Cosmological evolution of thermal relic particles in f(R)f(R) gravity

By considering $f(R)$ gravity models, the cosmic evolution is modified with respect to the standard $\Lambda$CDM scenario. In particular, the thermal history of particles results modified. In this paper, we derive the evolution of relics particles (WIMPs) assuming a reliable $f(R)$ cosmological solution and taking into account observational constraints. The connection to the PAMELA experiment is also discussed. Results are consistent with constraints coming from BICEP2 and PLANCK experiments.Comment: 8 pages, 4 figure

Autism Spectrum Disorder and Narcolepsy: A Possible Connection That Deserves to Be Investigated.

Narcolepsy in childhood-adolescence is characterized by a high occurrence of psychiatric comorbidities. The most frequent psychiatric disorders reported in these patients are attention deficit/hyperactivity disorder, depression, anxiety disorder, and schizophrenia. However, narcolepsy can be associated also with introversion, sorrowfulness, feelings of inferiority, impaired affectivity modulation, emotional lability, irritability, aggressiveness, and poor attention, that have been pooled by some authors under a definition of "narcoleptic personality." Some aspects of this "narcoleptic personality," and in particular introversion, impaired affectivity modulation, irritability, and poor attention, partially overlap with the clinical features of the individuals with autism spectrum disorder, considering also those that are not regarded as core autism symptoms. Till now, in literature the number of cases affected by both narcolepsy and autism spectrum disorder (seven patients) has been clearly too small to demonstrate the presence of a pathogenetic link between these two conditions, but this possible connection has not yet been adequately investigated, despite the presence of several points in common. The finding of a connection between narcolepsy and autism spectrum disorder could boost the study of possible etiopathogenetic mechanisms shared between these two apparently so distant disorders. Basing on the literature data summarized in this paper, in the diagnostic work-up of a child with narcolepsy it is essential to evaluate also the social-communicative behavior using standardized tools in order to detect the real recurrence of clinical features suggesting an autism spectrum disorder. At the same time, it appears necessary to screen in the individuals with autism spectrum disorder for the possible presence of evoking symptoms of narcolepsy

Cognitive Health of Nonagenarians in Southern Italy: A Descriptive Analysis from a Cross-Sectional, Home-Based Pilot Study of Exceptional Longevity (Cilento Initiative on Aging Outcomes Or CIAO).

Background: Nonagenarians and centenarians (NCs) are an extremely fragile population, particularly in regard to their physical and cognitive function. The aim of this study was to define the neurocognitive profiles among 29 NCs and their 49 younger cohabitants aged 50-75 years from The Cilento Initiative on Aging Outcomes (CIAO) Pilot study in the South of Italy that had provided initial hypotheses regarding positive psychological traits related to exceptional longevity. Methods: During the home visits, lifestyle information with specific questionnaires, functional autonomy and the neuropsychological Mini Mental Scale Examination (MMSE), and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) scale were obtained by qualified study personnel. The total blood oxidative capacity was also determined by testing the reactive derivative of oxygen metabolites (d-ROM) and by the Biological Antioxidant Potential (BAP). In all individuals, the APOE genotype determination was also performed. Results: All the subjects in both groups showed high adherence to the Mediterranean Diet. None of the NCs had severe cognitive impairment, and a very low incidence of dementia was found. The data obtained on the Activities ed Instrumental Activities of Daily Living (ADL-IADL) scale showed that the majority of NCs (16/29) were autonomous in daily life activities. The comparative assessment of NCs and cohabitants showed no significant differences in the laboratory assessment of oxidative stress and APOE genotype. Conclusion: In the Cilento Region of Southern Italy, NCs seemed to have good cognitive status when compared to younger cohabitants aging 50-65 years without significant differences in oxidative stress markers or APOE genotype. These results might be related to optimal adherence to the Mediterranean diet, although other lifestyle factors and positive personality traits may also contribute to their healthy aging. Further studies on a larger population should be performed to confirm the results of this pilot study

The treatment of hyperinsulinemic hypoglycaemia in adults: an update

Treatment of hyperinsulinemic hypoglycaemia (HH) is challenging due to the rarity of this condition and the difficulty of differential diagnosis. The aim of this article is to give an overview of the recent literature on the management of adult HH

Auxological and endocrine findings in narcolepsy type 1: seventeen-year follow-up from a pediatric endocrinology center

