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Textile, apparel, and fashion (TAF) industries contribute significantly to global environmental pollution at every point of the supply chain. Clothing manufacturing and transportation produce a large volume of waste and high greenhouse gas emissions, often taking advantage of cheap labor in developing countries. As a result, stakeholders are becoming more aware of the effect of the textile, apparel, and fashion industries on the climate and human rights, thus pushing businesses to mitigate their environmental damage. This paper offers a systematic literature review of sustainability trends in the TAF industries in the last 20 years. Bibliometric tools are also used to support the content analysis of the papers. The findings reveal three primary research areas in the TAF context: consumers’ behaviour towards sustainable clothing, circular economy initiatives, and sustainability challenges across the whole supply chain. As a result, this study highlights literature gaps and provides future research suggestions for each identified research cluster. In addition, drivers and barriers to implementing corporate social responsibility and circular economy practices are identified. Consequently, this study will help researchers and academicians work in this area to identify unexplored sub-fields, which reflect some potential investigation areas for expanding scientific literature on the topic. Finally, this study supports practitioners and managers in exploring the main research themes addressed in the scientific field, providing knowledge to improve and align business models with current sustainability trends.

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies. Graphical abstract: [Figure not available: see fulltext.]

Patients with craniopharyngioma often have comorbidities, such as obesity and hypopituitarism. These two conditions affect each other and worsen the quality of life of patients, which lead to a higher risk of morbidity and mortality. In addition, abdominal obesity, measured as waist circumference (WC), is together with other parameters [arterial hypertension, hyperglycemia, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol], one of the components of metabolic syndrome (MS). Each one of these morbidities occurs in patients with craniopharyngioma more frequently than in the remaining population. On these bases, we evaluated metabolic parameters in patients with craniopharyngioma at the time of diagnosis and after a 5-year follow-up, which compares these data with those of age-, gender-, WC-, and body mass index (BMI)-matched controls. In addition, we evaluated the prevalence of MS according to IDF criteria (MS-IDF) and the prevalence of MS according to ATP III (MS-ATPIII) criteria in patients and controls at baseline and after 5 years. We recruited 20 patients with craniopharyngioma (age 38.5 ± 15 years, 10 M) and 20 age-, gender-, WC- and BMI-matched controls (age 34.16 ± 13.19 years, 10 M). In all patients and controls, we evaluated the following: anthropometric features [height, weight, BMI, WC, hip circumference (HC) and waist-to-hip ratio (WHR)], systolic blood pressure (SBP) and diastolic blood pressure (DBP), lipid profile [total cholesterol (TC), HDL, low-density lipoprotein (LDL) cholesterol, triglycerides (TG)], and blood glucose at baseline and after 5 years. The prevalence of MS, according to IDF and ATPIII criteria, was calculated in the two groups at baseline and after 5 years. According to our results, at baseline, patients with craniopharyngioma had a worse metabolic profile than controls and a higher prevalence of MS. Besides, at a 5-year follow-up, patients still had impaired metabolic characteristics and more frequent MS (according to IDF and ATPIII criteria) when compared to controls. These data confirm that MS in patients with craniopharyngioma is unresponsive to life-changing interventions and to a common pharmacological approach. Other factors may be involved in the evolution of these conditions; so, further studies are needed to establish the correct management of these patients.

Background: Speckle tracking advancements make now available the analysis of layer-specific myocardial deformation. This study investigated multilayer longitudinal strain in Anderson-Fabry disease (AFD) patients at diagnosis. Methods: In a case-control study, 33 newly diagnosed, untreated AFD patients and 33 healthy age- and sex-matched healthy controls underwent a complete echocardiogram, including assessment of left ventricular (LV) transmural global longitudinal strain (GLS), subendocardial longitudinal strain (LSsubendo), subepicardial longitudinal strain (LSsubepi), and strain gradient (LSsubendo-LSsubpepi). Results: Anderson-Fabry disease patients had similar blood pressure, heart rate, and ejection fraction but higher body mass index in comparison with controls. LV mass index, maximal, and relative wall thickness were significantly greater in AFD patients. LSsubendo was significantly higher than LSsubepi in both groups, but GLS (P

Chosen as word of the year in 2016 by the Oxford Dictionaries, post-truth is a very recent neologism, spread on the wave of recent political events (particularly Brexit and Trump's election in 2016). What I would like to emphasise here is that post-truth, along with fake-news, refers to issues that are by no means new nor exclusively linked to modernity. I am referring in particular to the debate in ancient Greece on the relationship between truth and lies in political action and the relationship between 'fact' and the discourse that represents it (i.e. between ergon and logos).

This text explains the current call for direct (or pure) democracy as a consequence of the pervasive weight of visual culture in the contemporary world.

