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Abstract: We analyse how chronic overfeeding, by increasing circulating fatty acids, might lead to inflammation, insulin resistance (IR) and injury in the liver. Chronic overfeeding causes an increase in adipose tissue depots and is characterised by an increased presence of hypertrophic adipocytes when adipose tissue expandability is inadequate. Adipocyte hypertrophy is a possible stress condition for the endoplasmic reticulum (ER), which will activate inflammatory and apoptotic pathways and cause IR in adipose tissue. Insulin-resistant adipocytes, being more lipolytic and less liposynthetic, induce an increase in circulating free fatty acids. Moreover, the strongly compromised secretion/function of the adipocyte hormones, adiponectin and leptin, decreases lipid oxidation, particularly in the liver, causing lipid accumulation, ER stress and IR in hepatocytes. ER stress may lead to reduced very-low-density lipoprotein (VLDL) secretion and increased lipogenic gene expression despite the presence of IR. These events and reduced lipid oxidation may lead to further hepatic lipid accumulation. When the triglyceride storage capacity of hepatocytes is exceeded, hepatic injury may occur. ER-stressed steatotic hepatocytes activate apoptotic and inflammatory pathways, which trigger IR and the release of chemokines and cytokines, and these, in turn, elicit an increased influx of Kupffer cells (KCs) and hepatic stellate cells (HSCs) around dying hepatocytes. Soluble mediators, secreted mainly by ER-stressed steatotic hepatocytes and activated KCs, induce the transdifferentiation of HSCs to myofibroblasts, which secrete fibrogenic cytokines and matrix components that trigger fibrosis. In conclusion, chronic lipid overloading due to inadequate fat-storing capacity of adipose tissue can induce hepatic injury when triglyceride storage capacity of hepatocytes is exceeded. [Copyright &y& Elsevier]

• The DAS and the AES had similar diagnostic accuracy. • The DAS showed good acceptability and satisfactory internal consistency. • The DAS score ≥ 29 and the AES score ≥ 36 were optimal cut-off values. Apathy is a predictor of cognitive decline in the course of multiple sclerosis (MS). Early identification of apathetic patients is relevant in clinical settings. To assess applicability and psychometric properties of the self-rated version of the Dimensional Apathy Scale (DAS) in a large cohort of patients with MS and to compare its diagnosing accuracy with that of the Apathy Evaluation Scale (AES). One hundred and twenty-four patients underwent clinical interview based on diagnostic criteria for apathy, DAS, AES, and assessment of depression, global cognitive functioning, and non-verbal intelligence. According to diagnostic criteria, apathy occurred in 33.4% of the patients. The DAS showed high consistency, and good convergent, discriminant and criterion validity. Factor analysis indicated a three-factor structure: executive, behavioural and emotional apathy. Unlike AES, no significant association between DAS score and severity of neurological disability (expressed by EDSS total score) was found, suggesting that the DAS might be less related to levels of disability. Receiver operating characteristics analyses, with clinical diagnostic criteria for apathy as the gold standard, revealed that a DAS score of 28/29 and an AES score of 35/36 were optimal cut-off values for identifying clinically relevant apathy. The two scales had similar diagnostic accuracy in the present sample. The DAS is a valid and reliable multidimensional tool to assess apathy in MS, with diagnostic accuracy similar to that of the AES. However, the DAS score appears to be less strongly related to neurological disability. [ABSTRACT FROM AUTHOR]