Introduction: Narcolepsy Type 1 (NT1) is a rare hypersomnia of central origin linked to hypocretin deficiency, most frequently arising at pediatric age. NT1 could be associated with endocrine comorbidities involving the neuroendocrine axis, predominantly obesity, and Central Precocious Puberty (CPP). The primary aim of this study is the evaluation of endocrine and auxological parameters at diagnosis and during follow-up in patients with NT1, treated with Sodium Oxybate (SO) or not. Methods: We retrospectively evaluated the auxological, biochemical, and radiological parameters of 112 patients referred to our Center between 2004-2022. The design of our study is cross-sectional at the time of diagnosis followed by a longitudinal follow-up. Results: Our study confirms an increased frequency of CPP and obesity in patients with NT1. At first evaluation, obesity was found in 31.3% of patients, while overweight was found in 25.0%. A diagnosis of CPP was made in 19.6% of patients. Interestingly, this group showed a significantly lower level of CSF-hypocretin (hrct-1) at diagnosis compared to others. We found an improvement in BMI SDS in the SO-treated group compared to untreated patients, and this trend persisted also at 36 months of follow-up (0.0 ± 1.3 vs 1.3 ± 0.4; p<0.03). Sixty-three patients reached their final height, with a median SDS of 0.6 ± 1.1 in boys and 0.2 ± 1.2 in girls. Discussion: To our knowledge, these are the first results regarding the final height in a large series of pediatric patients with NT1, with a normal range of IGF1-SDS levels and stature SDS

Polycystic Ovary Syndrome and Hepatic Steatosis: Could Low-Grade Chronic Inflammation Be Mediated by the Spleen?:

Polycystic Ovary Syndrome (PCOS) is characterized by an extreme variety of phenotypes and controversial metabolic implications. Hepatic Steatosis (HS) and low-grade chronic inflammation (LGCI) might be common findings in PCOS. We conducted a cross-sectional study to evaluate the LGCI and HS in young women with PCOS according to their Body Mass index (BMI), Insulin Resistance (IR), and PCOS phenotypes. Sixty young premenopausal PCOS women and 20 age-matched controls participated. Primary outcome measures were the presence/severity of HS; LGCI index evaluated as spleen longitudinal diameter (SLD) by UltraSound, C-Reactive Protein (CRP) and Interleukin (IL)-6 levels; BMI and the Homeostasis Model Assessment (HoMA) of IR. The second outcome measures were testosterone, Sex Hormone-Binding Globulin (SHBG) levels, and Free Androgen Index (FAI). The presence of HS and LGCI was not significantly different between NW and O/O patients, while there were significant differences particularly when the PCOS-women were grouped according to IR or to PCOS phenotypes. At multiple regression adjusted for BMI, HoMA-IR and the spleen size were the major determinants of the severity of HS (β= 0.36, p=0.007, and β= 0.28, p=0.034, respectively). At multiple regression SLD represented the unique predictor of FAI (β=0.32; p=0.018). In young women with PCOS, HS was detected independently from obesity and was well predicted not only by IR but also by spleen size, with variable expression of the liver-spleen axis across the different PCOS subtypes. A possible role of the spleen in determining LGCI also in women with PCOS is emphasized

Aging yeast gain a competitive advantage on non-optimal carbon sources

Animals, plants and fungi undergo an aging process with remarkable physiological and molecular similarities, suggesting that aging has long been a fact of life for eukaryotes and one to which our unicellular ancestors were subject. Key biochemical pathways that impact longevity evolved prior to multicellularity, and the interactions between these pathways and the aging process therefore emerged in ancient single-celled eukaryotes. Nevertheless, we do not fully understand how aging impacts the fitness of unicellular organisms, and whether such cells gain a benefit from modulating rather than simply suppressing the aging process. We hypothesized that age-related loss of fitness in single-celled eukaryotes may be counterbalanced, partly or wholly, by a transition from a specialist to a generalist life-history strategy that enhances adaptability to other environments. We tested this hypothesis in budding yeast using competition assays and found that while young cells are more successful in glucose, highly aged cells outcompete young cells on other carbon sources such as galactose. This occurs because aged yeast divide faster than young cells in galactose, reversing the normal association between age and fitness. The impact of aging on single-celled organisms is therefore complex and may be regulated in ways that anticipate changing nutrient availability. We propose that pathways connecting nutrient availability with aging arose in unicellular eukaryotes to capitalize on age-linked diversity in growth strategy and that individual cells in higher eukaryotes may similarly diversify during aging to the detriment of the organism as a whole

