A Gaussian-Mixture based stochastic framework for the interpretation of spatial heterogeneity in multimodal fields

We provide theoretical formulations enabling characterization of spatial distributions of variables (such as, e.g., conductivity/permeability, porosity, vadose zone hydraulic parameters, and reaction rates) that are typical of hydrogeological and/or geochemical scenarios associated with randomly heterogeneous geomaterials and are organized on various scales of heterogeneity. Our approach and ensuing formulations embed the joint assessment of the probability distribution of a target variable and its associated spatial increments, DY, taken between locations separated by any given distance (or lag). The spatial distribution of Y is interpreted through a bimodal Gaussian mixture model. The modes of the latter correspond to an indicator random field which is in turn related to the occurrence of different processes and/or geomaterials within the domain of observation. The distribution of each component of the mixture is governed by a given length scale driving the strength of its spatial correlation. Our model embeds within a unique theoretical framework the main traits arising in a stochastic analysis of these systems. These include (i) a slight to moderate asymmetry in the distribution of Y and (ii) the occurrence of a dominant peak and secondary peaks in the distribution of DY whose importance changes with lag together with the moments of the distribution. This causes the probability distribution of increments to scale with lag in way that is consistent with observed experimental patterns. We analyze the main features of the modeling and parameter estimation framework through a set of synthetic scenarios. We then consider two experimental datasets associated with different processes and observation scales. We start with an original dataset comprising microscale reaction rate maps taken at various observation times. These are evaluated from AFM imaging of the surface of a calcite crystal in contact with a fluid and subject to dissolution. Such recent high resolution imaging techniques are key to enhance our knowledge of the processes driving the reaction. The second dataset is a well established collection of Darcy-scale air-permeability data acquired by Tidwell and Wilson (1999) [Water Resour Res, 35, 3375-3387] on a block of volcanic tuff through minipermeameters associated with various measurement scales

COVID-19–related skin manifestations: Update on therapy

An increasing body of evidence has been produced in a very limited period to improve the understanding of skin involvement in the current coronavirus 2019 disease pandemic, and how this novel disease affects the management of dermatologic patients. A little explored area is represented by the therapeutic approach adopted for the different skin manifestations associated with the infection. An overview of the current scenario is provided, through review of the English-language literature published until October 30, 2020, and comparison with the personal experience of the authors. As dermatologists, our primary aim is to support patients with the highest standard of care and relieve suffering, even with lesions not life-threatening. With asymptomatic COVID-19 patients, patient discomfort related to skin lesions should not be undervalued and intervention to accelerate healing should be provided. Consensus protocols are warranted to assess the best skin-targeted treatments in COVID-19 patients

Early predictors of smoking cessation after myocardial infarction

The determinants of long-term smoking cessation were evaluated in 80 patients who smoked cigarettes and survived a myocardial infarction. All patients underwent a program of rehabilitation and secondary prevention including in-hospital counseling and physician-guided reinforcing sessions at 1, 3, and 6 months after discharge. At 18 months of follow-up, 53 patients (66.3%) had quit smoking. Variables associated with smoking cessation were duration of hospital stay greater than or equal to 19 days (79 vs. 48%; p less than 0.005) and peak creatine phosphokinase (CPK) elevation greater than or equal to 500 U/l (76 vs. 54%; p less than 0.05). Males tended to quit in higher proportion than females (68 vs. 44%). Age, prior myocardial infarction, other cardiovascular risk factors, infarction location, Killip class at entry, and duration of stay in coronary care unit did not significantly affect the quitting rates. Logistic regression analysis singled out the duration of hospital stay as a significant predictor of smoking cessation (p less than 0.005). Early and intensive secondary prevention during the hospital stay is crucial in promoting sustained smoking cessation after myocardial infarction

Vegetating nodules following erosions on the oral cavity : a quiz

Acta Derm Venereol 95 © 2015 The Authors. doi: 10.2340/00015555-1936 Journal Compilation © 2015 Acta Dermato-Venereologica. ISSN 0001-5555 A 68-year-old Italian man presented with a 7-month history of multiple erosions on the trunk as well as lips and oral cavity. Before admission to our department, he was treated in another institution with systemic corticosteroids (oral prednisone at the initial dose of 1 mg/kg/day, with progressively tapering dosages for 2 months) and other immunosuppressants, such as azathioprine (1.25 mg/kg/ day for 2 months), intravenous immunoglobulins (one cycle consisting of one infusion of 400 mg/kg/day for 5 consecutive days), and rituximab (one cycle consisting of one infusion of 375 mg/m2/every week for 4 weeks), achieving resolution of the cutaneous manifestations but without control of the oral involvement. Upon admission, he had multiple lip and oral erosions (Fig. 1a). In the following days, he developed erythematous-violaceous vegetating nodules that coalesced into ulcerated plaques on the lips and tongue (Fig. 1b). The patient's general condition was compromised; he was asthenic and, due to dysphagia, had lost about 15 kg in the last 3 months. Staging fibroscopy revealed nodules that induced marked stenosis of the larynx and pharynx (Fig. 1c). Within a few days, an emergency tracheotomy was required because of acute dyspnea. Biopsy specimens from a nodule were submitted for histology (Fig. 1d)