An interesting interpretation of embodiment highlights the critical role of mental body representations (BR), including motor, somatosensory, and interoceptive formats, for social cognition. However, the nature of this relationship is still debated at the empirical level, with various studies arriving at different conclusions. Here, we present a systematic review and meta-analysis aimed to summarize data from 3466 participants in 21 studies to provide a more comprehensive understanding of the relationship between inner and outer BR and social cognition. We focused on two core social cognition aspects: empathy and Theory of Mind (ToM). Concerning the inner BR, our meta-analytic findings reveal a significant correlation between specific interoceptive dimensions (i.e., interoceptive sensibility and accuracy) and social cognition, which was stronger for empathy than ToM. Conversely, although further research is needed, functional BR that mainly involve the outer body processing (i.e., nonaction-oriented BR) may show positive links with ToM. These findings point to specific interactions between BR and social cognition skills, supporting multi-faceted and embodied social cognition models. However, we also identified critical knowledge gaps and highlighted the need for further investigation to deepen our theoretical understanding of these relationships and their implications for clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The mental representation of the body (or body representation, BR) derives from the processing of multiple sensory and motor inputs and plays a crucial role in guiding our actions and in how we perceive our body. Fundamental inputs for BR construction come also from the interoceptive systems which refer to the whole bidirectional processes between the brain and the body. People with Multiple sclerosis (MS) show an abnormal multisensory integration which may compromise BR and interoception integrity. However, no study has evaluated possible deficits on distinct and dissociable dimensions of body representation (i.e., action-oriented, aBR; and a nonaction-oriented body representation, NaBR) and interoception (i.e., interoceptive accuracy, interoceptive sensibility, and interoceptive awareness) in MS., Objective: In the present study, we aimed to determine whether participants with MS present changes in BR and interoceptive dimensions., Methods: We performed comparison analyses on tasks and questionnaires tapping all BR and interoceptive dimensions between 36 people with relapsing-remitting MS (RRMS) and 42 healthy controls, and between 23 people with progressive MS (PMS) and 33 healthy controls., Results: Overall, patients with MS exhibited lower interoceptive accuracy than matched controls. The RRMS group also showed higher visceral interoceptive sensibility levels. No differences were found in BR accuracy measures, but the PMS reported longer response times when performing the aBR task., Conclusion: These findings open a new issue on the role of inner-signal monitoring in the body symptomatology of MS and highlight the need for an accurate BR and interoceptive assessment in a clinical setting., Competing Interests: Declaration of competing interest The authors state that there is no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Mild cognitive impairment (MCI) or mild neurocognitive disorder is an intermediate stage of cognitive impairment between normal cognitive aging and dementia. Given the absence of effective pharmacological treatments for MCI, increasing numbers of studies are attempting to understand how cognitive training (CT) could benefit MCI. This meta-analysis aims to update and assess the efficacy of CT on specific neuropsychological test performance (global cognitive functioning, short-term verbal memory, long-term verbal memory, generativity, working memory, and visuospatial abilities) in individuals diagnosed with MCI, as compared to MCI control groups. After searching electronic databases for randomized controlled trials, 31 studies were found including 2496 participants. Results showed that CT significantly improved global cognitive functioning, short-term and long-term verbal memory, generativity, working memory, and visuospatial abilities. However, no significant effects were observed for shifting, abstraction ability/concept formation, processing speed, and language. The mode of CT had a moderating effect on abstraction ability/concept formation. The findings provide specific insights into the cognitive functions influenced by CT and guide the development of tailored interventions for MCI. While CT holds promise, further research is needed to address certain cognitive deficits and assess long-term effects on dementia progression.

Background: The COVID-19 pandemic has underlined the need to evaluate cognitive profile via videoconferencing (teleneuropsychology, TeleNP) as a suitable alternative to face-to-face assessment (F-F)., Objective: To evaluate the feasibility and the reliability of Rao's Brief Repeatable Battery of Neuropsychological Tests (R-BRB) remote administration in people with multiple sclerosis (PwMS)., Methods: Sixty PwMS underwent R-BRB in two conditions: F-F and TeleNP, 1 month apart., Results: Cognitive test performance was similar, regardless of the administration type, but visuospatial test performance was better in F-F., Conclusion: These data suggest that TeleNP is feasible and highly reliable in MS clinical practice.

Atypical Parkinsonism (AP) syndromes are characterized by a wide spectrum of non-motor symptoms including prominent attentional and executive deficits. However, the cognitive profile of AP and its differences and similarities with that of Parkinson's Disease (PD) are still a matter of debate. The present meta-analysis aimed at identifying patterns of cognitive impairment in AP by comparing global cognitive functioning, memory, executive functions, visuospatial abilities, language, non-verbal reasoning, and processing speed test performances of patients with AP relative to healthy controls and patients with PD. All investigated cognitive domains showed a substantial impairment in patients with AP compared to healthy controls. When AP syndromes were considered separately, their cognitive functioning was distributed along a continuum from Multiple Systemic Atrophy at one extreme, with the least impaired cognitive profile (similar to that observed in PD) to Progressive Supranuclear Palsy, with the greatest decline in global cognitive and executive functioning (similar to Corticobasal Syndrome). These findings indicate that widespread cognitive impairment could represent an important clinical indicator to distinguish AP from other movement disorders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Mental representations with bodily contents or in various bodily formats have been suggested to play a pivotal role in social cognition, including empathy. However, there is a lack of systematic studies investigating, in the same sample of participants and using an individual differences approach, whether and to what extent the sensorimotor, perceptual, and interoceptive representations of the body could fulfill an explanatory role in the empathic abilities.To address this goal, we carried out two studies in which healthy adults were given measures of interoceptive sensibility (IS), action (aBR), and nonaction-oriented body representations (NaBR), and affective, cognitive, and motor empathy. A higher tendency to be self-focused on interoceptive signals predicted higher affective, cognitive, and motor empathy levels. A better performance in tasks probing aBR and NaBR predicted, respectively, higher motor and cognitive empathy levels.These findings support the view that the various facets of the empathic response are differently grounded in the body since they diversely involve representations with a different bodily format.Individual differences in the focus on one's internal body state representation can directly modulate all the components of the empathic experience. Instead, a body representation used interpersonally to represent both one's own body and others' bodies, in particular in its spatial specificity, could be necessary to accurately understand other people's minds (cognitive empathy), while a sensorimotor body representation used to represent both one's own body and others' bodies actions, could be fundamental for the self-awareness of feelings expressed in actions (motor empathy)., (© 2022. The Psychonomic Society, Inc.)

