Androgen Receptor (AR) Gene (CAG)n and (GGN)n Length Polymorphisms and Symptoms in Young Males With Long-Lasting Adverse Effects After Finasteride Use Against Androgenic Alopecia

INTRODUCTION: Long-term adverse symptoms of men who used oral finasteride against androgenic alopecia have been recently described as post-finasteride syndrome (PFS). AIM: To determine whether (CAG)n-rs4045402 and (GGN)n-rs3138869 polymorphisms in the androgen receptor (AR) gene are implicated in PFS. METHODS: AR polymorphisms were studied according to PFS symptoms in 66 white participants (31.8% Italian, 28.8% American, and 39.4% other). MAIN OUTCOME MEASURES: Symptoms were investigated by an ad hoc 100-item questionnaire and the Arizona Sexual Experience Scale and Aging Male Symptom Scale (AMS). (CAG)n and (GGN)n repeats were categorized as short ([CAG]9-19, [GGN]23). RESULTS: Median age was 32 years, duration of finasteride use was 360 days, and time from finasteride discontinuation was 1,053 days. We observed several frequency differences in symptoms according to (CAG)n and (GGN)n repeat numbers. Three AMS items were worse for medium (GGN)23 than for long (GGN)>23 carriers and one item was worse for short (GGN)2 kg), increased skin dryness, and onset of symptoms after finasteride use. CONCLUSION: This study showed that short and/or long (CAG)n and (GGN)n repeats had different frequencies according to symptoms reported by patients with PFS, likely reflecting the vast array of genes modulated by the AR. This study showed a U-curvilinear profile of (CAG)n repeats for skin dryness symptoms, where the two extremes exhibited a worse condition than medium repeats. Further studies are necessary to investigate the PFS pathophysiology using a precision medicine approach

CommonSpaces: an approach to web learning based on OERs, mentoring and collaborative learning

[EN] Currently, the internet is full of freely accessible resources that can provide excellent learning opportunities. However, these resources are usually not well organized, and for many users it is often difficult to use these dispersed sources of knowledge in a coordinated way. The project CommonS aims at building a space - called CommonSpaces - dedicated to communities of practice in which participants learn through the cataloguing, re-use, adaptation and sequencing of Open Educational Resources (OERs) into socalled learning paths. We define a Learning Path as an organized set of interconnected OERs (created by communities of users) that can be created by users both to organize their learning experience and to provide consistent learning sequences for others. In this paper, we briefly present the rationale and the theoretical foundations of the project. Then we discuss the features of CommonSpaces in its first prototype version and describe the preliminary findings from a pioneering experience of collaborative learning carried out by means of CommonSpaces. We conclude discussing the ongoing collective modeling of the final version of CommonSpaces and its future directions.Lariccia, S.; Ritella, G.; Montanari, M.; Cesareni, D.; Toffoli, G. (2016). CommonSpaces: an approach to web learning based on OERs, mentoring and collaborative learning. En 2nd. International conference on higher education advances (HEAD'16). Editorial Universitat Politècnica de València. 326-333. https://doi.org/10.4995/HEAD16.2015.2733OCS32633

Breast Cancer-Related Neoplastic Alopecia: A Case Report and Review of the Literature

Neoplastic alopecia (NA) is defined as an organized hair loss in single or multiple areas of the scalp caused by a primary tumor that has metastasized to the skin of the scalp. Due to its localization and clinical appearance, NA should be placed in differential diagnosis with alopecia areata or other entities. To date, pathognomonic dermoscopic criteria of NA have not yet been described: the absence of classical criteria of other scalp diseases in addition to a major neovascularization with on-focus arborizing vessels and erosions or ulcerations may help the clinician to suspect a diagnosis of secondary alopecia. Dermatologists should pay more attention to these rare forms of secondarism because in exceptional cases, a simple alopecia of the scalp can hide a new, relapsing or metastatic neoplasia

A likely association between low mannan-binding lectin level and brain fog onset in long COVID patients

