Experimental assessment of an indirect method to measure the post-combustion flue gas flow rate in waste-to-energy plant based on multi-point measurements.

In waste-to-energy plants, the determination of the flue gas flow rate in the post-combustion section is of the utmost importance, e.g., for the verification of the compliance to the minimum residence time requirements (tres>2s) or for the control of flue gas treatment reactant injection, but the harsh conditions (high temperature and content of pollutants) do not allow for a direct measurement. The present work reports an experimental assessment of an indirect approach to estimate the flue gas flow rate in the post-combustion section of a rotary kiln plant with reduced uncertainty. This method consists on the direct measurement of the flow rate at a "colder" section of the plant (the boiler outlet) combined to the simultaneous measurements of flue gas composition measurements upstream and downstream of the boiler. From these measurements it is then possible to determine the mass of false air and to retrieve the actual flue gas flow-rate in the post-combustion chamber. A massive experimental campaign has been conducted at a full-scale medical waste incinerator, in which flue gas flow rate was estimated at different waste loads and ambient conditions. The results show that the percentage of false air can be significant and simply neglecting it can lead to substantial under-performance of the plant. Issues related to the practical implementation of the methods are illustrated in detail and the possibility to extend the methodology towards an online determination of post-combustion flue gas flow rate is discussed.

Early melanoma invasivity correlates with gut fungal and bacterial profiles.

BACKGROUND: The microbiome is emerging as a crucial player of the immune checkpoint in cancer. Melanoma is a highly immunogenic tumour, and the composition of the gut microbiome has been correlated to prognosis and evolution of advanced melanoma and proposed as a biomarker for immune checkpoint therapy. OBJECTIVES: We investigated the gut fungal and bacterial compositions in early-stage melanoma and correlated microbial profiles with histopathological features. METHODS: Sequencing of bacterial 16S rRNA and the fungal internal transcribed spacer region was performed on faecal samples of patients with stage I and II melanoma, and healthy controls. A meta-analysis with gut microbiota data from patients with metastatic melanoma was also carried out. RESULTS: We found a combination of gut fungal and bacterial profiles significantly discriminating patients with melanoma from controls. In patients with melanoma, we observed an abundance of Prevotella copri and yeasts belonging to the order Saccharomycetales. We found that the bacterial and fungal community correlated to melanoma invasiveness, whereas the specific fungal profile correlated to melanoma regression. Bacteroides was identified as general marker of immunogenicity, being shared by regressive and invasive melanoma. In addition, the bacterial communities in patients with stage I and II melanoma were different in structure and richer than those from patients with metastatic melanoma. CONCLUSIONS: The composition of the gut microbiota in early-stage melanoma changes along the gradient from in situ to invasive (and metastatic) melanoma. Changes in the microbiota and mycobiota are correlated to the histological features of early-stage melanoma, and to the clinical course and response to immune therapies of advanced-stage melanoma, through direct or indirect immunomodulation.

Treatment of recurrent pilonidal cysts with nd-YAG laser: report of our experience.

PURPOSE: Surgical treatment remains the first-line therapy of pilonidal cyst but is associated with high levels of postoperative pain, adverse events and a recurrence rate of 30%. We report our experience with laser hair removal using the Nd-YAG laser for the treatment of pilonidal cyst. MATERIALS AND METHODS: Ten patients affected by pilonidal cyst were examined and treated from October 2011 to November 2016. Treatments were carried out using the Nd-YAG laser (Deka M.E.L.A, Calenzano, Florence, Italy) at a wavelength of 1064 nm at 30-day interval. RESULTS: Nine patients were asymptomatic after the second treatment, while in one case the symptom disappeared after the fourth session. After 4-8 treatments, the pilonidal cyst had clinically disappeared and patients subjectively felt healed. In all cases, the soft-tissue ultrasounds performed before the first and after the last session showed the disappearance of the pilonidal cyst. In the follow-up, all the patients remained asymptomatic without any disease recurrence. CONCLUSIONS: Nd-YAG laser is an effective treatment for pilonidal cysts, providing excellent results with quick healing and no risk of serious adverse side-effects. It could be a very attractive alternative to open surgery, enabling patients to prevent the frequent and severe postoperative issues associated with surgery.

Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening.

Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients.

Hemodynamic and Anatomic Variations Require an Adaptable Approach during Intra-Arterial Chemotherapy for Intraocular Retinoblastoma: Alternative Routes, Strategies, and Follow-Up.