Background Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life‐long biweekly intravenous infusion may impact on patients’ quality of life. Moreover, regular infusions are time‐consuming: although a stepwise shortening of infusion duration is allowed up to a minimum of 1.5 hr, in most centers it remains ≥3 hr, and no data exists about the safety and tolerability of agalsidase beta administration at maximum tolerated infusion rate. Methods In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment‐naΪve), and explored factors predictive for the infusion rate increase tolerability. Results Fifty‐two patients (98%) reduced infusion duration ≤3 hr; of these, 38 (72%) even reached a duration ≤2 hr. We found a significant difference between the mean duration reached by already treated and naΪve patients (p, Although enzyme replacement therapy with agalsidase beta resulted in a variety of clinical benefits, life‐long biweekly intravenous infusion may impact on patients’ quality of life because regular infusions are time‐consuming. In this study, we reported our experience with a stepwise infusion rate escalation protocol developed in our center in a cohort of 53 Fabry patients (both already receiving and treatment‐naΪve), and explored factors predictive for the infusion rate increase tolerability. We showed that our infusion rate escalation protocol is safe and could improve patient compliance, satisfaction and quality of life.

Il contributo utilizza il modello teorico dell'Estetica relazionale di Nicolas Bourriaud per comprendere le dinamiche della comunicazione che la contemporaneità sta sperimentando sui social network. The contribution uses the theoretical model of Nicolas Bourriaud's Relational Aesthetics to understand the dynamics of communication that are used and experienced on social networks.

Background Fabry disease (FD) is a rare X-linked disease caused by mutations in GLA gene with consequent lysosomal accumulation of globotriaosylceramide (Gb3). Women with FD often show highly heterogeneous symptoms that can manifest from mild to severe phenotype. Main body The phenotypic variability of the clinical manifestations in heterozygous women with FD mainly depends on the degree and direction of inactivation of the X chromosome. Classical approaches to measure XCI skewness might be not sufficient to explain disease manifestation in women. In addition to unbalanced XCI, allele-specific DNA methylation at promoter of GLA gene may influence the expression levels of the mutated allele, thus impacting the onset and the outcome of FD. In this regard, analyses of DNA methylation at GLA promoter, performed by approaches allowing distinction between mutated and non-mutated allele, may be much more informative. The aim of this review is to critically evaluate recent literature articles addressing the potential role of DNA methylation in the context of FD. Although up to date relatively few works have addressed this point, reviewing all pertinent studies may help to evaluate the importance of DNA methylation analysis in FD and to develop new research and technologies aimed to predict whether the carrier females will develop symptoms. Conclusions Relatively few studies have addressed the complexity of DNA methylation landscape in FD that remains poorly investigated. The hope for the future is that ad hoc and ultradeep methylation analyses of GLA gene will provide epigenetic signatures able to predict whether pre-symptomatic female carriers will develop symptoms thus helping timely interventions.

Not only, as Barthes has shown, are photographs photographs are complex objects, endowed with a high degree of depth and of depth and considerable semantic possibilities but, as Floch has Floch argued, the testimonial one is only one effect of meaning among the many that they can produce. From this derives a twofold necessity. The first has to do with the caution that must characterize the approach to images. approach to images. A photograph is not a fact, it means it, and like every process of signification it presupposes a point of view a point of view, and therefore an ideology, which is revealed only when it becomes possible to only when it becomes possible to reconstruct what is missing in the frame, what is being marginalized and how, but also which instant has been fixed, thus altering the normal flow of time. time. The second necessity follows from the first and concerns the importance of a visual competence on the part of the spectator.

Il saggio affronta il tema di una memoria storica che non ricada nello storicismo e può essere solo l’esito di una narrazione pubblica e collettiva che non confluisce nella costruzione di un monumento. La condivisione di una memoria storica non va intesa come la costruzione di un prodotto condiviso, esito di un processo che sistematizza in senso teleologico le singole voci, dando vita ad una voce singola, bensì come la pratica delle posizioni eterogenee e antagoniste che rifuggono da qualsivoglia deriva sistematizzante che risponda al meccanismo di reductio ad unum matrice della modernità eurocentrica occidentale che assimila o espelle le posizioni differenti. Una memoria, dunque, che mostra una sorta di sincretismo, di ibridazione anti-sistematica che combina archivi, prospettive e linguaggi diversi. The essay deals with the theme of a historical memory that does not fall into historicism and can only be the result of a public and collective narrative that does not flow into the construction of a monument. The sharing of a historical memory should not be understood as the construction of a shared product, the result of a process that systematizes the individual voices in a teleological sense, giving life to a single voice, but rather as the practice of heterogeneous and antagonistic positions that shy away from any systematizing drift that responds to the mechanism of reductio ad unum matrix of Western Eurocentric modernity that assimilates or expels the different positions. A memory, therefore, that shows a kind of syncretism, of anti-systematic hybridization that combines different archives, perspectives and languages.

A clear evidence on the benefits of somatostatin analogues (SA) on liver outcome in patients affected by polycystic liver disease is still lacking. We performed a meta-analysis of RCTs and a trial sequential analysis (TSA) evaluating the effects of SA in adult patients with polycystic liver disease on change in liver volume. As secondary outcome, we evaluated the effects on quality of life as measured by SF36-questionnaire. Six RCTs were selected with an overall sample size of 332 adult patients with polycystic liver disease (mean age: 46 years). Mean liver volume at baseline was 3289 ml in SA group and 3089 ml in placebo group. Overall, unstandardized mean difference in liver volume was − 176 ml (95%CI, − 406, 54; p 2:0%, p p = 0.036). Cumulative Z-curve in TSA did not reach either significance and futility boundaries or required information size. Three RCTs have evaluated Quality of life parameters measured by SF36-QOL questionnaire for a total of 124 patients; no significant difference was found on the effect of SA on QOL parameters when compared with placebo. The present meta-analysis revealed a potential effect of SA on reduction of liver volume and quality of life parameters, but results did not reach a statistical significance. These data could be explained by the need of further studies, as demonstrated through TSA, to reach an adequate sample size to confirm the beneficial outcomes of SAs treatment.

L'introduzione al volume delinea il contesto, i temi, i protagonisti, gli obiettivi del volume, nato a seguito del Convegno tenutosi il 18 e 19 novembre 2019 presso l’Università degli Studi e realizzato dal Dipartimento di Scienze Umanistiche in collaborazione con il Centro di Studi filologici e linguistici siciliani, in occasione del trentennale dalla morte di Leonardo Sciascia. The introduction to the volume the describes, the themes, the protagonists, the objectives of the volume, born following the Conference held on 18 and 19 November 2019 at the University of Studies and created by the Department of Humanities in collaboration with the Center of Sicilian philological and linguistic studies, on the occasion of the thirtieth anniversary of the death of Leonardo Sciascia.

Lo Sciasciario dialettale è un contributo alla documentazione della lingua dell’autore di Racalmuto – con specifico riguardo al lessico dialettale – per offrire uno strumento utile per la comprensione della parole letteraria dell’autore di Racalmuto. Si tratta di una “lista di parole” ordinate alfabeticamente e riguardanti gli “autoctonismi” dialettali, le voci del dialetto usate nell’opera sciasciana che non trovano corrispondenti formali nell’italiano letterario (per es. sic. naca vs it. culla). In quanto voci “autenticamente” ed esclusivamente dialettali, esse esistono solo dentro l’orizzonte (etno)linguistico siciliano e svelano il tesoro più genuino del dialetto informando sulla parte più profonda e più autentica della storia e della cultura delle genti della più grande isola del Mediterraneo. Il loro percorso storico e sociale è, dunque, unico e va letto in intima relazione con il mondo culturale che le usa e le tramanda per “predicarsi”: Si tratta del mondo della “civiltà contadina”, quello della cultura dei campi, della «cultura dei mestieri », di cui partecipava anche chi contadino o artigiano non era e che, a ben pesarci, coincide con il mondo socio-culturale e con la parrocchia nei quali si è formato e dei quali si è nutrito Leonardo Sciascia.

Purpose Fabry Disease (FD) has been frequently proposed as possible underestimated differential diagnosis of Multiple Sclerosis (MS), but no study has been performed to test prevalence of GLA gene mutations in a population fulfilling diagnostic criteria of MS. Aim of this study is to determine the prevalence of GLA gene mutations in a large and representative population diagnosed with MS, simultaneously providing a critical revision of current literature reports of coexistence or misdiagnosis between these two conditions. Methods In this mono-centric cross-sectional study, 927 patients fulfilling McDonald diagnostic criteria and encompassing all MS phenotypes were enrolled. Patients underwent evaluation of α-GalA activity and genotyping. Both genetic variants annotated as pathogenic and GVUS were considered. Estimated alleles frequencies were then compared to the ones reported in the gnomAD database. Results GLA gene variants were found in seven individuals. Five patients carried variants previously described having controversial impact on FD phenotype, and the analysis of exome database revealed that they are not rare among healthy individuals. One patient showed a new variant never described before, and another one carried a late-onset FD cardiac variant. Conclusions The overall prevalence of GLA gene variants in MS patients is comparable to the one estimated in healthy population. This result is further supported by critical revision of current literature evidences of misdiagnosis between MS and FD, arguing in favour of independence between these disorders.

Lo studio usa strumenti della semiotica strutturale e interpretativa per proporre un close reading del Giorno della civetta. L’analisi così condotta mette in evidenza come il testo s’impegni a ristrutturare la competenza interpretativa del let-tore e, con essa, alcuni valori alla base della sua coscienza civile, con particolareriferimento alla verità e la giustizia. A partire dalla costruzione delle tensioni narrative intorno a questi due valori, si mette in evidenza lo slittamento semanticoche consente di leggere «il primo romanzo di mafia» come «il primo romanzosull’antimafia». The study uses tools of structural and interpretative semiotics to propose a close reading of the Day of the Owl. The analysis thus conducted highlights how the text undertakes to restructure the interpretative competence of the reader and, with it, some values ​​at the basis of his civil conscience, with particular reference to truth and justice. Starting from the construction of the narrative tensions around these two values, the semantic shift is highlighted which allows us to read "the first mafia novel" as "the first anti-mafia novel".

Nel secondo Novecento la minaccia nucleare angoscia l’intera umanità riaccendendo il dibattito sulla libertà della scienza e sull’intricato rapporto che questa intrattiene con il potere. Sciascia e Levi offrono nei loro scritti visioni della scienza assai diverse, talora opposte: Sciascia rivendica la superiorità della cultura umanistica (e letteraria) rispetto alla cultura scientifica, confermando la frattura denunciata da C. P. Snow che il chimico Levi considerava, invece, innaturale. Nonostante la differenza di prospettive, emerge tuttavia per entrambi la necessità che il discorso intorno alla scienza sia affrontato mediante il paradigma dell’etica.

Al di là del riferimento esplicito a temi, opere ed autori filosofici, la scrittura di Leonardo Sciascia appare percorsa dalle tracce di una unità mancata, di un bisogno di armonia tra i valori fondamentali dell'umano (verità, libertà, giustizia) che ne testimonia la vocazione filosofica profonda. La presenza di una componente critico-dialettica ne rende strutturalmente aperto, e quindi anche fallibile, il progetto sistematico. Ma proprio questo impedisce di leggere l'itinerario che va da "Il giorno della civetta" a "Una storia semplice" nel segno di un mero pessimismo antimetafisico, avvicinandolo piuttosto alle grandi (e incompiute) imprese filosofiche della tradizione.

Several studies highlight that testosterone deficiency is associated with, and predicts, an increased risk of developing metabolic disorders, and, on the other hand, is highly prevalent in obesity, metabolic syndrome and type-2 diabetes mellitus. Models of gonadotropin releasing hormone deficiency, and androgen deprivation therapy in patients with prostate cancer, suggest that hypogonadotropic hypogonadism might contribute to the onset or worsening of metabolic conditions, by increasing visceral adiposity and insulin resistance. Nevertheless, in functional hypogonadism, as well as in late onset hypogonadism, the relationship between hypogonadotropic hypogonadism and metabolic disorders is bidirectional, and a vicious circle between the two components has been documented. The mechanisms underlying the crosstalk between testosterone deficiency and metabolic disorders include increased visceral adipose tissue and insulin resistance, leading to development of metabolic disorders, which in turn contribute to a further reduction of testosterone levels. The decrease in testosterone levels might be determined by insulin resistance-mediated and, possibly, pro-inflammatory cytokine-mediated decrease of sex hormone binding globulin, resulting in a temporary increased free testosterone available for aromatization to estradiol in visceral adipose tissue, followed by a subsequent decrease in free testosterone levels, due to the excess of visceral adipose tissue and aromatization; by a direct inhibitory effect of increased leptin levels on Leydig cells; and by a reduced gonadotropin secretion induced by estradiol, inflammatory mediators, leptin resistance, and insulin resistance, with the ultimate determination of a substantial hypogonadotropic hypogonadism. The majority of studies focusing on the effects of testosterone replacement therapy on metabolic profile reported a beneficial effect of testosterone on body weight, waist circumference, body mass index, body composition, cholesterol levels, and glycemic control. Consistently, several interventional studies demonstrated that correction of metabolic disorders, in particular with compounds displaying a greater impact on body weight and insulin resistance, improved testosterone levels. The aim of the current review is to provide a comprehensive overview on the relationship between hypogonadotropic hypogonadism and metabolism, by clarifying the independent role of testosterone deficiency in the pathogenesis of metabolic disorders, and by describing the relative role of testosterone deficiency and metabolic impairment, in the context of the bidirectional relationship between hypogonadism and metabolic diseases documented in functional hypogonadotropic hypogonadism. These aspects will be assessed by describing metabolic profile in men with hypogonadotropic hypogonadism, and androgenic status in men with metabolic disorders; afterwards, the reciprocal effects of testosterone replacement therapy and corrective interventions on metabolic derangements will be reported.

Progressive nephropathy is one of the main features of Fabry disease. Although some clinical signs of Fabry nephropathy are already present in childhood, patients are often diagnosed relatively late in the course of the disease due to the absence of specific clinical markers, while a timely diagnosis and the prompt start of enzyme replacement therapy may be beneficial in stabilizing renal function or slowing its decline. Proteinuria/albuminuria has been accepted as the most important marker for Fabry nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. Therefore, early biomarkers may be useful for early identification of kidney involvement. The aim of this article is to review the current available literature on all biomarkers of Fabry nephropathy, with a comprehensive and critical description of their utilization in early recognition of renal damage.

This is the frst record in the literature of the benefcial efect of metformin on ADPKD progression in the same family: during 10 years of follow-up, eGFR decreased in three sisters, but in one of them, it decreased slower after the introduction of metformin and without adverse event . Our results confrm the benefcial efect of metformin in delaying the progression of renal dysfunction in ADPKD patients with moderately impaired eGFR

Background Fabry's disease (FD) is a rare, multi-organ lysosomal disease, caused by the deficiency of the enzyme α-galactosidase A, and is difficult to diagnose. Although parapelvic cysts (PC) were previously associated with FD, their prevalence and significance are unclear. Methods The present study aimed to: (i) evaluate, by renal ultrasound, the real prevalence of PC and of their determinants in a multicentre, nationwide cohort of FD patients (n = 173, Study 1) and (ii) ascertain whether a greater accuracy of PC detection improved their identification, in FD patients from a single centre (n = 67, Study 2). In both studies, for each FD patient, an age- and renal function-matched subject was selected for comparison (1:1). Results In Study 1, PC were detected in 28.9% of FD subjects and in only 1.1% of control subjects (P

Patients suffering from Fabry disease (FD), a lysosomal storage disorder, show a broad range of symptoms and the diagnosis followed by the therapeutic decision remains a great challenge. The biomarkers available today have not proven to be useful for predicting the evolution of the disease and for assessing response to therapy in many patients. Here, we used high-throughput microRNA profiling methodology to identify a specific circulating microRNA profile in FD patients. We discovered a pattern of 10 microRNAs able to identify FD patients when compared to healthy controls. Notably, two of these: the miR199a-5p and the miR-126-3p are able to discriminate FDs from the control subjects with left ventricular hypertrophy, a frequent but non-specific FD symptom. These same microRNAs are also sensitive to enzyme replacement therapy showing variation in the subjects under treatment. Furthermore, two other microRNAs of the profile, the miR-423-5p and the miR-451a, seem useful to highlight cardiac involvement in FD patients. A literature and database search revealed that miR-199a-5p, miR-126-3p, miR-423-5p and miR-451a are known to be linked to pathological states that occur during the FD development. In particular, miR-199a-5p, and miR-126-3p are involved in endothelial dysfunction and miR-423- 5p and miR-451a in myocardial remodeling. In conclusion, in this study we identified a common plasma microRNA profile in FD patients, useful not only for the correct classification of Fabry patients regardless of sex and age, but also to evaluate the response to therapy. Furthermore, our observations suggest that some microRNAs of this profile demonstrate prognostic qualities.

BACKGROUND: Proteinuria is the predominant risk factor for renal disease progression in Fabry disease (FD). When urine protein excretion is controlled to 0.50 g/24 h persisting despite ERT and anti-RAS therapy titrated to maximum tolerated dosage. METHODS: Fifteen FD patients were selected and studied in the first 6 months of add-on oral PCT (1 µg/day) and, in order to verify the dependence of proteinuria reduction on PCT, 3 months after drug withdrawal. RESULTS: At baseline, proteinuria was 1.3 ± 0.6 g/24 h. Six months of add-on PCT significantly decreased proteinuria to 0.4 ± 0.3 g/24 h, with levels

Fever of unknown origin (FUO) is a rather rare clinical syndrome representing a major diagnostic challenge. The occurrence of more than three febrile attacks with fever-free intervals of variable duration during 6 months of observation has recently been proposed as a subcategory of FUO, Recurrent FUO (RFUO). A substantial number of patients with RFUO have auto-inflammatory genetic fevers, but many patients remain undiagnosed. We hypothesize that this undiagnosed subgroup may be comprised of, at least in part, a number of rare genetic febrile diseases such as Fabry disease. We aimed to identify key features or potential diagnostic clues for Fabry disease as a model of rare genetic febrile diseases causing RFUO, and to develop diagnostic guidelines for RFUO, using Fabry disease as an example of inserting other rare diseases in the existing FUO algorithms. An international panel of specialists in recurrent fevers and rare diseases, including internists, infectious disease specialists, rheumatologists, gastroenterologists, nephrologists, and medical geneticists convened to review the existing diagnostic algorithms, and to suggest recommendations for arriving at accurate diagnoses on the basis of available literature and clinical experience. By combining specific features of rare diseases with other diagnostic considerations, guidelines have been designed to raise awareness and identify rare diseases among other causes of FUO. The proposed guidelines may be useful for the inclusion of rare diseases in the diagnostic algorithms for FUO. A wide spectrum of patients will be needed to validate the algorithm in different clinical settings.

// Francesca Scionti 1, * , Maria Teresa Di Martino 1, * , Simona Sestito 2 , Angela Nicoletti 2 , Francesca Falvo 2 , Katia Roppa 2 , Mariamena Arbitrio 3 , Pietro Hiram Guzzi 4 , Giuseppe Agapito 4 , Antonio Pisani 5 , Eleonora Riccio 5 , Daniela Concolino 2, # and Licia Pensabene 2, # 1 Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, Italy 2 Department of Medical and Surgical Sciences Pediatric Unit, Magna Graecia University, Catanzaro, Italy 3 ISN-CNR, Roccelletta di Borgia, Catanzaro, Italy 4 Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy 5 Department of Nephrology, University Federico II, Naples, Italy * These authors contributed equally to the work # These authors contributed equally to this work and share senior authorship Correspondence to: Maria Teresa Di Martino, email: teresadm@unicz.it Licia Pensabene, email: pensabene@unicz.it Keywords: Fabry disease; enzyme replacement therapy; DMET; ADH genes; oxidative stress Received: August 24, 2017 Accepted: October 29, 2017 Published: November 18, 2017 ABSTRACT Enzyme replacement therapy (ERT) has been widely used for the treatment of Fabry disease, a rare X-linked recessive disorder due to absent or reduced activity of lysosomal enzyme α-galactosidase A. It is still unclear why some patients under ERT show disease progression typically with renal, cardiovascular and cerebrovascular dysfunctions. Here, we investigated the involvement of drug absorption, distribution, metabolism, and excretion gene variants in response variability to ERT, genotyping 37 patients with the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET) Plus microarray. We found three single nucleotide polymorphisms in human alcohol dehydrogenase (ADH)4 gene (rs1126670, rs1126671, rs2032349) and one in ADH5 gene (rs2602836) associated with disease progression ( p < 0.05). Our data provide a basic tool for identification of patient with ERT non-response risk that may represent a framework for personalized treatment of this rare disease.

Background:In 2009, the agalsidase beta shortage resulted in switching to agalsidase alfa treatment for many Fabry disease patients, offering the unique opportunity to compare the effects of the two drugs. Because single studies describing effects of switching on the disease course are limited and inconclusive, we performed a systematic review and meta-Analysis of existing data.Methods:Relevant studies were identified in the PubMed, Cochrane, ISI Web, and SCOPUS databases from July 2009 to September 2015. The following parameters were analyzed: clinical events, changes in organ function or structure, disease-related symptoms, lyso-Gb3 plasma levels, and adverse effects.Conclusions:The nine studies (217 patients) included in our systematic review showed only marginal differences in most of the evaluated parameters. Seven of these studies were included in the meta-Analysis (176 patients). The pooled incidence rate of major adverse events was reported for five studies (150 patients) and was equal to 0.04 events per person-year. No significant change was observed after the shift in glomerular filtration rate, whereas left ventricular mass index, left ventricular posterior wall dimension, and ejection fraction were significantly reduced over time. Our data showed that the switch to agalsidase alfa was well tolerated and associated with stable clinical conditions.

Background. Depending on both membrane composition and solute transport rate across the membrane, protein composition of the dialysate of patients receiving peritoneal dialysis (PD) has recently become of great interest. Unfortunately, thus far few studies have focused on dialysate characterization, and further investigations are required to better understand the biological mechanisms influencing PD efficiency.Methods. Different classical proteomic approaches were combined with advanced mass spectrometric (MS) techniques to analyse peritoneal fluid (PF) protein composition of adult patients receiving PD. Characterization was performed by using 1D gel electrophoresis combined with nano-RPHPLCESIMS/MS and shotgun proteomics, while comparative analyses were performed coupling 2D gel electrophoresis with MALDI-TOF MS.Results. The study allowed the identification of 151 different proteins from PF, which are mainly of plasmatic origin. Comparison of PD effluents characterized by different glucose concentrations demonstrated four proteins (apolipoprotein A-IV, fibrinogen beta chain, transthyretin and alpha-1-antitrypsin) to be under-expressed in the highest osmolar solution having 4.25% compared to others having 1.5% and 2.5% glucose. All of them were found to be involved in the inflammatory processes.Conclusions. This study provides a possible platform for future diagnostic and therapeutic applications in the field of PD and allowed the identification of potential targets to be used in preventing inflammatory processes induced by the exposure to dialysis solutions. © 2009 The Author.

Fabry disease is a metabolic and lysosomal storage disorder caused by the functional defect of the α-galactosidase A enzyme; this defect is due to mutations in the GLA gene, that is composed of seven exons and is located on the long arm of the X-chromosome (Xq21–22). The enzymatic deficit is responsible for the accumulation of glycosphingolipids in lysosomes of different cellular types, mainly in those ones of vascular endothelium. It consequently causes a cellular and microvascular dysfunction. In this paper, we described five novel mutations in the GLA gene, related to absent enzymatic activity and typical manifestations of Fabry disease. We identified three mutations (c.846_847delTC, p.E341X and p.C382X) that lead to the introduction of a stop codon in positions 297, 341 and 382. Moreover we found a missense mutation (p.R227P) in the exon 5 of the GLA gene and a single point mutation (c.639 + 5 G > T) occurring five base pairs beyond the end of the exon 4. These mutations have never been found in our group of healthy control subjects > 2300. The studied patients presented some clinical manifestations, such as cornea verticillata, hypo-anhidrosis, left ventricular hypertrophy, cerebrovascular disorders and renal failure, that, considering the null enzymatic activity, suggest that the new mutations reported here are related to the classic form of Fabry disease. The identification of novel mutations in patients with symptomatology referable to FD increases the molecular knowledge of the GLA gene and it gives clinicians an important support for the proper diagnosis of the disease.

Background & Aims Short-term studies have shown that somatostatin analogues are effective in patients with polycystic kidney and liver disease. We evaluated the long-term effects of long-acting release octreotide (octreotide LAR), a somatostatin inhibitor, vs placebo in these patients. Methods We performed a controlled study of adults with polycystic kidney and liver disease (estimated glomerular filtration rate, 40 mL/min/1.73m 2 or more) at a single center in Italy. We analyzed data from 27 patients randomly assigned to groups given octreotide LAR (40 mg, n = 14) or placebo (n = 13) each month for 3 years. The primary outcome was absolute and percentage change in total liver volume (TLV), which was measured by magnetic resonance imaging at baseline, after 3 years of treatment, and then 2 years after treatment ended. Results Baseline characteristics were similar between groups. After 3 years, TLV decreased by 130.2 ± 133.2 mL in patients given octreotide LAR (7.8% ± 7.4%) ( P = .003) but increased by 144.3 ± 316.8 mL (6.1% ± 14.1%) in patients given placebo. Change vs baseline differed significantly between groups ( P = .004). Two years after treatment ended, TLV had decreased 14.4 ± 138.4 mL (0.8% ± 9.7%) from baseline in patients given octreotide LAR but increased by 224.4 ± 331.7 mL (11.0% ± 14.4%) in patients given placebo. Changes vs baseline still differed significantly between groups ( P = .046). Decreases in TLV were similar in each sex; the change in TLV was greatest among subjects with larger baseline TLV. No patient withdrew because of side effects. Conclusions In a placebo-controlled study of patients with polycystic kidney and liver disease, 3 years of treatment with octreotide LAR significantly reduced liver volume; reductions were maintained for 2 years after treatment ended. Octreotide LAR was well-tolerated. ClinicalTrials.gov number: NCT02119052.

Endocrine abnormalities are known to affect patients with Fabry disease (FD). Pituitary gland theoretically represents an ideal target for FD because of high vascularization and low proliferation rate. We explored pituitary morphology and function in a cohort of FD patients through a prospectic, monocentric study at an Academic Tertiary Center. The study population included 28 FD patients and 42 sex and age-matched normal subjects. The protocol included a contrast enhancement pituitary MRI, the assessment of pituitary hormones, anti-pituitary, and anti-hypothalamus antibodies. At pituitary MRI, an empty sella was found in 11 (39%) FD patients, and in 2 (5%) controls (p&nbsp

Background: Contrast media (CM)-induced nephropathy (CIN) is an acute deterioration of renal function following administration of CM mediated to a large extent by the increased production of ROS within the kidney. Aim of this study was to evaluate whether a novel isoform of a recombinant Manganese SOD (rMnSOD) could provide an effective protection against CIN; this molecule shares the same ability of physiological SODs in scavenging reactive oxygen species (ROS) but, due to its peculiar properties, enters inside the cells after its administration. Methods: We studied the effects rMnSOD on oxidative damage in a rat model of CIN in uninephrectomized rats, that were randomly assigned to 3 experimental Groups: Group CON, control rats treated with the vehicle of CM, Group HCM, rats treated with CM and Group SOD, rats treated with CM and rMnSOD. Results: In normal rats, pretreatment with rMnSOD, reduced renal superoxide anion production, induced by the activation of NAPDH oxidase, by 84 % (p < 0.001). In rats of Group HCM, ROS production was almost doubled compared to rat of Group CON (p < 0.01) but returned to normal values in rats of Group SOD, where a significant increase of SOD activity was detected (+16 % vs HCM, p < 0.05). Administration of CM determined a striking fall of GFR in rats of Group HCM (-70 %, p < 0.001 vs CON), greatly blunted in Group SOD (-28 % vs CON, p < 0.01); this was associated with a lower presence of both tubular necrosis and intratubular casts in SOD-treated rats (both p < 0.01 vs Group HCM). Conclusions: Our data indicate that rMnSOD is able to reduce renal oxidative stress, thus preventing the reduction of GFR and the renal histologic damage that follows CM administration. © 2013 Japanese Society of Nephrology.

A 68-year-old female treated by peritoneal dialysis (PD) for 4 years was hospitalized for cough and dyspnea without chest pain. Chest X-ray revealed massive right pleural effusion. High glucose content in pleural fluid in comparison with blood glucose level was suggestive of transdiaphragmatic leakage. To establish the communication between the peritoneal and pleural cavity, peritoneal scintigraphy was performed. Different 99mTc-labeled colloids have been used for peritoneal scintigraphy in the past years, such as sulfur colloid, macroaggregated albumin, and diethylenetriamine pentaacetic acid (DTPA), each with some important limitations. On the basis of the characteristics of icodextrin, an osmotic colloid agent routinely used in PD, such as its persistence in the peritoneal space, 99mTc-icodextrin scintigraphy was performed to confirm the diagnosis of peritoneopleural leakage (Fig. 1a, b). Therefore, 99mTc-icodextrin scintigraphy may represent a new, simple, noninvasive, cost-effective, well-tolerated, and safe radionuclide imaging method to clearly detect some causes of peritoneal dialysis failure.