Background: Apathy is relatively frequent and significantly associated with clinical and cognitive outcomes in Multiple Sclerosis (MS), even if previous research has produced mixed results. This varied picture could be due to most studies treating apathy as a unitary construct, despite the evidence showing that apathy is a multifaceted syndrome including three different sub-domains (i.e., cognitive, affective, and behavioral). This study aims to investigate the neuropsychological correlates of apathy fractionated into its three sub-domains in participants with MS., Methods: Eighty-five participants with MS underwent a comprehensive neuropsychological battery. The severity of apathy symptoms was assessed by the self-report version of the Apathy Evaluation Scale., Results: Correlational analysis showed that cognitive apathy sub-domain scores had a high correlation with the performances obtained at cognitive tests tapping into inhibitory control (i.e., IML and Strop test-interference task), whereas the affective apathy sub-domain scores had a high correlation with the performances obtained at cognitive test tapping into the use of executive functions in visuospatial abilities (i.e., Clock Drawing Test). Moreover, linear regression analysis results showed that the cognitive apathy sub-domain scores predicted executive functioning domain scores and that the cognitive and affective apathy sub-domains scores predicted visuospatial abilities domain scores., Conclusion: These results confirm that apathy is a multidimensional concept with important neuropsychological correlates, visible only when it is fractionated into its sub-domains.

