Gender differences in the immune system activities of sea urchin Paracentrotus lividus

In the immune system of vertebrates, gender-specific differences in individual immune competence are well known. In general, females possess more powerful immune response than males. In invertebrates, the situation is much less clear. For this purpose we have chosen to study the immune response of the two sexes of the echinoderm Paracentrotus lividus in pre- and post-spawning phases. The coelomic fluid from the echinoderms contains several coelomocyte types and molecules involved in innate immune defenses. In this article we report that the degree of immune responses in the P. lividus differs according to sex in both pre- and post-spawning phases. We found in all tests that females were more active than males. The results indicate that females possess a significant higher number of immunocytes consisting of phagocytes and uncolored spherulocytes. Since the immunological activity is mainly based on immunocytes, it was not surprising that females possessed the highest values of cytotoxicity and hemolysis activity and showed a greater ability to uptake neutral red and phagocyte yeasts cells, while the average number of ingested particles per active phagocyte was not significantly different. Furthermore, agglutinating activity was more evident in the coelomocyte lysate and coelomic fluid of females than in those of males. Finally we found that the acidic extract of female gonads possessed greater antimicrobial activity than that of male gonads. These results make it very likely that gender differences in the immune response are not restricted to vertebrates; rather, they are a general evolutionary phenomenon

Immune mediators of sea-cucumber Holothuria tubulosa (Echinodermata) as source of novel antimicrobial and anti-staphylococcal biofilm agents

The present study aims to investigate coelomocytes, immune mediators cells in the echinoderm Holothuria tubulosa, as an unusual source of antimicrobial and antibiofilm agents. The activity of the 5kDa peptide fraction of the cytosol from H. tubulosa coelomocytes (5-HCC) was tested against a reference group of Gram-negative and Gram-positive human pathogens. Minimal inhibitory concentrations (MICs) ranging from 125 to 500 mg/ml were determined against tested strains. The observed biological activity of 5-HCC could be due to two novel peptides, identified by capillary RP-HPLC/nESI-MS/MS, which present the common chemical-physical characteristics of antimicrobial peptides. Such peptides were chemically synthesized and their antimicrobial activity was tested. The synthetic peptides showed broad-spectrum activity at 12.5 mg/ml against the majority of the tested Gram-positive and Gram-negative strains, and they were also able to inhibit biofilm formation in a significant percentage at a concentration of 3.1 mg/ml against staphylococcal and Pseudomonas aeruginosa strains. The immune mediators in H. tubulosa are a source of novel antimicrobial peptides for the development of new agents against biofilm bacterial communities that are often intrinsically resistant to conventional antibiotics

A Stage-Based Approach to Therapy in Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD

The factitious/malingering continuum and its burden on public health costs: a review and experience in an Italian neurology setting

Abstract: Factitious disorder is classified as one of the five aspects of somatic symptom disorders. The fundamental element of factitious disorder is deception, i.e., pretending to have a medical or psychiatric disorder, but the enactment of deception is considered unconscious. Indeed, volition, i.e., the perception of deliberate deception, is blurred in patients presenting with factitious disorder. In the USA and the UK, factitious disorder has received constant media attention because of its forensic implications and outrageous costs for the National Health Systems. Unfortunately, a comparable level of attention is not present in Italian National Health System or the Italian mass media. The review analyzes the classifications, disorder mechanisms, costs, and medico-legal implications in the hope of raising awareness on this disturbing issue. Moreover, the review depicts 13 exemplification cases, anonymized and fictionalized by expert writers. Finally, our paper also evaluates the National Health System’s expenditures for each patient, outlandish costs in the range between 50,000 and 1 million euros.Peer reviewe

Functional Neurologic Disorders, disorders to be managed by neurologists, or are neurologists wandering in a dangerous field with inadequate resources?

© 2023 Onofrj, Ajdinaj, Digiovanni, Malek, Martinotti, Ferro, Russo, Thomas and Sensi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/In recent years, some neurologists reconsidered their approach to Medically Unexplained Symptoms and proposed Functional Neurologic Disorders (FND) as a new entity, claiming that neurology could offer alternative treatment options to the psychotherapies provided in psychiatry settings. FNDs, for this purpose, should include only the disorders listed as Conversion from the Somatic Symptom and Related Disorders (SSRD) group. The present review analyzes the rationale of this position and challenges the arguments provided for its support. The review also discusses the systematization of these disorders as provided by public health systems. It outlines risks stemming from economic support and public funding uncertainty, given their negligible epidemiological dimensions resulting from the parcellation of SSRD. The review underlines the unresolved issue of Factitious Disorders, which are in the same SSRD category of the international classification but are, nonetheless, overlooked by the theoretical proponents of the FND entity. Comorbidity with other psychiatric disorders is also analyzed. We propose a model that supports the continuum between different SSRD conditions, including Factitious Disorders. The model is based on the emergence of feigned death reflex and deception from frontal lobe dysfunction. Finally, the paper summarizes the wealth of historical psychiatric and psychodynamic approaches and critical reviews. The study also puts in context the categorization and interpretation efforts provided by the most eminent researchers of the past century.Peer reviewe

Clinical presentation of strokes confined to the insula: a systematic review of literature

