Impact of sleeve gastrectomy on red blood cell aggregation: a 12-month follow-up study.

OBJECTIVE: To investigate the effects of weight loss due to laparoscopic sleeve gastrectomy (LSG) on erythrocyte aggregation and the relationship of anthropometric and plasmatic factors, such as plasma viscosity, fibrinogen and lipids, with erythrocyte aggregation. DESIGN AND SUBJECTS: The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser (LORCA). Before the LSG and 6 and 12 months after the LSG, we evaluated the aggregation index (AI), amplitude (AMP) and aggregation half-time (t1/2), plasma viscosity, fibrinogen, glucose and lipids patterns in 15 non-diabetic obese subjects. RESULTS: The static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery were calculated and significant differences were observed at 12 months after surgery. AI and AMP decreased from 69.81±5.12% and 27.43±2.9 a.u. at baseline to 64.91±5.94% and 22.15±4.3 a.u. 12 months after surgery, respectively. The t1/2 increased from 1.7 (1.32-2.24) s at baseline compared with 2.02 (1.68-2.42) s at 12 months after the surgery. Plasma viscosity and fibrinogen decreased from 1.50±0.093 mPa s and 3.0±0.41 g l(-1) at baseline to 1.407±0.062 mPa s and to 2.66±0.25 g l(-1) 12 months after surgery, respectively. AI correlated positively with BMI (r=0.74, P=0.001), waist circumference (r=0.68, P=0.005), fibrinogen (r=0.52, P=0.045) and plasma viscosity (r=0.76, P=0.001) and negatively with percentages of weight lost after surgery (r=-0.54, P=0.034). Multivariate analyses found that the BMI, fibrinogen and plasma viscosity independently influenced the AI. CONCLUSION: The study demonstrated that weight loss due to restrictive bariatric surgery can beneficially affect red cell aggregation parameters. The improvement of the RBC aggregation behaviours among obese subjects with weight loss due to LSG was associated with changes in plasmatic factors, especially fibrinogen.

Cortisol and ghrelin concentrations following a cold pressor stress test in overweight individuals with and without night eating.

OBJECTIVE: To explore appetite-related hormones following stress in overweight individuals, and their relationship with night eating (NE) status. METHOD: We measured plasma cortisol and ghrelin concentrations, and recorded ratings of stress and hunger in response to a physiological laboratory stressor (cold pressor test, CPT), in overweight women with (n=11; NE) and without (n=17; non-NE) NE. RESULTS: Following the CPT, cortisol (P<0.001) and ghrelin (P<0.05) levels increased, as did stress and hunger ratings (all P<0.001), across all subjects (NE and non-NE). NE exhibited higher baseline cortisol (P<0.05) levels than non-NE. NE also had greater cortisol area under the curve (AUC) than non-NE (P=0.019), but not when controlling for baseline cortisol levels. Ghrelin baseline and AUC did not differ between groups. NE showed higher AUC stress (P<0.05), even when controlling for baseline stress. DISCUSSION: Overweight individuals showed increased cortisol, ghrelin, stress and hunger following a laboratory stressor, and there was some evidence for greater increases in cortisol and subjective stress among NE. The greater AUC cortisol level in NE was due to higher baseline levels, but the group difference in stress was in direct response to the stressor. Our results support a role for cortisol and stress in NE.

Industrial support of university research in biotechnology.

A 1984 study of biotechnology companies reveals that nearly one-half of all such firms fund research in universities. Industry may support as much as one-quarter of all biotechnology research in institutions of higher education. These investments seem to be yielding substantial benefits to involved firms. Per dollar invested, university research is generating more patent applications than is other company research. Research relationships do pose some risks to traditional university values such as openness of communication among scholars. These risks may be greater in relationships involving small firms. The data also reveal that government is now, and seems likely to remain, the principal source of support for university research in biotechnology.

University-industry research relationships in biotechnology: implications for the university.

The growth of university-industry research relationships in biotechnology has raised questions concerning their effects, both positive and negative, on universities. A survey of over 1200 faculty members at 40 major universities in the United States reveals that biotechnology researchers with industrial support publish at higher rates, patent more frequently, participate in more administrative and professional activities and earn more than colleagues without such support. At the same time, faculty with industry funds are much more likely than other biotechnology faculty to report that their research has resulted in trade secrets and that commercial considerations have influenced their choice of research projects. Although the data do not establish a causal connection between industrial support and these faculty behaviors, our findings strongly suggest that university-industry research relationships have both benefits and risks for academic institutions. The challenge for universities is to find ways to manage these relationships that will preserve the benefits while minimizing the risks.