: Brain fog can be described as a constellation of new-onset neuropsychiatric sequelae in the post-acute phase of COVID-19 (long COVID). The symptoms include inattention, short-term memory loss, and reduced mental acuity, which may undermine cognition, concentration, and sleep. This cognitive impairment, persisting for weeks or months after the acute phase of SARS-CoV-2 infection, can significantly impact on daily activities and the quality of life. An important role for the complement system (C) in the pathogenesis of COVID-19 has emerged since the beginning of pandemic outbreak. A number of pathophysiological characteristics including microangiopathy and myocarditis have been attributed to dysregulated C activation due to SARS-CoV-2 infection. Mannan-binding lectin (MBL), the first recognition subcomponent of the C lectin pathway, has been shown to bind to glycosylated SARS-CoV-2 spike protein, genetic variants of MBL2 are suggested to have an association with severe COVID-19 manifestations requiring hospitalization. In the present study, we evaluated MBL activity (lectin pathway activation) and levels in the sera of a cohort of COVID-19 patients, presenting brain fog or only hyposmia/hypogeusia as persistent symptoms, and compared them with healthy volunteers. We found significantly lower levels of MBL and lectin pathway activity in the sera of patients experiencing brain fog as compared to recovered COVID-19 patients without brain fog. Our data indicate that long COVID-associated brain fog can be listed among the variegate manifestations of increased susceptibility to infections and diseases contributed by MBL deficiency

Electronic properties of the boroxine–gold interface: evidence of ultra-fast charge delocalization

We performed a combined experimental and theoretical study of the assembly of phenylboronic acid on the Au(111) surface, which is found to lead to the formation of triphenylboroxines by spontaneous condensation of trimers of molecules. The interface between the boroxine group and the gold surface has been characterized in terms of its electronic properties, revealing the existence of an ultra-fast charge delocalization channel in the proximity of the oxygen atoms of the heterocyclic group. More specifically, the DFT calculations show the presence of an unoccupied electronic state localized on both the oxygen atoms of the adsorbed triphenylboroxine and the gold atoms of the topmost layer. By means of resonant Auger electron spectroscopy, we demonstrate that this interface state represents an ultra-fast charge delocalization channel. Boroxine groups are among the most widely adopted building blocks in the synthesis of covalent organic frameworks on surfaces. Our findings indicate that such systems, typically employed as templates for the growth of organic films, can also act as active interlayers that provide an efficient electronic transport channel bridging the inorganic substrate and organic overlayer

A New Genetic Risk Score to Predict the Outcome of Locally Advanced or Metastatic Breast Cancer Patients Treated With First-Line Exemestane: Results From a Prospective Study

Currently there are no reliable biomarkers to predict outcome of exemestane treatment. We designed a prospective study to investigate whether constitutive genetic background might affect response to therapy. In a population of 302 advanced breast cancer patients treated with exemestane we showed that a 5-polymorphism-based genetic score could be used to identify patients with different risks of progression and death.Introduction: Approximately 50% of locally advanced or metastatic breast cancer (MBC) patients treated with first-line exemestane do not show objective response and currently there are no reliable biomarkers to predict the outcome of patients using this therapy. The constitutive genetic background might be responsible for differences in the outcome of exemestane-treated patients. We designed a prospective study to investigate the role of germ line polymorphisms as biomarkers of survival. Patients and Methods: Three hundred two locally advanced or MBC patients treated with first-line exemestane were genotyped for 74 germ line polymorphisms in 39 candidate genes involved in drug activity, hormone balance, DNA replication and repair, and cell signaling pathways. Associations with progression-free survival (PFS) and overall survival (OS) were tested with multivariate Cox regression. Bootstrap resampling was used as an internal assessment of results reproducibility. Results: Cytochrome P450 19A1-rs10046TC/CC, solute carrier organic anion transporter 1B1-rs4149056TT, adenosine triphosphate binding cassette subfamily G member 2-rs2046134GG, fibroblast growth factor receptor-4-rs351855TT, and X-ray repair cross complementing 3-rs861539TT were significantly associated with PFS and then combined into a risk score (0-1, 2, 3, or 4-6 risk points). Patients with the highest risk score (4-6 risk points) compared with ones with the lowest score (0-1 risk points) had a median PFS of 10 months versus 26.3 months (adjusted hazard ratio [AdjHR], 3.12 [95% confidence interval (CI), 2.18-4.48]; P < .001) and a median OS of 38.9 months versus 63.0 months (AdjHR, 2.41 [95% CI, 1.22-4.79], P = .012), respectively. Conclusion: In this study we defined a score including 5 polymorphisms to stratify patients for PFS and OS. This score, if validated, might be translated to personalize locally advanced or MBC patient treatment and management