Background: Cognitive impairment (CI) is common in Multiple Sclerosis (MS), and its prevalence rate ranges between 22% and 70%. Because CI significantly impacts vocational status, caregiver burden, and quality of life, an accurate neuropsychological assessment is required. Three widely used and validated batteries for MS-associated CI are the Brief Repeatable Neuropsychological Battery (BRN-B), the Minimal Assessment of Cognitive Function (MACFIMS), and the Brief International Cognitive Assessment (BICAMS). Although similar, these batteries differ in time-consuming and in specific tests employed. This study aims to assess the sensitivity of cognitive tests included in these batteries through an Item Response Theory approach., Methods: Ninety-seven patients with MS and 91 demographically matched controls (HC) were consecutively assessed using the three neuropsychological batteries (i.e., BRN-B, MACFIMS, and BICAMS). Continuous Response Model (CRM) was used to identify the cognitive test(s) that best discriminate patients with MS from HC. Receiver Operating Characteristic (ROC) curve analysis was used to determine the accuracy of the CRM results., Results: Cognitive tests loaded on two different latent variables: the 'higher-order executive functioning,' consisting of tests assessing concept formation, problem-solving, and inhibitory control, and the 'memory and information processing speed,' comprising tests assessing long-term, working memory, and information processing speed. The Delis Kaplan Executive Functioning System-Sorting Test and the Stroop Test were the most sensitive tests in differentiating cognitive functioning between MS and HC., Conclusions: This study confirms the importance of including a more extensive executive assessment in MS clinical practice since higher-order executive functions (e.g., abstraction and inhibitory control) significantly impact patients' quality of life and functional autonomy. Clinical implications of careful dissection of executive functioning in MS neuropsychological assessment are discussed., Competing Interests: Declaration of Competing Interest The authors state that there is no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objective: Theory of mind (ToM), the ability to understand other minds-that is, their beliefs, intentions (cognitive ToM), or emotions (affective ToM)-and its neuropsychological mechanisms in migraine have been poorly investigated. The aim of the study was to explore the deficit of cognitive and affective ToM and its possible associations with cognitive functioning in patients with chronic migraine (CM)., Method: Forty participants with CM and 40 age-, education-, and sex-matched healthy controls (HC) underwent clinical assessment, cognitive (the ToM Pictures Sequencing Task and the Advanced Test of ToM) and affective ToM (the Reading the Mind in the Eyes Task and the Emotion Attribution Task) tasks, and a comprehensive neuropsychological battery., Results: Patients with CM significantly reported a lower performance on tasks assessing ToM compared to HC, with an impairment demonstrated for cognitive ToM. Moreover, patients with CM achieved significantly lower scores on tests assessing cognitive flexibility, planning, abstract reasoning, and long-term memory with respect to HC. ToM abilities were significantly related to migraine severity, executive, and memory functions in CM patients., Conclusions: The findings demonstrated that patients with CM present difficulties in inferring others' mental states, which would be related to clinical and cognitive functioning. The clinical importance of these findings, implications for clinical practice, and future research are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background: Cognitive dysfunctions are highly prevalent in multiple sclerosis (MS) and negatively impact occupational and social functioning., Objective: In the present longitudinal study, we aimed at modeling cognitive changes and at assessing whether apathy could be a predictor of cognitive decline in MS., Methods: We assessed 67 people with MS at two-time points (baseline, T0; 4-year follow-up, T1), by means of several clinical, behavioural, and cognitive measures. We used a delta approach to measure cognitive decline during the follow-up period. We applied a mixed factorial design and a linear regression model to explore factors associated with cognitive changes over time., Results: A higher level of apathy at baseline predicted the progressive cognitive decline at follow-up, whereas a higher level of depression did not. Among demographic and clinical characteristics, only low education level was significantly associated with cognitive decline over time. Interestingly, participants with persistent apathy (diagnosis of apathy at T0 and T1, A+A+) and those who developed apathy (A-A+) showed poorer inhibitory control and a larger decline in executive functioning during the 4-year follow-up than participants who had never received the diagnosis of apathy (A-A-)., Conclusion: Apathy represents an early marker of cognitive decline in MS. These findings have important clinical and prognostic implications., (Copyright © 2022. Published by Elsevier B.V.)

Background: Interoceptive information plays a pivotal role in building higher-order cognitive body representations (BR) that neuropsychological and neuroimaging evidence classifies as action-oriented (i.e., body schema) or non-action-oriented (i.e., visuo-spatial body map). This study aimed to explore the development of BR, considering the association with the interoceptive sensibility throughout the lifespan., Methods: Two hundred thirty-nine healthy participants divided into five age groups (7 to 8 years; 9 to 10 years; 18 to 40 years; 41 to 60 years; over 60 years) completed a self-report measure of interoceptive sensibility (the Self-Awareness Questionnaire; SAQ) and were given tasks assessing the two BR (action-oriented: hand laterality task; non-action-oriented: frontal body evocation task)., Results: Both children (7-8 and 9-10 years) and older adults (over 60 years) performed worse than young (18-40 years) and middle-aged adults (41-60 years) in action- and non-action-oriented BR tasks. Moderation analyses showed that the SAQ score significantly moderated the relationship between age and action-oriented BR., Conclusions: The current results are consistent with inverted U-shaped developmental curves for action- and non-action-oriented BR. As an innovative aspect, the ability to mentally represent one's own body parts in diverse states could be negatively affected by higher interoceptive sensibility levels in childhood and late adulthood.

Background: Prospective memory (PM) deficits are often reported in multiple sclerosis (MS), but their relationship with neuropsychological characteristics and personality traits remains to be explored., Objective: To systematically investigate both time-based and event-based PM abilities in a sample of MS without clinically relevant disability or global cognitive decline and to explore cognitive, neuropsychiatric characteristics and personality traits associated with PM deficits., Methods: Thirty-three patients with MS and 33 healthy individuals were enrolled in the study. All participants underwent a standardized measure of PM to evaluate both time-based and event-based PM. Moreover, patients with MS completed the Brief Repeatable Battery to assess cognitive functioning, the Beck Depression Inventory-II and the Dimensional Apathy Scale to assess neuropsychiatric characteristics, and the NEO Personality Inventory-3 to assess personality traits., Results: Individuals with MS demonstrated impaired time-based PM compared to healthy individuals. The regression analysis showed that poor performance in time-based PM was significantly related to lower extroversion and openness traits, whereas poor performance in event-based PM was significantly related to lower visuospatial memory abilities., Conclusions: Low levels of openness and extroversion traits are associated with a greater risk of developing time-based PM deficit. Therefore, personality assessment and behavioural interventions should be encouraged in MS clinical practice.