BACKGROUND AND PURPOSE: Intra-arterial chemotherapy for retinoblastoma is not always a straightforward procedure, and it may require an adaptable approach. This study illustrates strategies used when the ophthalmic artery is difficult to catheterize or not visible, and it ascertains the effectiveness and safety of these strategies. MATERIALS AND METHODS: A retrospective study was performed on a series of 108 eyes affected by intraocular retinoblastoma and selected for intra-arterial chemotherapy (follow-up range, 6-82 months). We recognized 3 different patterns of drug delivery: a fixed pattern through the ophthalmic artery, a fixed pattern through branches of the external carotid artery, and a variable pattern through either the ophthalmic or the external carotid artery. RESULTS: We performed 448 sessions of intra-arterial chemotherapy, 83.70% of them through the ophthalmic artery and 16.29% via the external carotid artery. In 24.52% of eyes, the procedure was performed at least once through branches of the external carotid artery. In 73 eyes, the pattern of drug delivery was fixed through the ophthalmic artery; for 9 eyes, it was fixed through branches of the external carotid artery; and for 17 eyes, the pattern was variable. Statistical analysis did not show any significant difference in the clinical outcome of the eyes (remission versus enucleation) treated with different patterns of drug delivery. Adverse events could not be correlated with any particular pattern. CONCLUSIONS: Alternative routes of intra-arterial chemotherapy for intraocular retinoblastoma appear in the short term as effective and safe as the traditional drug infusion through the ophthalmic artery.

High prevalence of circulating autoantibodies against thyroid hormones in vitiligo and correlation with clinical and historical parameters of patients.

BACKGROUND: Autoantibodies against thyroid hormones (THAbs) directed towards triiodothyronine (T3-Ab) and/or thyroxine (T4-Ab) are very rare in the general population. They are increased in some nonthyroidal autoimmune diseases, where they seem to predict autoimmune thyroid disorders (ATDs). So far, their presence in patients with vitiligo has not been evaluated, but it might have a possible predictive role. OBJECTIVES: To assess the prevalence of THAbs in a group of vitiligo patients and to correlate their presence with clinical and historical parameters. METHODS: In total 79 patients with nonsegmental vitiligo and 100 controls were examined. Clinical characteristics of vitiligo and family and personal medical history were evaluated. Antinuclear autoantibodies, thyroid hormones and thyroid autoantibodies were measured. IgM T3-Ab, IgG T3-Ab, IgM T4-Ab and IgG T4-Ab were assayed by a radioimmunoprecipitation technique. Fisher's test, Student's t-test and χ(2)-test were used for statistical analysis. RESULTS: Overall 77 of 79 patients (97%) had at least one type of THAb (11 T3-Ab, 10 T4-Ab, 56 both). In the control group, only one person (1%) had THAbs. In patients with vitiligo, T3-Abs were significantly associated with leucotrichia (IgM+IgG, P = 0.033; IgG, P = 0.039; IgM, P = 0.005) and thyroglobulin autoantibodies (IgM+IgG, P = 0.031; IgG, P = 0.058), while the absence of T3-Ab was related to personal history of cancer (IgM+IgG, P = 0.021; IgG, P = 0.039). T4-Abs were significantly associated with vitiligo activity (IgM+IgG, P < 0.001; IgM, P = 0.037) and duration (IgG, P = 0.013). CONCLUSIONS: The surprisingly high prevalence of THAb in patients with vitiligo and their associations suggest a possible pathogenetic role in the disease and stress the tight link between vitiligo and ATDs. Further evaluation in a larger group of patients and an adequate follow-up are needed to define their potential predictive role.

Efficacy and safety evaluation of an innovative CO2 laser/radiofrequency device in dermatology.

BACKGROUND: CO2 laser has not only become the most widely used laser in dermatological surgical practice, but it has also proved to be highly effective in treating aesthetic imperfections. OBJECTIVE: To examine the efficacy and safety of a novel fractional CO2 laser combined with a radiofrequency device in different dermatological, surgical and aesthetic fields. METHODS: A total of 79 patients were treated in our Outpatient Service with a novel fractional CO2 laser combined with a bipolar radiofrequency device for a maximum of 5 months. Group A consisted of 39 patients with lesions requiring complete excision, whereas Group B consisted of 40 subjects seeking to enhance aesthetic facial imperfections. The results were assessed by three 'blind' investigators using photographs and clinical observations; in addition, the patients had to give their own subjective assessment of the results. RESULTS: At the 6-month follow-up, the lesions of the Group A patients had been completely removed, except for one case of a large sebaceous nevus on the scalp. All the Group B patients showed global improvement in skin tightening, removal of fine lines and rhytides and correction of dilated pores and hyperpigmentation, with no significant side-effects and short downtimes. CONCLUSION: This kind of laser meets the needs of the majority of dermatologists requiring a unique, versatile tool to remove cutaneous lesions and at the same time, safely and effectively treat skin imperfections.