Background and purpose The insular cortex serves a wide variety of functions in humans, ranging from sensory and affective processing to high-level cognition. Hence, insular dysfunction may result in several different presentations. Ischemic strokes limited to the insular territory are rare and deserve a better characterization, to be quickly recognized and to receive the appropriate treatment (e.g. thrombolysis). Methods We reviewed studies on patients with a first-ever acute stroke restricted to the insula. We searched in the Medline database the keywords “insular stroke” and “insular infarction”, to identify previously published cases. Afterwards, the results were divided depending on the specific insular region affected by the stroke: anterior insular cortex (AIC), posterior insular cortex (PIC) or total insula cortex (TIC). Finally, a review of the clinical correlates associated with each region was performed. Results We identified 25 reports including a total of 49 patients (59.7 ± 15.5 years, 48% male) from systematic review of the literature. The most common clinical phenotypes were motor and somatosensory deficits, dysarthria, aphasia and a vestibular-like syndrome. Atypical presentations were also common and included dysphagia, awareness deficits, gustatory disturbances, dysautonomia, neuropsychiatric or auditory disturbances and headache. Conclusions The clinical presentation of insular strokes is heterogeneous; however, an insular stroke should be suspected when vestibular-like, somatosensory, speech or language disturbances are combined in the same patient. Further studies are needed to improve our understanding of more atypical presentations

Case report: a typical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum

The amount of Insulin Growth Factor 2 (IGF2) controls the rate of embryonal and postnatal growth. The IGF2 and adjacent H19 are the imprinted genes of the telomeric cluster in the 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-DMR (IC1). Dysregulation due to IC1 Loss-of-Methylation (LoM) or Gain-of-Methyaltion (GoM) causes Silver–Russell syndrome (SRS) or Beckwith–Wiedemann syndrome (BWS) disorders associated with growth retardation or overgrowth, respectively. Specific features define each of the two syndromes, but isolated asymmetry is a common cardinal feature, which is considered sufficient for a diagnosis in the BWS spectrum. Here, we report the case of a girl with right body asymmetry, which suggested BWS spectrum. Later, BWS/SRS molecular analysis identified IC1_LoM revealing the discrepant diagnosis of SRS. A clinical re-evaluation identified a relative macrocephaly and previously unidentified growth rate at lower limits of normal at birth, feeding difficulties, and asymmetry. Interestingly, and never previously described in IC1_LoM SRS patients, since the age of 16, she has developed hand-writer’s cramps, depression, and bipolar disorder. Trio-WES identified a VPS16 heterozygous variant [NM_022575.4:c.2185C>G:p.Leu729Val] inherited from her healthy mother. VPS16 is involved in the endolysosomal system, and its dysregulation is linked to autosomal dominant dystonia with incomplete penetrance and variable expressivity. IGF2 involvement in the lysosomal pathway led us to speculate that the neurological phenotype of the proband might be triggered by the concurrent IGF2 deficit and VPS16 alteration

A Machine Learning-Based Holistic Approach to Predict the Clinical Course of Patients within the Alzheimer’s Disease Spectrum

Background: Alzheimer’s disease (AD) is a neurodegenerative condition driven by multifactorial etiology. Mild cognitive impairment (MCI) is a transitional condition between healthy aging and dementia. No reliable biomarkers are available to predict the conversion from MCI to AD. Objective: To evaluate the use of machine learning (ML) on a wealth of data offered by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Alzheimer’s Disease Metabolomics Consortium (ADMC) database in the prediction of the MCI to AD conversion. Methods: We implemented an ML-based Random Forest (RF) algorithm to predict conversion from MCI to AD. Data related to the study population (587 MCI subjects) were analyzed by RF as separate or combined features and assessed for classification power. Four classes of variables were considered: neuropsychological test scores, AD-related cerebrospinal fluid (CSF) biomarkers, peripheral biomarkers, and structural magnetic resonance imaging (MRI) variables. Results: The ML-based algorithm exhibited 86% accuracy in predicting the AD conversion of MCI subjects. When assessing the features that helped the most, neuropsychological test scores, MRI data, and CSF biomarkers were the most relevant in the MCI to AD prediction. Peripheral parameters were effective when employed in association with neuropsychological test scores. Age and sex differences modulated the prediction accuracy. AD conversion was more effectively predicted in females and younger subjects. Conclusion: Our findings support the notion that AD-related neurodegenerative processes result from the concerted activity of multiple pathological mechanisms and factors that act inside and outside the brain and are dynamically affected by age and sex

Digital Pixel Test Structures implemented in a 65 nm CMOS process

The ALICE ITS3 (Inner Tracking System 3) upgrade project and the CERN EP R&D on monolithic pixel sensors are investigating the feasibility of the Tower Partners Semiconductor Co. 65 nm process for use in the next generation of vertex detectors. The ITS3 aims to employ wafer-scale Monolithic Active Pixel Sensors thinned down to 20 to 40 um and bent to form truly cylindrical half barrels. Among the first critical steps towards the realisation of this detector is to validate the sensor technology through extensive characterisation both in the laboratory and with in-beam measurements. The Digital Pixel Test Structure (DPTS) is one of the prototypes produced in the first sensor submission in this technology and has undergone a systematic measurement campaign whose details are presented in this article. The results confirm the goals of detection efficiency and non-ionising and ionising radiation hardness up to the expected levels for ALICE ITS3 and also demonstrate operation at +20 C and a detection efficiency of 99% for a DPTS irradiated with a dose of $10^{15}$ 1 MeV n$_{\mathrm{eq}}/$cm$^2$. Furthermore, spatial, timing and energy resolutions were measured at various settings and irradiation levels.Comment: Updated threshold calibration method. Implemented colorblind friendly color palette in all figures. Updated reference

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients