Hemochromatosis Mimicked Gaucher Disease: Role of Hyperferritinemia in Evaluation of a Clinical Case

Gaucher disease is a disorder of lysosomes caused by a functional defect of the glucocere-brosidase enzyme. The disease is mainly due to mutations in the GBA1 gene, which determines the gradual storage of glucosylceramide substrate in the patient’s macrophages. In this paper, we describe the case of a 38-year-old man who clinically presented with hyperferritinemia, thrombocytopenia, leukopenia, anemia and mild splenomegaly; a diagnosis of hemochromatosis was made 10 years earlier. Re-evaluation of the clinical case led to a suspicion of Gaucher disease, which was confirmed by enzymatic analysis, which was found to be below the normal range, and genetic evaluation, which identified compound heterozygosity N370S/RecNciI. We know that patients suffering from Gaucher disease can also have high ferritin levels. Even if the mechanism underlying the changes in iron metabolism is not yet elucidated, the chronic mild inflammatory state present in these patients probably causes the storage of ferritin in macrophages, resulting in hyperferritinemia. Therefore, in the presence of few typical signs and symptoms of the disease should raise an alarm bell in the clinicians, inducing clinical suspicion of Gaucher disease. Misdiagnosis and diagnostic delay in metabolic diseases could cause irreversible organ damage and delay the start of specific therapy for these patients

A new hard-particle model for anisotropic fluids

We report a new hard-particle model system consisting of hard cylinders, we have determined the geometrical conditions that let us know whether or not two given cylinders overlap. In addition we have carried out Monte Carlo simulations sampling the canonical ensemble on this system, the numerical results indicate that this system exhibits mesomorphic behaviour

The signature of longevity in Sicily

Ageing is a natural and physiological condition that is the result of compromised stress response, homeostatic imbalance and increased risk of developing diseases. However, if aging with good health and functions (successful ageing) and aging with disease and disability (unsuccessful ageing) depends on a combination of “positive features”, including genetic, epigenetic and phenotypic characteristics in combination with favourable environment, economic status and social involvement. In our study, we summarize some key points for the identification of a longevity signature, with a particular focus on long-living Sicilian individuals and centenarians. Analysing three different Sicilian cohorts (young, people with no centenarian parents and long-living individuals (LLI) aged >90) we found APOE e3e3 in our LLIs and no presence of e4. Regarding FOXO rs2802292 G-allele (G>T) we did not observe an association with longevity, probably because of the small sample of centenarians studied. Regarding haematological and anthropometric results, it is still difficult to point specific longevity features and so far, we cannot specify a single one. On the other hand, we believe that the synergy among genetics and environment might create successful interaction to achieve and obtain effective longevity

Discriminative capacity and construct validity of the Clock Drawing Test in Mild Cognitive Impairment and Alzheimer's disease

OBJECTIVES: The aim of this study was to analyze the psychometric and diagnostic properties of the Clock Drawing Test (CDT), scored according to the Babins, Rouleau, and Cahn scoring systems, for Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) screening, and develop corresponding cutoff scores. Additionally, we assessed the construct validity of the CDT through exploratory and confirmatory factor analysis. METHODS: We developed a cross-sectional study of ambulatory MCI and AD patients, divided in two clinical groups (450 MCI and 250 mild AD patients) and a normal control group (N = 400). All participants were assessed with the CDT, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) for convergent validity. RESULTS: The selected scoring systems presented adequate validity and reliability values. The proposed cutoff scores showed 60 to 65% sensitivity and 58 to 62% specificity to identify MCI patients. The corresponding values for AD were 84 to 90% sensitivity and 76 to 78% specificity. Exploratory and confirmatory factor analysis revealed that the Babins scoring system had good construct validity and allowed us to propose a three-factor model for this system. CONCLUSIONS: Our results confirmed the complexity of the CDT and support it as a cognitive screening instrument particularly sensitive to AD. The use of the CDT with MCI patients should be interpreted with more caution due to the lower sensitivity and specificity for milder forms of cognitive impairment.info:eu-repo/semantics/publishedVersio

MicroRNA deregulation and chemotaxis and phagocytosis impairment in Alzheimer's disease

AbstractIntroductionMononuclear phagocytes play a critical role during Alzheimer's disease (AD) pathogenesis due to their contribution to innate immune responses and amyloid beta (Aβ) clearance mechanisms.MethodsBlood-derived monocytes (BDMs) and monocyte-derived macrophages (MDMs) were isolated from blood of AD, mild cognitive impairment (MCI) patients, and age-matched healthy controls for molecular and phenotypic comparisons.ResultsThe chemokine/chemokine receptor CCL2/CCR2 axis was impaired in BDMs from AD and MCI patients, causing a deficit in cell migration. Changes were also observed in MDM-mediated phagocytosis of Aβ fibrils, correlating with alterations in the expression and processing of the triggering receptor expressed on myeloid cells 2 (TREM2). Finally, immune-related microRNAs (miRNAs), including miR-155, -154, -200b, -27b, and -128, were found to be differentially expressed in these cells.DiscussionThis work provides evidence that chemotaxis and phagocytosis, two crucial innate immune functions, are impaired in AD and MCI patients. Correlations with miRNA levels suggest an epigenetic contribution to systemic immune dysfunction in AD

Non-CO2 generating energy shares in the world : cross-country differences and polarization.

