The Use of Peripheral Blood-Mononuclear Cells in Scleroderma Patients: An Observational Preliminary Study

Introduction: Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by vasculopathy and excessive production of collagen, which lead to skin and visceral fibrosis. The aim of our study is to assess the potential benefits of autologous peripheral blood mononuclear cells (PBMCs) implants in the treatment of clinical manifestations such as mouth impairment, hand disability, digital ulcers and Raynaud’s phenomenon in Scleroderma patients. Methods: From February 2016 to May 2019, 10 female patients were enrolled from the outpatient clinic of the Plastic Surgery Unit of Sapienza University of Rome. Parameters evaluated were: patients’ disability, using the Health Assessment Questionnaire (HAQ) disability index (DI) and the scleroderma HAQ (sHAQ); mouth opening capacity, by measuring the maximum interincisal distance and the mouth perimeter; hand mobility, assessed with clinical exam and the Hand Mobility in Scleroderma (HAMIS) scale; Raynaud’s phenomenon, evaluated through nailfold capillaroscopy; digital ulcers, examined through their features and incidence of appearance. SPSS software was used for a simple descriptive statistical analysis performed by the Student’s paired t-test. P values less than 0.05 were considered statistically significant. Results: The treatment showed a significant improvement of all the parameters evaluated at 1-year follow-up, it was well-tolerated by all the patients and the only complications noticed were small areas of ecchymosis. Conclusions: With our preliminary study we tought to exploit PBMCs capability to induce angiogenesis widely described in literature in order to treat the vasculopathy-related manifestations of SSc, in patients with no chance for lipofilling. Our results suggest that PBMCs injection could represent a treatment option to take into account for SSc patients. The procedure we used is easy and fast to perform, minimally invasive and not-operator dependent. We hope our observational and preliminary study could be considered as a starting point for further research studies

The Role of MN1-TEL, MN1 and TEL2 in Leukemia

Blood cells arise from a common totipotent hematopoietic stem cell after sequential differentiative steps in a process termed hematopoiesis. Abnormal proliferation along this process is crucial in the occurrence of leukemias. Understanding the relationships among cells of the hematopoietic system and the mechanisms underlying leukemogenesis constitutes a key priority of modern cancer research. The first goal of this thesis was to clarify the role of TEL2 in hematopoiesis and leukemogenesis. Our data show that TEL2 behaves as a bona fide oncogene in vivo, causing myeloproliferative disease (MPD) in mice. However, development of leukemia upon TEL2 overexpression requires cooperation of secondary mutations. Indeed, expressing TEL2 in Arf-/- bone marrow the onset of disease accelerates and phenotype shifts from MPD to B-cell lymphoma. Most importantly, we show that TEL2 directly regulates mTOR in Arf-/- pro-B cells, and propose a model whereby TEL2-dependent upregulation of mTOR is partly responsible for increased proliferation and survival rates of malignant cells, but must cooperate with additional growth-promoting signals dependent on TEL2 function. The second part of this thesis analyzes the role of MN1-TEL as hematopoietic oncogene, demonstrating its ability to cause myeloid malignance when expressed in murine bone marrow. These studies led us to discover that MN1 can per se stimulate the growth of mouse myeloid progenitors, causing MPD in mice. In addition we show that MN1 is upregulated in inv(16) AML patients, and when expressed in mice it cooperates with Cbfβ-SMMHC (the product of inv(16) rearrangements), leading to AML

Design thinking for entrepreneurship: An explorative inquiry into its practical contributions

Design thinking (DT) is expanding its horizons across a variety of different domains. One of the early and debated contributions regarding DT addressed its relationship with the entrepreneurial field. Today, there are numerous contributions that design thinking can offer in the creation of new ventures. However, there are few examples in the literature that discuss the concrete impacts and benefits of adopting DT in this field, demonstrating it through entrepreneurial projects. This paper aims to explore practitioners’ experiences with the application of theories from design thinking inside an entrepreneurial context. The impacts of the learning and the relative application of the main design thinking principles are evaluated via a sample of 50 participants in an international summer academy that offered education on DT concepts and practices. Through this research, a deep understanding of how design thinking can contribute to entrepreneurship is provided, highlighting which specific DT abilities enable the development of entrepreneurial activity

Exposure to High Levels of Noise Poses Hazards and Risks for Development of Hypertension and Heart Disease: Potential Roles of Unrecognized Ionized Hypomagnesemia and Release of Ceramides and Platelet-Activating Factor