KIE: An analysis is provided of a survey of over 1,200 faculty members at 40 major U.S. universities concerning their research activities and funding by industrial sources. The survey findings suggest that university-industry biotechnology research relationships have both benefits and risks for the university. Faculty members receiving industry support tend to be more productive. They publish, patent, and earn more. They participate in more administrative and professional activities, while teaching as much as other faculty members. However, their research also leads to more unpublished trade secrets, and commercial considerations may influence their choice of projects. The authors recommend public as well as commercial funding of research, protection of the right to publish research results, and university-industry agreements that do not unduly restrict faculty behavior.

Serum Irisin, Adropin, and Preptin in Obese Patients 6 Months After Bariatric Surgery.

BACKGROUND/OBJECTIVES: The reduction of body mass after bariatric surgery affects energy metabolism and may involve changes in irisin, preptin, and adropin production. SUBJECTS AND METHODS: Fifty-five morbidly obese patients with a mean body mass index (BMI) of 45.7 ± 5.8 kg/m2 were treated with either laparoscopic sleeve gastrectomy(n = 30) or laparoscopic adjustable gastric banding (n = 25). Forty-six (83.6%) were followed-up 6 months after surgery. The control group included 15 healthy non-obese participants. Anthropometric measurements, lipid profiles, HbA1c, and serum irisin, preptin, and adropin were assessed at baseline and on follow-up. RESULTS: The serum concentrations of all three peptides were higher at 6 months than at baseline but only irisin (p = 0.02) and adropin (p = 0.000001) were significantly higher. The increase in preptin was borderline significant (p = 0.051). Changes of serum concentrations of all three peptides were bidirectional. CONCLUSION: Body mass reduction resulting from bariatric procedures may change the production of energy regulating peptides, but not always in a favorable manner.

Basal ganglia and dopamine contributions to probabilistic category learning.

Studies of the medial temporal lobe and basal ganglia memory systems have recently been extended towards understanding the neural systems contributing to category learning. The basal ganglia, in particular, have been linked to probabilistic category learning in humans. A separate parallel literature in systems neuroscience has emerged, indicating a role for the basal ganglia and related dopamine inputs in reward prediction and feedback processing. Here, we review behavioral, neuropsychological, functional neuroimaging, and computational studies of basal ganglia and dopamine contributions to learning in humans. Collectively, these studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences. The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli and support flexible generalization of learning to novel contexts and stimuli. By breaking down our understanding of the cognitive and neural mechanisms contributing to different aspects of learning, recent studies are providing insight into how, and when, these different processes support learning, how they may interact with each other, and the consequence of different forms of learning for the representation of knowledge.

Probabilistic categorization: how do normal participants and amnesic patients do it?

In probabilistic categorization tasks, various cues are probabilistically (but not perfectly) predictive of class membership. This means that a given combination of cues sometimes belongs to one class and sometimes to another. It is not yet clear how categorizers approach such tasks. Here, we review evidence in favor of two alternative conceptualizations of learning in probabilistic categorization: as rule-based learning, or as incremental learning. Each conceptualization forms the basis of a way of analyzing performance: strategy analysis assumes rule-based learning, while rolling regression analysis assumes incremental learning. Here, we contrasted the ability of each to predict performance of normal categorizers. Both turned out to predict responses about equally well. We then reviewed performance of patients with damage to regions deemed important for either rule-based or incremental learning. Evidence was again about equally compatible with either alternative conceptualization of learning, although neither predicted an involvement of the medial temporal lobe. We suggest that a new way of conceptualizing probabilistic categorization might be fruitful, in which the medial temporal lobe help set up representations that are then used by other regions to assign patterns to categories.

Comparison of eating disorders and body image disturbances between Eastern and Western countries.

