Infectious agents and inflammation. The role of microbiota in autoimmune arthritis

In higher vertebrates, mucosal sites at the border between the internal and external environments, directly interact with bacteria, viruses, and fungi. Through co-evolution, hosts developed mechanisms of tolerance or ignorance toward some infectious agents, because hosts established "gain of function" interactions with symbiotic bacteria. Indeed, some bacteria assist hosts in different functions, among which are digestion of complex carbohydrates, and absorption and supply of vitamins. There is no doubt that microbiota modulate innate and acquired immune responses starting at birth. However, variations in quality and quantity of bacterial species interfere with the equilibrium between inflammation and tolerance. In fact, correlations between gut bacteria composition and the severity of inflammation were first described for inflammatory bowel diseases and later extended to other pathologies. The genetic background, environmental factors (e.g., stress or smoking), and diet can induce strong changes in the resident bacteria which can expose the intestinal epithelium to a variety of different metabolites, many of which have unknown functions and consequences. In addition, alterations in gut permeability may allow pathogens entry, thereby triggering infection and/or chronic inflammation. In this context, a local event occurring at a mucosal site may be the triggering cause of an autoimmune reaction that eventually involves distant sites or organs. Recently, several studies attributed a pathogenic role to altered oral microbiota in rheumatoid arthritis (RA) and to gut dysbiosis in spondyloarthritis (SpA). There is also growing evidence that different drugs, such as antibiotics and immunosuppressants, can influence and be influenced by the diversity and composition of microbiota in RA and SpA patients. Hence, in complex disorders such RA and SpA, not only the genetic background, gender, and immunologic context of the individual are relevant, but also the history of infections and the structure of the microbial community at mucosal sites should be considered. Here the role of the microbiota and infections in the initiation and progression of chronic arthritis is discussed, as well as how these factors can influence a patient's response to synthetic and biologic immunosuppressive therapy

Microbiota and chronic inflammatory arthritis. an interwoven link

Background: Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance. Main body: Correlations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course. In the context of dysbiosis it is also important to remember that different environmental factors like stress, smoke and dietary components can induce strong bacterial changes and consequent exposure of the intestinal epithelium to a variety of different metabolites, many of which have an unknown function. In this perspective, and in complex disorders like autoimmune diseases, not only the genetic makeup, sex and immunologic context of the individual but also the structure of his microbial community should be taken into account. Conclusions: Here we provide a review of the role of the microbiota in the onset, severity and progression of chronic inflammatory arthritis as well as its impact on the therapeutic management of these patients. Furthermore we point-out the complex interwoven link between gut-joint-brain and immune system by reviewing the most recent data on the literature on the importance of environmental factors such as diet, smoke and stress

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer’s disease: current trends and future perspectives

Alzheimer’s disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to the increase in life expectancy of world population, including developing countries, AD, whose incidence rises dramatically with age, is at the forefront among neurodegenerative diseases. Moreover, a definitive cure is not yet within reach, imposing substantial medical and public health burdens at every latitude. Therefore, the effort to devise novel and effective therapeutic strategies is still of paramount importance. Genetic, functional, structural and biochemical studies all indicate that new and efficacious drug delivery strategies interfere at different levels with various cellular and molecular targets. Over the last few decades, therapeutic development of nanomedicine at preclinical stage has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including AD. Clinical translation of nano-based therapeutics, despite current limitations, may present important advantages and innovation to be exploited in the neuroscience field as well. In this state-of-the-art review article, we present the most promising applications of polymeric nanoparticle-mediated drug delivery for bypassing the blood-brain barrier of AD preclinical models and boost pharmacological safety and efficacy. In particular, novel strategic chemical functionalization of polymeric nanocarriers that could be successfully employed for treating AD are thoroughly described. Emphasis is also placed on nanotheranostics as both potential therapeutic and diagnostic tool for targeted treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications against this chronic neurodegenerative disease

Rilievi e indagini diagnostiche non distruttive per l’individuazione delle cripte - La Cattedrale di Ragusa