Multifaceted Aspects of Metabolic Plasticity in Human Cholangiocarcinoma : An Overview of Current Perspectives

Cholangiocarcinoma (CCA) is a deadly tumor without an effective therapy. Unique metabolic and bioenergetics features are important hallmarks of tumor cells. Metabolic plasticity allows cancer cells to survive in poor nutrient environments and maximize cell growth by sustaining survival, proliferation, and metastasis. In recent years, an increasing number of studies have shown that specific signaling networks contribute to malignant tumor onset by reprogramming metabolic traits. Several evidences demonstrate that numerous metabolic mediators represent key-players of CCA progression by regulating many signaling pathways. Besides the well-known Warburg effect, several other different pathways involving carbohydrates, proteins, lipids, and nucleic acids metabolism are altered in CCA. The goal of this review is to highlight the main metabolic processes involved in the cholangio-carcinogeneis that might be considered as potential novel druggable candidates for this disease

Un caso di linfoma cutaneo T gamma/delta

Secondo la classificazione della WHO/EORTC del 2008, fra i linfomi cutanei, una variante molto rara \ue8 rappresentata dal linfoma T cutaneo gamma/delta. Questa entit\ue0 rappresenta circa l'1% dei linfomi T cutanei e si manifesta clinicamente in modo analogo ad altre forme linfoproliferative cutanee. La diagnosi \ue8 istologica, immunoistochimica e molecolare; l'infiltrato neoplastico \ue8 rappresentato da piccole-medie e grandi cellule ed elementi blastici distribuiti secondo 3 diversi pattern: epidermotropo, dermico e sottocutaneo. Le indagini di biologia molecolare risultano caratteristicamente negative per il TCR-beta e evidenziano un riarrangiamento clonale per il TCR-delta1 e TCR-gamma. Descriviamo il caso di una donna di 70 anni in buone condizioni di salute, che presentava da 2 anni lesioni sottocutanee a tipo lupus panniculite ad evoluzione necrotico-ulcerativa in prevalenza localizzate agli arti. La paziente era stata inizialmente sottoposta a terapia con steroidi per via orale, ma la patologia era lentamente progredita. Veniva pertanto eseguita una biopsia cutanea per esame istologico, indagini di immunoistochimica e biologia molecolare. Le indagini eseguite evidenziavano la presenza di un infiltrato linfocitario superficiale e profondo esteso al tessuto adiposo con cellule pleomorfe di piccola e media taglia CD2+, CD3+, CD56+, TCR-delta-1+, Mib-1++, TIA-1++. La paziente \ue8 stata sottoposta a cicli di polichemioterapia (CHOP) con parziale risposta clinica. Nonostante la terapia, il quadro clinico \ue8 andato incontro a progressione con coinvolgimento viscerale in 6 mesi ed exitus per complicazioni cardiocircolatorie e polmonari dopo circa 2 mesi. Questo caso appare peculiare per il suo andamento clinico; il linfoma gamma/delta si caratterizza, infatti, per una iniziale lenta evoluzione ed un successivo rapido coinvolgimento sistemico con importante sintomatologia generale. Il trattamento polichemioterapico non sembra influenzare la prognosi che \ue8 generalmente sfavorevole

Due casi di linfoma cutaneo anaplastico a grandi cellule (C-ALC) CD30+ CD8+ aggressivi

Descriviamo 2 casi inusuali. Il primo caso riguarda una donna di 79 anni, affetta da morbo di Alzheimer, che presentava da un anno lesioni agli arti superiori, insorte inizialmente come chiazze eritematose e diventate nodulari con componente ulcerativa in circa 40 giorni. L\u2019esame istologico ha mostrato densa infiltrazione perivascolare di piccoli linfociti ed elementi linfoidi di medie dimensioni e di aspetto blastico frammisti a polvere cromatinica ed elementi plasmocitoidi. All\u2019immunoistochimica l\u2019infiltrato era CD3+, CD30+, CD8+, Granzyme B+, CD56-, ALK1-, EMA-. Alla biologia molecolare era presente un riarrangiamento policlonale del TCR-gamma. Si \ue8 verificato un rapido coinvolgimento viscerale con interessamento gastrico e linfonodale toracico. La prognosi \ue8 stata infausta nonostante il trattamento polichemioterapico con CVP. Il secondo caso riguarda un uomo di 58 anni, diabetico e cardiopatico. Due anni prima aveva presentato una lesione nodulare al polso sinistro, biopsiata c/o altra sede con diagnosi di LNH a grandi cellule anaplastico primitivo cutaneo. Per la comparsa di analoga lesione alla gamba dx era stato sottoposto a stadiazione con riscontro di linfoadenopatia toracica multipla, per cui era stata intrapresa polichemioterapia con CHOP ed in seguito con VNCOP-B, con buoni risultati clinici. Giunto alla nostra osservazione due mesi fa si \ue8 eseguita biopsia cutanea sulle lesioni nodulari della gamba dx con reperto di infiltrato dermico non epidermotropo di elementi linfocitari medio-grandi, marcatamente pleomorfi con nucleo ipercromatico. All\u2019immunoistochimica le cellule risultavano CD3+, CD8+, CD30+, Granzyme B+, CD56-, ALK1-, EMA-. Alla biologia molecolare si rilevava riarrangiamento monoclonale del TCR-gamma. Il paziente \ue8 attualmente in trattamento con radioterapia locale. La diagnosi istologica e molecolare dei due casi descritti era orientativa per linfoma anaplastico a grandi cellule primitivo cutaneo CD8+ CD30+. In considerazione del polimorfismo clinico e della rapida evoluzione sistemica, tali casi potrebbero rappresentare un subset pi\uf9 aggressivo nel gruppo dei linfomi ALC primitivi della cute

