Metabolic origin of insulin resistance in obesity with and without type 2 (non-insulin-dependent) diabetes mellitus.

A metabolic hypothesis is presented for insulin resistance in obesity, in the presence or absence of Type 2 (non-insulin-dependent) diabetes mellitus. It is based on physiological mechanisms including a series of negative feed-back mechanisms, with the inhibition of the function of the glycogen cycle in skeletal muscle as a consequence of decreased glucose utilization resulting from increased lipid oxidation in the obese. It considers the inhibition of glycogen synthase activity together with inhibition of glucose storage and impaired glucose tolerance. The prolonged duration of increased lipid oxidation, considered as the initial cause, may lead to Type 2 diabetes. This hypothesis is compatible with others based on the inhibition of insulin receptor kinase and of glucose transporter activities.

Identification of particular groups of microRNAs that positively or negatively impact on beta cell function in obese models of type 2 diabetes.

AIMS/HYPOTHESIS: MicroRNAs are key regulators of gene expression involved in health and disease. The goal of our study was to investigate the global changes in beta cell microRNA expression occurring in two models of obesity-associated type 2 diabetes and to assess their potential contribution to the development of the disease. METHODS: MicroRNA profiling of pancreatic islets isolated from prediabetic and diabetic db/db mice and from mice fed a high-fat diet was performed by microarray. The functional impact of the changes in microRNA expression was assessed by reproducing them in vitro in primary rat and human beta cells. RESULTS: MicroRNAs differentially expressed in both models of obesity-associated type 2 diabetes fall into two distinct categories. A group including miR-132, miR-184 and miR-338-3p displays expression changes occurring long before the onset of diabetes. Functional studies indicate that these expression changes have positive effects on beta cell activities and mass. In contrast, modifications in the levels of miR-34a, miR-146a, miR-199a-3p, miR-203, miR-210 and miR-383 primarily occur in diabetic mice and result in increased beta cell apoptosis. These results indicate that obesity and insulin resistance trigger adaptations in the levels of particular microRNAs to allow sustained beta cell function, and that additional microRNA deregulation negatively impacting on insulin-secreting cells may cause beta cell demise and diabetes manifestation. CONCLUSIONS/INTERPRETATION: We propose that maintenance of blood glucose homeostasis or progression toward glucose intolerance and type 2 diabetes may be determined by the balance between expression changes of particular microRNAs.

Personality traits and behavioural and psychological symptoms in patients with mild cognitive impairment.

BACKGROUND AND AIMS: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. METHOD: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. RESULTS: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. CONCLUSIONS: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

A morphological, isoenzymatic and behavioural study of ten populations of Anopheles(Nyssorhynchus) albitarsis Lynch-Arribalzaga, 1878 (Diptera: culicidae) including from the type-locality - Baradero, Argentina

Anopheles (Nyssorhynchus) albitarsis Lynch-Arribalzaga, 1878 shows morphological and behavioural variations which results in it being sometimes considered as a major malaria vector and at other times as playing no important role in epidemiology. With the aim of clarifying the taxonomy of the species, comparative morphological and isoenzymatic studies were made in populations from the type-locality, Baradero, Argentina and from 9 different localities inBrazil. Morphological studies consisted of the observation of eggs in scanning electron microscopy, of complete chaetotaxy of larvae and pupae and of the detailed drawing of male and female adults. Only Guajara-Mirim and Rio Branco populations, described previously as Anopheles deaneorum sp.n., showed morphological differences. Isoenzymes were studied using 4th instar larvae homogenate and agarosegel electrophoresis. Eleven enzymatic loci were analyzed. By calculation of Nei's Genetic Distance (D), the populations could be separated into 5 groups: i)Baradero, ii)Marajo, iii)Boa Vista, iv)Angra, Itaguai and Paraipaba and v)Guajara-Mirim and Rio Branco. These groups belong to 2 major clusters called I and II, separated by D = 0.345. In the I cluster are groups i, ii and iii and in II clusteriv and v. In I, D=0.246 separates i and ii from iii, while i is separated by D =0.181 from ii. In II, D = 0.223 between iv and v. Only the population of group vcould be distinguished morphologically from the others, leading to the description of an independent species An. deaneorum.

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.