MOLECULAR CHARACTERISATION OF A NOVEL ADP-RIBOSYLATING PUTATIVE TOXIN OF NEISSERIA MENINGITIDIS

Molecular characterisation of a novel ADP-ribosylating putative toxin of Neisseria meningitidis VEGGIi D, *BALDUCCI E, MASIGNANI V, DI MARCELLO F, SAVINO S, ARICO’ B, COMANDUCCI M, PIZZA M, RAPPUOLI R IRIS, Chiron SpA, Via Fiorentina 1, 53100 Siena Italy; *Dipartimento Scienze morfologiche e Biochimiche Comparate, Università degli Studi di Camerino, Camerino, Italy Session: Surface antigens Introduction: By computer analysis on the Neisseria meningitidis (serogroup B, MC 58 strain) genome sequence, a protein with a feature similar to known bacterial ADP-ribosylating toxins (CT produced by Vibrio cholerae, LT by Escherichia coli and PT by Bordetella pertussis) has been identified. Enzymatic assay has shown that this protein (NM-ADPRT) possesses both NAD glycohydrolase and ADP-ribosyltransferase activity. In this study we describe the identification of the putative catalytic residues, their site-directed mutagenesis, and the resulting activity of the mutants. Materials and methods: The novel NM-ADPRT and the correspondent mutants, were expressed in E. coli as C-terminus His-tag protein fusions. Site-directed mutagenesis was performed using the Multi Site-Directed Mutagenesis Kit (QuikChange). Recombinant NM-ADPRT forms were purified from E. coli in their soluble form by metal chelate affinity chromatography. Both the wild-type and the mutants were assayed for their ADP-ribosylation and NAD-glycohydolase activites, using [adenine –U-14C] NAD and agmatine as ADP-ribose acceptor. Antisera against NM-ADPRT and the mutant derivatives were obtained by immunization of CD1 mice. 20μg of each recombinant protein were given i.p. together with CFA for the first dose and IFA for the second (day 21) and the third (day 35) booster doses. Blood sample were taken on days 34 and 49. Immune sera were used in western blot and tested in a bactericidal assay. Results and discussion: On the basis of sequence homology of NM-ADPRT with LT, CT and PT we have identified the putative residues involved in enzymatic activity. These residues have been changed by site-directed mutagenesis and the purified mutant toxins have been tested for both ADP-ribosylating and NAD-glycohydrolase activities. Interestingly, some of the mutants show reduced or abolished enzymatic activity indicating that the identified residues play a role in catalysis. Antisera against the wild-type and mutant toxins have bactericidal activity. The titers induced by two mutants were higher than those induced by the wild-type form. These data suggest that the mutations introduced could influence not only the enzymatic activity but also the in vivo stability of the toxin. Conclusion: A novel ADP-ribosyltransferase has been identified in meningococcus B. Catalytic residues have been predicted by sequence homology and their role in catalysis has been confirmed by site-directed mutagenesis. These molecules are also able to induce a bactericidal response

Crura ultrastructural alterations in patients with hiatal hernia: a pilot study

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A comparative blind study between skin biopsy and seed amplification assay to disclose pathological α-synuclein in RBD

To compare the diagnostic accuracy of the immunofluorescence (IF) technique and aSyn-seed amplification assay (aSyn-SAA) of skin and cerebrospinal fluid (CSF) in disclosing pathological α-syn in idiopathic idiopathic REM sleep behavior disorder (iRBD) as early phase of a synucleinopathy. We prospectively recruited 41 patients with iRBD and 40 matched clinical controls including RBD associated with type 1 Narcolepsy (RBD-NT1, 21 patients), iatrogenic causes (2 pt) or OSAS (6 pt) and 11 patients with peripheral neuropathies. IF from samples taken by skin biopsy and aSyn-SAA from skin and CSF samples were analysed blinded to the clinical diagnosis. IF showed a good diagnostic accuracy (89%) that was lower in the case of skin and CSF-based aSyn-SAA (70% and 69%, respectively) because of a lower sensitivity and specificity. However, IF showed a significant agreement with CSF aSyn-SAA. In conclusion, our data may favor the use of skin biopsy and aSyn-SAA as diagnostic tools for a synucleinopathy in iRBD