Development of a questionnaire specifically for patients with Ileal Orthotopic Neobladder (IONB)

The ileal orthotopic neobladder (IONB) is often used in patients undergoing radical cystectomy. The IONB allows to void avoiding the disadvantages of the external urinary diversion.In IONB patients the quality of life (QoL) appears compromised by the need to urinate voluntarily. The patients need to wake up at night interrupting the sleep-wake rhythm with consequences on social and emotional life.At present the QoL in IONB patients is evaluated by generic questionnaires. These are useful when IONB patients are compared with patients with different urinary diversions but they are less effective when only IONB patients are evaluated. To address this problem a specific questionnaire-the IONB-PRO-was developed. METHODS: A) Based on a conceptual framework, narrative-based interviews were conducted on 35 IONB patients. A basic pool of 43 items was produced and organized throughout two clinical and four QoL dimensions. An additional 15 IONB patients were interviewed for face validity testing.B) Psychometric testing was conducted on 145 IONB patients. Both classic test strategy and Rasch analysis were applied. Psychometric properties of the resulting scales were comparatively tested against other QoL-validated scales. RESULTS: The IONB-PRO questionnaire includes two sections: one on the QoL and a second section on the capability of the patient to manage the IONB. For evaluation of the QoL, three versions were delivered: 1) a basic 23-item QoL version (3 domains 23-items; alpha 0.86÷ 9.69), 2) a short-form 12-item QoL scale (alpha = 0.947), and 3) a short-form 15-item Rasch QoL scale (alpha = 0.967). Correlations of the long version scales with the corresponding dimensions of the EORTC-QLQ C30 and the EORTC-BLM30 were significant. The short forms exhibited significant correlations with the global health dimension of the EORTC-QLQ and with the urinary subscales of the EORTC-BLM30. The effect size was approximately 1.00 between patients at the 1-year follow-up period and those with 3, 5, and > 5-year follow-up periods for all scales. No relevant differences were observed between the 12-item short-form and the Rasch scale. CONCLUSIONS: The IONB-PRO long and short-forms demonstrated a high level of internal consistency and reliability with an excellent discriminanting validity

Automi e linguaggio nell'ecosistema delle reti digitali

In questo lavoro di rassegna vogliamo presentare alcuni strumenti interessanti nell’ambito del NLP (Natural Language Processing) per esemplificare quali obbiettivi ci si può proporre di raggiungere, quali strumenti abbiamo a disposizione, quali raffinamenti è possibile prevedere e in quale arco temporale. Insomma, si potrebbe riassumere, quale futuro ha la futurologia? Accanto alle opportunità che questo panorama offre agli studiosi del linguaggio e delle applicazioni delle tecnologie dell’informazione nel dominio delle scienze umane, emergono anche grandi interrogativi etici: è possibile accettare che il progresso tecnologico avanzi seguendo meccanismi autonomi di avanzamento? È immaginabile proporre di istituire regole di governance per l’ecosistema linguistico concettuale del WorldWideWeb

Chi controlla i controllori? Una rivisitazione del concetto di «top-down» nelle funzioni esecutive e relative implicazioni per lo sviluppo cognitivo tipico e atipico

Classicamente le funzioni esecutive, o controllo cognitivo (CC), sono state associate all’azione top-down di meccanismi di controllo cognitivo che consentono la messa in atto consapevole di comportamento organizzato sulla base di richieste esplicite. Questi meccanismi sono stati tradizionalmente contrapposti a quelli automatici, impliciti e bottom-up dell’apprendimento associativo. Nel presente lavoro si ripercorrono i principali contributi che hanno supportato tale visione teorica per introdurre di seguito la recente «Prospettiva dell’Apprendimento sul Controllo Cognitivo» (Abrahamse et al., 2016), che adotta una visione dimensionale del CC considerato come proprietà emergente del sistema cognitivo, in parte plasmato dalle caratteristiche implicite di regolarità e contingenza presenti nell’ambiente. All’interno di questa prospettiva i meccanismi impliciti assumono un ruolo centrale nel costruire la capacità di usare un comportamento finalizzato e consentono una gestione ottimale delle risorse cognitive grazie all’adozione di strategie di controllo reattive e proattive. Infine, vengono discusse le implicazioni di questa nuova corrente teorica per le traiettorie di sviluppo e le possibili applicazioni nella pratica clinica