p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by resident intestinal bacteria. In patients with chronic kidney disease, the accumulation of p-cresol and of its metabolite p-cresyl-sulphate, that represents more than 95% of circulating p-cresol, causes endothelial dysfunction and ultimately increases the cardiovascular risk of these patients. Therapeutic strategies able to reduce plasma p-cresol levels are highly demanded but unfortunately not available yet. Because it has been reported that the phosphate binder sevelamer also sequesters p-cresol in vitro we hypothesized that it could do so also in peritoneal dialysis patients. To explore this hypothesis we measured total cresol plasma concentrations in 57 patients with end-stage renal disease on peritoneal dialysis patients, 29 receiving sevelamer for the treatment of hyperphosphatemia and 28 patients not assuming this drug. Among the patients not assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12 received no drug because they were not hyperphosphatemic. When we compared total p-cresol plasma concentrations in these different groups of patients, we, we found that plasma p-cresol levels were significantly lower in patients receiving sevelamer than in subjects receiving lanthanum or no drug. Patients assuming sevelamer had also lower high sensitivity C-reactive protein serum concentrations compared to patients not assuming this drug. Multiple linear regression analysis showed that Conversely, no difference either in residual glomerular filtration rate, total weekly dialysis dose or serum phosphate levels were observed among the different groups. These results suggest that sevelamer could be an effective strategy to lower p-cresol circulating levels in peritoneal dialysis patients in which it could also favorably affect the cardiovascular risk because of its anti-inflammatory effect.

Aims. Our group investigated albumin gene expression in human adipocytes, its regulation by inflammation and the possible contribution of adipose tissue to albumin circulating levels.Methods. Both inflamed and healthy subjects provided adipose tissue samples. RT-PCR, Real-Time PCR, and Western Blot analysis on homogenates of adipocytes and pre-adipocytes were performed. In sixty-three healthy subjects and fifty-four micro-inflamed end stage renal disease (ESRD) patients circulating levels of albumin were measured by nephelometry; all subjects were also evaluated for body composition, calculated from bioelectrical measurements and an thropometric data.Results. A clear gene expression of albumin was showed in pre-adipocytes and, for the first time, in mature adipocytes. Albumin gene expression resulted significantly higher in pre-adipocytes than in adipocytes. No significant difference in albumin gene expression was showed between healthy controls and inflamed patients. A significant negative correlation was observed between albumin levels and fat mass in both healthy subjects and inflamed ESRD patients.Conclusions. In the present study we found first time evidence that human adipocytes express albumin. Our results also showed that systemic inflammation does not modulate albumin gene expression. The negative correlation between albumin and fat mass seems to exclude a significant contributing role of adipocyte in plasma albumin.

In this introduction to the first section of the volume, I mention to the various definitions of transnationalism and to the diverse transnational perspectives on migration. Furthermore, I discuss the economic and political dimension of transnationalism by focusing respectively on socio-economic remittances, co-development on the one hand, and, on the other hand, on long distance nationalism. In the second part I take into account some of the analytical characteristics of methodological nationalism and the cosmopolitan ambition of the anthropology of migration. In the field of anthropology and the social sciences, Wimmer and Glick Schiller (2002) define methodological nationalism” as “the assumption that the nation/state/society is the natural social and political form of the modern world” (Wimmer, Schiller, 2002: 302). And it is this process of naturalisation in the empirical studies of migration that have been particularly challenged by the transnational perspective on migration. Yet, some authors have expressed some perplexity about the novelty both of transnationalism and of a transnational approach to migration. Indeed, the premise that multiple networks connect several contexts in a continuous manner has been previously illustrated in some work of British anthropology of the colonial and post-colonial era (Werbner, 2008). These studies were already dealing with the circularity, which binds together the rural and the urban contexts through social networks. Furthermore, Werbner argues that in anthropology, which she defines as “the study of part-societies and social fields”, one cannot find the sin of methodological nationalism. Instead, she believes that anthropology has always been characterised by a cosmopolitan take towards the people and the subject under study. Yet, this reminder of a hidden continuity may run the risk of underestimating the epistemological break provided to the evolution of anthropological thought by the processual approaches of Marxist political economy and Manchester school. Moreover, despite disagreements over methodological nationalism, one aspect in common between the two articles introduced here is an historical sensitivity that one finds in Werbner theoretical reflections as much as in the historical discussion of Nation-building provided by Glick Schiller. Somehow both anthropologists urge us to avoid the mistake of considering recent migration trends as the mechanical rise of novel forms of social relations and of neglecting, from a phenomenological and epistemological viewpoint, the central role played by long lasting historical processes surviving technological change.

A 31-year-old male with Marfan syndrome was hospitalized for gross haematuria and abdominal pain. He was diagnosed with Marfan syndrome at 26 years of age because of his family history (paternal inheritance) and his manifestations. Contrast-enhanced computed tomography of the abdomen revealed an aneurysm of the abdominal aorta (Fig. 1a) and of the hepatic artery (Fig. 1b), as well as multiple hepatic and bilateral renal cysts with increased kidney size (Fig. 1b), suggesting a diagnosis of autosomal dominant polycystic kidney disease (ADPKD). A positive family history was not elicited; however, his mother died at 38 years of age due to a ruptured dissecting aneurysm of the thoracic aorta, a feature rarely reported in ADPKD [1, 2]. To clarify the diagnosis of ADPKD, a genetic analysis was performed, and revealed a nonsense mutation in exon 4 of the PKD2 gene (c.916C[Tp.R306X). The association between ADPKD and Marfan syndrome is rare, and is reported in few cases in the literature [3]. Although renal cysts are the cardinal manifestations of ADPKD, it presents multiple extra-renal manifestations, encompassing both cystic involvement of the organs and