The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative stress, and the deregulation of hypothalamic nuclei plays an important role in this mechanism. One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. Omega (ω)3-polyunsaturated fatty acids (PUFA) are dietary compounds known to attenuate the obesity-related diseases, although the molecular mechanisms underlying their actions in the hypothalamus are not completely understood. We hypothesized that the beneficial effects of PUFA may be mediated by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or isocaloric HFD containing either fish oil (FD; rich in ω3-PUFA) or lard for 6 weeks, and the activation of AMPK, inflammatory state (IKKβ, TNF-α) and oxidative stress were analyzed in the hypothalamus. In addition, we also studied serum lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory parameters. Our results showed, at the hypothalamic level of LD-fed rats, an increase of AMPK activation, inflammation and oxidative stress, while no modifications were detected in FD-fed animals compared to CD. In addition body weight gain, serum lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD animals compared to LD. In conclusion, our data indicate that the substitution of saturated by unsaturated fatty acids in the diet has beneficial effects on modulation of hypothalamic inflammation and function in obesity, underlying, at hypothalamic level, the interaction among insulin and/or leptin resistance, AMPK activation and hyperphagia.

Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Oxidative stress, hepatic steatosis, and mitochondrial dysfunction are key pathophysiological features of nonalcoholic fatty liver disease. A conjugated linoleic acid (CLA) mixture of cis9,trans11 (9,11-CLA) and trans10,cis12 (10,12-CLA) isomers enhanced the antioxidant/detoxifying mechanism via the activation of nuclear factor E2-related factor-2 (Nrf2) and improved mitochondrial function, but less is known about the actions of specific isomers. The differential ability of individual CLA isomers to modulate these pathways was explored in Wistar rats fed for 4 weeks with a lard-based high-fat diet (L) or with control diet (CD), and, within each dietary treatment, two subgroups were daily administered with 9,11-CLA or 10,12-CLA (30 mg/day). The 9,11-CLA, but not 10,12-CLA, supplementation to CD rats improves the GSH/GSSG ratio in the liver, mitochondrial functions, and Nrf2 activity. Histological examination reveals a reduction of steatosis in L-fed rats supplemented with both CLA isomers, but 9,11-CLA downregulated plasma concentrations of proinflammatory markers, mitochondrial dysfunction, and oxidative stress markers in liver more efficiently than in 10,12-CLA treatment. The present study demonstrates the higher protective effect of 9,11-CLA against diet-induced pro-oxidant and proinflammatory signs and suggests that these effects are determined, at least in part, by its ability to activate the Nrf2 pathway and to improve the mitochondrial functioning and biogenesis.

Background: Mitochondria are dynamic organelles that frequently undergo fission and fusion processes, and imbalances in these processes may be involved in obesity and insulin resistance., Aims: The present work had the following aims: (a) to evaluate whether the mitochondrial dysfunction present in the hepatic steatosis induced by a high-fat diet is associated with changes in mitochondrial dynamics and morphology; (b) to evaluate whether effects on the above parameters differ between high-lard and high-fish-oil diets, as it has been suggested that fish oil may have anti-obesity and anti-steatotic effects by stimulating fatty acids utilisation., Methods: The development of hepatic steatosis and insulin resistance was monitored in rats fed a high-lard or high-fish-oil diet. Immunohistochemical and electronic microscopic observations were performed on liver sections. In isolated liver mitochondria, assessments of fatty acids oxidation rate, proton conductance and oxidative stress (by measuring H2O2 release and aconitase activity) were performed. Western blot and immunohistochemical analyses were performed to evaluate the presence of proteins involved in mitochondrial dynamics (i.e., fusion and fission processes). To investigate the fusion process, mitofusin 2 and autosomal dominant optic atrophy-1 (OPA1) were analysed. To investigate the fission process, the presence of dynamin-related protein 1 (Drp1) and fission 1 protein (Fis1) was assessed., Results: High-lard feeding elicited greater hepatic lipid accumulation, insulin resistance with associated mitochondrial dysfunction, greater oxidative stress and a shift towards mitochondrial fission processes (versus high-fish-oil feeding, which had an anti-steatotic effect associated with increased mitochondrial fusion processes)., Conclusions: Different types of high-fat diets differ in their effect on mitochondrial function and dynamic behaviour, leading to different cellular adaptations to over-feeding.

Dietary PUFA, mainly those of the n-3 family, are known to play essential roles in the maintenance of energy balance and in the reduction of body fat deposition through the upregulation of mitochondrial uncoupling that is the main source of reactive oxygen species. We hypothesized that rat supplementation with raw donkey's milk (DM), characterized by low-fat content and higher n3:n6 ratio, may affect energy balance, lipid metabolism, and prooxidant status as compared to animals treated with cow's milk. In the present study, the effects of drinking raw DM (for 4 weeks) on energy balance, lipid metabolism, antiinflammatory, and antioxidant/detoxifying defences was compared to that produced by rat intake of an iso-energetic amount of raw cow's milk. The hypolipidemic effect produced by DM paralleled with the enhanced mitochondrial activity/proton leakage and with the increased activity or expression of mitochondrial markers namely, carnitine palmitoyl transferase and uncoupling protein 2. The association of decreased energy efficiency with reduced proinflammatory signs (TNF-α and LPS levels) with the significant increase antioxidant (total thiols) and detoxifying enzyme activities (glutathione-S-transferase NADH quinone oxidoreductase) in DM-treated animals, indicated that beneficial effects were attributable, at least in part, to the activation of nuclear factor 2 erythroid-related factor 2 pathway., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The psychological correlates of enuresis are receiving growing attention, coherently with a multi-factorial approach to this problem, but to date the empirical findings are still inconsistent and incomplete. The aim of this study is to contribute to the understanding of the socio-affective functioning of enuretic children by exploring four central dimensions: attachment, self-esteem, self-control, and temperament. Twenty-two enuretic children with their mothers were enrolled in the study and matched, based on gender and age, to a control group of continent healthy children. Measures were collected through mothers' reports and individual administrations to all children. Controlling for socio-demographic variables, we found a significantly lower incidence of secure attachment, lower self-esteem, and higher rates of behavioral problems among the enuretic group, compared with the control group. No differences in the temperamental dimensions were found. These preliminary findings support the view of enuresis as a bio-behavioral problem and, from a practical standpoint, underline the urgency for physicians not to underestimate this disturbance, but, indeed, to treat the problem through medical strategies and to devote attention to the psychological difficulties of these patients.

A methodology based on matrix-assisted laser desorption ionization-time of flight mass spectrometry of intact bacterial cells was used for rapid discrimination of 24 bacterial species, and detailed analyses to identify Escherichia coli O157:H7 were carried out. Highly specific mass spectrometric profiles of pathogenic and nonpathogenic bacteria that are well-known major food contaminants were obtained, uploaded in a specific database, and made available on the Web. In order to standardize the analytical protocol, several experimental, sample preparation, and mass spectrometry parameters that can affect the reproducibility and accuracy of data were evaluated. Our results confirm the conclusion that this strategy is a powerful tool for rapid and accurate identification of bacterial species and that mass spectrometric methodologies could play an essential role in polyphasic approaches to the identification of pathogenic bacteria.

Celiac disease, triggered by wheat gliadin and related prolamins from barley and rye, is characterized by a strong association with HLA-DQ2 and HLA-DQ8 genes. Gliadin is a mixture of many proteins that makes difficult the identification of major immunodominant epitopes. To address this issue, we expressed in Escherichia coli a recombinant alpha-gliadin (r-alpha-gliadin) showing the most conserved sequence among the fraction of alpha-gliadins. HLA-DQ8 mice, on a gluten-free diet, were intragastrically immunized with a chymotryptic digest of r-alpha-gliadin along with cholera toxin as adjuvant. Spleen and mesenteric lymph node T cell responses were analyzed for in vitro proliferative assay using a panel of synthetic peptides encompassing the entire sequence of r-alpha-gliadin. Two immunodominant epitopes corresponding to peptide p13 (aa 120-139) and p23 (aa 220-239) were identified. The response was restricted to DQ and mediated by CD4+ T cells. In vitro tissue transglutaminase deamidation of both peptides did not increase the response; furthermore, tissue transglutaminase catalyzed extensive deamidation in vitro along the entire r-alpha-gliadin molecule, but failed to elicit new immunogenic determinants. Surprisingly, the analysis of the cytokine profile showed that both deamidated and native peptides induced preferentially IFN-gamma secretion, despite the use of cholera toxin, a mucosal adjuvant that normally induces a Th2 response to bystander Ags. Taken together, these data suggest that, in this model of gluten hypersensitivity, deamidation is not a prerequisite for the initiation of gluten responses.