Autoimmune signals in non-segmental vitiligo patients are associated with distinct clinical parameters and toxic exposures.

BACKGROUND: Although non-segmental vitiligo is commonly considered an autoimmune disease, the possible differences between non-segmental vitiligo patients with and without autoimmune signals have not been clearly established. OBJECTIVE: To perform a comparison of non-segmental vitiligo patients with autoimmune signals (AIS) vs. those without autoimmune signals (NAIS) in regards to clinical characteristics and toxic/drug exposure. METHODS: 112 vitiligo patients were selected for a sex and age matched (1 : 1) case control study at an university based dermatology outpatient hospital specialized in pigmentary disorders. Medical assessment was performed by dermatologists using the modified Vitiligo European Task Force form and serological and clinical signs of autoimmunity were evaluated. RESULTS: Disease duration, age of onset, patient history of cardiovascular disease, past smoking history, use of drugs, and consummation of goitrogenic foods were all significantly increased in the AIS group using McNemar's test for matched pairs. In our conditional regression model, the simultaneous presence of disease duration, use of prescription drugs, and consummation of goitrogenic foods were the best predictors of AIS vitiligo patients. CONCLUSION: The evaluation of non-segmental vitiligo patients according to the presence vs. the absence of autoimmune signals allows us to correlate patients exhibiting autoimmune phenomenon with certain clinical characteristics, namely long disease duration, use of prescription drugs, and consumption of goitrogenic substances. In the presence of the aforementioned clinical profile, we suggest an evaluation of autoimmune signals.

Laser use in infantile hemangiomas, when and how.

Infantile hemangiomas (IHs) are proliferating embrional tumors which can stem from placented tissue and are constituted by endothelial cell hyperproliferation. The management of the IHs is always challenging for all the specialists because of the heterogeneous behavior of these lesions. The factors leading to an aggressive position are essentially these: the prevention or reduction of aesthetic risks, the prevention or treatment of ulcerated hemangiomas, the prevention or impairment of functional risks and pain, and the removal of life-threatening risks. The treatment of vascular lesions is one of the mostly sought and performed cutaneous laser procedures, and in the field of IH treatments the more used laser devices certainly are pulsed dye lasers. Early laser therapy is able to reduce the possibility that the lesion will reach its full size, preventing several complications, connected to the hemangioma's growth, and providing psychological relief for pediatric patients and their parents.

Valproic acid induces differentiation and transient tumor regression, but spares leukemia-initiating activity in mouse models of APL.

Aberrant histone acetylation was physiopathologically associated with the development of acute myeloid leukemias (AMLs). Reversal of histone deacetylation by histone deacetylase inhibitor (HDACis) activates a cell death program that allows tumor regression in mouse models of AMLs. We have used several models of PML-RARA-driven acute promyelocytic leukemias (APLs) to analyze the in vivo effects of valproic acid, a well-characterized HDACis. Valproic acid (VPA)-induced rapid tumor regression and sharply prolonged survival. However, discontinuation of treatment was associated to an immediate relapse. In vivo, as well as ex vivo, VPA-induced terminal granulocytic differentiation. Yet, despite full differentiation, leukemia-initiating cell (LIC) activity was actually enhanced by VPA treatment. In contrast to all-trans retinoic acid (ATRA) or arsenic, VPA did not degrade PML-RARA. However, in combination with ATRA, VPA synergized for PML-RARA degradation and LIC eradication in vivo. Our studies indicate that VPA triggers differentiation, but spares LIC activity, further uncouple differentiation from APL clearance and stress the importance of PML-RARA degradation in APL cure.

The self-association coiled-coil domain of PML is sufficient for the oncogenic conversion of the retinoic acid receptor (RAR) alpha.

In acute promyelocytic leukemia (APL) the retinoic acid receptor alpha (RARα) becomes an oncogene through the fusion with several partners, mostly with promyelocytic leukemia protein (PML), all of which have in common the presence of a self-association domain. The new fusion proteins, therefore, differently from the wild-type RARα, which forms only heterodimers with retinoic X receptor alpha, are also able to homo-oligomerize. The presence of such a domain has been suggested to be crucial for the leukemogenic potential of the chimeric proteins found in APL blasts. Whether or not any self-association domain is sufficient to bestow a leukemogenic activity on RARα is still under investigation. In this work, we address this question using two different X-RARα chimeras, where X represents the coiled-coil domain of PML (CC-RARα) or the oligomerization portion of the yeast transcription factor GCN4 (GCN4-RARα). We demonstrate that in vitro both proteins have transforming potential, and recapitulate the main PML-RARα biological properties, but CC-RARα is uniquely able to disrupt PML nuclear bodies. Indeed, in vivo only the CC-RARα chimera induces efficiently APL in a murine transplantation model. Thus, the PML CC domain represents the minimal structural determinant indispensable to transform RARα into an oncogenic protein.