I diversi operatori, che si occupano di Beni Storici e Culturali, si avvalgono sempre più spesso delle soluzioni tecnologiche avanzate offerte dalla moderna Geomatica, facendo ricorso ad integrazioni delle sue discipline, per meglio studiare, indagare e monitorare un bene di interesse storico. Oggi si tentano nuove integrazioni con altre discipline che, tradizionalmente, non riguardano il campo del rilievo propriamente detto. Questo è, ad esempio, il caso dello studio condotto sulla Cattedrale di San Giovanni a Ragusa, nel quale si è partiti dal rilievo laser scanning di una porzione della chiesa e del suo pregiatissimo pavimento, sotto il quale secondo uno schizzo dei primi anni del XIX secolo (Fig. 1) dovrebbero trovarsi delle sepolture, per poi proseguire lo studio con l’ausilio del Georadar, strumento utilizzato tradizionalmente da geofisici e geologi per indagare il terreno. Ciò è stato fatto al fine di verificare l’effettiva presenza di strutture ipogee senza però agire con indagini invasive. Il risultato dell’elaborazione dei dati georadar, trasformato in una ricostruzione tridimensionale del sottopavimento, è stato affiancato alla ricostruzione tridimensionale della chiesa, realizzata dall’elaborazione dei dati del rilievo laser scanning. Tale integrazione ha permesso di confermare la presenza di strutture ipogee e di capire in che relazione sono queste ultime con gli avvallamenti presenti nel pavimento della chiesa. Del modello tridimensionale completo si è, infine, realizzata una versione navigabile (VRML), capace di offrire una visualizzazione e un’interazione anche ad utenti privi di conoscenze informatiche approfondite

Comparative Transcriptomics Reveals Clues for Differences in Pathogenicity between Hysterothylacium aduncum, Anisakissimplex sensu stricto and Anisakis pegreffii

Ascaridoid nematodes are widespread in marine fishes. Despite their major socioeconomic importance, mechanisms associated to the fish-borne zoonotic disease anisakiasis are still obscure. RNA-Seq and de-novo assembly were herein applied to RNA extracted from larvae and dissected pharynx of Hysterothylacium aduncum (HA), a non-pathogenic nematode. Assembled transcripts in HA were annotated and compared to the transcriptomes of the zoonotic species Anisakis simplex sensu stricto (AS) and Anisakis pegreffii (AP). Approximately 60,000,000 single-end reads were generated for HA, AS and AP. Transcripts in HA encoded for 30,254 putative peptides while AS and AP encoded for 20,574 and 20,840 putative peptides, respectively. Differential gene expression analyses yielded 471, 612 and 526 transcripts up regulated in the pharynx of HA, AS and AP. The transcriptomes of larvae and pharynx of HA were enriched in transcripts encoding collagen, peptidases, ribosomal proteins and in heat-shock motifs. Transcripts encoding proteolytic enzymes, anesthetics, inhibitors of primary hemostasis and virulence factors, anticoagulants and immunomodulatory peptides were up-regulated in AS and AP pharynx. This study represents the first transcriptomic characterization of a marine parasitic nematode commonly recovered in fish and probably of negligible concern for public health

Comparative transcriptomics reveals clues for differences in pathogenicity between hysterothylacium aduncum, Anisakis simplex sensu stricto and Anisakis pegreffid

Ascaridoid nematodes are widespread in marine fishes. Despite their major socioeconomic importance, mechanisms associated to the fish-borne zoonotic disease anisakiasis are still obscure. RNA-Seq and de-novo assembly were herein applied to RNA extracted from larvae and dissected pharynx of Hysterothylacium aduncum (HA), a non-pathogenic nematode. Assembled transcripts in HA were annotated and compared to the transcriptomes of the zoonotic species Anisakis simplex sensu stricto (AS) and Anisakis pegreffii (AP). Approximately 60,000,000 single-end reads were generated for HA, AS and AP. Transcripts in HA encoded for 30,254 putative peptides while AS and AP encoded for 20,574 and 20,840 putative peptides, respectively. Differential gene expression analyses yielded 471, 612 and 526 transcripts up regulated in the pharynx of HA, AS and AP. The transcriptomes of larvae and pharynx of HA were enriched in transcripts encoding collagen, peptidases, ribosomal proteins and in heat-shock motifs. Transcripts encoding proteolytic enzymes, anesthetics, inhibitors of primary hemostasis and virulence factors, anticoagulants and immunomodulatory peptides were up-regulated in AS and AP pharynx. This study represents the first transcriptomic characterization of a marine parasitic nematode commonly recovered in fish and probably of negligible concern for public health

The scent of emotions: A systematic review of human intra- and interspecific chemical communication of emotions.