It has been demonstrated in numerous human and animal studies that audiogenic stress (AS) can induce elevation of arterial blood pressure and cardiac damage and that noise –induced hearing loss may be associated with alterations in magnesium (Mg) metabolism. Our laboratories, over a period of approximately 40 years, have been investigating why AS causes high blood pressure and cardiac damage. This review focuses on a number of newer discoveries on why AS causes dysfunctions of the cardiovascular system (CVS) This review discusses the pivotal physiological and biochemical importance of Mg to body health and the fact that most Americans and Europeans are deficient in daily Mg intake which perforce can cause severe dysfunctions of the CVS. Our ongoing studies clearly provide a solid microcirculatory basis for how and why AS above 65dB(A) often induces elevated blood pressure and cardiac damage. We review a body of data that points to the fact that AS does the latter, but appears to do so because noise stress levels result in Mg deficiency followed by release of certain sphingolipids (e.g., ceramides) and generation and release of platelet- activating factor (PDF). It is our opinion that all people exposed to high degrees of noise stress should be monitored for cardiovascular functions, ionized Mg levels, blood ceramide levels and levels of PDF. Lastly, we believe all people exposed to high levels of AS (i.e., maintenance people and pilots on aircraft carriers, musicians [particularly at rock concerts], motorman and conductors on trains and subways, construction site workers, etc.) should have at least the equivalent daily intake of 500-600 mg of Mg/day

Synthesis of highly regioregular poly[3-(4-alkoxyphenyl)-thiophene]s by oxidative catalysis using copper complexes

A novel, easy, and cost-effective synthetic procedure is reported for the production of very highly regioregular poly[3-(4-alkoxyphenyl)thiophene]s by means of oxidative coupling. Four copper complexes were synthesized and used as catalysts to obtain polymers with higher regioregularity compared to the previous oxidative coupling methodologies reported in the literature and similar to that obtained by McCullough and Rieke methods in the synthesis of poly-3-alkylthiophenes. The regioregularity of the synthesized polymers was investigated by UV-Visible characterization on polymer thin films and 1H NMR analysis. The remarkable potentialities of these polymers have emerged from field-effect transistor mobility measurements operated on devices with bottom-contact configuration and hexamethyldisilazane-treated SiO 2 gate dielectric, showing a well-defined p-type field-effect response and maximum mobility values in air higher than 10-4 cm 2 V-1 s-1. © 2013 Wiley Periodicals, Inc

Estimating sea surface temperature measurement methods using characteristic differences in the diurnal cycle

Lack of reliable observational metadata represents a key barrier to understanding sea surface temperature (SST) measurement biases, a large contributor to uncertainty in the global surface record. We present a method to identify SST measurement practice by comparing the observed SST diurnal cycle from individual ships with a reference from drifting buoys under similar conditions of wind and solar radiation. Compared to existing estimates, we found a larger number of engine room-intake (ERI) reports post War World II and in the period 1960 – 1980. Differences in the inferred mixture of observations lead to a systematic warmer shift of the bias adjusted SST anomalies from 1980 compared to previous estimates, while reducing the ensemble spread. Changes in mean field differences between bucket and ERI SST anomalies in the Northern Hemisphere over the period 1955 – 1995 could be as large as 0.5 °C and are not well reproduced by current bias adjustment models

Diagnostic accuracy of short-time inversion recovery sequence in Graves' ophthalmopathy before and after prednisone treatment

Introduction: In Graves' Ophthalmopathy, it is important to distinguish active inflammatory phase, responsive to immunosuppressive treatment, from fibrotic unresponsive inactive one. The purpose of this study is, first, to identify the relevant orbital magnetic resonance imaging signal intensities before treatment, so to classify patients according to their clinical activity score (CAS), discriminating inactive (CAS3) subjects and, second, to follow post-steroid treatment disease. Methods: An observational study was executed on 32 GO consecutive patients in different phases of disease, based on clinical and orbital Magnetic Resonance Imaging parameters, compared to 32 healthy volunteers. Orbital Magnetic Resonance Imaging was performed on a 1.5 tesla Magnetic Resonance Unit by an experienced neuroradiologist blinded to the clinical examinations. Results: In pre-therapy patients, compared to controls, a medial rectus muscle statistically significant signal intensity ratio (SIR) in short-time inversion recovery (STIR) (long TR/TE) sequence was found, as well as when comparing patients before and after treatment, both medial and inferior rectus muscle SIR resulted significantly statistically different in STIR. These increased outcomes explain the inflammation oedematous phase of disease, moreover after steroid administration, compared to controls; patients presented lack of that statistically significant difference, thus suggesting treatment effectiveness. Conclusion: In our study, we proved STIR signal intensities increase in inflammation oedematous phase, confirming STIR sequence to define active phase of disease with more sensibility and reproducibility than CAS alone and to evaluate post-therapy involvement. © 2014 Springer-Verlag