Factors associated with the development of eating disorders in countries with non-Western cultures have not been adequately investigated in relation to Westernized countries. We therefore studied 243 girls [age =16.5+/-1.2 (SD)], recruited from schools in India, Tibet, the US and France. They completed the Figure Rating Scale (FRS), the Eating Attitudes Test (EAT), and the Beck Depression Inventory (BDI). The Tibetan group had a lower body mass index (BMI) than the other groups (p<0.0001), which did not differ from each other. All groups differed significantly on socio-economic status (SES), with those living in India having the highest (p<0.0001). Prior to controlling for age, SES, and BMI, there were no significant differences on any psychological measure between the individual countries, or when collapsed by East vs. West. However, after controlling for the same covariates, the Tibetan group selected a significantly larger current (p<0.0001) and ideal body size (p=0.03), compared to all the other countries, and had more body image discrepancy than the American group (p=0.04). After controlling only for BMI, the girls from the East had a larger current and ideal, but no difference on body image discrepancy. Body image discrepancy scores were best predicted by EAT scores and BMI, accounting for 35% of the variance (p<0.0001). EAT scores themselves were best predicted by mother's education, BDI, body image discrepancy, and drug and tobacco use, accounting for 33% of the variance (p<0.0001). Unlike some other studies, we did not observe greater body image discrepancy and eating pathology in Western cultures, whether or not controlling for age, SES, and BMI. There were no differences in eating and depression pathology between those in the US, France, or India. Indeed, the Tibetans, after controlling for their low BMI and SES, had the greatest body image discrepancy.

Night eating status and influence on body weight, body image, hunger, and cortisol pre- and post- Roux-en-Y Gastric Bypass (RYGB) surgery.

Night Eating Syndrome is a common disorder in severely obese individuals and may be associated with hypothalamic pituitary adrenal (HPA) axis dysregulation. This study compared night eaters (NE) and comparably obese controls (C) pre- and post-Roux-en- Y Gastric Bypass surgery at 2 and 5 months, following an overnight fast on hormonal measures associated with HPA axis and related appetite and psychological measures. There were 24 (10 NE, 14 C) clinically severely obese participants (body mass index =47.0+/-8.4 SD). At pre-surgery baseline, afternoon fasting hunger ratings differed significantly and were lower for NE than for C (p=0.01). Eight of the participants (4 NE, 4C) returned for all 3 study visits. At 5 months post-surgery, NE and C did not differ in weight loss, reductions in waist circumference, insulin levels, and insulin resistance (homeostasis model assessment). However, NE as compared to C, did not improve in self ratings of body image (p<0.05), and had significant increases in fasting afternoon cortisol levels 5 months after surgery (p=0.01).

Conditional discrimination and reversal in amnesia subsequent to hypoxic brain injury or anterior communicating artery aneurysm rupture.

Human anterograde amnesia can develop following bilateral damage to the hippocampus and medial temporal lobes, as in hypoxic brain injury, or following damage to the basal forebrain, as following anterior communicating artery (ACoA) aneurysm rupture. In both cases, the mnestic deficit may be similar when assessed by standard neuropsychological measures. However, animal and computational models suggest that there are qualitative differences in the pattern of impaired and spared memory abilities following damage to hippocampus versus basal forebrain. Here, we show such a dissociation in human amnesia using a single two-stage task, involving conditional discrimination and reversal. Consistent with a prior study, 10 individuals with anterograde amnesia subsequent to hypoxic brain injury were spared on acquisition but impaired at reversal. However, 10 individuals with amnesia subsequent to ACoA aneurysm showed the opposite pattern of impaired acquisition but spared reversal. The differences between groups cannot be easily ascribed to severity of mnestic or cognitive deficit, since the two amnesic groups performed similarly on neuropsychological tests of memory, intelligence and attention. The results illustrate qualitative differences in memory impairments in hypoxic and ACoA amnesics and highlight the importance of considering etiology in evaluating mnemonic deficits in amnesic populations.

13C-NMR of Clostridium pasteurianum ferredoxin after reductive methylation of the amines using [13C]formaldehyde.