The sense of olfaction has been considered of minor importance in human communication. In recent years, evidence has emerged that humans might be influenced by unconscious messages sent through chemosignals in body odors. Data concerning the ability of humans to recognize fear, maybe related to the evolutionary role of these emotions in the fight-or-flight reactions, are well known. To further understand the role of emotional chemosignals in mediating communication in humans and its influence on animal behaviors, we conducted a systematic literature review. Chemosignals derived from axillary odors collected under a variety of emotional stimuli and sad tears in humans affect receivers' social interactions, danger detection and risk-taking behavior, social aspects of eating, and performance under stressing conditions. In addition, beyond the fight-or-flight response, even the body odors of happiness can be perceived by others. Furthermore, human chemosignals can influence behaviors and stressful responses in animals, particularly dogs and horses, which may partially explain their special relationship with humans. Our review highlights the importance of chemosignaling in human intra- and interspecific interactions and suggests the need for further investigations, both in physiological conditions and in patients with psychiatric or neurodegenerative disorders

Changes in the folding landscape of the WW domain provide a molecular mechanism for an inherited genetic syndrome

WW domains are small domains present in many human proteins with a wide array of functions and acting through the recognition of proline-rich sequences. The WW domain belonging to polyglutamine tract-binding protein 1 (PQBP1) is of particular interest due to its direct involvement in several X chromosome-linked intellectual disabilities, including Golabi-Ito-Hall (GIH) syndrome, where a single point mutation (Y65C) correlates with the development of the disease. The mutant cannot bind to its natural ligand WBP11, which regulates mRNA processing. In this work we use high-field high-resolution NMR and enhanced sampling molecular dynamics simulations to gain insight into the molecular causes the disease. We find that the wild type protein is partially unfolded exchanging among multiple beta-strand-like conformations in solution. The Y65C mutation further destabilizes the residual fold and primes the protein for the formation of a disulphide bridge, which could be at the origin of the loss of function

Toxoplasmosis and knowledge. What do the Italian women know about?

Toxoplasmosis is a worldwide zoonotic infectious disease caused by Toxoplasma gondii. This infection is estimated to affect about a third of the world’s population. The aim of this study was to evaluate the knowledge of Italian women about toxoplasmosis and its forms of transmission, clinical manifestations, diagnosis, and prevention through two different modalities (e-research and traditional research). In a cross-sectional study 808 Italian women were interviewed, using a self-administered questionnaire, through two different modalities: an e-research or web survey and a traditional paper research. By the 84% of women interviewed, it was reported to have hear about toxoplasmosis, but from the most of the sample, it resulted that the knowledge of protozoan disease was superficial and incomplete. The assessment of the dimensionality related to the toxoplasmosis knowledge’s instrument showed that the scale is composed by two stable and reliable factors which explain 58.6% of the variance: a) the basic knowledge (α=0.83), which explains the 45.2% of the variance, and b) the specialist knowledge (α=0.71), which explains the 13.4% of the variance. The variance and the multiple linear regression data analysis showed significant predictors of correct basic knowledge of toxoplasmosis: the highest age, the highest degree of study, to have previously contracted illness or to know someone who had contracted, to be working or to be housewives. In conclusion, this study showed limited awareness of toxoplasmosis and suggested the implementation of the effective education and learning programs. The results also showed that online data collection, in academic research, might be a valid alternative to more traditional (paper-and-pencil) surveys

Stroke incidence and case fatality: a 9-year prospective population-based study in an elderly population of Bagheria, Italy

Background: The incidence of stroke in high-income countries has been on the decline; however, few epidemiological surveys have been conducted in recent years to specifically estimate the incidence along with outcome of stroke, in Italy. This study aimed to examine the incidence and case fatality rates of stroke in an elderly Italian population. Methods: A cohort of 2200 people > 65 years was randomly stratified from the total elderly population of Bagheria, Italy. A 9-year prospective population-based study was performed (19,800 person/years). Results: We identified 112 first-ever strokes, 53 females and 59 males: 82 (73.1%) ischemic, 13(11.6%) intracerebral haemorrhages, 6 (5.35%) subarachnoid haemorrhages, while 11(9.8%) were classified as undetermined strokes. The crude overall annual incidence was 5.65 per 1000 (95%CI: 4.61 to 6.70) for first-ever stroke. The overall crude incidence rates were 4.74 per 1000 (5.08 for males and 4.46 for females) for ischemic stroke, 0.65 (0.99 for males and 0.37 for females) for intracerebral haemorrhage, and 0.03 for subarachnoid haemorrhage. The incidence rate for first-ever stroke was 5.4 per 1000 (95% CI: 5.36 to 5.45) after adjustment for the 2015 World population and 5.56 (95% CI: 5.52 to 5.61), compared to the 2015 European population. Overall case fatality rates for first-ever stroke was 8.19% at 28 days and 24.1% at 1 year. Conclusion: Our study shows that in the elderly population investigated, stroke incidence and case fatality rates resulted being lower, compared to those from Italian and most European populations. Similar to previous studies, these rates increased linearly with age and were higher in males