Il desiderio materno nei casi di maltrattamento infantile

The work of this thesis would like to investigate two particular questions about the care of underage: on the one hand, the maltreatment, and the mother's desire on the other hand. About the first, this proposal try to underscore the elaborate irregularity and disparity related to this phenomenon and his historical evolution. The objective's thesis propose to underline that the abuse crosses the crisis of educational dimension inside and outside the family. We are talking about a type of crisi that places at the origin of a specific clinic and that it is about the maltreatment designated, at the same time, to cope with the educational void and with the ill-treated under age's hardships. The so-called clinic of the maltreatment horns, therefore, with the purpose to join and to set in order the normative and educational aspects. However, the prescriptive requirement is intended to measure against the same one crisis in a paradoxical way; the laws and the juveniles court must make up for the lack absence of the rules that characterized the maltreatment, getting around to use the typical reference that traditionally were been at the base of the educational way's construction. The same crimes on underage often found in the father the responsibility. The requirements and the therapeutic needs has utilized the theoretical construct of the trauma as the key line of clinical practice. On the one hand, the trauma was been paired controversially to the psychoanalytical concepts as the notion of the phantom, in the same manner that the objective truth is been opposed to the notion of the imagination and fantasy; on the other hand, the trauma was gotten to be the mark and the characteristic that defined the individual identity of the mistreated persons, regardless of the person's clinical structure or, generally, regardless of the their individual position. Both the normative demand and therapeutic converge on the idealization of the imaginary figure that is able to supply to every type of maltreatment: the mother. This position is connected on theoretical construct well-established in the mythology, that associated the mother figure to a natural dimension; this is related to the second point at issue: the mother's desire. The awareness of the mother figure in natural and idealized terms describes accusingly and negatively the trauma, without seeing the difference between trauma that helps to give a structure to the individual position from the trauma solely devastating. The mother's mythology, therefore, is in an evident antagonism with the female figure and woman's sexuality. In these way the maltreatment's clinic suggests that a woman is able to be a mother only when she doesn't appreciate the rule of female. This situation preclusives a comparison with own sexuality and gives to the women a complex of castration. The clinic cases reported highlight as these difficulties are the expression of the familiarity's heredity that wasn't been sufficiently elaborated. This condition (into the relation between mother and his child) turn the infant in the incapacity to symbolized and it doesn't help him to accede to the positive trauma, to the language and to the edipic rule; this is the reason why the child toils difficulties to approach to own personality and to orient himself in the relation with his body, with the body of the adults and the same age children.

Indirect costs of parasitism are shaped by variation in the type of immune challenge and food availability

Parasites can inflict indirect fitness costs to their hosts by eliciting costly immune responses. These costs depend on the type and amount of immunostimulants presented to the host immune system but also on the amount of resources available to fuel host immune responses. Here, we investigated how the relative costs of two different types of immune challenge are modulated by variation in food availability. We injected nestling tawny owls (Strix aluco) with either 10 mu g of phytohaemagglutinin (PHA) or 20 mu g of lipopolysaccharide (LPS), and subsequently raised them under two different food regimes (food-restricted vs. ad libitum). After controlling for food consumption, we found that LPS-injected nestlings lost more body mass than PHA-injected ones only when food-restricted. We also found that body mass gain of owlets fed ad libitum decreased with the intensity of the skin swelling response against LPS, but not PHA. These experimental and correlative results suggest that nestling tawny owls suffered greater immune costs when treated with LPS than PHA, and that variation in the costs of two different types of immune challenge can be exacerbated under conditions of low food availability. Our study highlights the importance of taking into consideration the interplay between host immunity and nutrition in the study of indirect costs of parasitism.

Use of an indirect haemagglutination test, for the detection of Clostridium perfringens type A enterotoxin

An indirect haemagglutination (IH) test is described for the detection of Clostridium perfringens type A enterotoxin, produced by strains isolated from human cases of food poisoning and from contaminated food. Though no strict relationship could be observed between titers in the IH test and the time it took mice to die from the intravenous inoculation of mice (IIM), results of the supernatants examined by both methods demonstrated that the IH test was more sensitive than the ILM one. No unspecific reaction was obtanined int he IH wirh a negative control and the inhibitions of the IH and IIM tests by specific antiserum against C. perfringens enterotoxin showed that the IH test is very spcific. The IH assay is recommended for its sensitivity and easy performance by less-equipped laboratories, by these and other data.

Type II Errors in IO Multipliers

This paper compares methods for calculating Input-Output (IO) Type II multipliers. These are formulations of the standard Leontief IO model which endogenise elements of household consumption. An analytical comparison of the two basic IO Type II multiplier methods with the Social Accounting Matrix (SAM) multiplier approach identifies the treatment of non-wage income generated in production as a central problem. The multiplier values for each of the IO and SAM methods are calculated using Scottish data for 2009. These results can be used to choose which Type II IO multiplier to adopt where SAM multiplier values are unavailable.

Personality traits and behavioral and psychological symptoms in patients at an early stage of Alzheimer's disease.