Clostridium pasteurianum 2(4Fe-4S) ferredoxin has been reductively methylated using [13C]formaldehyde and sodium cyanoborohydride. Lys3 and the N-terminal alanine, the only amines in the protein, are both dimethylated by this procedure. 13C-NMR titration of the apo, oxidized and reduced modified ferrodoxin indicate that the lysine pK is slightly over 10 in all three forms of the protein. In contrast, the N-terminal alanine shifts from a pK of 7.7 in the apoprotein to greater than 9 in both the oxidized and reduced modified ferredoxin. The unexpectedly high pK observed for the N-terminus is consistent with the presence of an ion pair in both the oxidized and reduced native forms of the protein. The methylated ferrodoxin is considerably less stable than the native protein, indicating an important role for the amines in protein stability.

Epidemiology and immunogenetic background of islet cell antibody--positive nondiabetic schoolchildren. Ulm-Frankfurt population study.

Islet cell antibodies (ICAs) were determined in a large cohort of white nondiabetic schoolchildren (n = 4287) from a homogenous population in southern Germany. The prevalence of ICA levels greater than or equal to 5 Juvenile Diabetes Foundation (JDF) U was 1.05% (95% confidence interval 0.8-1.4%). Analysis of HLA-DR beta and -DQ beta alleles revealed that the specificities found to be increased in insulin-dependent (type I) diabetic subjects with the same ethnic background were also associated with ICA positivity in the nondiabetic schoolchildren. HLA-DR3 (P less than 0.01) and -DR4 (P less than 0.01) phenotypes and absence of Asp residue (P less than 0.01) at codon 57 of the HLA-DQ beta-chain were significantly increased in ICA+ compared with control subjects. High levels of ICAs, which were categorized as either greater than or equal to 17 or greater than or equal to 30 JDF U, were found to be associated with amino acids other than Asp at position 57 of the HLA-DQ beta-chain. No association of ICA level was found for HLA-DR phenotypes.

Mitochondrial inhibition and oxidative stress: reciprocating players in neurodegeneration.

Although the etiology for many neurodegenerative diseases is unknown, the common findings of mitochondrial defects and oxidative damage posit these events as contributing factors. The temporal conundrum of whether mitochondrial defects lead to enhanced reactive oxygen species generation, or conversely, if oxidative stress is the underlying cause of the mitochondrial defects remains enigmatic. This review focuses on evidence to show that either event can lead to the evolution of the other with subsequent neuronal cell loss. Glutathione is a major antioxidant system used by cells and mitochondria for protection and is altered in a number of neurodegenerative and neuropathological conditions. This review also addresses the multiple roles for glutathione during mitochondrial inhibition or oxidative stress. Protein aggregation and inclusions are hallmarks of a number of neurodegenerative diseases. Recent evidence that links protein aggregation to oxidative stress and mitochondrial dysfunction will also be examined. Lastly, current therapies that target mitochondrial dysfunction or oxidative stress are discussed.

Integrating incremental learning and episodic memory models of the hippocampal region.

By integrating previous computational models of corticohippocampal function, the authors develop and test a unified theory of the neural substrates of familiarity, recollection, and classical conditioning. This approach integrates models from 2 traditions of hippocampal modeling, those of episodic memory and incremental learning, by drawing on an earlier mathematical model of conditioning, SOP (A. Wagner, 1981). The model describes how a familiarity signal may arise from parahippocampal cortices, giving a novel explanation for the finding that the neural response to a stimulus in these regions decreases with increasing stimulus familiarity. Recollection is ascribed to the hippocampus proper. It is shown how the properties of episodic representations in the neocortex, parahippocampal gyrus, and hippocampus proper may explain phenomena in classical conditioning. The model reproduces the effects of hippocampal, septal, and broad hippocampal region lesions on contextual modulation of classical conditioning, blocking, learned irrelevance, and latent inhibition.

Costs and health consequences of cholesterol screening for asymptomatic older Americans.

To predict the consequences of cholesterol screening among elderly Americans who do not have symptoms of heart disease, we explore the cost implications of a cholesterol screening program, evaluate evidence linking hypercholesterolemia to coronary heart disease and mortality in the elderly, and describe the likely effects of therapy of hypercholesterolemia. According to our calculations, if all Americans 65 years of age and older adhered to a cholesterol screening program similar to the one proposed by the National Cholesterol Education Program, minimum annual expenditures for screening and treatment would be between $1.6 billion and $16.8 billion, depending on the effectiveness of diet and the cost of the medications used to treat hypercholesterolemia. There is no direct evidence that this program would lessen overall morbidity or extend the lives of elderly Americans.