The effects of alcoholism pharmacotherapy on immune responses in alcohol-dependent patients.

Chronic alcohol use has profound modulatory effects on the immune system. Both the innate and the acquired immunity are compromised. The use of pharmacotherapy is increasingly applied to enhance the percentage of success in maintaining alcoholic patients in remission. Disulfiram, naltrexone and gamma hydroxybutiric acid are the drugs used for this purpose in Italian Addiction Services. In this study we analyze the effect of pharmacotherapy of alcohol dependence on immune responses in alcoholics. Six groups were studied. Group A included 10 patients who were still using alcohol. Group B consisted of 10 patients abstinent from alcohol in treatment only with group therapy. Groups C, D and E were composed of 10 patients each, treated for at least 6 months with oral doses of gamma hydroxybutiric acid, naltrexone or disulfiram respectively. Ten age- and sex-matched healthy volunteers who never misused alcohol were included as a control group. Lymphoproliferation and peripheral mononuclear cell production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokines IL-1 and TNF-alpha were evaluated in all the patients and controls. The level of activity of the hypothalamus pituitary adrenal axis was assessed. Both ACTH and cortisol levels in plasma were elevated in alcoholic patients with no treatment. In this group a significant alteration of cytokine production was observed. TNF and IFN-gamma were lower than controls, while the Th2 cytokine IL-4 was increased. These altered levels state for a Th1/Th2 unbalance characterized by decreased Th1 response in the presence of Th2 predominance. In patients undergoing pharmacological treatment, none of the immune parameters were different from those observed in healthy controls, independently of the type of drug administered. These data indicate that pharmacotherapy more than group therapy treatment is able to ameliorate the immune system functioning in alcoholic patients.

Stress as a possible mechanism in melanoma progression.

The incidence of melanoma, the most aggressive type of cutaneous malignant tumor, is currently on the rise. Treatment in advanced stages is still unsuccessful compared with other malignant tumors, thus it is important to indentify the key mechanisms responsible for melanoma progression and metastasis. Genetic and molecular components, in particular, that are up- or downregulated in melanoma cells, affect the invasive potential of melanoma. Another possible important cofactor highlighted by recent studies is chronic stress, involving environmental and psychological factors, which can be an important cofactor in not only cancer progression in general but also in melanoma spreading. The negative effects of chronic stress have been evaluated epidemiologically in patients with breast and prostate cancer. In particular, the effects of stress mediators, namely, catecholamines have been studied on various human malignancies, including melanoma and have highlighted a significant increase of progression-related molecules. As such, this could be the starting point for a new approach in the treatment of advanced melanoma, in which the negative effects of stress are reduced or blocked.

Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis.

Innate responses combine with adaptive immunity to generate the most effective form of anti-Aspergillus immune resistance. Although some degree of inflammation is required for protection, progressive inflammation may worsen disease and ultimately prevents pathogen eradication. To define molecular pathways leading to or diverting from pathogenic inflammation in infection, we resorted to dendritic cells (DCs), known to activate distinct signaling pathways in response to pathogens. We found that distinct intracellular pathways mediated the sensing of conidia and hyphae by lung DCs in vitro, which translate in vivo in the activation of protective Th1/Treg responses by conidia or inflammatory Th2/Th17 responses by hyphae. In vivo targeting inflammatory (PI3K/Akt/mTOR) or anti-inflammatory (STAT3/IDO) DC pathways by intranasally delivered small interfering RNA (siRNA) accordingly modified inflammation and immunity to infection. Thus, the screening of signaling pathways in DCs through a systems biology approach may be exploited for the development of siRNA therapeutics to attenuate inflammation in respiratory fungal infections and diseases.

Lymphocyte apoptosis, caspase activation and inflammatory response in septic shock.