OBJECTIVE: The origins of behavioral and psychological symptoms (BPS) in Alzheimer's disease (AD) are still poorly understood. Focusing on individual personality structure, we explored the relationship between premorbid personality and its changes over 5 years, and BPS in patients at an early stage of AD. METHOD: A total of 54 patients at an early stage of AD according to ICD-10 and NINCDS-ADRDA criteria and 64 control subjects were included. Family members filled in the Neuropsychiatric Inventory Questionnaire to evaluate their proxies' current BPS and the NEO Personality Inventory Revised twice, the first time to evaluate the participants' current personality and the second time to assess personality traits as they were remembered to be 5 years earlier. RESULTS: Behavioral and psychological symptoms, in particular apathy, depression, anxiety, and agitation, are frequent occurrences in early stage AD. Premorbid personality differed between AD patients and normal control, but it was not predictive of BPS in patients with AD. Personality traits clearly change in the course of beginning AD, and this change seems to develop in parallel with BPS as early signs of AD. CONCLUSIONS: Premorbid personality was not associated with BPS in early stage of AD, although complex and non-linear relationships between the two are not excluded. However, both personality and behavioral changes occur early in the course of AD, and recognizing them as possible, early warning signs of neurodegeneration may prove to be a key factor for early detection and intervention. Copyright © 2012 John Wiley & Sons, Ltd.

Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency) is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i) 3-OHGA causes the death of astrocytes, (ii) deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii) high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

Relations of the job demands-control-support model of job strain with personality attributes : a cross-cultural study in Switzerland and South Africa

Among the various work stress models, one of the most popular to date is the job demands-­‐control (JDC) model developed by Karasek (1979), which postulates that work-­‐related strain will be the highest under work conditions characterized by high demands and low autonomy. The absence of social support at work will further increase negative outcomes. However, this model does not apply equally to all individuals and to all cultures. In the following studies, we assessed work characteristics, personality traits, culture-­‐driven individual attributes, and work-­‐related health outcomes, through the administration of questionnaires. The samples consist of Swiss (n = 622) and South African (n = 879) service-­‐oriented employees (from health, finance, education and commerce sectors) and aged from 18 to 65 years old. Results generally confirm the universal contribution of high psychological demands, low decision latitude and low supervisor support at work, as well as high neuroticism predict the worse health outcomes among employees in both countries. Furthermore, low neuroticism plays a moderating role between psychological demands and burnout, while high openness and high conscientiousness each play a moderating role between decision latitude and burnout in South Africa. Results also reveal that culture-­‐driven individual attributes play a role in both countries, but in a unique manner and according to the ethnic group of belonging. Given that organizations are increasingly characterized with multicultural employees as well as increasingly adverse and complex job conditions, our results help in identifying more updated and refined dynamics that are key between the employee and the work environment in today's context. -- L'un des modèles sur le stress au travail des plus répandus est celui développé par Karasek (1979), qui postule qu'une mauvaise santé chez les employés résulte d'une combinaison de demandes psychologiques élevées, d'une latitude décisionnelle faible et de l'absence de soutien social au travail. Néanmoins, ce modèle ne s'applique pas de façon équivalente chez tous les individus et dans toutes les cultures. Dans les études présentées, nous avons mesuré les caractéristiques de travail, les traits de personnalité, les traits culturels et les effets lies à la santé à l'aide de questionnaires. L'échantillon provient de la Suisse (n = 622) et de l'Afrique du Sud (n = 879) et comprend des employés de domaines divers en lien avec le service (notamment des secteurs de la santé, finance, éducation et commerce) tous âgés entre 18 et 65 ans. Les résultats confirment l'universalité des effets directs des demandes au travail, la latitude décisionnelle faible, le soutien social faible provenant du supérieur hiérarchique, ainsi que le névrosisme élevé qui contribuent à un niveau de santé faible au travail, et ce, dans les deux pays. De plus, un niveau faible de névrosisme a un effet de modération entre les demandes au travail et l'épuisement professionnel, alors que l'ouverture élevée et le caractère consciencieux élevé modèrent la relation entre la latitude décisionnelle et l'épuisement professionnel en Afrique du Sud. Nous avons aussi trouvé que les traits culturels jouent un rôle dans les deux pays, mais de façon unique et en fonction du groupe ethnique d'appartenance. Sachant que les organisations sont de plus en plus caractérisées par des employés d'origine ethnique variées, et que les conditions de travail se complexifient, nos résultats contribuent à mieux comprendre les dynamiques entre l'employé et l'environnement de travail contemporain. personnalité, différences individuelles, comparaisons culturelles, culture, stress au travail, épuisement professionnel, santé des employés.