Lupus nephritis. Clinical course as related to morphologic forms and their transitions.

An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms. The present observations serve to emphasize the importance of strict morphologic classification in the comparison of different treatment regimens for lupus nephritis. In view of the grave prognosis of established diffuse proliferative lupus nephritis, which probably evolves from a mesangial involvement common to all patients with SLE from its onset, early therapy may be the key to the management of lupus nephritis.

Reactivity and intracellular location of the ACTH cell autoantigen in human fetal and adult anterior pituitary tissue.

Autoantibodies to anterior pituitary ACTH cells have been described in the sera from patients with Cushing's disease. We were here able to show that true ACTH cell autoantibodies do not react with the hormone itself or with Fc receptors in ACTH cells. They rather recognize a distinct pituitary cell-specific cytoplasmatic autoantigen located in a juxtanuclear position. ACTH cells from human adult pituitaries express Fc receptors producing a non-specific broad and diffuse cytoplasmic binding of normal immunoglobulins. After preparation of Fc-free F(ab)2 fractions from human immunoglobulins it could be demonstrated by immunohistochemical methods that human adult pituitary ACTH cells also contain the fetal ACTH cell autoantigen. However, Fc receptors, ACTH hormone or other proopiomelanocortin- (POMC-) derived fragments and the ACTH cell autoantigen are all located at distinct intracellular sites. ACTH cells in human fetal pituitaries were shown to lack Fc receptors. Thus, with this source of antigen the characteristic autoantibody pattern can be detected with undigested sera.

The level and the persistence of islet cell antibodies in healthy schoolchildren are associated with polymorphic residues of the HLA-DQ beta chain.

Cytoplasmic islet cell antibodies (ICA) were determined in a group of non-diabetic Caucasian schoolchildren (n = 4208). The prevalence rate for ICA positivity was 1.05 per cent (95 per cent confidence interval: 0.8-1.4 per cent). Analysis of HLA risk factors revealed that HLA-DRB1*03 (p less than 0.01), HLA-DRB1*04 (p less than 0.01) and HLA haplotypes with non-charged amino acids (non-Asp) at codon 57 of the HLA-DQ beta (p less than 0.01) chain were significantly increased when compared to controls. High levels of islet cell antibodies, i.e. Juvenile Diabetes Federation units (JDF units) equal to or greater than 30 JDF units were found to be associated with amino acids other than aspartic acid at codon 57 of the DQ beta chain molecule. Also the persistence of circulating ICA was found to be associated with non-Asp homozygosity of the proband (p less than 0.03).

From conditioning to category learning: an adaptive network model.

We used adaptive network theory to extend the Rescorla-Wagner (1972) least mean squares (LMS) model of associative learning to phenomena of human learning and judgment. In three experiments subjects learned to categorize hypothetical patients with particular symptom patterns as having certain diseases. When one disease is far more likely than another, the model predicts that subjects will substantially overestimate the diagnosticity of the more valid symptom for the rare disease. The results of Experiments 1 and 2 provide clear support for this prediction in contradistinction to predictions from probability matching, exemplar retrieval, or simple prototype learning models. Experiment 3 contrasted the adaptive network model with one predicting pattern-probability matching when patients always had four symptoms (chosen from four opponent pairs) rather than the presence or absence of each of four symptoms, as in Experiment 1. The results again support the Rescorla-Wagner LMS learning rule as embedded within an adaptive network model.

Context, conditioning, and hippocampal rerepresentation in animal learning.

The researchers argue that a previous computational account of hippocampal region function in associative learning (M. Gluck & C. Myers, 1993) has emergent implications that accurately describe the role of the hippocampal region in contextual processing. This article unifies 2 seemingly conflicting views of contextual processing: It accords contextual cues no special representational status (e.g., R. Rescorla & A. Wagner, 1972), yet it also allows context to stand in a superordinate relationship to the cues it contains (e.g., L. Nadel & J. Willner, 1980). As a result, the account correctly expects that context can develop occasion-setting properties and that context shifts can weaken learned responses or attenuate latent inhibition. The article also explains data suggesting that hippocampal lesions reduce contextual sensitivity. It may help unify several previous theoretical accounts of the hippocampal region's role in contextual processing.