre study of 513 Danish patients with systemic lupus erythematosus. II. Disease mortality and clinical factors of prognostic value.

In this Danish multicentre study, predictive clinical factors of mortality and survival were calculated for 513 patients with systemic lupus erythematosus (SLE), 122 of whom died within a mean observation period of 8.2 years equalling a mortality rate of 2.9% per year. Survival rates were 97%, 91%, 76% and 64% after 1, 5, 10 and 15 years, respectively. The direct causes of death included SLE (n = 35), infections (n = 25), malignancy (n = 9), cardiovascular disease (n = 32) and other causes (n = 21). Uni- and multivariate analyses of survival and mortality were performed for all deaths and for SLE-related deaths. Azotaemia (one-fifth of the patients) was a strong predictor of increased overall and SLE-related mortality, but nephropathy per se (one-half of the patients) and large proteinuria (one-sixth of the patients) were unrelated to survival. Haemolytic anaemia had a significant negative influence on survival related to mortality caused by infections. Diffuse central nervous system disease and myocarditis were related to increased SLE-related mortality, whereas photosensitivity predicted a decreased mortality. Non-fatal infections and thrombotic events predicted a decreased overall survival. Since 1980 the mortality caused by SLE manifestations has decreased significantly.

Revised Craig Lipreading Inventory.

The two purposes of this study were to shorten the Craig Lipreading Inventory without affecting its reliability and validity and to establish normative data on the revised version. The full inventory was administered to 75 children. By item analysis, half of the items were selected to comprise the brief version; both versions were administered to another group of 75 children. Scores on the two versions correlated (.91 and .92, respectively, for Word Forms A and B and .97 and .95, respectively, for Sentence Forms A and B), thereby substantiating the construct validity of the briefer version. There was significantly high intertest reliability for the Word Forms (.80) and Sentence Forms (.82) of the briefer inventory. Normative data were computed for each age group. This briefer version is a temporally efficient tool for evaluating lipreading ability of children.

[Meningococcal disease in the Faroe Islands during the period 1978-1985]. / Meningokoksygdom på Faerøerne 1978-1985.

On the Faroe Islands (45,000 inhabitants), a total of 203 cases of meningococcal disease (MD) were recorded during the period 1978-1985. The peak incidence was 95/100,000 in 1981. MD mainly attacked children, 30% were below two years and 75% were below 11 years of age. The lethality rate was 5.4% (11 deaths). In 1981, rifampicin was introduced as a prophylactic treatment against secondary cases and at the same time, a decrease in incidence occurred. The decrease was more pronounced in the part of the country where the number of prescribed prophylactic doses per case of MD was greatest. These observations indicate that the introduction of rifampicin may have modified the course of the epidemic. None of the MD-patients had received prophylactic treatment with rifampicin. Of 132 examined, one patient with complement deficiency was identified, indicating that complement deficiencies were not a major risk factor in the epidemic of MD on the Faroe Islands.

Sociological perspectives on self-help groups: reflections on conceptualization and social processes.

AIM: The paper discusses two themes: first, professional involvement in self-help groups and secondly, sociological evidence on self-help groups in postmodern society. BACKGROUND: Self-help groups are a growing phenomenon across national borders and social/political systems. They affect the individual participants' activity level, strengthening of their self-perception and sense of belonging. METHODS: The methodological approach chosen is cross-sectional analysis of empirical findings, which is used for concept evaluation. Selected sociological theory is brought into the discussion of the role and significance of self-help groups. FINDINGS: New empirical sociological evidence shows that health care professionals - nurses, psychologists, social workers - have become an integrated part and thus essential actors in self-help groups within as well as outside the framework of the formal health care system. Involvement in self-help groups is a relatively new area of nursing practice and nursing research and serves an important function in that it sheds light on a rather unique form of social practice that is partly organized and managed by the participants themselves. By implementing modern sociological theory, which does in fact discuss social processes and relations as well as network formation, it is possible to investigate group processes unique to self-help groups and whether self-help groups potentially suppress or liberate at the individual as well as at the institutional level. CONCLUSIONS: The pronounced professional involvement leads us to question if it would not be time to re-conceptualize the self-help phenomenon, which on the one hand presupposes professional interaction and on the other hand introduces consultative services in connection with group processes. This indicates that it is necessary to introduce new aspects and themes for discussion in the health care debate and the work that goes beyond the predominantly individual orientated treatment and care function.

The haematological and biochemical pattern in occupational organic solvent poisoning and exposure.

A haematological and biochemical investigation was undertaken in 122 consecutive male patients with suspected organic solvent poisoning due to exposure to a mixture of organic solvents such as turpentine, toluene and xylene. Sixty-four healthy solvent exposed and 91 healthy non-exposed male volunteers were used as controls. The only statistically significant differences were that in the patients (B)-leucocytes and S-creatinine were lower than in the controls. (B)-monocytes were higher in all exposed groups than in the controls. S-creatine kinase was higher in patients actually exposed at the examination time, than in all other groups. B-hemoglobin, B-erythrocytes, (B)-Erc-reticulocytes, (B)-hematocrit, (B)-MCHC, (B)-MCV, (B)-Lkcs-differential count except monocytes, (B)-thrombocytes, B-sedimentation rate, P-orosomucoid, P-immunoglobulins (IgG, IgA and IgM), S-alanine amino transferase, S-urate, U-glucose, U-albumin and U-hemoglobin were unchanged. It is concluded that there was no characteristic haematological and biochemical pattern that could be of value in the individual diagnosis of organic solvent poisoning. The patients and the controls were seen as out-patients. In all groups studied, more than 10% of the results of reticulocytes, leucocytes, sedimentation rate, orosomucoid and creatine kinase exceeded the upper level of the reference interval, which is based on in-patients. New reference intervals for these 5 analyses, valid for ambulantly examined subjects, should be worked out.

The influence of C3-coated homologous erythrocytes on pokeweed-mitogen-induced polyclonal differentiation of human B cells.

The present study was undertaken in order to test the hypothesis that homologous erythrocytes (E) coated in vivo with C3d could modulate the immunoglobulin (Ig) synthesis of human peripheral blood mononuclear cells (PBMC), stimulated with pokeweed mitogen (PWM) in vitro. E from healthy individuals were found to enhance markedly the Ig synthesis of PMBC cultures stimulated with suboptimal doses (0.01 microgram/ml) of PWM. E coated in vivo with increasing amounts of C3d (1.4-6.3 times the amounts on normal E), obtained from patients with systemic lupus erythematosus, failed to induce any significant increase in Ig synthesis of PBMC cultures stimulated with suboptimal PWM doses, compared with cultures co-stimulated in parallel with normal E. In contrast, an increase in IgM and IgG synthesis was observed in about 50% of PBMC cultures from different donors when stimulated with PWM in the presence of E coated with C3b in vivo (from a patient with congenital factor I deficiency), compared with the Ig synthesis in cultures co-stimulated in parallel with normal E. In contrast to the inability of C3d-coated E to modulate B-cell proliferation, the monoclonal anti-CR2 antibody OKB7 was found to be mitogenic for unstimulated peripheral B cells.