The aim of this paper is to examine the spatial distribution of non-CO2 generating energy sources in the world for the period 1990–2009, paying special attention to the evolution of cross-country disparities. To this end, after carrying out a classical convergence analysis, a more thorough investigation of the entire distribution is presented by examining its external shape, the intra-distribution dynamics and the long-run equilibrium distribution. This analysis reveals the existence of a weak, rather insignificant, convergence process and that large crosscountry differences are likely to persist in the long-run. Next, as polarization indicators are a proper way of appraising potential conflict in international environmental negotiations, we test whether, or not, the distribution dynamics concurs with the presence of polarization. Our results indicate that two poles can be clearly differentiated, one with high and other with low non-CO2 generating energy shares. In view of these findings, and to ensure a fair transition to a sustainable energy system, the paper calls for the development of an ambitious clean energy agenda, especially in countries with low non-CO2 generating energy shares

Targeting Alzheimer’s disease with multimodal polypeptide-based nanoconjugates

Alzheimer’s disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moieties and bisdemethoxycurcumin or genistein afforded neuroprotection and displayed neurotrophic effects, as evidenced by an increase in dendritic density of pyramidal neurons in organotypic hippocampal culture. The additional conjugation of the Angiopep-2 targeting moiety enhanced nanoconjugate passage through the blood-brain barrier and modulated brain distribution with nanoconjugate accumulation in neurogenic areas, including the olfactory bulb. Nanoconjugate treatment effectively reduced neurotoxic amyloid aggregate levels and rescued impairments to olfactory memory and object recognition in APP/PS1 transgenic AD model mice. Overall, this study provides a description of a targeted multimodal polyglutamate-based nanoconjugate with neuroprotective and neurotrophic potential for AD treatment. Copyrigh

Age-Related Inflammation: the Contribution of Different Organs, Tissues and Systems. How to Face it for Therapeutic Approaches

A typical feature of ageing is a chronic, low-grade inflammation characterized by a general increase in the production of proinflammatory cytokines and inflammatory markers (“inflamm-ageing”). This status may slowly damage one or several organs, especially when unfavorable genetic polymorphisms and epigenetic alterations are concomitant, leading to an increased risk of frailty together with the onset of age-related chronic diseases. The contribution of different tissues (adipose tissue, muscle), organs (brain, liver), immune system and ecosystems (gut microbiota) to age-related inflammation (“inflamm-ageing”) will be discussed in this review in the context of its onset/progression leading to site-restricted and systemic effects. Moreover, some of the possible strategies and therapies to counteract the different sources of molecular mediators which lead to the age-related inflammatory phenotype will be presente

Can Be miR-126-3p a Biomarker of Premature Aging? An Ex Vivo and In Vitro Study in Fabry Disease

Fabry disease (FD) is a lysosomal storage disorder (LSD) characterized by lysosomal accumulation of glycosphingolipids in a wide variety of cytotypes, including endothelial cells (ECs). FD patients experience a significantly reduced life expectancy compared to the general population; therefore, the association with a premature aging process would be plausible. To assess this hypothesis, miR-126-3p, a senescence-associated microRNA (SA-miRNAs), was considered as an aging biomarker. The levels of miR-126-3p contained in small extracellular vesicles (sEVs), with about 130 nm of diameter, were measured in FD patients and healthy subjects divided into age classes, in vitro, in human umbilical vein endothelial cells (HUVECs) "young" and undergoing replicative senescence, through a quantitative polymerase chain reaction (qPCR) approach. We confirmed that, in vivo, circulating miR-126 levels physiologically increase with age. In vitro, miR-126 augments in HUVECs underwent replicative senescence. We observed that FD patients are characterized by higher miR-126-3p levels in sEVs, compared to age-matched healthy subjects. We also explored, in vitro, the effect on ECs of glycosphingolipids that are typically accumulated in FD patients. We observed that FD storage substances induced in HUVECs premature senescence and increased of miR-126-3p levels. This study reinforces the hypothesis that FD may aggravate the normal aging process