Induction of erythroferrone in healthy humans by micro-dose recombinant erythropoietin or high-altitude exposure

The erythropoietin (Epo)-erythroferrone (ERFE)-hepcidin axis coordinates erythropoiesis and iron homeostasis. While mouse studies have established that Epo-induced ERFE production represses hepcidin synthesis by inhibiting hepatic BMP/SMAD signaling, evidence for the role of ERFE in humans is limited. To investigate the role of ERFE as a physiological erythroid regulator in humans, we conducted two studies: first, 24 males received six injections of saline (placebo), recombinant Epo (rhEpo) 20 UI kg-1 (micro-dose) or 50 UI kg-1 (low-dose). Second, we quantified ERFE in 22 subjects exposed to high altitude (3800 m) for 15 hours. In the first study, total hemoglobin mass (Hbmass) increased after low- but not after micro-dose injections, when compared to placebo. Serum ERFE levels were enhanced by rhEpo, remaining higher than after placebo for 48 (micro-dose) or 72 hours (low-dose) post-injections. Conversely, hepcidin levels decreased when Epo and ERFE arose, before any changes in serum iron parameters occurred. In the second study, serum Epo and ERFE increased at high altitude. The present results demonstrate that in healthy humans ERFE responds to slightly increased Epo levels not associated with Hbmass expansion and down-regulates hepcidin in an apparently iron-independent way. Notably, ERFE flags micro-dose Epo, thus holding promise as novel anti-doping biomarker

Epidermolisi bollosa acquisita a IgA

L\u2019Epidermolisi Bollosa Acquisita (EBA) \ue8 una rara dermatosi bollosa ad andamento cronico della giunzione dermo-epidermica clinicamente e istopatologicamente polimorfa. E' caratterizzata dalla presenza di autoanticorpi circolanti di tipo IgG, forniti di specifica attivit\ue0 patogena, rivolti contro la porzione C-terminale del procollagene di tipo VII nella sua porzione non collagenica. La variante ad IgA \ue8 ancora pi\uf9 rara (82 casi in letteratura), analoga dal punto di vista clinico e prognostico all'EBA a IgG. Si pu\uf2 associare ad alcune patologie reumatiche o neoplastiche come l\u2019artrite reumatoide ed il linfoma di Hodgkin o all\u2019assunzione di particolari classi di farmaci. Descriviamo il caso di una donna di 61 anni, affetta da LLC a cellule B dal 1996, in progressione di malattia ed in trattamento con Fludarabina, anti-CD20 e Ciclofosfamide, che giungeva alla nostra osservazione per la comparsa di lesioni vescico-bollose al dorso delle mani e dei piedi associate a fragilit\ue0 cutanea al minimo traumatismo da circa 2 anni. Gli esami ematochimici mettevano in evidenza un incremento delle IgM sieriche e la presenza all\u2019elettroforesi sieroproteica di una componente monoclonale IgM kappa in zona gamma1 e di una componente monoclonale IgG kappa in zona gamma. L\u2019IFD su cute sana perilesionale rivelava la presenza di depositi lineari di IgA alla giunzione dermo-epidermica ed una positivit\ue0 nucleare (lupus-like) e intercellulare (pemfigo-like) dei cheratinociti con depositi anche a livello della giunzione dermoepidermica con anti- IgM; IgG e C3 risultavano negativi. L\u2019 IFI su cute splittata dimostrava la presenza di depositi di IgA a livello del pavimento della bolla, mentre su cute sana rivelava la presenza di anticorpi IgM anti-nucleo e anti-giunzione dermo-epidermica. Inoltre si evidenziava la presenza di anticorpi circolanti di tipo punteggiato e fuso mitotico di classe IgM su HEP-2. Il quadro clinico-anamnestico e laboratoristico erano compatibili con un\u2019 epidermolisi bollosa ad IgA e reazione lupus-like/pemphigus-like in assenza di manifestazioni cliniche di queste ultime patologie. Alla paziente, in terapia con anti CD20, \ue8 stata consigliata l\u2019assunzione di Prednisone 12.5 mg/die in caso di aggravamento del quadro clinico. L'interesse del caso risiede nella coesistente presenza di una variante rara di EBA (IgA) con un quadro laboratoristico lupus like e pemphigus like dimostrato all\u2019IFD e IFI in una paziente affetta da LLC