BACKGROUND: We examined lymphocyte apoptosis, activity of caspases-1, -3, -8 and -9 and the relationship between those two events and inflammation response in septic shock. MATERIALS AND METHODS: Blood samples were obtained within 24 h after diagnosis of septic shock from 16 patients to measure apoptosis, caspases-3, -8, -9 expression, changes in mitochondrial transmembrane potential and expression of Fas/FasL system of peripheral blood mononuclear cells (PBMCs). Moreover, serum levels of caspase-1 and blood concentrations of IL-6, IL-12, IL-15 and IL-18 were assessed. RESULTS: PBMCs from patients with septic shock compared to control individuals exhibited a greatly increased frequency of apoptosis (39.10 +/- 7.33% vs 4.19 +/- 1.13%; p < 0.001), an over expression of caspases-3, -8, and -9 (p < 0.01, p < 0.05, p < 0.001 for caspases-3, -8 and -9, respectively) as well as of Fas/FasL system (p < 0.05) and significant changes in mitochondrial transmembrane potential. Blood levels of caspase-1 (101.5 +/- 18.2 pg/ml vs 9.09 +/- 2.7 pg/ml, p < 0.001) and of IL-6, IL-12, IL-15 and IL-18 were significantly higher in septic patients vs control (p < 0.0001, p < 0.05, p < 0.05 and p < 0.0001, respectively). Furthermore, a correlation linking IL-6 blood level with both the apoptotic rate (r(2) = 0.75; p = 0.001) and caspase-9 expression (r(2) = 0.92; p = 0.0001) of PBMCs was observed.

A functional role for soluble HLA-G antigens in immune modulation mediated by mesenchymal stromal cells.

BACKGROUND: It has been suggested that soluble factors produced by bone marrow (BM) mesenchymal stromal cells (MSC) play a fundamental role in mediating immune modulation. HLA-G antigens (Ag) are major histocompatibility complex (MHC) class Ib molecules characterized by a limited polymorphism and a splicing mechanism that regulates the production of membrane-bound and soluble isoforms. Interleukin-10 (IL-10) cytokine is one of the main up-modulators of soluble HLA-G Ag (sHLA-G) production by CD14+ peripheral blood monocyte cells and increased IL-10 levels are reported to be associated with MSC immune modulation. METHODS: We investigated, by specific enzyme-linked immunosorbent assay (ELISA), the possible role of sHLA-G molecules in the inhibition of the peripheral blood mononuclear cell (PBMC) response to phytohemagglutinin (PHA) mediated by MSC from different sources. RESULTS: There was a significant correlation between the presence of increased levels of sHLA-G and IL-10 in the MSC/PBMC/PHA culture supernatants and lymphoproliferative inhibition. Neutralizing experiments performed with monoclonal Ab directed against HLA-G and IL-10 molecules confirmed the inhibitory ability of sHLA-G Ag. Furthermore, exogenous IL-10 induced sHLA-G molecule secretion by MSC alone in a polymorphic way, while a longitudinal analysis confirmed the loss of MSC inhibitory functions in relation to in vitro MSC aging. DISCUSSION: Overall the results obtained suggest a functional role for sHLA-G molecules in inhibiting the PBMC response mediated by MSC. Moreover, the ability of IL-10 to induce sHLA-G Ag production by MSC alone could be proposed as a marker of MSC functional ability.

Loss of Thy-1 (CD90) antigen expression on mesenchymal stromal cells from hematologic malignancies is induced by in vitro angiogenic stimuli and is associated with peculiar functional and phenotypic characteristics.

BACKGROUND: Little is known about human mesenchymal stromal cell (hMSC) phenotypic and functional subsets in response to environmental stimuli. The strategy used in this study focused on defining hMSC functional subpopulations based in particular on their Thy-1 (CD90) antigen (Ag) surface expression. METHODS: The effect of different in vitro microenvironmental conditions on the isolation and expansion of bone marrow-derived (BM) hMSC from hematologic malignancies (HM) and normal samples (NS) was assayed. hMSC clonogenic and differentiation potential, phenotypic profile and long-term capacity to sustain in vitro hemopoiesis were considered in relation to the different expansion protocols. RESULTS: The results showed that angiogenic supplements used in combination with low serum content gave rise to the appearance of Thy-1(-) HM-MSC with high proliferative potential, capable of restoring the typical HM stromal impairment. The expression of the CD271 was partially maintained. We further report an enhancement towards the osteogenic and adipogenic differentiation capacity by the Thy-1(-) HM-MSC subset. Despite the angiogenic treatment, the Thy-1(-) MSC stopped short of full endothelial differentiation. DISCUSSION: In this paper we provide evidence that in vitro angiogenic stimuli generate HM-MSC lacking CD90 Ag expression. The Thy-1(-) MSC subset is characterized by peculiar functional and phenotypic characteristics, thus supporting the role played by the microenvironment in selecting particular hMSC subsets maintaining normal tissue homeostasis or inducing pathologic processes.